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.
KSCI제15권15호
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He, Jin-Peng;Hao, Yun;Wang, Xiao-Lin;Yang, Xiao-Jin;Shao, Jing-Fan;Guo, Feng-Jin;Feng, Jie-Xiong 5967
Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA. -
Nogueira, Daniele Rubert;Yaylim, Ilhan;Aamir, Qurratulain;Kahraman, OzlemTimirci;Fayyaz, Sundas;Naqvi, Syed Kamran-Ul-Hassan;Farooqi, Ammad Ahmad 5977
Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced by findings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites. -
Emerging and Established Global Life-Style Risk Factors for Cancer of the Upper Aero-Digestive TractIntroduction: Upper aero-digestive tract cancer is a multidimensional problem, international trends showing complex rises and falls in incidence and mortality across the globe, with variation across different cultural and socio-economic groups. This paper seeks some explanations and identifies some research and policy needs. Methodological Approach: The literature illustrates the multifactorial nature of carcinogenesis. At the cellular level, it is viewed as a multistep process involving multiple mutations and selection for cells with progressively increasing capacity for proliferation, survival, invasion, and metastasis. Established and emerging risk factors, in addition to changes in incidence and prevalence of cancers of the upper aero-digestive tract, were identified. Risk Factors: Exposure to tobacco and alcohol, as well as diets inadequate in fresh fruits and vegetables, remain the major risk factors, with persistent infection by particular so-called "high risk" genotypes of human papillomavirus increasingly recognised as also playing an important role in a subset of cases, particularly for the oropharynx. Chronic trauma to oral mucosa from poor restorations and prostheses, in addition to poor oral hygiene with a consequent heavy microbial load in the mouth, are also emerging as significant risk factors. Conclusions: Understanding and quantifying the impact of individual risk factors for these cancers is vital for health decision-making, planning and prevention. National policies and programmes should be designed and implemented to control exposure to environmental risks, by legislation if necessary, and to raise awareness so that people are provided with the information and support they need to adopt healthy lifestyles.
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Ye, Ni;Wang, Bin;Quan, Zi-Fang;Cao, San-Jie;Wen, Xin-Tian;Huang, Yong;Huang, Xiao-Bo;Wu, Rui;Ma, Xiao-Ping;Yan, Qi-Gui 5993
The discovery of long noncoding RNA (LncRNA) changes our view of transcriptional and posttranscriptional regulation of gene expression. With application of new research techniques such as high-throughput sequencing, the biological functions of LncRNAs are gradually becoming to be understood. Multiple studies have shown that LncRNAs serve as carcinogenic factors or tumor suppressors in breast cancer with abnormal expression, prompts the question of whether they have potential value in predicting the stages and survival rate of breast cancer patients, and also as therapeutic targets. Focusing on the latest research data, this review mainly summarizes the tumorigenic mechanisms of certain LncRNAs in breast cancer, in order to provide a theoretical basis for finding safer, more effective treatment of breast cancer at the LncRNA molecular level. -
Pesticides used in Korea are grouped by four classes of hazard (extremely, highly, moderately and slightly hazardous) based on acute oral and dermal toxicity in the rat. However, there is little information of carcinogenic effects. The aim of this study was to evaluate potential carcinogenicity for active ingredients of pesticides used in Korea. A total of 1,283 pesticide items were registered under the Pesticide Control Act of which 987 were commercially available. Of these 987 items, 360 active ingredients not duplicated were evaluated for carcinogenicity using the carcinogen list established by the US Environmental Protection Agency (EPA). Some 25 out of 360 ingredients were classified as likely to be carcinogenic (probable) to humans and 52 had suggestive evidence of carcinogenic potential (suspected) based on the US EPA classification. Some 31% of 987 items contained probable or suspected human carcinogenic ingredients. Carcinogenic pesticides accounted for 24% (5,856/24,795 tons) of the total volume of consumption in Korea. Interestingly, pesticides with lower acute toxicity were found to have higher carcinogenic potential. Based on these findings, the study suggests that it is important to provide information on long-term toxicity to farmers, in addition to acute toxicity data.
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Boonlikit, Sathone;Srichongchai, Hemwadee 6005
Aim: To compare recurrence rates of large loop excision of the transformation zone (LLETZ) with those of contour-loop excision of the transformation zone (C-LETZ) in the management of cervical intraepithelial neoplasia (CIN). Materials and Methods: The medical records of 177 patients treated consecutively by LLETZ and C-LETZ for CIN at Rajavithi Hospital between 2006 and 2009 were retrospectively reviewed. Results: Of the 87 women in the C-LETZ group, 2 cases (2.30%) had recurrence compared with 13 cases (14.4%) of the 90 women in the LLETZ group, the higher recurrence rate in the latter being statistically significant (p<0.05). Median times of follow up in the C-LETZ and LLETZ groups were 12 months and 14 months respectively (p>0.05). The C-LETZ group showed less intraoperative bleeding compared to the LLETZ group, but the rate of achievement of single specimens and positive margins were similar in the two groups. Conclusions: The present study demonstrated the superiority of C-LETZ over LLETZ in terms of efficacy; C-LLETZ is associated with a lower recurrence rate and also carries a smaller risk of intraoperative bleeding than LLETZ. The rotating technique still has a potential role in treating precancerous lesions of the cervix. -
Jin, Congguo;Li, Jia;Wang, Yeying;Chen, Xiaoqun;Che, Yanhua;Liu, Xin;Wang, Xicai;Sriplung, Hutcha 6009
Aims: To investigate changes in cellular immune function of patients with lung cancer before and after cytokine-induced killer (CIK) cell therapy and to identify variation effects on overall survival (OS) and progression-free survival (PFS). Materials and Methods:A total of 943 lung cancer patients with immune dysfunction were recruited from January 2002 to January 2010, 532 being allocated to conventional therapy and 411 to CIK therapy after a standard treatment according to the NCCN Clinical Practice Guidelines. All the patients were investigated for cellular immune function before and after therapy every three months. and clinical prognostic outcomes were analyzed. Results: After six courses of treatment, immune function was much improved in patients receiving CIK cells therapy as compared to controls. The percentages of recurrence and/or metastases for patients undergoing CIK cell therapy was 56.2% and 49.1% respectively but 78.6% and 70.3% among controls (p<0.001). The median OS times for CIK cell therapy and control groups were 48 and 36 months respectively. The OS rates at 12, 36, 60, 84 months in CIK treated patients were 97.8%, 66.9%, 27.7%, and 4.1% while they were 92.3%, 44.5%, 9.2%, and 1.5% in controls. OS and PFS were significantly different by log rank test between the two groups and across the three immune improvement classes. Conclusions: The immune function of lung cancer patients was improved by CIK cell therapy, associated with an increase in the OS rate and extension of the time to recurrence and/or metastasis. -
Ma, Xue-Lei;Li, Yan-Yan;Zhang, Jing;Huang, Jing-Wen;Jia, Hong-Yuan;Liu, Lei;Li, Ping 6015
Background: Isolation and characterization of circulating tumor cells (CTCs) in patients suffering from a variety of different cancers have become hot biomarker topics. In this study, we evaluated the prognostic value of CTCs in pancreatic cancer. Materials and Methods: Initial literature was identified using Medline and EMBASE. The primary data were hazard ratios (HRs) with 95% confidence intervals (CIs) of survival outcomes, including overall survival (OS) and progression free survival/recurrence free survival (PFS/RFS). Results: A total of 9 eligible studies were included in this meta-analysis, published between 2002 and 2013. The estimated pooled HR and 95%CI for OS for all studies was 1.64 (95%CI 1.39-1.94, p<0.00001) and the pooled HR and 95%CI for RFS/DFS was 2.36 (95%CI 1.41-3.96, p<0.00001). The HRs and 95%CIs for OS and RFS/DFS in patients before treatment were 1.93 (95%CI 1.26-2.96, p=0.003) and 1.82 (95%CI 1.22-2.72, p=0.003), respectively. In patients receiving treatment, the HRs and 95%CI for OS and RFS/DFS were 1.37 (95%CI 1.00-1.86, p=0.05) and 1.89 (95%CI 1.01-3.51, p=0.05), respectively. Moreover, the pooled HR and 95%CI for OS in the post-treatment group was 2.20 (95%CI 0.80-6.02, p=0.13) and the pooled HR for RFS/DFS was 8.36 (95%CI 3.22-21.67, p<0.0001). Conclusions: The meta-analysis provided strong evidence supporting the proposition that CTCs detected in peripheral blood have a fine predictive role in pancreatic patients especially on the time point of post-treatment. -
Chen, Guang-Lie;Hou, Gai-Ling;Sun, Fei;Jiang, Hong-Li;Xue, Jin-Feng;Li, Xiu-Shen;Xu, En-Hui;Gao, Wei-Shi;Cao, Jian-Ping 6021
Background: The STK15 gene located on chromosome 20q13.2 encodes a centrosome-associated kinase critical for regulated chromosome segregation and cytokinesis. Recent studies have demonstrated STK15 to be significantly associated with many tumors, with aberrant expression obseved in many human malignancies. The purpose of this study was to investigate expression of STK15 in esophageal squamous cell carcinomas (ESCCs) in a Mongolian population. Methods: Two non-synonymous single nucleotide polymorphisms in the coding region of STK15, rs2273535 (Phe31Ile) and rs1047972 (Val57Ile) were assessed in 380 ESCC patients and 380 healthy controls. We also detected STK15 mRNA expression in 39 esophageal squamous cell carcinomas and corresponding adjacent tissues by real time PCR. Results: rs2273535 showed a significant association with ESCC in our Mongolian population (rs227353, P allele = 0.0447, OR (95%CI) = 1.259 (1.005~1.578)). Real time PCR analysis of ESCC tissues showed that expression of STK15 mRNA in cancer tissues was higher than in normal tissues (p = 0.013). Conclusions: Our study showed that functional SNPs in the STK15 gene are associated with ESCC in a Mongolian population and up-regulation of STK15 mRNAoccurs in ESCC tumors compared adjacent normal tissues. STK15 may thus have an important role in the prognosis of ESCC and be a potential therapeutic target. -
Akca, Zeki;Mutlu, Hasan;Erden, Abdulsamet;Buyukcelik, Abdullah;Cihan, Yasemin Benderli;Goksu, Sema Sezgin;Aslan, Tuncay;Sezer, Emel Yaman;Inal, Ali 6025
Background: Because of the relative rarity of biliary tract cancers (BTCs), defining long term survival results is difficult. In the present study, we aimed to evaluate the survival of a series of cases in Turkey. Materials and Methods: A totally of 47 patients with billiary tract cancer from Mersin Goverment Hospital, Acibadem Kayseri Hospital and Kayseri Training and Research Hospital were analyzed retrospectively using hospital records between 2006-2012. Results: The median overall survival was$19.3{\pm}3.9$ months for all patients. The median disease free and overall survivals were$24.3{\pm}5.3$ and$44.1{\pm}12.9$ months in patients in which radical surgery was performed, but in those with with inoperable disease they were only$5.3{\pm}1.5$ and$10.7{\pm}3.2$ months, respectively. Conclusions: BTCs have a poor prognosis. Surgery with a microscopic negative margin is still the only curative treatment. -
Che, Yanhua;You, Jing;Zhou, Shaojiang;Li, Li;Wang, Yeying;Yang, Yue;Guo, Xuejun;Ma, Sijia;Sriplung, Hutcha 6029
The burden and severity of a cancer can be reflected by patterns of survival. Breast cancer prognosis between two countries with a different socioeconomic status and cultural beliefs may exhibit wide variation. This study aimed to describe survival in patients with breast cancer in China and Thailand in relation to demographic and clinical prognostic information. Materials and Methods: We compared the survival of 1,504 Chinese women in Yunnan province and 929 Thai women in Songkhla with breast cancer from 2006 to 2010. Descriptive prognostic comparisons between the Chinese and Thai women were performed by relative survival analysis. A Cox regression model was used to calculate the hazard ratios of death, taking into account the age, disease stage, period of diagnosis and country. Results: The overall 5-year survival proportion for patients diagnosed with breast cancer for Yunnan province (0.72) appeared slightly better than Songkhla (0.70) without statistical significance. Thai women diagnosed with distant and regional breast cancer had poorer survival than Chinese women. Disease stage was the most important determinant of survival from the results of Cox regression model. Conclusions: Breast cancer patients in Kunming had slightly greater five-year survival rate than patients in Songkhla. Both Chinese and Thai women need improvement in prognosis, which could conceivably be attained through increased public education and awareness regarding early detection and compliance to treatment protocols. -
Mahmoudi, Touraj;Karimi, Khatoon;Arkani, Maral;Farahani, Hamid;Nobakht, Hossein;Dabiri, Reza;Asadi, Asadollah;Zali, Mohammad Reza 6035
Background: Substantial evidence from epidemiological studies has suggested that increased levels of calcium may play a protective role against colorectal cancer (CRC). Given the vital role of calcium sensing receptor (CaSR) and parathyroid hormone (PTH) in the maintenance of calcium homeostasis, we explored whether the rs1801725 (A986S) variant located in exon 7 of the CaSR gene and the rs6256 variant located in exon 3 of PTH gene might be associated with CRC risk. Materials and Methods: In this study 860 subjects including 350 cases with CRC and 510 controls were enrolled and genotyped using PCR-RFLP methods. Results: We observed no significant difference in genotype or allele frequencies between the cases with CRC and controls for both CaSR and PTH genes either before or after adjustment for confounding factors including age, BMI, sex, smoking status, and family history of CRC. Furthermore, no evidence for effect modification of any association of rs1801725 and rs6256 variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI <$25kg/m^2$ ) cases and overweight/obese (BMI${\geq}25kg/m^2$ ) cases for the two SNPs. Conclusions: These data indicated that the CaSR gene A986S variant is not a genetic contributor to CRC risk in the Iranian population. Furthermore, our results suggest for the first time that PTH gene variant does not affect CRC risk. Nonetheless, further studies with larger sample size are needed to validate these findings. -
Lu, Jing;Qin, Qin;Zhan, Liang-Liang;Yang, Xi;Xu, Qing;Yu, Jing;Dou, Li-Na;Zhang, Hao;Yang, Yan;Chen, Xiao-Chen;Yang, Yue-Hua;Cheng, Hong-Yan;Sun, Xin-Chen 6041
Objective: Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20% of all mesenchymal malignancies, often occurring in deep soft tissue of retroperitoneal space. Accurate preoperative diagnosis is therefore necessary. We explored whether computed tomography (CT) could be used to differentiate between the various types of retroperitoneal liposarcoma (RPLS). Method: Forty-seven cases of RPLS, diagnosed surgically and histologically, were analyzed retrospectively. CT features were correlated with postoperative pathological appearance. Results: The study radiologist identified 29, 11, 2, 2 and 3 RPLS as atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), dedifferentiated liposarcoma (DDL), myxoid/round cell liposarcoma (ML/RCL), pleomorphic liposarcoma (PL) and mixed-type liposarcoma. Analysis of CT scans revealed the following typical findings of the different subtypes of RPLS: ALT/WDL was mainly visible as a well-delineated fatty hypodense tumor with uniform density and integrity margin; DDL was marked by the combination of focal nodular density and hypervascularity. ML/RCL, PL and mixed liposarcoma showed malignant biological behaviour and CT findings need further studies. Conclusions: CT scanning can reveal important details including internal components, margins and surrounding tissues. Based on CT findings, tumor type can be roughly evaluated and biopsy location and therapeutic scheme guided. -
Lu, Zhi-Hao;Yang, Li;Yu, Jing-Wei;Lu, Ming;Li, Jian;Zhou, Jun;Wang, Xi-Cheng;Gong, Ji-Fang;Gao, Jing;Zhang, Xiao-Tian;Li, Jie;Li, Yan;Shen, Lin 6047
Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy:>5% weight loss group and${\leq}5%$ weight loss group. Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss >5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) Conclusions: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients. -
Oz, Murat;Ozgu, Emre;Korkmaz, Elmas;Bayramoglu, Hatice;Erkaya, Salim;Gungor, Tayfun 6053
Aim: To determine utility of the frozen section (FS) in the operative management of endometrial pre-malignant lesions. Materials and Methods: We retrospectively analyzed patients who underwent abdominal hysterectomy with preoperative diagnosis of complex atypical endometrial hyperplasia (CAEH) and simple endometrial hyperplasia (SEH) between May 2007 and December 2013. Frozen and paraffin section (PS) results were compared. Sensitivity, specificity, the positive predictive value (PPV), the negative predictive value (NPV) and the accuracy in predicting EC on FS were evaluated with 95% confidence intervals (CIs) for each parameter. The correlation between FS and PS was calculated as an${\kappa}$ coefficient. Results: Among 143 preoperatively diagnosed CAEH cases, 60 (42%) were malignant and 83 (58%) were benign in PS; and among 60 malignant cases diagnosed in PS, 43 (71%) were "malignant" in FS. Sensitivity, specificity, PPV and NPV for FS were 76%, 100%, 100% and 87.5%, respectively. Conclusions: We found that FS is reliable and applicable in the management of endometrial hyperplasias. It is important that the pathologist should be experienced because FS for endometrial pre-malignant lesions has significant inter-observer variability. The other conclusion is that patients with the diagnosis of EH, especially those who are postmenopausal, should undergo surgery where FS investigation is available. -
Magaji, Bello Arkilla;Moy, Foong Ming;Roslani, April Camilla;Law, Chee Wei 6059
Background: Colorectal cancer is the second most frequent cancer in Malaysia. Nevertheless, there is little information on treatment and outcomes nationally. We aimed to determine the demographic, clinical and treatment characteristics of colorectal cancer patients treated at the University Malaya Medical Centre (UMMC) as part of a larger project on survival and quality of life outcomes. Materials and Methods: Medical records of 1,212 patients undergoing treatment in UMMC between January 2001 and December 2010 were reviewed. A retrospective-prospective cohort study design was used. Research tools included the National Cancer Patient Registration form. Statistical analysis included means, standard deviations (SD), proportions, chi square, t-test/ANOVA. P-value significance was set at 0.05. Results: The male: female ratio was 1.2:1. The mean age was 62.1 (SD12.4) years. Patients were predominantly Chinese (67%), then Malays (18%), Indians (13%) and others (2%). Malays were younger than Chinese and Indians (mean age 57 versus 62 versus 62 years, p<0.001). More females (56%) had colon cancers compared to males (44%) (p=0.022). Malays (57%) had more rectal cancer compared to Chinese (45%) and Indians (49%) (p=0.004). Dukes' stage data weres available in 67%, with Dukes' C and D accounting for 64%. Stage was not affected by age, gender, ethnicity or tumor site. Treatment modalities included surgery alone (40%), surgery and chemo/radiotherapy 32%, chemo and radiotherapy (8%) and others (20%). Conclusions: Significant ethnic differences in age and site distribution, if verified in population-based settings, would support implementation of preventive measures targeting those with the greatest need, at the right age. -
Chim-ong, Anongruk;Thawornkuno, Charin;Chavalitshewinkoon-Petmitr, Porntip;Punyarit, Phaibul;Petmitr, Songsak 6065
Background: Breast cancer is the most common malignancy in women worldwide, including Thailand, and is a major cause of mortality and morbidity, despite advances in diagnosis and treatment. Novel gene expression in breast cancer is a focus in searches for prognostic biomarkers and new therapeutic targets. Materials and Methods: The mRNA expression of novel B4GALT4, SLC35B2, and WDHD1 genes in breast cancer were examined in invasive ductal breast carcinoma (IDC) patients using quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR). Results: Among these genes, increased expression of SLC35B2 mRNA was significantly associated with TNM stage III + IV of IDC (p<0.001). Hence, up-regulation of SLC35B2 may serve as a prognostic biomarker for poor prognosis, and is also a potential therapeutic target in breast cancer. -
Ma, Yong-Jun;Feng, Sheng-Chun;Hu, Shao-Long;Zhuang, Shun-Hong;Fu, Guan-Hua 6071
Background: Evidence suggests that the rs11615 (C>T) polymorphism in the ERCC1 gene may be a risk factor for gynecological tumors. However, results have not been consistent. Therefore we performed this meta-analysis. Methods: Eligible studies were identified by search of PubMed, MEDLINE and Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess associations between rs11615 (C>T) and gynecological tumor risk. Heterogeneity among studies was tested and sensitivity analysis was applied. Results: A total of 6 studies were identified, with 1,766 cases and 2,073 controls. No significant association was found overall between rs11615 (C>T) polymorphism and gynecological tumors susceptibility in any genetic model. In further analysis stratified by cancer type, significantly elevated ovarian cancer risk was observed in the homozygote and recessive model comparison (TT vs. CC: OR=1.69, 95% CI=1.03-2.77, heterogeneity=0.876; TT vs. CT/CC: OR=1.72, 95% CI=1.07-2.77, heterogeneity=0.995). Conclusion: The results of the present meta-analysis suggest that there is no significant association between the rs11615 (C>T) polymorphism and gynecological tumor risk, but it had a increased risk in ovarian cancer. -
Liu, Dan-Dan;Ye, Yi-Lu;Zhang, Jing;Xu, Jia-Ni;Qian, Xiao-Dong;Zhang, Qi 6075
Lung cancer is the leading cause of cancer-related death worldwide. Here we investigated the antitumor effect and mechanism of Zhejiang (Huzhou and Jiande) saffron against lung cancer cell lines, A549 and H446. Using high performance liquid chromatography (HPLC), the contents of crocin I and II were determined. In vitro, MTT assay and annexin-V FITC/PI staining showed cell proliferation activity and apoptosis to be changed in a dose- and time-dependent manner. The inhibition effect of Jiande saffron was the strongest. In vivo, when mice were orally administered saffron extracts at dose of 100mg/kg/d for 28 days, xenograft tumor size was reduced, and ELISA and Western blotting analysis of caspase-3, -8 and -9 exhibited stronger expression and activity than in the control. In summary, saffron from Zhejiang has significant antitumor effects in vitro and in vivo through caspase-8-caspase-9-caspase-3 mediated cell apoptosis. It thus appears to have more potential as a therapeutic agent. -
Ibrahim, Suzan Seif;Al-Attas, Safia Ali;Darwish, Zeinab Elsayed;Amer, Hala Abbas;Hassan, Mona Hassan 6081
Background: To evaluate the effectiveness of Microlux/DL with and without toluidine blue in screening of potentially malignant and malignant oral lesions. Materials and Methods: In this diagnostic clinical trial clinical examination was carried out by two teams: 1) two oral medicine consultants, and 2) two general dentists. Participants were randomly and blindly allocated for each examining team. A total of 599 tobacco users were assessed through conventional oral examination (COE); the examination was then repeated using Microlux/DL device and toluidine blue. Biopsy of suspicious lesions was performed. Also clinicians opinions regarding the two tools were obtained. Results: The sensitivity and, specificity and positive predictive value (PVP) of Microlux/DL for visualization of suspicious premalignant lesions considering COE as a gold standard (i.e screening device) were 94.3%, 99.6% and 96.2% respectively, while they were 100%, 32.4% and 17.9% when considering biopsy as a gold standard. Moreover, Microlux/DL enhanced detection of the lesion and uncovered new lesions compared to COE, whereas it did not alter the provisional clinical diagnosis, or alter the biopsy site. On the other hand, adding toluidine blue dye did not improve the effectiveness of the Microlux/DL system. Conclusions: The Microlux/DL seems to be a promising adjunctive screening device. -
Arikan, Sevim Kalsen;Kasap, Burcu;Yetimalar, Hakan;Yildiz, Askin;Sakarya, Derya Kilic;Tatar, Sumeyra 6087
Purpose: The aim of the present study was to invesitigate the impact of significant clinico-pathological prognostic factors on survival rates and to identify factors predictive of poor outcome in patients with ovarian carcinoma. Materials and Methods: A retrospective chart review of 74 women with pathologically proven ovarian carcinoma who were treated between January 2006 and April 2011 was performed. Patients were investigated with respect to survival to find the possible effects of age, gravida, parity, menstruel condition, pre-operative Ca-125, treatment period, cytologic washings, presence of ascites, tumor histology, stage and grade, maximal tumor diameter, adjuvan chemotherapy and cytoreductive success. Also 55 ovarian carcinoma patients were investigated with respect to prognostic factors for early 2-year survival. Results: The two-year survival rate was 69% and the 5-year survival rate was 25.5% for the whole study population. Significant factors for 2-year survival were preoperative CA-125 level, malignant cytology and FIGO clinical stage. Significant factors for 5-year survival were age, preoperative CA-125 level, residual tumor, lymph node metastases, histologic type of tumor, malignant cytology and FIGO clinical stage. Logistic regression revealed that independent prognostic factors of 5-year survival were patient age, lymph node metastasis and malignant cytology. Conclusions: We consider quality registries with prospectively collected data to be one important tool in monitoring treatment effects in population-based cancer research. -
Swapnajaswanth, M.;Suman, G.;Suryanarayana, S.P.;Murthy, N.S. 6095
Background:Cervical cancer is potentially the most preventable and treatable cancer. Despite the known efficacy of cervical screening, a significant number of women do not avail themselves of the procedure due to lack of awareness. Objectives: This study was conducted to elicit information on the knowledge, attitude and practice (KAP) regarding screening (Pap test) and vaccination for carcinoma cervix among female doctors and nurses in a tertiary care hospital in Bangalore and to assess barriers to acceptance of the Pap test. Materials and Methods: A cross-sectional, descriptive study was conducted with semi-structured, self-administered questionnaire among female health professionals. The study subjects were interviewed for KAP regarding risk factors for cancer cervix, Pap test and HPV vaccination for protection against carcinoma cervix. Results: Higher proportion of doctors 45 (78.9%) had very good knowledge as compared to only 13 (13.3%) of the nurses, about risk factors for cancer cervix and Pap test (p=0.001). As many as 138(89.6%) of the study subjects had favorable attitude towards Pap test and vaccination, but 114 (73.6%) of the study subjects never had a Pap test and the most common reason 35 (31%) for not practicing was absence of disease symptoms. Conclusions: In spite of good knowledge and attitudes towards cancer cervix and Pap test being good, practice remained low among the study subjects and most common reasons for not undergoing Pap test was absence of disease symptoms. The independent predictors of ever having a Pap test done was found to be the occupation and duration of married life above 9yrs. Hence there is a strong need to improve uptake of Pap test by health professionals by demystifying the barriers. -
Zhang, Xue-Zhong;Su, Ai-Ling;Hu, Ming-Qiu;Zhang, Xiu-Qun;Xu, Yan-Li 6099
Purpose: To retrospectively analyze variability and clinical significance of serum ferritin levels in Chinese patients with hematologic malignancies. Materials and Methods: Serum ferritin were measured by radioimmunoassay, using a kit produced by the Beijing Institute of Atomic Energy. Patients with hematologic malignancies, and treated in the Department of Hematology in Nanjing First Hospital and fulfilled study criteria were recruited. Results: Of 473 patients with hematologic malignancies, 262 patients were diagnosed with acute leukemia, 131 with lymphoma and 80 with multiple myeloma. Serum ferritin levels of newly diagnosed and recurrent patients were significantly higher than those entering complete remission stage or in the control group (p<0.001). Conclusions: Serum ferritin lever in patients with hematologic malignancies at early stage and recurrent stage are significantly increased, so that detection and surveillance of changes of serum ferritin could be helpful in assessing conditions and prognosis of this patient cohort. -
Zeng, Rong;Duan, Lei;Kong, Yu-Ke;Wu, Xiao-Lu;Wang, Ya;Xin, Gang;Yang, Ke-Hu 6103
Many studies have reported${\beta}$ -catenin involvement in the development of esophageal carcinoma (EC), but its prognostic significance for EC patients remains controversial. Therefore, we conducted this meta-analysis to explore the issue in detail. After searching PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature Database, we included a total of ten relevant studies. We pooled the overall survival (OS) data using RevMan 5.2 software. The results showed that aberrant expression of${\beta}$ -catenin was associated with a significant increase of mortality risk (hazard ratio 1.71, 95%CI 1.46-2.01; p<0.00001). Subgroup analyses further suggested that aberrant expression of${\beta}$ -catenin resulted in poor OS of EC patients regardless of histological type of EC, study location or criteria for aberrant expression of${\beta}$ -catenin, and the sensitivity analyses revealed that the result was robust. The meta-analysis revealed that aberrant expression of${\beta}$ -catenin could be a predicative factor of poor prognosis for EC patients. -
Widodo, Irianiwati;Dwianingsih, Ery Kus;Triningsih, Ediati;Utoro, Totok;Soeripto, Soeripto 6109
Background: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. Aim: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. Materials and Methods: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's Chi-Square test. A p-value of <0.05 was considered statistically significant. Results: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal-like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. Conclusions: This study suggests that immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype. -
Padoongcharoen, Prawat;Krusun, Srichai;Palusuk, Voranipit;Pesee, Montien;Supaadirek, Chunsri;Thamronganantasakul, Komsan 6115
Background: To compare the KKU-model rectal tube (KKU-tube) and the conventional rectal tube (CRT) for checking rectal doses during high-dose-rate intracavitary brachytherapy (HDR-ICBT) of cervical cancer. Materials and Methods: Between February 2010 and January 2011, thirty -two patients with cervical cancer were enrolled and treated with external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT). The KKU-tube and CRT were applied intrarectally in the same patients at alternate sessions as references for calculation of rectal doses during ICBT. The gold standard references of rectum anatomical markers which are most proximal to radiation sources were anterior rectal walls (ARW) adjacent to the uterine cervix demonstrated by barium sulfate suspension enema. The calculated rectal doses derived from actual anterior rectal walls, CRT and the anterior surfaces of the KKU-tubes were compared by using the paired t-test. The pain caused by insertion of each type of rectal tube was assessed by the visual analogue scale (VAS). Results: The mean dose of CRT was lower than the mean dose of ARW ($Dmean_0-Dmean_1$ ) by$80.55{\pm}47.33cGy$ (p-value <0.05). The mean dose of the KKU-tube was lower than the mean dose of ARW ($Dmean_0-Dmean_2$ ) by$30.82{\pm}24.20cGy$ (p-value <0.05). The mean dose difference [($Dmean_0-Dmean_1$ )-($Dmean_0-Dmean_2$ )] was$49.72{\pm}51.60cGy$ , which was statistically significant between 42.32 cGy -57.13 cGy with the t-value of 13.24 (p-value <0.05). The maximum rectal dose by using CRT was higher than the KKU-tube as much as 75.26 cGy and statistically significant with the t-score of 7.55 (p-value <0.05). The mean doses at the anterior rectal wall while using the CRTs and the KKU-tubes were not significantly different (p-value=0.09). The mean pain score during insertion of the CRT was significantly higher than the KKU-tube by a t-score of 6.15 (p-value <0.05) Conclusions: The KKU-model rectal tube was found to be an easily producible, applicable and reliable instrument as a reference for evaluating the rectal dose during ICBT of cervical cancer without negative effects on the patients. -
Bidgoli, Sepideh Arbabi;Jabari, Nasim;Zavarhei, Mansour Djamali 6121
Background: Prostate-specific antigen (PSA) is a potential biomarker for early detection of prostate cancer (PCa) but its level is known to be affected by many background factors and roles of ubiquitous toxicants have not been determined. Endocrine disrupting chemicals (EDCs) are ubiquitous reproductive toxicants used in consumer products, which promote tumor formation in some reproductive model systems by binding to AhR, but human data on its expression in prostate cancer as well as its association with PSA levels are not clear. This study aimed to evaluate the expression levels of AhR and its association with serological levels of PSA and to detect possible effects of background factors and EDC exposure history on PSA levels in PCa cases. Materials and Methods: A cross-sectional study was conducted on the tissue levels of AhR and serum levels of PSA in 53 PCa cases from 2008-2011 and associations between each and background and lifestyle related factors were determined. Results: Although the AhR was overexpressed in PCa and correlated with the age of patients, it did not correlate with PSA levels.Of nutritional factors, increased intake of polysaturated fats and fish in the routine regimen of PCa cases increased the PSA levels significantly. Conclusions: AhR overexpression in PCa pontws to roles of EDCs in PCa but without any direct association with PSA levels. However, PSA levels are affected by exposure to possible toxicants in foods whichneed to be assessed as possible risk factors of PCa in future studies. -
Dong, Wei-Min;Cao, Xiang-Shan;Wang, Biao;Lin, Yun;Hua, Xiao-Ying;Qiu, Guo-Qiang;Gu, Wei-Ying;Xie, Xiao-Bao 6127
Objective: Explore the feasibility of allo-hemopietic stem cell transplants in treating patients with B cell acute lymphocytic leukemia. Methods: Between september 2006 and February 2011, fifteen patients with B cell acute lymphocytic leukemia (ALL) were treated by allo-hemopietic stem cell transplants (HSCT). Stem cell sources were peripheral blood. Six patients were conditioned by busulfan (BU) and cyclophosphamide (CY) and nine patients were conditioned with TBI and cyclophosphamide (CY). Graft versus host disease (GVHD) prophylaxis regimen consisted of cyclosporine A (CSA), methotrex ate (MTX) and mycophenolatemofetil (MMF). Results: Patients received a median of$7.98{\times}10^8{\cdot}kg^{-1}$ ($5.36-12.30{\times}10^8{\cdot}kg^{-1}$ ) mononuclear cells (MNC). The median time of ANC>$0.5{\times}10^9/L$ was day 12 (10-15), and PLT>$20.0{\times}10^9/L$ was day 13 (11-16). Extensive acute GVHD occurred in 6 (40.0%) patients, and extensive chronic GVHD was recorded in 6 (40.0%) patients. Nine patients were alive after 2.5-65 months follow-up. Conclusion: Allogeneic stem cell transplant could be effective in treating patients with B cell acute lymphocytic leukemia. -
Han, Li-Yuan;Liu, Kui;Lin, Xia-Lu;Zou, Bao-Bo;Zhao, Jin-Shun 6131
Objective: Epidemiology studies have reported conflicting results between glutathione S-transferase Mu-1 (GSTM1), glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase pi-1 (GSTP1) and ovarian cancer (OC) susceptibility. In this study, an updated meta-analysis was applied to determine whether the deletion of GSTM1, GSTT1 and GSTP1 has an influence on OC susceptibility. Methods: A published literature search was performed through PubMed, Embase, Cochrane Library, and Science Citation Index Expanded database for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity between studies was assessed using the Cochrane Q test and$I^2$ statistics. Sub-group analysis was conducted to explore the sources of heterogeneity. Sensitivity analysis was employed to evaluate the respective influence of each study on the overall estimate. Results: In total, 10 published studies were included in the final analysis. The combined analysis revealed that there was no significant association between GSTM1 null genotype and OC risk (OR=1.01, 95%CI: 0.91-1.12). Additionally, there was no significant association between GSTT1 genetic polymorphisms and OC risk (OR=0.98, 95% CI: 0.85-1.13). Similalry, no significant associations were found concerning the GSTP1 rs1695 locus and OC risk. Meanwhile, subgroup analysis did not show a significant increase in eligible studies with low heterogeneity. However, sensitivity analysis, publication bias and cumulative analysis demonstrated the reliability and stability of the current meta-analysis. Conclusions: These findings suggest that GSTs genetic polymorphisms may not contribute to OC susceptibility. Large epidemiological studies with the combination of GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and more specific histological subtypes of OC are needed to prove our findings. -
Lee, Sang-Ah;Sung, Hyuna;Han, Wonshik;Noh, Dong-Young;Ahn, Sei-Hyun;Kang, Daehee 6137
Limited numbers of epidemiological studies have examined the relationship between adipokines and breast cancer survival. Preoperative serum levels of obesity-related adipokines (leptin and adiponectin) were here measured in 370 breast cancer patients, recruited from two hospitals in Korea. We examined the association between those adipokines and disease-free survival (DFS). The TNM stage, ER status and histological grade were aslo assessed in relation to breast cancer survival. Elevated adiponectin levels were associated with reduced DFS of breast cancer ($P_{trend}=0.03$ ) among patients with normal body weight, predominantly in postmenopausal women. There was no association of leptin with breast cancer survival. In conclusion, our study suggests that high levels of adiponectin at diagnosis are associated with breast cancer survival among women with normal body weight. -
Fehri, Emna;Ennaifer, Emna;Ardhaoui, Monia;Ouerhani, Kaouther;Laassili, Thalja;Rhouma, Rahima Bel Haj;Guizani, Ikram;Boubaker, Samir 6145
Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin-embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells. -
Paengchit, Kannika;Kietpeerakool, Chumnan;Lalitwongsa, Somkiet 6151
A growing body of literature is evidence that identifying subtypes of high-risk human papillomavirus (HR-HPV) has impacted on various steps of cervical cancer prevention.Thus, it is mandatory to determine the background prevalence and distribution of HPV subtypes for designing and implementing area-specific management. The present study was conducted to evaluate prevalence and distribution of HPV subtypes among women aged 30-70 years living in Lampang, an area with a high incidence of cervical cancer, through use of a mobile screening unit. Of 2,000 women recruited in this study, 108 (5.40%, 95%CI: 4.45-6.48) were found to have HR-HPV infection. Risk was significantly correlated with age and number of partners. Singly or in combination, the most common genotype was HPV 52 (17.6%), followed by HPV 16 (14.81%), HPV 58 (13.89%), HPV 33 (11.11%), HPV 51 (11.11%), and HPV 56 (9.26%). HPV 18 was found in only 5.6% of cases. Together, HPV 16/18 were noted in approximately 20.4% of cases. Eighteen(16.67%) women were positive with multiple subtypes of HR-HPV. Co-infection most frequently involved HPV 16 or HPV 58. These findings have obvious implications for vaccine policy. -
Han, Xue;Dong, Yin;Xiu, Jian-Jun;Zhang, Jie;Huang, Zhao-Qin;Cai, Shi-Feng;Yuan, Xian-Shun;Liu, Qing-Wei 6155
Background: This study was conducted to investigate whether apparent diffusion coefficient (ADC) measurements by dividing the liver into left and right hepatic lobes may be utilized to improve the accuracy of differential diagnosis of benign and malignant focal liver lesions. Materials and Methods: A total of 269 consecutive patients with 429 focal liver lesions were examined by 3-T magnetic resonance imaging that included diffusion-weighted imaging. For 58 patients with focal liver lesions of the same etiology in left and right hepatic lobes, ADCs of normal liver parenchyma and focal liver lesions were calculated and compared using the paired t-test. For all 269 patients, ADC cutoffs for focal liver lesions and diagnostic accuracy in the left hepatic lobe, right hepatic lobe and whole liver were evaluated by receiver operating characteristic curve analysis. Results: For the group of 58 patients, mean ADCs of normal liver parenchyma and focal liver lesions in the left hepatic lobe were significantly higher than those in the right hepatic lobe. For differentiating malignant lesions from benign lesions in all patients, the sensitivity and specificity were 92.6% and 92.0% in the left hepatic lobe, 94.4% and 94.4% in the right hepatic lobe, and 90.4% and 94.7% in the whole liver, respectively. The area under the curve of the right hepatic lobe, but not the left hepatic lobe, was higher than that of the whole liver. Conclusions: ADCs of normal liver parenchyma and focal liver lesions in the left hepatic lobe were significantly higher than those in the right hepatic lobe. Optimal ADC cutoff for focal liver lesions in the right hepatic lobe, but not in the left hepatic lobe, had higher diagnostic accuracy compared with that in the whole liver. -
Gao, Ling;Li, Feng-Sheng;Chen, Xiao-Hua;Liu, Qiao-Wei;Feng, Jiang-Bin;Liu, Qing-Jie;Su, Xu 6161
Background: We have reported the radiation could activate STAT3, which subsequently promotes the invasion of A549 cells. We here explored the dose- and time-response of STAT3 to radiation and the effect of radiation on upstream signaling molecules. Materials and Methods: A549 cells were irradiated with different doses of${\gamma}$ -rays. The expression of and nucleus translocation of p-STAT3 in A549 cells were detected by immunoblotting and immunofluorescence, respectively. The level of phosphorylated EGFR was also assessed by immunoblotting, and IL-6 expression was detected by real time PCR and ELISA. Results: Radiation promoted the phosphorylation of STAT3 at Y705 in a dose- and time-dependent manner and nuclear translocation. The level of phosphorylated EGFR in A549 cells increased after radiation. In additional, the mRNA and protein levels of IL-6 in A549 cells were also up regulated by radiation. Conclusions: STAT3 is activated by radiation in a dose-and time-dependent manner, probably due to radiation-induced activation of EGFR or secretion of IL-6 in A549 cells. -
Unal, Olcun Umit;Yilmaz, Ahmet Ugur;Yavuzsen, Tugba;Akman, Tulay;Ellidokuz, Hulya 6165
Background: The advantage of intra-peritoneal (IP) chemotherapy (CT) in the initial management of ovarian cancer after cytoreductive surgery is well known. The feasibility and toxicity of a treatment regimen with an IP + intravenous CT (IPIVCT) for optimally debulked stage III ovarian cancer were here evaluated retrospectively. Materials and Methods: A total of 30 patients were treated in our institution between October 2006 and February 2011. Patients received IV paclitaxel$175mg/m^2$ over 3 hours followed by IP cisplatin$75mg/m^2$ on day 1; they also received IP paclitaxel$60mg/m^2$ on day 8. They were also scheduled to receive 6 courses of CT every 21 days. Results: The median age of the patients was 55 years (35-77), and the majority had papillary serous ovarian cancer (63.3%). The patients completed a total of 146 cycles of IPIVCT. Twenty-eight were able to receive at least three cycles of IPIVCT and 18 (60%) completed the scheduled 6 cycles. Two patients discontinued the IPIVCT because of toxicity of chemotherapy agents and 6 had to stop treatment due to intolerable abdominal pain during IP drug administration, obstruction and impaired access. Grade 3/4 toxicities included neutropenia (6 patients; 20%), anemia (2 patients; 6.7%) and nausea-vomiting (2 patients; 6.7%). Doses were delayed in 12 cycles (8%) for neutropenia (n=6), thrombocytopenia (n=3) and elevated creatinine (n=3). Drug doses were not reduced. The median duration of progression-free survival (PFS) was 47.7 months (95%CI, 38.98-56.44) and overall survival (OS) was 51.7 months (95%CI, 44.13-59.29). Two and five-year overall survival rates were 75.6 % and 64.8%, respectively. Conclusions: IPIVCT is feasible and well-tolerated in this setting. Its clinically proven advantages should be taken into consideration and more efforts should be made to administer IPIVCT to suitable patients. -
Shahrokni, Armin;Mahmoudzadeh, Sanam;Lu, Bryan Tran 6171
Background: In order to design effective educational intervention for cancer survivors, it is necessary to identify most-trusted sources for health-related information and the amount of attention paid to each source. Objective: The objective of our study was to explore the sources of health information used by cancer survivors according to their access to the internet and levels of trust in and attention to those information sources. Materials and Methods: We analyzed sources of health information among cancer survivors using selected questions adapted from the 2012 Health Information National Trends Survey (HINTS). Results: Of 357 participants, 239 (67%) had internet access (online survivors) while 118 (33%) did not (offline survivors). Online survivors were younger (p<0.001), more educated (p<0.001), more non-Hispanic whites (p<0.001), had higher income (p<0.001), had more populated households (p<0.001) and better quality of life (p<0.001) compared to offline survivors. Prevalence of some disabilities was higher among offline survivors including serious difficulties with walking or climbing stairs (p<0.001), being blind or having severe visual impairment (p=0.001), problems with making decisions (p<0.001), doing errands alone (p=0.001) and dressing or bathing (p=0.001). After adjusting for socio-demographic status, cancer survivors who were non-Hispanic whites (OR= 3.49, p<0.01), younger (OR=4.10, p<0.01), more educated (OR= 2.29, p=0.02), with greater income (OR=4.43, p<0.01), and with very good to excellent quality of life (OR=2.60, p=0.01) had higher probability of having access to the internet, while those living in Midwest were less likely to have access (OR= 0.177, p<0.01). Doctors (95.5%) were the most and radio (27.8%) was the least trusted health related information source among all cancer survivors. Online survivors trusted internet much more compared to those without access (p<0.001) while offline cancer survivors trusted health-related information from religious groups and radio more than those with internet access (p<0.001 and p=0.008). Cancer survivors paid the most attention to health information on newsletters (63.8%) and internet (60.2%) and the least to radio (19.6%). More online survivors paid attention to internet than those without access (68.5% vs 39.1%, p<0.001) while more offline survivors paid attention to radio compared to those with access (26.8% vs 16.5%, p=0.03). Conclusions: Our findings emphasize the importance of improving the access and empowering the different sources of information. Considering that the internet and web technologies are continuing to develop, more attention should be paid to improve access to the internet, provide guidance and maintain the quality of accredited health information websites. Those without internet access should continue to receive health-related information via their most trusted sources. -
Background: Our study objectives were to evaluate the medical economics of cervical cancer prevention and thereby contribute to cancer care policy decisions in Japan. Methods: Model creation: we created presence-absence models for prevention by designating human papillomavirus (HPV) vaccination for primary prevention of cervical cancer. Cost classification and cost estimates: we divided the costs of cancer care into seven categories (prevention, mass-screening, curative treatment, palliative care, indirect, non-medical, and psychosocial cost) and estimated costs for each model. Cost-benefit analyses: we performed cost-benefit analyses for Japan as a whole. Results: HPV vaccination was estimated to cost $291.5 million, cervical cancer screening $76.0 million and curative treatment $12.0 million. The loss due to death was $251.0 million and the net benefit was -$128.5 million (negative). Conclusion: Cervical cancer prevention was not found to be cost-effective in Japan. While few cost-benefit analyses have been reported in the field of cancer care, these would be essential for Japanese policy determination.
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Liu, Jin-Xin;Luo, Rong-Cheng;Li, Rong;Li, Xia;Guo, Yu-Wu;Ding, Da-Peng;Chen, Yi-Zhi 6181
This meta-analysis was conducted to examine whether the genotype status of Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with endometrial and ovarian cancer risk. Eligible studies were identified by searching several databases for relevant reports published before January 1, 2014. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. In total, 15 studies (1,293 cases and 2,647 controls for ovarian cancer and 2,174 cases and 2,699 controls for endometrial cancer) were included in the present meta-analysis. When all studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val158Met polymorphism and ovarian cancer risk (Val/Met versus Val/Val: OR=0.91, 95% CI=0.76-1.08; Met/Met versus Val/Val: OR=0.90, 95% CI=0.73-1.10; dominant model: OR=0.90, 95% CI=0.77-1.06; recessive model: OR=0.95, 95% CI=0.80-1.13). Similarly, no associations were found in all comparisons for endometrial cancer (Val/Met versus Val/Val: OR 0.97, 95% CI=0.77-1.21; Met/Met versus Val/Val: OR=1.02, 95% CI=0.73-1.42; dominant model: OR=0.98, 95% CI=0.77-1.25; recessive model: OR=1.02, 95% CI=0.87-1.20). In the subgroup analyses by source of control and ethnicity, no significant associations were found in any subgroup of population. This meta-analysis strongly suggests that COMT Val158Met polymorphism is not associated with increased endometrial and ovarian cancer risk. -
Fu, Chun-Jing;Pan, Xiong-Fei;Zhao, Zhi-Mei;Saheb-Kashaf, Michael;Chen, Feng;Wen, Ying;Yang, Chun-Xia;Zhong, Xiao-Ni 6187
Objectives: To evaluate medical students' knowledge of HPV and HPV related diseases and assess their attitudes towards HPV vaccination. Methods: A total of 605 medical undergraduates from Chongqing Medical University in China were surveyed using a structured and pretested questionnaire on HPV related knowledge. Results: Some 68.9% of the medical students were females, and mean age was 21.6 (${\pm}1.00$ ) years. Only 10.6% correctly answered more than 11 out of 14 questions on HPV related knowledge, 71.8% being willing to receive/advise on HPV vaccination. Female students (OR: 2.69; 95% CI: 1.53-4.72) and students desiring more HPV education (OR: 4.24; 95% CI: 1.67-10.8) were more willing to accept HPV vaccination. HPV vaccination acceptability was observed to show a positive association with HPV related knowledge. Conclusions: Our survey found low levels of HPV related knowledge and HPV vaccination acceptability among participating medical students. HPV education should be systematically incorporated into medical education to increase awareness of HPV vaccination. -
Purpose: We examined tobacco use pattern and its correlates among older adults. Materials and Methods: We used data of 9,852 older adults (
${\geq}60$ years) (men 47% mean age 68 years) collected by the United Nations Population Fund on Ageing from seven Indian states. Logistic regression analysis was used to assess the correlates of tobacco use. Results: Current use of any form of tobacco was reported by 27.8% (men 37.9%, women 18.8%); 9.2% reported only smoking tobacco, 16.9% smokeless tobacco only and 1.7% used both forms. Alcohol users (OR:5.20, 95% CI:4.06-6.66), men (OR:2.92, CI :2.71-3.47), those reporting lower income (OR:2.74, CI:2.16-3.46), rural residents (OR 1.34, CI 1.17-1.54) and lower castes (OR:1.29, CI:1.13-1.47) were more likely to use any form of tobacco compared to their counterparts. Conclusions: Tobacco cessation interventions are warranted in this population focusing on alcohol users, men, those from lower income, rural residents and those belonging to a lower caste. -
Yari, Kheirollah;Rahimi, Ziba;Moradi, Mohamad Taher;Rahimi, Zohreh 6199
Background: The expression of MMP genes has been demonstrated to be associated with tumor invasion, metastasis and survival rate for a variety of cancers. The functional promoter polymorphism MMP-2 C-735T is associated with decreased expression of the MMP-2 gene. The aim of present study was to detect any association between MMP-2 C-735T and susceptibility to breast cancer. Materials and Methods: The MMP-2 C-735T polymorphism was studied in 233 women (98 with breast cancer and 135 healthy controls). All studied women were from Kermanshah and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MMP-2 CC, CT and TT genotypes in healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed (p=0.077). In patients the frequency of the MMP-2 C allele was significantly higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI 1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in patients${\leq}40$ years (88.9%) than those aged${\geq}41$ years (67.5%, p=0.07). In addition, the frequency of MMP-2 C allele tended to be higher in patients with a family history of cancer in first-degree relatives (76.6%) compared to that without a family history of cancer (67.3%, p=0.31). Conclusions: Our findings indicate that the C allele of MMP-2 C-735T polymorphism is associated with increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk of young onset breast cancer in our population. -
Seyedrasooli, Alehe;Rahmani, Azad;Howard, Fuchsia;Zamanzadeh, Vahid;Mohammadpoorasl, Asghar;Aliashrafi, Raha;Pakpour, Vahid 6205
Background: The aim of this study was to investigate Iranian cancer patient perceptions of their prognosis, factors that influence perceptions of prognosis and the effect this has on patient level of hope. Materials and Methods: Iranian cancer patients (n=200) completed self-report measures of their perceptions of their prognosis and level of hope, in order to assess the relationship between the two and identify factors predictive of perceptions by multiple linear regression analysis. Results: Cancer patients perceived of their prognosis positively (mean 11.4 out of 15), believed their disease to be curable, and reported high levels of hope (mean 40.4 out of 48.0). Multiple linear regression analyses demonstrated that participants who were younger, perceived they had greater family support, and had higher levels of hope reported more positive perceptions of their cancer prognosis. Conclusions: Positive perceptions of prognosis and its positive correlation with hope in Iranian cancer patients highlights the importance of cultural issues in the disclosure of cancer related information. -
Zeng, Hui;Wang, Xue-Bin;Cui, Ning-Hua;Nam, Seungyoon;Zeng, Tuo;Long, Xinghua 6211
Previous genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B) gene with childhood acute lymphoblastic leukemia (ALL). However, replicated studies reported some inconsistent results in different populations. Using meta-analysis, we here aimed to clarify the nature of the genetic risks contributed by the two polymorphisms (rs10994982, rs7089424) for developing childhood ALL. Through searches of PubMed, EMBASE, and manually searching relevant references, a total of 14 articles with 16 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated to assess the associations. Both SNPs rs10994982 and rs7089424 showed significant associations with childhood ALL risk in all genetic models after Bonferroni correction. Furthermore, subtype analyses of B-lineage ALL provided strong evidence that SNP rs10994982 is highly associated with the risk of developing B-hyperdiploid ALL. These results indicate that SNPs rs10994982 and rs7089424 are indeed significantly associated with increased risk of childhood ALL. -
Luo, Li-Ping;Han, Bin;Yu, Xiao-Ping;Chen, Xiang-Yan;Zhou, Jie;Chen, Wei;Zhu, Yan-Feng;Peng, Xiao-Li;Zou, Qiang;Li, Sui-Yan 6219
Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules. -
Abbasi, Mehran Mesgari;Monfaredan, Amir;Hamishehkar, Hamed;Seidi, Khaled;Jahanban-Esfahlan, Rana 6227
Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. The aim of present study was to evaluate the efficacy of novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in terms of their potential to change the VEGF-C expression profile in a rat OSCC model. Materials and Methods: 120 male rats were divided into 8 groups of 15 animals administrated with 4-nitroquinoline-1-oxide to induce OSCCs. Newly formulated doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) and free doxorubicin were IV and orally administered. Results: Results indicated that both oral and IV forms of DOX-MTX-nanoparticle complexes caused significant decrease in the mRNA level of VEGF-C compared to untreated cancerous rats (p<0.05). Surprisingly, the VEGF-C mRNA was not affected by free DOX in both IV and oral modalities (p>0.05). Furthermore, in DOX-MTX NP treated group, less tumors characterized with advanced stage and VEGF-C mRNA level paralleled with improved clinical outcome (p<0.05). In addition, compared to untreated healthy rats, the VEGF-C expression was not affected in healthy groups that were treated with IV and oral dosages of nanodrug (p>0.05). Conclusions: VEGF-C is one of the main prognosticators for lymph node metastasis in OSCC. Down-regulation of this lymph-angiogenesis promoting factor is a new feature acquired in group treated with dual action DOX-MTX-NPs. Beside the synergic apoptotic properties of concomitant use of DOX and MTX on OSCC, DOX-MTX NPs possessed anti-angiogenesis properties which was related to the improved clinical outcome in treated rats. Taking together, we conclude that our multifunctional doxorubicin-methotrexate complex exerts specific potent apoptotic and anti-angiogenesis properties that could ameliorate the clinical outcome presumably via down-regulating dissemination factor-VEGF-C expression in a rat OSCC model. -
Yildirim, Mustafa;Demirpence, Ozlem;Kaya, Vildan;Suren, Dinc;Karaca, Mehmet;Evliyaoglu, Osman;Yilmaz, Necat;Gunduz, Seyda 6233
Background: Intraperitoneal spread of gynecologic cancers is a major cause of mortality and morbidity and often presents with malignant ascites. Microscopic tumor spread can be demonstrated by a peritoneal wash cytology and help assess the prognosis of the disease. In our study, the roles of paraoxonase and ceruloplasmin, measured in peritoneal washing fluid of patients operated for gynecologic pathologies in differential diagnosis was investigated. Materials and Methods: Patients operated for malign or benign gynecologic pathologies in Antalya Education and Research Hospital Gynecology Clinic between 2010-2012 were included in the study. Samples were obtained during surgery. Results: A statistically significant difference was detected between patients with benign and malign diseases with regards to PON1 levels measured in peritoneal washing fluid (p:0.044), the average values being$64.2{\pm}30.8$ (Range 10.8-187.2) and$41.4{\pm}21.4$ (Range 10.4-95.5), respectively. No significant variation was evident for ceruloplasmin. Conclusions: Paraoxonase levels measured in peritoneal washing fluid may contribute to the differentiation of malign-benign diseases in gynecologic pathologies. -
Topcu, Hasan Onur;Guzel, Ali Irfan;Ozer, Irfan;Kokanali, Mahmut Kuntay;Gokturk, Umut;Muftuoglu, Kamil Hakan;Doganay, Melike 6239
Purpose: To compare the diagnostic accuracy of the neutrophil/lymphocyte ratio (NLR) with the platelet/lymphocyte ratio (PLR) in predicting malignancy of pelvic masses which are pre-operatively malignant suspicious. Materials and Methods: In this retrospective study we evaluated the clinical features of patients with ovarian masses which had pre-operatively been considered suspicious for malignancy. The patients whose intraoperative frozen sections were malign were classified as the study group, while those who had benign masses were the control group. Data recorded were age of the patient, diameter of the mass, pre-operative serum Ca 125 levels, platelet count, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. Results: There was statistically significantly difference between the groups in terms of age, diameter of the mass, serum Ca 125 levels, platelet number and platelet/lymphocyte ratio. Mean neutrophil/lymphocyte ratios showed no difference between the groups. ROC curve analysis showed that age, serum Ca 125 levels, platelet number and PLR were discriminative markers in predicting malignancy in adnexal masses. Conclusions: According to the current study, serum Ca 125 levels, pre-operative platelet number and PLR may be good prognostic factors, while NLR is an ineffective marker in predicting the malignant characteristics of a pelvic mass. -
Yang, Nian-Qin;Zhang, Jian;Tang, Qun-Ye;Guo, Jian-Ming;Wang, Guo-Min 6243
To investigate the role of miR-1297 and the tumor suppressor gene PTEN in cell proliferation of testicular germ cell tumors (TGCT). MTT assays were used to test the effect of miR-1297 on proliferation of the NCCIT testicular germ cell tumor cell line. In NCCIT cells, the expression of PTEN was assessed by Western blotting further. In order to confirm target association between miR-1297 and 3'-UTR of PTEN, a luciferase reporter activity assay was employed. Moreover, roles of PTEN in proliferation of NCCIT cells were evaluated by transfection of PTEN siRNA. Proliferation of NCCIT cells was promoted by miR-1297 in a concentration-dependent manner. In addition, miR-1297 could bind to the 3'-UTR of PTEN based on luciferase reporter activity assay, and reduced expression of PTEN at protein level was found. Proliferation of NCCIT cells was significantly enhanced after knockdown of PTEN by siRNA. miR-1297 as a potential oncogene could induce cell proliferation by targeting PTEN in NCCIT cells. -
Sui, Jia-Qi;Xie, Kun-Peng;Zou, Wei;Xie, Ming-Jie 6247
Background: The aim of the present study was to investigate the involvement of emodin on the growth of human breast cancer MCF-7 and MDA-MB-231 cells and the estrogen (E2) signal pathway in vitro. Materials and Methods: MTT assays were used to detect the effects of emodin on E2 induced proliferation of MCF-7 and MDA-MB-231 cells. Flow cytometry (FCM) was applied to determine the effect of emodin on E2-induced apoptosis of MCF-7 cells. Western blotting allowed detection of the effects of emodin on the expression of estrogen receptor${\alpha}$ , cyclin D1 and B-cell lymphoma-2 (Bcl-2), mitogen-activated protein kinases (MAPK) and phosphatidylinostiol 3-kinases (PI3K). Luciferase assays were emplyed to assess transcriptional activity of$ER{\alpha}$ . Results: Emodin could inhibit E2-induced MCF-7 cell proliferation and anti-apoptosis effects, and arrest the cell cycle in G0/G1 phase, further blocking the effect of E2 on expression and transcriptional activity of$ER{\alpha}$ . Moreover, Emodin influenced the ER${\alpha}$ genomic pathway via downregulation of cyclin D1 and Bcl-2 protein expression, and influenced the non-genomic pathway via decreased PI3K/Akt protein expression. Conclusions: These findings indicate that emodin exerts inhibitory effects on MCF-7 cell proliferation via inhibiting both non-genomic and genomic pathways. -
Baghestani, Ahmad Reza;Daneshvar, Tahoura;Pourhoseingholi, Mohamad Amin;Asadzade, Hamid 6253
Background: Colorectal cancer (CRC) is considered to be a main cause of malignancy-related death in the world, being commonly diagnosed in both men and women. It is the third leading cause of cancer dependent death in the world and there are one million new cases diagnosed per year. In Iran the incidence of colorectal cancer has increased during the last 25 years and it is the fifth cause of cancer in men and the third in women. Materials and Methods: In this article we analyzed the survival of 475 colorectal patients of Taleghani hospital in Tehran with the semi-parametric competing-risks model. Results: There were 55% male cases and at the time of the diagnosis most of the patients were between 48 and 67years old. The probability of a patient death from colorectal cancer with survival of more than 25 years was about 0.4. Body mass index, height, tumour site and gender had no influence. Conclusions: According to these data and by using semi-parametric competing-risks method, we found out that only age at diagnosis has a significant effect on these patient survival time. -
Sohrabi, Amir;Mirab-Samiee, Siamak;Modarressi, Mohammad Hossein;Izadimood, Narge;Azadmanesh, Kayhan;Rahnamaye-Farzami, Marjan 6257
Background: HPV related cervical cancer as one of the most common women cancers in developing countries. Regarding accessibility of commercial vaccines, any long or short term modality for integrating preventive immunization against HPV in a national program needs comprehensive information about HPV prevalence and its genotypes. The important role of selecting most accurate diagnostic technologies for obtaining relevant data is underlined by different assays proposed in the literature. The main objective of the present study was to introduce an in-house HPV typing assay using multiplex real time PCR with reliable results and affordable cost for molecular epidemiology surveys and diagnosis. MATERIALS AND METHODS: 112 samples of formalin fixed paraffin embedded tissues and liquid based cytology specimens from patients with known different grades of cervical dysplasia and invasive cancer, were examined by this method and the result were verified by WHO HPV LabNet proficiency program in 2013. RESULTS: HPV was detected in 105 (93.7%) out of 112 samples. The dominant types were HPV 18 (61.6%) and HPV 16 (42.9%). Among the mixed genotypes, HPV 16 and 18 in combination were seen in 12.4% of specimens. CONCLUSIONS: According to acceptable performance, easy access to primers, probes and other consumables, affordable cost per test, this method can be used as a diagnostic assay in molecular laboratories and for further planning of cervical carcinoma prevention programs. -
Bayman, Evrim;Etiz, Durmus;Akcay, Melek;Ak, Guntulu 6263
Background: It is standard treatment to combine chemotherapy (CT) and thoracic radiotherapy (TRT) in treating patients with limited stage small cell lung cancer (LS-SCLC). However, optimal timing of TRT is unclear. We here evaluated the survival impact of early versus late TRT in patients with LS-SCLC. Materials and Methods: Follow-up was retrospectively analyzed for seventy consecutive LS-SCLC patients who had successfully completed chemo-TRT between January 2006 and January 2012. Patients received TRT after either 1 to 2 cycles of CT (early TRT) or after 3 to 6 cycles of CT (late TRT). Survival and response rates were evaluated using the Kaplan-Meier method and comparisons were made using the multivariate Cox regression test. Results: Median follow-up was 24 (5 to 57) months. Carboplatin+etoposide was the most frequent induction CT (59%). Median overall, disease free, and metastasis free survivals in all patients were 15 (5 to 57), 5 (0 to 48) and 11 (3 to 57) months respectively. Late TRT was superior to early TRT group in terms of response rate (p=0.05). 3 year overall survival (OS) rates in late versus early TRT groups were 31% versus 17%, respectively (p=0.03). Early TRT (p=0.03), and incomplete response to TRT (p=0.004) were negative predictors of OS. Significant positive prognostic factors for distant metastasis free survival were late TRT (p=0.03), and use of PCI (p=0.01). Use of carboplatin versus cisplatin for induction CT had no significant impact on OS (p=0.634), DFS (p=0.727), and MFS (p=0.309). Conclusions: Late TRT appeared to be superior to early TRT in LS-SCLC treatment in terms of complete response, OS and DMFS. Carboplatin or cisplatin can be combined with etoposide in the induction CT owing to similar survival outcomes. -
Wang, Wei-Hua;Chen, Jie;Zhao, Feng;Zhang, Bu-Rong;Yu, Hong-Sheng;Jin, Hai-Ying;Dai, Jin-Hua 6269
Growing evidence suggests that miR-150-5p has an important role in regulating genesis of various types of cancer. However, the roles and the underlying mechanisms of miR-150-5p in development of colorectal cancer (CRC) remain largely unknown. Transwell chambers were used to analyze effects on cell migration and invasion by miR-150-5p. Quantitative real-time PCR (qRT-PCR), Western blotting and dual-luciferase 3' UTR reporter assay were carried out to identify the target genes of miR-150-5p. In our research, miR-150-5p suppressed CRC cell migration and invasion, and MUC4 was identified as a direct target gene. Its effects were partly blocked by re-expression of MUC4. In conclusiomn, miR-150-5p may suppress CRC metastasis through directly targeting MUC4, highlighting its potential as a novel agent for the treatment of CRC metastasis. -
Wen, Jing-Yun;Li, Mai;Li, Xing;Chen, Jie;Lin, Qu;Ma, Xiao-Kun;Dong, Min;Wei, Li;Chen, Zhan-Hong;Wu, Xiang-Yuan 6275
Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received$2500IU/m^2$ /IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL. -
Turkeri, Levent;Mangir, Naside;Gunlusoy, Bulent;Yildirim, Asif;Baltaci, Sumer;Kaplan, Mustafa;Bozlu, Murat;Mungan, Aydin 6283
In patients with microscopic hematuria there is a need for better identification of those who are at greater risk of harbouring bladder tumors. The RisikoCheck(C) questionnaire has a strong correlation with the presence of urothelial carcinoma (UC) of the bladder and in combination with other available tests may help identify patients who require detailed clinical investigations due to increased risk of presence of bladder tumors. This study aimed to evaluate the efficacy of RisikoCheck(C) questionnaire together with NMP-22(R) (BladderChek(R)) as a point-of-care urine test in predicting the presence of bladder tumors in patients presenting with microscopic hematuria as the sole finding. In this multi-institutional prospective evaluation of 303 consecutive patients without a history of urothelial carcinoma (UC), RisikoCheck(C) risk group assessment, urinary tract imaging and cystourethroscopy as well as urine cytology and Nuclear Matrix Protein-22 (NMP-22 BladderChek) testing were performed where available. The sensitivity, specificity, negative predictive value (NPV), and positive predictive values (PPV) for the risk adapted approach were calculated. All patients underwent cystoscopy, and tumors were detected in 18 (5.9%). Urine cytology and NMP-22 was positive for malignancy in 9 (3.2%) and 12 (7.5%) of patients, respectively. A total of 43 (14%) patients were in the high risk group according to the RisikoCheck(C) questionnaire. The sensitivity and specificity of the questionnaire in detecting a bladder tumor was 61.5 % and 84.0 % in the high risk group. In patients with either a positive NMP-22 test or high risk category RisikoCheck(C), 23.6% had bladder tumors with a corresponding sensitivity of 54.2% and specificity of 88.6%. If both tests were negative only 3.3% of the patients had bladder tumors. The results of our study suggest that the efficacy of diagnostic evaluation of patients with microscopic hematuria may be further enhanced by combining RisikoCheck(C) questionnaire with NMP-22. -
Sahoo, Pradyumna Kumar;Jana, Debarshi;Mandal, Palash Kumar;Basak, Samindranath 6287
Background: Invasion of breast cancer cells into blood and lymphatic vessels is one of the most important steps for metastasis. In this study the prognostic relevance of lymphangiogenesis and lymphovascular invasion (LVI) in breast cancer patients was evaluated in terms of survival. Materials and Methods: This retrospective study concerned 518 breast cancer patients who were treated at Department of Surgical Oncology, Saroj Gupta Cancer Centre and Research Institute, Kolkata-700063, West Bengal, India, a reputed cancer centre and research institute of eastern India between January 2006 and December 2007. Results: The median overall survival and disease free survival of the patients were 60 months and 54 months respectively. As per Log-rank test, poor overall as well as disease free survival pattern was observed for LVI positive patients as compared with LVI negative patients (p<0.01). Also poor overall as well as disease free survival pattern was observed for perineural invasion (PNI) positive patients as compared to PNI negative patients (p<0.01). Conclusions: From this study it is evident that LVI and PNI are strongly associated with outcome in terms of disease free as well as overall survival in breast cancer patients. Thus LVI and PNI constitute potential targets for treatment of breast cancer patients. We advocate incorporating their status into breast cancer staging systems. -
Tian, Shu-Bo;Yu, Jian-Chun;Kang, Wei-Ming;Ma, Zhi-Qiang;Ye, Xin;Cao, Zhan-Jiang;Yan, Chao 6295
Our aim was to investigate the value of combined detection of serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 242 and CA 50 in diagnosis and assessment of prognosis in consecutive gastric cancer patients. Clinical data including preoperative serum CEA, CA 19-9, CA 242, and CA 50 values and information on clinical pathological factors were collected and analyzed retrospectively. Univariate and multivariate survival analyses were used to explore the relationship between tumor markers and survival. Positive rates of tumor markers CEA, CA 19-9, CA 242 and CA 50 in the diagnosis of gastric cancer were 17.7, 17.1, 20.4 and 13.8%, respectively, and the positive rate for all four markers combined was 36.6%. Patients with elevated preoperative serum concentrations of CEA, CA 19-9, CA 242 and CA 50, had late clinical tumor stage and significantly poorer overall survival. Five-year survival rates in patients with elevated CEA, CA 19-9, CA 242 and CA 50 were 28.1, 25.8, 27.0 and 24.1%, respectively, compared with 55.0, 55.4, 56.4 and 54.5% in patients with these markers at normal levels (p<0.01). In multivariate Cox proportional hazards analyses, an elevated CA 242 level was determined to be an independent prognostic marker in gastric cancer patients. Combined detection of four tumor markers increased the positive rate for gastric cancer diagnosis. CA 242 showed higher diagnostic value and CA 50 showed lower diagnostic value. In resectable gastric carcinoma, preoperative CA 242 level was associated with disease stage, and was found to be a significant independent prognostic marker in gastric cancer patients. -
Huang, Yin-Jiu;Zhang, Yu-Yuan;Liu, Gang;Tang, Jie;Hu, Jian-Guo;Feng, Zhen-Zhong;Liu, Fang;Wang, Qi-Yi;Li, Dan 6301
Cervical cancer is one the most common malignancies among females. In recent years, its incidence rate has shown a rising trend in some countries so that development of anticancer drugs for cervical cancer is an urgent priority. In our recent anticancer drug discovery screen, 1, 2-di (quinazolin-4-yl)diselane (LG003) was found to possess wide spectrum anticancer efficacy. In the present work, the in vitro anticancer activity of LG003 was evaluated in the SiHa cervical cancer cell line. Compared with commercial anticancer drugs 10-hydroxycamptothecin, epirubicin hydrochloride, taxol and oxaliplatin, LG003 showed better anticancer activity. Furthermore, inhibition effects were time- and dose-dependent. Morphological observation exhibited LG003 treatment results in apoptosis like shrinking and blebbing, and cell membrane damage. Lactate dehydrogenase release assay revealed that LG003 exerts such effects in SiHa cells through a physiology pathway rather than cytotoxicity, which suggests that title compound LG003 can be a potential candidate agent for cervical cancer. -
Saeed, Raed Saeed;Bakir, Yousif Yacoub;Ali, Layla Mohammed 6307
The aim of this study was to examine the knowledge and awareness of women in Kuwait with regard to risk factors, symptoms and diagnostic procedures of breast cancer. A total of 521 questionnaires were distributed among women in Kuwait. Results showed that 72% of respondents linked breast cancer factors to family history, while 69.7% scored abnormal breast enlargement as the most detectable symptom of the disease. Some 84% of participants had heard about self-examination, but knowledge about mammograms was limited to 48.6% and only 22.2% were familiar with diagnostic procedures. Some 22.9% of respondents identified the age over 40 years as the reasonable age to start mammogram screening. Risk factor awareness was independent on age groups (p>0.05), but both high education and family history increased the likelihood of postivie answers; the majority knew about a few factors such as aging, pregnancy after age 30, breast feeding for short time, menopause after age of 50, early puberty, and poor personal hygiene. In conclusion, 43.1% of participants had an overall good knowledge of breast cancer with regards to symptoms, risk factors and breast examination. Very highly significant associations (p<0.005) were evident for all groups except for respondents distributed by nationality (p=0.444). Early campaigns for screening the breast should be recommended to eliminate the confusion of wrong perceptions about malignant mammary disease. -
Hashemi, Forough;Naderian, Majid;Kadivar, Maryam;Nilipour, Yalda;Gheytanchi, Elmira 6315
Background: Immunohistochemical markers are considered as important factors in diagnosis of malignant astrocytomas. The aim of the current study was to investigate the frequency of the immunohistochemical markers neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP) in malignant astrocytoma tumors in Firoozgar and Rasool-Akram hospitals from 2005 to 2010. Materials and Methods: In this cross-sectional study, immunohistochemical analysis of NFP and GFAP was performed on 79 tissue samples of patients with the diagnosis of anaplastic and glioblastoma multiform (GBM) astrocytomas. Results: The obtained results demonstrated that all patients were positive for GFAP and only 3.8% were positive for NFP. There was no significant association between these markers and clinical, demographic, and prognostic features of patients (p>0.05). Conclusions: NFP was expressed only in GBMs and not in anaplastic astrocytomas. It would be crucial to confirm the present findings in a larger number of tumors, especially in high grade gliomas. -
${\alpha}$ -Methyl-n-butylshikonin (MBS), one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we assess the molecular mechanisms of MBS in causing apoptosis of SW620 cells. MBS reduced the cell viability of SW620 cells in a dose-and time-dependent manner and induced cell apoptosis. Treatment of SW620 cells with MBS down-regulated the expression of Bcl-2 and up-regulated the expression of Bak and caused the loss of mitochondrial membrane potential. Additionally, MBS treatment led to activation of caspase-9, caspase-8 and caspase-3, and cleavage of PARP, which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. MBS also induced significant elevation in the phosphorylation of JNK and p38. Pretreatment of SW620 cells with specific inhibitors of JNK (SP600125) and p38 (SB203580) abrogated MBS-induced apoptosis. Our results demonstrated that MBS inhibited growth of colorectal cancer SW620 cells by inducing JNK and p38 signaling pathway, and provided a clue for preclinical and clinical evaluation of MBS for colorectal cancer therapy. -
Chen, Peng-Lai;Zhao, Ting;Feng, Rui;Chai, Jing;Tong, Gui-Xian;Wang, De-Bin 6327
National cancer registration reports provide a huge potential for identifying patterns and trends of important policy, research, prevention and treatment significance. As summary reports written on an annual basis, the China Cancer Registry Annual Reports (CCRARs) fall short from fully addressing their potential. This paper attempts to explore part of the patterns and trends hidden behind published CCRARs. It extracted data for cancer incidence rates (IRs) and mortality rates (MRs) for 2004, 2006 and 2009 from relevant CCRARs and portrayed 4 kinds of indicators in line graphs. The study showed that: a) all of the line graphs of age-specific IRs and MRs characterized typical "growth curves or histogram"; b) graphs of IRs and MRs for males and urban areas had higher peaks than that for females and rural regions; c) most of the line graphs of IR/MR ratios comprised a starting peak, a secondary peak and a decreasing tail and the secondary peaks for females and urban areas were higher than those for males and rural areas; d) most of the urban versus rural IR ratios valued above one, but most the urban versus rural MR ratios, below one; e) the accumulative IRs and MRs showed a stable increasing trend from 2004 to 2009 for urban areas, but mixed for rural regions. -
Yilmaz, Meral;Kacan, Turgut;Sari, Ismail;Kilickap, Saadettin 6333
Background: In this case-control study, we aimed to investigate the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and lung cancer. Materials and Methods: Total 200 individuals including 100 patients with lung cancer and 100 controls were analyzed. Genotyping of MTHFR C677T was performed using PCR and RFLP methods. Results: The majority of the patients were men and 90% were smokers. We found that the risk ratio for development of LC was 13-times higher in smokers compared with non-smokers between patient and control groups in our study (OR:13.5, 95%CI:6.27-29.04, p:0.0001). Besides, the risk ratio for development of LC was nine times higher in individuals with cancer history in their family than those without cancer history (OR:9.65, 95%CI: 2.79-33.36; p:0.0001). When genotype distributions and allele frequencies were analyzed in the study groups, no significant difference was apparent (${\chi}^2$ :0.53, p=0.76). In addition, no correlation between genotypes of MTHFRC677T polymorphism and histological type of LC was found (${\chi}^2$ :0.99, p=0.60). Conclusions: These results suggest that there was no association between the MTHFR C677T polymorphism and lung cancer in the Turkish population. -
Akbar, Ali;Bhatti, Abu Bakar Hafeez;Khattak, Shahid;Syed, Aamir Ali;Kazmi, Ather Saeed;Jamshed, Aarif 6339
Background: The incidence of rectal cancer is increasing in younger age groups. Limited data is available regarding survival outcome in younger patients with conflicting results from western world. The goal of this study was to determine survival in patients with rectal cancer <30 years of age and compare it with their older counterparts in the Pakistani population. Materials and Methods: A retrospective chart review of patients operated for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided into two groups, Group 1 aged${\leq}30years$ and Group 2 aged >30years. Patient characteristics, surgical procedure, histopathological details and number of loco-regional and distant failures were compared. Expected 5 year survival was calculated using Kaplan Meier curves and significance was determined using the Log rank test. Results: There were 38 patients in group 1 and 144 in group 2. A significantly high number of younger patients presented with poorly differentiated histology (44.7% vs 9.7%) (p=0.0001) and advanced pathological stage (63.1% vs 38.1%) (p=0.04). Predicted overall 5 year survival was 38% versus 57% in groups I and II, respectively (p=0.05). Disease free survival was 37% versus 52% and was significantly different (p=0.007). Conclusions: Early onset rectal cancer is associated with poor pathological features and a worse outcome in Pakistani population. -
Wang, Xue-Jian;Duan, Yu;Li, Zong-Tao;Feng, Jin-Hong;Pan, Xiang-Po;Zhang, Xiu-Rong;Shi, Li-Hong;Zhang, Tao 6343
Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT-011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent. -
The present study was undertaken to determine the roles of insulin in the growth of transplanted breast cancer in nude mice, and the proliferation and migration of MCF-7 human breast cancer cells and assess its influence on downstream signaling pathways. In a xenograft mouse model with injection of MCF-7 human breast cancer cells, tumor size was measured every other day. The insulin level and insulin receptor (IR) were increased in the breast cancer patient tissues. Insulin injected subcutaneously around the tumor site in mice caused increase in the size and weight of tumor masses, and promoted proliferation and migration of MCF-7 cells. The effects of insulin on the increase in the proliferation and migration of MCF-7 human breast cancer cells were abolished by pretreatment with the extracellular regulated kinase (ERK) inhibitor PD98059. Insulin increased the phosphorylation of ERK in the MCF-7 cells. These results indicate that insulin promotes the growth of breast cancer in nude mice, and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway.
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Cetinkaya, Kadir;Atalay, Funda;Bacinoglu, Ahmet 6353
Background: The purpose of this study was to investigate and evaluate risk factors for lymph node metastases (LNM) in cases of endometrial cancer (EC). Materials and Methods: A retrospective single institution analysis of patients surgically staged for EC at Ankara Oncology Education and Research Hospital from 1996 to 2010 was performed. Roles of prognostic factors, such as age, histological type, grade, depth of myometrial invasion, cervical involvement, peritoneal cytology, and tumor size, in the prediction of LNM were evaluated. Fisher's exact test and logistic regression analysis were used to assess the effects of various factors on LNM. Results: LNM was observed in 22 out of 247 patients (8.9%) and was significantly more common in the presence of tumors of higher grade, deep myometrial invasion (DMI), cervical involvement, size >2cm, and with positive peritoneal cytology. Logistic regression analysis revealed that DMI remained the only independent risk factor for LNM. NPV, PPV, sensitivity, and specificity for satisfying LNM risk were 98.0, 19.5, 86.3, and 65.3%, respectively for DMI. Conclusions: The incidence of LNM is influenced independently by DMI. If data support a conclusion of DMI, LND should be seriously considered. -
Mohammad, Ibnu Ayyub;Bujang, Mas Rina Wati;Telisinghe, Pemasari Upali;Abdullah, Muhd Syafiq;Chong, Chee Fui;Chong, Vui Heng 6357
Background: Globally, the overall incidence of cancer is increasing as a result of ageing populations and changing lifestyles. Cancer is one of the leading causes of death, especially in the developed nations. Cancers affecting the young population are generally considered uncommon. This study assessed the demography and trends of cancers of the young in Brunei Darussalam, a small and developing Southeast Asia nation. Materials and Methods: All patients diagnosed with cancers between 2000 and 2012 were identified from the cancer registry maintained by the State Histopathology Laboratory. Cancers of the young was defined as any cancers diagnosed under the age of 40 years. Demographic data and the type of cancers were collected and analysed using SPSS Statistics 17.0. Results: Among the 6,460 patients diagnosed with cancer over the study period, 18.7% (n=1,205) were categorized as young with an overall decline in the proportion from 26.6% in 2000 to 18.8% in 2012 (p<0.001 for trend). Among all cancers of the young, the most common systems affected were gynecological (24.1%), hematological/lymphatic (15.8%), subcutaneous/dermatological/ musculoskeletal (10.5%), breast (10.5%) and gastrointestinal (9.9%). Overall, among the different systems, neurological (54.9%) had the highest proportion of cancers of the young followed by gynecological/reproductive (30.6%), hematological/lymphatic (39.9%), endocrine (38.7%), subcutaneous/dermatological/ musculoskeletal (22.3%) and the head and neck region (20.1%). There was a female predominance (66.9%) and the incidence was significantly higher among the Malays (20.1%) and expatriates (25.1%) groups compared to the Chinese (10.7%) and indigenous (16.8%) groups (p<0.001 for trend). Conclusions: Cancers of the young (<40 years) accounted for almost a fifth of all cancers in Brunei Darussalam with certain organ systems more strongly affected. There was a female preponderance in all racial groups. Over the years, there has been a decline in the overall proportion of cancers of the young. Selective screening programs should nevertheless be considered. -
Wang, Xia;Liu, Hao;Wang, Xin;Zeng, Zhi;Xie, Li-Qun;Sun, Zhi-Guang;Wei, Mu-Xin 6363
Purpose: This study was conducted to assess the preventive effect of Actinidia valvata Dunn (AVD) extract on an animal model of gastrointestinal carcinogenesis on the basis of changes in tumor incidence, cell proliferation, and apoptosis. Materials and Methods: Seventy-five male Wistar rats were divided into five different treatment groups with 15 rats in each group. Group I was given normal feed, whereas Groups II to IV were treated with 10% sodium chloride in the first six weeks and 100ug/mL of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 24 weeks. Group II was then given normal feed, whereas Group III was given AVD extract (0.24g/kg/day) for 12 weeks. Group IV was given AVD extract from the first week to the 36th week, whereas Group V was treated with AVD extract alone for 36 weeks. All rats were sacrificed at the end of the 36-week experiment and assessed for the presence of gastrointestinal tumors. The occurrence of cancer was evaluated by histology. Bax, Bcl-2, Caspase-3, and cyclinD1 were determined by immunohistochemical staining and Western blotting. Results: The incidences of gastric cancer were 0% in Group I, 73.3% in Group II, 33.3% in Group III, 26.7% in Group IV, and 0% in Group V. Bcl-2 and cyclinD1 expression was decreased in AVD extract treated groups, whereas Bax and Caspase-3 expression was increased. Comparison with group II revealed significant differences (p<0.01). Conclusions: AVD extract exhibits an obvious preventive effect on gastrointestinal carcinogenesis induced by MNNG in rats through the regulation of cell proliferation and apoptosis. -
Cheng, Min;Liu, Lin;Yang, Hai-Shan;Liu, Gui-Feng 6369
Lung cancer (LC) is the leading cause of cancer mortality worldwide, predominantly due to the difficulty of early diagnosis and its high metastatic potential. Recently, increasing evidence suggests that circulating tumour cells (CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted interest in cancer metastasis detection and quantification. In present study, we collected blood samples from 67 patients with bone metastasis, and 30 patients without such metastasis, and searched for CTCs. Then the association of CTC numbers with bone metastasis and other clinico-pothological variants was analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the CTC number, there were significantly higher positivity of CTCs in the bone metastasis group than in the non-metastasis group. While the increase in CTC number was not significantly associated with any other clinicopathological factor, including age, gender, pathological type, intrapulmonary metastasis and lymph node metastasis, the CTC number in patients with positivity of the last above mentioned variants was obviously higher than in patients with negativity of the two variants. Taken together, the CTC number appears to be significantly associated with the bone metastasis from lung cancer. -
Tanik, Serhat;Albayrak, Sebahattin;Zengin, Kursad;Borekci, Hasan;Bakirtas, Hasan;Imamoglu, M. Abdurrahim;Gurdal, Mesut 6375
Purpose: The aim of this study was to evaluate inflammation parameters and assess the utility of the neutrophil-lymphocyte ratio (NLR) as a simple and readily available predictor for clinical disease activity in patients with nenign prostate hyperplasia BPH. We also aimed to investigate the relationship between inflammatory parameters with${\alpha}$ -blocker therapy response, and evaluate the potential association between NLR and the progression of benign prostatic hyperplasia (BPH). Materials and Methods: We examined 320 consecutive patients (July 2013-December 2013) admitted to our outpatient clinic with symptoms of the lower urinary tract at Bozok University. The mean age was 60 (range, 51-75) years. Complete blood count (CBC), prostate-specific antigen (PSA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed. Correlations between PSA, CRP, ESR, prostate volume, International Prostate Symptom Score (IPPS), maximum urinary flow rate (Qmax), and NLR were assessed statistically. Patients were divided into two groups: high and low risk of progression. Results: NLR was positively correlated with IPSS (p=0.001, r=0.265), PSA (p=0.001, r=0.194), and negatively correlated with Qmax (p<0.001, r=-0.236). High-risk patients a had a higher NLR compared with low-risk patients, based on IPSS (p<0.001), PSA (p=0.013), and Qmax (p<0.001); however, there were no significant differences between the groups in terms of age (p>0.05), and prostate volume (p>0.05). Conclusions: NLR can predict BPH progression. We propose that increased inflammation is negatively associated with clinical status in BPH patients and suggest that NLR can give information along with LUTS severity which may be used as a readikly accessible marker for patient follow-up. -
Sharma, Jagannath Dev;Kalita, Manoj;Barbhuiya, Jamil Ahmed;Lahon, Ranjan;Sharma, Arpita;Barman, Debanjana;Kataki, Amal Chandra;Roy, Barsha Deka 6381
Background: The global burden of cancer is continuously increasing. According to recent report of the National Cancer Registry Programme (NCRP) on time trends it is estimated that future burden of cancer cases for India in 2020 will be 1,320,928. It is well known that knowledge of the incidence of cancer is a fundamental requirement of rational planning and monitoring of cancer control programs. It would help health planners to formulate public health policy if relevant ethnic groups were considered. North East-India alone contains over 160 Scheduled Tribes and 400 other sub-tribal communities and groups, whose cancer incidence rates are high compared to mainland India. As since no previous study was done focusing on ethnicity, the present investigation was performed. Materials and Methods: In this paper PBCR-Guwahati data on all cancer registrations from January 2009 to December 2011 for residents of the Kamrup Urban District, comprising an area of 261.8 sq. km with a total population of 900,518, including individual records with information on sex, age, ethnicity and cancer site are provided. Descriptive statistics including age adjusted rates (AARs) were taken as provided by NCRP. For comparison of proportional incidence ratios (PIR) the Student's t test was used, with p<0.05 considered as statistically significant. Results and Conclusions: Differences in leading sites of Kamrup Urban District since from the beginning of the PBCR-Guwahati were revealed among different ethnic groups by this study. The results should help policy makers to formulate different strategies to control the level of burden as well as for treatment planning. This study also suggests that age is an important factor of cancer among different ethnic populations as well as for overall population of Kamrup District of Assam. -
Lin, Gui-Nan;Jiang, Xiao-Mei;Peng, Jie-Wen;Xiao, Jian-Jun;Liu, Dong-Ying;Xia, Zhong-Jun 6387
Background: The prognostic significance of the circulating absolute monocyte count (AMC) in patients with locally advanced hepatocellular carcinoma (HCC) is uncertain. This study was designed to assess the association of circulating AMC with survival outcomes in patients diagnosed with locally advanced or metastatic HCC receiving systemic chemotherapy. Materials and Methods: Between January 1, 2005 and December 30, 2012, locally advanced or metastatic HCC patients who had Child-Pugh stage A or B disease and received systemic chemotherapy were retrospectively enrolled. Patient features including gender, age, extrahepatic metastasis, Child-Pugh stage, serum alpha-fetoprotein(AFP) level and AMC were collected to investigate their prognostic impact on overall survival(OS). Results: A total of 216 patients were eligible for the study. The optimal cut-off value of AMC for OS analysis was$0.38{\times}10^9/L$ . Median OS was 5.84 months in low-AMC group (95% confidence interval [CI], 5.23 to 6.45), and 5.21 months in high-AMC group (95% CI, 4.37 to 6.04; p=0.003). In COX multivariate analysis, elevated AMC remained as an independent prognostic factor for worse OS (HR, 1.578; 95% CI, 1.120 to 2.223, p=0.009). Conclusions: Our results indiicate that circulating AMC is confirmed to be an independent prognostic factor for OS in patients with locally advanced or metastatic HCC receiving systemic chemotherapy. -
Shi, Yong-Hua;Tuokan, Talaf;Lin, Chen;Chang, Heng 6391
Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24h and 48h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway. -
Asiaf, Asia;Ahmad, Shiekh Tanveer;Aziz, Sheikh Aejaz;Malik, Ajaz Ahmad;Rasool, Zubaida;Masood, Akbar;Zargar, Mohammad Afzal 6397
Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information. -
Pittyanont, Sirida;Yuthavisuthi, Prapap;Sananpanichkul, Panya;Thawonwong, Nutchanok;Techapornroong, Malee;Suwannarurk, Komsun;Bhamarapravatana, Kornkarn 6405
Background: To study the prevalence of abnormal anal cytology by Papanicolaou (Pap) technique in HIV-infected women who attended a HIV clinic at Prapokklao Hospital, Chanthaburi, Thailand. Materials and Methods: HIV-infected women who attended a HIV clinic at Prapokklao Hospital from March 2013 to February 2014 were recruited for anal Pap smears. Participants who had abnormal results of equally or over "abnormal squamous/glandular cells of undetermined significance" (ASC-US) were classified as abnormal anal cytology. Results: A total of 590 anal Pap smears were performed at HIV clinic of Prapokklao Hospital during the study period. There were only 13 patients who had abnormal Pap tests, which were: 11 ASC-US and 2 HSIL (high grade squamous intraepithelial lesion). The prevalence of abnormal anal Pap smears in HIV-infected women who attended HIV clinic at Prapokklao Hospital was 2.2 percent. Percentage of high risk HPV in patients who had abnormal Pap test was 88.9 (8/9). Conclusions: The prevalence of abnormal anal Papanicolaou smears in HIV-infected women who attended the HIV clinic at Prapokklao hospital was quite low in comparison to the earlier literature. -
Liu, Jing;Liu, Pei-Fang;Li, Jun-Nan;Qing, Chun;Ji, Yu;Hao, Xi-Shan;Zhang, Xue-Ning 6411
Background: A dense breast not only reduces the sensitivity of mammography but also is a moderate independent risk factor for breast cancer. The percentage of Western women with fat breast tissue is higher aged 40 years or older. To a certain extent, mammography as a first choice of screening imaging method for Western women of this group is reasonable. Hitherto, the frequency and age distribution of mammographic breast density patterns among Chinese women had not been characterized. The purpose of this study was to investigate the frequency and age distribution of mammographic breast density patterns among a group of Chinese screening women and breast cancer patients in order to provide useful information for age-specific guidelines for breast cancer screening in Chinese women. Methods: A retrospective review of a total of 3,394 screening women between August and December 2009 and 2,527 breast cancer patients between July 2011 and June 2012 was conducted. Descriptive analyses were used to examine the association between age and breast density. The significance of differences of breast density between the screening women and the breast cancer patients was examined using nonparametric tests. Results: There was a significant inverse relationship between age and breast density overall (r=-0.37, p< 0.01). Breast density of the breast cancer patients in the subgroups of 40-49 years old was greater compared with that of the screening women, the same in those aged 50-54 years and in those 55 years old or older, less than in the screening group. Conclusions: With regard to the Chinese women younger than 55 years old, the diagnostic efficiency of breast cancer screening imaging examinations may be potentially improved by combining screening mammography with ultrasound. -
Xiao, Xiao-Guang;Wang, Shu-Jing;Hu, Li-Ya;Chu, Qian;Wei, Yao;Li, Yang;Mei, Qi;Chen, Yuan 6415
Purpose: To explore the relationship between SER (time between the start of any treatment and the end of radiation therapy) and the survival of patients with limited-stage small cell lung cancer. Materials and Methods: Between 2008 and 2013, 135 cases of limited-stage small cell lung cancer (LS-SCLC) treated with consecutively curative chemoradiotherapy were included in this retrospective analysis. In terms of SER, patients were divided into early radiotherapy group (SER<30 days, n=76) and late radiotherapy group ($SER{\geq}30$ days, n=59) with a cut-off of SER 30 days. Outcomes of the two groups were compared for overall survival. Results: For all analyzable patients, median follow-up time was 23.8 months and median overall survival time was 16.8 months. Although there was no significant differences in distant metastasis free survival between the two groups, patients in early radiotherapy group had a significantly better PFS (p=0.003) and OS (p=0.000). Conclusions: A short SER may be a good prognostic factor for LD-SCLC patients treated with concurrent chemoradiotherapy. -
Tunce, Tolga;Ozgun, Alpaslan;Emirzeoglu, Levent;Celik, Serkan;Bilgi, Oguz;Karagoz, Bulent 6421
Background: Recent studies have revealed a prognostic impact of the MPV (mean platelet volume)/platelet count ratio in terms of survival in advanced non-small cell lung cancer. However, there has been no direct analysis of the survival impact of MPV in patients with mCRC. The aim of the study is to evaluate the pretreatment MPV of patients with metastatic and non-metastatic colorectal cancer (non-mCRC) and also the prognostic significance of pretreatment MPV to progression in mCRC patients treated with bevacizumab-combined chemotherapy. Materials and Methods: Fifty-three metastatic and ninety-five non-metastatic colorectal cancer patients were included into the study. Data on sex, age, lymph node status, MPV, platelet and platecrit (PCT) levels were obtained retrospectively from the patient medical records. Results: The MPV was significantly higher in the patients with mCRC compared to those with non-mCRC ($7.895{\pm}1.060$ versus$7.322{\pm}1.136$ , p=0.013). The benefit of bevacizumab on PFS was significantly greater among the patients with low MPV than those with high MPV. The hazard ratio (HR) of disease progression was 0.41 (95%CI, 0.174-0.986; p=0.04). In conclusion, despite the retrospective design and small sample size, MPV can be considered a prognostic factor for mCRC patients treated with bevacizumab-combined chemotherapy. -
Zahir, Shokouh Taghipour;Tafti, Hamid Fallah;Rahmani, Koorosh 6425
Background: Prostatic adenocarcinoma is one of the main causes of cancer death, and its timely diagnosis and preventing its progression dramatically helps improve life indexes. Given the high disease recurrence rate, today, research is more inclined toward exploring causes of recurrence and development, and innovation of modern treatment methods. Several studies have explored over-expression of human epidermal growth factor receptor 2 (HER-2/neu) in prostatic cancer so far, with different results. Thus, it was decided to investigate HER-2/neu overexpression in patients with prostatic adenocarcinoma in Iran. Materials and Methods: A sample size of 40 patients with prostate cancer entered the study, using a cross-sectional, non-randomized sampling method. Parameters studied included patient age at surgery, Gleason score, serum prostatic specific antigen (PSA) before surgery, and positive sample rate after immunohistochemical staining to investigate HER-2/neu overexpression. Results: In terms of HER-2/neu receptor staining rate, of 40 slides, 16 (40%) scored 0, 13 (32.5%) 1+, 7 (17.5%) 2+, and 4 (10%) 3+. In total 27.5% of slides showed HER-2/neu overexpression. In terms of age, an inverse correlation was found (-0.181), but without significance (p=0.263). In terms of serum PSA, the correlation coefficient was 0.449 (p=0.004). With respect to Gleason score, the coefficient was 0.190 (p=0.240). Conclusions: In this study, HER-2/neu overexpression occurred in 27.5% of prostate cancer cases, which is a relatively high figure, compared to similar studies elsewhere. While, we failed to reveal any relationship between HER-2/neu expression status with progression and prognosis of disease, it was demonstrated that the serum PSA level was significantly higher in cases with increased receptor expression. -
Poly-ADP-ribosylation (PAR) is a post-translational modification of mainly chromosomal proteins. It is known to be strongly involved in several molecular events, including nucleosome-remodelling and carcinogenesis. In this investigation, it was attempted to evaluate PAR level as a reliable biomarker for early detection of cancer in blood lymphocyte histones. PAR of isolated histone proteins was monitored in normal and dimethylnitrosamine (DMN)-exposed mice tissues using a novel ELISA-based immuno-probe assay developed in our laboratory. An inverse relationship was found between the level of PAR and period of DMN exposure in various histone proteins of blood lymphocytes and spleen cells. With the increase in the DMN exposure period, there was reduction in the PAR level of individual histones in both cases. It was also observed that the decrease in the level of PAR of histones resulted in progressive relaxation of genomic DNA, perhaps triggering activation of genes that are involved in initiation of transformation. The observed effect of carcinogen on the PAR of blood lymphocyte histones provided us with a handy tool for monitoring biochemical or physiological status of individuals exposed to carcinogens without obtaining biopsies of cancerous tissues, which involves several medical and ethical issues. Obtaining blood from any patient and separating blood lymphocytes are routine medical practices involving virtually no medical intervention, post-procedure medical care or trauma to a patient. Moreover, the immuno-probe assay is very simple, sensitive, reliable and cost-effective. Therefore, combined with the ease of preparation of blood lymphocytes and the simplicity of the technique, immuno-probe assay of PAR has the potential to be applied for mass screening of cancer. It appears to be a promising step in the ultimate goal of making cancer detection simple, sensitive and reliable in the near future.
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Gao, Shi-Yong;Li, Jun;Qu, Xiao-Ying;Zhu, Nan;Ji, Yu-Bin 6437
Background: Oridonin isolated from Rabdosia rubescens, a plant used to treat cancer in Chinese folk medicine, is one of the most important antitumor active ingredients. Previous studies have shown that oridonin has antitumor activities in vivo and in vitro, but little is known about cell cycle effects of oridonin in gastric cancer. Materials and Methods: MTT assay was adopted to detect the proliferation inhibition of SGC-7901 cells, the cell cycle was assessed by flow cytometry and protein expression by Western blotting. Results: Oridonin could inhibit SGC-7901 cell proliferation, the$IC_{50}$ being$15.6{\mu}M$ , and blocked SGC-7901 cell cycling in the$G_2/M$ phase. The agent also decreased the protein expression of cyclinB1 and CDK1. Conclusions: Oridonin may inhibit SGC-7901 growth and block the cells in the$G_2/M$ phase by decreasing Cdk1 and cyclinB1 proteins. -
Fatima, Nosheen;uz Zaman, Maseeh;Ikram, Mubashir;Akhtar, Jaweed;Islam, Najmul;Masood, Qamar;Zaman, Unaiza;Zaman, Areeba 6443
Background: To determine the predictive value of the baseline stimulated thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC). Materials and Methods: This retrospective study accrued 64 patients (23 male and 41 female; mean age of$40{\pm}14$ years) who had total thyroidectomy followed by RRA for DTC from January 2012 till April 2014. Patients with positive anti-Tg antibodies and distant metastasis on post-ablative whole body iodine scans (TWBIS) were excluded. Baseline STg was used to predict successful ablation (follow-up STg <2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at 7-12 months follow-up. Results: Overall, successful ablation was noted in 37 (58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off level of baseline STg level of${\leq}14.5ng/ml$ was found to be most sensitive and specific for predicting successful ablation. Successful ablation was thus noted in 25/28 (89%) of patients with baseline STg${\leq}14.5ng/ml$ and 12/36 (33%) patients with baseline STg >14.5 ng/ml ((p value <0.05). Age >40 years, female gender, PTS >2 cm, papillary histopathology, positive cervical nodes and positive TWBIS were significant predictors of ablation failure. Conclusions: We conclude that in patients with total thyroidectomy followed by I-131 ablation for DTC, the baseline STg level is a good predictor of successful ablation based on a stringent triple negative criteria (i.e. follow-up STg < 2 ng/ml, a negative DWBIS and a negative US neck). -
Duran, Ayse Ocak;Inanc, Mevlude;Karaca, Halit;Dogan, Imran;Berk, Veli;Bozkurt, Oktay;Ozaslan, Ersin;Ucar, Mahmut;Eroglu, Celalettin;Ozkan, Metin 6449
Background: Prior studies showed a relationship between serum albumin and the albumin to globulin ratio with different types of cancer. We aimed to evaluate the predictive value of the albumin-globulin ratio (AGR) for survival of patients with lung adenocarcinoma. Materials and Methods: This retrospective study included 240 lung adenocarcinoma patients. Biochemical parameters before chemotherapy were collected and survival status was obtained from the hospital registry. The AGR was calculated using the equation AGR=albumin/(total protein-albumin) and ranked from lowest to highest, the total number of patients being divided into three equal tertiles according to the AGR values. Furthermore, AGR was divided into two groups (low and high tertiles) for ROC curve analysis. Cox model analysis was used to evaluate the prognostic value of AGR and AGR tertiles. Results: The mean survival time for each tertile was: for the$1^{st}$ 9.8 months (95%CI:7.765-11.848),$2^{nd}$ 15.4 months (95%CI:12.685-18.186), and$3^{rd}$ 19.9 months (95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher survival rates with the third and high tertiles of AGR in comparison with the first and low tertiles, respectively. At multivariate analysis low levels of albumin and AGR, low tertile of AGR and high performance status remained an independent predictors of mortality. Conclusions: Low AGR was a significant predictor of long-term mortality in patients with lung adenocarcinoma. Serum albumin measurement and calculation of AGR are easily accessible and cheap to use for predicting mortality in patients with lung adenocarcinoma. -
Siti-Azrin, Ab Hamid;Norsa'adah, Bachok;Naing, Nyi Nyi 6455
Background: Nasopharyngeal carcinoma (NPC) is the fourth most common cancer in Malaysia. The objective of this study was to determine the five-year survival rate and median survival time of NPC patients in Hospital Universiti Sains Malaysia (USM). Methods: One hundred and thirty four NPC cases confirmed by histopathology in Hospital USM between$1^{st}$ January 1998 and$31^{st}$ December 2007 that fulfilled the inclusion and exclusion criteria were retrospectively reviewed. Survival time of NPC patients were estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare survival of cases among presenting symptoms, WHO type, TNM classification and treatment modalities. Results: The overall five-year survival rate of NPC patients was 38.0% (95% confidence interval (CI): 29.1, 46.9). The overall median survival time of NPC patients was 31.30 months (95%CI: 23.76, 38.84). The significant factors that altered the survival rate and time were age (p=0.041), cranial nerve involvement (p=0.012), stage (p=0.002), metastases (p=0.008) and treatment (p<0.001). Conclusion: The median survival of NPC patients is significantly longer for age${\leq}50$ years, no cranial nerve involvement, and early stage and is dependent on treatment modalities. -