Asian Pacific Journal of Cancer Prevention
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
- 월간
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
과학기술표준분류
- 보건의료 ＞ 의약품/의약품개발
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
KSCI제14권11호
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Cancers will continue to be a threat to health unless they can be controlled by combinations of treatment modalities. In this review, evaluate the role of resveratrol (RSV) as a radiosensitizing agent was evaluated and underlying mechanisms holistically explored in different cancer models focusing on therapeutic possibilities. The ability of RSV to modify the effect of radiation exposure in normal and cancer cells has indeed been shown quite convincingly, the combination of RSV and IR exhibiting synergistic effects on different cancer cells. This is relevant since controlled exposure to IR is one of the most frequently applied treatments in cancer patients. However, radiotherapy (XRT) treatment regimes are very often not effective in clinical practice as observed in patients with glioma, prostate cancer (PCa), melanoma, for example, largely due to tumour radioresistant properties. Sensitization of IR-induced apoptosis by natural products such as RSV is likely to be relevant in cancer control and treatment. However, all cancers do not respond to RSV+IR in a similar manner. Therefore, for those such as the radioresistant PCa or melanoma cells, the RSV+IR regime has to be very carefully chosen in order to achieve effective and desirable outcomes with minimum toxicity to normal cells. They are reports that the highest concentration of 100
${\mu}M$ RSV and highest dose of 5 Gy IR are sufficient to kill cells by induction of apoptosis, indicating that RSV is effective in radiosensitizing otherwise radioresistant cells. In general, it has been shown in different cancer cells that RSV+XRT effectively act by enhancing expression of anti-proliferative and pro-apoptotic molecules, and inhibiting pro-proliferative and anti-apoptotic molecules, leading to induction of apoptosis through various pathways, and cell death. If RSV+XRT can suppress the signature of cancer stemness, enhance the radiosensitivity by either targeting the mitochondrial functionality or modulating the tumour necrosis factor-mediated or Fas-FasL-mediated pathways of apoptosis in different cancers, particularly in vivo, its therapeutic use in the control of cancers holds promise in the near future. -
Zaman, Maseeh Uz;Fatima, Nosheen;Padhy, Ajit Kumar;Zaman, Unaiza 6209
Well differentiated thyroid cancers (WDTC), including papillary (80%) and follicular (10%) types, are the most common endocrine cancers globally. Over the last few decades most the diagnosed cases have fallen into low risk categories. Radioactive iodine-131 (RAI) has an established role in reducing recurrence and improving the survival in high risk patients. In patients with primary tumor size <1 cm, RAI is not recommended by many thyroid societies. However, low risk WDTC has been an arena of major controversies, most importantly the role and dose of adjuvant RAI for remnant ablation to minimize chances of recurrence and improving survival. This review is an attempt to update readers about the previous and existing practice based on results of non-randomized trials and evolving trends fueled by recently published randomized studies. -
Prabhu, Venugopal Vinod;Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekharan 6215
Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP-10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic approach for cancers. Further investigations are essential to elucidate the complex pathways regulated by the Kisspeptins and how these pathways might be involved in the suppression of metastasis across a range of cancers. -
Hu, Qing;Chen, Wei-Xian;Zhong, Shan-Liang;Li, Jian;Luo, Zhou;Tang, Jin-Hai;Zhao, Jian-Hua 6221
Metaplastic breast cancer (MBC) is a rare type of breast carcinoma, characterized by various combinations of mesenchymal, adenocarcinoma and other epithelial components. MBC often manifests as a large mass, with low axillary lymph node involvement and poor prognosis. Knowledge and treatment patterns about MBC demographics, presentation and tumor characteristics are very limited. In clinical practice, MBC is usually treated based on the guidelines developed for infiltrating ductal carcinoma (IDC). The ideal treatment paradigm for MBC is unknown due to its low incidence and pathological variability, so potential predictors of treatment efficacy need to be explored. This review summarizes the current models and strategies for MBC according to the published literature. -
Yeo, Yohwan;Gwack, Jin;Kang, Seokin;Koo, Boyeon;Jung, Sun Jae;Dhamala, Prakash;Ko, Kwang-Pil;Lim, Young-Khi;Yoo, Keun-Young 6227
In the past, hepatitis B virus (HBV) infection was endemic in the general Korean population. The association of HBV infection with the occurrence of liver cancer has been well demonstrated in several epidemiologic studies. While the mortality rates of liver cancer in Korea have decreased steadily over the last decade, the presence of hepatitis B surface antigen (HBsAg) in mothers remains high at 3-4%, and 25.5% of these HBsAg positive mothers are positive for hepatitis B e antigen (HBeAg). HBV infection caused almost a quarter of hepatocellular carcinoma (HCC) cases and one-third of deaths from HCC. These aspects of HBV infection prompted the Korean government to create a vaccination program against HBV in the early 1980s. In 1995, the Communicable Disease Prevention Act (CDPA) was reformed, and the government increased the number of HBV vaccines in the National Immunization Program (NIP), driving the vaccination rate up to 95%. In 2000, the National Health Insurance Act (NHIA) was enacted, which provided increased resources for the prevention of perinatal HBV infection. Then in 2002, the Korean government, in conjunction with the Korean Medical Association (KMA), launched an HBV perinatal transmission prevention program. The prevalence of HBsAg in children had been high (4-5%) in the early 1980s, but had dropped to below 1% in 1995, and finally reached 0.2% in 2006 after the NIP had been implemented. After the success of the NIP, Korea finally obtained its first certification of achievement from the Western Pacific Regional Office of the World Health Organization (WPRO-WHO) for reaching its goal for HBV control. An age-period-cohort analysis showed a significant reduction in the liver cancer mortality rate in children and adolescents after the NIP had been implemented. In addition to its vaccination efforts, Korea launched the National Cancer Screening Program (NCSP) for 5 leading sites of cancer, including the liver, in 1999. As a consequence of this program, the 5-year liver cancer survival rate increased from 13.2% (1996-2000) to 23.3% (2003-2008). The development of both the primary and secondary prevention for liver cancer including HBV immunization and cancer screening has been of critical importance. -
Franca, Eduardo Luzia;Franca-Botelho, Aline Do Carmo;Franca, Juliana Luzia;Ferrari, Carlos Kusano Bucalen;Honorio-Franca, Adenilda Cristina 6233
Diabetes represents a serious health problem. In the diabetic state, alterations in metabolism, increased susceptibility to infections and immunological changes occur. The suppression of the immune response has been identified as a relevant factor that contributes to the increase in the rate of infections in these patients. At the same time, breast cancer is the most frequent malignant tumor in women. The molecular and cellular mechanisms underlying cancer development have revealed that immune cells functionally regulate epithelial cancer development and progression. Breastfeeding has been hypothesized to reduce the risk of breast cancer. However, early systematic reviews have not yielded consistent findings for this association. The demand for human milk is increasing due to the promotion and consumer acceptance of the health benefits of consuming a natural product rich in bioactive components. However, due to changes in glucose metabolism, the components of the milk from diabetic women are modified depending on the time of evaluation. In this literature review, we summarize important new findings revealing the paradoxical role of breastfeeding in preventing the onset of breast cancer in diabetic mothers. We hypothesized that the milk component production in diabetic mothers is affected by changes in glucose metabolism. Therefore, adequate maternal glycemic control and an adequate duration of breastfeeding for diabetic mothers are crucial to ensure that the immunity components are able to confer protection against breast cancer. -
Bian, Jing;Li, Bo;Kou, Xian-Juan;Liu, Tian-Zhou;Ming, Liang 6241
Objective: To explore the predictive value of tumor markers, including cancer antigen 72-4 (CA72-4), cancer antigen 15-3 (CA15-3) and cancer antigen 125 (CA125), in single or combined detection, for the diagnosis of ovarian cancer. Methods: 120 patients diagnosed with ovarian cancer from August 2011 to March 2013 and 80 patients diagnosed with benign ovarian tumors were enrolled in this test, along with 50 health examination women randomly selected from the database as controls. Serum levels of CA72-4, CA15-3 and CA125 in this study were determined by electrochemiluminescence (ECL). Results: Serum levels of CA72-4, CA15-3 and CA125 in ovarian cancer were higher than those in healthy group and benign group (P<0.01).The sensitivity of combined detection of those three tumor markers for diagnosis of ovarian cancer was obviously higher than with single detection with each marker (P<0.01). Conclusions: CA72-4, CA15-3 and CA125 could be a good combination in the diagnosis of ovarian cancer. Patients whose tumor markers continue to increase should be highly suspected of malignancy. -
Xia, Yong-Hua;Li, Min;Fu, Dan-Dan;Xu, Su-Ling;Li, Zhan-Guo;Liu, Dong;Tian, Zhong-Wei 6245
Aims: To study effects of down-regulation of pituitary tumor-transforming gene (PTTG) on proliferation and metastasis ability of the SCL-1 cutaneous squamous cell carcinoma (CSCC) cell line and explore related mechanisms. Methods: SCL-1 cells were divided into 3 groups (untreated, siRNA control and PTTG siRNA). Cell proliferation assays were performed using a CCK-8 kit and proliferation and metastasis ability were analyzed using Boyden chambers. In addition, expression of MMP-2 and MMP-9 was detected by r-time qPCR and Western blotting. Results: Down-regulation of PTTG could markedly inhibit cell proliferation in SCL-1 cells, compared to untreated and control siRNA groups (P < 0.05). Real-time qPCR demonstrated that expression levels of PTTG, MMP-2 and MMP-9 in the PTTG siRNA group were 0.8%, 23.2% and 21.3% of untreated levels. Western blotting revealed that expression of PTTG, MMP-2 and MMP-9 proteins in the PTTG siRNA group was obviously down-regulated. The numbers of migrating cells ($51.38{\pm}4.71$ ) in the PTTG siRNA group was obviously lower than that in untreated group ($131.33{\pm}6.12$ ) and the control siRNA group ($127.72{\pm}5.20$ ) (P < 0.05), suggesting that decrease of proliferation and metastasis ability mediated by PTTG knock-down may be closely correlated with down-regulation of MMP-2 and MMP-9 expression. Conclusion: Inhibition of PTTG expression may be a new target for therapy of CSCC. -
Morita, Makiko;Yin, Guang;Yoshimitsu, Shin-Ichiro;Ohnaka, Keizo;Toyomura, Kengo;Kono, Suminori;Ueki, Takashi;Tanaka, Masao;Kakeji, Yoshihiro;Maehara, Yoshihiko;Okamura, Takeshi;Ikejiri, Koji;Futami, Kitaroh;Maekawa, Takafumi;Yasunami, Yohichi;Takenaka, Kenji;Ichimiya, Hitoshi;Terasaka, Reiji 6249
One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin$B_6$ intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin$B_2$ , vitamin$B_6$ , and vitamin$B_{12}$ with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin$B_{12}$ intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin$B_6$ . The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity. -
Hussain, Saad Muhmood;Al-Jashamy, Karim Alwan 6257
Gallstone disease is a major surgical problem in many populations; it is probably related to diet, especially excessive consumption of meat. The objective of this study was to determine the chemical composition of gallstones and their association with neoplastic changes including cholangiocarcinomas in cholecystectomised patients. The chemical composition of gallstones from 40 patients (8 males and 32 females) was analyzed. This is a prospective study performed in Baquba teaching hospital in the period from 1/10/2012 to 1/1/2013 in which we collected the gallstones for the patients who underwent cholecystectomy, whether open or laparoscopic. The stones were classified according to their chemical composition as a mixed stones (MS), and examined using a stone analysis set (chemical qualitative method) for calcium, magnesium, phosphate, uric acid and oxalate which was used reagent for qualitative determination of main individual components of stones. The results of this study showed the highest incidence of gallstones in the age group 40-49 was 13 cases followed by 11, 8 and 4 cases for age groups 30-39, 50-59, 20-29 and 60 and above, respectively. The chemical analysis showed the majority of gallstones were mixed, 38 containing calcium followed by 37 cases with uric acid, 28 with magnesium, and 25 and 22 stones with oxalate and phosphate, respectively. Microscopically, we confirmed neoplastic changes (17.5%) as cholangiocarcinomas (CCCs) (7.55%) and dysplastic cells of carcinoma in situ in 4 (10%), 31 (77.5%) cases were chronic cholecystitis and 2 (5%) cases were acute cholecystitis with empyema out of bile duct disorders patients. In conclusion, majority of cases had mixed gallstones that involved five and four of inorganic chemicals of calcium, magnesium and phosphate, the highest incidence of gallstones in age group 40-49 years old was 13 cases, and neoplastic changes were confirmed (17.5%) including CCCs, (7.5%) and dysplastic cells of carcinoma in situ (10%), while 31 (77.5%) cases were chronic cholecystitis. -
Chen, Hong;Pan, Ying;Cheng, Zheng-Yuan;Wang, Zhi;Liu, Yang;Zhao, Zhu-Jiang;Fan, Hong 6261
Background: Recent studies have suggested that expression of the RAS protein activator like-1 gene (RASAL1) is decreased in gastric carcinoma tissues and cell lines, indicated a role in tumorigenesis and development of gastric cancer. Reduced expression of RASAL1 could result in aberrant increase of activity of RAS signaling pathways in cancer cells. However, the exact mechanism which induces down-regulation of the RASAL1 gene remains unclear. This study aimed to determine the methylation status and regulation of RASAL1 in gastric cancer. Materials and Methods: Using the methylation-specific polymerase chain reaction (MSP), the methylation status of CpG islands in the RASAL1 promoter in gastric cancers and paired adjacent non-cancerous tissues from 40 patients was assessed and its clinicopathological significance was analyzed. The methylation status of RASAL1 in gastric cancer lines MKN-28, SGC-790l, BGC-823, as well as in normal gastric epithelial cell line GES-l was also determined after treatment with a DNA methyltransferase inhibitor, 5-aza-2'-doexycytidine (5-Aza-CdR). RAS activity (GAS-GTP) was assessed through a pull-down method, while protein levels of ERK1/2, a downstream molecule of RAS signaling pathways, were determined by Western blotting. Results: The frequencies of RASAL1 promoter methylation in gastric cancer and paired adjacent non-cancerous tissues were 70% (28/40) and 30% (12/40) respectively (P<0.05). There were significantly correlations between RASAL1 promoter methylation with tumor differentiation, tumor size, invasive depth and lymph node metastasis in patients with gastric cancer (all P<0.05), but no correlation was found for age or gender. Promoter hypermethylation of the RASAL1 gene was detected in MKN-28, SGC-790l and BGC-823 cancer cells, but not in the normal gastric epithelial cell line GES-1. Elevated expression of the RASAL1 protein, a decreased RAS-GTP and p-ERK1/2 protein were detected in three gastric cancer cell lines after treatment with 5-Aza-CdR. Conclusions: Aberrant hypermethylation of the RASAL1 gene promoter frequently occurs in gastric cancer tissues and cells. In addition, the demethylating agent 5-Aza-CdR can reverse the hypermethylation of RASAL1 gene and up-regulate the expression of RASAL1 significantly in gastric cancer cells in vivo. Our study suggests that RASAL1 promoter methylation may have a certain relationship with the reduced RASAL1 expression in gastric cancer. -
Objective: To determine clinical efficacy, safety and prognostic factors of pemetrexed plus platinum as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Clinical characteristics, short-term efficacy, survival and adverse reactions of 47 advanced non-squamous NSCLC patients who had received pemetrexed plus platinum as first-line treatment in Shanghai Pulmonary Hospital from January 2009 to June 2011 were retrospectively analyzed. The Chi-squared test was applied to statistically analyze the overall response rate (ORR), disease control rate (DCR) and toxicity reactions in both groups, while survival data wereanalyzed by Kaplan-Meier and logrank methods, and the COX proportional hazards model was adopted for a series of multi-factor analyses. Results: Only two patients were lost to follow-up. The ORR, DCR, medium progression-free survival time (PFS) and medium overall survival (OS) were 31.9%, 74.5%, 5 months and 15.2 months, while 1- and 2-year survival rates were 63.8% (30/47) and 19.2% (9/47), respectively. Single-factor analysis showed that tumor pathological patterns and efficacy were in association with medium PFS (P<0.05), whereas tumor pathological patterns, smoking history and efficacy were closely connected with medium OS (P<0.05). Multi-factor analyses demonstrated that pathological patterns and efficacy were independent factors influencing OS (P<0.05). The rate of toxicity reactions in degree III/IV was low, including hematologic toxicity marked by decline in white blood cell count and decrease in the platelet count (PLT), and non-hematologic toxicity manifested by gastrointestinal reactions, such as nausea and vomiting. Conclusions: Pemetrexed plus platinum as first-line treatment has excellent efficacy and slight adverse reactions with favorable drug-tolerance in patients with advanced non-squamous NSCLC.
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Alabsi, Aied Mohammed;Ali, Rola;Ali, Abdul Manaf;Harun, Hazlan;Al-Dubai, Sami Abdo Radman;Ganasegeran, Kurubaran;Alshagga, Mustafa Ahmed;Salem, Sameer Dirhim;Kasim, Noor Hayaty Binti Abu 6273
Goniothalamin, a natural compound extracted from Goniothalamus sp. belonging to the Annonacae family, possesses anticancer properties towards several tumor cell lines. This study focused on apoptosis induction by goniothalamin (GTN) in the Hela cervical cancer cell line. Cell growth inhibition was measured by MTT assay and the$IC_{50}$ value of goniothalamin was$3.2{\pm}0.72{\mu}g/ml$ . Morphological changes and biochemical processes associated with apoptosis were evident on phase contrast microscopy and fluorescence microscopy. DNA fragmentation, DNA damage, caspase-9 activation and a large increase in the sub-G1 and S cell cycle phases confirmed the occurrence of apoptosis in a time-dependent manner. It could be concluded that goniothalamin show a promising cytotoxicity effect against cervical cancer cells (Hela) and the cell death mode induced by goniothalamin was apoptosis. -
Liu, Ming;Pan, Hong;Zhang, Feng;Zhang, Yong-Biao;Zhang, Yang;Xia, Han;Zhu, Jing;Fu, Wei-Ling;Zhang, Xiao-Li 6281
Background: To further investigate the molecular basis of lung cancer development, we utilize a microarray to identify differentially expressed genes associated with various TNM stages of adenocarcinoma, a subtype with increasing incidence in recent years in China. Methods: A 35K oligo gene array, covering about 25,100 genes, was used to screen differentially expressed genes among 90 tumor samples of lung adenocarcinoma in various TNM stages. To verify the gene array data, three genes (Zimp7, GINS2 and NAG-1) were confirmed by real-time RT-PCR in a different set of samples from the gene array. Results: First, we obtained 640 differentially expressed genes in lung adenocarcinomas compared to the surrounding normal lung tissues. Then, from the 640 candidates we identified 10 differentially expressed genes among different TNM stages (Stage I, II and IIIA), of which Zimp7, GINS2 and NAG-1 genes were first reported to be present at a high level in lung adenocarcinoma. The results of qRT-PCR for the three genes were consistent with those from the gene array. Conclusions: We identified 10 candidate genes associated with different TNM stages in lung adenocarcinoma in the Chinese population, which should provide new insights into the molecular basis underlying the development of lung adenocarcinoma and may offer new targets for the diagnosis, therapy and prognosis prediction. -
Ustaalioglu, Bala Basak Oven;Unal, Olcun Umit;Turan, Nedim;Bilici, Ahmet;Kaya, Serap;Eren, Tulay;Ulas, Arife;Inal, Ali;Berk, Veli;Demirci, Umut;Alici, Suleyman;Bal, Oznur;Benekli, Mustafa;Gumus, Mahmut 6287
Background: Surgery is the only curative treatment for operable non-small lung cancer (NSCLC) and the importance of adjuvant chemotherapy for stage IB patients is unclear. Herein, we evaluated prognostic factors for survival and factors related with adjuvant treatment decisions for stage I and IIA NSCLC patients without lymph node metastasis. Materials and Methods: We retrospectively analyzed 302 patients who had undergone curative surgery for prognostic factors regarding survival and clinicopathological factors related to adjuvant chemotherapy. Results: Nearly 90% of the patients underwent lobectomy or pneumonectomy with mediastinal lymph node resection. For the others, wedge resection were performed. The patients were diagnosed as stage IA in 35%, IB in 49% and IIA in 17%. Histopathological type (p=0.02), tumor diameter (p=0.01) and stage (p<0.001) were found to be related to adjuvant chemotherapy decisions, while operation type, lypmhovascular invasion (LVI), grade and the presence of recurrence were important factors in predicting overall survival (OS), and operation type, tumor size greater than 4 cm, T stage, LVI, and visceral pleural invasion were related with disease free survival (DFS). Multivariate analysis showed operation type (p<0.001, hazard ratio (HR):1.91) and the presence of recurrence (p<0.001, HR:0.007) were independent prognostic factors for OS, as well visceral pleural invasion (p=0.01, HR:0.57) and LVI (p=0.004, HR:0.57) for DFS. Conclusions: Although adjuvant chemotherapy is standard for early stage lymph node positive NSCLC, it has less clear importance in stage I and IIA patients without lymph node metastasis. -
Gao, Chun;Li, Jing-Tao;Fang, Long;Wen, Si-Wei;Zhang, Lei;Zhao, Hong-Chuan 6293
Background: A number of clinicopathologic factors have been found to be associated with pathological lymph node metastasis (pLNM) in rectal cancer; however, most of them can only be identified by expensive high resolution imaging or obtained after surgical treatment. Just like the Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease (MELD) scores which have been widely used in clinical practice, our study was designed to assess the pre-operative factors which could be obtained easily to predict intra-operative pLNM in rectal cancer. Methods: A cohort of 469 patients who were treated at our hospital in the period from January 2003 to June 2011, and with a pathologically hospital discharge diagnosis of rectal cancer, were included. Clinical, laboratory and pathologic parameters were analyzed. A multivariate unconditional logistic regression model, areas under the curve (AUC), the Kaplan-Meier method (log-rank test) and the Cox regression model were used. Results: Of the 469 patients, 231 were diagnosed with pLNM (49.3%). Four variables were associated with pLNM by multivariate logistic analysis, age<60 yr (OR=1.819; 95% CI, 1.231-2.687; P=0.003), presence of abdominal pain or discomfort (OR=1.637; 95% CI, 1.052-2.547; P=0.029), absence of allergic history (OR=1.879; 95% CI, 1.041-3.392; P=0.036), and direct$bilirubin{\geq}2.60{\mu}mol/L$ (OR=1.540; 95% CI, 1.054-2.250; P=0.026). The combination of all 4 variables had the highest sensitivity (98.7%) for diagnostic performance. In addition, age<60 yr and direct$bilirubin{\geq}2.60{\mu}mol/L$ were found to be associated with prognosis. Conclusion: Age, abdominal pain or discomfort, allergic history and direct bilirubin were associated with pLNM, which may be helpful for preoperative selection. -
Mutlu, Hasan;Buyukcelik, Abdullah;Aksahin, Arzu;Kibar, Mustafa;Cihan, Yasemin Benderli;Kaya, Eser;Seyrek, Ertugrul;Yavuz, Sinan;Erden, Abdulsamet;Calikusu, Zuleyha;Aslan, Tuncay;Akca, Zeki 6301
Background: Some epidemiological studies reported that sunlight exposure and highvitamin D levels may decrease the morbidity and mortality related to cancer. We aimed to evaluate whether sunlight exposure has an impact on survival in patients with non small cell lung cancer. Materials and Methods: A total of 546 patients with NSCLC from two different regions (Kayseri and Adana) differing according to sunlight exposure were analysed retrospectively. Results: The median overall survival (OS) rates were 11. 6 (CI: 9.50-13.6) and 15.6 months (CI: 12.4-18.8) for Kayseri and Adana, respectively, in all patients (p=0.880). Conclusions: There were no differences between groups in terms of OS. While there is strong evidence regarding inverse relationship between cancer incidence and sunlight exposure, it is still controversial whether sunlight exposure is a good prognostic factor for survival in patients with lung cancer. -
Zhao, Zheng-Yuan;Han, Chen-Guang;Liu, Jun-Tao;Wang, Chang-Lei;Wang, Yi;Cheng, Li-Ya 6305
Background: TIAM2, a Rac guanine nucleotide exchange factor, is closely associated with cell adherence and migration. Here, we aimed to investigate the role of TIAM2 in non-small cell lung cancer (NSCLC) cells. Materials and Methods: A small interference RNA (siRNA) was introduced to silence the expression of TIAM2. Invasion and motility assays were then performed to assess the invasion and motility potential of NSCLC cells. GST-pull down assays were used to detect activation of Rac1. Results: TIAM2 was highly expressed in NSCLC cells. Knockdown of TIAM2 inhibited the invasion and motility, and suppressed activation of Rac1. Further experiments demonstrated that knockdown of TIAM2 could up-regulate the expression of E-cadherin, and down-regulate the expression of MMP-3, Twist and Snail. Conclusions: Our data suggest that TIAM2 can promote invasion and motility of NSCLC cells. Activation of Rac1 and regulation of some EMT/invasion-related genes may be involved in the underlying processes. -
Akita, Hidetoshi;Nakane, Akihiro;Ando, Ryosuke;Yamada, Kenji;Kobayashi, Takahiro;Okamura, Takehiko;Kohri, Kejiro 6311
Background: While 5-port laparoendoscopic radical prostatectomy is standard practice, efforts have been focused in developing a single port surgery for cosmetic reasons. However, this is still in the pioneering stage considering the challenging nature of the surgical procedures. We have therefore focused on reduced port surgery, using only 2-ports. In this study, we compared 2-port laparoendoscopic radical prostatectomy (2-port RP) and conventional 5-port laparoscopic radical prostatectomy (LRP) for clinically localized prostate carcinoma and evaluated the potential advantages of each. Materials and Methods: From January 2010 to December 2010, all 23 patients with clinically localized prostate cancer underwent LRP. Starting November, 2010, when we introduced the reduced port approach, we performed this procedure for 22 consecutive patients diagnosed with early-stage prostate cancer (cT1c, cT2N0). The patients were matched 1:1 to 2-port RP or LRP for age, preoperative serum PSA level, clinical stage, biopsy and pathological Gleason grade, surgical margin status, pad-free rates and post-operative pain. Results: There was a significant difference in operative time between the 2-port RP and LRP groups ($286.5{\pm}63.3$ and$351.8{\pm}72.4$ min: p=0.0019, without any variation in blood loss (including urine) ($945.1{\pm}479.6$ vs$1271.1{\pm}871.8ml$ : p=0.13). The Foley catheter indwelling period was shorter in the 2 port RP group, but without significance ($5.6{\pm}1.8$ vs$8.0{\pm}5.6$ days: p=0.057) and the total perioperative complication rates for 2 port RP and LRP were comparable at 4.5% and 8.7% (p=0.58). There was an improvement in pad-free rates up to 6 months follow-up (p=0.090), and significantly improvement at 1 year (p=0.040). PSA recurrence was 1 (4.5%) in 2-port RP and 2 (8.7%) in LRP. Continuous epidural anesthesia was used in most of LRP patients (95.7%) and in early 2-port RP patients (40.9%). In these patients, average total amount of Diclofenac sodium was 27.8mg/patient in 2-port RP and 50.0mg/patient in LRP. Conclusions: Thus the reduced port approach is as efficacious as LRP in terms of many outcome measures, with significant cosmetic advantages and reduction in post surgical pain. This method can be readily performed safely and therefore can be recommended as a standard laparoscopic surgery for prostate cancer in the future. -
Jiao, Wei;Liu, Fei;Tang, Feng-Zhu;Lan, Jiao;Xiao, Rui-Ping;Chen, Xing-Zhou;Ye, Hui-Lan;Cai, Yong-Lin 6315
To study the differentiated expression of the proto-oncogene Pokemon in nasopharyngeal carcinoma (NPC) cell lines and tissues, mRNA and protein expression levels of CNE1, CNE2, CNE3 and C666-1 were detected separately by reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and Western-blotting. The immortalized nasopharyngeal epithelial cell line NP69 was used as a control. The Pokemon protein expression level in biopsy specimens from chronic rhinitis patients and undifferentiated non keratinizing NPC patients was determined by Western-blotting and arranged from high to low: C666-1>CNE1>CNE2> CNE3>NP69. The Pokemon mRNA expression level was also arranged from high to low: CNE1>CNE2>NP69>C666-1>CNE3. Pokemon expression of NP69 and C666-1 obviously varied from mRNA to protein. The Pokemon protein level of NPC biopsy specimens was obviously higher than in chronic rhinitis. The data suggest that high Pokemon protein expression is closely associated with undifferentiated non-keratinizing NPC and may provide useful information for NPC molecular target therapy. -
Yu, Hao-Gang;Wei, Wei;Xia, Li-Hong;Han, Wei-Li;Zhao, Peng;Wu, Sheng-Jun;Li, Wei-Dong;Chen, Wei 6321
Introduction: Lung cancer is extremely harmful to human health and has one of the highest worldwide incidences of all malignant tumors. Approximately 80% of lung cancers are classified as non-small cell lung cancers (NSCLCs). Cisplatin-based multidrug chemotherapy regimen is standard for such lesions, but drug resistance is an increasing problem. F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box protein family that regulates cell cycle progression, and cell growth and differentiation. FBW7 also functions as a tumor suppressor. Methods: We used cell viability assays, Western blotting, and immunofluorescence combined with siRNA interference or plasmid transfection to investigate the underlying mechanism of cisplatin resistance in NSCLC cells. Results: We found that FBW7 upregulation significantly increased cisplatin chemosensitivity and that cells expressing low levels of FBW7, such as NCI-H1299 cells, have a mesenchymal phenotype. Furthermore, siRNA-mediated silencing or plasmid-mediated upregulation of FBW7 resulted in altered epithelial-mesenchymal transition (EMT) patterns in NSCLC cells. These data support a role for FBW7 in regulating the EMT in NSCLC cells. Conclusion: FBW7 is a potential drug target for combating drug resistance and regulating the EMT in NSCLC cells. -
Tan, Guan Hee;Shah, Shamsul Azhar;Ann, Ho Sue;Hemdan, Siti Nurhafizah;Shen, Lim Chun;Abdul Galib, Nurudin Al-Fahmi;Singam, Praveen;Kong, Ho Chee Christopher;Hong, Goh Eng;Bahadzor, Badrulhisham;Zainuddin, Zulkifli Md 6327
Haematuria is a common presentation of bladder cancer and requires a full urologic evaluation. This study aimed to develop a scoring system capable of stratifying patients with haematuria into high or low risk groups for having bladder cancer to help clinicians decide which patients need more urgent assessment. This cross-sectional study included all adult patients referred for haematuria and subsequently undergoing full urological evaluation in the years 2001 to 2011. Risk factors with strong association with bladder cancer in the study population were used to design the scoring system. Accuracy was determined by the area under the receiver operating characteristic (ROC) curve. A total of 325 patients with haematuria were included, out of which 70 (21.5%) were diagnosed to have bladder cancer. Significant risk factors associated with bladder cancer were male gender, a history of cigarette smoking and the presence of gross haematuria. A scoring system using 4 clinical parameters as variables was created. The scores ranged between 6 to 14, and a score of 10 and above indicated high risk for having bladder cancer. It was found to have good accuracy with an area under the ROC curve of 80.4%, while the sensitivity and specificity were 90.0% and 55.7%, respectively. The scoring system designed in this study has the potential to help clinicians stratify patients who present with haematuria into high or low r isk for having bladder cancer. This will enable high-risk patients to undergo urologic assessment earlier. -
Song, Li-Ping;Zhang, Wen-Hong;Xiang, Yang;Zhao, Na 6331
Objective:To evaluate the performance of combined quantitative analysis of thyroid blood flow and static imaging data in the differential diagnosis of thyroid nodules. Method: Thyroid blood flow and static imaging were performed in 165 patients with thyroid nodules. Patients were divided into a benign thyroid nodule group (BTN, n=135) and a malignant thyroid nodule group (MTN, n=30) based on the results of post-surgical pathologic examination. Carotid artery thyroid transit times (CTTT), perfusion ratio of thyroid nodule blood/thyroid blood (TNB/TB), and perfusion ratio of thyroid nodule blood/carotid artery blood (TNB/CAB) were measured using thyroid blood flow imaging. The ratios between thyroid nodule and ipsilateral submandibular gland (TN/SG) and thyroid nodule and normal thyroid tissue (TN/T) were measured from thyroid static imaging. The differences between the BTN and MTN groups were compared. Results: 1) CTTT was markedly lower in the MTN group than the BTN group, the difference being statistically significant. 2) TNB/TB and TNB/CAB were both significantly higher in MTN than BTN groups. 3) TN/T was significantly lower in MTN group than BTN group. 4) TN/SG was lower in MTN group than BTN group, but the difference was not statistically significant. 5) Using the combination of CTTT and TN/T, the sensitivity, specificity and accuracy were 93.1%, 95.3% and 94.9% respectively for the diagnosis of MTN. Using the combination of CTTT, TNB/TB and TN/T, the sensitivity, specificity and accuracy changed to 89.7%, 100%, and 98.1% respectively. 6) Correlation analysis demonstrated a significant correlation between TN/T and TNB/TB (r=-0.384, P=0.036) and TNB/CAB (r=-0.466, P=0.009) in the MTN group. Conclusion: The combination of quantitative markers from thyroid blood flow and thyroid static imaging had high specificity and accuracy in differential diagnosis of benign and malignant thyroid nodules, thus providing an important imaging diagnostic approach. -
Wu, Qing-Wu;Yan, Rui-Fang;Li, Qiang;Hu, Ying;Zhou, Feng-Mei;Ren, Ji-Peng;Yang, Rui-Min;Zhang, Yan 6337
Through retrospective analysis of 13 cases of magnetic resonance image (MRI) manifestations of atypical meningiomas confirmed by operation and pathology in the First Affiliated Hospital of Xinxiang Medical University, the objective of this study was to evaluate the diagnostic value of MRI in order to improve the accuracy rate of preoperative diagnosis. In this retrospective analysis of MRI findings for atypical meningiomas in First Affiliated Hospital of Xinxiang Medical University from January to July in 2012, the location, morphology and tumor signals and other tumor imaging characteristics were covered. In 13 cases of atypical meningioma patients of this group, most tumors were located at typical sites (10/13), mainly the falx cerebri, parasagittal, convexity, saddle area. Only two cases were at atypical locations, 1 in the cerebellar hemisphere and 1 in a lateral ventricle. Most of the tumors showed T1 and T2 isointensity signals, and necrosis, calcification, and peritumoral edema were always featured. DWI showed isointensity in 11 cases (11/13), and hyperintensity in 2. Some 9 cases had dural tail signs, 12 had accurate positioning (12/13), and 2 were postoperative recurrences. MRI has high value in the diagnosis of atypical meningiomas, with important roles in early clinical diagnosis, treatment and prognosis evaluation. -
To clarify the role of stem cells in hepatocarcinogenesis, glypican-3 (GPC-3) and E-cadherin expression was investigated in embryonic cell lineages. Mouse embryonic stem cells (ESCs), hepatic progenitor cells (HPCs) and hepatocyte like cells (HCs), representing 0, 22 and 40 days of differentiation, respectively, were treated in vitro with diethylnitrosamine (DEN) at four doses (0, 1, 5 and 15 mM; G1, G2, G3 and G4, respectively) for 24 h and GPC-3 and E-cadherin expression was examined by relative quantitative real-time PCR and immunocytochemistry. GPC-3 mRNA expression was significantly different for G4 at day 0 (p<0.001) and for G4 at day 22 (p<0.01) compared with the control (G1). E-cadherin mRNA expression was significantly different for G3 and G4 at day 0 (p<0.05 and p<0.001, respectively), for G2 and G4 (p<0.05 and p<0.001, respectively) at day 22 and for G2 and G4 (p<0.01 and p<0.001, respectively) at day 40 compared with G1. Immunofluorescence staining for GPC-3 showed a membranous and/or granular expression in cytoplasm of ESCs and HPCs and granular and/or diffuse expression in cytoplasm of HCs, which were also stained by E-cadherin. DEN treatment increased GPC-3 expression in ESCs, HPCs and HCs, with increase of E-cadherin expression. Taken together, the expression of GPC-3 was altered by DEN treatment. However, its expression pattern was different at the stage of embryo stem cells and its derived hepatic lineage cells. This suggests that GPC-3 expression may be modulated in the progeny of stem cells during their differentiation toward hepatocytes, associated with E-cadherin expression.
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Wu, Sa;Zhang, Xin;Li, Zhi-Ming;Shi, Yan-Xia;Huang, Jia-Jia;Xia, Yi;Yang, Hang;Jiang, Wen-Qi 6347
Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study. -
Abe, Hajime;Kawai, Yuki;Mori, Tsuyoshi;Tomida, Kaori;Kubota, Yoshihiro;Umeda, Tomoko;Tani, Tohru 6351
Background: Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients. Materials and Methods: Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500${\mu}g/day$ B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design. Results: The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was$2.7{\pm}2.2$ . In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was$4.9{\pm}2.4$ . Conclusions: Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen. -
Jiang, Yuan;Hou, Jing;Zhang, Qiang;Jia, Shu-Ting;Wang, Bo-Yuan;Zhang, Ji-Hong;Tang, Wen-Ru;Luo, Ying 6357
Background: The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has been associated with acute lymphoblastic leukemia (ALL). However, results were conflicting. The aim of this study was to quantitatively summarize the evidence for the MTHFRC677T polymorphism and ALL risk. Methods: Electronic searches of PubMed and the Chinese Biomedicine database were conducted to select case-control studies containing available genotype frequencies of C677T and the odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of any association. Results: Case-control studies including 6,371 cases and 10,850 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had decreased risk of ALL (OR= 0.776, 95% CI: 0.687~0.877, p< 0.001) in Caucasians (OR= 0.715, 95% CI: 0.655~0.781, p= 0.000). However, results among Asians (OR=0.711, 95% CI: 0.591~1.005, p= 0.055) and others (OR=0.913, 95% CI: 0.656~1.271, p= 0. 590) did not suggest an association. A symmetric funnel plot, the Egger's test (P=0.093), and the Begg- test (P=0.072) were all suggestive of the lack of publication bias. Conclusion: This meta-analysis supports the idea that the MTHFR C677T genotype is associated with risk of ALL in Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between the MTHFRC677T polymorphism and ALL. -
Guo, Wei-Qiang;Li, Liang-Zhi;He, Zhuo-Yang;Zhang, Qi;Liu, Jia;Hu, Cui-Ying;Qin, Fen-Ju;Wang, Tao-Yun 6363
Atractylis lancea (Thunb.) DC. (AL), an important medicinal herb in Asia, has been shown to have anti-tumor effects on cancer cells, but the involved mechanisms are poorly understood. This study focused on potential effects and molecular mechanisms of AL on the proliferation of the Hep-G2 liver cancer cell line in vitro. Cell viability was assessed by MTT test in Hep-G2 cells incubated with an ethanol extract of AL. Then, the effects of AL on apoptosis and cell cycle progression were determined by flow cytometry. Telomeric repeat amplification protocol (TRAP) assays was performed to investigate telomerase activity. The mRNA and protein expression of human telomerase reverse transcriptase (hTERT) and c-myc were determined by real-time RT-PCR and Western blotting. Our results show that AL effectively inhibits proliferation in Hep-G2 cells in a concentrationand time-dependent manner. When Hep-G2 cells were treated with AL after 48h,the$IC_{50}$ was about 72.1${\mu}g/mL$ . Apoptosis was induced by AL via arresting the cells in the G1 phase. Furthermore, AL effectively reduced telomerase activity through inhibition of mRNA and protein expression of hTERT and c-myc. Hence, these data demonstrate that AL exerts anti-proliferative effects in Hep-G2 cells via down-regulation of the c-myc/hTERT/telomerase pathway. -
Zare, Ali;Mahmoodi, Mahmood;Mohammad, Kazem;Zeraati, Hojjat;Hosseini, Mostafa;Naieni, Kourosh Holakouie 6369
Background: Gastric cancer is one of the most common causes of cancer deaths all over the world and the most important reason for its high rate of death is its belated diagnosis at advanced stages of the disease. Events occur in patients which are regarded not only as themselves factors affecting patients' survival but also which can be affected by other factors. This study was designed and implemented aiming to identify these events and to investigate factors affecting their occurrence. Materials and Methods: Data from 330 patients with gastric cancer undergoing surgery at the Iran Cancer Institute from 1995-1999 were analyzed. The survival time of these patients was determined after surgery and the effects of various factors including demographic, diagnostic and clinical as well as medical, and post-surgical varuiables on the occurrence of death hazard without relapse, hazard of relapse, and death hazard with a relapse were assessed. Results: The median survival time for these patients was 16.3 months and the 5-year survival rate was 21.6%. Based on the results of multi-state model, age and distant metastases affected relapse whereas disease stage, type and extent of surgery, lymph nodes metastases, and number of renewed treatments affected death hazard without relapse. Moreover, age, type and extent of surgery, number of renewed treatments, and liver metastases were identified as factors affecting death hazard in patients with relapse. Conclusions: Most cancer studies pay heed to factors which have effect on death occurrence, but some events occur which should be taken into consideration to better describe the natural process of the disease and provide researchers with more accurate data. -
Pandith, Arshad Ahmad;Lateef, Adil;Shahnawaz, Sheikh;Hussain, Aashaq;Malla, Tahir Mohiuddin;Azad, Niyaz;Shehjar, Fahim;Salim, Mosin;Shah, Zafar Amin 6375
Background: The glutathione S transferase (GST) family of enzymes plays a vital role in the phase II biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and polymorphisms in GST genes have been associated with cancer susceptibility and prognosis. GSTP1 is associated with risk of various cancers including bladder cancer. A case control study was conducted to determine the genotype distribution of GSTP1 A>G SNP, to elucidate the possible role of this SNP as a risk factor in urinary bladder cancer (UBC) development and to examine its correlation with clinico-pathologic variables inUBC cases. Materials and Methods: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, we tested the genotype distribution of 180 bladder cancer patients in comparison with 210 cancer-free controls from the same geographical region with matched frequency in age and gender. Results: We did not observe significant genotype differences between the control and bladder cancer patients overall with an odds ratio (OR)=1.23 (p>0.05). The rare allele (AG+GG) was found to be present more in cases (28.3%) than in controls (24%), though the association was not significant (p<0.05). However, a significant risk of more than 2-fold was found for the variant allele (AG+GG) with smokers in cases as compared to controls (p>0.05). Conclusions: Thus, it is evident from our study that GSTP1 SNP is not implicated overall in bladder cancer, but that the rare, valine-related allele is connected with higher susceptibility to bladder cancer in smokers and also males. -
Sun, Hua-Jun;Meng, Lin-Yi;Shen, Yang;Zhu, Yi-Zhun;Liu, Hong-Rui 6379
S-benzyl-cysteine (SBC) is a structural analog of S-allylcysteine (SAC), which is one of the major water-soluble compounds in aged garlic extract. In this study, anticancer activities and the underlying mechanisms of SBC action were investigated and compared these with those of SAC using human gastric cancer SGC-7901 cells. SBC significantly suppressed the survival rate of SGC-7901 cells in a concentration- and time-dependent manner, and the inhibitory activities of SBC were stronger than those of SAC. Flow cytometry revealed that SBC induced G2-phase arrest and apoptosis in SGC-7901 cells. Typical apoptotic morphological changes were observed by Hoechst 33258 dye assay. SBC-treatment dramatically induced the dissipation of mitochondrial membrane potential (${\Delta}{\Psi}m$ ), and enhanced the enzymatic activities of caspase-9 and caspase-3 whilst hardly affecting caspase-8 activity. Furthermore, Western blotting indicated that SBC-induced apoptosis was accompanied by up-regulation of the expression of p53, Bax and the down-regulation of Bcl-2. Taken together, this study suggested that SBC exerts cytotoxic activity involving activation of mitochondrial-dependent apoptosis through p53 and Bax/Bcl-2 pathways in human gastric cancer SGC-7901 cells. -
Honarmand, Marieh;Farhadmollashahi, Leila;Bekyghasemi, Mahmoud 6385
Background: Smokeless tobacco consumption is one of the causes of oral cancer. The aim of this study was to determine the prevalence of smokeless tobacco consumption among male students of Zahedan universities and associated factors in 2012. Materials and Methods: In this cross-sectional study, 431 students were selected from the universities of Zahedan using multi-stage random cluster sampling. The data collection tool was a questionnaire including questions about demographic information, history of smokeless tobacco consumption, and awareness of smokeless tobacco hazards. Data were analyzed by SPSS19 using Chi-square test and multinomial logistic regression, with p<0.05 considered significant. Results: At the time of conducting this study, 102 students (23.7%) had already consumed smokeless tobacco and 49 students (11.4%) were current users (consuming at least once in 30 days before the study). There was a significant relationship between history of smokeless tobacco consumption, university/college, place of living, mean GPA, and mother's education level (p<0.05). Also there was a significant association between knowledge and prevalence of smokeless tobacco use (p<0.001). Conclusions: There is a relatively high prevalence of smokeless tobacco consumption among the male students of universities of Zahedan, which shows the need to emphasize the provision and implementation of prevention programs in universities. -
Coskun, Savas;Can, Huseyin;Turan, Sercan 6389
Background: Cervical cancer is one of the ten most frequent cancers in Turkey. We here examined knowledge about cervical cancer in relation to Papanicolaou (Pap) testing among female primary health care workers in Hatay, a city is located in the south of Turkey. Materials and Methods: The study was completed on 261 women healthcare workers who were or had been sexually active and who accepted to participate to the study. The participants gave verbal informed consent and thereafter questionnaires prepared by the investigators were administered by personal interview. Results: Only 30.3% (n=79) of the participants regularly had a gynecologic examination. While 87.4% (n=228) of the participants reported that they had already heard about the Pap smear test, only 45.2% (n=118) had undergone this test. It was determined that had undergone an average of$1.66{\pm}0.89$ times (1-4) within the last five years. Some 56.0% (n=117) of the participants were well informed about the Pap smear test (p<0,001) and 81.1% (n=63) of the participants who regularly had gynecological examinations (p<0,001) had this test. Conclusions: For the early diagnosis of the cervical cancer, regularly having a Pap smear test is crucial. Healthcare workers should also demonstrate sensitivity about this issue. We think that the importance of the issue should be re-highlighted by organizing in-service training for female primary healthcare workers. Studies are warranted to determine the psychosociological factors that cause individuals to not have the test. -
Li, X.Y.;Wang, M.Y.;Zhang, J.Y.;Li, J.Z.;Gong, J.P.;Zhang, Wei 6393
In this research, we used$GdCl_3$ (gadolinium chloride) to restrain the function of Kupffer cells and assessed effects on hepatocarcinogenesis and metastasis in the Kunming mouse. A 0.25%$GdCl_3$ solution (10 mg/kg b.w.) was infused via the vena caudalis of each mouse 1 week before inoculation of H22 cells and was continued once per three days. Then we observed the follow indexes 3 weeks after injection of H22 cells: tumor weight, histologic characteristics of tumor tissue by light microscopy, ultramicrostructure of Kupffer cells under the electron microscope, distribution and number of Kupffer cells by histochemical staining, and TNF-${\alpha}$ and IFN-${\gamma}$ levels in blood-serum and liver tissue by ELISA and RT-PCR. MMP-2 protein expression was tested by immunohistochemistry. The$GdCl_3$ pretreatment had no effect on the quantity of Kupffer cells, but clearly restrained their functions, with decrease of TNF-${\alpha}$ and IFN-${\gamma}$ levels and elevation of MMP2. Tumor immunity functions were markedly suppressed and tumor growth was accelerated with appearance of metastasis. Furthermore, survival time of trial mice was shortened. -
Ozbas-Gerceker, Filiz;Bozman, Nazli;Kok, Selcuk;Pehlivan, Mustafa;Yilmaz, Mehmet;Pehlivan, Sacide;Oguzkan-Balci, Sibel 6399
Hematological malignancies (HM) are a group of neoplasms derived from the cells of the bone marrow and lymphatic system. Genetic factors leading to susceptibility to HM have been investigated for years but little is known yet. Low molecular weight polypeptide (LMP) 2 and LMP7 genes are important subunits of the immunoproteasome and play significant role in antigen presentation. The polymorphisms of LMP genes have been reported to be risk factors for various types of diseases. The aim of this study was to investigate the association of LMP2 and LMP7 polymorphisms with the occurrence of particular types of HM. A total of 132 patients with HM and 130 control subjects were investigated. No significant difference was obtained in the distribution of genotype and allele frequencies of LMP7 gene in HM patients and the control group. On the other hand, the prevalence of LMP2-AA genotype was found to be higher in acute myeolid leukemia (AML) patients while it was significantly lower in multiple myeloma (MM) cases than in the control subjects. Our results suggested that LMP7 could not be a risk factor for susceptibility to HM, whereas LMP2 polymorphisms could play a role in the development of AML and MM. -
Yang, Liu;Huang, Xin-En;Xu, Lin;Zhou, Jian-Nong;Yu, Dong-Sheng;Zhou, Xin;Li, Dong-Zheng;Guan, Xin 6403
Purpose: Biallelic germline variants of the 8-hydroxyguanine (8-OG) repair gene MYH have been associated with colorectal neoplasms that display somatic$G:C{\rightarrow}T:A$ transversions. However, the effect of single germline variants has not been widely studied, prompting the present investigation of monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC) in a Chinese population. Patients and Methods: Between January 2006 and December 2012, 400 cases of sporadic CRC and 600 age- and sex-matched normal blood donors were screened randomly for 7 potentially pathogenic germline MYH exons using genetic testing technology. Variants of heterozygosity at the MYH locus were assessed in both sporadic cancer patients and healthy controls. Univariate and multivariate analyses were performed to determine risk factors for cancer onset. Results: Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls. The region of exon 1 proved to be a linked polymorphic region for the first time, a triple linked variant including exon 1-316$G{\rightarrow}A$ , exon 1-292$G{\rightarro w}A$ and intron 1+11$C{\rightarrow}T$ , being identified in 13 CRC patients and 2 normal blood donors. A variant of base replacement, intron 10-2$A{\rightarrow}G$ , was identified in the exon 10 region in 21 cases and 7 controls, while a similar type of variant in the exon 13 region, intron 13+12$C{\rightarrow}T$ , was identified in 8 cases and 6 controls. Not the only but a newly missense variant in the present study, p. V463E (Exon 14+74$T{\rightarrow}A$ ), was identified in exon 14 in 6 patients and 1 normal control. In exon 16, nt. 1678-80 del GTT with loss of heterozygosity (LOH) was identified in 27 CRC cases and 26 controls. There was no Y165C in exon 7 or G382D in exon 14, the hot-spot variants which have been reported most frequently in Caucasian studies. After univariate analysis and multivariate analysis, the linked variant in exon 1 region (p=0.002), intron 10-2$A{\rightarrow}G$ (p=0.004) and p. V463E (p=0.036) in the MYH gene were selected as 3 independent risk factors for CRC. Conclusions: According to these results, the linked variant in Exon 1 region, Intron 10-2$A{\rightarrow}G$ of base replacement and p. V463E of missense variant, the 3 heterozygosity variants of MYH gene in a Chinese population, may relate to the susceptibility to sporadic CRC. Lack of the hot-spot variants of Caucasians in the present study may due to the ethnic difference in MYH gene. -
Kong, Feng;Han, Xue-Ying;Luan, Yun;Qi, Tong-Gang;Sun, Chao;Wang, Jue;Hou, Hua-Ying;Jiang, Yu-Hua;Zhao, Jing-Jie;Cheng, Guang-Hui 6411
Adenocarcinoma of esophagus (AE) is a complex disease, affected by a variety of genetic and environmental factors. Much evidence has shown that the MutY glycosylase homologue (MUTYH) plays a key role in the pathogenesis of many cancers. However, there have been no reports on influence on AE in the Han Chinese population. The objective of this study was to investigate this issue. A gene-based association study was conducted using three single nucleotide polymorphisms(SNPs) reported in previous studies. The three SNPs (rs3219463, rs3219472, rs3219489) were genotyped in 207 unrelated AE patients and 249 healthy controls in a case-control study using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results revealed that the genotype distribution of rs3219472 differed between the case and control groups (OR=1.66,95%CI=1.11-2.48, P=0.012), indicating that an association may exist between MUTYH and AE. These findings support a signifcant role for MUTYH in AE pathogenesis in the Han Chinese population. -
Abusail, Mustafa Saadalnour;Dirweesh, Ahmed Mohmed Ahmed;Salih, Rashid Awad Abdalla;Gadelkarim, Ahmed Hussain 6415
Background: The aim of this study was to assess EGFR and p53 expression in head and neck tumors among Sudanese patients using immunohistochemistry. Materials and Methods: A retrospective descriptive study was performed on 150 samples from patients diagnosed with HNCs as well as 50 from individuals with benign head and neck tumors. EGFR and p53 expression was assessed using immunohistochemistry (IHC). Results: EGFR was expressed in 126/150 (84%) of HNCS and 6/50 (12%) benign head and neck tumors where as p53 was expressed in 29/150 (19.3%) of HNCs and 2/50 (4%) of benign head and neck tumors, with significance at p values of 0.001 and 0.009 respectively. Conclusions: There is a significant association between EGFR, P53 expression and head and neck cancers among Sudanese patients. -
Sarkar, Shreya;Maiti, Guru Prasad;Jha, Jayesh;Biswas, Jaydip;Roy, Anup;Roychoudhury, Susanta;Sharp, Tyson;Panda, Chinmay Kumar 6419
Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT. -
Zhang, Jun;Wang, Rui;Ma, Yan-Yun;Chen, Lin-Qi;Jin, Bo-Han;Yu, Hua;Wang, Jiu-Cun;Gao, Chun-Fang;Liu, Jie 6427
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world and deeply threatens people's health, especially in China. Techniques of early diagnosis, prevention and prediction are still being discovered, among which the approaches based on single nucleotide polymorphisms in microRNA genes (miRNA SNPs) are newly proposed and show prospective potential. In particular, the association between SNPs in miRNA196a-2 (rs11614913) and miRNA146a (rs2910164) and HCC has been investigated. However, the conclusions made were conflicting, possibly due to insufficient sample size or population stratification. Further confirmations in well-designed large samples are still required. In this study, we verified the association between these two SNPs and the susceptibility to HCC by MassARRAY assay in a 2,000 large Chinese case-control sample. Significant association between rs11614913 and HCC was confirmed. Subjects with the genotype of CT+TT or T allele in rs11614913 were more resistant to HCC (CT+TT: OR (95% CI)=0.73 (0.57-0.92), P=0.01; T allele: OR (95% CI)=0.85 (0.75-0.97), P=0.02) and HBV-related HCC (CT+TT: OR (95% CI)=0.69 (0.53-0.90), P=0.01; T allele: OR (95% CI)=0.82 (0.71-0.95), P=0.01). The affected carriers of CT or TT also tended to have lower levels of serum AFP (P=0.01). This study demonstrated a role of rs11614913 in the etiology of HCC. Further research should focus on the clinical use of this miRNA SNP, so as to facilitate conquering HCC. -
Liu, Wei-Jun;Ren, Jian-Guo;Li, Ting;Yu, Guo-Zheng;Zhang, Jin;Li, Chang-Sheng;Liu, Zhi-Su;Liu, Quan-Yan 6433
In hepatocellular cancer (HCC), lack of response to chemotherapy and radiation treatment can be caused by a loss of epigenetic modifications of cancer cells. Methionine adenosyltransferase 1A is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation. Therefore, drugs releasing epigenetic repression have been proposed to reverse this process. We studied the effect of the demethylating reagent 5-aza-2'-deoxycitidine (5-Aza-CdR) on MAT1A gene expression, DNA methylation and S-adenosylmethionine (SAMe) production in the HCC cell line Huh7. We found that MAT1A mRNA and protein expression were activated in Huh7 cells with the treatment of 5-Aza-CdR; the status of promoter hypermethylation was reversed. At the same time, MAT2A mRNA and protein expression was significantly reduced in Huh7 cells treated with 5-Aza-CdR, while SAMe production was significantly induced. However, 5-Aza-CdR showed no effects on MAT2A methylation. Furthermore, 5-Aza-CdR inhibited the growth of Huh7 cells and induced apoptosis and through down-regulation of Bcl-2, up-regulation of Bax and caspase-3. Our observations suggest that 5-Aza-CdR exerts its anti-tumor effects in Huh7 cells through an epigenetic change involving increased expression of the methionine adenosyltransferase 1A gene and induction of S-adenosylmethionine production. -
Zhu, Wen-Wen;Kang, Li;Gao, Ya-Ping;Hei, Yan;Dong, Jie;Liu, Yu;Xiao, Li-Hua;Yang, Guang 6439
Objective: To investigate whether the expression level of valosin-containing protein (VCP) is correlated with the prognosis of primary orbital mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: VCP expression in 58 samples from primary orbital MALT lymphoma patients was determined by immunohistochemisty using monoclonal antibodies. Correlations between VCP expression level and prognosis were clarified by statistical analysis. Results: It was found that the percentage of VCP positive cells in samples of primary orbital MALT lymphoma ranged from 32% to 95%. The samples were divided into two groups (level 1 and level 2) according to the median value (45%) of the percentage of VCP positive cells. It was found that the expression level of VCP was significantly correlated with recurrence (P=0.003) and tumor size (P=0.008). At the same time, the 5-year disease-free and overall survival rate of patients of level 1 was significantly better than that of level 2 (P=0.001; P=0.032). There was no observed correlation between the expression level of VCP and other clinical features. Conclusion: VCP could be a useful marker for predicting the prognosis of primary orbital MALT lymphoma. -
Schoueri-Mychasiw, Nour;McDonald, Paul Wesley 6445
Background: Cervical cancer is the second most common cancer among women worldwide. Failure to prevent cervical cancer is partly due to non-participation in regular screening. It is important to plan and develop screening programs directed towards underscreened women. In order to identify the factors associated with underscreening for cervical cancer among women, this study examined Pap test participation and factors associated with not having a time-appropriate (within 3 years) Pap test among a representative sample of women in Ontario, Canada using Canadian Community Health Survey (CCHS) data. Materials and Methods: Univariate analyses, cross-tabulations, and logistic regression modeling were conducted using cross-sectional data from the 2007-2008 CCHS. Analyses were restricted to 13,549 sexually active women aged 18-69 years old living in Ontario, with no history of hysterectomy. Results: Almost 17% of women reported they had not had a time-appropriate Pap test. Not having a time-appropriate Pap test was associated with being 40-69 years old, single, having low education and income, not having a regular doctor, being of Asian (Chinese, South Asian, other Asian) cultural background, less than excellent health, and being a recent immigrant. Conclusions: Results indicate that disparities still exist in terms of who is participating in cervical cancer screening. It is crucial to develop and implement cervical cancer screening programs that not only target the general population, but also those who are less likely to obtain a Pap tests. -
Lin, Mei-Hsiang;Huang, Sheu-Jen;Shih, Whei-Mei Jean;Wang, Pao-Yu;Lin, Li-Hui;Hsu, Hsiu-Chin 6451
Background and Purpose: Indigenous people who leave their hometowns and move to the city to earn a living became urban aboriginals. During the process of adapting to urban living situations, they may use various coping strategies such as smoking to overcome their stress. Therefore, it is crucial to provide health education including smoking prevention, increasing knowledge regarding of tobacco hazard, self-efficacy of anti-smoking, and adjusting smoking behavior so as to empower their anti-smoking motivation to prevent lung cancer. The purpose of this study was to explore the effectiveness of an anti-smoking program on urban aboriginals in Taiwan. Methods: A quasi-experimental study design with purposeful sampling was employed. A total of 125 aboriginal subjects were recruited from two local churches at Shu Lin area in northern Taiwan. Subjects were divided into an experimental group (n =64 ) and a control group (n = 61). Both took pre-tests in order to set baseline values, and only the experimental group participated for 3-weeks in the anti-smoking program classes. Both groups took post-tests immediately after the intervention in order to evaluate the immediate effects of the teaching program, and a follow-up test was conducted four weeks after the intervention. Data were analyzed using descriptive statistics, one-way ANCOVA, and repeat measure ANCOVA. Results: After controlling for confounding variables, the results showed that there were statistically significant differences in the self-efficacy of anti-smoking and smoking behavior between experimental and control groups in the immediately post-test and the follow-up test (p < 0.05). However, there was no significant differences in the recognition of hazards of smoking at eiter time point. Conclusions and Implications for Practice: The findings of this study revealed that the anti-smoking program effectively improved self-efficacy of anti-smoking, and decreased the smoking behavior in urban aboriginals. They provide useful information as a reference regarding of aboriginal health promotion to health providers. It is imperative that anti-smoking be reinforced for those regular smokers to prevent induction of lung cancer. -
Suh, Mina;Choi, Kui Son;Lee, Yoon Young;Park, Boyoung;Jun, Jae Kwan 6459
We investigated the cancer screening rates for five types of cancer (stomach, liver, colorectal, breast, and cervix uteri) using data from the Korean National Cancer Screening Survey (KNCSS), which is a nationwide, annual cross-sectional survey. The eligible study population included cancer-free men 40 years of age and older and women 30 years of age and older. The lifetime screening rate and screening rate with recommendation were calculated. The lifetime screening rates for gastric, liver, colorectal, breast, and cervical cancers were 77.9%, 69.9%, 65.8%, 82.9%, and 77.1%, respectively. The screening rates with recommendation were 70.9%, 21.5%, 44.7%, 70.9%, and 67.9%, respectively. The most common reason for all types of cancer was "no symptoms", followed by "lack of time" and "fear of the examination procedure". Efforts to facilitate participation in liver and colorectal cancer screening among Korean men and women are needed. -
Lotrean, Lucia Maria;Ailoaiei, Roxana;Torres, Gabriela Mejia 6465
This study aimed to assess body features, and alimentary and lifestyle behavior related to cancer prevention among Romanian adults having relatives with cancer. The study was performed in 2010/2011 in an oncological hospital in Cluj-Napoca, Romania. It involved 320 adults who had relatives with cancer. An anonymous questionnaire was filled in by each participants; their weights and heights were measured and body mass index (BMI) was calculated, 56.6% of the participants having a value higher than 24.9. Almost all subjects ate less than 400g of fruits and vegetables daily and 56% of the participants consumed more than 500 g of red meat weekly. One quarter of the study sample was performing less than 30 minutes of moderate physical activity daily. Some 28.1% of the subjects were smokers. These data call for comprehensive actions to help Romanian cancer patient relatives to respect the recommendations regarding healthy lifestyle promotion and cancer prevention. Health professionals should periodically assess body composition and lifestyle components of adults who have relatives with cancer in order to identify unhealthy behavior and offer them personalized education and counseling. -
Elmahi, Aadil Yousif;Niu, Chao;Li, Wei;Li, Dan;Wang, Guan-Jun;Hao, Shan-Shan;Cui, Jiu-Wei 6469
The aim of this study was to detect the efficiency of arsenic trioxide (ATO) alone or together with bortezomib to inhibit proliferation and induce apoptosis in a multiple myeloma (MM) RPMI 8266 cells. Mechanisms of action were also investigated. RPMI 8266 cells were treated with ATO alone and in combination with bortezomib for 24 hours, and cell viability was assessed by modified MTT. Annexin V-F1TC and PI staining was used to detect the apoptosis rate and cell cycling was investigated by flow cytometry, along with expression of cell surface death receptor-4(DR4) and death receptor-5 (DR5). Western blotting was applied to detect the expression of bcl-2, caspase-3, caspase-8, and caspase-9. As a result, the ATO combined with bortezomib group showed more inhibition of RPMI 8266 cell viability than theATO group. Expression of DR4 and DR5 on the cell surfaces, and the apoptosis rate were increased after treatment by ATO alone or combined with bortezomib. The cells appeared to arrest in G2/M phase after treatment. Expression of bcl-2 was more significantly decreased in the combination group, and that of caspase-3, caspase-8 and caspase-9 was significantly increased as well. Therefore, bortezomib can enhance ATO actions to induce apoptosis in RPMI 8266 cells, with decrease in expression of bcl-2 and increase of caspase-3, caspase-8 and caspase-9 proteins. -
Chen, Szu-Han;Wu, Wen-Jeng;Tu, Hung-Pin;Li, Wei-Ming;Huang, Chun-Nung;Li, Ching-Chia;Lin, Hui-Hui;Ke, Hung-Lung 6475
Objectives: Glutathione S-transferase (GST) isoenzymes play important roles in resistance to cell apoptosis and carcinogenesis. We aimed to establish the relationship between GST expression and the prognosis of upper urinary tract urothelial carcinoma (UTT-UC) in Taiwan. Methods: This study retrospectively reviewed 46 patients with pathologically confirmed UUT-UC at Kaohsiung Medical University Hospital. In each patient, expression of GSTT1 and GSTP1 was compared between urothelial carcinoma and normal urothelial cells by Western blotting. Results: GSTP1 expression in the UUT-UC cells was significantly higher than that in normal urothelial cells (1.6 fold, p<0.001). Expression of GSTT1 was significantly associated with the invasiveness of the carcinoma (p=0.006). Conclusions: In UUT-UC, GSTP1 might be a potential tumor marker, whereas high GSTT1 expression could be used as an indicator of cancer progression. This study is the first to demonstrate potential applications of different GST isoenzymes for biomolecular analysis of UUT-UCs in Taiwan. -
Yang, Bo;Wang, Yi-Qi;Cheng, Ru-Bin;Chen, Jia-Li;Chen, Jin;Jia, Li-Tao;Zhang, Ru-Song 6481
Background: Our previous study demonstrated cytotoxicity of a crude extract from Patrinia heterophylla Bunge (PHEB). In the present study, we aimed to investigate the effects of isovaltrate acetoxyhydrin (IA) isolated from PHEB on the gastric cancer cell SGC-7901, in order to explore a potential treatment for gastric cancer. Methods: MTT assays were employed to determine the effects of IA on cell vitality and proliferation, with monitoring of cell morphology changes and examination of apoptosis with Annexin V-PI staining. Flow cytometry was used to assess cell cycle progression and mitochondrial membrane potential. The activity of caspase 3, 9 was evaluated by spectrophotometry, and the protein levels of Bax, Bcl2 and Cyclin B1 were analyzed with Western blotting of total proteins extracted from cultured cells. Results: The results demonstrated direct toxicity of IA towards SGC-7901 cells. Evidence of apoptosis included blebbing and chromatin condensation. Annexin V-PI assays revealed early apoptosis, involving rapid depolarization of mitochondrial membranes and activity of caspase 3, 9 signaling pathways. Western blotting showed that Bcl2 and Bax proteins was down- and up-regulated, respectively, and cyclin B1 was up-regulated. Cell cycle analysis further indicated that IA could induce G2/M phase arrest in SGC-7901 cells. Conclusions: In conclusion, we believe that IA induces apoptosis of SGC-7901 cells, therefore providing a potential therapeutic agent for treatment of gastric cancer. -
Chen, Yao-Sheng;Xu, Song-Xin;Ding, Yan-Bing;Huang, Xin-En;Deng, Bin;Gao, Xue-Feng;Wu, Da-Cheng 6487
To investigate the cognition of medical professionals when following screening guidelines for colorectal cancer (CRC) and barriers to CRC screening. Between February 2012 and December 2012, an anonymous survey with 19-questions based on several CRC screening guidelines was randomly administered to gastroenterologists, oncologists, general surgeons, and general practitioners in Jiangsu, a developed area in China where the incidence of CRC is relatively high. The average cognitive score was 26.4% among 924 respondents. Gastroenterologists and oncologists had higher scores compared with others (p<0.01 and p<0.01, respectively); doctor of medicine (M.D.) with or without doctor of philosophy (Ph.D.) or holders with bachelor of medical science (BMS) achieved higher scores than other lower degree holders (P<0.05). More importantly, doctors who finished CRC related education in the past year achieved higher scores than the others (p<0.001). The most commonly listed barriers to referring high-risk patients for CRC screening were "anxiety about colonoscopy without anesthesia", "lack of awareness of the current guidelines" and "lack of insurance reimbursement". Lack of cognition was detected among doctors when following CRC screening guidelines for high-risk populations. Educational programs should be recommended to improve their cognition and reduce barriers to CRC screening. -
Bilici, Ahmet;Inanc, Mevlude;Ulas, Arife;Akman, Tulay;Seker, Mesut;Babacan, Nalan Akgul;Inal, Ali;Bal, Oznur;Koral, Lokman;Sevinc, Alper;Tufan, Gulnihal;Elkiran, Emin Tamer;Ustaalioglu, Bala Basak Oven;Yavuzsen, Tugba;Alkis, Necati;Ozkan, Metin;Gumus, Mahmut 6493
Background: Non-epithelial malignant ovarian tumors and clear cell carcinomas, Brenner tumors, transitional cell tumors, and carcinoid tumors of the ovary are rare ovarian tumors (ROTs). In this study, our aim was to determine the clinicopathological features of ROT patients and prognostic factors associated with survival. Materials and Methods: A total of 167 patients with ROT who underwent initial surgery were retrospectively analyzed. Prognostic factors that may influence the survival of patients were evaluated by univariate and multivariate analyses. Results: Of 167 patients, 75 (44.9%) were diagnosed with germ-cell tumors (GCT) and 68 (40.7%) with sex cord-stromal tumors (SCST); the remaining 24 had other rare ovarian histologies. Significant differences were found between ROT groups with respect to age at diagnosis, tumor localization, initial surgery type, tumor size, tumor grade, and FIGO stage. Three-year progression-free survival (PFS) rates and median PFS intervals for patients with other ROT were worse than those of patients with GCT and SCST (41.8% vs 79.6% vs 77.1% and 30.2 vs 72 vs 150 months, respectively; p=0.01). Moreover, the 3-year overall survival (OS) rates and median OS times for patients with both GCT and SCST were better as compared to patients with other ROT, but these differences were not statistically significant (87.7% vs 88.8% vs 73.9% and 170 vs 122 vs 91 months, respectively; p=0.20). In the univariate analysis, tumor localization (p<0.001), FIGO stage (p<0.001), and tumor grade (p=0.04) were significant prognostic factors for PFS. For OS, the univariate analysis indicated that tumor localization (p=0.01), FIGO stage (p=0.001), and recurrence (p<0.001) were important prognostic indicators. Multivariate analysis showed that FIGO stage for PFS (p=0.001, HR: 0.11) and the presence of recurrence (p=0.02, HR: 0.54) for OS were independent prognostic factors. Conclusions: ROTs should be evaluated separately from epithelial ovarian cancers because of their different biological features and natural history. Due to the rarity of these tumors, determination of relevant prognostic factors as a group may help as a guide for more appropriate adjuvant or recurrent therapies for ROTs. -
Liu, Ju;Li, Ni;Chang, Sheng;Xu, Zhi-Jian;Zhang, Kai 6501
To obtain a screening and early detection reference for individuals who have a family history of cancer on the paternal side, we collected and analyzed data from 240 pairs in which both fathers and their children were diagnosed with cancer. Disease categories of fathers and sons were similar to that of the general population of China, whereas daughters were different from general female population with high incidence of breast cancer and gynecological cancer. Sons were more likely than daughters to have the same type of cancer, or to have cancer in the same organ system as their fathers (P < 0.0001). Sons and daughters developed malignant diseases 11 and 16 years earlier than their fathers, respectively (P < 0.0001 for both sons and daughters). Daughters developed malignant diseases 5 years earlier than sons (P < 0.0001). Men with a family history of malignant tumors on the paternal side should be screened for malignancies from the age of 45 years, or 11 years earlier than the age of their fathers' diagnosis, and women should be screened from the age of 40 years, or 16 years earlier than the age at which their fathers were diagnosed with cancer. Lung cancer should be investigated in both men and women, whilst screening should focus on cancer of the digestive system in men and on breast and gynecological cancer (ovary, uterine and cervical cancer) in women. -
Yun, Yu-Xia;Wang, Yan-Ping;Wang, Peng;Cui, Li-Hong;Wang, Kai-Juan;Zhang, Jian-Ying;Dai, Li-Ping 6507
The purpose of this study was to evaluate the associations of CYP1A1 genetic polymorphisms with the risk of developing esophageal cancer (EC). A case-control study was carried out in a Chinese population in which 157 hospital based EC cases and 157 population based healthy controls with 1:1 match by age and sex were included. PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect genotypes in case and control groups. For the CYP1A1 Ile/Val polymorphism, comparing with wild genotype Ile/Ile, both the heterozygote genotype Ile/Val and the combined variant genotype Ile/Val+Val/Val increased the risk of esophageal cancer (OR: 2.05, 95%CI: 1.19-3.54, OR: 1.86, 95%CI: 1.11-3.12). No significant association was found between the CYP1A1 MspI polymorphism and EC. According to analysis of combined genotypes, the TC/AG combined genotype which contained both variant alleles of these two polymorphisms increased the risk of developing EC (OR: 2.12, 95%CI: 1.16-3.85). Our results suggested that genetic polymorphisms of CYP1A1 may increase the susceptibility to EC. -
Cheah, Soon Keat;Lau, Fen Nee;Yusof, Mastura Md;Phua, Vincent Chee Ee 6513
Background: To evaluate the treatment outcome and major late complications of all patients with recurrent nasopharyngeal carcinoma (NPC) treated with intracavitary brachytherapy (ICBT) in Hospital Kuala Lumpur. Materials and Methods: This retrospective study was conducted at the Department of Radiotherapy and Oncology, Hospital Kuala Lumpur, Malaysia. All patients with histologically confirmed recurrent NPC in the absence of distant metastasis treated in the period 1997-2010 were included in this study. These patients were treated with ICBT alone or in combination with external beam radiotherapy (EBRT). Treatment outcomes measured were local recurrence free survival (LRFS), disease free survival (DFS) and overall survival (OS). Results: Thirty three patients were eligible for this study. The median age at recurrence was 56 years with a median time to initial local recurrence of 27 months. Majority of patients were staged as rT1-2 (94%) or rN0 (82%). The proportion of patients categorised as stage III-IV at first local recurrence was only 9%. Twenty one patients received a combination of ICBT and external beam radiotherapy while 12 patients were treated with ICBT alone. Median interval of recurrence post re-irradiation was 32 months (range: 4-110 months). The median LRFS, DFS and OS were 30 months, 29 months and 36 months respectively. The 5 year LRFS, DFS and OS were 44.7%, 38.8% and 28.1% respectively. The N stage at recurrence was found to be a significant prognostic factor for LRFS and DFS after multivariate analysis. Major late complications occurred in 34.9% of our patients. Conclusions: Our study shows ICBT was associated with a reasonable long term outcome in salvaging recurrent NPC although major complications remained a significant problem. The N stage at recurrence was a significant prognostic factor for both LRFS and DFS. -
Yin, Zhi-Hua;Cui, Zhi-Gang;Ren, Yang-Wu;Su, Meng;Ma, Rui;He, Qin-Cheng;Zhou, Bao-Sen 6519
Background: Genetic polymorphisms of TP63 have been suggested to influence susceptibility to lung adenocarcinoma development in East Asian populations. This study aimed to investigate the relationship between common polymorphisms in the TP63 gene and the risk of lung adenocarcinoma, as well as interactions of the polymorphisms with environmental risk factors in Chinese non-smoking females. Methods: A case-control study of 260 cases and 318 controls was conducted. Data concerning demographic and risk factors were obtained for each subject. The genetic polymorphisms were determined by Taqman real-time PCR and statistical analyses were performed using SPSS software. Results: For 10937405, carriers of the CT genotype or at least one T allele (CT/TT) had lower risks of lung adenocarcinoma compared with the homozygous wild CC genotype in Chinese nonsmoking females (adjusted ORs were 0.68 and 0.69, 95%CIs were 0.48-0.97 and 0.50-0.97, P values were 0.033 and 0.030, respectively). Allele comparison showed that the T allele of rs10937405 was associated with a decreased risk of lung adenocarcinoma with an OR of 0.78 (95%CI=0.60-1.01, P=0.059). Our results showed that exposure to cooking oil fumes was associated with increased risk of lung adenocarcinoma in Chinese nonsmoking females (adjusted OR=1.58, 95%CI=1.11-2.25, P=0.011). However, we did not observe a significant interaction of cooking oil fumes and TP63 polymorphisms. Conclusion: TP63 polymorphism might be a genetic susceptibility factor for lung adenocarcinoma in Chinese non-smoking females, but no significant interaction was found with cooking oil fume exposure. -
Washio, Masakazu;Mori, Mitsuru;Mikami, Kazuya;Miki, Tsuneharu;Watanabe, Yoshiyuki;Nakao, Masahiro;Kubo, Tatsuhiko;Suzuki, Koji;Ozasa, Kotaro;Wakai, Kenji;Tamakoshi, Akiko 6523
Background: Cigarette smoking is the largest single recognized cause of human cancers. In Western countries, many epidemiologists have reported risk factors for kidney cancer including smoking. However, little is known about the Japanese population. Materials and Methods: We evaluated the association of smoking with the risk of kidney cancer death in the Japan Collaborative Cohort (JACC) Study. Participants included 46,395 males and 64,190 females. The Cox proportional hazards model was used to determine age-and-sex adjusted relative risks. Results: A total of 62 males and 26 females died from kidney cancer during the follow-up of 707,136 and 1,025,703 person-years, respectively. Heavy smokers (Brinkman index >1200), fondness of fatty foods, hypertension, diabetes mellitus (DM), and obesity were suggested to increase the risk of renal cell carcinoma while walking was suggested to decrease the risk. Even after controlling for age, sex, alcohol drinking and DM, heavy smoking significantly increased the risk. Conclusions: The present study suggests that six factors including smoking may increase and/or reduce the risk of kidney cancer in the Japanese population. Because of the small number of outcomes, however, we did not evaluate these factors after adjusting for all possible confounding factors. Further studies may be needed to confirm the findings in this study. -
Alipour, Sadaf;Omranipour, Ramesh;Jahanzad, Issa;Bagheri, Khojasteh 6529
Background: Breast cancer is mostly the disease of postmenopausal women but very young affected women are seen more than occasionally in developing countries. We reviewed our cases of very young breast cancer in order to help in better understanding of such cases. Materials and Methods: The records of patients 25 years of age or less who had been admitted for breast cancer surgery in the Cancer Institute of Tehran from 1979 to 2012 were reviewed and relevant data were extracted. Results: From 5,265 cases of breast cancer, 62 patients had 25 years of age or less. There were 55 cases of breast adenocarcinoma, all female. More than 78% of the patients had presented with a palpable mass, the family history was positive in 2% of cases, and about 94% of the histologies were invasive ductal carcinoma. Gestational breast cancer constituted 10% of the cancers; another 10%were bilateral. The median size of the tumors was 5.72 centimeters, 63.2% of them had axillary lymphatic involvement, and more than half were negative for hormone receptors. Conclusions: Our study shows an incidence of 1.17% for very young breast cancer and a 10% rate of bilaterality which probably warrants special guidelines for contralateral screening. Cancer stage and features were poor in comparison with breast cancer in all ages. -
Sun, Hong-Gang;Dong, Xue-Jun;Lu, Tao;Yang, Ming-Feng;Wang, Xing-Mu 6533
Background: The purpose of this study was to evaluate a new type of tumor biomarker, eukaryotic elongation factor 2 (eEF2), in serum for the early diagnosis, confirmative diagnosis as well as assessment of treatment of non-small cell lung cancer (NSCLC). Methods: 130 patients with NSCLC and 50 healthy individuals undergoing physical examination in our hospital provided the observation and healthy control groups. An enzyme linked immune sorbent assay (ELISA) method was applied to determine serum eEF2 levels. Serum neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group were assessed with an automatic biochemical analyzer. Results: The median levels of eEF2 in the serum of NSCLC patients was found to be significantly higher than the healthy control group (p < 0.01) and it was markedly higher in stages III, IV than stages I, II (p < 0.05). eEF2 was higher with tumor size${\geq}2$ cm than <2 cm (P< 0.01). Furthermore, two weeks after surgery patients showed a significant trend for eEF2 decrease (p < 0.05). Conclusions: The eukaryotic elongation factor 2 (eEF2) has certain clinical values for early diagnosis, verification, and prognosis as well as classification of lung cancer patients. -
Background: Music therapy is a common complementary and alternative therapy in addition to medical treatment for patients with cancer. If music therapy, which is known has a positive effect on human emotions and behaviors, is a useful additional therapy, it should be more integrated into pyscho-oncology. In this study, we aimed to determine medical oncologist attitudes to music therapy for patients with cancer and knowledge about musicology and music therapy in Turkey. Materials and Methods: This survey study included questions about participant attitudes and knowledge regarding music therapy as well as demographic characteristics. The population of the study were 402 physicians working in medical oncology in Turkey and the sample covered 112 participants in the the survey. For statistical analyses the chi-square test, Fischer exact test, and Mann-Whitney U analysis are applied. Results: In our study the rate for medical oncologists who were interested in music therapy was 28% (n=112). Some 30% (n=34) of medical oncologists recommended music therapy for their patients and 55% (n=61) recommended music therapy to prevent anxiety in patients with cancer. Conclusions: In this study, for more harmony with patients and in order to ensure management of adverse effect, it was concluded that music therapy should be regrded as an additional therapy in oncology clinics.
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Banjerdpongchai, Ratana;Wudtiwai, Benjawan;Sringarm, Korawan 6541
Pigmented rice is mainly black, red, and dark purple, and contains a variety of flavones, tannin, polyphenols, sterols, tocopherols,${\gamma}$ -oryzanols, amino acids, and essential oils. The present study evaluated the cytotoxic effects of purple rice extracts (PREs) combined with chemotherapeutic drugs on human cancer cells and mechanisms of cell death. Methanolic (MeOH) and dichloromethane (DCM) extracts of three cultivars of purple rice in Thailand: Doisaket (DSK), Nan and Payao (PYO), were tested and compared with white rice (KK6). Cytotoxicity was determined by 3-(4, 5-dimethyl)-2, 5-diphenyltetrazolium bromide (MTT) assay in human hepatocellular carcinoma HepG2, prostate cancer LNCaP and murine normal fibroblast NIH3T3 cells. MeOH-PYO-PRE was the most cytotoxic and inhibited HepG2 cell growth more than that of LNCaP cells but was not toxic to NIH3T3 cells. When PREs were combined with paclitaxel or vinblastine, they showed additive cytotoxic effects on HepG2 and LNCaP cells, except for MeOH-PYO-PRE which showed synergistic effects on HepG2 cells when combined with vinblastine. MeOH-PYO-PRE plus vinblastine induced HepG2 cell apoptosis with loss of mitochondrial transmembrane potential (MTP) but no ROS production. MeOH-PYO-PRE-treated HepG2 cells underwent apoptosis via caspase-9 and-3 activation. The level of${\gamma}$ -oryzanol was highest in DCM-PYO-PRE (44.17 mg/g) whereas anthocyanin content was high in MeOH-PYO-PRE (5.80 mg/g). In conclusion, methanolic Payao purple rice extract was mostly toxic to human HepG2 cells and synergistically enhanced the cytotoxicity of vinblastine. Human HepG2 cell apoptosis induced by MeOH-PYO-PRE and vinblastine was mediated through a mitochondrial pathway. -
Liu, Jun;Xu, Chun-Yan;Cai, Shi-Zhong;Zhou, Yue;Li, Jing;Jiang, Rong;Wang, Ya-Ping 6549
Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thus represent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeutic strategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectively inhibited human AML$CD34^+CD38^-$ cell proliferation in vitro culture in a dose-dependent manner while sparing normal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASP exerted cytotoxic effects on AML K562 cells, especially LSC-enriched$CD34^+CD38^-$ cells. Colony formation assays further showed that ASP significantly suppressed the formation of colonies derived from AML$CD34^+CD38^-$ cells but not those from normal$CD34^+CD38^-$ cells. Examination of the underlying mechanisms revealed that ASP induced$CD34^+CD38^-$ cell senescence, which was strongly associated with a series of characteristic events, including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16, P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of these findings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy. -
Xu, Rong;Guo, Long-Jiang;Xin, Jun;Li, Wen-Mao;Gao, Yan;Zheng, You-Xian;Guo, You-Hong;Lin, Yang-Jun;Xie, Yong-Hua;Wu, Ya-Qing;Xu, Rui-An 6557
Objective: Specific promoters could improve efficiency and ensure the safety of gene therapy. The aim of our study was to screen examples for lung cancer. Methods: The firefly luciferase gene was used as a reporter, and promoters based on serum markers of lung cancer were cloned. The activity and specificity of seven promoters, comprising CEACAM5 (carcinoembryonic antigen, CEA), GRP (Gastrin-Releasing Peptide), KRT19 (cytokeratin 19, KRT), SFTPB (surfactant protein B, SP-B), SERPINB3 (Squamous Cell Carcinoma Antigen, SCCA), SELP (Selectin P, Granule Membrane Protein 140kDa, Antigen CD62, GMP) and DKK1 (Dickkopf-1) promoters were compared in lung cancer cells to obtain cancer-specific examples with strong activity. Results: The CEACAM5, DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB promoters were cloned. Furthermore, we successfully constructed recombinant vector pGL-CEACAM5 (DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB) contained the target gene. After cells were transfectedwith recombinant plasmids, we found that the order of promoter activity from high to low was SERPINB3, DKK1, SFTPB, KRT19, CEACAM5, SELP and GRP and the order for promoters regarding specificity and high potential were SERPINB3, DKK1, SELP, SFTPB, CEACAM5, KRT19 and GRP. Conclusion: The approach adopted is feasible to screen for new tumour specific promoters with biomarkers. In addition, the screened lung-specific promoters might have potential for use in lung cancer targeted gene therapy research. -
Jena, Pratap Kumar;Kishore, Jugal;Pati, Sanghamitra;Sarkar, Bidyut Kanti;Das, Sagarika 6563
Background: Tobacco use and quit attempts are two key indicators of the Global Adult Tobacco Survey (GATS) that assess quit attempts among current as well as former tobacco users. The relevant data have inherent policy implications for tobacco cessation programme evaluation. This study aimed to review the concepts of quit attempt assessment and quantifying invalid responses considering GATS-India data. Materials and Methods: GATS assessment of tobacco use and quit attempts were examined in the current literature. Two categories of invalid responses were identified by stratified analysis of the duration of last quit attempt among current users and duration of abstinence among former users. Category A included absolute invalid responses when time-frame of assessment of current tobacco use and less than former tobacco use were violated. Category B included responses that violated the unit of measurement of time. Results: Current daily use, current less than daily use and former use in GATS were imprecisely defined with overlapping of time-frame of assessment. Overall responses of 3,102 current smokers, 4,036 current smokeless users, 1,904 former smokers and 1,343 former smokeless users were analyzed to quantify invalid responses. Analysis indicated overall 21.2% (category A: 7.32%; category B: 17.7%) and 22.7% (category A: 8.05%; category B: 18.1%) invalid responses among current smokers and smokeless users respectively regarding their duration of last quit attempt. Similarly overall 6.62% (category A: 4.7%; category B: 2.3%) and 10.6% (category A: 8.6%; category B: 3.5%) invalid responses were identified among former smokers and smokeless users respectively regarding their duration of abstinence. Conclusions: High invalid responses for a single assessment are due to the imprecise definition of current use, former use and quit attempt; and failure to utilize opportunity of direct data entry interface use during the survey to validate responses instantly. Redefining tobacco use and quit attempts considering an appropriate timeframe would reduce invalid responses. -
Yu, Qing;Liu, Shan-Ling;Wang, He;Shi, Gang;Yang, Pei;Chen, Xin-Lian 6569
In cervical cancer, one of the most common malignant tumors in women worldwide, miR-126 has been reported to exhibit decreased expression. However, its role in cervical cancer cell proliferation and drug sensitivity has remained relatively unexplored. Here, we compared the expression of miR-126 in cervical cancer tissues (n = 20) with that in normal cervical tissue (n = 20) using quantitative RT-PCR. The viability of Siha cervical cancer cells was further measured by MTT assay after transfection with miR-126 mimic (Siha-miR-126 mimic) or microRNA mimic negative control (Siha-miR mimic NC) and after treatment with various concentrations of bleomycin (BLM). IC50s were calculated, and the survival rates (SRs) of Siha cells were calculated. miR-126 expression in cervical cancer tissue was significantly decreased compared with that in normal cervical tissue (P < 0.01). The relative SRs of Siha-miR-126 mimic cells were also significantly decreased compared with those of Siha-miR mimic NC cells at 24-96 h after transfection. The IC50 of BLM in Siha-miR-126 mimic cells ($50.3{\pm}2.02{\mu}g/mL$ ) was decreased compared with that in Siha-miR mimic NC cells ($70.5{\pm}4.33{\mu}g/mL$ ) at 48 h after transfection (P < 0.05). Finally, the SRs of Siha-miR-126 mimic cells were significantly lower than those of SihamiR mimic NC cells after cultured in medium containing 40${\mu}g/mL$ BLM for 24-96 h (P < 0.05). These results suggest that miR-126 is expressed at low levels in cervical cancer. Upregulation of miR-126 inhibited cervical cancer cell proliferation and enhanced the sensitivity to BLM. Thus, miR-126 may represent a novel approach to cervical cancer treatment. -
Canyilmaz, Emine;Serdar, Lasif;Uslu, Gonca Hanedan;Soydemir, Gulsen;Bahat, Zumrut;Yoney, Adnan 6573
Background: The goal of this retrospective study was to evaluate patient characteristics, treatment modalities and prognostic factors in Turkish patients with pancreatic cancer. Materials and Methods: Between January 1997 and December 2012, 64 patients who presented to the Department of Radiation Oncology, Karadeniz Technical University, Faculty of Medicine with a diagnosis of pancreatic cancer were evaluated. The E/K ratio of the cases was 2.4/1 and the median age was 59.6 (32-80) years, respectively. Some 11 cases (18%) were stage 1, 21 (34.4%) were stage 2, 10 (16.4%) were stage 3, and 19 (31.1%) were metastatic. Results: The mean follow-up time was 15.7 months (0.7-117.5) and loco-regional recurrence was noted in 11 (40.7%) who underwent surgery while metastases were observed in 41 patients (66.1%). The median overall survival (OS) was 11.2 months and the 1, 3 and 5-year OS rates were 41.7%, 9.9% and 7.9% respectively. The median disease-free survival (DFS) was 5.2 month and the1, 2 and 5 year DFS were 22.6%, 7.6% and 3.8% respectively. On univariate analysis, prognostic factors affecting OS included status of the operation (p<0.001), tumor stage (p=0.008), ECOG performance status (p=0.005) and CEA level (p=0.017).On multivariate analysis, prognostic factors affecting survival included status of the operation (p=0.033) and age (p= 0.023). Conclusions: In the current study, age and operation status were independent prognostic factors for overall survival with pancreatic patients. Thus, the patients early diagnosis and treatment ars essential. However, prospective studies with more patients are needed for confirmation. -
Pan, Xiong-Fei;Fei, Man-Dong;Zhang, Kenneth Y.;Fan, Zhen-Lie;Fu, Feng-Huan;Fan, Jin-Hu 6579
Background: With effective early treatments, many breast cancer patients suffer from psychological distress due to adverse effects and lifelong physical disfigurement. Our study aimed to evaluate the psychopathological profile of breast cancer patients in comparison with healthy women and explored demographic correlates. Method: We consecutively enrolled breast cancer patients who came to the hospital for follow-up or rehabilitation care after primary treatment, and healthy female relatives or friends of inpatients in the Cancer Institute of Chinese Academy of Medical Sciences between August 30, 2010 and January 1, 2012. Psychopathological profile was assessed based on the Symptom Checklist-90-R (SCL-90-R) for patients and controls. We compared demographics such as age, ethnicity, education, marriage, and occupation, and incorporated these data plus cancer status for the association with the general SCL-90-R index and scores for 9 major symptom dimensions in multiple regression analysis. Results: We surveyed a total of 291 female breast cancer patients and 531 healthy women. The average age was$55.1{\pm}6.40$ years for breast cancer patients and$43.1{\pm}12.8$ for healthy controls (P<0.01). The mean survival was 5.20 years for cancer patients (range, 0.60-9.90 years). There were statistically significant differences in education, marriage, and occupation between the two groups (P<0.01). General index ($1.45{\pm}0.45$ versus$1.32{\pm}0.37$ ) and 8 dimension scores (excluding anxiety) on SCL-90-R were significantly higher in patients (P<0.05). Multiple regression analysis showed that the breast cancer status was positively correlated with general SCL-90-R index and 6 dimension scores (excluding the anxiety, phobic anxiety and paranoid ideation dimensions) (P<0.05). Regression coefficients ranged from 0.10 (depression) to 0.19 (somatization). Higher interpersonal sensitivity was noticed in single women compared to married women. Conclusions: Chinese patients with breast cancer demonstrate greater psychopathology compared to healthy controls. The breast cancer status is an independent contributing factor to the general psychopathological profile. Breast cancer patients should be given particular counseling and care to alleviate their psychological distress. -
Chiu, Joanne;Tang, Vikki;Leung, Roland;Wong, Hilda;Chu, Kin Wah;Poon, Jensen;Epstein, Richard J.;Yau, Thomas 6585
Background: Although FOLFOX (infusional fluorouracil/leucovorin plus oxaliplatin) is established as a standard chemotherapeutic regimen, the long term efficacy of adjuvant XELOX (oral capecitabine plus intravenous oxaliplatin) in Asian colorectal cancer (CRC) patients remains anecdotal. Moreover, uncertainties persist as to whether pharmacogenetic differences in Asian populations preclude equally tolerable and effective administration of these drugs. Method: One hundred consecutive patients with resected colorectal cancer received adjuvant XELOX (oxaliplatin 130$mg/m^2$ on day 1 plus capecitabine 900$mg/m^2$ twice daily on day 1 to 14 every 3 weeks for 8 cycles) at Queen Mary Hospital, Hong Kong. Endpoints monitored during follow-up were disease-free survival (DFS) and disease recurrence, overall survival (OS) and adverse events (AEs). Results: The median patient age was 56 years, 56% were diagnosed with rectal cancer and 44% with colonic cancer. After a median follow-up of 4.3 years (95% confidence interval, 3.2-4.7), 24 recurrences were confirmed including 13 patients who died due to progressive disease. Four-year DFS was 81% in colon cancer patients and 67% in rectal cancer patients (p=0.06 by log-rank test). For the cohort as a whole, OS was 90% at 3 years and 84% at 5 years. Treatment-related AEs led to early withdrawal in four patients. The commonest non-hematological AEs were neuropathy (91%), hand-foot syndrome (49%) and diarrhea (46%), while the commonest grade 3/4 AEs were neutropenia (11%) and diarrhea (10%). Conclusion: These results confirm the favourable long term survival benefit with good tolerability in using adjuvant XELOX in treating East Asian colorectal cancer patients. -
Hwang, Sang-Hyun;Ryu, Hye-Jung;Kang, Soo Jin;Yun, E. Hwa;Lim, Min Kyung;Kim, Heung Tae;Lee, Jin Soo;Lee, Do-Hoon 6591
Background: Environmental tobacco smoking (ETS) significantly contributes to morbidity and mortality and is a known risk factor for lung cancer development in lifelong nonsmokers. The metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs) have now emerged as leading biomarkers for the study of carcinogen exposure in non-smokers exposed to ETS. Materials and Methods: We carried out our study on NNAL in the urine of non-smokers exposed to ETS and the association between ETS and lung cancer. Subjects were enrolled from 2008-2010. NNAL was analyzed for 74 non-smoking lung cancer and 85 healthy controls. The main objective of this study was to provide an estimate of the risk of lung cancer from exposure to ETS in the Korean population. Results: The mean NNAL concentration in urine was significantly lower in non-smoking patient groups (n=74) than in control groups (n=85) ($4.7{\pm}15.0$ pg/mg,$6.5{\pm}17.9$ pg/mg, respectively, Mann-Whitney U test, p<0.001). Conclusions: The urine NNAL of non-smoking patients with lung cancer was not elevated with regard to the non-smoking control group. This may be due to life-style changes after diagnosis. A prospective study will be needed to evaluate the association of NNAL and non-smoking lung cancer. -
Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl;Pourhasan-Moghaddam, Mohammad;Abhari, Alireza;Dariushnejad, Hassan 6595
Leptin and its receptor are involved in breast carcinogenesis as mitogenic factors. Therefore, they could be considered as targets for breast cancer therapy. Expression of the leptin receptor gene could be modulated by leptin secretion. Silibinin and curcumin are herbal compounds with anti-cancer activity against breast cancer. The aim of this study was to assess their potential to inhibit of expression of the leptin gene and its receptor and leptin secretion. Cytotoxic effects of the two agents on combination on T47D breast cancer cells was investigated by MTT assay test after 24h treatment. With different concentrations the levels of leptin, leptin receptor genes expression were measured by reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. The silibinin and curcumin combination inhibited growth of T47D cells in a dose dependent manner. There were also significant difference between control and treated cells in leptin expression and the quantity of secreted leptin with a relative decrease in leptin receptor expression. In conclusion, these herbal compounds inhibit the expression and secretion of leptin and it could probably be used as drug candidates for breast cancer therapy through leptin targeting in the future. -
Hao, Yu-Xia;Wang, Jun-Ping;Zhao, Long-Feng 6601
Aim: Associations between polymorphisms in miR-146aG>C, miR-196a2C>T and miR-499A>G and risk of HCC, and interaction with HBV infection in a Chinese population, were the target of the present research. Methods: The duplex polymerase-chain-reaction with confronting-two-pair primers (PCR-RFLP) was performed to determine the genotypes of the miR-146aG>C, miR-196a2C>T and miR-499A>G genotypes. Associations of polymorphisms with the risk of HCC were estimated by conditional logistic regression analysis. Results: Drinking, family history of cancer, HBsAg and HCV were risk factors for HCC. Multivariate regression analyses showed that subjects carrying the miR-196a2 CC genotype had significantly increased risk of HCC, with an adjusted OR (95% CI) of 2.18 (1.23-3.80). In addition, cases carrying the miR-196a2 C allele had a 1.64-fold increase in the risk for HCC (95%CI=1.03-2.49). The miR-196a2 CT and TT genotypes greatly significantly increased the risk of HCC in subjects with HBV infection, with adjusted ORs (95% CI) of 2.02 (1.12-3.68) and 2.69 (1.28-5.71), respectively. Conclusion: Our results demonstrate that miR-196a2 CC genotype and C allele have an important role in HCC risk in Chinese, especially in patients with HBV infection. -
Ghiasi, Naghmeh;Habibagahi, Mojtaba;Rosli, Rozita;Ghaderi, Abbas;Yusoff, Khatijah;Hosseini, Ahmad;Abdullah, Syahrilnizam;Jaberipour, Mansooreh 6605
Background: WEE1 is a G2/M checkpoint regulator protein. Various studies have indicated that WEE1 could be a good target for cancer therapy. The main aim of this study was to asssess the tumor suppressive potential of WEE1 silencing in two different breast cancer cell lines, MCF7 which carries the wild-type p53 and MDA-MB468 which contains a mutant type. Materials and Methods: After WEE1 knockdown with specific shRNAs downstream effects on cell viability and cell cycle progression were determined using MTT and flow cytometry analyses, respectively. Real-time PCR and Western blotting were conducted to assess the effect of WEE1 inhibition on the expression of apoptotic (p53) and anti-apoptotic (Bcl2) factors and also a growth marker (VEGF). Results: The results showed that WEE1 inhibition could cause a significant decrease in the viability of both MCF7 and MDA-MB-468 breast cancer cell lines by more than 50%. Interestingly, DNA content assays showed a significant increase in apoptotic cells following WEE1 silencing. WEE1 inhibition also induced upregulation of the apoptotic marker, p53, in breast cancer cells. A significant decrease in the expression of VEGF and Bcl-2 was observed following WEE1 inhibition in both cell lines. Conclusions: In concordance with previous studies, our data showed that WEE1 inhibition could induce G2 arrest abrogation and consequent cell death in breast cancer cells. Moreover, in this study, the observed interactions between the pro- and anti-apoptotic proteins and decrease in the angiogenesis marker expression confirm the susceptibility to apoptosis and validate the tumor suppressive effect of WEE1 inhibition in breast cancer cells. Interestingly, the levels of the sensitivity to WEE1 silencing in breast cancer cells, MCF7 and MDA-MB468, seem to be in concordance with the level of p53 expression. -
Gao, Chang-Ming;Ding, Jian-Hua;Li, Su-Ping;Liu, Yan-Ting;Cao, Hai-Xia;Wu, Jian-Zhong;Tang, Jin-Hai;Tajima, Kazuo 6613
To evaluate the relationship between alcohol drinking, XRCC1 codon 194 and 399 polymorphisms and risk of colorectal cancer, we conducted a case-control study with 315 colorectal cancer cases (105 colon, 210 rectal) and 439 population-based controls in Jiangsu Province of China. The XRCC1 codon 194 and 399 genotypes were identified using polymerase chain reaction and restrictrion fragment length polymorphism methods (PCR-RFLP). A structured questionnaire was used to elicit detailed information. Odds ratios (ORs) were estimated with an unconditional logistic model. In this study no significant differences were observed among the studied groups with regard to the genotype distribution of the XRCC1 codons 194 and 399 and the risk of colorectal cancer did not appear to be significantly influenced by genotype alone, whereas alcohol consumption showed a positive association (P for trend <0.01). When combined effects of XRCC1 polymorphisms and alcohol consumption were analyzed, we found that the 194Trp or 399Gln alleles further increased the colorectal cancer risk due to high alcohol intake. These findings support the conclusion that colorectal cancer susceptibility may be altered by gene-environment interactions. -
Jing, Chang-Wen;Wang, Zhuo;Cao, Hai-Xia;Ma, Rong;Wu, Jian-Zhong 6619
Background:The aim of the research was to explore a cost effective, fast, easy to perform, and sensitive method for epidermal growth factor receptor (EGFR) mutation testing. Methods: High resolution melting analysis (HRM) was introduced to evaluate the efficacy of the analysis for dectecting EGFR mutations in exons 18 to 21 using formalin-fixed paraffin-embedded (FFPE) tissues and plasma free DNA from 120 patients. Results: The total EGFR mutation rate was 37.5% (45/120) detected by direct sequencing. There were 48 mutations in 120 FFPE tissues assessed by HRM. For plasma free DNA, the EGFR mutation rate was 25.8% (31/120). The sensitivity of HRM assays in FFPE samples was 100% by HRM. There was a low false-positive mutation rate but a high false-negative rate in plasma free DNA detected by HRM. Conclusions: Our results show that HRM analysis has the advantage of small tumor sample need. HRM applied with plasma free DNA showed a high false-negative rate but a low false-positive rate. Further research into appropriate methods and analysis needs to be performed before HRM for plasma free DNA could be accepted as an option in diagnostic or screening settings. -
Seifi-Alan, Mahnaz;Shamsi, Roshanak;Ghafouri-Fard, Soudeh;Mirfakhraie, Reza;Zare-Abdollahi, Davood;Movafagh, Abolfazl;Modarressi, Mohammad Hossein;Kazemi, Golnesa;Geranpayeh, Lobat;Najafi-Ashtiani, Mitra 6625
Breast cancer accounts for one third of new cancer cases among women. The need for biomarkers for early detection is the stimulus to researchers to evaluate altered expression of genes in tumours. Cancer-testis (CT) genes are a group with limited expression in normal tissues except testis but up-regulation in a wide variety of cancers. We here evaluated expression of two CT genes named FBXO39 and TDRD4 in 32 invasive ductal carcinoma samples, 10 fibroadenomas and 6 normal breast tissue samples, in addition to two breast cancer cell lines, MCF-7 and MDA-MB-231, by the means of quantitative real time RT-PCR. FBXO39 showed significant up-regulation in invasive ductal carcinoma samples in comparison with normal samples. It also was expressed in both cell lines and after RHOXF1 gene knock down it was down-regulated in MCF-7 but up-regulated in the MDA-MB-231 cell line. TDRD4 was not expressed in the MCF-7 cell line and any of the tissue samples except testis. However, it was expressed in MDA-MB-231 and was up-regulated after RHOXF1 gene knock down. Our results show that FBXO39 but not TDRD4 can be used for cancer detection and if proved to be immunogenic, might be a putative candidate for breast cancer immunotherapy. -
Li, Jie;Xu, Zhi-Wen;Wang, Kun-Hao;Wang, Ning;Li, De-Qiang;Wang, Shang 6631
Through years of effort, researchers have made notable progress in gene and microRNA fields about retinoblastoma morbidity. However, experimentally validated data for genes, microRNAs (miRNAs) and transcription factors (TFs) can only be found in a scattered form, which makes it difficult to conclude the relationship between genes and retinoblastoma systematically. In this study, we regarded genes, miRNAs and TFs as elements in the regulatory network and focused on the relationship between pairs of examples. In this way, we paid attention to all the elements macroscopically, instead of only researching one or several. To show regulatory relationships over genes, miRNAs and TFs clearly, we constructed 3 regulatory networks hierarchically, including a differentially expressed network, a related network and a global network, for analysis of similarities and comparison of differences. After construction of the three networks, important pathways were highlighted. We constructed an upstream and downstream element table of differentially expressed genes and miRNAs, in which we found self-adaption relations and circle-regulation. Our study systematically assessed factors in the pathogenesis of retinoblastoma and provided theoretical foundations for gene therapy researchers. In future studies, especial attention should be paid to the highlighted genes and miRNAs. -
Yuksel, Mehmet Bilgehan;Karakose, Ayhan;Gumus, Bilal;Tarhan, Serdar;Atesci, Yusuf Ziya;Akan, Zafer 6637
Background: To evaluate the results of various types of radiofrequency ablation (RFA) treatment of renal tumors in patients with excessive anesthetic and surgical risk. Materials and Methods: Data for RFA performed in in high risk patients were retrospectively evaluated. Other RFA applications in patients with no anesthetic and/or surgical risk were excluded. RFA was by ultrasound or CT guided percutaneous (USG/CT-PRFA) and retroperitoneally or transperitoneally laparoscopic (R/T-LRFA) techniques under general or local anethesia. Follow-up data of enhanced CT or MRI after 1, 3 and 6 months were analysed for twelve RFA applications. Results: The RFA applications included 4 (40%) left-sided, 5 (50%) right-sided and 1 (10%) bilaterally RFA (simultaneously 1 right and 2 left). The localizations of tumors were 2 (16.6%) upper, 5 (41.6%) mid and 5 (41.6%) lower pole. The RFA applications included 9 (75%) USG-PRFA, 1 (8.3%) CT-PRFA, 1 (8.3%) T-LRFA and 1 (8.3%) R-LRFA. The mean age was$65.3{\pm}8.5$ (52-76) years. The mean tumor size was$29.6{\pm}6.08$ (15-40) mm. No complications related to the RFA were encountered in any of the cases. Failure (residual tumour) was determined in 8.3% (1/12) of USG-RFA application. The success rate was thus 91.7% (11/12). Other 1st, 3rd and 6th months follow-up data revealed no residua and recurrence. Conclusions: RFA application appears to be safe as a less invasive and effective treatment modality in selected cases of small renal tumors in individuals with excessive anesthetic and also surgical risk. -
Ilic, Milena;Vlajinac, Hristina;Marinkovic, Jelena 6643
Background: Despite the fact that breast cancer is the most common female cancer worldwide, more than half of the breast cancer risk factors remained unexplained. The aim of this study was to investigate the association of cigarette smoking with risk of breast cancer. Materials and Methods: A case-control study was conducted in the Clinical Centre of Kragujevac, Serbia, covering 382 participants (191 cases and 191 controls). In the analysis of data logistic regression was used. Results: Breast cancer risk was significantly increased in those who quit smoking at${\leq}50$ years of age (OR=2.72; 95% confidence interval - 95%CI=1.02-7.27) and in those who quit smoking less than 5 years before diagnosis of the disease (OR=4.36; 95%CI=1.12-16.88). When smokers were compared with nonsmokers without passive exposure to smoking, former smoking significantly increased breast cancer risk (OR=2.37; 95%CI=1.07-5.24). Risk for breast cancer was significantly increased in those who quit smoking at${\leq}50$ years of age (OR=3.29; 95%CI=1.17-9.27) and in those who quit smoking less than 5 years before diagnosis of the disease (OR=5.46; 95%CI=1.34-22.28). Conclusions: These data suggest that cigarette smoking is associated with an elevated risk of breast cancer among former smokers in Serbia. -
Song, Bo;Duan, Zhong-Yu;Zhong, Yun-Hua;Lei, Na;Yang, Yu-Qing;Luo, Kai-Yuan 6649
Background: Mdm2 binds to the amino-terminus of p53 to induce its degradation and a single nucleotide polymorphism in the MDM2 promoter region (T309G) has been reported to increase the risk of several carcinomas, such as gastric cancer. However, the results of published studies to analyze the association between MDM2 T309G and gastric cancer havve often conflicted. Methods: To better illustrate the filiation between MDM2 T309G and gastric cancer, we performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the relationship. The pooled ORs were performed for 4 models, additive, recessive, co-dominant model, and dominant. Results: Nine published case-control studies including 3,225 gastric cancer cases and 4,118 controls were identified. The MDM2 T309G polymorphism was associated with a significantly increased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, OR=1.57; 95%CI=1.57-2.12; p=0.003) and GG versus GT/TT, OR=1.52; 95%CI=1.217-1.90; p<0.001). Furthermore, Egger's test did not show any evidence of publication bias (P = 0.608 for GG versus TT). Conclusion: Our results suggest that the MDM2 T309G polymorphism is indeed associated with a significantly increased risk of gastric cancer. -
Kooshyar, Mohammad Mahdi;Ayatollahi, Hossein;Keramati, Mohammad Reza;Sadeghian, Mohammad Hadi;Miri, Mohsen;Sheikhi, Maryam 6653
Background: The single most common proto-oncogene change in human neoplasms is a point mutation in RAS genes. A wide range of variation in frequency of KRAS mutations has been seen in hematologic malignancies. Despite this, RAS roles in leukemogenesis remain unclear. The frequency of KRAS mutations in CML has been reported to be between zero an 10%. Many attempts have been done to develop an anti-RAS drug as a therapeutic target. Materials and Methods: This cross sectional study was performed in Mashhad University of Medical Sciences, Mashhad, Iran from 2010-2012. In 78 CML patients (diagnosed according to WHO 2008 criteria) in chronic or accelerated phases, KRAS mutations in codons 12 and 13 were analyzed using a modified PCR-restriction fragment length polymorphism (RFLP) method. Results: We did not detect any KRAS mutations in this study. Conclusions: KRAS mutations are overall rare in early phase CML and might be secondary events happening late in leukemogenesis cooperating with initial genetic lesions. -
Rokayya, Sami;Li, Chun-Juan;Zhao, Yan;Li, Ying;Sun, Chang-Hao 6657
Background: The objective of this study was to investigate antioxidant and anti-inflammatory activity of cabbage phytochemicals. Materials and Methods: Color coordinates were evaluated by colorimetry, and the antioxidant and anti-inflammatory activities were analyzed by spectrophotometer for some common cabbage varieties. Results: Red heads had the highest total antioxidant contents followed by Savoy, Chinese and green heads. The Chinese variety had the highest ABTS (2,2-azino-di-(3-ethylbenzthiazoline-sulfonic acid) antioxidant activity, was 5.72${\mu}mol$ TE/g fw (Trolox equivalent). The green variety had the highest DPPH (free radical scavenging activity) antioxidant activity, which was 91.2${\mu}mol$ TE/g fw. The red variety had the highest FRAP (ferric reducing antioxidant power) antioxidant activity, which was 80.8${\mu}mol$ TE/g fw. The total phenol amounts were 17.2-32.6 mM trolox equivalent antioxidant capacity (TEAC) and the total flavonoid amounts were 40.0-74.2 mg quercetin per gram. Methanolic extracts of different cabbage heads showed different anti-inflammatory activity values. Chinese, Savoy and green heads had the highest anti-inflammatory activity, while red heads had the lowest. Conclusions: The results suggest that these varieties of cabbage heads could contribute as sources of important antioxidant and anti-inflammatory related to the prevention of chronic diseases associated to oxidative stress, such as in cancer and coronary artery disease. -
Huang, Xin-En;Tian, Guang-Yu;Cao, Jie;Xu, Xia;Lu, Yan-Yan;Wu, Xue-Yan;Liu, Jin;Shi, Lin;Xiang, Jin 6663
Purpose: The current research was conducted to investigate the efficacy and safety of pemetrexed given continuously as a basement agent for first-, second- to third line chemotherapy of patients with metastatic lung adenocarcinoma. Patients and Methods: Patients with metastatic lung adenocarcinoma who were diagnosed in Jiangsu Cancer Hospital and Research Insitute, were enrolled. All received pemetrexed 500$mg/m^2$ (intravenous; on day 1), and another chemotherapieutic agent every 3 weeks until disease progression, or intolerable toxicity. Then the patients were changed to a second line chemotherapy that was still based on pemetrexed 500$mg/m^2$ and another chemotherapeutic agent differing from the first line example, until disease progression, or intolerable toxicity. When third line chemotherapy was needed, pemetrexed 500$mg/m^2$ and another new chemotherapeutic agent were combined until disease progression. Evaluation of efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to NCI Criteria for Adverse Events version 3.0. Results: From January 2010 to September 2013, 15 patients were enrolled. Their median age was 56 years (range 43 to 77 years). Eight patients were male and 7 female. Five patients (33.3%) achieved PR, while 6 patients (40.0%) remained stable, no CR on first line; and 1 PR (7.7%), 5 stable (38.5%) were recorded when pemetrexed was ordered in second line; 5 patients (41.7%) were stable after pemetrexed was combined in third line; no complete response was observed. Main side effects were grade 1 to 2 neutrophil suppression and thrombocytopenia. Other toxicities included elevated transaminase and oral mucositis, but no treatment related death occurred. Conclusions: Pemetrexed continuously as a basement agent from first-, second- to third line chemotherapy is mildly effective in treating patients with metastatic lung adenocarcinoma with tolerable toxicity. -
Pandurangan, Ashok Kumar;Sadagopan, Suresh Kumar Ananda;Dharmalingam, Prakash;Ganapasam, Sudhandiran 6669
Colon cancer (CRC) is a serious health problem throughout the world. Development of novel drugs without side effects for this cancer is crucial. Luteolin (LUT), a bioflavonoid, has many beneficial effects such as antioxidant, anti-inflammatory and anti-proliferative potential. was a potent chemical carcinogen used for the induction of colon cancer. Colon carcinogenesis was initiated by intraperitoneal injection of azoxymethane (AOM) to mice at the dose of 15 mg/body kg weight in Balb/C mice for 3 weeks. Mice were treated with LUT at the dose of 1.2 mg/body kg weight orally. Mitochondrial enzymes such as isocitrate dehydrogenase (ICDH),${\alpha}$ -keto dehydrogenase (${\alpha}$ -KDH), succinate dehydrogenase (SDH) and the activities of respiratory chain enzymes NADH dehydrogenase and cytochrome c oxidase were found to be elevated in AOM-treated animals. Treatment with LUT decreased the activities of all the parameters significantly. Hence, LUT might be a potent anticancer agent against colorectal cancer. -
Hu, Xiao-Qin;Yuan, Ping;Luan, Rong-Sheng;Li, Xiao-Ling;Liu, Wen-Hui;Feng, Fei;Yan, Jin;Yang, Yan-Fang 6673
Objective: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC). Given that CRC and IR physiologically overlap and the calpain-10 gene (CAPN10) is a candidate for IR, we explored the association between CAPN10 and CRC risk. Methods: Blood samples of 400 case-control pairs were genotyped, and the lifestyle and dietary habits of these pairs were recorded and collected. Unconditional logistic regression (LR) was used to assess the effects of CAPN10 SNP43 and SNP19, and environmental factors. Both generalized multifactor dimensionality reduction (GMDR) and the classification and regression tree (CART) were used to test gene-environment interactions for CRC risk. Results: The GA+AA genotype of SNP43 and the Del/Ins+Ins/Ins genotype of SNP19 were marginally related to CRC risk (GA+AA: OR = 1.35, 95% CI = 0.92-1.99; Del/Ins+Ins/Ins: OR = 1.31, 95% CI = 0.84-2.04). Notably, a high-order interaction was consistently identified by GMDR and CART analyses. In GMDR, the four-factor interaction model of SNP43, SNP19, red meat consumption, and smoked meat consumption was the best model, with a maximum cross-validation consistency of 10/10 and testing balance accuracy of 0.61 (P < 0.01). In LR, subjects with high red and smoked meat consumption and two risk genotypes had a 6.17-fold CRC risk (95% CI = 2.44-15.6) relative to that of subjects with low red and smoked meat consumption and null risk genotypes. In CART, individuals with high smoked and red meat consumption, SNP19 Del/Ins+Ins/Ins, and SNP43 GA+AA had higher CRC risk (OR = 4.56, 95%CI = 1.94-10.75) than those with low smoked and red meat consumption. Conclusions: Though the single loci of CAPN10 SNP43 and SNP19 are not enough to significantly increase the CRC susceptibility, the combination of SNP43, SNP19, red meat consumption, and smoked meat consumption is associated with elevated risk. -
Zhang, Xin-Ji;Zhang, Tian-Yi;Yu, Fei-Fei;Wei, Xin;Li, Ye-Sheng;Xu, Feng;Wei, Li-Xin;He, Jia 6681
Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer. -
Yucel, Birsen;Babacan, Nalan Akgul;Kacan, Turgut;Eren, Ayfer Ay;Eren, Mehmet Fuat;Bahar, Seher;Celasun, Mustafa Gurol;Seker, Mehmet Metin;Hasbek, Zekiye 6687
Background: This study aimed to determine the demographical distribution, survival and prognostic factors for neuroendocrine tumors monitored in our clinic. Materials and Methods: Data for 52 patients who were admitted to Cumhuriyet University Medical Faculty Training Research and Practice Hospital Oncology Center between 2006 and 2012 and were diagnosed and treated for neuroendocrine tumors were investigated. Results: Of the total, 30 (58%) were females and 22 (42%) were males. The localization of the disease was gastroenteropancreatic in 29 (56%) patients and other sites in 23 (44%). The most frequently involved organ in the gastroenteropancreatic system was the stomach (n=10, 19%) and the most frequently involved organ in other regions was the lungs (n=10, 19%). No correlation was found between immunohistochemical staining for proteins such as chromogranin A, synaptophysin, and NSE and the grade of the tumor. The patients were followed-up at a median of 24 months (1-90 months). The three-year overall survival rate was 71%: 100% in stage I, 88% in stage II, 80% in stage III, and 40% in stage IV. The three-year survival rate was 78% in tumors localized in the gastroenteropancreatic region, and 54% in tumors localized in other organs. In the univariate analysis, gender, age, performance status of the patients, grade, localization, surgical treatment, and neutrophil/lymphocyte ratio (${\leq}5$ versus >5) affected the prognosis of the patients. Conclusions: Most of the tumors were localized in the gastroenteropancreatic region, and the three-year survival rate in tumors localized in this region was better than the tumors localized in other sites. Surgical treatment was a positive independent prognostic factor, whereas Grade 3 and a neutrophil/lymphocyte ratio of >5 were negative independent prognostic factors. -
Baser, Eralp;Ozgu, Emre;Erkilinc, Selcuk;Yalcin, Hakan;Cetinkaya, Nilufer;Sirvan, Levent;Erkaya, Salim;Gungor, Tayfun 6693
Background: Cold knife conization is a surgical procedure that allows both diagnosis and treatment of cervical lesions at the same time. It is mainly performed for indications of high-grade cervical intraepithelial neoplasia (CIN). In this study, we aimed to investigate the clinical outcome of cases without CIN in cold knife conization specimen, following a high-grade lesion (CIN2/3) in cervical biopsy. Materials and Methods: We performed a retrospective cohort study at a tertiary referral hospital between January$1^{st}$ 2008 and August$1^{st}$ 2012. Cases that underwent cold knife conization for CIN2/3 within the study period were included. Cone-negative (Group 1) and cone-positive (Group 2) cases were analyzed for various clinical parameters, and were compared in the 1-year post-conization period for histological recurrence and human papillomavirus (HPV) DNA status. Results: A total of 173 women underwent cold knife conization for CIN2/3 within the study period. Twenty-two cases (12.7%) were included in Group 1 and 151 cases (87.3%) in Group 2. There were no significant differences between the two groups in terms of age, gravidity, parity, menopausal status and HPV-DNA status (pre-conization and 1 year post-conization) (p>0.05). Recurrence rates were also similar between the groups (9.1% vs 9.9%, p>0.05). Conclusions: Clinical outcomes were similar in terms of histological recurrence and HPV persistence after 1 year of follow-up between cone-negative and cone-positive cases. Clinical follow-up of cone-negative cases should therefore be performed similar to cone-positive cases. -
Ma, Chun-Hua;Jiang, Rong;Li, Jin-Duo;Wang, Bin;Sun, Li-Wei;Lv, Yuan 6697
Objective: To explore the inhibiting effect and mechanism of Endostar injection concomitant with cryoablation on lung adenocarcinoma A549 xenografts in nude mice. Materials and Methods: A total of 24 nude mice with subcutaneous xenografts of the A549 cell line were established and divided into 4 groups when the maximal diameters of tumors became 1 cm: control group, Endostar group, cryoablation group and combination group (Endostar concomitant with cryoablation). The nude mice were sacrificed after 21-days treatment, tumour tissues were removed to measure their volume, in situ test of TdT-mediated dUTP nick end labeling (TUNEL) was adopted to determine the cellular apoptosis around freezing injury zones, and immunohistochemical SP test was applied for the detection of micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression levels. Results: At 21-days after treatment, the growth velocities of control group, Endostar group, cryoablation group and combination group were$236.7{\pm}51.2%$ ,$220.0{\pm}30.6%$ ,$159.5{\pm}29.3%$ and$103.3{\pm}25.5%$ (P<0.01), while cellular apoptosis rates of tumors were$21.7{\pm}2.34%$ , ($22.17{\pm}1.47$ )%,$38.3{\pm}1.37%$ and$49.2{\pm}1.72%$ , (P<0.01), respectively, according to the immunohistochemical test. MVD and VEGF expression levels in the combination group were both lower than in other groups (P<0.01), also being positively related (r=0.925, P<0.01). Conclusions: Endostar can significantly improve the inhibitory effects of cryoablation on xenografts of lung adenocarcinoma A549, and the mechanism is probably associated with its function as an inhibitor of tumour neo-angiogenesis through down-regulating VEGF expression. -
Qin, Ling-Yan;Chen, Xu;Li, Ping;Yang, Zheng;Mo, Wu-Ning 6703
Background: Numerous epidemiological studies have been conducted to evaluate the association between variants of the DNA repair gene XRCC3 and cancer risk. Here we focused on one XRCC3 polymorphism and development of cervical cancer, performing a meta-analysis. Methods: The pooled association between the XRCC3 Thr241Met polymorphism and cervical cancer risk was assessed by odds ratios (ORs) and their 95% confidence intervals (95%CIs). Results: A total of 5 case-control studies met the inclusion criteria. The pooled ORs for the total included studies showed no association among homozygotes TT vs. CC: OR=1.93, 95%CI=0.68-5.49, P=0.22; dominant model TT+TC vs. CC: OR=1.37, 95%CI=0.90-2.06, P=0.14; and recessive model TT vs. TC+CC: OR=1.76, 95%CI=0.68-4.55, P=0.25, but might be a slight risk factor for cervical cancer in heterozygote contrast TT vs. CT: OR= 1.33, 95%CI=1.04-1.71, P=0.02. In subgroup analysis, significant associations were found for Asians under all genetic models. Conclusions: Our meta-analysis suggested the XRCC3 Thr241Met polymorphism might not act as a cervical cancer risk factor overall. However, in subgroup analysis, a significant association was found in Asians under all genetic models. The association should be studied with a larger, stratified population, especially for Asians. -
Fouz, Nour;Amid, Azura;Hashim, Yumi Zuhanis Has-Yun 6709
Background: Breast cancer is a leading cause of death in women. The available chemotherapy drugs have been associated with many side effects. Bromelain has novel medicinal qualities including anti-inflammatory, anti-thrombotic, fibrinolytic and anti-cancer functions. Commercially available bromelain is obtained through tedious methods; therefore, recombinant bromelain may provide a cheaper and simpler choice with similar quality. Materials and Methods: This study aimed to assess the effects of commercial and recombinant bromelain on the cytokinetic behavior of MCF-7 breast cancer cells and their potential as therapeutic alternatives in cancer treatment. Cytotoxic activities of commercial and recombinant bromelain were determined using (sulforhodamine) SRB assay. Next, cell viability assays were conducted to determine effects of commercial and recombinant bromelain on MCF-7 cell cytokinetic behavior. Finally, the established growth kinetic data were used to modify a model that predicts the effects of commercial and recombinant bromelain on MCF-7 cells. Results: Commercial and recombinant bromelain exerted strong effects towards decreasing the cell viability of MCF-7 cells with$IC_{50}$ values of 5.13${\mu}g/mL$ and 6.25${\mu}g/mL$ , respectively, compared to taxol with an$IC_{50}$ value of 0.063${\mu}g/mL$ . The present results indicate that commercial and recombinant bromelain both have anti-proliferative activity, reduced the number of cell generations from 3.92 to 2.81 for commercial bromelain and to 2.86 for recombinant bromelain, while with taxol reduction was to 3.12. Microscopic observation of bromelain-treated MCF-7 cells demonstrated detachment. Inhibition activity was verified with growth rates decreased dynamically from 0.009$h^{-1}$ to 0.0059$h^{-1}$ for commercial bromelain and to 0.0063$h^{-1}$ for recombinant bromelain. Conclusions: Commercial and recombinant bromelain both affect cytokinetics of MCF-7 cells by decreasing cell viability, demonstrating similar strength to taxol. -
Zhang, Su-Jie;Hu, Yi;Cao, Jing;Qian, Hai-Li;Jiao, Shun-Chang;Liu, Zhe-Feng;Tao, Hai-Tao;Han, Lu 6715
Objective: To explore the incidence, clinical characteristics, diagnosis and treatment strategies, prognosis of patients with malignancy-associated hypercalcemia (MAH). Methods: The data of 115 patients with MAH who were treated at the Medical Oncology Department of Chinese PLA General Hospital from Jan., 2001 to Dec., 2010 was retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier method and the Cox proportional hazard model with statistic software SPSS 18.0. Results: The patients had blood calcium levels ranging from 2.77 to 4.87 mmol/L. Except for 9 cases who died or were discharged within 5 days after admission, all other patients recovered to normal blood calcium level after treatment with bisphosphonates or intravenous hydration and diuretics; their survival after occurrence of MAH was from 1 day to 4,051 days, and the median survival time was only 50 days. In the log-rank test, the male, renal metastasis, central nervous system symptoms and hypercalcemia occurring over 140 days after cancer diagnosis were predictors of poor survival (P=0.002, P=0.046, P=0.000, P=0.009). In the COX analysis, being male, central nervous system symptoms and hypercalcemia lasting over 140 days after cancer diagnosis were independent prognostic factors for survival time (RR=2.131, P=0.027; RR=3.054, P=0.002; RR=2.403, P=0.001). According to these factors, a score system was established to predict the patient prognosis and adjust the treatment. Conclusion: Cancer patients with MAH have an extremely poor median survival. Some independent factors indicate poor prognosis, including male gender, central nervous system symptoms and hypercalcemia lasting over 140 days after cancer diagnosis. The prognostic score can serve as a reference for MAH prognosis and treatment, worthy of further investigation. -
Zekri, Abd El-Rahman Nabawy;Nassar, Auhood Abdel-Monem;El-Rouby, Mahmoud Nour El-Din;Shousha, Hend Ibrahim;Barakat, Ahmed Barakat;El-Desouky, Eman Desouky;Zayed, Naglaa Ali;Ahmed, Ola Sayed;Youssef, Amira Salah El-Din;Kaseb, Ahmed Omar;El-Aziz, Ashraf Omar Abd;Bahnassy, Abeer Ahmed 6721
Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer. -
Fayaz, Shima;Karimmirza, Maryam;Tanhaei, Shokoofeh;Fathi, Mozhde;Torbati, Peyman Mohammadi;Fard-Esfahani, Pezhman 6727
Homologous recombination (HR) repair has a crucial role to play in the prevention of chromosomal instability, and it is clear that defects in some HR repair genes are associated with many cancers. To evaluate the potential effect of some HR repair gene polymorphisms with differentiated thyroid carcinoma (DTC), we assessed Rad51 (135G>C), Rad52 (2259C>T), XRCC2 (R188H) and XRCC3 (T241M) polymorphisms in Iranian DTC patients and cancer-free controls. In addition, haplotype analysis and gene combination assessment were carried out. Genotyping of Rad51 (135G>C), Rad52 (2259C>T) and XRCC3 (T241M) polymorphisms was determined by PCR-RFLP and PCR-HRM analysis was carried out to evaluate XRCC2 (R188H). Separately, Rad51, Rad52 and XRCC2 polymorphisms were not shown to be more significant in patients when compared to controls in crude, sex-adjusted and age-adjusted form. However, results indicated a significant difference in XRCC3 genotypes for patients when compared to controls (p value: 0.035). The GCTG haplotype demonstrated a significant difference (p value: 0.047). When compared to the wild type, the combined variant form of Rad52/XRCC2/XRCC3 revealed an elevated risk of DTC (p value: 0.007). It is recommended that Rad52 2259C>T, XRCC2 R188H and XRCC3 T241M polymorphisms should be simultaneously considered as contributing to a polygenic risk of differentiated thyroid carcinoma. -
Zhao, Cheng-Xiao;Liu, Ming;Wang, Jian-Ye;Xu, Yong;Wei, Dong;Yang, Kuo;Yang, Ze 6733
Multiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (PCa). As PCa risk SNPs may also influence disease outcome, we studied here eight 8q24 risk alleles, and evaluated their role in PCa clinical covariates in northern Chinese men. Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=289) and from age-matched normal controls (n=288). Eight 8q24 SNPs were genotyped by polymerase chain reaction-high- resolution melting analysis in 577 subjects. We examined the prevalence distribution of 8q24 risk alleles and analyzed the associations between the risk allele and PCa and clinical covariates to infer their impact on aggressive PCa. Three of the eight SNPs were associated with PCa risk in northern Chinese men, including rs16901966 (OR 1.31, 95% CI 1.01-1.70, p=0.042), rs1447295 (OR 1.47, 95% CI 1.09-1.98, p=0.011) and rs10090154 (OR 1.55, 95% CI 1.14-2.12, p=0.005). Haplotype analysis based association with the risk alleles revealed significant differences between cases and controls (OR 1.43, 95%CI 0.99-2.06, p=0.049). The risk alleles rs16901966, rs1447295 and rs10090154 were associated with age at diagnosis and tumor stage as compared with controls, while rs16901966 was associated with aggressive PCa (OR 1.43, 95% CI 1.01-2.03, p=0.042). The evidence for 8q24 SNPs with PCa risk in northern Chinese men showed rs16901966, rs1447295 and rs10090154 at 8q24 (region 1, region 2) to be strongly associated with PCa and clinical covariates. The three SNPs at 8q24 could be PCa susceptible genetic markers in northern Chinese men. -
Hassan, Zeinab Korany;Elamin, Maha Hussein;Omer, Sawsan Ali;Daghestani, Maha Hassan;Al-Olayan, Ebtesam Salah;Elobeid, Mai AbdelRahman;Virk, Promy 6739
Background: Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. Materials and Methods: p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. Results: Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. Conclusions: Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway. -
Lu, Hong;Chen, Dong;Hu, Li-Ping;Zhou, Lian-Lian;Xu, Hui-Ying;Bai, Yong-Heng;Lin, Xiang-Yang 6743
Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene (ESR-${\alpha}$ ) are associated with breast cancer risk. However, previous results from many molecular studies have been inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-${\alpha}$ gene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms and breast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysis of 24 published studies evaluating the association. No significant associations were found between the PvuII polymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observed among carriers of the XbaI 'G' allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers of the 'A' allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the 'CG' haplotype (OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI 'G' allele was associated with an overall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII 'C' allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an association between the PvuII 'C' and XbaI 'G' alleles and breast cancer risk was significant in Asians ('C' vs. 'T': OR = 0.93, 95% CI = 0.85- 1.00; 'G' vs. 'A': OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, our results provide evidence that ESR-${\alpha}$ polymorphisms are associated with susceptibility to breast cancer. These associations may largely depend on population characteristics and geographic location. -
Zare, Ali;Mahmoodi, Mahmood;Mohammad, Kazem;Zeraati, Hojjat;Hosseini, Mostafa;Naieni, Kourosh Holakouie 6751
Background: Research on cancers with a high rate of mortality such as those occurring in the stomach requires using models which can provide a closer examination of disease processes and provide researchers with more accurate data. Various models have been designed based on this issue and the present study aimed at evaluating such models. Materials and Methods: Data from 330 patients with gastric cancer undergoing surgery at Iran Cancer Institute from 1995 to 1999 were analyzed. Cox-Snell Residuals and Akaike Information Criterion were used to compare parametric and semi-parametric Cox models in modeling transition rates among different states of a multi-state model. R 2.15.1 software was used for all data analyses. Results: Analysis of Cox-Snell Residuals and Akaike Information Criterion for all probable transitions among different states revealed that parametric models represented a better fitness. Log-logistic, Gompertz and Log-normal models were good choices for modeling transition rate for relapse hazard (state$1{\rightarrow}state$ 2), death hazard without a relapse (state$1{\rightarrow}state$ 3) and death hazard with a relapse (state$2{\rightarrow}state$ 3), respectively. Conclusions: Although the semi-parametric Cox model is often used by most cancer researchers in modeling transition rates of multistate models, parametric models in similar situations- as they do not need proportional hazards assumption and consider a specific statistical distribution for time to occurrence of next state in case this assumption is not made - are more credible alternatives. -
Zhu, Chun-Yu;Lv, Yan-Ping;Yan, Deng-Feng;Gao, Fu-Lian 6757
Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug-sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells. -
Yaacob, Nik Soriani;Nasir, Rabail;Norazmi, Mohd Nor 6761
The nuclear receptor, peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$ ), is expressed in various cancer cells including breast, prostate, colorectal and cervical examples. An endogenous ligand of$PPAR{\gamma}$ , 15-deoxy-${\Delta}^{12,14}$ prostaglandin$J_2$ (PGJ2), is emerging as a potent anticancer agent but the exact mechanism has not been fully elucidated, especially in breast cancer. The present study compared the anticancer effects of PGJ2 on estrogen receptor alpha ($ER{\alpha}$ )-positive (MCF-7) and$ER{\alpha}$ -negative (MDA-MB-231) human breast cancer cells. Based on the reported signalling cross-talk between$ER{\alpha}$ and$ER{\alpha}$ , the effect of the$ER{\alpha}$ ligand,$17{\beta}$ -estradiol (E2) on the anticancer activities of PGJ2 in both types of cells was also explored. Here we report that PGJ2 inhibited proliferation of both MCF-7 and MDA-MB-231 cells by inducing apoptotic cell death with active involvement of mitochondria. The presence of E2 potentiated PGJ2-induced apoptosis in MCF-7, but not in MDA-MB-231 cells. The$ER{\alpha}$ antagonist, GW9662, failed to block PGJ2-induced activities but potentiated its effects in MCF-7 cells, instead. Interestingly, GW9662 also proved capable of inducing apoptotic cell death. It can be concluded that E2 enhances$ER{\alpha}$ -independent anticancer effects of PGJ2 in the presence of its receptor. -
Jeganathan, Premila Devi;Hairi, Noran N.;Al Sadat, Nabilla;Chinna, Karuthan 6769
Background: Few local studies have explored the process of adverse transition of smoking stages among adolescents. The present investigation aimed to identify adverse transitions prospectively from the early stages till the escalation of the stages after one year. Materials and Methods: Data were collected in two waves from a cohort of 2,552 adolescents aged 12-13 years old studying in 15 secondary schools based in Kinta, Perak. A multistage sampling method was used to select the schools and a self-administered structured questionnaire was applied to help categorize the participants into five different smoking stages. Nonsmokers were divided into never smokers and susceptible never smokers. Ever-smokers were categorized as experimenters, current smokers or ex-smokers. Results: Among the participants 46.8% were Malay, 33.5% Chinese and 17.1% Indians. At baseline, we had 85.3% non-smokers and 14.6% ever smokers. Incidence of adverse transition among all our participants was 24.1%, with a higher value among male participants (16.8%). A higher proportion of susceptible never smokers and experimenters progressed to current smoking stage compared to never smokers. Conclusions: This study highlights the changes and patterns of adverse transition among adolescents. Male adolescents, those who are susceptible to smoking and those who had already tried experimenting with cigarettes have a higher chance of escalating to a higher smoking stage. -
Genc, Rabia Ekti;Sarican, Emine Serap;Turgay, Ayse San;Icke, Sibel;Sari, Dilek;Saydam, Birsen Karaca 6775
Human papilloma virus (HPV) is one of the most common sexually transmitted agents and its infection is the most established cause of cervical cancer. Midwives play a key position in the implementation of cervical cancer. This descriptive study aimed to determine the level of knowledge concerning HPV and HPV vaccination among 268 midwifery students. Data were collected between November 15 and 30, 2011, through a self-reported questionnaire. The mean age of participants was$20.75{\pm}1.60$ . Among all students, 44.4% had heard of HPV, while 40.4% had heard of HPV vaccinatiob. The relationship between the midwifery student knowledge on HPV and HPV vaccine and their current educational year was significant (p=0.001). In conclusion midwifery students have moderate level of knowledge about HPV and its vaccine and relevant information should be included in their teaching curriculum. -
Khan, Nighat Parveen;Pandith, Arshad Ahmad;Yousuf, Adfar;Khan, Nuzhat Shaheen;Khan, Mosin Saleem;Bhat, Imtiyaz Ahmad;Nazir, Zahoor Wani;Wani, Khursheed Alam;Hussain, Mahboob Ul;Mudassar, Syed 6779
Background: The DNA repair gene XRCC1 Arg399Gln gene polymorphism has been found to be implicated in the development of various cancers, including colorectal cancer (CRC), in different populations. We aimed to determine any association of this polymorphism with the risk of CRC in Kashmir. Materials and Methods: A total of 120 confirmed cases of CRC and 146 healthy cancer free controls from the Kashmiri population were included in this study. Genotyping was carried out by the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Results: Genotype frequencies of XRCC1 Arg399Gln observed in controls were 34.2%, 42.5% and 23.3% for GG (Arg/Arg), GA (Arg/Gln), AA( Gln/Gln), respectively, and 28.3%, 66.7% and 5% in cases, with an odds ratio (OR)=5.7 and 95% confidence interval (CI) =2.3-14.1 (p=0.0001). No significant association of Arg399Gln SNP with any clinicopathological parameters of CRC was found. Conclusions: We found the protective role of 399Gln allele against risk to the development of CRC. The XRCC1 heterozygote status appears to be a strong risk factor for CRC development in the Kashmiri population. -
Subramanian, Pathmawathi;Oranye, Nelson Ositadimma;Masri, Azimah Mohd;Taib, Nur Aishah;Ahmad, Nora 6783
Background: Breast cancer is the commonest type of cancer among women, and in Malaysia 50-60% of the new cases are being detected at late stages. Do age, education level, income, ethnicity, relationship with breast cancer patients and knowledge of breast cancer risk factors influence breast screening practices? This study revealed interesting but significant differences. Objectives: To assess the knowledge of breast cancer risk factors and early detection measures among women in a high risk group. Materials and Methods: A cross sectional survey of one hundred and thirty one women relatives of breast cancer patients was carried out. Participants were selected through purposive sampling, during hospital visits. A self-administered questionnaire was used for data collection. Results: The majority of the respondents (71%) had poor knowledge of the risk factors for breast cancer. Income, relationship with a patient and practise of breast cancer screening predicted performance of mammography,$R^2$ =0.467, F=12.568, p<0.0001. Conclusions: The finding shows inadequate knowledge of breast cancer risk factors and poor cancer screening practise among women with family history of breast cancer. Poor knowledge and practise of breast screening are likely to lead to late stage presentation of breast cancer disease. Some important predictors of breast cancer screening behaviour among women with positive family history of breast cancer were identified. An understanding of the strengths and significance of the association between these factors and breast screening behaviour is vital for developing more targeted breast health promotion. -
Apoptotic and cytotoxic activity of plant extracts obtaining from naturally growing Cynara syriaca in Turkey and cultivated C cardunculus against DLD1 colorectal cancer cells was determined. Extracts from wild and cultivated Cynara species were obtained from their vegetative parts and receptacles using hexane and applied with five different dose (0.1-1 mg/ml) as well as apigenin for MTT tests for three time periods (24, 48 and 72 hours). After cells were treated with
$IC_{50}$ doses for each extract total DNA and RNA were isolated for determination of the cause of cell death. From isolated RNAs, cDNA were synthesized and amplification of p21, BCL-2 and BAX gene regions was carried out. Consequently, we found that pro-apoptotic (BAX) gene expression and a cell cycle inhibitor (p21) were induced in the presence of our artichoke extracts. In contrast, anti-apoptotic BCL-2 gene expression was reduced compared to the control group. In addition DNA fragmentation results demonstrated DLD1 cell death via apoptosis. -
Jayakrishnan, Radhakrishnan;Uutela, Antti;Mathew, Aleyamma;Auvinen, Anssi;Mathew, Preethi Sara;Sebastian, Paul 6797
Background: Prevalence of tobacco use is higher in the rural than urban areas of India. Unlike tobacco cessation clinics located in urban areas, community-based smoking cessation intervention has the potential to reach a wider section of the community to assist in smoking cessation in the rural setting. The present study aimed to assess the effectiveness of a cessation intervention in rural Kerala state, India. Materials and Methods: Current daily smoking resident males in the age group 18-60 years from four community development blocks in rural Kerala were randomly allocated to intervention and control groups. The intervention group received multiple approaches in which priority was given to face-to-face interviews and telephone counselling. Initially educational materials on tobacco hazards were distributed. Further, four rounds of counselling sessions were conducted which included a group counselling with a medical camp as well as individual counselling by trained medical social workers. The control group received general awareness training on tobacco hazards along with an anti-tobacco leaflet. Self-reported smoking status was assessed after 6 and 12 months. Factors associated with tobacco cessation were estimated using binomial regression method. Results: Overall prevalence of smoking abstinence was 14.7% in the intervention and 6.8% in the control group (Relative risk: 1.85, 95% CI: 1.05, 3.25). A total of 41.3% subjects in the intervention area and 13.6% in the control area had reduced smoking by 50% or more at the end of 12 months. Lower number of cigarettes/ bidi used, low nicotine dependence and consultation with a doctor for a medical ailment were the statistically significant predictors for smoking cessation. Conclusions: Rigorous approaches for smoking cessation programmes can enhance quit rates in smoking in rural areas of India. -
Melath, Anil;Santhakumar, Gopi Krishnan;Madhavannair, Shyam Sunder;Nedumgottil, Binoy Mathews;Ramanathan, Arvind 6803
Background: Interferon regulatory factor 6 (IRF6) is a transcription factor with distinct and conserved DNA and protein binding domains. Mutations within the protein binding domain have been significantly observed in subjects with orofacial cleft relative to healthy controls. In addition, recent studies have identified loss of expression of IRF6 due to promoter hypermethylation in cutaneous squamous cell carcinomas. Since mutational events occurring within the conserved domains are likely to affect the function of a protein, we investigated whether regions within the IRF6 gene that encodes for the conserved protein binding domain carried mutations in oral squamous cell carcinoma (OSCC). Materials and Methods: Total chromosomal DNA extracted from 32 post surgical OSCC tissue samples were amplified using intronic primers flanking the exon 7 of IRF6 gene, which encodes for the major region of protein binding domain. The PCR amplicons from all the samples were subsequently resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: Sequencing analysis resulted in the identification of a mutation within exon 7 of IRF6 that occurred in heterozygous condition in 9% (3/32) of OSCC samples. The wild type codon TTC at position 252 coding for phenylalanine was found to be mutated to TAC that coded for tyrosine (F252Y). Conclusions: The present study identified for the first time a novel mutation within the conserved protein binding domain of IRF6 gene in tissue samples of subjects with OSCC. -
Kang, Hyun Goo;Kwon, Kyoung Hyun;Lee, In Wook;Jung, Boyoung;Park, Eun-Cheol;Jang, Sung-In 6807
Background: Lung cancer is a major cause of Korean female mortality and is clearly associated with smoking. The Korean National Health and Nutrition Examination Survey (KNHANES IV-2,3), which included both self-reports of smoking and urinary cotinine data, revealed a significant discrepancy between the prevalence of self-reported and biochemically-verified female smokers. The factors associated with accurate self-reporting of current smoking status remain poorly understood, however. Materials and Methods: We assessed the prevalence of smoking in KNHANES using both self-report and urinary cotinine data. Subsequently, using univariate and multivariate tests, we assessed whether age, intensity of smoking, marital status, relationship with cohabitants, education, occupation, residential area, or annual household income were associated with inaccurate self-reporting in Korean females. We also investigated whether the prevalence of inaccurate self-reports changed over the survey period, 2008-2009. Results: The prevalence of self-reported smoking was 47.8% in males and 6.6% in females. By contrast, the prevalence of smoking as assessed by urinary cotinine levels was 52.2% in males and 14.5% in females. Of the 746 females with urinary cotinine levels >50ng/ml, 407 (56.0%) provided inaccurate self-reports. In a multivariate model, age group(40-49: OR 3.54, 95%CI 1.42-8.86, p=0.007; ref :20-29), cotinine intensity(OR 0.999, 95%CI 0.998-0.999, p<0.001), marital status (married but without spouse: OR 0.37, 95%CI 0.15-0.94, p=0.037; ref :never married), relationship with cohabitants (living with a spouse and unmarried child: OR 2.63, 95%CI 1.44-4.80, p=0.002; living with 2 generations except unmarried child: OR 2.53, 95%CI 1.09-5.87, p=0.030; living with${\geq}3$ generations: OR 3.25, 95%CI 1.48-7.10, p=0.003; ref :spouse only) and education(college or higher: OR 2.73, 95%CI 1.04-7.18, p=0.042; ref :elementary or less) were independently associated with inaccurate self-reports. Conclusions: The trend of smoking prevalence of Korean females is likely to decrease. However, an elevated prevalence of inaccurate self-reports by females remains. Factors related to the intensity of smoking and family status appear to influence whether a Korean female provides an accurate self-report when asked about smoking behavior. -
Tripsianis, Gregory;Papadopoulou, Evropi;Romanidis, Konstantinos;Katotomichelakis, Michael;Anagnostopoulos, Kostas;Kontomanolis, Emmanuel;Botaitis, Sotirios;Tentes, Ioannis;Kortsaris, Alexandros 6813
The present study was conducted to investigate the prognostic significance of co-expression patterna of HER-2, IL-6, TNF-a and TGF-${\beta}1$ in breast cancer, by correlating the number of markers with positive expression with clinicopathological characteristics indicative of tumor progression and overall survival. One hundred thirty consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of the above markers were measured by ELISA. Median split was used to subdivide patients with marker positive or negative expression. The presence of${\geq}3$ positive markers was independently associated with extended lymph node (>3) involvement (aOR, 11.94, p=0.001) and lymphovascular invasion (aOR, 12.04, p=0.018), increasing the prognostic significance of each marker considered separately. Additional prognostic information regarding survival was also provided; as the number of positive markers increased, a gradually reduction of survival time was observed. In addition, patients with 4 positive markers had significantly shorter survival (25 vs 39 months, p=0.006) and a more than 4 fold increased risk of death (aHR, 4.35, p=0.003) compared to patients with 3 positive markers. Our findings suggest that the coexpression pattern of these four markers could be used clinically as a useful marker for tumor extension and outcome of breast cancer. -
Ngan, Roger;Wang, Edward;Porter, David;Desai, Jayesh;Prayogo, Nugroho;Devi, Beena;Quek, Richard 6821
Background: Soft-tissue sarcomas require tailored and multidisciplinary treatment and management. However, little is known about how sarcomas are treated and managed throughout the Asia-Pacific region. Materials and Methods: MEDLINE was systematically searched using prespecified criteria. Publications (previous 10 years) that reported tumour characteristics, treatment patterns, survival outcomes, and/or safety outcomes of patients with soft-tissue sarcoma were selected. Exclusion criteria were studies of patients <18 years of age;${\leq}10$ patients; countries other than Australia, Hong Kong, Indonesia, Korea, Malaysia, New Zealand, Philippines, Singapore, Taiwan, or Thailand; >20% benign tumours; sarcomas located in bones or joints; gastrointestinal stromal tumour; Kaposi's sarcoma; or not reporting relevant outcomes. Results: Of the 1,822 publications retrieved, 35 (32 studies) were included. Nearly all patients (98%, 1,992/2,024; 31 studies) were treated with surgery, and more studies used adjuvant radiotherapy than chemotherapy (24 vs 17 studies). Survival outcomes and recurrence rates varied among the studies because of the different histotypes, sites, and disease stages assessed. Only 5 studies reported safety findings. Conclusions: These findings highlight the lack of specific data available about soft-tissue sarcomas in the Asia-Pacific region. Better efforts to understand how the sarcoma is managed and treated will help improve patient outcomes in the region. -
The purpose of this descriptive study was to determine the hopelessness and depression levels of parents of children diagnosed with cancer and undergoing cancer treatment and factors affecting these levels. The study was carried out with parents of 44 children receiving treatment in a paediatric haematology clinic of a university hospital. Data were collected using a survey form, the Beck Hopelessness Scale (BHS) and the Beck Depression Scale (BDS). The mean BDS score of the mothers and fathers was
$18.3{\pm}11.30$ and$15.2{\pm}11.33$ , respectively. The mean BHS score of the mothers was$6.45{\pm}4.40$ , whereas the mean BHS score of the fathers was$5.88{\pm}4.27$ . The results showed that the levels of hopelessness and depression among the mothers were higher than among the fathers (p<0.001). There was a positive relationship between the hopelessness and depression scores of the mothers and the fathers (p<0.05), and the levels of hopelessness and depression scores of the fathers increased as those of the mothers increased. A weak financial situation of the family increased the hopelessness and depression levels of the fathers. The hopelessness and depression levels of the mothers who were supported by their families and relatives were decreased compared to those without such support (p<0.05). The results show that the parents of children with cancer face many psychosocial and spiritual problems. Using simple screening tools, nurses can identify at-risk parents and direct them to support services. We conclude that actively encouraging families to avail themselves of support resources and supporting them financially would positively affect the levels of depression and hopelessness of parents of children with cancer. -
Romeiro-Lopes, Tiara Cristina;Dell'Agnolo, Catia Millene;Rocha-Brischiliari, Sheila Cristina;Gravena, Angela Andreia Franca;de Barros Carvalho, Maria Dalva;Pelloso, Sandra Marisa 6839
This study was conducted to analyze the prevalence of non-performance of mammography, and associated factors, among postmenopausal women. This analytical, exploratory, cross-sectional study, of a domicile population inquiry type, was performed in the municipality of Maringa, Parana, Brazil. A total of 456 women were interviewed, aged 45 to 69 years, who presented with natural menopause and cessation of menstruation for at least twelve months. Statistical associations were found between the non-performance of mammography and schooling of less than seven years, paid employment, sedentary lifestyle, smoking, the non-use of hormone replacement therapy, not having consulted a doctor in the previous year, not having consulted a gynecologist, lacking a family history of breast cancer, not having performed the Papanicolaou test, not having performed clinical breast examination, and not having difficult access to health services. After logistic regression analysis, not performing mammography was associated with reports of a fair or bad health status. The study data revealed factors "responsible" for the non-performance of mammography, and the results should contributing to improvement/enhancement of healthy behaviour of Brazilian women in the post-menopausal phase. -
Abidin, Emilia Zainal;Hashim, Zailina;Semple, Sean 6845
Background: This study was performed to gather data on second-hand smoke (SHS) concentrations in a range of public venues following the implementation of partial Smoke-Free Legislation in Malaysia in 2004. Materials and Methods:$PM_{2.5}$ was measured as a marker of SHS levels in a total of 61 restaurants, entertainment centres, internet caf$\acute{e}$ s and pubs in Kuala Lumpur, Malaysia. Results: Under the current smoke-free laws smoking was prohibited in 42 of the 61 premises. Active smoking was observed in nearly one-third (n=12) of these. For premises where smoking was prohibited and no active smoking observed, the mean (standard deviation) indoor$PM_{2.5}$ concentration was 33.4 (23.8)${\mu}g/m^3$ compared to 187.1 (135.1)${\mu}g/m^3$ in premises where smoking was observed The highest mean$PM_{2.5}$ was observed in pubs [361.5 (199.3)${\mu}g/m^3$ ]. Conclusions: This study provides evidence of high levels of SHS across a range of hospitality venues, including about one-third of those where smoking is prohibited, despite 8 years of smoke-free legislation. Compliance with the legislation appeared to be particularly poor in entertainment centres and internet caf$\acute{e}$ s. Workers and non-smoking patrons continue to be exposed to high concentrations of SHS within the hospitality industry in Malaysia and there is an urgent need for increased enforcement of existing legislation and consideration of more comprehensive laws to protect health. -
Madrigal-Bujaidar, Eduardo;Roaro, Laura Martino;Garcia-Aguirre, Karol;Garcia-Medina, Sandra;Alvarez-Gonzalez, Isela 6851
In the present report we determined the protective capacity of grapefruit juice (GJ) against molecular and cellular damage in azoxymethane (AOM) treated mice. Animals were daily administered GJ orally (0.8, 4.1, and 8.2${\mu}l/g$ ) for seven weeks, as well as intraperitoneally (ip) injected with AOM twice (weeks 2 and 3 of the assay). Control groups administered with water, with the high dose of GJ, and with AOM injected in weeks 2 and 3 were also included. The results showed a significant, dose-dependent protection of GJ on the number of colon aberrant crypts (AC) induced by AOM. The highest inhibitory effect was reached with the highest tested dose of GJ, decreasing ACF by 51% and 43% at weeks 4 and 7 of the assay. Regarding protein and lipid oxidation we also found a dose-dependent decrease caused with GJ in comparison with the increased levels produced by AOM. Therefore, our results established chemopreventive potential for GJ, and suggested effects related to its antioxidant capacity. Finally, we found that the tested agents induced neither micronuclei increase nor alteration in bone marrow cytotoxicity. -
Fouladi, Nasrin;Pourfarzi, Farhad;Mazaheri, Effat;Asl, Hossein Alimohammadi;Rezaie, Minoo;Amani, Fiouz;Nejad, Masumeh Rostam 6857
Background: Breast cancer is the most common cancer in women. All ages are susceptible and more than 90% of the patients can be cured with early diagnosis. Breast self-examination (BSE) and mammography can be useful for this aim. In this study we examined the components of the Champion health belief model to identify if they could predict the intentions of women to perform such screening. Materials and Methods: A total of 380 women aged 30 and above who had referred to health-care centers were assessed for use of breast cancer screening over the past year with a modified health belief model questionnaire. Logistic regression was applied to identify leading independent predictors. Results: In this study 27% of the women performed BSE in the last year but only 6.8% of them used mammography as a way of screening. There were significant differences regarding all components of the model except for perceived severity between women that underwent BSE. over the past year and those that did not. Findings were similar for mammography. Regression analysis revealed that intentions to perform BSE were predicted by perceived self-efficacy and perceived barriers to BSE while intentions to perform mammography were predicted by perceived barriers. Conclusions: This study indicated that self-efficacy can support performance of BSE while perceived barriers are important for not performing both BSE and mammography. Thus we must educate women to increase their self-efficacy and decrease their perceived barriers. -
Yahayo, Waraporn;Supabphol, Athikom;Supabphol, Roongtawan 6863
Phyllanthus emblica (PE) is known to exhibit various pharmacological properties. This study aimed to evaluate the antimetastatic potential of a PE aqueous extract. Cytotoxicity to human fibrosarcoma cells, HT1080, was determined by viability assay using the 3-(4,5-dimethylthiazol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Cell migration and invasion were investigated using chemotaxis chambers containing membranes precoated with collagen IV and Matrigel, respectively. Cell attachment onto normal surfaces of cell culture plates was tested to determine the cell-adhesion capability. The molecular mechanism of antimetastatic activity was assessed by measuring the gene expression of matrix metalloproteinases, MMP2, and MMP9, using reverse transcription-polymerase chain reaction (RT-PCR) assay. The mRNA levels of both genes were significantly down-regulated after pretreatment with PE extract for 5 days. Our findings show the antimetastatic function of PE extract in reducing cell proliferation, migration, invasion, and adhesion in both dose- and time-dependent manners, especially growth arrest with low$IC_{50}$ value. A decrease in the expression of both MMP2 and MMP9 seems to be the cellular mechanism for antimetastasis in this case. There is a high potential to use PE extracts clinically as an optional adjuvant therapeutic drug for therapeutic intervention strategies in cancer therapy or chemoprevention. -
Darakhshan, Sara;Bidmeshkipour, Ali;Khazaei, Mozafar;Rabzia, Arezou;Ghanbari, Ali 6869
Background: Vascular endothelial growth factor and matrix metalloproteinases are two important factors for angiogenesis associated with breast cancer growth and progression. The present study was aimed to examine the effects of tamoxifen and tranilast drugs singly or in combination on proliferation of breast cancer cells and also to evaluate VEGF and MMP-9 expression and VEGF secretion levels. Materials and Methods: Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with tamoxifen and/or tranilast alone or in combination and percentage cell survival and proliferative activity were evaluated using LDH leakage and MTT assays. mRNA expression and protein levels were examined by real-time RT-PCR and ELISA assay, respectively. Results: LDH and MTT assays showed that the combined treatment of tamoxifen and tranilast resulted in a significant decrease in cell viability and cell proliferation compared with tamoxifen or tranilast treatment alone, with significant decrease in VEGF mRNA and protein levels. We also found that tamoxifen as a single agent rarely increased MMP-9 expression. A decrease in MMP-9 expression was seen after treatment with tranilast alone and in the combined treatment MMP-9 mRNA level was decreased. Conclusions: This combination treatment can able to inhibit growth, proliferation and angiogenesis of breast cancer cells. -
Hawari, Feras Ibrahim;Obeidat, Nour Ali;Ayub, Hiba Salem;Dawahrah, Sahar Sattam;Hawari, Saif Feras 6875
Background: Studies evaluating smoking cessation treatment outcomes in cancer patients are scarce, despite smoking cessation importance in cancer care. We sought to add to the literature by evaluating smoking cessation in a challenging group of cancer patients (medium-to-heavy smokers) visiting an out-patient smoking cessation clinic (SCC) in a cancer center in Amman, Jordan. Materials and Methods: Patients smoking >9 cigarettes per day (CPD) and referred to the SCC between June 2009 and May 2012 were studied. Clinic records were reviewed to measure demographic and baseline clinical characteristics, and longitudinal (3-, 6- and 12- month) follow-up by phone/clinic visit was conducted. At each follow-up, patients were asked if they experienced medication side-effects, if they had returned to smoking, and reasons for failing to abstain. Descriptive and multivariable logistic regression analyses were performed. Results: A total of 201 smokers were included in the analysis. The 3-month abstinence was 23.4% and significantly associated with older age, being married, and presenting with lower (${\leq}10ppm$ ) baseline carbon monoxide (CO) levels. On a multivariable level, lower CO levels, a higher income (relative to the lowest income group), being older, and reporting severe dependence (relative to dependence reported as 'somewhat' or 'not') were significant predictors of higher odds of abstinence at three months. Reasons for failing to quit included not being able to handle withdrawal and seeing no value in quitting. Long-term ARs did not reach 7%. Conclusions: In a sample of Jordanian smokers (>9CPD) with cancer and receiving smoking cessation treatment, ARs were low and further declined with time. Results underscore the need for more aggressive patient management and rigorous follow-up during and after smoking cessation treatment, particularly when this takes place in challenging settings. Observed reasons for failure to abstain should be used to tailor counseling practices. -
Dimri, Kislay;Pandey, Awadhesh Kumar;Trehan, Romeeta;Rai, Bhavana;Kumar, Anup 6883
Background: Platinum based concurrent chemo-radiation is the de-facto standard of care in the non-surgical management of locally-advanced head and neck cancer of squamous origin. Three-weekly single agent cisplatin at 100$mg/m^2$ concurrent with radical radiotherapy has demonstrated consistent improvement in loco-regional control and survival. This improvement is however at the cost of considerable hematologic toxicity and poor overall compliance. The routine use of this regime is improbable in developing countries with limited resources. We therefore aimed to determine the safety and efficacy of an alternative regime of weekly cisplatin and concurrent radiotherapy in such patients. Materials and Methods: January-05 and April-12, 188 patients of locally-advanced head and neck cancer of squamous origin were treated with concurrent weekly-cisplatin at$35mg/m^2$ and conventional radiotherapy 60-66Gy/30-33 fractions/5days per week. Results: Overall, 95% patients received planned doses of RT while 74% completed within the stipulated overall treatment time of <50 days. Eighty-two percent received at-least 5 weekly cycles. Grade-III/IV mucositis was seen in 58%/9% respectively, which resulted in mean weight loss of 9.2% from a pre-treatment mean of 54.5 kg. Grade-III hematologic toxicity-0.5%; grade II nephrotoxicity-2.5% and grade III emesis-3% were also seen. Grade-III/IV subcutaneous toxicity-10%/1% and grade-III/IV xerostomia-10%/0% were observed. Complete responses at the primary site, regional nodes and overall disease were seen in 86%, 89% and 83% patients respectively. The median and 5-years disease-free survival were 26 months and 39.4% respectively, while the median and overall survival were 27 months and 41.8% respectively. Conclusions: Weekly-cisplatin at 35$mg/m^2$ when delivered concurrently with conventional radical RT (at-least 66y/33 fractions) in locally-advanced head and neck cancer is well tolerated with minimal hematologic and neprologic toxicity and can be routinely delivered on an out-patient basis. It is an effective alternative to the standard 3-weekly cisplatin especially in the context of developing countries. -
Clinicopathological Features and Survival of Young Turkish Patients with Testicular Germ Cell TumorsOzgun, Alpaslan;Karagoz, Bulent;Tuncel, Tolga;Emirzeoglu, Levent;Celik, Serkan;Bilgi, Oguz 6889
Background: Testicular germ cell tumors (TGCTs) are a relatively common malignancy in young men. The aim of this study was to investigate the clinicopathological features and survival of young Turkish patients with TGCT. Materials and Methods: In this retrospective study, the clinical and pathological characteristics of young Turkish patients with TGCT who were monitored by the Department of Medical Oncology of a military hospital between 2008 and 2013 were investigated. Overall survival data were analyzed. Results: Ninety-six patients were included in the study. The mean age was 26.4 years. Among the patients, 17.7% had seminoma and 43.8% had mixed non-seminomatous germ cell tumors. Some 46.9% were Stage I, 30.2% were Stage II, and 22.9 were Stage III. Of the patients, 83.3% received chemotherapy, 25% underwent retroperitoneal lymph node dissection (RPLND), 3.1% received radiotherapy, and 12.5% were followed-up without treatment. In addition, 18.8% of the patients were administered salvage chemotherapy due to relapse or progression. The 5-year overall survival rate was 90.2% for all patients. The 2-year overall survival rate was 100% for Stage I patients, 94% for Stage II patients, and 70.2% for Stage III patients. The difference between the survival curves of stages was statistically significant (p=0.029). Conclusions: In young Turkish patients with TGCT, good results were obtained with appropriate treatment, most receiving chemotherapy. The prognosis of the disease was good even in the advanced stage. -
Kanda, Hideyuki;Sugaya, Nagisa;Takahashi, Kenzo;Mizushima, Shunsaku;Koyama, Kikuo 6893
Background: During and after the Fukushima nuclear disaster (FND), many parents were concerned about the effects of radiation on the health of their children. Purpose: To clarify the factors that influenced general workers living with children and the effect of child age groups in implementing preventive behaviorsagainst radiation following the FND. Materials and Methods: A descriptive study of preventive behaviors among general workers was carried out 3-5 months after the nuclear disaster. The subjects were 1,394 regular workers, who took part in radiation seminars run by the Fukushima Occupational Health Promotion Center between July and September, 2011. In total, 1,217 responses were submitted, of which 1,110 were eligible for the present study. This anonymous questionnaire survey inquired about the presence and age of children in the household and about radiation preventive behavior implemented after the FND. The contribution of each variable was assessed by logistic regression analysis. Results: General workers in Fukushima who lived with younger children performed more preventive behavior against radiation during and after the FND. In particular, both location-related and daily routines were practiced significantly more frequently (p<0.01) by workers living with a child in the age ranges of 0-6 (8 of 10 items) and 7-12 (5 of 10 items). Conclusions: This is the first study to assess the positive association between living with children by age group and increased preventive behavior against radiation implemented by general workers after the FND. -
Background: Prevalence is a statistic of primary interest in public health. In the absence of good follow-up facilities, it is difficult to assess the complete prevalence of cancer for a given registry area. Objective: An attempt was here made to arrive at complete prevalence including limited duration prevalence with respect to selected sites of cancer for India by fitting appropriate models to 1, 3 and 5 years cancer survival data available for selected population-based registries. Materials and Methods: Survival data, available for the registries of Bhopal, Chennai, Karunagappally, and Mumbai was pooled to generate survival for breast, cervix, ovary, lung, stomach and mouth cancers. With the available data on survival for 1, 3 and 5 years, a model was fitted and the survival curve was extended beyond 5 years (up to 35 years) for each of the selected sites. This helped in generation of survival proportions by single year and thereby survival of cancer cases. With the help of survival proportions available year-wise and the incidence, prevalence figures were arrived for selected cancer sites and for selected periods. Results: The prevalence to incidence ratio (PI ratio) stabilized after a certain duration for all the cancer sites showing that from the knowledge of incidence, the prevalence can be calculated. The stabilized P/I ratios for the cancer sites of breast, cervix, ovary, stomach, lung, mouth and for life time was observed to be 4.90, 5.33, 2.75, 1.40, 1.37, 4.04 and 3.42 respectively. Conclusions: The validity of the model approach to calculate prevalence could be demonstrated with the help of survival data of Barshi registry for cervix cancer, available for the period 1988-2006.
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Afsharfard, Aboulfazl;Mozaffar, Mohammad;Orang, Elahe;Tahmasbpour, Eisa 6905
Background: Breast cancer (BC) is the top cancer among women worldwide and the most frequent malignancy among Iranian women over the past few decades. The increasing trend and high mortality rate of BC in the developing world necessitates studies concentrating on its characteristics in countries in Asia. The current study focused on clinical and histopathological features of BC among Iranian females. Materials and Methods: This retrospective study involved 714 Iranian patients with histopathologically proven BC undergoing resection of primary tumours and axillary clearance. Demographic, clinical and histopathological data were obtained and studied between ten year age groups (${\leq}40$ years, 41-50 years, 51-60 years, 61-70 years, and${\leq}71$ years) in four chronologic phases from 1994-2009. Results: Mean age of patients was$49.4{\pm}13.1$ years. Most of cases (33.2%) were in 41-50 group. Mean size of primary tumors was$3.94{\pm}2.47$ cm and 87.1% of cases had infiltrative ductal carcinoma. Modified radical mastectomy was the most common method of surgery carried out (48.8%). Some 57.1% of tumors were in pT2 and tumor size decreased significantly during the period (p<0.05). The most common BC stage was llla (27%). Lower BC stages (0 and 1) constituted 13.9% of the diagnosed tumors. Our series of patients aged${\leq}40$ had larger tumors (mean$4.73{\pm}3.02$ cm) compared to older age groups (p=0.003). Lower stages (0 and I) were more frequent among the oldest patients while nearly 50% of patients aged${\leq}40$ had tumor stage III. We also observed a significant decreasing trend in the mean LN count (p<0.05) and blood vessel invasion (p=0.023) from younger to older age groups. Conclusions: More aggressive disease for younger age groups, earlier peak incidence age and high rate of advanced BC at the time of diagnosis among Iranian women, were the main findings of this study. -
Kang, Dong Il;Chung, Jae Il;Ha, Hong Koo;Min, Kweonsik;Yoon, Jangho;Kim, Wansuk;Seo, Won Ik;Kang, Pil Moon;Jung, Soo Jin;Kim, Isaac Yi 6913
Background: Although the PSA test has been used in Korea for over 20 years, the incidence of prostate cancer has risen, and the associated mortality has increased about 13-fold over the 20-year period. Also, several investigators have suggested that Asians in America are more likely to present with more advanced prostate cancer than Caucasians. We compared the characteristics of native Koreans and Americans (Caucasians and African-Americans) undergoing radical prostatectomies in Korea and the US. Materials and Methods: Study subjects comprised patients at Korean and US hospitals from 2004 to 2012 who had undergone radical prostatectomies. We compared the characteristics of the subjects, including age, preoperative prostate-specific antigen (PSA) levels, body mass index (BMI), Gleason score, and pathological T stage. Results: In total, 1,159 males (502 Koreans, 657 Americans) were included. The Korean and American patients had mean ages of$67.1{\pm}6.6$ and$59.2{\pm}6.7$ years, respectively. The mean preoperative PSAs were$15.4{\pm}17.9$ and$6.2{\pm}4.6ng/mL$ (p=0.0001) and the mean BMIs were$23.6{\pm}2.6$ and$28.7{\pm}4.4kg/m^2$ (p=0.0001), respectively. Pathological localized prostate cancer represented 71.7% of cases for Koreans and 77.6% for Americans (p=0.07). According to age, Koreans had higher T stages than Americans in their 50s (p=0.021) and higher Gleason scores than Americans in all age groups. According to PSA, Koreans had higher Gleason scores than Americans for PSA >10 ng/mL (p<0.05). According to prostate size and Gleason scores, Koreans had higher PSA values than Americans (p<0.01). Conclusions: These results show that Korean patients have elevated risk of malignant prostate cancers, as indicated by the significantly higher Gleason scores and PSAs, suggesting a need for novel prostate cancer treatment strategies in Korea. -
Kim, Hyoshin;Oh, Jin-Kyoung;Lim, Min Kyung;Jeong, Bo Yoon;Yun, E Hwa;Park, Eun Young 6919
Background: Between 1998-2009 South Korea experienced significant progress in reducing the male smoking rate from 66.3% to 46.9%. As part of a significant government effort in the area of smoking cessation intervention, the Korean government implemented the national "Smoking Cessation Clinics (SCC)" program in 2004. Materials and Methods: Data covered 804,334 adult male smokers participating in SCC program at 253 public health centers between 2006-2009. We examined participant cessation rates with the SCC program, their characteristics and program intervention components using health insurance status as a socioeconomic status (SES) indicator. Multivariate logistic regression analyses were performed correcting for intra-class correlations within public health centers. Results: The overall 6-month quit rate was high (46.8%). Higher odds of smoking cessation were positively associated with higher levels of behavioral counseling sessions, but not nicotine replacement therapy (NRT). Cessation rates were lower for Medicaid participants than for regular health insurance participants. Disadvantaged younger smokers were less likely to participate in the program. Older smokers were more likely to quit regardless of SES. Stress was cited as major reason for failure. Conclusions: SES inequalities across different age groups exist in smoking cessation among Korean adult male smokers. There is a need for intervention programs specifically targeting sub-populations of SES by different age groups. -
Mollazade, Mahdie;Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl;Zarghami, Nosratollah;Nasiri, Marzieh;Jahanban-Esfahlan, Rana;Alibakhshi, Abbas 6925
Background: Despite numerous useful anticancer properties of curcumin, its utility is limited due to its hydrophobic structure. In this study, we investigated the comparative antiproliferative effect of PAMAM encapsulating curcumin with naked curcumin on the T47D breast cancer cell line. Materials and Methods: Cytotoxic effects of PAMAM dendrimers encapsulating curcumin and curcumin alone were investigated by MTT assay. After treating cells with different concentrations of both curcumin alone and curcumin encapsulated for 24h, telomerase activity was determined by TRAP assay. Results: While PAMAM dendrimers encapsulating curcumin had no cytotoxicity on cancer cells, they decreased the$IC_{50}$ for proliferation and also increased the inhibitory effect on telomerase activity. Conclusions: Considering the non-toxicity in addition to effectiveness for enhancing curcumin anticancer properties, dendrimers could be considered good therapeutic vehicles for this hydrophobic agent. -
Khodabandehloo, Mazaher;Hosseini, Weria;Rahmani, Mohammad-Reza;Rezaee, Mohammad-Ali;Hakhamaneshi, Mohammad-Saied;Nikkhoo, Bahram;Jalili, Ali 6929
Background: Multiple etiologies have been hypothesized for prostate cancer, including genetic defects and infectious agents. A recently reported gamaretrovirus, xenotropic murine leukemia virus-related virus (XMRV) has been reported to be detected in prostate cancer. However, this virus has not been detected in similar groups of patients in other studies. Herein, we sought to detect XMRV in prostate cancers and benign controls in Sanandaj, west of Iran. Materials and Methods: In a case-control study, genomic DNA was extracted from formalin fixed and paraffin embedded prostate tissues from a total of 163 Iranian patients. We developed a conventional and a nested PCR assay using primers targeting to an env specific sequence of XMRV. PCR assays were carried out on 63 prostate cancers and 100 benign prostate hyperplasias. Results: Beta-actin sequences were successfully detected in the DNA extracts from all prostate tissues, confirming DNA extraction integrity. We did not detect XMRV in samples either from prostate cancers or benign prostate hyperplasias using XMRV specific primers. Conclusions: We conclude that in our population XMRV does not play a role in genesis of prostate cancer. -
Khunamornpong, Surapan;Lekawanvijit, Suree;Settakorn, Jongkolnee;Sukpan, Kornkanok;Suprasert, Prapaporn;Siriaunkgul, Sumalee 6935
Background: This study aimed to develop a prognostic model in patients with early-stage cervical squamous cell carcinoma based on clinicopathological features, including invasive margin characteristics. Materials and Methods: Clinicopathological features and outcomes of 190 patients with FIGO stage IB-IIA cervical squamous cell carcinoma treated by surgery were collected and analyzed for factors associated with tumor recurrence. In addition to well-recognized pathological risk factors, the pathological characteristics of invasive margin (type of invasive pattern and degree of stromal desmoplasia and peritumoral inflammatory reaction) were also included in the analysis. Multiple scoring models were made by matching different clinicopathological variables and/or different weighting of the score for each variable. The model with the best performance in the prediction of recurrence and decreased survival was selected. Results: The model with the best performance was composed of a combined score of invasive pattern, lymphovascular space invasion (LVSI), and degree of inflammatory reaction and stromal desmoplasia (total score =10). Compared to those with score${\leq}8$ , the patients with score 9-10 had a significantly higher recurrence rate in the overall group (p<0.001) and the subgroup without adjuvant therapy (p<0.001), while the significance was marginal in the subgroup with adjuvant therapy (p=0.069). In addition, the patients with score 9-10 had a higher rate of tumor recurrence at distant sites (p=0.007). The disease-free survival was significantly lower in the patients with score 9-10 than those with score${\leq}8$ among the overall patients (p<0.001), in the subgroup without adjuvant therapy (p<0.001), and the subgroup with adjuvant therapy (p=0.047). Conclusions: In this study, a prognostic model based on a combination of pathological characteristics of invasive margin and LVSI proved to be predictive of tumor recurrence and decreased disease-free survival in patients with early-stage cervical squamous cell carcinoma. -
Budak, Adnan;Gulhan, Ibrahim;Aldemir, Onur Suleyman;Ileri, Alper;Tekin, Emine;Ozeren, Mehmet 6941
Objective: The aim of this study is to investigate the influence of pregnancy on prognosis of thyroid cancer. Methods: A total of 72 patients aged between 15-45 years who underwent total or subtotal thyroidectomy and subsequently radioablation were followed up under suppression. Individuals who had term pregnancies after diagnosis of cancer (group 1, n: 36) and who were non-pregnant (group 2, n:36) were included in the study. Both groups were compared in terms of scintigraphic relapse and metastasis, ultrasonographic relapse, stage change of lympadenopathy at the beginning and at the end of the study. Results: Relapse was detected in 4 out of 36 pregnant patients (11.1%) and in 5 out of 36 non-pregnant patients (13.9%) with no significant difference between groups (p=1.00). Pathologic lymphadenopathy was detected in 2 out of 36 pregnant patients (5.6%) and in 2 out of 36 non-pregnant patients (5.6%) (p=1.00), and metastasis in 3 (8.3%) and in 1 (2.8%), respectively (p=0.61). While stage change was detected in only one pregnant patient (2.8%), and none of the non-pregnant again there was no significant difference (p=1.00). Conclusions: We conclude that pregnancy does not have an influence on prognosis of thyroid cancer. -
Mohammad, Rahmati Yamchi;Somayyeh, Ghareghomi;Gholamreza, Haddadchi;Majid, Mobasseri;Yousef, Rasmi 6945
Background: Diosgenin, a steroidal saponin from a therapeutic herb, fenugreek (Trigonellafoenum-graceum L.), has been recognized to have anticancer properties. Telomerase activity is not detected in typical healthy cells, while in cancer cell telomerase expression is reactivated, therefore providing a promising cancer therapeutic target. Materials and Methods: We studied the inhibitory effect of diosgenin on human telomerase reverse transcriptase gene (hTERT) expression which is critical for telomerase activity. MTT- assays and qRT-PCR analysis were conducted to assess cytotoxicity and hTERT gene expression inhibition effects, respectively. Results: MTT results showed that$IC_{50}$ values for 24, 48 and 72h after treatment were 47, 44 and$43{\mu}M$ , respectively. Culturing cells with diosgenin treatment caused down-regulation of hTERT expression. Discussion: These results show that diosgenin inhibits telomerase activity by down-regulation of hTERT gene expression in the A549 lung cancer cell line. -
Ghasemali, Samaneh;Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl;Tafsiri, Elham;Zarghami, Nosratollah;Rahmati-Yamchi, Mohamad;Alizadeh, Effat;Barkhordari, Amin;Tozihi, Majid;Kordi, Shirafkan 6949
Background: Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in${\beta}$ -cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability.${\beta}$ -Cyclodextrin (${\beta}$ -CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds. Materials and Methods: To test our hypothesis, we prepared${\beta}$ -cyclodextrin-helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay. Results: MTT assay showed that not only${\beta}$ -cyclodextrin has no cytotoxic effect on its own but also it demonstrated that${\beta}$ -cyclodextrin-helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of${\beta}$ -cyclodextrin-helenalin complexes increased. Conclusions:${\beta}$ -Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore,${\beta}$ -cyclodextrin could be superior carrier for this kind of hydrophobic agent. -
Norsa'adah, Bachok;Nurhazalini-Zayani, Che Ghazali Che 6955
The incidence of hepatocellular carcinoma (HCC) is relatively high in Southeast Asia. Globally, HCC has a high fatality rate and short survival. The objectives of this retrospective cohort study were to review the epidemiology and survival of HCC patients at a tertiary centre in north-east of Peninsular Malaysia. Subjects were adult HCC patients diagnosed by histopathology or radio-imaging. Secondary liver carcinoma was excluded. Kaplan Meier and multiple Cox proportional hazard survival analyses were used. Only 210 HCC cases from years 1987-2008, were included in the final analysis. The number of cases was increasing annually. The mean age was 55.0 (SD 13.9) years with male:female ratio of 3.7:1. Approximately 57.6% had positive hepatitis B virus, 2.4% hepatitis C virus, 20% liver cirrhosis and 8.1% chronic liver disease. Only 2.9% had family history and 9.0% had frequently consumed alcohol. Most patients presented with abdominal pain or discomfort and had hepatomegaly, 47.9% had an elevated${\alpha}$ -fetoprotein level of 800 IU/ml or more, 51.9% had multiple tumors and 44.8% involved multiple liver lobes. Approximately 63.3% were in stage 3 and 23.4% in stage 4, and 82.9% did not receive any treatment. The overall median survival time was 1.9 months (95% confidence interval (CI): 1.5, 2.3). The 1-month, 6-month, 1-year and 2-year survival rates were 71.8%, 23.3%, 13.0% and 7.3% respectively. Significant prognostic factors were Malay ethnicity [Adjusted hazard ratio (AHR) 1.6; 95%CI: 1.0, 2.5; p=0.030], no chemotherapy [AHR 1.7; 95%CI: 1.1, 2.5; p=0.017] and Child-Pugh class C [AHR 2.6; 95%CI: 1.4, 4.9; p=0.002]. HCC in our study affected a wide age range, mostly male, in advanced stage of disease, with no treatment and very low survival rates. Primary prevention should be advocated in view of late presentation and difficulty of treatment. Vaccination of hepatitis virus and avoidance of liver toxins are to be encouraged. -
Natphopsuk, Sitakan;Settheetham-Ishida, Wannapa;Pientong, Chamsai;Sinawat, Supat;Yuenyao, Pissamai;Ishida, Takafumi;Settheetham, Dariwan 6961
Human papillomavirus (HPV) is a major cause of cervical cancer. More than 100 HPV genotypes have been identified; however the distribution varies geographically and according to ethnicity. The purpose of this study was to investigate the prevalence and distribution of HPV subtypes among Northeast Thai women. Subjects included 198 cases of SCCA and 198 age-matched, healthy controls. HPV-DNA was amplified by PCR using the consensus primers GP5+/6+ system followed by reverse line blot hybridization genotyping. The prevalence of high-risk HPV infection was 21 (10.1%) and 152 (76.8%) in the controls and in the cases, respectively. High-risk HPV significantly increased the risk for cervical cancer with an OR of 42.4 (95%CI: 22.4-81.4, p<0.001) and an adjusted OR of 40.7-fold (95%CI: 21.5-76.8, p <0.001). HPV-16 was the most prevalent HPV type in the SCCA (56.2%) followed by HPV-58 (17.8%) and HPV-18 (13.6%); whereas HPV-58 (46.4%) was a prominent genotype in the controls followed by HPV-16 (39.3%) and unidentified HPV types (25.0%). These findings indicate that HPV infection remains a critical risk factor for SCCA; particularly, HPV-16, HPV-58 and HPV-18. In order to eradicate cervical cancer, sustained health education, promoted use of prophylactics and a HPV-58 vaccine should be introduced in this region. -
Thakur, Jarnail Singh;Prinja, Shankar;Bhatnagar, Nidhi;Rana, Saroj;Sinha, Dhirendra Narain;Singh, Poonam Khetarpal 6965
Background: Tobacco consumption has been identified as the single biggest cause of inequality in morbidity and mortality. Understanding pattern of socioeconomic equalities in tobacco consumption in India will help in designing targeted public health control measures. Materials and Methods: Nationally representative data from the India Global Adult Tobacco Survey (GATS) conducted in 2009-2010 was analyzed. The survey provided information on 69,030 respondents aged 15 years and above. Data were analyzed according to regions for estimating prevalence of current tobacco consumption (both smoking and smokeless) across wealth quintiles. Multiple logistic regression analysis predicted the impact of socioeconomic determinants on both forms of current tobacco consumption adjusting for other socio-demographic variables. Results: Trends of smoking and smokeless tobacco consumption across wealth quintiles were significant in different regions of India. Higher prevalence of smoking and smokeless tobacco consumption was observed in the medium wealth quintiles. Risk of tobacco consumption among the poorest compared to the richest quintile was 1.6 times higher for smoking and 3.1 times higher for smokeless forms. Declining odds ratios of both forms of tobacco consumption with rising education were visible across regions. Poverty was a strong predictor in north and south Indian region for smoking and in all regions for smokeless tobacco use. Conclusions: Poverty and poor education are strong risk factors for both forms of tobacco consumption in India. Public health policies, therefore, need to be targeted towards the poor and uneducated. -
Hock, Lim Kuang;Ghazali, Sumarni Mohd;Cheong, Kee Chee;Kuay, Lim Kuang;Li, Lim Hui;Ying, Chan Ying;Huey, Tay Chien;Yee, Lai Wai;Ying, Ong Shiau;Yen, Yeo Lay;Abdullah, Norhamimah;Wymen, Seet;Ibrahim, Normala 6971
Background: Smoking among adolescents has been linked to a variety of adverse and long term health consequences. "Susceptibility to smoking" or the lack of cognitive commitment to abstain from smoking is an important predictor of adolescent smoking. In 2008, we conducted a study to determine the psycho-sociological factors associated with susceptibility to smoking among secondary school students in the district of Kota Tinggi, Johor. Materials and Methods: Two thousand seven hundred students were randomly selected by proportional stratified sampling. Analyses on 1,736 non-smoking students revealed that prevalence of adolescents susceptible to smoking was 16.3%. Results: Male gender (aOR=2.05, 95%CI= 1.23-3.39), poor academic achievement (aOR 1.60, 95%CI 1.05-2.44), ever-smoker (aOR 2.17, 95%CI 1.37-3.44) and having a smoking friend (aOR 1.76, 95%CI 1.10-2.83) were associated with susceptibility to smoking, while having the perception that smoking prohibition in school was strictly enforced (aOR 0.55, 95%CI 0.32-0.94), and had never seen friends smoking in a school compound (aOR 0.59, 95%CI 0.37-0.96) were considered protective factors Conclusions: These results indicate that follow-up programmes need to capitalise on the modifiable factors related to susceptibility to smoking by getting all stakeholders to be actively involved to stamp out smoking initiation among adolescents. -
Zargaran, Massoumeh;Jamshidi, Shokoofeh;Eshghyar, Nosratollah;Moghimbeigi, Abbas 6979
Background: Oral lichen planus (OLP) is categorized as premalignant lesion although its malignant potential is a matter of controversy. The objective of this study was to investigate Ki67 expression in OLP, oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). Materials and Methods: Expression of Ki67 was evaluated through immunohistochemistry (IHC) in groups of A (17 cases of epithelial hyperplasia), B (16 cases of OLP), C1 (10 cases of mild epithelial dysplasia), C2 (10 cases of severe epithelial dysplasia), D1 (10 cases of well-differentiated OSCC), and D2 (10 cases of poorly-differentiated OSCC). Results: There was a significant difference in Ki67 expression based on quantitative analysis among the six studied groups as well as group B compared bilaterally with groups C2, D1 and D2 (p< 0.0001). However, there was no significant difference between groups B and C1 or between groups D1 and D2 (p> 0.05). Conclusions: Based on the results of the present study it may not be possible to definitely consider malignant transformation potential for OLP. However, expression of Ki67 was significantly higher in OLP than that of epithelial hyperplasia with no significant difference from that of mild epithelial dysplasia. This should be considered by clinicians to carefully and regularly follow up OLP lesions to detect potential subtle changes at an early stage. -
You, Chang Hoon;Kang, Sungwook;Kwon, Young Dae;Choi, Ji Heon 6985
Background: This study aimed to examine out-of-pocket expenditure for cancer treatments of hospitalized patients and to analyze changing patterns over time. Materials and Methods: This study examined data of all cancer patients receiving inpatient care from two tertiary hospitals from January 2003 to December 2010. Medical expenditures per admission were calculated and classified into those covered and uncovered by the Korean National Health Insurance (NHI) and co-payment. Results: The medical expenditure per admission increased slowly from 3,455 thousand Korean won (KRW) to 4,068 thousand KRW. While expenditures covered by the NHI have increased annually, co-payments have generally decreased. The out-of-pocket expenditure ratio, which means the proportion of uncovered expenditure and co-payment among total medical expenditure dropped sharply from 2005 to 2007 and was maintained at a similar level after 2007. Medical expenditures, NHI coverage, and the out-of-pocket expenditure ratio differed across cancer types. Conclusions: It is necessary to continually monitor the expenditure of uncovered services by the NHI, and to provide policies to reduce this economic burden. In addition, an individual approach considering cancer type-specific characteristics and medical utilization should be provided. -
Khacha-ananda, Supakit;Tragoolpua, Khajornsak;Chantawannakul, Panuwan;Tragoolpua, Yingmanee 6991
Antioxidant activity, total phenolic, total flavonoid compounds and cytotoxicity to cancer cell lines of propolis extracts from two extraction methods were investigated in this study. Propolis was collected from Phayao province and extracted with 70% ethanol using maceration and sonication techniques. The antioxidant activity was evaluated by DPPH assay. Total phenolic and flavonoid compounds were also determined. Moreover, the cytotoxicity of propolis was evaluated using MTT assay. The percentage propolis yield after extraction using maceration (18.1%) was higher than using sonication (15.7%). Nevertheless, antioxidant and flavonoid compounds of the sonication propolis extract were significant greater than using maceration. Propolis extract from sonication showed antioxidant activity by$3.30{\pm}0.15$ mg gallic acid equivalents/g extract. Total phenolic compound was$18.3{\pm}3.30$ mg gallic acid equivalents/g extract and flavonoid compound was$20.49{\pm}0.62$ mg quercetin/g extract. Additionally, propolis extracts from two extraction methods demonstrated the inhibitory effect on proliferation of A549 and HeLa cancer cell lines at 24, 48 and 72 hours in a dose-dependent manner. These results are of interest for the selection of the most appropriate method for preparation of propolis extracts as potential antioxidant and anticancer agents. -
Ahmad, Zubair;Arshad, Huma;Fatima, Saira;Idrees, Romana;Ud-Din, Nasir;Ahmed, Rashida;Ahmed, Arsalan;Memon, Aisha;Minhas, Khurram;Arif, Muhammad;Fatima, Samia;Haroon, Saroona;Pervez, Shahid;Hasan, Sheema;Kayani, Naila 6997
Aim: To present an epidemiological and histological perspective of diseases of the gastrointestinal tract (including liver and biliary tract) at the Section of Histopathology, Department of Pathology, AKUH, Karachi, Pakistan. Materials and Methods: All consecutive endoscopic biopsies and resections between October 1 and December 31, 2012 were included. Results: A total of 2,323 cases were included. Carcinoma was overwhelmingly the commonest diagnosis on esophageal biopsies (69.1%); chronic helicobacter gastritis (45.6%) followed by adenocarcinoma (23.5%) were the commonest diagnoses on gastric biopsies; adenocarcinoma (27.3%) followed by ulcerative colitis (13.1%) were the commonest diagnoses on colonic biopsies; acute appendicitis (59.1%) was the commonest diagnosis on appendicectomy specimens; chronic viral hepatitis (44.8%) followed by hepatocellular carcinoma (23.4%) were the commonest diagnoses on liver biopsies; chronic cholecystitis was the commonest diagnosis (over 89%) on cholecystectomy specimens. Conclusions: Squamous cell carcinoma comprised 88.8% of esophageal cancers. About 67% were in the lower third and 56.5% were moderately differentiated; mean ages 49.8 years for females and 55.8 years for males; 66% cases were from South West Pakistan. Over 67% patients with gastric adenocarcinoma were males; mean ages 59 and 44 years in males and females respectively, about 74% gastric carcinomas were poorly differentiated; and 62.2% were located in the antropyloric region. About 63% patients with colorectal adenocarcinoma were males; mean ages 46.1 and 50.5 years for males and females respectively; tumor grade was moderately differentiated in 54%; over 80% were located in the left colon. In 21.2% appendicectomies, no acute inflammation was found. Acute appendicitis was most common in young people. Hepatitis C (66.3%) was more common than hepatitis B (33.7%); about 78% cases of hepatocellular carcinoma occurred in males; females comprised 76.7% patients with chronic cholecystitis; and 77.8% patients with gall bladder carcinoma. All resection specimens showed advanced cancers. Most cancers occurred after the age of 50 years. -
Atoum, Manar Fayiz;Tanashat, Reem Qasem;Mahmoud, Sameer Al Haj 7007
Background: In the literature, data concerning the relationship between breast cancer and HLA class II gene polymorphisms are limited, so the aim of this study was to determine if HLA-DQB1 and HLA-DRB1 MHC class-II alleles may confer susceptibility or resistance to the disease among Jordanian females. Materials and Methods: This case control study enrolled 56 Royal Hospital breast cancer patients and 60 age matched healthy controls, all of whom provided blood samples (2011-2013). A questionnaire was filled after signing a consent form and DNA was extracted, nucleic acids being amplified for assessment of HLA-DQB1 and HLA-DRB1 alleles by muliplex INNO-LiPA and allele typing carried out by reverse hybridization. Comparison of HLA-DQB1 and HLA-DRB1 allele distributions was carried out with paired t-test and chi-square statistics. Risk factors were assessed by odd ratios with 95% confidence intervals. Results: A significant negative correlation was observed between$HLADQB1^*$ 02 alleles and breast cancers (p=0.013). No significant associations were observed among$HLADQB1^*$ 03, 04, 05 and 06 or among$HLA-DRB1^*$ 01, 03, 04, 07, 08, 10, 11, 13, 14 and 15. Conclusions:$HLADQB1^*$ 02 alleles may provide positive protection against breast tumor risk among Jordanians, but not$HLADQB1^*$ 03, 04, 05 and 06 or$HLA-DRB1^*$ 01, 03, 04, 07, 08, 10, 11, 13, 14 and 15 alleles. -
Kamsa-Ard, Supot;Laopaiboon, Malinee;Luvira, Vor;Bhudhisawasdi, Vajarabhongsa 7011
Background: The liver fluke, Opisthorchis viverrini, and the associated incidence of subsequent cholangiocarcinoma (CCA) are still a public health problem in Thailand, and praziquantel (PZQ) remains the antihelminthic drug of choice for treatment. Evidence in hamsters shows that repeated infection and PZQ treatments could increase the risk of CCA. However, the existing evidence in humans is inconclusive regarding increased risk of CCA with frequency of PZQ intake. Objectives: To investigate the relationship between number of repeated PZQ treatments and CCA in patients with O viverrini infection. Materials and Methods: The reviewed studies were searched in EMBASE, MEDLINE, ProQuest, PubMed and SCOPUS from inception to October, 2012 using prespecified keywords. The risk of bias (ROB) of included studies was independently assessed by two reviewers using a quality scale from the Newcastle-Ottawa Scale (NOS). Risk effect of PZQ was estimated as a pooled odds ratio (OR) with its 95% confidence interval (95%CI) in the random-effects model using DerSimonian and Laird's estimator. Results: Three studies involving 637 patients were included. Based on the random effects model performed in two included studies of 237 patients, the association between PZQ treatments and CCA was not statistical significant with a pooled OR of 1.8 (95%CI; 0.81 to 4.16). Conclusions: The present systematic review and meta-analysis provides inconclusive evidence of risk effect of PZQ on increasing the risk of CCA and significant methodological limitations. Further research is urgently needed to address the shortcomings found in this review, especially the requirement for histological confirmation. -
Lotrean, Lucia Maria;Loghin, Cornel Radu;Popa, Monica;Vries, Hein De 7017
This study had two objectives. The first was to assess the frequency and content of school-based anti-smoking education received by Romanian adolescents aged 14-15. Secondly, the study aimed to evaluate to what extent the implementation of a specific 5 lessons smoking prevention program influences the quality of anti-smoking school education among Romanian adolescents. The investigation was performed in twenty schools from Cluj-Napoca, Romania, which were randomly assigned to the control and experimental conditions, resulting in 55 participating classes from the seventh grade (28 in the control group and 27 in the experimental group). The experimental group participated in a school-based smoking prevention program consisting of 5 lessons. The control group beneficiated only in the standard anti-smoking education offered by their schools. Six months after the program implementation, students from both experimental and control groups filled in a questionnaire, assessing several issues regarding their exposure to anti-smoking school education in the last year. The results showed a low exposure to anti-smoking school education among the Romanian adolescents. The implementation of the specific school-based smoking prevention program increased the exposure of Romanian adolescents to a higher number of lessons of smoking prevention and influenced positively the quality of these lessons. The study identified several gaps with respect to anti-smoking education in Romanian schools. It underlines the benefits of the implementation of a school based smoking prevention program with a clear structure, which contains appropriate educational messages and it is easy to implement. -
Sangrajrang, Suleeporn;Chaiwerawattana, Arkom;Ploysawang, Pattama;Nooklang, Kanjamad;Jamsri, Paphawin;Somharnwong, Sopittra 7023
To evaluate the relationship between obesity, diet, physical activity and breast cancer in Thai women, we conducted a case control study with 1,130 cases and 1,142 controls. Informed consent was obtained from all participants and a structured questionnaire was performed by trained interviewers to collect information on demographic and anthropometric data, reproductive and medical history, residential history, physical activity and occupation as well as dietary habits. A significant positive association with an increased risk of breast cancer was observed in women body mass index (BMI) of${\geq}25mg/m^2$ (OR=1.33, 95%CI 1.07-1.65), the risk being higher in postmenopausal women (OR=1.67, 95%CI 1.24-2.25). In addition, underweight BMI at ages 10 and 20 years showed an inverse association in all women (OR=0.70, 95%CI 0.56-0.88 and OR=0.74, 95%CI 0.59-0.93, respectively) and in those with a premenopausal status (OR=0.69, 95%CI 0.51-0.93 and OR=0.76, 95%CI 0.56-0.99, respectively). Regular exercise was associated with a decreased risk of breast cancer (OR=0.78, 95%CI 0.68-0.98). Interestingly, analysis by type of activity revealed significant protective effects for women who reported the highest levels of walking for shopping (OR=0.58, 95%CI 0.38-0.88). High consumption of vegetables and fruit were associated with a decreased risk of breast cancer, while high consumption of animal fat showed an increased risk in postmenopausal women. In conclusion, our results indicate that obesity and high consumption of animal fat are associated with breast cancer risk, particularly in postmenopausal women, while recreational physical activity has protective effects. It seems that primary prevention of breast cancer should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles. -
Thunyaharn, Nut;Promthet, Supannee;Wiangnon, Surapon;Suwanrungruang, Krittika;Kamsa-ard, Supot 7029
Background: Cholangiocarcinoma (CCA) is a very common cancer in Northeastern Thailand. Most CCA patients see a physician at a late stage when curative surgery is not possible. After diagnosis, they generally are treated by partial surgery/percutaneous drainage, chemotherapy and supportive treatment. Objective: This study aimed to assess the survival rates of CCA patients after supportive treatment. Methods: A retrospective cohort design was applied in this study. Data for 746 CCA patients were extracted from the hospital-based cancer registry of Srinagarind Hospital, Khon Kaen University. The patients were diagnosed (at least by ultrasonography) between 1 January, 2009 and 31 December, 2009 and then followed up for current status until 30 June, 2011. The cumulative survival rate was calculated by the Kaplan-Meier method, and independent prognostic factors were investigated using Cox regression. Results: The total follow-up time was 5,878 person-months, and the total number of deaths was 637. The mortality rate was therefore 10.8 per 100 person-year (95%CI : 10.1-11.7). The cumulative 3, 6, 9, 12 and 24 month survival rates were 59%, 39%, 31%, 24% and 14%, respectively. The median survival time after supportive treatment was 4 months. After adjusting for gender, age, stage, distant metastasis, histological grading and treatment, stage was a significant predictor of survival of CCA patients. Those in stage III and stage IV had a 6.78 fold higher mortality than the stage I and stage II cases (95% CI : 1.6-28.7). Conclusion: It is very important to encourage patients to see health personnel at an early stage. -
Igissinov, Nurbek;Zatoskikh, Vera;Moore, Malcolm Anthony;Igissinov, Saginbek;Aldiyarova, Gulmira;Tokmurziyeva, Gulmira;Valieva, Saule;Alpeissova, Sholpan;Sarsenova, Samal 7033
The purpose of the present study was to provide an assessment of the incidence of cancer of the larynx in Kazakhstan with especial attention to ethnicity and gender, as well as age. The retrospective design covered all new cases of laryngeal cancer in 11 years (1999-2009). The total number was 4,967 cases, 4,535 (91.3%) in males and 432 (8.7%) in women, with a gender ratio of 10.5:1. Patients of Kazakh (31.2%) and Russian (51.4%) ethnicity accounted for the vast majority (82.6%), with Russians predominating in both sexes, but particularly in females. Age peak in Kazakhs was 70 years and older ($14 .6{\pm}0.70/0000$ ), and in Russians was 60-69 years ($21.6{\pm}1.30/0000$ ). In the dynamics, the rates had the tendency to decrease more markedly in Russian than Kazakh men, especially in the younger groups, while increase was noted in the youngest females of both ethnicities, but again greater in Russians, presumably reflecting change in underlying lifestyle factors. -
Duangsong, Rujira;Promthet, Supannee;Thaewnongiew, Kesorn 7039
A liver fluke, Opisthorchis viverrrini (OV), is the major cause of the high incidence of cholangiocarcinoma in North-eastern Thailand. The prevalence of OV infection remains high in various parts of the country, especially in wetland rural areas where a large proportion of the community work in agriculture and continue the traditional practice of eating raw or uncooked cyprinoid fish products. The national control program seems to have had little impact in many of these areas, and it has been difficult to make precise assessments of the overall effectiveness of the program. Therefore there is a need for a community-based approach to prevent infection with the parasite, ideally involving as many players as possible. Here we document an attempt to assess the best means to prevention on the basis of a community intervention in three villages in north-east Thailand, with participation of representatives of Health Promotion Hospitals of the Ministry of Public Health with dedicated staff, but also school teachers, independent government sponsored village health volunteers, and housewives responsible for cooking and diet selection. An action plan was followed, allowing detailed discussions of practical proposals, their introduction and then repeated reflection and further proposals at the individual village level.