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.
KSCI제15권17호
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Orang, Ayla Valinezhad;Barzegari, Abolfazl 6989
Colorectal cancer (CRC) is one of the major healthcare problems worldwide and its processes of genesis include a sequence of molecular pathways from adenoma to carcinoma. The discovery of microRNAs, a subset of regulatory non-coding RNAs, has added new insights into CRC diagnosis and management. Together with several causes of colorectal neoplasia, aberrant expression of oncomiRs (oncogenic and tumor suppressor miRNAs) in cancer cells was found to be indirectly result in up- or down-regulation of targeted mRNAs specific to tumor promoter or inhibitor genes. The study of miRNAs as CRC biomarkers utilizes expression profiling methods from traditional tissue samples along with newly introduced non-invasive samples of faeces and body fluids. In addition, miRNAs could be employed to predict chemo- and radio-therapy responses and be manipulated in order to alleviate CRC characteristics. The scope of this article is to provide a comprehensive review of scientific literature describing aberrantly expressed miRNAs, and consequently dysregulation of targeted mRNAs along with the potential role of miRNAs in CRC diagnosis and prognosis, as well as to summarize the recent findings on miRNA-based manipulation methods with the aim of advancing in anti-CRC therapies. -
Isoflavones are phytoestrogens and natural plant compounds which are similar to 17-
${\beta}$ -estradiol in chemical structure. It is known that they can act as estrogen agonists or antagonists, depending on endocrine estrogenic levels, but actions of isoflavones are rather complex due to large number of variables such as chemical structures and mechanisms. Some hypotheses on biological mechanisms have not satisfactorily been confirmed to date and human epidemiological and experimental studies have been relatively limited. Nevertheless, isoflavones and isoflavone rich foods have become a focus onf interest due to positive health benefits on many diseases, especially prevention of hormone-related cancers, cardiovascular disease, osteoporosis, and adverse postmenopausal symptoms, and improvement of physiological condition such as maintaining cognitive function. This review provides an overview of chemistry, analytical techniques (focused on human biospecimens), functions including biological mechanisms, and effects of isoflavones, on the basis of the available meta-analysis and review articles and some original articles, on health and cancer. -
Tokmak, Aytekin;Kokanali, Mahmut Kuntay;Guzel, Ali Irfan;Kara, Aydan;Topcu, Hasan Onur;Cavkaytar, Sabri 7011
The polycystic ovary syndrome is the most common endocrinological disorder of reproductive age women with a prevalence of 5 to 8 %. The most common diagnostic criteria used for polycystic ovary syndrome are oligo- or an-ovulation, clinical and/ or biochemical signs of hyperandrogenism and polycystic ovaries. Hyperandrogenism results in increased estrogen levels and lack of cyclic progesterone due to anovulation and persistent stimulation of the endometrium may lead to endometrial hyperplasia or adenocarcinoma development. In this mini review, we aimed to evaluate the possible relationship between polycystic ovary syndrome and endometrial cancer. -
Metabolism lies at the heart of cell biology. The metabolism of cancer cells is significantly different from that of their normal counterparts during tumorigenesis and progression. Elevated glucose metabolism is one of the hallmarks of cancer cells, even under aerobic conditions. The Warburg effect not only allows cancer cells to meet their high energy demands and supply biological materials for anabolic processes including nucleotide and lipid synthesis, but it also minimizes reactive oxygen species production in mitochondria, thereby providing a growth advantage for tumors. Indeed, the mitochondria also play a more essential role in tumor development. As information about the numorous microRNAs has emerged, the importance of metabolic phenotypes mediated by microRNAs in cancer is being increasingly emphasized. However, the consequences of dysregulation of Warburg effect and mitochondrial metabolism modulated by microRNAs in tumor initiation and progression are still largely unclear.
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Mukti, Roushney Fatima;Samadder, Pratul Dipta;Emran, Abdullah Al;Ahmed, Farzana;Imran, Iqbal Bin;Malaker, Anyanna;Yeasmin, Sabina 7021
Background: The problem of cancer, especially lung cancer, is very acute in Bangladesh. The present study was conducted to evaluate the risk of lung cancer among Bangladeshi people based on hereditary, socio-economic and demographic factors. Materials and Methods: This study was carried out in 208 people (patients-104, controls-104) from January 2012 to September 2013 using a structured questionnaire containing details of lung cancer risk factors including smoking, secondhand smoke, tobacco leaf intake, age, gender, family history, chronic lung diseases, radiotherapy in the chest area, diet, obesity, physical activity, alcohol consumption, occupation, education, and income. Descriptive statistics and testing of hypotheses were used for the analysis using SPSS software (version 20). Results: According to this study, lung cancer was more prevalent in males than females. Smoking was the highest risk factor (OR=9.707; RR=3.924; sensitivity=0.8872 and P<0.0001) followed by previous lung disease (asthma, tuberculosis etc.) (OR=7.095; RR=1.508; sensitivity=0.316 and P<0.0001)) for male patients. Highly cooked food (OR=2.485; RR=1.126; sensitivity=0.418 and P=0.004)) and also genetic inheritance (OR=1.93; RR=1.335; sensitivity=0.163 and P=0.138) demonstrated significant correlation with lung cancer as risk factors after these two and alcohol consumption was not prevalent. On the other hand, for female patients, tobacco leaf intake represented the highest risk (OR=2.00; RR=1.429; sensitivity= 0.667 and P=0.5603) while genetic inheritance and highly cooked food also correlate with lung cancer but not so significantly. Socioeconomic status and education level also play important roles in causing lung cancer. Some 78.5% male and 83.3% of female cancer patients were rural residents, while 58.2% lived at the margin or below the poverty line. Most male (39.8%) and female (50.0%) patients had completed only primary level education, and 27.6% male and 33.3% female patients were illiterate. Smoking was found to be more prevalent among the less educated persons. Conclusions: The results obtained in this study indicate the importance of creating awareness about lung cancer risk factors among Bangladeshi people and making appropriate access to health services for the illiterate, poor, rural people. -
Jalilvand, Somayeh;Shoja, Zabihollah;Hamkar, Rasool 7029
Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investiagtion covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer and head and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV. -
Liu, Wei;Fang, Yong;Wang, Xiao-Tong;Liu, Ju;Dan, Xing;Sun, Lu-Lu 7037
Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers. -
Han, Fei-Fei;Li, Liang;Shang, Bo-Yang;Shao, Rong-Guang;Zhen, Yong-Su 7043
Inhibition of heat shock protein 90 (Hsp90) leads to inappropriate processing of proteins involved in DNA damage repair pathways after DNA damage and may enhance tumor cell radio- and chemotherapy sensitivity. To investigate the potentiation of antitumor efficacy of lidamycin (LDM), an enediyne agent by the Hsp90 inhibitorgeldanamycin (GDM), and possible mechanisms, we have determined effects on ovarian cancer SKOV-3, hepatoma Bel-7402 and HepG2 cells by MTT assay, apoptosis assay, and cell cycle analysis. DNA damage was investigated with H2AX C-terminal phosphorylation (${\gamma}H2AX$ ) assays. We found that GDM synergistically sensitized SKOV-3 and Bel-7402 cells to the enediyne LDM, and this was accompanied by increased apoptosis. GDM pretreatment resulted in a greater LDM-induced DNA damage and reduced DNA repair as compared with LDM alone. However, in HepG2 cells GDM did not show significant sensitizing effects both in MTT assay and in DNA damage repair. Abrogation of LDM-induced$G_2/M$ arrest by GDM was found in SKOV-3 but not in HepG2 cells. Furthermore, the expression of ATM, related to DNA damage repair responses, was also decreased by GDM in SKOV-3 and Bel-7402 cells but not in HepG2 cells. These results demonstrate that Hsp90 inhibitors may potentiate the antitumor efficacy of LDM, possibly by reducing the repair of LDM-induced DNA damage. -
Moosavi, Seyed Alireza;Abdirad, Afshin;Omranipour, Ramesh;Hadji, Maryam;Razavi, Amirnader Emami;Najafi, Massoome 7049
Background: Almost half of the breast cancer patients with positive sentinel lymph nodes have no additional disease in the remaining axillary lymph nodes. This group of patients do not benefit from complete axillary lymph node dissection. This study was designed to assess the clinicopathologic factors that predict non-sentinel lymph node metastasis in Iranian breast cancer patients with positive sentinel lymph nodes. Materials and Methods: The records of patients who underwent sentinel lymph node biopsy, between 2003 and 2012, were reviewed. Patients with at least one positive sentinel lymph node who underwent completion axillary lymph node dissection were enrolled in the present study. Demographic and clinicopathologic characteristics including age, primary tumor size, histological and nuclear grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and number of harvested lymph nodes, were evaluated. Results: The data of 167 patients were analyzed. A total of 92 (55.1%) had non-sentinel lymph node metastasis. Univariate analysis of data revealed that age, primary tumor size, histological grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio, were associated with non-sentinel lymph node metastasis. After logistic regression analysis, age (OR=0.13; 95% CI, 0.02-0.8), primary tumor size (OR=7.7; 95% CI, 1.4-42.2), lymphovascular invasion (OR=19.4; 95% CI, 1.4-268.6), extracapsular invasion (OR=13.3; 95% CI, 2.3-76), and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio (OR=20.2; 95% CI, 3.4-121.9), were significantly associated with non-sentinel lymph node metastasis. Conclusions: According to this study, age, primary tumor size, lymphovascular invasion, extracapsular invasion, and the ratio of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes, were found to be independent predictors of non-sentinel lymph node metastasis. -
Tayarani-Najaran, Zahra;Hajian, Zahra;Mojarrab, Mahdi;Emami, Seyed Ahmad 7055
Artemisia, as one of the largest genera in the tribe Anthemideae of the Asteraceae comprises an important part of Iranian flora. While cytotoxic and apoptotic properties have already been reported for some species of the genus there is not any report on cytotoxic effects of A. ciniformis. Petroleum ether (40-60), dichloromethane, ethyl acetate, ethanol and ethanol-water (50:50) extracts of the aerial parts of A. cinformis were subjected to cytotoxic and apoptotic evaluations on two cancer human cell lines (K562 and HL-60) and on J774 normal cells. Among multiple extracts evaluated for cytotoxicity, dichloromethane ($CH_2Cl_2$ ) and petroleum ether (PE) extracts were shown to possess the highest anti-proliferative effects on HL-60 and K562 cells with$IC_{50}$ values of 31.3 and$25.5{\mu}g/ml$ respectively. Apoptosis induction verified by sub-G1 peaks was seen in flow cytometry histograms. Increase in the amount of Bax protein, formation of DNA fragments, and cleavage of PARP to 24 and 89kDa sub units all confirmed induction of apoptosis by A. cinformis extracts. Taken together according to the result of the present study some extracts of A. cinformis could be considered as sources for natural cytotoxic compounds and further mechanistic and phytochemical studies are recommended to fully understand the underlying mechanisms of cnacer cell death as well as identification of responsible phytochemicals. -
Accuracy of Intraoperative Gross Examination of Myometrial Invasion in Stage I-II Endometrial CancerSethasathien, Prauk;Charoenkwan, Kittipat;Siriaunkgul, Sumalee 7061
Background: To assess the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of intraoperative gross examination (IGE) of uterine specimens in determining deep myometrial invasion and cervical invasion compared to final histology. Materials and Methods: The clinical, surgical and histological data of all FIGO stage I-II endometrial cancer (EC) patients who had primary surgery were reviewed. Results of the IGE for myometrial invasion and cervical invasion were compared to the final histology. The sensitivity, specificity, PPV, NPV, and accuracy of the IGE in determining deep myometrial invasion and cervical invasion were calculated. Association between clinico-pathological factors and discrepancy between IGE and final histology in the determination of myometrial invasion was also assessed. A p-value of <0.05 was considered significant. Results: From January 2007 to December 2012, 179 patients diagnosed with clinical stage I-II endometrial cancer underwent surgical staging. The sensitivity and specificity of IGE in detecting deep myometrial invasion were 42.4% and 90.0%, respectively, and the PPV and NPV were 67.6% and 76.1%. The overall accuracy of IGE was 74.3%. The sensitivity and specificity of IGE in identifying cervical invasion were 28.6% and 97.5%, respectively, while the PPV and NPV were 60.0% and 91.1%. The overall accuracy of IGE was 89.4%. Conclusions: The sensitivity of IGE for detecting deep myometrial invasion and cervical invasion in early-stage EC is too low to be used alone. Alternative methods including intraoperative frozen section analysis, preoperative three dimensional ultrasound, and preoperative magnetic resonance imaging should be strongly considered. -
Pan, Li-Li;Wang, Ai-Yan;Huang, Yong-Qi;Luo, Yu;Ling, Min 7065
To investigate the anti-proliferative mechanism of mangiferin in a human nasopharyngeal carcinoma cell line, CNE2 cells were incubated with different concentrations of mangiferin (12.5, 25, 50, 100, 150 and$200{\mu}M$ ) or with PBS as a control for 72 hours. Analyses were made of the cell cycle and apoptosis with measurement of mRNA and protein levels of two apoptosis-related genes, Bcl-2 and Bax. Flow cytometry assays showed mangiferin could inhibit CNE2 cell proliferation via G2/M arrest and induction of early apoptosis. Real time PCR and Western blotting showed the mRNA and protein level of Bcl-2 to be down-regulated, while those of Bax were upregulated, when CNE2 cells were treated with mangiferin. This investigation indicated anti-proliferation effects of mangiferin through induction of cell apoptosis regulated by Bcl-2 and Bax expression. -
Yang, Jian;Li, Chuan;Wen, Tian-Fu;Yan, Lu-Nan;Li, Bo;Wang, Wen-Tao;Yang, Jia-Yin;Xu, Ming-Qing 7069
Background: This retrospective study aimed to validate the safety and effectiveness of hepatectomy for huge hepatocellular carcinoma (HCC). Materials and Methods: Data of patients who underwent hepatectomy for HCC between January 2006 and December 2012 were reviewed. The patients were divided into three groups: huge HCC(${\geq}10cm$ in diameter), large HCC(${\geq}5$ but<10 cm in diameter) and small HCC(<5cm in diameter). Results: Characteristics of pre-operative patients in all three groups were homogeneously distributed except for alpha fetal protein (AFP)(p<0.001).The 30, 60, 90-day post-operative mortality rates were not different among the three groups (p=0.785, p=0.560, and p=0.549). Laboratory data at 1, 3, and 7 days after surgery also did not vary. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates in the huge and large HCC groups were lower than that of the small HCC group (OS: 32.5% vs 36.3% vs 71.2%, p=0.000; DFS: 20.0% vs 24.8% vs 40.7%, p=0.039), but there was no difference between the huge and large HCC groups (OS: 32.5% vs 36.3%, p=0.667; DFS: 20.0% vs 24.8%, p=0.540). In multivariate analysis, five independent poor prognostic factors that affected OS were significantly associated with worse survival (p<0.05), namely, AFP level, macrovascular invasion, Edmondsone Steiner grade, surgical margin and Ishak score. AFP level, macrovascular invasion, microvascular invasion, and surgical margin influenced disease-free survival independently (p<0.05). Conclusions: The safety of hepatectomy for huge HCC is similar to that for large and small HCC; and this approach for huge HCC may achieve similar long-term survival and disease-free survival as for large HCC. -
Kitagawa, Yasuhide;Urata, Satoko;Narimoto, Kazutaka;Nakagawa, Tomomi;Izumi, Kouji;Kadono, Yoshifumi;Konaka, Hiroyuki;Mizokami, Atsushi;Namiki, Mikio 7079
The International Prostate Symptom Score (IPSS) is often used as an interview sheet for assessing lower urinary tract symptoms (LUTS) at the time of prostate-specific antigen (PSA) testing during population-based screening for prostate cancer. However, the relationship between prostate cancer detection and LUTS status remains controversial. To elucidate this relationship, the cumulative probability of prostate cancer detection using IPSS in biopsy samples from patients categorized by serum PSA levels was investigated. The clinical characteristics of prostate cancer detected using IPSS during screening were also investigated. A total of 1,739 men aged 54-75 years with elevated serum PSA levels who completed the IPSS questionnaire during the initial population screening in Kanazawa City, Japan and underwent systematic transrectal ultrasonography-guided prostate biopsy between 2000 and 2013 were enrolled in the present study. Of the 1,739 men, 544 (31.3%) were diagnosed with prostate cancer during the observation period. The probability of cancer detection at 3 years in the entire study population was 27.4% and 32.7% for men with$IPSS{\leq}7$ and those with$IPSS{\geq}8$ , respectively; there was no statistically significant difference between groups. In men with serum PSA levels of 6.1 to 12.0ng/mL at initial screening, the probability of cancer detection was significantly higher in men with$IPSS{\leq}7$ than in those with$IPSS{\geq}8$ . There were no significant differences in clinical characteristics between groups of patients stratified by IPSS. These findings indicate that the use of IPSS for LUTS status evaluation may be useful for prostate cancer detection in the limited range of serum PSA levels. -
Wang, Shao-Ming;Hu, Shang-Ying;Chen, Feng;Chen, Wen;Zhao, Fang-Hui;Zhang, Yu-Qing;Ma, Xin-Ming;Qiao, You-Lin 7085
Objective: To make the clinical evaluation of a solid-state human papillomavirus (HPV) sampling medium in combination with an economical HPV testing method ($careHPV^{TM}$ ) for cervical cancer screening. Methods: 396 women aged 25-65 years were enrolled for cervical cancer screening, and four samples were collected. Two samples were collected by woman themselves, among which one was stored in DCM preservative solution (called "liquid sample") and the other was applied on the Whatman Indicating FTA$Elute^{(R)}$ card (FTA card). Another two samples were collected by physician and stored in DCM preservative solution and FTA card, respectively. All the samples were detected by$careHPV^{TM}$ test. All the women were administered a colposcopy examination, and biopsies were taken for pathological confirmation if necessary. Results: FTA card demonstrated a comparable sensitivity of detecting high grade Cervical Intraepithelial Neoplasia (CIN) with the liquid sample carrier for self and physician-sampling, but showed a higher specificity than that of liquid sample carrier for self-sampling (FTA vs Liquid: 79.0% vs 71.6%, p=0.02). Generally, the FTA card had a comparable accuracy with that of Liquid-based medium by different sampling operators, with an area under the curve of 0.807 for physician &FTA, 0.781 for physician &Liquid, 0.728 for self & FTA, and 0.733 for self &Liquid (p>0.05). Conclusions: FTA card is a promising sample carrier for cervical cancer screening. With appropriate education programmes and further optimization of the experimental workflow, FTA card based self-collection in combination with centralized$careHPV^{TM}$ testing can help expand the coverage of cervical cancer screening in low-resource areas. -
Sangplod, Patcharaporn;Kanngurn, Samornmas;Boonpipattanapong, Teeranut;Ruangrat, Pritsana;Sangkhathat, Surasak 7091
Background: The study aimed to evaluate the incidence of CpG island promoter methylation of BMP6, a member of the transforming growth factor beta family, in tissue samples from colorectal cancers (CRC) and look for its association with BMP6 expression and clinicopathological correlation. Materials and Methods: Methylation specific PCR for the BMP6 promoter region was performed with 85 frozen tissue samples of CRC and 45 of normal colon. Methylation status of MLH1 was also determined by the same method. Expression of BMP6 was evaluated by immunohistochemistry (IHC), using Allred's scoring system. The methylation status was analyzed against clinical and pathological parameters in CRC. Results: The study revealed BMP6 hypermethylation in 34 of 85 tumor specimens (40%), and 15 out of 45 normal tissue samples from CRC (33%). The incidence of hypermethylation was inversely correlated with IHC score. Allred's scores of 7 or more were correlated with lower frequency of BMP6 hypermethylation (29% compared to 50% in the remaining, p-value 0.049). However, there was no association between hypermethylation status and any clinicopathological parameters. The methylation status of BMP6 was not correlated with that of MLH1, a key methylation determinant in CRC. On survival analysis, there was no significant difference in progress-free survival (PFS) between the cases with and without hypermethylation (2-year PFS 74% and 76%, respectively). Conclusions: CpG island methylation of BMP6 is found in high frequency in CRC and this epigenetic event is associated with suppressed protein expression in the tumor tissue. However, the marker is not associated with tumor progression of the disease. -
Jin, Xin;Zhang, Ke-Jin;Guo, Xu;Myers, Ronald;Ye, Zhong;Zhang, Zhi-Pei;Li, Xiao-Fei;Yang, Hu-Shan;Xing, Jin-Liang 7097
Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery. -
Gao, Mei-Li;Chen, Lei;Li, Yong-Fei;Xue, Xiao-Chang;Chen, Lan;Wang, Li-Na;Shah, Walayat;Kong, Yu 7105
In this study, we investigated oxidative stress and tumor marker levels of polycyclic aromatic hydrocarbons (PAHs) in 136 coke oven workers and in 60 control subjects, and evaluated the correlation between oxidative stress and tumor marker levels. Questionnaires on basic demographic information were also administered. Significant differences in employment time and percentages of alcohol drinkers were observed between the control and exposed groups. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. Significant differences (P<0.001) of MDA, GST, LDH, NSE, Cyfra21-1, and of SCC and TNF-a (P<0.0001 and P<0.05, P<0.001, respectively) levels were observed among controls and coke-oven workers, except for bottom coke oven workers. Associations between age and risk of increased TNF-a, smoking and increased GST activities, and drinking with increased MDA concentrations, were marginal (P=0.055, P=0.048, P=0.057, respectively). The association between smoking with MDA (P=0.004), NSE (P=0.005), SCC (P=0.004) andTNF-a (P<0.001), and drinking with TNF-a levels was significant (P=0.012). In addition, a significant positive correlation between oxidative stress and tumor markers was found in the present study. These results suggest that a synergistic increase of oxidative stress and tumor markers induced by PAHs may play a role in toxic responses for PAHs in coke oven workers. -
Ghalhar, Masoud Gandomkar;Akbarzadeh, Abolfazl;Rahmati, Mohammad;Mellatyar, Hassan;Dariushnejad, Hassan;Zarghami, Nosratallah;Barkhordari, Amin 7113
Background: HSP90 may be overexpressed in cancer cells which are greatly dependent on Hsp90 function. Geldanamycin derivative 17 allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the function and expression of HSP90. 17-AAG has poor water-solubility which is a potential problem for clinical practice. In this study for improving the stability and solubility of molecules in drug delivery systems we used a${\beta}$ -cyclodextrin-17AAG complex. Materials and Methods: To assess cytotoxic effects of${\beta}$ -cyclodextrin-17AAG complexes and free 17AAG, colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of${\beta}$ -cyclodextrin- 17AAG complex and free 17AAG and Hsp90 gene expression levels in the two groups was compared by real-time PCR. Results: MTT assay confirmed that${\beta}$ -cyclodextrin- 17AAG complex enhanced 17AAG cytotoxicity and drug delivery in T47D breast cancer cells. The level of Hsp90 gene expression in cells treated with${\beta}$ -cyclodextrin- 17AAG complex was lower than that of cells treated with free 17AAG (P=0.001). Conclusions: The results demonstrated that${\beta}$ -cyclodextrin- 17AAG complexes are more effective than free 17AAG in down-regulating HSP90 expression due to enhanced${\beta}$ -cyclodextrin-17AAG uptake by cells. Therefore,${\beta}$ -cyclodextrin could be superior carrier for this kind of hydrophobic agent. -
Bayoglu, Ibrahim Vedat;Varol, Umut;Yildiz, Ibrahim;Muslu, Ugur;Alacacioglu, Ahmet;Kucukzeybek, Yuksel;Akyol, Murat;Demir, Lutfiye;Dirican, Ahmet;Cokmert, Suna;Yildiz, Yasar;Karabulut, Bulent;Uslu, Ruchan;Tarhan, Mustafa Oktay 7119
Background: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin$130mg/m^2$ and capecitabine$1000mg/m^2$ twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2. -
Ahmed, Zeeshan Ansar;Moatter, Tariq;Siddiqui, Areeba;Pervez, Shahid 7125
Background: Acquired genetic alterations and presence of sensitizing mutations in the tyrosine kinase domain of EGFR and other signaling molecules have been found in different subsets of primary lung adenocarcinoma. The commonest EGFR mutations are small in frame deletions of exon 19 and a point mutation (L858R) in exon 21, having a combined occurrence of around 90%. The objective of this study was to determine the frequency and types of EGFR mutations in primary lung adenocarcinomas in Pakistan. Materials and Methods: EGFR mutations in tumor samples were screened by multiplex real time PCR. Briefly, DNA from formalin fixed paraffin-embedded tissue was amplified with primers and probes specific to 43 different EGFR mutations in a Cobas z 480 instrument. The assay detects mutations in four exons (18-21) of the EGFR gene. Results: Out of 94 patients, 65 were males and 29 females with a M:F ratio of 2.2: 1. The median age was 62 years (range, 28 - 85 years). In our biopsy samples 70 (74%) cases were of primary lung adenocarcinoma, whereas 24 (26%) were confirmed metastatic adenocarcinoma of primary lung origin. EGFR mutation was positive in 29% of the patients. The highest frequency of L858R was observed in 48% of these, followed by deletion in exon 19 (44%). In addition, other rare mutations such as compound G718X:S768I and insertions in exon 20 insertion were detected in approximately 4% of the patients. Conclusions: This study showed that Del 19 and L858R are the most frequent mutations in Pakistani lung adenocarcinoma patients and around 29% of the patients were found eligible for erlotinib therapy. -
Background: In this study, we aimed to evaluate the growth inhibitory effect of the combination of ethaselen (BBSKE) and low fixed dose of selenite against A549 human non-small cell lung cancer cells in vitro. Materials and Methods: Growth inhibitory effects against A549 cells were determined by SRB assay. Combination index (CI) values were calculated based on Chou-Talalay median-effect analyses. Dose reduction index (DRI) values were applied to calculate dose reduction of selenite. Contents of free thiols and GSH were determined by DTNB assay and intracellular ROS levels by DCFH-DA fluorescence labeling. Results: Compared with BBSKE or selenite single treatment, the combined application of ethaselen and a low fixed dose of selenite shortened the onset time of sodium selenite, reduced
$IC_{50}$ values, and increased the maximum inhibition rates, suggesting a possible molecular mechanism of the synergism. Obvious synergistic effects were observed after different times of combination treatment, especially after 24 h. Compared with selenite single treatment, dosage of selenite could be remarkably reduced in combination therapy to gain the same inhibitory effect on cell proliferation. Compared with BBSKE single treatment, the content of free thiols and GSH were significantly reduced and ROS levels greatly elevated in the combination group. For the combination treatment, cell viability increased as greater concentrations of GSH were added. Conclusions: All these results indicate that the combination treatment of BBSKE and selenite showed synergism to inhibit A549 cell proliferation in vitro, and also reduced the selenite dosage to mitigate its toxicity which is very meaningful for combination chemotherapy of lung cancer. The synergism was probably caused by the accelerated exhaustion of intracellular reductive substances, such as free thiols and GSH, which ultimately leads to enhanced oxidative stress and apoptosis. -
Background: This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic gastric cancer (MGC) as a salvage chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with gastric cancer were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In pemetrexed based regimens, 4 clinical studies including 171 patients with advanced gastric cancer were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 25.1% (43/171) in pemetrexed based regimens. Major adverse effects were neutropenia, anorexia, fatigue, and anemia. No treatment related death occurred in pemetrexed based treatment. Conclusion: This systemic analysis suggests that pemetrexed based regimens are associated with mild activity with good tolerability in treating patients with MGC.
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Krishnan, Rajkumar;Thayalan, Dinesh Kumar;Padmanaban, Rajashree;Ramadas, Ramya;Annasamy, Ramesh Kumar;Anandan, Nirmala 7141
Background: Oral squamous cell carcinoma (OSCC) is an important malignancy throughout the world; early detection is an important criterion for achieving high cure rate. Out of the many reported markers for OSCC, this study validated the efficacy of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$ ) in differentially diagnosing premalignant oral lesions and OSCC. Also, the study aimed to correlate the levels of salivary and serum TNF-${\alpha}$ with clinicopathologic factors. Materials and Methods: A prospective experimental laboratory study was designed. Serum and salivary samples from 100 subjects in each group of healthy control, premalignant disease (PMD) and OSCC were collected for the study following appropriate exclusion and inclusion criteria. Serum and salivary level of TNF-${\alpha}$ was analysed by enzyme linked immunosorbent assay. The data obtained were subjected to appropriate statistical analysis. Results: Increased level of both serum and salivary TNF-${\alpha}$ was observed in OSCC subjects compared to healthy control and PMD group. Receiver operator characteristic curve analysis and area under curve values showed high specificity and sensitivity for salivary TNF-${\alpha}$ in differentiating OSCC from PMD and healthy controls. There was significant increase in TNF-${\alpha}$ level in moderately and poorly differentiated lesion compared to well differentiated lesion and in stage IV of clinical stage. A positive correlation was observed only with histological grading of OSCC and TNF-${\alpha}$ . Conclusions: Salivary TNF-${\alpha}$ is proved to be superior for detecting OSCC. Increase in TNF-${\alpha}$ with histological grading and clinical staging suggests a role in prognosis. -
Takasu, Shinji;Ishii, Yuji;Matsushita, Kohei;Kuroda, Ken;Kijima, Aki;Kodama, Yukio;Ogawa, Kumiko;Umemura, Takashi 7149
A large number of epidemiological studies have demonstrated that obesity is a risk factor for several human cancers. Several animal studies using rodents with diet-induced or genetic obesity have also demonstrated that obesity can promote tumor development. However, the effects of obesity on the early stages of carcinogenesis, and especially on the spontaneous occurrence of somatic gene mutations, remain unclear. To investigate the effects of obesity on the rate of spontaneous gene mutations, we performed reporter gene mutation assays in liver, kidney, and colon, organs in which obesity appears to be associated with cancer development on the basis of epidemiological or animal studies, in mice with high fat diet (HFD)-induced obesity. Six-week-old male and female C57BL/6 gpt delta mice were fed HFD or standard diet (STD) for 13 or 26 weeks. At the end of the experiments, reporter gene mutation assays of liver, kidney, and colon were performed. Final body weights and serum leptin levels of male and female mice fed HFD for 13 or 26 weeks were significantly increased compared with corresponding STD-fed groups. Reporter gene mutation assays of liver, kidney, and colon revealed that there were no significant differences in gpt or$Spi^-$ mutant frequencies between STD- and HFD-fed mice in either the 13-week or 26-week groups. These results indicate that HFD treatment and consequent obesity does not appear to influence the spontaneous occurrence of somatic gene mutations. -
Background: Non-Hodgkin's lymphoma (NHL) patients demonstrate multiple symptoms in diagnosis and treatment processes. This cross-sectional descriptive study aimed to determine the symptoms and symptom clusters in such patients receiving chemotherapy. Materials and Methods: The study was carried out on a total of 110 inpatients and outpatients receiving treatment in 7 hospitals in Ankara, Turkey. A questionnaire form and the Memorial Symptom Assessment Scale (MSAS) were applied. Percentages, means, t test, one way analysis of variance (ANOVA) and cluster analysis were used for statistical analyses. Results: The most prevalent symptoms in this study were lack of energy, hair loss and change in the way food tastes. The most severe symptoms were hair loss, change in the way food tastes and constipation. The top three most distressing symptoms were taste change, constipation and mouth sores. Seven symptom clusters were determined in this study. Conclusions: Findings of the study will provide an understanding of symptom experiences of Non-Hodgkin's lymphoma patients receiving chemotherapy and will guide determining appropriate nursing interventions. Receiving care of desired quality will contribute to increasing quality of life of affected individuals.
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Wei, Mei-Yang;Zhuang, Yan-Feng;Wang, Wan-Ming 7159
Background: Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with recurrent or refractory osteosarcoma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In gemcitabine based regimens, 4 clinical studies which included 66 patients with recurrent or refractory osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 12.1% (8/66) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia in gemcitabine based treatment. No treatment related death occurred in gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with recurrent or refractory osteosarcoma. -
Wu, Yao;Tong, Xiang;Tang, Ling-Li;Zhou, Kai;Zhong, Chuan-Hong;Jiang, Shu 7163
Background: Associations between the rs6010620 polymorphism in the regulator of telomere elongation helicase1 (RTEL1) gene and glioma have been widely reported but the results were not inconclusive. The aim of the current study was to investigate the association between the rs6010620 polymorphism in RTEL1 gene and risk of glioma by meta-analysis. Materials and Methods: We searched PubMed, Embase, Wanfang Weipu and CNKI (China National Knowledge Infrastructure) databases, which included all research published 05 May 2014. A total of 8,292 cases and 12,419 controls from 14 case-control studies involving the rs6010620 polymorphism in the RTEL1 gene were included. Statistical analysis was performed using STATA 12.0 software. Results: The results indicated that the rs6010620 polymorphism in RTEL1 gene was indeed associated with risk of glioma (OR=1.474, 95%CI=1.282-1.694, p<0.001). On subgroup analysis by ethnicity, we found associations between the rs6010620 polymorphism in the RTEL1 gene and risk of glioma in both Caucasians and Asians. Conclusions: The current meta-analysis suggested that the rs6010620 polymorphism in the RTEL1 gene might increase risk of glioma. In future, larger case-control studies are needed to confirm our results. -
Rana, Sobia;Shahid, Adeela;Ullah, Hafeez;Mahmood, Saqib 7169
Background: NPAS2 is a product of the circadian clock gene. It acts as a putative tumor suppressor by playing an important role in DNA damage responses, cell cycle control and apoptosis. Chronic lymphocytic leukemia (CLL) appears to be an apoptosis related disorder and alteration in the NPAS2 gene might therefore be directly involved in the etiology of CLL. Here, the Ala394Thr polymorphism (rs2305160:G>A) in the NPAS2 gene was genotyped and melatonin concentrations were measured in a total of seventy-four individuals, including thirty-seven CLL cases and an equal number of age- and sex-matched healthy controls in order to examine the effect of NPAS2 polymorphism and melatonin concentrations on CLL risk in a Pakistani population. Materials and Methods: Genotyping of rs2305160:G>A polymorphism at NPAS2 locus was carried out by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Melatonin concentrations were determined by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistical Package for Social Sciences software. Results: Our results demonstrated no association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with risk of CLL. Similarly, no association of rs2305160 with CLL was observed in either females or males after stratification of study population on a gender basis. Moreover, when the subjects with CLL were further stratified into shift-workers and non-shift-workers, no association of rs2305160 with CLL was seen in either case. However, significantly low serum melatonin levels were observed in CLL patients as compared to healthy subjects (p<0.05). Also, lower melatonin levels were seen in shift-workers as compared to non-shift-workers (p<0.05). There was no significant difference (p>0.05) in the melatonin levels across NPAS2 genotypes in all subjects, subjects with CLL who were either shift workers or non-shift-workers. General Linear Model (GLM) univariate analysis revealed no significant association (p>0.05) of the rs2305160 polymorphism of the NPAS2 gene with melatonin levels in any of the groups. Conclusions: While low melatonin levels and shift-work can be considered as one of the risk factors for CLL, the NPAS2 rs2305160 polymorphism does not appear to have any association with risk of CLL in our Pakistani population. -
Che, Chong Chin;Coomarasamy, Jeya Devi;Suppayah, Balakrishnan 7175
Background: Breast cancer is the most common cancer among women in Malaysia, about one in 19 women being at risk. This study aimed to investigate knowledge and practice of breast self-examination (BSE), as well as knowledge of risk factors for breast cancer amongst female adolescents in Malaysia. Subsequently, relationships between demographic characteristics and knowledge level of BSE, risk factors for breast cancer and BSE practice were assessed. Materials and Methods: A descriptive, cross sectional survey was conducted using a sample of 500 Malaysian adolescents from the age of 15 to 19 years. A self-administered questionnaire was used to gather socio-demographic characteristics, knowledge of BSE, knowledge of risk factors for breast cancer and BSE practices. Results: The findings of this study indicated that female adolescents in Malaysia demonstrated an inadequate knowledge level of BSE and risk factors for breast cancer. Only 27.8% of female adolescents performed BSE regularly. BSE practice, knowledge of BSE and knowledge of risk factors for breast cancer showed significant positive relationships. Conclusions: The study highlighted the importance of planning and implementing breast health education programs for female students in secondary schools in Malaysia. It will also provide the health care providers an avenue to stress on the importance of imparting breast health education to adolescents. -
Aytekin, Turkan;Aytekin, Alper;Maralcan, Gokturk;Gokalp, M. Avni;Ozen, Dogukan;Borazan, Ersin;Yilmaz, Latif 7181
Cyclin D1 is an important positive regulator of the G1/S phase of the cell cycle. We investigated the association between the CCND1 G870A polymorphism and susceptibility to papillary thyroid cancer in Turkish people. This study covered 102 patients with papillary thyroid cancer and 174 healthy controls. CCND1 genotyping was determined by the PCR-RFLP method. We found that the A allele frequency was higher in the cases than in the controls (p=0.042). On stratification analysis, papillary thyroid cancer risk was significantly elevated in individuals older than 45 years with the A allele (OR=1.91, 95% CI, 1.09-3.35, p=0.024) and in females with the A allele (OR=1.73, 95% CI, 1.06-2.84, p=0.029), compared to the G allele. According to the subject age, there was an increased papillary thyroid cancer risk for the individuals older than 45 years with the AA genotype (OR=2.28, 95% CI, 1.02-5.13, p=0.046) compared to the AG+GG combined genotypes. In conclusion, it is suggested that the CCND1 G870A polymorphism may contribute to the susceptibility to papillary thyroid cancer, especially in those who were older subjects ($45{\leq}$ years old) and female, in the Turkish population. -
Li, Lei;Chen, Bao-Ding;Zhu, Hai-Feng;Wu, Shu;Wei, Da;Zhang, Jian-Quan;Yu, Li 7187
Background: The aim of this meta-analysis was to compare sensitivities and specificities of fine needle aspiration (FNA) and core needle biopsy (CNB) in the diagnosis of thyroid cancer. Materials and Methods: Articles were screened in Medline, the Cochrane Library, EMBASE and Google Scholar, and subsequently included and excluded based on the patient/problem-intervention-comparison-outcome (PICO) principle. Primary outcome was defined in terms of diagnostic values (sensitivity and specificity) of FNA and CNB for thyroid cancer. Secondary outcome was defined as the accuracy of diagnosis. Compiled FNA and CNB results from the final studies selected as appropriate for meta-analysis were compared with cases for which final pathology diagnoses were available. Statistical analyses were performed for FNA and CNB for all of the selected studies together, and for individual studies using the leave-one-out approach. Results: Article selection and screening yielded five studies for meta-analysis, two of which were prospective and the other three retrospective, for a total of 1,264 patients. Pooled diagnostic sensitivities of FNA and CNB methods were 0.68 and 0.83, respectively, with specificities of 0.93 and 0.94. The areas under the summary ROC curves were 0.905 (${\pm}0.030$ ) for FNA and 0.745 (${\pm}0.095$ ) for CNB, with no significant difference between the two. No one study had greater influence than any other on the pooled estimates for diagnostic sensitivity and specificity. Conclusions: FNA and CNB do not differ significantly in sensitivity and specificity for diagnosis of thyroid cancer. -
Chen, Jia;Zheng, Xin;Liu, Dong-Yang;Zhao, Qian;Wu, Yi-Wen;Tan, Fen-Lai;Wang, Yin-Xiang;Jiang, Ji;Hu, Pei 7195
Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in$672^{nd}$ ($4^{th}$ week) and$1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations. -
Razmkhah, Mahboobeh;Arabpour, Fahimeh;Taghipour, Mousa;Mehrafshan, Ali;Chenari, Nooshafarin;Ghaderi, Abbas 7201
Chemokine and chemokine receptor expression by tumor cells contributes to tumor growth and angiogenesis and thus these factors may be considered as tumor markers. Here we aimed to characterize cells directly extracted from glioma, meningioma, and secondary brain tumors as well as non-tumoral cells in vitro. Cells were isolated from brain tissues using 0.2% collagenase and characterized by flow cytometry. Expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, MCP-1 and IP-10 was defined using flow cytometry and qRT-PCR methods. Brain tissue isolated cells were observed as spindle-shaped cell populations. No significant differences were observed for expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, and IP-10 transcripts. However, the expression of CXCR4 was approximately 13-fold and 110-fold higher than its counterpart, CXCR7, in meningioma and glioma cells, respectively. CXCR7 was not detectable in secondary tumors but CXCR4 was expressed. In non tumoral cells, CXCR7 had 1.3-fold higher mRNA expression than CXCR4. Flow cytometry analyses of RANTES, MCP-1, IP-10, CCR5 and CXCR4 expression showed no significant difference between low and high grade gliomas. Differential expression of CXCR4 and CXCR7 in brain tumors derived cells compared to non-tumoral samples may have crucial impacts on therapeutic interventions targeting the SDF-1/CXCR4/CXCR7 axis. -
Mertsoylu, Huseyin;Muallaoglu, Sadik;Besen, Ayberk Ali;Erdogdu, Suleyman;Sezer, Ahmet;Sedef, Ali Murat;Kose, Fatih;Arican, Ali;Ozyilkan, Ozgur 7207
Background: The aim of this study was to assess the epidemiological and clinicopathological characteristics of primary extranodal non-Hodgkin's lymphoma (pENL) patients, focusing on treatment and survival outcome. Materials and Methods: Between October 2003 and March 2012, 802 patients with non-Hodgkin's lymphoma (NHL) were diagnosed and treated in two different cancer centers of Southern Turkey. Results: pENL, constituted 12.4% (100/802) of all NHL studied during this period. Median age of the patients was 56 years (range 17-87 years) and the male: female distribution was 3:2. Eighty-five of 100 patients (85%) were in stage I/II, 9/100 (9%) in stage III, whereas 6/100 (6%) were in stage IV. Head and neck constituted the most common site (51/100, 51%), followed by gastrointestinal tract (GIL) (37/100, 37%), and cerebrum (CL) (5/100, 5%). Diffuse large B cell lymphoma (DLBCL) was the most common histological type, observed in 53% of patients, followed by marginal zone extranodal lymphoma (13%). Most of patients (76%) received a CHOP containing regimen. Complete remission (CR) were achieved in 71% of patients. The median follow-up duration of all patients was reported as 37.6 months (range, 0.8-165 months). This period was reported as 137.5 months (range, 117.5-1578.6 months) in gastrointestinal lymphoma (GIL) patients, 119.0 months (range, 91.8-146.1 months) in head and neck lymphoma (HNL) patients, and 18.4 months (range, 12.6-24.1 months) in cerebral lymphoma (CL) patients. Conclusions: Head and neck, and the gastrointestinal tract were the two most common extranodal sites observed. Histologically DLBC accounted for the majority of cases. Most patients were on earlier stages, had low-low intermediate IPI scores and had a favorable prognosis. -
IL28B rs12979860 Gene Polymorphism in Egyptian Patients with Chronic Liver Disease Infected with HCVZekri, Abdel-Rahman N.;Salama, Hosny;Medhat, Eman;Bahnassy, Abeer A.;Morsy, Heba M.;Lotfy, Mai M.;Ahmed, Rasha;Darwish, Tarneem;Marei, Mohamad S. 7213
Background: Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population. Materials and Methods: The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71). Results: The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification. Conclusions: 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation. -
Wang, Zheng;Ma, Li;Zhang, Xing-Mao;Zhou, Zhi-Xiang 7219
Background: Early gastric cancer (EGC) is well accepted as having a favorable prognosis, but some patients experience an ominous outcome after curative resection. This study was aimed at evaluating predictive factors associated with prognosis of D2 gastrectomies in patients with early gastric cancer. Materials and Methods: A total of 518 patients with early gastric cancer who underwent D2 gastrectomies were reviewed in this study. The clinicopathological features and surgical outcomes were analyzed. The survival rate was estimated using the Kaplan-Meier method and compared by log rank test. Prognostic factors were analyzed using a multivariate Cox proportional hazards model. Results: The 5-year survival rate was 90.3%. Tumor infiltration, lymph node metastasis and lymphovascular invasion were significant prognostic factors for survival. Gender, age, tumor size, tumor location, macroscopic type and histological type were not significant prognostic factors. Multivariate analysis indicated that lymph node metastasis was an independent poor prognosis factor. Conclusions: Early gastric cancers with lymph node metastasis have a relatively poor prognosis after standard surgery. Even after curative resection, patients with EGC with positive lymph nodes should be closely followed and be considered as candidates for comprehensive therapies. -
Down-regulated MYH11 Expression Correlates with Poor Prognosis in Stage II and III Colorectal CancerWang, Ren-Jie;Wu, Peng;Cai, Guo-Xiang;Wang, Zhi-Min;Xu, Ye;Peng, Jun-Jie;Sheng, Wei-Qi;Lu, Hong-Fen;Cai, San-Jun 7223
The MYH11 gene may be related to cell migration and adhesion, intracellular transport, and signal transduction. However, its relationship with prognosis is still uncertain. The aim of this study was to investigate correlations between MYH11 gene expression and prognosis in 58 patients with stage II and III colorectal cancer. Quantitative real-time polymerase chain reaction was performed in fresh CRC tissues to examine mRNA expression, and immunohistochemistry was performed with paraffin-embedded specimens for protein expression. On univariate analysis, MYH11 expression at both mRNA and protein levels, perineural invasion and lymphovascular invasion were related to disease-free survival (p<0.05; log-rank test). Cancers with lower MYH11 expression were more likely to have a poor prognosis. Otherwise, MYH11 expression was unrelated to patient clinicopathological features. On multivariate analysis, low MYH11 expression proved to be an independent adverse prognosticator (p<0.05). These findings show that MYH11 can contribute to predicting prognosis in stage II and III colorectal cancers. -
El-Rahman, Atef Abd El-Mohsen Abd;El-Shafei, Sally Mohamed Abd El-Aziz;Ivanova, Elena Vladimirovna;Fattakhova, Alfia Nurlimanovna;Pankova, Anna Victorovna;El-Shafei, Mohamed Abd El-Aziz;El-Morsi, El-Morsi Abu El-Fotouh;Alimova, Farida Kashifovna 7229
Trichoderma spp. are known as a rich source of secondary metabolites with biological activity belonging to a variety of classes of chemical compounds. These fungi also are well known for their ability to produce a wide range of antibiotic substances and to parasitize other fungi. In search for new substances, which might act as anticancer agents, the overall objective of this study was to investigate the cytotoxic effects of Trichoderma harzianum and Trichoderma asperellum cultural filtrates against human cervical and breast cancer cell lines (HeLa and MCF-7 cells respectively). To achieve this objective, cells were exposed to 20, 40, 60, 80 and 100 mg/ml of both T. harzianum cultural filtrate (ThCF) and T. asperellum cultural filtrate (TaCF) for 24h, then the cell viability and the cytotoxic responses were assessed by using trypan blue and 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assays. Morphological changes in cells were investigated by phase contrast inverted microscopy. The results showed that ThCF and TaCF significantly reduce the cell viability, have cytotoxic effects and alter the cellular morphology of HeLa and MCF-7 cells in a concentration dependent manner. A concentration of 80 and 100mg/ml of ThCF resulted in a sharp decline in the cell viability percent of HeLa and MCF-7 respectively (25.2%, 26.5%) which was recorded by trypan blue assay. The half-maximal inhibitory concentrations ($IC_{50}$ ) of ThCF and TaCF in HeLa and MCF-7 were recorded as 16.6, 12.0, 19.6 and 0.70mg/ml respectively by MTT assay. These results revealed that ThCF and TaCF have a substantial ability to reduce the viability and proliferation of human cervical and breast cancer cells. -
Cervical cancer, the third commonest cancer in women worldwide, can be prevented through early detection by cervical screening (Pap smear). The aim of this study was to investigate the attitudes and practice of cervical cancer screening among female undergraduate university students from 25 low, middle income and emerging economy countries. Using anonymous questionnaires, data were collected from 9,194 female undergraduate university students aged 18-26 years (mean age 20.9, SD=2.0) from 26 universities in 25 countries across Asia, Africa and the Americas. Overall, 11.6% of the female students indicated that they had conducted one or more times a cervical (Pap) smear test; 8.3% among 18-20 year-olds and 15.6% among 21-26 year-old students. There was considerable country variation on having had a cervical (Pap) smear test among 21-26 year-old female university students, ranging from 59.2% in Colombia and 50.9% in Barbados to 0% in India and 1.0% in Tunesia. Logistic regression showed that cervical cancer screening importance or positive attitude were highly associated with the cervical screening practice. Moreover, risky sexual behaviour and tobacco use, two cervical cancer risk factors, were associated with screening. Cervical cancer screening practices were found to be inadequate and e fforts should be made to develop programmes that can increase the uptake of cervical cancer screening.
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Woranisarakul, Varat;Ramart, Patkawat;Phinthusophon, Kittipong;Chotikawanich, Ekkarin;Prapasrivorakul, Siriluck;Lohsiriwat, Varut 7241
Background: To determine the accuracy of preoperative urinary symptoms, urinalysis, computed tomography (CT) and cystoscopic findings for the diagnosis of urinary bladder invasion in patients with colorectal cancer. Materials and Methods: Records of patients with colorectal cancer and a suspicion of bladder invasion, who underwent tumor resection with partial or total cystectomy between 2002 and 2013 at the Faculty of Medicine Siriraj Hospital, were reviewed. Correlations between preoperative urinary symptoms, urinalysis, cystoscopic finding, CT imaging and final pathological reports were analyzed. Results: This study included 90 eligible cases (71% male). The most common site of primary colorectal cancer was the sigmoid colon (44%), followed by the rectum (33%). Final pathological reports showed definite bladder invasion in 53 cases (59%). Significant features for predicting definite tumor invasion were gross hematuria (OR 13.6, sensitivity 39%, specificity 73%), and visible tumor during cystoscopy (OR 5.33, sensitivity 50%, specificity 84%). Predictive signs in CT imaging were gross tumor invasion (OR 7.07, sensitivity 89%, specificity 46%), abnormal enhancing mass at bladder wall (OR 4.09, sensitivity 68%, specificity 66%), irregular bladder mucosa (OR 3.53, sensitivity 70%, specificity 60% ), and loss of perivesical fat plane (OR 3.17, sensitivity 81%, specificity 43%). However, urinary analysis and other urinary tract symptoms were poor predictors of bladder involvement. Conclusions: The present study demonstrated that the most relevant preoperative predictors of definite bladder invasion in patients with colorectal cancer are gross hematuria, a visible tumor during cystoscopy, and abnormal CT findings. -
Fu, Rong;Yang, Peng;Wu, Hai-Li;Li, Zong-Wei;Li, Zhuo-Yu 7245
Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/${\beta}$ -catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling. -
Lin, Zhuo;Chen, Li;Song, Mei;Shi, Ke-Qing;Tang, Kai-Fu 7251
MicroRNAs (miRNAs) act as tumor suppressors or promoters in neoplasia by regulating relative geneexpression. The association between a single nucleotide polymorphism (SNP) rs4938723 in miR-34b/c and susceptibility to cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed, Web of Science and Embase to identify all relevant studies in this meta-analysis with 6,036 cases and 6,204 controls. We found that the miR-34b/c rs4938723 polymorphism was significantly associated with increased risk of cancers in the heterozygous model (TC versus TT, OR=1.09, 95% CI=1.01-1.18, P=0.02). Subgroup analysis also revealed increased risk for Asian ethnicity in the heterozygous model (TC versus TT, OR=1.12, 95% CI=1.02-1.22, P=0.02), but decreased risk of colorectal cancer in homozygote model (CC versus TT, OR=0.66, 95% CI=0.47-0.92, P=0.02) and in the recessive model (CC versus TC+TT, OR=0.67, 95% CI=0.48-0.93, P=0.02) by cancer type. The current meta-analysis indicated that the miR-34b/c rs4938723 polymorphism may decrease susceptibility to colorectal cancer. Well-designed studies with larger sample size are required to further validate the results. -
Dehdari, Tahereh;Hassani, Laleh;Hajizadeh, Ebrahim;Shojaeizadeh, Davoud;Nedjat, Saharnaz;Abedini, Mehrandokht 7257
Background: Few Iranian women take the Papanicolaou test despite its important role in preventing cervical cancer. This study aimed to determine the effectiveness of an educational intervention based on the protection motivation theory (PMT) variables and implementation intentions in the first and second Pap test practice among Iranian women. Materials and Methods: In this quasi-randomized controlled trial, 200 women who were referred to 30 primary health care clinics in Tehran were randomly selected. PMT variables and Pap test practice were measured at baseline and again after 3 and 15 months. The 4-week educational intervention program was conducted for the intervention group. Results: Following the intervention, the mean scores of self-efficacy, perceived vulnerability, and behavior intention variables were significantly higher in the intervention group when compared to the control group (p<0.05). No significant differences were found in the perceived severity, response efficacy, response cost, and fear between the two groups following the intervention. Higher percent of women in the intervention group had obtained first and second Pap test compared to the controls. Conclusions: The PMT and implementation intentions provide a suitable theory-based framework for developing educational interventions regarding Pap test practice in Iran. -
Kose, Dilek;Erkorkmaz, Unal;Cinar, Nursan;Altinkaynak, Sevin 7263
Background: Cervical cancer which is one of the most preventable cancers is an important public health problem worldwide, and especially in developing countries. The aim of this study was to determine knowledge and attitudes about the HPV vaccination of mothers with 0- to 18-year old children. Materials and Methods: Written approval was taken from the local authorities. The study subjects consisted of 799 mothers who agreed to participate. The data were collected via a "Personal Information Form" which included 30 questions that were prepared by the researchers themselves in line with the literature. The data were collected by face to face interviews with the mothers. Analyses were performed using commercial software. Results: The mean age of the mothers who participated in the study was$32.0{\pm}6.52$ , and 88.1% reported no information about HPV, and 83.5% no information about HPV vaccination. Only 0.7% of the mothers had daughters who had HPV vaccination, and 44.3% of the mothers who had sons were found out to be indecisive about having HPV vaccination. There was a significant corelation between the educational status of the mothers and their knowledge about HPV vaccination (p<0.05). However, there was no significant correlation in terms of economic conditions (p>0.05). Conclusions: This study suggested that mothers had very little information on HPV and HPV vaccination. Knowledge of the disease and its vaccination is an essential factor for the success of the vaccination program. It is of great importance that mothers are trained in this subject by health professionals. -
Sharma, Jagannath Dev;Kalita, Manoj;Barman, Debanjana;Sharma, Arpita;Lahon, Ranjan;Barbhuiya, Jamil Ahmed;Deka, Barsha;Kataki, Amal Chandra 7267
Background: The incidence of upper aero-digestive tract (UADT) cancers, including C00-C14, C30-C32, C15 and C16, is increasing rapidly in Kamrup Urban District (KUD) of Assam, North East (NE) India. According to the NCRP (2013) report 37.6% of all cancers in both sexes are UADT cancers in the NE region, accounting for 53.3% in males and about 27.5% in females of the total cases. Materials and Methods: A retrospective study was conducted for patient information from the period of 2008-2011. Age-standardized or age-adjusted rates (ASR or AAR) (per 100,000 person-years) were calculated using the World Standard Population as proposed by Segi and modified by Doll et al. The registry population area at risk was estimated using the 1991 and 2001 census population by sex, as well as the growth rate during that interval using the difference distribution method. Results: There were 5,638 cases registered during the last four years of the study (2008-2011) accounting for 56.7% (3,198/5,638) of the total in males and 43.3% (2,440/5,638) in females. The male: female ratio was 1.31:1.00. The overall age adjusted rates (AAR) were 179.4 and 153.8 per 100 000 males and females respectively. Cancer of the oesophagus was most common in both sexes, with most appreciable gender variation for tongue and hypopharynx, presumably reflecting differential expsoure to risk factors. -
Background: The aim of the present study was to evaluate the presentation, clinical course and outcome between children and young adults with differentiated thyroid cancer (DTC) treated in our hospital. Materials and Methods: The medical records of 145 patients with DTC who underwent surgery followed by radioiodine and thyroid hormone (TSH) suppression were retrospectively reviewed. The follow up was between January 2006 and June 2012. These patients consisted of 38 children (age
${\leq}18y$ ) and 107 young adult patients (age${\leq}30y$ ). The clinical characteristics and outcome were analyzed and compared, and the progression-free survival (PFS) was evaluated using the Kaplan-Meier method. Results: At initial diagnosis, a greater degree of extra thyroidal extension was found in children than adults patients (p<0.001). However, there was no significant difference between the two groups with regard to the tumor size and the presence of lymph node or distant metastasis (p=0.172, p=0.050 and p=0.068, respectively). The extent of surgery and the cumulative or mean dose of radioiodine were similar in both groups. During the follow up, the overall survival rate was 100% for both groups, and the PFS rate was similar in children and in young adults group (log rank test,${\chi}^2$ =0.126, p=0.723). Conclusions: In comparison to the young adult patients, DTC in children presents with more aggressive behavior, but outcomes are similar between the two groups after the intensive management of surgery followed by radioiodine and TSH suppression therapy. -
Zhang, Yong;Sun, Ling-Li;Li, Tao;Sun, Hui;Mao, Guo-Jia 7277
This analysis was conducted to evaluate the efficacy and safety of carboplatin based chemotherapy in treating pediatric patients with Wilms tumors. Methods: Clinical studies evaluating the efficacy and safety of carboplatin based regimens on response and safety for pediatric patients with Wilms tumors were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In carboplatin based regimens, 4 clinical studies which including 127 patients with advanced Wilms tumors were considered eligible for inclusion. With this carboplatin based chemotherapy, 2 clinical studies included carboplatin, ifosfamide and etoposide. Systemic analysis suggested that, in all patients, the pooled PR was 64.5% (82/127) in carboplatin based regimens. Thrombocytopenia and leukocytopenia were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with carboplatin based treatment. Conclusion: This systemic analysis suggests that carboplatine based regimens are associated with a reasonable response rate and accepted toxicities for treating pediatric patients with Wilms tumors. -
Chong, Vui Heng;Telisinghe, Pemasari Upali;Abdullah, Muhd Syafiq;Chong, Chee Fui 7281
Background: Gastric cancer is the second most common gastrointestinal cancer and is more common in the East, compared to the West. This study assesses the trend of gastric cancers in Brunei Darussalam, a developing nation with a predominantly Malay population. Materials and Methods: The cancer registry from 1986 to 2012 maintained by the Department of Pathology, the only State Laboratory at the RIPAS Hospital, Ministry of Health, was reviewed and data extracted for analyses. The age standardised rate (ASR) and age specific incidence rate were calculated based on the projected population. Cancers diagnosed below 45 years were categorised as young gastric cancer. Results: Over the study period, there were a total of 551 cases of gastric cancer diagnosed. The most common type was adenocarcinoma (87.9%), followed by lymphoma (6.1%) and gastrointestinal stromal tumour (2.8%). The overall mean age at diagnosis was 61.9 years old (range 15 to 98) with an increasing trend observed, but this was not significant (ANOVA). There were differences in the mean age at diagnosis for the different races (p=0.003 for trend), but not the gender (p=0.105). Young gastric cancer accounted for 14.9%, being more common in women, and in Expatriate and Malay populations compared to the Chinese. There was a decrease in the ASR, from 17.3/100,000 in 1986-1990 to 12.5/100,000 in 2006-2010. Chinese had a higher overall ASR (20.2/100,000) compared to the Malays (11.8/100,000). The age specific rates were comparable between men and women until the age group 55-59 years when the rates started to diverge, becoming higher in men. Chinese men had higher rates then Malay men whereas, the rates were higher or comparable between the women until the age group >70 when the rate for Chinese women overtook their Malay counterpart. Conclusions: Our study showed that there is a declining trend in the incidence of gastric cancer and higher rates were observed in men and Chinese. -
Han, Yung Wen;Mohammad, Mohazmi;Liew, Su May 7287
Background: Brief physician counselling has been shown to be effective in improving smokers' behaviour. If the counselling sessions can be given at the workplace, this would benefit a larger number of smokers. This study aimed to determine the effectiveness of a ten-minute physician counseling session at the workplace in improving smoking behaviour. Materials and Methods: This prospective randomised control trial was conducted on smokers in a factory. A total of 163 participants were recruited and randomised into control and intervention groups using a table of random numbers. The intervention group received a ten-minute brief physician counselling session to quit smoking. Stages of smoking behaviour were measured in both groups using a translated and validated questionnaire at baseline, one month and three months post intervention. Results: There was a significant improvement in smoking behaviour at one-month post intervention (p=0.024, intention to treat analysis; OR=2.525; CI=1.109-5.747). This was not significant at three-month post intervention (p=0.946, intention to treat analysis; OR=1.026; 95% CI=0.486-2.168). Conclusions: A session of brief physician counselling was effective in improving smokers' behaviour at workplace, but the effect was not sustained. -
Park, Ki-Woong;Kundu, Juthika;Chae, In Gyeong;Bachar, Sitesh Chandra;Bae, Jung-Woo;Chun, Kyung-Soo 7291
Different plant parts of Flacourtia indica have long been used in Ayurvedic medicine. Previous studies have demonstrated that the methanolic extract of F. indica possess anti-inflammatory properties. The present study was aimed at investigating the anticancer effects of methanol extract of Flacourtia indica (FIM) aerial parts in human colon cancer (HCT116) cells. Treatment of cells with FIM at a concentration of$500{\mu}g/ml$ for 24 hours significantly reduced cell viability and induced apoptosis, which was associated with the increased cytoplasmic expression of cytochrome c, activation of caspase-3, and the cleavage of poly-(ADP-ribose) polymerase. Incubation with FIM also inhibited the levels of Bcl-2, Bcl-xl and survivin, which are the markers of cell proliferation, whereas the expression of Bax remained unchanged. Treatment with FIM led to the generation of reactive oxygen species (ROS) in a concentration-dependent manner. Pharmacological inhibition of ROS generation by pretreatment of cells with N-acetyl cysteine abrogated FIM-induced apoptosis in HCT116 cells. Thus, these results demonstrate that FIM has anti-proliferative and pro-apoptotic effects in HCT116 cells and the effects are, at least in part, due to the ROS dependent activation of caspases. -
Cai, Yong;Sheng, Zhao-Ying;Liang, Shi-Xiong 7297
Objective: To explore the radiosensitization effect of overexpression of silent information regulator 6 (SIRT6) on A549 non-small cell lung cancer (NSCLC) cells. Methods: Adenovirus vector Ad-SIRT6 causing overexpression of SIRT6 was established. Western blotting and MTT assay were adopted to detect the level of SIRT6 protein and the inhibitory rate of A549 cell proliferation after different concentrations of adenovirus transduction (0, 25, 100, 200, and 400 pfu/cell) for 24 h. Control group, Ad-null group and Ad-SIRT6 group were designed in this experiment and virus concentration of the latter two groups was 200 pfu/cell. Colony formation assays were employed to test survival fraction (SF) of the 3 groups after 0, 2, 4, 6, 8, 10 X-ray irradiation. Flow cytometry was used to detect the status of cell cycle of 3 groups after 48 h of 4Gy X-ray irradiation and Western blotting was used to determine the expression of apoptosis-related genes of 3 groups after 48 h of 4GyX-ray irradiation. Results: In the range of 25~400 pfu/cell, the inhibitory rate of A549 cell proliferation increased as adenovirus concentration raised. The inhibitory rates under the concentrations of 0, 25, 100, 200, and 400 pfu/cell were 0%,$4.23{\pm}0.34%$ ,$12.7{\pm}2.57%$ ,$22.6{\pm}3.38%$ ,$32.2{\pm}3.22%$ ,$38.7{\pm}4.09%$ and$47.8{\pm}5.58%$ and there were significantly differences among groups (P<0.05). SF in Ad-SIRT6 group was lower than Ad-null and control groups after 4~10Gy X-ray irradiation (P<0.05) and the sensitization enhancement ratio (SER) was 1.35 when compared with control group. Moreover, after 48 h of 4Gy X-ray irradiation, there appeared a significant increase in G1-phase cell proportion, upregulated expression of the level of apoptosis-promoting genes (Bax and Cleaved caspase-3), but a obvious decline in S-phase and G2-phase cell proportion and a significant decrease of the level of apoptosis-inhibiting gene (Bal-2) in the Ad-SIRT6 group (P<0.05). Conclusion: The over-expression of adenovirus-mediated SIRT6, which has radiosensitization effect on A549 cells of NSCLC, can inhibit the proliferation of A549 cells and cause G0/G1 phase retardation as well as induce apoptosis of cells. -
Objective: To explore the clinical efficacy of gemcitabine concomitant with nedaplatin and drug resistance in the treatment of non-small cell lung cancer (NSCLC) and associated molecular predicators. Materials and Methods: A total of 68 patients diagnosed with NSCLC by histology served as the study objects and were randomly divided into an observation group treated with gemcitabine concomitant with nedaplatin and a control group with cisplatin concomitant with gemcitabine, 34 cases for each group. Short-term and long-term efficacies, adverse responses as well as the expression of nucleotide excision repair cross complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and lung resistance-related protein (LRP) in NSCLC tissues in both groups were assessed. Results: The short-term objective response rate (ORR) and disease control rate (DCR) were 35.3% (12/34) and 76.5% (26/34) in the observation group and 38.2% (13/34) and 85.3% (29/34) in the control group, respectively, the differences not being statistically significant. The time to progression (TTP) in both groups were 1~12 months, while the median TTP was 135 d and 144 d, respectively. Though the survival was slightly higher in the control group, there were no significant differences in TTP and survival time. The rates of decreased hemoglobin, vomiting and nausea as well as renal toxicity were evidently lower in the observation group, while other adverse responses demonstrated no significant difference. The positive expression rates of ERCC1, RRM1 and LRP were 47.1% (16/34), 61.8% (21/34) and 64.7% (22/34) in the observation group, respectively. Compared with negative ERCC1 expression, ORR had decreasing trend and the overall survival time (OS) decreased significantly in patients with positive ERCC1 expression, which were markedly decreased by the positive expressions of RRM1 and LRP. Conclusions: Gemcitabine concomitant with nedaplatin has significant effects in the treatment of NSCLC, with an adverse response rate obviously lower than for cisplatin concomitant with gemcitabine, suggesting that wider use in the clinic is warranted. Additionally, the positive expressions of ERCC1, RRM1 and LRP may increase patient drug resistance, so they can be applied as the chemotherapeutic predicators to guide individualized therapy of NSCLC patients.
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Taymoori, Parvaneh;Moshki, Mahdi;Roshani, Daem 7309
Background: While many researchers often use a theoretical framework for mammogram repeat interventions, it seems they do not apply an identified mediation analysis method. The aim of this study was to determine the mediators of mammogram replication behavior in two tailored interventions for non-adherent Iranian women. Materials and Methods: A sample population of 184 women over 50 years old in Sanandaj, Iran, was selected for an experiment. Participants were randomly allocated into one of the three conditions: 1) an intervention based on the Health Belief Model (HBM) 2) an intervention based on an integration of the HBM and selected constructs from the Theory of Planned Behavior (TPB), and 3) a control group. Constructs were measured before the intervention, and after a 6-month follow-up. Results: Perceived self-efficacy, behavioral control, and subjective norms were recognized as mediators in the HBM and selected constructs from the TPB intervention. Perceived susceptibility, severity, barriers, self-efficacy and behavioral control met the criteria for mediation in the HBM intervention. Conclusions: This study was successful in establishing mediation in a sample of women. Our findings enrich the literature on mammography repeat, indicating key intervention factors, and relegating redundant ones in the Iranian populations. The use of strategies to increase mammography repeat, such HBM and TPB constructs is suggested to be important for maintaining a screening behavior, once the behavior has been adopted. -
Mesci-Haftaci, Simender;Ankarali, Handan;Caglar, Mete;Yavuzcan, Ali 7317
Background: A cytologic reading of a Papanicolaou (pap) smear followed, if the result is positive, by a colposcopic search for abnormal cells is the most common screening method for cervical cancer used worldwide. We aimed to present the correlation of smear and colposcopic findings with 6- to 12-month follow-up results and related factors in women who underwent colposcopy in Turkey. Materials and Methods: The study population consisted of women who attended the gynecology department and were referred for colposcopic evaluation in 2011-2012. A total of 232 women between ages 17 and 68 years were included. Colposcopy indications were ASCUS and higher lesions at cervical smear, macroscopic suspicious lesions, post-coital bleeding history with suspicious smear, and repeated cervical inflammation. All patients were recalled for 6- to 12-month follow-ups. Results: The most common colposcopy indication was ASCUS, and the most common biopsy result was inflammation. Nearly half of the patients returned for the control 6-month follow-up, and almost 20% of patients for a 1-year follow up. Conclusions: Colposcopic biopsy is an effective method in indicated patients but is not sufficient in itself if awareness of the subject is not raised in the population. One of the most important aims of cancer screening programs should be enabling patients in developing countries to take responsibility. Patients must be encouraged to apply to the hospital for better disease control. -
Oskay, Umran;Can, Gulbeyaz;Basgol, Sukran 7321
Background: Sexual health and function frequently are overlooked by healthcare professionals despite being identified as an essential aspect of patient care. Patients with cancer have identified sexuality issues as being of equal importance to other quality-of-life issues. Objectives: The aim of this study was to determine the views and attitudes of oncology nurses caring for cancer patients regarding sexual counseling. Participants and Methods: A descriptive cross-sectional study was conducted on the web site of the Turkish Oncology Nurses Association. With the participation of 87 nurses from oncology departments, the study determined that most nurses do not evaluate and counsel patients regarding their sexual problems and many difficulties prevent them from focussing on sexual health. The most important reasons for ignoring sexual counseling were the absence of routine regarding sexual counseling in oncology departments, the belief that the patient may become ashamed and the nurses' self-evaluation that they have insufficient skills and education to counsel in this subject. Conclusions: The most important variables in sexual evaluation and counseling are long years of service in the profession and a postgraduate degree. -
He, Wen-Zhuo;Jiang, Chang;Yin, Chen-Xi;Guo, Gui-Fang;Rong, Ru-Ming;Qiu, Hui-Juan;Chen, Xu-Xian;Zhang, Bei;Xia, Liang-Ping 7327
Background: We had previously showed that the neutrophil lymphocyte ratio (NLR),${\gamma}$ -glutamyl transpeptidase (GGT) and carcinoembryonic antigen (CEA) are prognostic factors for metastatic colorectal cancer (mCRC) patients. In this study we developed a prognostic model based on these three indices. Materials and Methods: A total of 243 patients who were initially diagnosed as mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center were studied. The endpoint was overall survival (OS). Results: NLR>3, elevated GGT and elevated CEA were confirmed as independent risk factors which could predict poor prognosis. Patients could be divided into three groups according to the number of risk factors they had. Those with two or three were defined as the high risk group, individuals with one risk factor as the modest risk group and patients without risk factor as the low risk group. The OS values for these three groups were 16.2 months (2.80~68.8), 24.2 months (4.07~79.0), and 37.2 months (12.6~87.8), respectively (p<0.001). Conclusions: We developed a simple but useful model based on NLR, GGT and CEA to provide prognostic information to clinical practice in highly selected mCRC patients. Further prospective and multi-center studies are warranted to test our model. -
Wang, Xiao-Chuan;Sun, Liang-Qi;Ma, Li;Li, Hua-Xin;Wang, Xiu-Li;Wang, Xin;Yun, Tian;Meng, Nian-Long;Lv, Da-Le 7333
Human papillomavirus (HPV) infection has been implicated as a causative of cervical cancer. In the present study, a total of 578 samples from females attending the gynecological outpatient clinic in Henan province, China, were collected and the HPV genotypes were detected by gene chip and flow-through hybridization. Overall, 44.5% (257/578) females were found to be HPV DNA positive, and the high risk HPV (HR-HPV) rate was 35.1% (203/578). The first peak of HR-HPV infection appeared in the >60 year-old group (55.0%), and the second was within the 51-55 year-old group (50.0%) (${\chi}^2$ =19.497, p<0.05). HPV 16 was the most prevalent genotype (9.2%), followed by HPV 52 (7.8%), HPV 6 (6.9%), HPV 11 (5.9%) and HPV 42 (5.0%). The single type HPV infection was 30.4%, with the five majority prevalent genotype HPV 16 (16.5%), HPV 52 (14.3%), HPV 6 (12.6%), HPV 42 (8.6%), HPV 31 (5.1%). The multiple-type HPV infections were 14.0%, and HPV 16 was the most prevalent type (29.6%), followed by HPV 52 (24.7%), HPV 6 (22.2%), HPV 11 (22.2%), HPV 42 (17.3%) and HPV 39 (17.3%). -
Atoum, Manar Fayiz;Tchoporyan, Melya Nizar 7337
Background: The physiological role of vitamin D extends beyond bone health and calcium-phosphate homeostasis to effects on cancer risk, mainly for colorectal cancer. Vitamin D may have an anticancer effect in colorectal cancer mediated by binding of the active form$1,25(OH)_2D$ to the vitamin D receptor (VDR). The Taq1 VDR gene polymorphism, a C-to-T base substitution (rs731236) in exon 9 may influence its expression and function. The aim of this study wass to determine the 25(OH)D vitamin D level and to investigate the association between circulating vitamin D level and Taq1VDR gene polymorphism among Jordanian colorectal cancer patients. Materials and Methods: This case control study enrolled ninety-three patients and one hundred and two healthy Jordanian volunteers from AL-Basheer Hospital/Amman (2012-2013). Ethical approval and signed consent forms were obtained from all participants before sample collection. 25(OH)D levels were determined by competitive immunoassay Elecsys (Roche Diagnostic, France). DNA was extracted (Promega, USA) and amplified by PCR followed by VDR Taq1 restriction enzyme digestion. The genotype distribution was evaluated by paired t-test and chi-square. Comparison between vitamin D levels among CRC and control were assessed by odds ratio with 95% confidence interval. Results: The vitamin D serum level was significantly lower among colorectal cancer patients (8.34 ng/ml) compared to the healthy control group (21.02ng/ml). Patients deficient in vitamin D (less than 10.0 ng/ml) had increased colorectal cancer risk 19.2 fold compared to control. Only 2.2% of CRC patients had optimal vitamin D compared to 23.5% among healthy control. TT, Tt and tt Taq1 genotype frequencies among CRC cases was 35.5%, 50.5% and 14% compared to 43.1%, 41.2% and 15.7% among healthy control; respectively. CRC patients had lower mean vitamin D level among TT ($8.91{\pm}4.31$ ) and Tt ($9.15{\pm}5.25$ ) genotypes compared to control ($21.3{\pm}8.31$ ) and ($19.3{\pm}7.68$ ); respectively. Conclusions: There is significant association between low 25(OH)D serum level and colorectal cancer risk. The VDRTaq1 polymorphism was associated with increased colorectal cancer risk among patient with VDRTaq1 TT and Tt genotypes. Understanding the functional mechanism of VDRTaq1 TT and Tt may provide a strategy for colorectal cancer prevention and treatment. -
Cancer is one of the leading causes of death in Thailand as well as other countries. Evidences from studies in Asia show that alcohol consumption has been linked to an increased risk for various types of cancer. In the qualitative participatory action research presented here, the possibilities of a volunteer women's movement to reduce harmful alcohol consumption by facilitating the creation of emancipatory knowledge in the Thai-Isaan community was explored. During in-depth interviews with 10 female volunteer participants, the following themes emerged: merit making, developing a sense of personal empowerment, and the experience of participating in an action plan that utilized various strategies. The project activities empowered participants to create and share knowledge which was then applied toward action for change. Adoption of this type of program by local health care providers to reduce health problems and risks related to alcohol misuse in similar contexts and cultures is recommended.
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Kum, Rauf Oguzhan;Ozcan, Muge;Baklaci, Deniz;Kum, Nurcan Yurtsever;Yilmaz, Yavuz Fuat;Gungor, Volkan;Unal, Adnan 7351
Background: Laryngeal carcinogenesis is a multifactorial process that has not been fully elucidated. Despite extensive research, reliable markers with diagnostic and prognostic value are still lacking. It was recently reported that an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) may correlate with an increased risk of recurrence, tumor aggressiveness and poorer prognosis in various malignancies. The aim of this study was to examine whether NLR could be used as an inflammatory marker to differentiate laryngeal squamous cell carcinoma (LSCC) patients from benign laryngeal lesion (BLL) and precancerous laryngeal lesion (PLL) patients. Materials and Methods: This retrospective study was performed on 209 patients admitted to a tertiary referral center with laryngeal lesions and undergoing biopsies to establish their histopathological diagnosis. We reviewed the patient files for their clinical, histopathological and laboratory data. The patients were divided into three groups according to their histopathological findings, as BLL, PLL and LSCC groups. The patients in the PLL group were also divided into three subgroups as mild, moderate and severe dysplasia/carcinoma in situ (CIS) subgroups. The groups were compared for NLR and the other laboratory data. Results: The mean NLRs of the BLL, PLL and the LSCC groups were$2.12{\pm}0.86$ ,$2.32{\pm}0.68$ and$3.46{\pm}1.51$ , respectively, and the difference was statistically significant (p=0.001). The mean NLRs of the patients with PLL and LSCC were significantly higher than the patients with BLL (p=0.031 and p=0.001, respectively). The mean NLRs were similar among mild dysplasia, moderate dysplasia and severe dysplasia / CIS groups (p>0.05). Conclusions: To our knowledge, this is the first study investigating NLR in BLL, PLL and LSCC. NLR is an inexpensive, reproducible and widely available blood test, and could be a useful inflammatory marker to differentiate LSCC from BLL and PLL. -
Shi, Wen-Jing;Liu, Hao;Wu, Dan;Tang, Zhen-Hua;Shen, Yu-Chen;Guo, Lin 7357
Interleukin-6 (IL-6), a central proinflammatory cytokine, maintains immune homeostasis and also plays important roles in cervical cancer. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms at positions -174 and -572 with predisposition to cervical cancer in a Chinese population. The present hospital-based case-control study comprised 518 patients with cervical cancer and 518 healthy controls. Polymorphisms of the IL-6 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients with cervical cancer had a significantly higher frequency of the IL-6 -174 CC genotype [odds ratio (OR) =1.52, 95% confidence interval (CI) = 1.06-2.19; p=0.02], IL-6 -572 CC genotype (OR =1.91, 95% CI = 1.16-3.13; p=0.01) and IL-6 -174 C allele (OR =1.21, 95% CI = 1.02-1.44; p=0.03) compared to healthy controls. When stratifying by the FIGO stage, patients with III-IV cervical cancer had a significantly higher frequency of IL-6 -174 CC genotype (OR =1.64, 95% CI =1.04-2.61; p=0.04). The CC genotypes of the IL-6 gene polymorphisms at positions -174 and -572 may confer a high risk of cervical cancer. Additional studies with detailed human papillomavirus (HPV) infection data are warranted to validate our findings. -
Dong, Qing;Xie, Zuo-Xu;Xie, Cao;Lu, Wei-Yue;Zhang, Qian;Li, Xue;Liu, Min 7363
The present study aimed to prepare and evaluate polymeric micelles conjugated with folic acid through${\alpha}$ - or${\gamma}$ -carboxyl groups for antitumor efficacy. The isomeric block copolymers,${\alpha}$ - and${\gamma}$ -folate-polyethyleneglycol-distearoyl phosphatidylethanolamine (${\alpha}$ - and${\gamma}$ -Fol-PEG-DSPE), were produced by solid phase peptide synthesis. Three types of doxorubicin (DOX)-loaded polymeric micelles (MPEG-DSPE-DOX and${\alpha}$ - /${\gamma}$ -Fol-PEG-DSPEDOX micelles) were prepared via the film formation method. Compared with MPEG-DSPE-DOX micelles, the${\alpha}$ - /${\gamma}$ -Fol-PEG-DSPE-DOX micelles presented a higher cellular uptake behavior in the live cell study. Cell viability percentages were 81.8%, 57.3%, 56.6% at 2 hours for MPEG-DSPE-DOX,${\alpha}$ - and${\gamma}$ -Fol-PEG-DSPE-DOX micelles, respectively (p<0.05). Using the KB xenograft tumor model, both${\alpha}$ - and${\gamma}$ -folate-conjugated micelles were found to have better antitumor effects with lower toxicity in comparison with MPEG-DSPE-DOX micelles. No difference in in vivo antitumor efficacy was found between${\alpha}$ - and${\gamma}$ -Fol-PEG-DSPE-DOX micelles. The folate-conjugated micelles might be a potentially useful strategy for tumor targeting of therapeutic agents, whether grafting with folic acid through${\alpha}$ - or${\gamma}$ -carboxyl groups. -
Yilmaz, Sercan;Adas, Yasemin Guzle;Hicsonmez, Ayse;Andrieu, Meltem Nalca;Akyurek, Serap;Gokce, Saban Cakir 7371
Background: Concurrent chemo-radiotherapy is the recommended standard treatment modality for patients with locally advanced lung cancer. The purpose of three-dimensional conformal radiotherapy (3DCRT) is to minimize normal tissue damage while a high dose can be delivered to the tumor. The most common dose limiting side effect of thoracic RT is radiation pneumonia (RP). In this study we evaluated the relationship between dose-volume histogram parameters and radiation pneumonitis. This study targeted prediction of the possible development of RP and evaluation of the relationship between dose-volume histogram (DVH) parameters and RP in patients undergoing 3DCRT. Materials and Methods: DVHs of 41 lung cancer patients treated with 3DCRT were evaluated with respect to the development of grade${\geq}2$ RP by excluding gross tumor volume (GTV) and planned target volume (PTV) from total (TL) and ipsilateral (IPSI) lung volume. Results: Were admitted statistically significant for p<0.05. Conclusions: The cut-off values for V5, V13, V20, V30, V45 and the mean dose of TL-GTV; and V13, V20,V30 and the mean dose of TL-PTV were statistically significant for the development of Grade${\geq}2$ RP. No statistically significant results related to the development of Grade${\geq}2$ RP were observed for the ipsilateral lung and the evaluation of PTV volume. A controlled and careful evaluation of the dose-volume histograms is important to assess Grade${\geq}2$ RP development of the lung cancer patients treated with concurrent chemo-radiotherapy. In the light of the obtained data it can be said that RP development may be avoided by the proper analysis of the dose volume histograms and the application of optimal treatment plans. -
Goh, Lucky Poh Wah;Chong, Eric Tzyy Jiann;Chua, Kek Heng;Chuah, Jitt Aun;Lee, Ping-Chin 7377
CYP2E1 PstI polymorphism G-1259C (rs3813867) genotype distributions vary significantly among different populations and are associated with both diseases, like cancer, and adverse drug effects. To date, there have been limited genotype distributions and allele frequencies of this polymorphism reported in the three major indigenous ethnic groups (KadazanDusun, Bajau, and Rungus) in Sabah, also known as North Borneo. The aim of this study was to investigate the genotype distributions and allele frequencies of the CYP2E1 PstI polymorphism G-1259C in these three major indigenous peoples in Sabah. A total of 640 healthy individuals from the three dominant indigenous groups were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at G-1259C polymorphic site of CYP2E1 gene was performed using the Pst I restriction enzyme. Fragments were analyzed using agarose gel electrophoresis and confirmed by direct sequencing. Overall, the allele frequencies were 90.3% for c1 allele and 9.7% for c2 allele. The genotype frequencies for c1/c1, c1/c2 and c2/c2 were observed as 80.9%, 18.8%, and 0.3%, respectively. A highly statistical significant difference (p<0.001) was observed in the genotype distributions between indigenous groups in Sabah with all Asian and non-Asian populations. However, among these three indigenous groups, there was no statistical significant difference (p>0.001) in their genotype distributions. The three major indigenous ethnic groups in Sabah show unique genotype distributions when compared with other populations. This finding indicates the importance of establishing the genotype distributions of CYP2E1 PstI polymorphism in the indigenous populations. -
Chatchotikawong, Usanee;Ruengkhachorn, Irene;Leelaphatanadit, Chairat 7383
Background: To determine rates of residual disease along with influencing factors in women with stage IA to IB1 cervical carcinoma after conization. Materials and Methods: A retrospective study was conducted of medical records of 198 stage IA to IB1 cervical carcinoma patients who had undergoing cervical conization followed by primary surgical treatment during 2006-2013. Independent factors correlating with residual carcinoma in subsequent surgical specimens were analyzed by stepwise regression analysis. Results: Mean age was 48.9 years. Cone specimens demonstrated free margins in 36 women (18.8%). In case of having disease at margin, high-grade cervical intraepithelial neoplasia (CIN) and carcinoma were evidenced in 58 and 97 women, respectively. Pathology of subsequent specimens revealed residual carcinoma in 78 women (39.4%), high-grade CIN or adenocarcinoma in situ (AIS) in 45 (22.7%), and no residual pathology in 75 (37.9%). Age more than 35 years, postmenopausal status, having symptoms, diseases or invasive lesions at conization margins or disease on endocervical aspect, and higher stage were significantly correlated with residual cancer in surgical treatment specimens. On regression analysis, postmenopause and stage were independent factors associated with residual carcinoma.Conclusions: Patient and tumor characteristics are predictive factors for residual cancer in the studied group of women. -
Zheng, Xiao-Nan;Wang, Xiao-Wen;Li, Li-Ya;Xu, Zi-Wei;Huang, Hsin-Yi;Zhao, Jin-Sheng;Zhang, Duo;Yin, Xu;Sheng, Jun;Tang, Jin-Tian 7389
Background: Chemotherapy is one of the major means for control of malignancies, with cisplatin (CDDP) as one of the main agents, widely used for the treatment of various malignant solid tumors. However, prevention of hepatotoxicity from cisplatin is one of the urgent issues in cancer chemotherapy. In this study, we aimed to investigate the effects of pu-erh tea on hepatotoxicity through body weight and tissue antioxidant parameters like, liver coefficient, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde(MDA) and glutathione (GSH) levels, and light microscopic evaluation by histological findings. Materials and Methods: The rats were randomly divided into five groups: Control (n=10), cisplatin (3 mg/kg p.i., n=10), cisplatin+pu-erh (0.32 g/kg/day i.g., n=10), cisplatin+pu-erh (0.8 g/kg/day i.g., n=10) and cisplatin+pu-erh (1.6 g/kg/day i.g., n=10). Pu-erh tea powder was administrated for 31 consecutive days. The rats were sacrificed at the end on the second day after a single dose of cisplatin treatment for measuring indices. Results: Pu-erh tea powder exhibited a protective effect by decreasing MDA and GSH and increasing the SOD and GSH-PX levels and GSH-PX/MDA ratio in camparison with the control group. Besides, pu-erh tea was also able to alleviate the pathological damage to some extent. Conclusion: Pu-erh tea powder is protective against cisplatin-induced liver oxidative damages, especially at the medium dosage (0.8 g/kg/d). -
Zhou, Zhi-Xiang;Zhao, Chen;Li, Qian-Qian;Zeng, Yi 7395
Background: Persistent human papillomavirus (HPV) infection, especially with high-risk types such as HPV16 and HPV18, has been identified as the primary cause of cervical cancer. E6 and E7 are the major onco-proteins of high-risk HPVs, which are consistently expressed in HPV infected tissues but absent in normal tissues and represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this study, the optimized fusion gene HPV18 E6E7 (HPV18 ofE6E7) was constructed according to genetic codon usage for human genes. At the same time, for safety future clinical application, a mutant of HPV18 ofE6E7 fusion gene was generated by site-directed mutagenesis at L52G for the E6 protein and C98G for the E7 protein. Results: HPV18-E6E7 mutant (HPV18 ofmE6E7) constructed in this work not only lost the transformation capability for NIH 3T3 cells and tumorigenicity in BALB/c nude mice, but also maintained very good stability and antigenicity. Conclusion: These results suggest that the mutant should undergo further study for application as a safe antigenspecific therapeutic vaccine for HPV18-associated tumors. -
Adas, Yasemin Guzle;Andrieu, Meltem Nalca;Hicsonmez, Ayse;Atakul, Tugba;Dirican, Bahar;Aktas, Caner;Yilmaz, Sercan;Akyurek, Serap;Gokce, Saban Cakir;Ergocen, Salih 7401
Background: Postoperative chemoradiotherapy is accepted as standard treatment for stage IB-IV, M0 gastric cancer. Radiotherapy (RT) planning of gastric cancer is important because of the low radiation tolerance of surrounding critical organs. The purpose of this study was to compare the dosimetric aspects of 2-dimensional (2D) and 3-dimensional (3D) treatment plans, with the twin aims of evaluating the adequacy of 2D planning fields on coverage of planning target volume (PTV) and 3D conformal plans for both covering PTV and reducing the normal tissue doses. Materials and Methods: Thirty-six patients with stage II-IV gastric adenocarcinoma were treated with adjuvant chemoradiotherapy using 3DRT. For each patient, a second 2D treatment plan was generated. The two techniques were compared for target volume coverage and dose to normal tissues using dose volume histogram (DVH) analysis. Results: 3DRT provides more adequate coverage of the target volume. Comparative DVHs for the left kidney and spinal cord demonstrate lower radiation doses with the 3D technique. Conclusions: 3DRT produced better dose distributions and reduced radiation doses to left kidney and spinal cord compared to the 2D technique. For this reason it can be predicted that 3DRT will result in better tumor control and less normal tissue complications. -
Pimhanam, Chaisak;Sangrajrang, Suleeporn;Ekpanyaskul, Chatchai 7407
The incidence of urban female breast cancer has been continuously increasing over the past decade with unknown etiology. One hypothesis for this increase is carcinogen exposure from tobacco. Therefore, the objective of this study was to investigate the risk of urban female breast cancer from tobacco smoke exposure. The matched case control study was conducted among Thai females, aged 17-76 years and living in Bangkok or its surrounding areas. A total of 444 pairs of cases and controls were recruited from the Thai National Cancer Institute. Cases were newly diagnosed and histologically confirmed as breast cancer while controls were selected from healthy women who visited a patient, matched by age${\pm}5$ years. After obtaining informed consent, tobacco smoke exposure data and information on other potential risk factors were collected by interview. The analysis was performed by conditional logistic regression, and presented with odds ratio (ORs) and 95% confidence intervals(CI). From all subjects, 3.8% of cases and 3.4% of controls were active smokers while 11.0% of cases and 6.1% of controls were passive smokers. The highest to lowest sources of passive tobacco smoke were from spouses (40.8%), the workplace (36.8%) and public areas (26.3%), respectively. After adjusting for other potential risk factors or confounders, females with frequent low-dose passive smoke exposure (${\leq}7$ hours per week) from a spouse or workplace had adjusted odds ratio 3.77 (95%CI=1.11-12.82) and 4.02 (95%CI=1.04-15.50) higher risk of breast cancer compared with non-smokers, respectively. However, this study did not find any association of breast cancer risk in high dose passive tobacco smoke exposure, or a dose response relationship in cumulative passive tobacco smoke exposure per week, or in the active smoker group. In conclusion, passive smoke exposure may be one important risk factor of urban female breast cancer, particularly, from a spouse or workplace. This risk factor highlights the importance of avoiding tobacco smoke exposure as a key measure for breast cancer prevention and control. -
Moradi, Mohammad-Taher;Salehi, Zivar;Aminian, Keyvan;Yazdanbod, Abbas 7413
Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. Materials and Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR). Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC. -
Xu, Cheng;Chen, Pin;Liu, Wei;Gu, Ai-Hua;Wang, Xin-Ru 7419
Gliomas are the most common type of primary brain tumors. The XRCC1 Arg194Trp variant affects the proliferating cell nuclear antigen(PCNA) binding region, which suggests that this mutation may contribute to gliomagenesis and a number of articles have examine the association between XRCC1 Arg194Trp and the susceptibility to glioma. However, the results were conflicting. Test of heterogeneity, sensitivity analysis, meta-analysis, and assessment of publication bias were all performed in our present meta-analysis, covering a total of 5,407 patients and 7,715 healthy persons. In the overall analysis the XRCC1 Arg194Trp polymorphism showed a significant association with glioma susceptibility in a recessive mode l(for TrpTrp vs ArgArg+ArgTrp: OR=1.918, 95%CI=1.575-2.336,$I^2$ =2.3%). In addition, analysis of subgroups presented an increased risk in Asians and populations-based on hospitals. The results suggested that the XRCC1 Arg194Trp polymorphism is a genetic risk factor for glioma, especially in Asian population. To further evaluate gene-gene and gene-environment interactions on XRCC1 polymorphisms and glioma risk, thousands of subjects and tissue-specific biochemical characterizations are required. -
Guo, Miao;Liu, Chao;Qi, Feng-Jie;Zhang, Xiu-Mei;Ren, Li-Li;Liu, Yi-Meng;Meng, Zhi-Chao;Zhu, Zhi-Tu;Xiao, Jian-Ying 7425
Aim: To investigate the expression of protein kinase$CK2{\alpha}$ ($CK2{\alpha}$ ) in human thyroid disease and its relationship with thyroid cancer metastasis. Materials and Methods: Using immunohistochemistry we measured the expression of$CK2{\alpha}$ in 76 benign and malignant human thyroid cancer tissues, including 10 pairs of papillary carcinoma tissues with or without lymph node cancerous metastasis and similarly 10 pairs of lymph nodes. Results: The expression of$CK2{\alpha}$ was found to be higher in thyroid carcinoma cases (papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma) than in ones such as chronic lymphocytic thyroiditis, nodular goiter and adenoma. These findings were also confirmed by RT-PCR and Western blotting. More strikingly, elevated expression of$CK2{\alpha}$ in thyroid papillary carcinoma tissues was not only significantly associated with lymph node cancerous metastasis and clinical stage of thyroid cancers; but also correlated with epithelial-mesenchymal transition (EMT) and high tenascin C (TNC) expression. In addition, EMT and high TNC expression in thyroid carcinoma tissues was significantly associated with lymph node cancerous metastasis. Conclusions: Elevated expression of nuclear$CK2{\alpha}$ is a poor prognosis indicator in lymph node cancerous metastasis of human thyroid cancers. -
Nejadi-Kelarijani, Fatemeh;Roshandel, Gholamreza;Semnani, Shahryar;Ahmadi, Ali;Faghani, Behzad;Besharat, Sima;Akhavan-Tabib, Atefeh;Amiriani, Taghi 7433
Background: Gastric cancer (GC) is the second cause of cancer related death in the world. It may develop by progression from its precancerous condition, called gastric atrophy (GA) due to gastritis. The aim of this study was to evaluate the accuracy of serum levels of pepsinogens (Pg) and gastrin-17 (G17) as non-invasive methods to discriminate GA or GC (GA/GC) patients. Materials and Methods: Subjects referred to gastrointestinal clinics of Golestan province of Iran during 2010 and 2011 were invited to participate. Serum levels of PgI, PgII and G17 were measured using a GastroPanel kit. Based on the pathological examination of endoscopic biopsy samples, subjects were classified into four groups: normal, non-atrophic gastritis, GA, and GC. Receiver operating curve (ROC) analysis was used to determine cut-off values. Indices of validity were calculated for serum markers. Results: Study groups were normal individuals (n=74), non-atrophic gastritis (n=90), GA (n=31) and GC patients (n=30). The best cut-off points for PgI, PgI/II ratio, G17 and HP were$80{\mu}g/L$ , 10, 6 pmol/L, and 20 EIU, respectively. PgI could differentiate GA/GC with high accuracy (AUC=0.83; 95%CI: 0.76-0.89). The accuracy of a combination of PgI and PgI/II ratio for detecting GA/GC was also relatively high (AUC=0.78; 95%CI: 0.70-0.86). Conclusions: Our findings suggested PgI alone as well as a combination of PgI and PgI/II ratio are valid markers to differentiate GA/GC. Therefore, Pgs may be considered in conducting GC screening programs in high-risk areas. -
Oranratanaphan, Shina;Termrungruanglert, Wichai;Khemapech, Nipon 7437
Background: Acceptability of self-sampling HPV testing is confirmed worldwide. However, some cultural differences may affect this question. Therefore, this study was conducted to evaluate the acceptability of self-sampling HPV testing in Thai women. Materials and Methods: One hundred women aged 30-65 years with an intact cervix were included in this study. The participants were asked to do the Pap test by physicians and then brush type self-sampling instruments were assigned for self-collection and finally completed a questionnaire for acceptability evaluation. The questionnaire contains 2 parts. Part one covered general information of the participants and part two is the acceptability questions. Results: Mean age was 40.6 years. The incidence of high risk HPV detection in this study was 16%. The most common reason for doing Pap smear was for annual checkup. On the topic of ease of use, 85 % of the subjects agreed. Most of the participants (82%) reported that they felt less pain. However, reliability of the result was not satisfactory because 37% of the participants hesitated to rely on the results of the test. According to the price, if the price is less than 1,000 Baht (32.59 Baht = 1USD), 82% of the subjects would use it for their next screening. Conclusions: The acceptability of self-sampling device in this study is quite good but the reliability of the test was questioned by some of the participants. Moreover, the price of the test in Thailand may also influence the acceptability of the test. -
Yun, Byung Min;Song, Jung-Kook;Lee, Ji-Young 7443
Aim: Little is known about the genetic associations with Basal cell carcinoma (BCC) risk in non-Caucasian populations, in which BCC is rare, as in Korea. We here conducted a pilot genome-wide association study (GWAS) in 12 patients and 48 standard controls. Method: A total of 263,511 SNPs were analyzed with the Illumina HumanOmni1 Quad v1.0 DNA Analysis BeadChip for cases and Korean HapMap 570K for controls. Results: SNP-based analyses, based on the allele genetic model with adjustment for sex and age showed suggestive associations with BCC risk for 6 SNPs with a P-value (P < 0.0005). However, these associations were not statistically significant after Bonferroni correction: rs1040503, rs2216491, rs13407683, rs4751072, rs9891263, and rs1368474. In addition, results from gene-based analyses showed suggestive associations with BCC risk for 33 candidate genes with a P-value (P <0.0005). Consistent with previous GWAS and replication studies in Caucasian populations, PADI6, RHOU and SLC45A2 were identified as having null associations with BCC (P > 0.05), likely due to the smaller sample size. Conclusions: Although this was a small-scale negative study, to our knowledge, we have conducted the first GWAS for BCC risk in an Asian population. Further large studies in non-Caucasian populations are required to achieve statistical significance and confirm these findings. -
Zhou, Qi;Jiang, Jue;Shang, Xu;Zhang, Hong-Li;Ma, Wen-Qi;Xu, Yong-Bo;Wang, Hua;Li, Miao 7449
Background: The purpose of this study was to investigate the correlation of contrast-enhanced ultrasonographic (CEUS) features with microvessel density (MVD) in papillary thyroid carcinomas (PTCs). Materials and Methods: Contrast-enhanced ultrasonography (CEUS) was performed in 62 patients (17 men and 45 women) with PTC. Tomtec software was applied to analyze the time intensity curve of CEUS. Immunohistochemistry was performed to evaluate the level of MVD in papillary thyroid carcinoma. Then the relationship between quantitative feature and the level of MVD was analyzed using SPSS 16.0 software. Results: The mean peak intensity of PTC tissues was lower than that of peripheral thyroid parenchyma ($61.9{\pm}11.8%$ vs 100%, p<0.05). The MVDs of CD34 and CD31 antibodies staining were$38.0{\pm}6.1$ and$37.9{\pm}5.1$ respectively in 62 PTC samples. A significantly positive correlation was observed between peak intensity and MVD in PTC tissues ($P_{CD34}$ <0.01,$r_{CD34}$ =0.838,$P_{CD31}$ <0.01,$r_{CD31}$ =0.837). Conclusions: The peak intensity in CEUS could reflect the MVD in PTC tissues. Therefore, quantification of CEUS seems to be helpful for assessment of MVD in PTC tissues. -
Fang, Ying;Wang, Li;Xia, Guo-Hao;Shi, Mei-Qi 7453
Objective: To observe the efficacy and toxicity of nanoparticle albumin bound paclitaxel (nab-paclitaxel) plus platinum agent (cisplatin or carboplatin) as first line treatment for stage III/IV squamous non-small-cell lung cancer (NSCLC). Methods: Forty chemotherapy naive patients with stage III/IV squamous NSCLC received nab-paclitaxel$125mg/m^2$ on day 1 and day 8, cisplatin$75mg/m^2$ on day 1, carboplatin area under the concentration-time curve of 5 (AUC=5) on day 1. One cycle of treatment was 3 weeks, and at least two were completed in each case. Results: Of the 40 patients who participated in the study, 25 achieved partial responses (PR), 12 reached a stage of stable disease (SD), and 3 suffered progressive disease (PD). The overall response rate (ORR) was 62.5% and the disease control rate (DCR) was 92.5%. Of the 20 patients without surgery or radiotherapy, 10 achieved PR, 7 reached a stage of SD, and 3 PD. The ORR was 50.0% and the DCR was 85.0%. The median progression-free survival time (PFS) of patients without surgery or radiotherapy was 5.0 months. Of the 20 patients receiving surgery or radiotherapy, 15 had PR and 5 p had SD, with an ORR of 75.0% and a DCR of 85.0%. Specifically, the DDP arm demonstrated a significantly higher ORR than the CBP arm (100%vs 54.5%, P<0.05). Common treatment related adverse events were myelosuppression, gastrointestinal response, baldness and neurotoxicity, most of which were grade 1 to 2. Conclusion: Nab-paclitaxel plus platinum agent (cisplatin or carboplatin) is effective as a first-line chemotheraphy for stage III/IV squamous NSCLC, and its adverse effects are tolerable. -
Zhang, Ya-Xiong;Kang, Shi-Yang;Chen, Gang;Fang, Wen-Feng;Wu, Xuan;You, Hua-Jing;He, Da-Cheng;Cao, Ya-Lin;Liang, Wen-Hua;Zhang, Li 7459
Background: A prior study showed blood type A/AB to be associated with an increased risk of nasopharyngeal carcinoma (NPC) compared to subjects with blood type O. However, the relationship between ABO blood groups and prognosis of NPC patients is still questionable. In addition, whether Epstein-Barr virus (EBV) infection is associated with prognosis of NPC patients with different ABO blood groups is unclear. Materials and Methods: We conducted univariate and multivariable Cox regression analyses based on a consecutive cohort of 1,601 patients to investigate the above issues. Results: There was no significant difference in overall survival (OS) between different ABO blood groups (p=0.629), neither between A vs. non-A blood groups (p=0.895) nor AB vs. non-AB blood group (p=0.309) in univariate analyses and after adjusting for other factors. Interaction tests revealed that high immunoglobulin A against Epstein-Barr virus viral capsid antigen (VcA-IgA) level was associated with a favorable prognosis in male patients with UICC stage II disease who had an A blood type (p=0.008), compared with those with non-A blood type. In addition, male patients with an A blood group with a high blood lymphocyte level showeda tendency towards better survival in UICC stage III (p=0.096). Conclusions: ABO blood group status is not associated with the prognosis of patients with NPC. Additionally, blood group A male NPC patients with high VcA-IgA level or high blood lymphocyte counts might be correlated with a favorable prognosis in UICC stage II or III, respectively. -
Yang, Zhi-Ping;Xie, Yong-Hong;Ling, Dan-Yan;Li, Jin-Rui;Jiang, Jin;Fan, Yao-Hua;Zheng, Jia-Lian;Wu, Wan-Xin 7467
SCY1-like 1-binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is very important for the development of human cancer. However, the effects of SCYL1BP1 on human lung squamous carcinoma cell biological behavior remain poorly understood. In this study, we present evidence that SCYL1BP1 can promote the degradation of MDM2 protein and further inhibit the G1/S transition of lung squamous carcinoma cell lines. Functional assays found that reintroduction of SCYL1BP1 into lung squamous carcinoma cell lines significantly inhibited cell proliferation, migration, invasion and tumor formation in nude mice, suggesting strong tumor suppressive function of SCYL1BP1 in lung squamous carcinoma. Taken together, our data suggest that the interaction of SCYL1BP1/MDM2 could accelerate MDM2 degradation, and may function as an important tumor suppressor in lung squamous carcinomas. -
Janeklang, Somkid;Nakaew, Archawin;Vaeteewoottacharn, Kulthida;Seubwai, Wunchana;Boonsiri, Patcharee;Kismali, Gorkem;Suksamrarn, Apichart;Okada, Seiji;Wongkham, Sopit 7473
Cholangiocarcinoma (CCA) is a fatal cancer with poor prognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in unfavorable outcomes. At present, plant-derived compounds are gaining interest as potential cancer therapeutics, particularly for treatment-refractory cancers. In this study, antitumor activity of tiliacorinine, the major alkaloid isolated from a tropical plant, on CCA was first demonstrated. Antiproliferative effects of tiliacorinine on human CCA cell lines were investigated using SRB assays. Acridine orange/ethidium bromide staining, flow cytometric analysis and DNA laddering assays were used for apoptotic determination. Apoptosis-related proteins were verified by Western blotting and antitumor activity of tiliacorinine in vivo was demonstrated in CCA xenografted mice. Tiliacorinine significantly inhibited proliferation of human CCA cell lines with$IC_{50}$ $4.5-7{\mu}M$ by inducing apoptosis through caspase activation, upregulation of BAX, and downregulation of$Bcl_{xL}$ and XIAP. Tiliacorinine considerably reduced tumor growth in CCA xenografted mice. These results demonstrated antitumor effects of tiliacorinine on human CCA in vitro and in vivo. Tiliacorinine may be an effective agent for CCA treatment. -
Poomphakwaen, Kirati;Promthet, Supannee;Suwanrungruang, Krittika;Chopjitt, Peechanika;Songserm, Nopparat;Wiangnon, Surapon 7479
Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. This study aimed to investigate the interaction between the presence of a polymorphism of the XRCC1 gene and known risk factors for colorectal cancer in Thailand. Materials and Methods: A hospital-based case-control study was conducted in Thailand. The participants were 230 histologically confirmed new cases and 230 controls matched by sex and age and recruited from the same hospital. Information about demographic characteristics, life style, and dietary habits was collected using structured interviews, and blood samples were taken which were used for the detection of a homozygous and heterozygous polymorphisms of XRCC1. Associations were assessed using multiple conditional logistic regression. Results: In the univariate analysis, factors found to be significantly associated with an increased risk for CRC were the presence of the XRCC1 AA homozygote (OR= 4.95; 95% CI: 1.99-12.3), a first degree family history of cancer (OR= 1.74; 95% CI: 1.18-2.58), and a high frequency of pork consumption (OR= 1.49; 95% CI: 1.00-2.21). Intakes of fish fruit and vegetables appeared to be protective factors, but the associations were not statistically significant. In the multivariate analysis only the XRCC1 AA homozygote polymorphism and a family history of cancer emerged as risk factors (OR= 4.96; 95% CI: 1.90- 12.95 and OR=1.80; 95% CI: 1.18-2.72, respectively). Conclusions: While the XRCC1 AA homozygote and a family history of cancer were found to be associated with an increased risk of CRC, none of the dietary intake variables were clearly identified as risk or protective factors. There is a need for further research to determine the reasons for this. -