Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
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.
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Volume 14 Issue 7
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Scientific evidence for the primary prevention of cancer caused by physical activity of regular moderate-intensity or greater is rapidly accumulating in this field. About 300 epidemiologic studies on the association between physical activity and cancer risk have been conducted worldwide. The objectives of this paper were three-fold: (i) to describe briefly the components of physical activity and its quantification; (ii) to summarize the most important conclusions available from comprehensive reports, and reviews of the epidemiologic individual and intervention studies on a role physical activity in cancer prevention; (iii) to present proposed biological mechanisms accounting for effects of activity on cancer risk. The evidence of causal linked physical activity and cancer risk is found to be strong for colon cancer - convincing; weaker for postmenopausal breast and endometrium cancers - probable; and limited suggestive for premenopausal breast, lung, prostate, ovary, gastric and pancreatic cancers. The average risk reductions were reported to be 20-30%. The protective effects of physical activity on cancer risk are hypothesized to be through multiple interrelated pathways: decrease in adiposity, decrease in sexual and metabolic hormones, changes in biomarkers and insulin resistance, improvement of immune function, and reduction of inflammation. As there are several gaps in the literature for associations between activity and cancer risk, additional studies are needed. Future research should include studies dealing with limitations in precise estimates of physical activity and of a lack of consensus on what defines sedentary behavior of individuals and those linked with the proposed biomarkers to cancer risk and controlled exercise intervention trials.
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Background: Although breast cancer is a major public health worry among Asian women, adherence to screening for the disease remains an obstacle to its prevention. A variety of psycho-social and cultural factors predispose women to delay or avoidance of screening for breast cancer symptoms at the early stages when cure is most likely to be successful. Yet few interventions implemented to date to address this condition in this region have drawn on health behavior theory. Materials and Methods: This paper reviews the existing literature on several cognitive theories and models associated with breast cancer screening, with an emphasis on the work that has been done in relation to Asian women. To conduct this review, a number of electronic databases were searched with context-appropriate inclusion criteria. Results: Little empirical work was found that specifically addressed the applicability of health theories in promoting adherence to the current breast cancer prevention programs Among Asian women. However, a few studies were found that addressed individual cognitive factors that are likely to encourage women's motivation to protect themselves against breast cancer in this region of the world. The findings suggest that multi-level, socio-cultural interventions that focus on cognitive factors have much promise with this issue. Conclusions: Interventions are needed that effectively and efficiently target the personal motivation of at-risk Asian women to seek out and engage in breast cancer prevention. Concerning implications, personal motivation to seek out and engage in individual preventive actions for breast cancer prevention among Asian women is a timely, high priority target with practical implications for community development and health promotion. Further studies using qualitative, anthropologic approaches shaped for implementation in multi-ethnic Asian settings are needed to inform and guide these interventions.
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Li, Jing;Huang, Rong;Schmidt, Johannes E.;Qiao, You-Lin 4015
Cancer of the cervix is the third most common cancer in women worldwide, more than 85% of the cases occurring in developing countries such as China. In China, since a national cancer registry is already set up but with geographically limited data generated, the burden of cervical cancer is believed to be underestimated. High-risk human papillomavirus (HR-HPV) prevalence among women attending routine cervical cancer screening programs has been shown to correlate well with cervical cancer incidence rates based on independently obtained HPV prevalence data as well as findings for the worldwide cervical cancer burden. Therefore, reviewing data on HR-HPV prevalence in population-based screening studies and hospital-based case studies will be important in the context of better understanding the cervical cancer burden and for the evaluation of the potential impact of HPV vaccination in the country. With the advent of prophylactic vaccines, significant progress is likely to be made in cervical cancer prevention. This article reviews available data on the HPV epidemiology over a 12-year time period (2001-2012) in mainland China under different epidemiological aspects: by age group of study population, by ethnicity, by geographic area, as well as time period. The authors also review the potential acceptability of HPV vaccination among Chinese women. -
Objectives: Colorectal cancer (CRC) is the most commonly diagnosed cancer for all US populations including Asian Americans. CRC screening has considerable benefits to prevent CRC and reduce mortality. The purpose of this article was to review the published literature on rates of colorectal cancer screening and factors associated with colorectal cancer screening practice among Asian Americans. Methods: Through searching electronic reference databases from 2000 to 2013, 30 articles were found on Chinese, Filipino, Japanese, Korean, and Vietnamese Americans. Findings: Asian Americans had significantly low ratesfor CRC screening; Korean Americans reported the lowest rates, while higher screening rates were found among Japanese Americans. Older age, longer length of stay in the US, and having a physician's recommendation were the most common facilitators to receiving screening. The common inhibiting factors were financial issues, employment status, and worries/fears about the procedure. Conclusions: Despite a number of Asian Americans being vulnerable to CRC, individual Asian subgroups were underserved with CRC screening and intervention. Further studies should focus on each individual Asian subgroup and culturally proficient CRC screening intervention programs should be developed for each.
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Han, Dong;Li, Shao-Jun;Zhu, Yan-Ting;Liu, Lu;Li, Man-Xiang 4033
Links between cancer and metabolism have been suggested for a long time but compelling evidence for this hypothesis came from the recent molecular characterization of the LKB1/AMPK signaling pathway as a tumor suppressor axis. Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. In addition, AMPK plays a central role in the control of cell growth, proliferation and autophagy through the regulation of mTOR activity, which is consistently deregulated in cancer cells. Targeting of AMPK/mTOR is thus an attractive strategy in the development of therapeutic agents against non-small-cell lung cancer (NSCLC). In this review, the LKB1/AMPK/mTOR signaling pathway is described, highlighting its protective role, and opportunities for therapeutic intervention, and clinical trials in NSCLC. -
Sankar, Shanju;Nayanar, Sangeetha K.;Balasubramanian, Satheesan 4041
Cancer vaccine development is in the process of becoming reality in future, due to successful phase II/III clinical trials. However, there are still problems due to the specificity of tumor antigens and weakness of tumor associated antigens in eliciting an effective immune response. Computational models to assess the vaccine efficacy have helped to improve and understand what is necessary for personalized treatment. Further research is needed to elucidate the mechanisms of activation of antigen specific cytotoxic T lymphocytes, decreased TREG number functionality and antigen cascade, so that overall improvement in vaccine efficacy and disease free survival can be attained. T cell epitomic based in sillico approaches might be very effective for the design and development of novel cancer vaccines. -
Xu, Chao-Yang;Jiang, Zhi-Nong;Zhou, Ying;Li, Jia-Jia;Huang, Li-Ming 4049
Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor${\alpha}$ , P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II.$ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive$ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of$ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes. -
Baser, Eralp;Togrul, Cihan;Ozgu, Emre;Esercan, Alev;Caglar, Mete;Gungor, Tayfun 4053
Background: Colposcopy is the gold standard procedure for evaluating cervical cytological abnormalities. Although it is essentially a minimally invasive intervention, referral for colposcopy may cause significant distress on patients. In this study, we aimed to determine if pre-procedural anxiety levels have a significant association with procedure related pain and discomfort in women undergoing colposcopy for evaluation of abnormal cervical cytology. We also assessed the impact of various clinical factors on anxiety, pain and discomfort in these patients. Materials and Methods: This prospective study was performed at the gynecologic oncology department of Zekai Tahir Burak Women's Health Education and Research Hospital in Ankara, Turkey between January and June 2013. After taking informed consent, State-Trait Anxiety Inventory (STAI) form and a 14-item questionnaire were filled for women who were admitted to our outpatient colposcopy unit for evaluation of abnormal cervical cytology. STAI scores were calculated for each participant. Immediately after the procedure, visual analog scale (VAS) scores for procedure-related pain and discomfort were obtained. Associations between STAI and VAS scores were investigated using correlation analyses. The effect of various contributing factors on anxiety, pain and discomfort were evaluated with linear regression analysis. The p values less than 0.05 were considered statistically significant. Results: A total of 222 women met the inclusion criteria within the study period. Mean patient age was$38.5{\pm}9.6$ . Median state and trait anxiety scores were 47 and 46, respectively. Median VAS scores for pain and discomfort were 4 for both variables. State anxiety had a significant correlation with procedure related discomfort (p=0.02). Colposcopy related pain VAS scores were significantly affected by state anxiety level, marital status and prior gynecological examination (p<0.05). Colposcopy related discomfort VAS scores were significantly affected by state anxiety level, marital status, prior gynecological examination and educational status. Conclusions: Additional measures should be implemented in women that carry higher risk for experiencing pain and discomfort. Social, cultural and lifestyle issues may also affect women's experiences during colposcopy, therefore further studies are needed to define specific determining factors in various populations. -
Ho, Christopher Chee Kong;Tan, Wei Phin;Pathmanathan, Rajadurai;Tan, Wei Keith;Tan, Hui Meng 4057
Background: Fluorescence in situ hybridization (FISH) testing may be useful to screen for bladder carcinoma or dysplasia by detecting aneuploidy chromosomes 3, 7, 17 and deletion of the chromosome 9p21 locus in urine specimens. This study aimed to assess the sensitivity, specificity, positive and negative predictive value of FISH in a multi-ethnic population in Asia. Materials and Methods: Patients with haematuria and/or past history of urothelial cancer on follow-up had their voided urine tested with FISH. Patients then underwent cystoscopy/ureteroscopy and any lesions seen were biopsied. The histopathological reports of the bladder or ureteroscopic mucosal biopsies were then compared with the FISH test results. Results: Two hundred sixty patients were recruited. The sensitivity and specificity of the FISH test was 89.2% and 83.4% respectively. The positive (PPV) and negative predictive values (NPV) were 47.1% and 97.9%. By excluding patients who had positive deletion of chromosome 9, the overall results of the screening test improved: sensitivity 84.6%; specificity 96.4%; PPV 75.9% and NPV 97.9%. Conclusions: UroVysion FISH has a high specificity of detecting urothelial cancer or dysplasia when deletion of chromosome 9 is excluded. Negative UroVysion FISH-tests may allow us to conserve health resources and minimize trauma by deferring cystoscopic or ureteroscopic examination. -
Zhang, Jing;Zhu, Meng-Yuan;Wang, Liang;Wang, Hua;Wang, Wei-Da;Geng, Qi-Rong;Lu, Yue 4061
The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined. A total of one hundred and twenty-one patients with ENKTL receiving sandwich CT with RT were reviewed between January 2003 and August 2012. The primary endpoints were the response rate, progression-free survival (PFS), overall survival (OS), and the relapse rate. After the initial CT, there were 84 (69.4%) patients in CR, 22 (18.2%) patients in PR, 9 (7.4%) patients in SD, and 6 (5%) patients in PD, respectively. At the end of RT, the CR, PR, SD, and PD rates for all patients were 90.9% (n=110), 1.7% (n=2), 4.1% (n=5), and 3.3% (n=4), respectively. After a median follow-up of 42.3 months (3.5~112.3 months), the 5-year PFS was 74.7% (95% CI 70.4%~79.0%), and 5-year OS was 77.3% (95% CI 67.9%~86.7%). Disease progression was documented in 25 (20.7%) patients. The rates of systemic failure, local failure, and regional failure were 18.2%, 5.8%, 1.7%, respectively. Twenty death events (16.5%) were observed for the entire group of patients (18 deaths related to PD). Furthermore, CR to the initial CT and low Korean Prognostic Index (KPI) can independently predict long PFS and OS. The sandwich CMT achieved an excellent outcome for localized ENKTL with acceptable toxicity. We recommend it can be applied as the optimal choice for localized ENKTL. -
Jha, Dipendra Kumar;Mittal, Ankush;Gupta, Satrudhan Pd;Sathian, Brijesh 4067
Background: The present study was undertaken to establish any correlation of elevated levels of CA19-9 with tumor stage or grade of urothelial carcinoma. Materials and Methods: This hospital based study was carried out in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between$1^{st}$ July 2012 and$31^{st}$ December 2012. Approval for the study was obtained from the institutional research ethical committee. CA19-9 was assayed with an ELISA reader for all cases and expressed in U/ml with 37U/ml taken as the cut-off upper value for normal. Results: Out of 20 cases enrolled, 15 were of urothelial carcinoma and the remaining 5 were controls. There was marked difference between the mean values of CA19-9 in cases$40.2{\pm}19.3U/ml$ of urothelial carcinoma and controls$7.98{\pm}7.34U/ml$ . The number of cases in Ta, TI, T2, T3, T4 stages of urothelial carcinoma were 2, 6, 3, 3, 1 respectively. The percentage rise in CA19-9 was less with low grade tumors (22.2%) when compared with high grade tumors (66.6%) (p value$0.001^*$ ). The percentage of rise in CA19-9 for muscle invasive tumors was very high when compared to superficial tumors. Similarly, the percentage of rise in CA19-9 for metastatic disease was very high when compared to non-metastatic disease and it was found statistically significant (p value$0.001^*$ ). Conclusion: Serum CA19-9 levels predicts the prognosis of urothelial carcinoma as it is almost invariably raised in tumors having metastatic spread. -
Guo, Run-Sheng;Shi, Pei-Dong;Zhou, Jie;Chen, Yue-Yu 4071
Expression changes of somatostatin receptor subtypes (SSTRs) including SSTR1, SSTR2, SSTR3, SSTR4 and SSTR5 in the development of gallbladder cancer were assessed with attention to relationships with clinical pathological characteristics. SSTRs in 29 gallbladder cancer and 25 normal gallbladder tissue specimens were examined by immunohistochemical staining. Differences between SSTRs expressions and clinical pathological parameters were analyzed by chi-square test. The five subtypes of SSTR were all expressed in gallbladder cancer tissues and SSTR3 presented the highest expression. SSTR5 expression was increased significantly in gallbladder cancer (P<0.05) compared with that in normal gallbladder tissue. SSTR3 expression in highly and moderately differentiated gallbladder cancer was significantly higher than that in poorly differentiated lesions (P<0.05). SSTR4 expression was lower in gallbladder cancer with lymph node metastasis than that in gallbladder cancer without lymph node metastasis (P<0.05). Therfore, these results indicated that SSRT5, SSTR3 and SSTR4 may play important roles in the formation and development of gallbladder cancer. -
Liang, Shu-Yuan;Wang, Tsae-Jyy;Wu, Shu-Fang;Chao, Ta-Chung;Chuang, Yeu-Hui;Tsay, Shiow-Luan;Tung, Heng-Hsin;Lee, Ming-Der 4077
The purpose of this descriptive and comparative study was to examine gender differences relevant to pain intensity, opioid prescription patterns and opioid consumption in Taiwanese oncology outpatients. The 92 participants had been prescribed opioid analgesics for cancer-related pain at least once in the past week and were asked to complete the Brief Pain Inventory - Chinese questionnaire and to recall the dosage of each opioid analgesic that they had ingested within the previous 24 hours. For opioid prescriptions and consumption, all analgesics were converted to morphine equivalents. The results revealed a significant difference between males and female minimum pain thresholds (t = 2.38, p = 0.02) and current pain thresholds (t = 2.12, p = 0.04), with males reporting a higher intensity of pain than females. In addition, this study found that males tended to use prescribed opioid analgesics more frequently than females on the bases of both around the clock (ATC) (t = 1.90, p = 0.06) and ATC plus as needed (ATC + PRN) (t = 2.33, p = 0.02). However, there was no difference between males and females in opioid prescriptions on an ATC basis (t = 0.52, p = 0.60) or at an ATC + PRN basis (t = 0.40, p = 0.69). The results suggest that there may be a gender bias in the treatment of cancer pain, supporting the proposal of routine examination of the effect of gender on cancer pain management. These findings suggest that clinicians should be particularly aware of potential gender differences during pain monitoring and the consumption of prescribed opioid analgesics. -
Cheng, Hong-Bin;Xie, Chen;Zhang, Ru-You;Hu, Shao-Shan;Wang, Zhi;Yue, Wu 4083
We conducted an exploratory investigation of whether variation in six common SNPs of xeroderma pigmentosum complementation group F (XPF) is associated with risk of glioma in a Chinese population. Six single nucleotide polymorphisms (SNPs) were genotyped in 207 glioma cases and 236 cancer-free controls by a 384-well plate format on the Sequenom MassARRAY platform (Sequenom, San Diego, USA). The rs1800067 G and rs2276466 G allele frequencies were significantly higher in the glioma group than controls. Individuals with the rs1800067 GG genotype were at greater risk of glioma when compared with the A/A genotype in the codominant model, with an OR (95% CI) of 2.63 (1.04-7.25). The rs2276466 polymorphism was significantly associated with moderate increased risk of glioma in codominant and dominant models, with ORs (95% CI) of 1.90 (1.05-3.44) and 1.55 (1.07-2.47), respectively. The combination genotype of rs1800067 G and rs2276466 G alleles was associated with a reduced risk of glioma (OR=0.44, 95% CI=0.19-0.98). These findings indicate that genetic variants of the XPF gene have critical functions in the development of glioma. -
Zhang, Wei-Ling;Zhang, Yi;Huang, Dong-Sheng;Guo, Fang;Han, Tao;Hong, Liang;Hu, Hui-Min;Zhi, Tian 4089
Objective: The rhabdomysarcoma (RMS) is most common soft tissue carcinoma in children, mostly found in the head and neck with high degree of malignancy. The current study aimed to summarize clinical data and evaluate treatment outcome of cases in a single hospital. Methods: Forty-one (24 male, 17 female) children with newly diagnosed RMS in Beijing Tong Ren Hospital were enrolled between November, 2004 and May, 2011. The. Students' t and Chi tests were then performed on retrospectively reviewed clinical data, followed by survival analysis based on the Kaplan Meier method using SPSS 17.0 software. Results: Of all cases, 32 were treated by common chemotherapy, and 3 cases with stage III RMS received high-dose chemotherapy and auto-peripheral blood stem cell transplantation (APBSCT). Side-effects in the former were: I grade for 62.5% (20/32), II grade for 28.1% (9/32), III grade account for 9.275% (3/32). Side-effects of 3 cases with APBSCT: 2 were I grade, 1 was III grade. The median follow-up time of 41 RMS cases was 41 months. Four cases were lost to follow-up, 7 cases recurred, and 5 cases died of cerebral metastasis, witha total survival rate was 86.5% (32/37). CR rate was 67.6% (25/37), PR was 18.9% (7/37). Conclusion: Multidiscipline treatment including chemotherapy, radiotherapy, surgery and auto-PBSCT is highly recommended for pediatric patients with head and neck RMS. -
Oxidative stress induces apoptosis in many cellular systems including glioblastoma cells, with caspase-8 activation was regarded as a major contribution to
$H_2O_2$ -induced cell death. This study focused on the role of the autophagic protein p62 in$H_2O_2$ -induced apoptosis in U87MG cells. Oxidative stress was applied with$H_2O_2$ , and cell apoptosis and viability were measured with use of caspase inhibitors or autophagic mediators or siRNA p62, GFP-p62 and GFP-p62-UBA (del) transfection. We found that$H_2O_2$ -induced U87MG cell death was correlated with caspase-8. To understand the role of p62 in MG132-induced cell death, the levels of p62/SQSTM1 or autophagy in U87MG cells were modulated with biochemical or genetic methods. The results showed that the over-expression of wild type p62/SQSTM1 significantly reduced$H_2O_2$ induced cell death, but knockdown of p62 aggravated the process. In addition, inhibition of autophagy promoted p62 and active caspase-8 increasing$H_2O_2$ -induced apoptosis while induction of autophagy manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 required its C-terminus UBA domain to attenuate$H_2O_2$ cytotoxity by inhibition of caspase-8 activity. Our results indicated that p62/SQSTM1 was a potential contributor to mediate caspase-8 activation by autophagy in oxidative stress process. -
Zeybek, Umit;Yaylim, Ilhan;Ozkan, Nazli Ezgi;Korkmaz, Gurbet;Turan, Saime;Kafadar, Didem;Cacina, Canan;Kafadar, Ali Metin 4101
Alterations of cyclin D1, one of the main regulators of the cell cycle, are known to be involved in various cancers. The CCDN1 G870A polymorphism causes production of a truncated variant with a shorter half-life and thus thought to impact the regulatory effect of CCDN1. The aim of the present study was to contribute to existing results to help to determine the prognostic value of this specific gene variant and evaluate the role of CCDN1 G870A polymorphism in brain cancer susceptibility. A Turkish study group including 99 patients with primary brain tumors and 155 healthy controls were examined. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The CCDN1 genotype frequencies in meningioma, glioma and control cases were not significantly different (p>0.05). No significant association was detected according to clinical parameters or tumor characteristics; however, a higher frequency of AG genotype was recorded within patients with astrocytic or oligoastrocytic tumors. A significant association between AG genotype and gliobilastoma multiforme (GBM) was recorded within the patients with glial tumors (p value=0.048 OR: 1.87 CI% 1.010-3.463). According to tumor characteristics, no statistically significant difference was detected within astrocytic, oligoasltrocytic tumors and oligodentrioglias. However, patients with astrocytic astrocytic or oligoastrocytic tumors showed a higher frequency of AG genotype (50%) when compared to those with oligodendrioglial tumors (27.3%). Our results indicate a possible relation between GBM formation and CCDN1 genotype. -
Objective: Matrix metalloproteinase-9(MMP-9) plays an important role in tumor cell invasion. Although it has been studied frequently in ovarian cancer, its prognostic impact is still equivocal. The aim of this study was to more precisely estimate its prognostic significance. Method:We searched Pubmed, Embase, OVID, Sciencedirect and CBM databases to identify eligible studies. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were pooled across studies using fixed-effects or random-effects models. We also performed subgroup analysis. Results: 30 studies (n=2552 patients) focusing on prognosis or expression of MM-9 were included. Increased expression of MMP-9 was associated with poor prognosis in ovarian cancer patients (HR=1.68, 95%CI 1.09-2.59, p=0.02). Besides, MMP-9 expression in ovarian cancer was significantly higher than non-malignant tumors (OR=11.46, 95%CI 8.47-15.50, P<0.00001). Moreover, increased expression of MMP-9 was significantly associated with FIGO stage (OR=4.85, 95%CI 2.60-9.04, P<0.00001), grade of differentiation (OR=3.34, 95%CI 2.46-4.54, P<0.00001), lymph node metastasis (OR=5.75, 95%CI 3.71-8.92, P<0.00001) and there was no association with histological type of ovarian cancer. Conclusions: Increased expression of MMP-9 was associated with poor prognosis in ovarian cancer patients. Down-regulation of MMP-9 is an attractive therapeutic approach which might improve outcome of ovarian cancer.
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Olmez, Omer Fatih;Evrensel, Turkkan;Cubukcu, Erdem;Ugras, Nesrin;Avci, Nilufer;Canhoroz, Mustafa;Deligonul, Adem;Hartavi, Mustafa;Olmez, Fatma;Cubukcu, Sinem;Tolunay, Sahsine;Kurt, Ender;Kanat, Ozkan;Manavoglu, Osman 4115
Background: Previous reports have shown that human epidermal receptor (HER)-3 overexpression may be associated with poor prognosis in patients with breast cancer, but results have been conflicting. In this study, we sought to investigate the prognostic significance of HER-3 immunohistochemical expression in patients with metastatic breast cancer. Methods: We retrospectively analyzed HER-3 immunohistochemical expression profiles in 45 paraffin-embedded specimens from patients who had been treated between 1996 and 2006 in the Department of Oncology of the Uludag University School of Medicine, Bursa, Turkey. Membranous or cytoplasmic dominant expression patterns of HER-3 were analyzed using the Rajkumar score and a cytoplasmic 4-point scoring system, respectively. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. Results: The median PFS in the study participants was 9 months (interquartile range: 4.5-13 months), whereas the median OS was 20 months (interquartile range: 7.5-28 months). Categorization of the patient population according to HER-3 positive immunohistochemical expression did not reveal any statistically significant difference in terms of both PFS (p=0.70) and OS (p=0.81). The results of multivariable Cox regression analysis indicated that tumor size was the only independent predictor of PFS, whereas estrogen and progesterone receptor status was independently associated with OS. Conclusions: HER-3 immunohistochemical expression did not correlate with outcomes in Turkish patients with metastatic breast cancer. Although our results suggest that HER-3 expression in cancer specimens is not of prognostic significance, further prospective studies are warranted to confirm these results. -
Yu, Hong-Sheng;Liu, Zi-Min;Yu, Xiao-Yun;Song, Ai-Qin;Liu, Ning;Wang, Hao 4121
Objective: Low dose radiation may stimulate the growth and development of animals, increase life span, enhance fertility, and downgrade the incidence of tumor occurrence.The aim of this study was to investigate the antitumor effect and hormesis in an erythrocyte system induced by low-dose radiation. Methods: Kunming strain male mice were subcutaneously implanted with S180 sarcoma cells in the right inguen as an experimental in situ animal model. Six hours before implantation, the mice were given 75mGy whole body X-ray radiation. Tumor growth was observed 5 days later, and the tumor volume was calculated every other day. Fifteen days later, all mice were killed to measure the tumor weight, and to observe necrotic areas and tumor-infiltration-lymphoreticular cells (TILs). At the same time, erythrocyte immune function and the level of 2,3-diphosphoglyceric acid (2,3-DPG) were determined. Immunohistochemical staining was used to detect the expression of EPO and VEGFR of tumor tissues. Results: The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without low dose radiation (P < 0.05). The tumor growth slowed down significantly in mice pre-exposed to low dose radiation; the average tumor weight in mice pre-exposed to low dose radiation was lighter too (P < 0.05). The tumor necrosis areas were larger and TILs were more in the radiation group than those of the group without radiation. The erythrocyte immune function, the level of 2,3-DPG in the low dose radiation group were higher than those of the group without radiation (P < 0.05). After irradiation the expression of EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from sham-irradiation group. The expression of VEGFR also decreased, and LDR-24h group was the lowest (P < 0.05). Conclusion: Low dose radiation could markedly increase the anti-tumor ability of the organism and improve the erythrocyte immune function and the ability of carrying$O_2$ . Low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself. -
MicroRNA-16 (miR-16) has been demonstrated to regulate proliferation and apoptosis in many types of cancers, but its biological function in bladder cancer remains unknown. Here, we found expression of miR-16 to be downregulated in bladder cancer in comparison with the adjacent normal tissues. Enforced expression of miR-16 was able to inhibit cell proliferation in TCHu-1 cells, in line with results for miR-16 antisense oligonucleotides (antisense miR-16). At the molecular level, our results further revealed that cyclin D1 expression was negatively regulated by miR-16. Therefore, the data reported here demonstrate that miR-16 is an important regulator in bladder cancer, which will contribute to better understanding of important mis-regulated miRNAs.
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Zhou, Xiao-Feng;Ding, Zhen-Shan;Liu, Nai-Bo 4131
Objective: To evaluate the relationship between allium vegetable intake and risk of prostate cancer. Methods: A systematic literature search up to May 2013 was carried out in PubMed, EMBASE, Scopus, Web of Science, Cochrane register, and Chinese National Knowledge Infrastructure (CNKI) databases, and the references of retrieved articles were also screened. The summary relative risks with 95% confidence interval for the highest versus the lowest intake of allium vegetables were calculated. Heterogeneity and publication bias were also evaluated. Results: A total of nine epidemiological studies consisting of six case-control and three prospective cohort studies were included. We found a significantly decreased risk of prostate cancer for intake of allium vegetables (OR=0.82, 95% CI 0.70, 0.97). Moreover, in the subgroup analysis stratified by allium vegetable types, significant associations were observed for garlic (OR=0.77, 95% CI 0.64-0.91) but not onions (OR=0.84, 95% CI 0.62-1.13). Conclusions: Allium vegetables, especially garlic intake, are related to decreased risk of prostate cancer. Because of the limited number of studies, further well-designed prospective studies are warranted to confirm the findings of our study. -
Nojiri, Ayumi;Toyoda, Takeshi;Tanaka, Takuji;Yoshida, Toshimichi;Tatematsu, Masae;Tsukamoto, Tetsuya 4135
Inflammation is potential risk factor of various human malignancies. Inflammatory bowel syndromes such as ulcerative colitis are well known as risk factors for colon cancer. Here, we examined enhancing effects of dextran sulfate sodium (DSS)-associated inflammation on X-irradiation induced colonic tumorigenesis in Min and wild-type (WT) mice. Animals were X-irradiated at 1.5 Gy at 5 weeks of age (at 0 experimental week) and 2% DSS in drinking water was administered at 5 or 11 experimental weeks. Mice were sacrificed at 16 weeks and incidence and multiplicity of colonic tumors were assessed. Incidence of colonic tumors in Min mouse was increased from 33.3% to 100% (p<0.05) with X-irradiation alone, whereas no tumors were developed in WT mice. In DSS-treated Min mice, X-irradiation increased the number of colonic tumors. Total number of colonic tumors was increased 1.57 times to$30.7{\pm}3.83$ tumors/mouse with X-irradiation+DSS at 5 weeks comapared to$19.6{\pm}2.9$ in corresponding DSS alone group (p<0.05). When the duration of inflammation was compared, longer period of DSS effect promoted more colonic tumorigenesis. Collectively, we conclude that X-irradiation and DSS-induced inflammation act synergistically for colonic tumorigenesis. -
Yoo, Ki-Bong;Kwon, Jeoung A;Cho, Eun;Kang, Moon Hae;Nam, Jung-Mo;Choi, Kui Son;Kim, Eun Kyung;Choi, Yun Jeong;Park, Eun-Cheol 4141
Background: Mammography is considered the gold standard of breast cancer mass screening and many countries have implemented this as an established breast cancer screening strategy. However, although the incidence of breast cancer and racial characteristics are different between Western and Asian countries, many Asian countries adopted mammography for mass screening. Therefore, the objective of this research was to determine whether mammography mass screening is cost-effective for both Western and Asian countries. Materials and Methods: A systematic review was performed of 17 national mammography cost-effectiveness data sets. Per capita gross domestic product (GDP), breast cancer incidence rate, and the most optimal cost-effectiveness results [cost per life year saved (LYS)] of a mammography screening strategy for each data set were extracted. The CE/per capita GDP ratio is used to compare the cost-effectiveness of mammography by countries. Non-parametric regression was used to find a cut-off point which indicated the breast cancer incidence rate boundary line determining whether mammography screening is cost-effective or not. Results: We found that the cost-effective cut-off point of breast cancer incidence rate was 45.04; it exactly divided countries into Western and Asian countries (p<0.0014). Conclusions: Mammography screening is cost-effective in most of Western countries, but not in Asian countries. The reason for this result may be the issues of incidence rate or racial characteristics, such as dense breast tissue. The results indicate that mammography screening should be adopted prudently in Asian countries and other countries with low incidence rates. -
Fang, W.J.;Lam, K.O.;Ng, S.C.Y.;Choi, C.W.;Kwong, D.L.W.;Zheng, S.S.;Lee, V.H.F. 4151
Background: To compare response evaluation criteria in solid tumours (RECIST) and volumetric evaluation (VE) for colorectal cancer with liver-limited metastasis. Patients and Methods: VE of liver metastases was performed by manual contouring before and after chemotherapy on 45 pairs of computed tomography (CT) images in 36 patients who suffered from metastatic colorectal cancer (mCRC) with liver metastasis only. Cohen kappa was used to compare the agreement between VE and RECIST. Pearson correlation was performed for their comparison after cubic root transformation of the aggregate tumor volumes. Logistic regression was done to identify clinical and radiographic factors to account for the difference which may be predictive in overall response (OR). Results: There were 16 partial response (PR), 23 stable disease (SD) and 6 progressive disease (PD) cases with VE, and 14 PR, 23 SD and 8 PD with RECIST. VE demonstrated good agreement with RECIST (${\chi}$ =0.779). Discordant objective responses were noted in 6 pairs of comparisons (13.3%). Pearson correlation also showed excellent correlation between VE and RECIST ($r^2$ =0.966, p<0.001). Subgroup analysis showed that VE was in slightly better agreement with RECIST for enlarging lesions than for shrinking lesions ($r^2$ =0.935 and$r^2$ =0.780 respectively). No factor was found predictive of the difference in OR between VE and RECIST. Conclusions: VE exhibited good agreement with RECIST. It might be more useful than RECIST in evaluation shrinking lesions in cases of numerous and conglomerate liver metastases. -
Li, Xiao-Pan;Xie, Zhen-Yu;Fu, Yi-Fei;Yang, Chen;Hao, Li-Peng;Yang, Li-Ming;Zhang, Mei-Yu;Li, Xiao-Li;Feng, Li-Li;Yan, Bei;Sun, Qiao 4157
Objectives: Understanding the situation of cancer awareness which doctors give to patients might lead to prognostic prediction in cases of of colorectal cancer (CRC). Methods: Subsets of 10,779 CRC patients were used to screen the risk factors from the Cancer Registry in Pudong New Area in cancer awareness, age, TNM stage, and gender. Survival of the patients was calculated by the Kaplan-Meier method and assessed by Cox regression analysis. The views of cancer awareness in doctors and patients were surveyed by telephone or household. Results: After a median observation time of 1,616 days (ranging from 0 to 4,083 days) of 10,779 available patients, 2,596 of the 4,561 patients with cancer awareness survived, whereas 2,258 of the 5,469 patients without cancer awareness and 406 of the 749 patients without information on cancer awareness died of the disease. All-cause and cancer-specific survival were poorer for the patients without cancer awareness than those with (P < 0.001 for each, log-rank test). Cox multivariate regression analysis showed that cancer concealment cases had significantly lower cancer-specific survival (hazard ratio (HR) = 1.299; 95 % confidence interval (CI): 1.200-1.407)and all-cause survival (HR = 1.324; 95 % CI: 1.227-1.428). Furthermore, attitudes of cancer awareness between doctors and patients were significantly different (P < 0.001). Conclusion: Cancer concealment, not only late-stage tumor and age, is associated with a poor survival of CRC patients. -
Li, Pei;Yang, Juan;Ma, Qing-Yong;Wu, Zheng;Huang, Chen;Li, Xu-Qi;Wang, Zheng 4161
Objective: To investigate discriminating protein patterns and potential biomarkers in serum samples between pre/postoperative pancreatic cancer patients and healthy controls. Methods: 23 serum samples from PC patients (12 preoperative and 11 postoperative) and 76 from healthy controls were analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique combined with magnetic beads-based weak cation-exchange chromatography (MB-WCX). ClinProTools software selected several markers that made a distinction between pancreatic cancer patients and healthy controls. Results: 49 m/z distinctive peaks were found among the three groups, of which 33 significant peaks with a P < 0.001 were detected. Two proteins could distinguish the preoperative pancreatic cancer patients from the healthy controls. About 15 proteins may be potential biomarkers in assessment of pancreatic cancer resection. Conclusion: MB-MALDI-TOF-MS method could generate serum peptidome profiles of pancreatic cancer and provide a new approach to identify potential biomarkers for diagnosis and prognosis of this malignancy. -
Nirmala, Subramanian;Sudandiradoss, Chinnappan 4167
A najor current challenge and constraint in cervical cancer research is the development of vaccines against human papilloma virus (HPV) epitopes. Although many studies are done on epitope identification on HPVs, no computational work has been carried out for high risk forms which are considered to cause cervical cancer. Of all the high risk HPVs, HPV 16, HPV 18 and HPV 45 are responsible for 94% of cervical cancers in women worldwide. In this work, we computationally predicted the promiscuous epitopes among the E6 proteins of high risk HPVs. We identified the conserved residues, HLA class I, HLA class II and B-cell epitopes along with their corresponding secondary structure conformations. We used extremely precise bioinformatics tools like ClustalW2, MAPPP, NetMHC, Epi,Jen, EpiTop 1.0, ABCpred, BCpred and PSIPred for achieving this task. Our study identified specific regions 'FAFR(K)DL' followed by 'KLPD(Q)LCTEL' fragments which proved to be promiscuous epitopes present in both human leukocyte antigen (HLA) class I, class II molecules and B cells as well. These fragments also follow every suitable character to be considered as promiscuous epitopes with supporting evidences of previously reported experimental results. Thus, we conclude that these regions should be considered as the important for design of specific therapeutic vaccines for cervical cancer. -
Amani, Firouz;Ahari, Saeid Sadeghieh;Akhghari, Lyla 4177
Background: The aim of this research was to perform an epidemiologic survey of esophageal cancer in Ardabil province. Materials and Methods: In this cross-sectional descriptive study, 661 patients diagnosed with EC were studied from March 2002 to May 2011 e. The necessary data were collected with a checklist from the documents in Ardabil Cancer Registry (ACR) and analyzed by statistical methods with SPSS.18 software. Results: Of the total new cases of EC registered in ARC during study period, 430 (65.1%) of patients were male with the male to female standard ratio was 1.18, with a statistically significant gender bias. The most common morphology of EC was squamous cell carcinoma (SCC, 68.8%) followed by adenocarcinoma (28.5%). It was observed that in most of patients, EC lesions were in the middle third of esophagus. In addition, most patients were rural and about 40% had smoking habits. The age-standardized incidence rate of cancers was 48.4 per 100,000 among females and males. The annual incidence rates in males and females was 7.1 and 6.7 per 100,000; respectively. Conclusions: Results showed that the prevalence and annual incidence rate of cancer in Ardabil province is lower than other areas of the country with a male predominance and a relatively high proprortion of adenocarcinomas. -
Igissinov, Nurbek;Akshulakov, Serik;Igissinov, Saginbek;Moore, Malcolm;Adilbekov, Yerzhan;Gaitova, Kamilla;Kissaev, Yermek;Mustafina, Meruert 4181
In the article were observed the epidemiological aspects of malignant tumors of the central nervous system (MT CNS) in Kazakhstan in a retrospective study for the years 2004-2011. The material of the study was consolidated accounting data of oncology centers on patients with MT CNS (C70-72) with first time established diagnosis. Calculated were crude, age, standardized (world standard), aligned and predicted incidence of MT CNS among both male and female populations. It was found that over the studied period, there were 4,604 cases of MT CNS. The average annual crude incidence rate of MT CNS in total population was$3.7{\pm}0.1^0/_{0000}$ . Trends in aligned incidence rates in the whole country had a tendency to increase (T=+0.9%). Defined levels of morbidity MT CNS in the whole population in different regions of Kazakhstan: low up to$2.87^0/_{0000}$ , the average from 2.87 to$4.45^0/_{0000}$ and high from$4.45^0/_{0000}$ and above on the basis of which was given the space-time estimate. Age and sex differences in MT CNS incidence were also clearly established. -
Mohiuddin, Mohammed Khaliq;Chava, Srinivas;Upendrum, Pavani;Latha, Madhavi;Zubeda, Syeda;Kumar, Ajith;Ahuja, Yog Raj;Hasan, Qurratulain;Mohan, Vasavi 4187
Background: Evaluation of Human papilloma virus (HPV) and its association with promoter methylation of candidate genes, p53 and Aurora A in esophageal cancer. Materials and Methods: One hundred forty-one esophageal tissue samples from different pathologies were evaluated for HPV infection by PCR, while the promoter methylation status of p53 and Aurora A was assessed by methylation-specific restriction based PCR assay. Statistical analyses were performed with MedCalc and MDR software. Results: Based on endoscopy and histopathology, samples were categorized: cancers (n=56), precancers (n=7), esophagitis (n=19) and normals (n=59). HPV infection was found to be less common in cancers (19.6%), whereas its prevalence was relatively high in precancers (71.4%), esophagitis (57.8%) and normals (45.7%). p53 promoter methylation did not show any significant difference between cancer and normal tissues, whereas Aurora A promoter methylation demonstrated significant association with disease (p=0.00016, OR:5.6452, 95%CI:2.18 to 14.6) when compared to normals. Aurora A methylation and HPV infection was found in a higher percentages of precancer (66.6%), esophagitis (54.5%) and normal (45.2%) when compared to cancers (14.2%). Conclusions: Aurora A promoter methylation is significantly associated with esophageal cancer, but the effect of HPV infection on this epigenetic alteration is not significant. However MDR analysis showed that the hypostatic effect of HPV was nullified when the cases had Aurora methylation and tobacco exposure. Further HPV sub-typing may give an insight into its reduced prevalence in esophageal cancer verses normal tissue. However, with the present data it is difficult to assign any significant role to HPV in the etiopathology of esophageal cancer. -
Zhang, Zhi-Gang;Zhang, Qiu-Ning;Wang, Xiao-Hu;Tian, Jin-Hui 4195
Background and Objective: Though researched for years, the prognostic role of hypoxia-inducible factor 1 alpha (HIF-$1{\alpha}$ ) in gastric cancer is still controversial. We thus undertook a systematic review to assess the relationship. Method: A systematically literature search of Pubmed, Embase, Web of Science, China Biological Medicine Disc and Cochrane Library was undertaken in February 2013, and the reference lists of articles were retrieved. Results: 12 trials (1,555 participants) were included to assess the association between HIF-$1{\alpha}$ expression and survival. Summary hazard ratios (HRs) were calculated. HIF-$1{\alpha}$ expression was significantly correlated with poor overall survival of gastric cancer patients (HR=1.34, 95%CI: 1.13-1.58; P=0.0009), but not with poor disease free survival of gastric cancer patients (HR=1.67, 95%CI: 0.99-2.82; P=0.06). Conclusion: HIF-$1{\alpha}$ was associated with poor OS, but not DFS, especially for Asian patients. But studies evaluating relationships of HIF-$1{\alpha}$ with OS and DFS in non-Asian gastric cancer patients appear needed. -
Cihan, Yasemin Benderli;Baykan, Halit;Kavuncuoglu, Erhan;Mutlu, Hasan;Kucukoglu, Mehmet Burhan;Ozyurt, Kemal;Oguz, Arzu 4199
Background: This investigation focused on possible relationships between skin cancers and ABO/Rh blood groups. Materials and Methods: Between January 2005 and December 2012, medical data of 255 patients with skin cancers who were admitted to Kayseri Training and Research Hospital, Radiation Oncology and Plastic Surgery Outpatient Clinics were retrospectively analyzed. Blood groups of these patients were recorded. The control group consisted of 25701 healthy volunteers who were admitted to Kayseri Training and Research Hospital, Blood Donation Center between January 2010 and December 2011. The distribution of the blood groups of the patients with skin cancers was compared to the distribution of ABO/Rh blood groups of healthy controls. The association of the histopathological subtypes of skin cancer with the blood groups was also investigated. Results: Of the patients, 50.2% had A type, 26.3% had O type, 16.1% had B type, and 7.5% had AB blood group with a positive Rh (+) in 77.3%. Of the controls, 44.3% had A type, 31.5% had 0 type, 16.1% had B type, and 8.1% had AB blood group with a positive Rh (+) in 87.8%. There was a statistically significant difference in the distribution of blood groups and Rh factors (A Rh (-) and 0 Rh positive) between the patients and controls. A total of 36.8% and 20.4% of the patients with basal cell carcinoma (BCC) had A Rh (+) and B Rh (+), respectively, while 39.2% and 27.6% of the controls had A Rh (+) and B Rh (+), respectively. A significant relationship was observed between the patients with BCC and controls in terms of A Rh (-) (p=0.001). Conclusion: Our study results demonstrated that there is a significant relationship between non-melanoma skin cancer and ABO/Rh factors. -
Qin, Hai-Feng;Qu, Li-Li;Liu, Hui;Wang, Sha-Sha;Gao, Hong-Jun 4205
Objective: The aim of this study was to explore change and significance of serum carcino-embryonic antigen (CEA) before and after gefitinib therapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods: Forty patients with advanced NSCLCs in III~IV stages were selected as study objects given gefitinib therapy combined with routine local radiotherapy until tumor progression or intolerable toxicity. After treatment, all patients were divided into control and non-control groups according to the results of evaluation based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors in 2009). Peripheral fasting blood from all patients was collected in the early morning and serum CEA was assessed by electro-chemiluminescence immunoassay (ECLIA) before and after treatment. Before treatment, patients were divided into high CEA group (CEA level > 50 ng/mL) and low CEA group (CEA level${\leq}$ 50 ng/mL). Adverse reactions were noted and progression-free survival (PFS) in both groups was recorded after long-term follow-up that ended in December, 2012. Results: There was no difference between control and non-control groups in CEA level before treatment (P>0.05), whereas serum CEA decreased more markedly lower in the control group after treatment (P<0.01). All patients were divided into high CEA group (26) and low CEA group (14) according to serum CEA level. There was no statistically significant difference between two groups in adverse reactions (P>0.05) but the rate in former group was lower. Additionally, survival rates at 9 and 12 months in high CEA group were clearly higher than in the low CEA group (P<0.01). Conclusions: Serum CEA level can serve as a biochemical index to evaluate the prognosis with gefitinib treatment for NSCLC. -
Rostamizadeh, Leila;Fakhrjou, Ashraf;Montazeri, Vahid;Estiar, Mehrdad Asghari;Naghavi-Behzad, Mohammad;Hosseini, Somayyeh;Sakhinia, Masoud;Sakhinia, Ebrahim 4209
Background: Breast cancer is among the five most common cancers and ranks first among cancers diagnosed in Iranian women. Screening and treatment of this disease with molecular methods, especially regarding high incidences at early age and advanced stage, is essential. Several genes with altered expression have been identified by cDNA microarray studies in breast cancer, with the Bcl-2 gene indicated as a likely candidate. In this study, we studied Bcl-2 gene expression levels in parallel tumor and non-tumor breast tissues. Materials and Methods: Forty samples including 21 tumor, 16 non tumor (marginal) and 3 benign breast tissues which were all pathologically diagnosed, were subjected to RNA extraction and polyA RT-PCR with the expression level of Bcl-2 quantified using real-time PCR. Results: There is higher expression levels of the Bcl-2 gene in tumor samples compared with marginal samples, but not attaining significance(p>0.05). Bcl-2 expression in 14 (66.7%) of the cases of tumor samples and 9 (56.3%) cases of the marginal samples were positive. Comparison of the expression of the Bcl-2 gene in histological grade showed that a high expression of Bcl-2 was associated with a high histological grade (p<0.41). Conclusions: Our data suggests that dysregulated Bcl-2 gene expression is potentially involved in the pathogenesis of breast cancer. Using gene expression analysis may significantly improve our ability for screening cancer patients and will prove a powerful tool in the diagnosis and prognostic evaluation of the disease whilst aiding the cooperative group trials in the Bcl-2 based therapy project. -
Zhang, Dai;Ren, Wei-Hong;Gao, Yun;Wang, Nian-Yue;Wu, Wen-Jun 4215
Purposes: Lung cancer is prevalent worldwide and improvements in timely and effective diagnosis are need. Pentraxin-3 as a novel serum marker for lung cancer (LC) has not been validated in large cohort studies. The aim of the study was to assess its clinical value in diagnosis and prognosis. Methods: We analyzed serum PTX-3 levels in a total of 1,605 patients with LC, benign lung diseases and healthy controls, as well as 493 non-lung cancer patients including 12 different types of cancers. Preoperative and postoperative data were further assessed in patients undergoing LC resection. The diagnostic performance of PTX-3 for LC and early-stage LC was assessed using receiver operating characteristics (ROC) by comparing with serum carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1). Results: Levels of PTX-3 in serum were significantly higher in patients with LC than all controls. ROC curves showed the optimum diagnostic cutoff was 8.03ng/mL (AUC 0.823, [95%CI 0.789-0.856], sensitivity 72.8%, and specificity 77.3% in the test cohort; 0.802, [95%CI 0.762-0.843], sensitivity 69.7%, and specificity 76.4% in the validate cohort). Similar diagnostic performance of PTX-3 was observed for early-stage LC. PTX-3 decreased following surgical resection of LC and increased with tumor recurrence. Significantly elevated PTX-3 levels were also seen in patients with non-lung cancers. Conclusions: The present data revealed that PTX-3 was significantly increased in both tissue and serum samples in LC patients. PTX-3 is a valuable biomarker for LC and improved identification of patients with LC and early-stage LC from those with non-malignant lung diseases. -
Etiz, Durmus;Bayman, Evrim;Akcay, Melek;Sahin, Bilgehan;Bal, Cengiz 4223
Background: The purpose of this study was to determine the clinical and dosimetric factors associated with acute esophagitis (AE) in lung cancer patients treated with conformal radiotherapy (RT) in Turkey. Materials and Methods: In this retrospective review 104 lung cancer patients were examined. Esophagitis grades were verified weekly during treatment, and at 1 week, and 1 and 2 months afterwards. The clinical parameters included patient age, gender, tumor pathology, number of chemotherapy treatments before RT, concurrent chemotherapy, radiation dose, tumor response to RT, tumor localization, interruption of RT, weight loss, tumor and nodal stage and tumor volume. The following dosimetric parameters were analyzed for correlation of AE: The maximum ($D_{max}$ ) and mean ($D_{mean}$ ) doses delivered to the esophagus, the percentage of esophagus volume receiving${\geq}10$ Gy ($V_{10}$ ),${\geq}20$ Gy ($V_{20}$ ),${\geq}30$ Gy ($V_{30}$ ),${\geq}35$ Gy ($V_{35}$ ),${\geq}40$ Gy ($V_{40}$ ),${\geq}45$ Gy ($V_{45}$ ),${\geq}50$ Gy ($V_{50}$ ) and${\geq}60$ Gy ($V_{60}$ ). Results: Fifty-five patients (52.9%) developed AE. Maximum grades of AE were recorded: Grade 1 in 51 patients (49%), and Grade 2 in 4 patients (3.8%). Clinical factors had no statistically significant influence on the incidence of AE. In terms of dosimetric findings, correlation analyses demonstrated a significant association between AE and$D_{max}$ (>5117 cGy),$D_{mean}$ (>1487 cGy) and$V_{10-60}$ (percentage of volume receiving >10 to 60 Gy). The most significant relationship between RT and esophagitis were in$D_{max}$ (>5117 cGy) (p=0.002) and percentage of esophageal volume receiving >30 Gy ($V_{30}$ >31%) (p=0.008) in the logistic regression analysis. Conclusions: The maximum dose esophagus greater than 5117 cGy and approximately one third (31%) of the esophageal volume receiving >30 Gy was the most statistically significant predictive factor associated with esophagitis due to RT. -
Abraxane (nab-paclitaxel) is a member of the group of nano chemotherapeutics. It is approved for metastatic breast cancer and non small cell lung cancer. Trials for several cancer types including gynecological cancers, head and neck, and prostatic cancer are being studied. In this study, the antiproliferative and apoptotic effect of abraxane was evaluated on HeLa cell line originated from human cervix carcinoma. Three different doses (
$D_1$ =10 nM,$D_2$ =50 nM,$D_3$ =100 nM) were administered to HeLa cells for 24, 48 and 72 h. The 50 nM dose of abraxane decreased DNA synthesis from 4.62-0.08%, mitosis from 3.36-1.89% and increased apoptosis from 10.6-30% at 72 h. Additionally, tripolar metaphase plates were seen in mitosis preparations. In this study, abraxane effected cell kinetic parameters significantly. This results are consistent with other studies in the literature. -
Abdull Razis, Ahmad Faizal;Noor, Noramaliza Mohd 4235
Glucoraphanin is the main glucosinolate found in broccoli and other cruciferous vegetables (Brassicaceae). The objective of the study was to evaluate whether glucoraphanin and its breakdown product sulforaphane, are potent modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro. The glucosinolate glucoraphanin was isolated from cruciferous vegetables and exposed to human hepatoma cell line HepG2 at various concentrations (0-25${\mu}M$ ) for 24 hours. Glucoraphanin at higher concentration (25${\mu}M$ ) decreased dealkylation of methoxyresorufin, a marker for cytochrome P4501 activity; supplementation of the incubation medium with myrosinase (0.018 U), the enzyme that converts glucosinolate to its corresponding isothiocyanate, showed minimal induction in this enzyme activity at concentration 10${\mu}M$ . Quinone reductase and glutathione S-transferase activities were unaffected by this glucosinolate; however, supplementation of the incubation medium with myrosinase elevated quinone reductase activity. It may be inferred that the breakdown product of glucoraphanin, in this case sulforaphane, is superior than its precursor in modulating carcinogen-metabolising enzyme systems in vitro and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption. -
Li, Bing;Liu, Hong-Yi;Guo, Shao-Hua;Sun, Peng;Gong, Fang-Ming;Jia, Bao-Qing 4239
It is reported that the expression level of MLL3 in gastric cancer tissue highly correlates with tumor progression. However, whether MLL3 genetic variants are associated with the risk of gastric cancer remains unclear. In this study, we conducted a genotyping analysis for MLL3 in 314 cases of gastric cancer and 322 controls from the Chinese Han population. 4 SNPs (rs6943984, rs4725443, rs3800836, rs6464211) were selected for the present analysis. We found 2 SNPs (rs6943984, rs4725443) of MLL3 gene were significantly associated with the risk of gastric cancer : the rs6943984 with the minor allele A and rs4725443 with the minor allele C revealed strong associations with increased gastric cancer risk [P < 0.001, OR=1.97, 95% CI=1.48~2.64 and P <0.001, OR=2.23, 95% CI=1.54~3.24]. Haplotype analysis of the four SNPs showed that haplotype A-T-A-C, G-T-G-C, and G-C-A-C increased the risk of gastric cancer (P <0.001, P=0.18, and P<0.001, respectively), while haplotype G-T-A-C significantly reduced the risk of gastric cancer (P <0.001). We concluded that MLL3 variants are significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of MLL3 gene variants in carcinogenesis of gastric cancer of the Chinese Han population. -
Liang, Hong-Jie;Yan, Yu-Lan;Liu, Zhi-Ming;Chen, Xu;Peng, Qi-Liu;Wang, Jian;Mo, Cui-Ju;Sui, Jing-Zhe;Wu, Jun-Rong;Zhai, Li-Min;Yang, Shi;Li, Tai-Jie;Li, Ruo-Lin;Li, Shan;Qin, Xue 4243
The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36-2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results. -
Zhao, Shuang;Sun, Hong-Zhi;Zhu, Shi-Tu;Lu, Hang;Niu, Zhe-Feng;Guo, Wen-Feng;Takano, Yasuo;Zheng, Hua-Chuan 4249
Background: Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressor gene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectal carcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevant mechanisms of DLD-1 colon carcinoma cells. Methods: DLD-1 cells transfected with a parafibromin-expressing plasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migration and invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expression was detected by immunohistochemistry on tissue microarrays. Results: The transfectants showed higher proliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptotic resistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexin V, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibromin expression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78,$GSK3{\beta}$ -ser9, and Caspase-9. However, no difference was detectable in caspase-12 and -8 expression. A positive relationship was noted between parafibromin and ki-67 expression in colorectal carcinoma. Conclusions: Parafibromin overexpression could promote cell proliferation, apoptotic resistance, and differentiation of DLD-1 cells. -
Zhang, Lu-Ping;Liao, Xing-Yun;Xu, Yan-Mei;Yan, Lv-Jun;Yan, Gui-Fang;Wang, Xin-Xin;Duan, Yu-Zhong;Sun, Jian-Guo 4255
Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed. Objective: To evaluate the efficacy and safety of Endostar$^{(R)}$ combined with chemotherapy in patients with advanced STS. Methods: A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar$^{(R)}$ were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed. Results: In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P=0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P=0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups. Conclusions: Endostar$^{(R)}$ combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable. -
Zhang, Xiong;Jin, Fen-Shu;Zhang, Li-Guo;Chen, Rui-Xue;Zhao, Jin-Hui;Wang, Yan-Nan;Wang, En-Fu;Jiang, Zhen-Dong 4261
Increasing scientific evidence suggests that ribonucleotide reductase M1 (RRM1) may be a powerful predictor of survival in patients with pancreatic cancer treated with adjuvant gemcitabine-based chemotherapy after operative resection, but many existing studies have yielded inconclusive results. This meta-analysis aimed to assess the prognostic role of RRM1 in predicting survival in patients with pancreatic cancer treated with gemcitabine. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software and crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Eight clinical studies were included in this meta-analysis with a total of 665 pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy, including 373 patients in the high RRM1 expression group and 292 patients in the low RRM1 expression group. Our meta-analysis revealed that high RRM1 expression was associated with improved overall survival (OS) of pancreatic cancer patients (HR=1.56, 95%CI=0.95-2.17, P<0.001). High RRM1 expression also was linked to longer disease-free survival (DFS) than low RRM1 expression (HR=1.37, 95%CI=0.25-2.48, P=0.016). In conclusion, our meta-analysis suggests that high RRM1 expression may be associated with improved OS and DFS of pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy. Detection of RRM1 expression may be a promising biomarker for gemcitabine response and prognosis in pancreatic cancer patients. -
Cai, Ying-Ying;Lin, Wei-Ping;Li, Ai-Ping;Xu, Jian-Yang 4267
Background: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. Methods: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. Results: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. Conclusions: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications. -
Li, Xiao-Ming;Di, Bin;Shang, Yao-Dong;Tao, Zhen-Feng;Cheng, Ji-Min;He, Zhan-Guo 4273
Objective: We aimed to define clinicopathologic risk factors associated with regional recurrence (RR) and thus the effectiveness of postoperative radiotherapy (PORT) for neck control for head and neck squamous cell carcinomas (HNSCCs) with differing cervical lymph node status. Methods: A retrospective study was performed in 196 HNSCC patients with pathologically positive neck node (N+) to evaluate the high-risk factors for RR and to define the role of PORT in control after neck dissection and postoperative radiotherapy (PORT). Results: Overall, the RR rate after neck dissection and PORT was 29%. Extracapsular spread (ECS) was confirmed to be the only independent risk factor for RR. There were no significant risk factors associated with RR in the ECS- group. The 5-year disease-specific survival rate was 45%, which descended to 10% with the emergence of RR. Conclusions: ECS remains a determined risk factor for RR after neck dissection and PORT in patients with N+. PORT alone is not adequate for preventing RR in the neck with ECS after neck dissection. More intensive postoperative adjuvant therapies, especially combined chemotherapy and radiotherapy, are needed to prevent regional failure in HNSCC patients with ECS. -
Background: The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far. Materials and Methods: Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed. Conclusions: The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.
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Rahim, Fakher;Jalali, Amir;Tangestani, Raheleh 4283
Background: In this meta-analysis we review evidence suggesting that exposure to cadmium is a cause of breast cancer. Materials and Methods: We conducted Medline/PubMed and Scopus searches using selected MeSH keywords to identify papers published from January 1, 1980 through January 1, 2013. Data were merged and summary mean differences were estimated using either a random-effects model or a fixed-effects model. Results: There were 13 studies including 978 exposed cases and 1,279 controls. There was no statistically significant difference in the frequencies of breast cancer between cadmium-exposed and control groups, and the summary estimate of mean difference was 0.71 (95%CI: 0.33-1.08). However, stratification showed that there were statistically significant differences in the frequencies of breast cancer between cadmium-exposed and control groups among Asian compared with Caucasian population, and the summary estimates of mean difference were 1.45 (95%CI: 0.62-2.28) vs. 0.25 (95%CI: -0.09-0.6), respectively. There was a difference in the frequencies of breast cancer between cadmium-exposed and control groups in peripheral venous blood sampling methods, and the summary estimate of mean difference was 1.41 (95%CI: 0.46-2.37). Conclusions: Data indicate that the frequencies of breast cancer might be an indicator of early genetic effects for cadmium-exposed populations. However, our meta-analysis was performed on population-based studies; meta-analysis based on individual data might provide more precise and reliable results. Therefore, it is necessary to construct an international database on genetic damage among populations exposed to cadmium that may contain all raw data of studies examining genetic toxicity. -
Sisik, Abdullah;Kaya, Mustafa;Bas, Gurhan;Basak, Fatih;Alimoglu, Orhan 4289
Background: The purpose of this study was to assess the predictive effect of preoperative CEA and CA 19-9 levels on the prognosis of colorectal and gastric cancer patients. Materials and Methods: CEA and CA 19-9 were evaluated preoperatively in patients undergoing surgery for colorectal cancer (n=116) and gastric cancer (n=49). Patients with CEA levels <5 ng/mL were classified as CEA Group 1, 5-30 ng/mL as CEA Group 2 and >30 ng/mL were classified as CEA Group 3. Similarly the patients with a CA 19-9 level <35 U/mL were classified as CA 19-9 Group 1, with 35-100 U/mL as Group 2 and with >100 U/mL as Group and 3. TNM stages and histologic grades were noted according to histopathological reports. Patients with a TNM grade 0 or 1 were classified as Group A, TNM grade 2 patients constituted Group B and TNM grade 3 and 4 patients constituted Group C. Demographic characteristics, tumor locations and blood types of the patients were all recorded and these data were compared with the preoperative CEA and CA19-9 values. Results: A significant correlation between CA 19-9 levels (>100 U/mL) and TNM stage (in advanced stages) was determined. We also determined a significant correlation between TNM stages and positive vlaues for both CEA and CA 19-9 in colorectal and gastric cancer patients. In comparison between CEA and CA 19-9 levels and age, gender, tumor location, ABO blood group, and tumor histologic grade, no significant correlation was found. Conclusions: Positive levels of both CEA and CA 19-9 can be considered to indicate an advanced stage in colorectal and gastric cancer patients. -
Background: Pretreatment serum p53 and epidermal growth factor receptor (EGFR) were assessed using enzyme-linked immunosorbent assay (ELISA) in patients with acute leukemia to analysis their roles in characterization of different subtypes of the disease. Materials and Methods: Serum samples from thirty two patients with acute myeloid leukemia (AML) and fourteen patients with acute lymphoid leukemia (ALL) were analysed, along with 24 from healthy individuals used as a control group. Results: The results demonstrated a significant increase of serum p53 and EGFR in patients with AML (p<0.0001) compared to the control group. Also, the results showed a significant increase of both markers in patients with ALL (p<0.05, p<0.0001 respectively). Sensitivities and specificities for these variables were 52% and 100% for p53, and 73.9%, 95.8% for EGFR. Serum p53 and EGFR could successfully differentiate between M4 and other AML subtypes, while these variables failed to discriminate among ALL subtypes. A positive significant correlation was noted between p53 and EGFR. Negative significant correlations were observed between these variables and both of hemoglobin (Hg) content and RBC count. Conclusions: Mutant p53 and EGFR are helpful serological markers for diagnosis of patients with AML or ALL and can aid in characterization of disease. Moreover, these markers may reflect carcinogenesis mechanisms.
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Li, Qiong;Yin, Jun;Wang, Xu;Wang, Li-Ming;Shi, Yi-Jun;Zheng, Liang;Tang, Wei-Feng;Ding, Guo-Wen;Liu, Chao;Liu, Rui-Ping;Gu, Hai-Yong;Sun, Jia-Ming;Chen, Suo-Cheng 4301
Aim: Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related genetic factors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. Methods: We conducted a hospital based case.control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T, ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCA cases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The BCL2 rs17757541 C>G polymorphism was associated with increased risk of GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicated a significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males, older patients and those with a history of smoking or drinking. Conclusion: These findings indicated that the functional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our results were limited by small sample size. Future larger studies are required to confirm our current findings. -
Breast cancer is the most frequent malignancy of women worldwide. It is the leading cause of female cancer related disability and mortality. In Saudi Arabia breast cancer ranks first among cancerous diseases in females. In the Gulf region, and especially in Saudi Arabia, few studies have been conducted to address breast cancer awareness. The purpose of the current study was therefore to investigate the level of breast cancer awareness among Saudi females in Jeddah, focusing on knowledge of breast cancer warning signs, risk factors, screening programs and breast self-examination (BSE). The design of this study was an exploratory correlational analysis. The sample comprised 200 Saudi females aged 20 and older living in Jeddah. Data were collected using face-to-face interviews. Breast cancer awareness was measured using a modified Arabic version of the Breast Cancer Awareness Measure (Breast CAM) version 2. Descriptive statistical analysis, Pearson's Product Moment correlation coefficients and ANOVA test were used to answer study questions. Out of 200 participants, 50.5% were aware of breast lump as a warning sign of breast cancer, 57.5% claimed that family history was risk factor, 20.5% had undergone breast screening, 79% heard about BSE, and 47.5% knew how to perform BSE. Findings indicated that Saudi females level of awareness of breast cancer is very inadequate. Public awareness interventions are needed in order to overcome an ever-increasing burden of this disease among Saudi females.
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This study aimed to explore attitudes towards cervical cancer screening among Japanese university students who had never had a Pap smear. Four focus-group discussions, each with 15 female university students, took place in November and December 2009. Discussions were recorded and transcripts were analyzed to extract attitudes of young women towards cervical cancer screening. The four themes that emerged were: i) a low sense of reality about cervical cancer; ii) a lack of knowledge about both cervical cancer and Pap smears; iii) a lack of motivation to get screened, and iv) a reluctance to visit the gynecologist. Participants who were interested in undergoing screening for cervical cancer cited the influence of conversations with friends and family, a diagnosis of cancer within their family, and relevant information from the media. The results indicate the importance of getting young women more interested in cervical cancer screening and overcoming their tendency to avoid visiting a gynecologist.
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Background: Hookah smoking has been referred to as a global tobacco epidemic by public health officials. This study aimed to investigate the characteristics, behaviour and perceptions related to hookah smoking among the youth smokers in Pune. Methods: Two hundred and eighty established hookah smokers participated in this study. Data was collected using a 29-item questionnaire, constructed using three main domains: Characteristics (socio-demographic and personal), behaviour and perceptions (about harmful effects in comparison to cigarette smoking). Results: The results indicated that the mean age of starting hookah smoking was 17.3 years; 75% of participants did not have parental acceptance; light-headedness, dizziness and headache were most common reported nicotine effects, post hookah smoking. Hookah smoking on a daily basis was reported by 24.6% participants. The mean time of hookah session was 1 hour and 19 minutes. 68.2% participants were reported to smoke hookah in hookah-cafes and 35.7% participants were found to share the hookah. Some 66.7% participants had no intention to quit. Most of them (71-80%) had misperception about the safety of hookah smoking over cigarette smoking and 54-82% participants were unaware of health effects. Conclusions: Educational intervention is urgently needed to create awareness among the youth about the harmful effects of hookah smoking.
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Oguz, Arzu;Unal, Dilek;Kurtul, Neslihan;Aykas, Fatma;Mutlu, Hasan;Karagoz, Hatice;Cetinkaya, Ali 4325
Introduction: The influence of season at diagnosis on cancer survival has been an intriguing issue for many years. Most studies have shown a possible correlation in between the seasonality and some cancer type survival. With short expected survival, lung cancer is an arena that still is in need of new prognostic factors and models. We aimed to investigate the effect of season of diagnosis on 3 months, 1 and 2 years survival rates and overall survival of non small cell lung cancer patients. Materials and Methods: The files of non small cell lung cancer patients that were stages IIIB and IV at diagnosis were reviewed retrospectively. According to diagnosis date, the patients were grouped into 4 season groups, autumn, winter, spring and summer. Results: A total of 279 advanced non small cell lung cancer patients' files were reviewed. Median overall survival was 15 months in the entire population. Overall 3 months, 1 and 2 years survival rates were 91.0%, 58.2% and 31.2% respectively. The season of diagnosis was significantly correlated with 3 months survival rates, being diagnosed in spring being associated with better survival. Also the season was significantly correlated with T stage of the disease. For 1 and 2 years survival rates and overall survival, the season of diagnosis was not significantly correlated. There was no correlation detected between season and overall survivals according to histological subtypes of non small cell lung cancer. Conclusion: As a new finding in advanced non small cell lung cancer patients, it can be concluded that being diagnosed in spring can be a favorable prognostic factor for short term survival. -
Cho, Eun;Kang, Moon Hae;Choi, Kui Son;Suh, MiNa;Jun, Jae Kwan;Park, Eun-Cheol 4329
Background: Cervical cancer, which is common in developing countries, is also a major health issue in Korea. Our aim was to evaluate the cost-effectiveness of Korea's National Cancer Screening Program (NCSP), implemented in 1999. Materials and Methods: The target population was Korean women 30 years or over who were invited to take part in the NCSP in 2002-2007. By merging NCSP records with Korean Central Cancer Registry data, patients diagnosed with cervical cancer who had been screened were assigned to a "screened group," while patients diagnosed elsewhere were assigned to a "non-screened group." Clinical outcomes were measured in terms of life-years saved (LYS), derived from 5-year mortality rates supplied by the Korean National Health Insurance Corporation and National Statistical Office. Direct and travel costs associated with screening were evaluated from the perspective of the payer, the NCSP. Results: A diagnosis via screening was associated with 2.30 LYS, and the incremental cost-effectiveness ratio (ICER) estimate for screening was 7,581,679 KW/LYS (6,727 USD/LYS). ICER estimates were lower for older patients (${\geq}$ 50 years) than younger patients (4,047,033 KW/LYS vs 5,680,793 KW/LYS). The proportion of early-stage cancers detected was 16.3% higher in the screened group. Conclusions: In light of Korea's per capita gross domestic product (32,272 USD in 2012), the current NCSP's incremental cost per LYS appears acceptable. -
Kampangsri, Wilas;Vatanasapt, Patravoot;Kamsa-ard, Siriporn;Suwanrungruang, Krittika;Promthet, Supannee 4335
Background: This study aimed to determine the association between betel quid chewing and the occurrence of upper aerodigestive tract (UADT) cancers. Methods: A cohort of 17,388 subjects, recruited and interviewed over the 1990-2001 period, in Khon Kaen, Thailand, was followed up until 2011. The data were linked to the Khon Kaen Population-Based Cancer Registry. Results: The prevalence of betel quid chewing was 15.9%, with a female predominance (97.7%); the mean age of chewers was 57.7 years (SD 6.6). The overall incidence of UADT cancers from the cohort was 14.7 per 100,000 person-years, whereas the incidence among the chewers was 45.7. Betel nut chewing was the only major risk factor for UADT cancers in this population (HR=5.26, 95%CI=2.51-11.0), while weak associations were found for tobacco smoking and alcohol (HR=1.16, 95%CI=0.45-3.01 and 1.47, 95%CI=0.72-3.03 respectively). Conclusions: We found betel quid chewing to be a main risk factor for UADT cancers, resulting in a higher incidence in females. However, further study is required to explore the potential risk factors among non-chewers, non-smokers, and non-drinkers. -
Kooshyar, Mohammad Mahdi;Nassiri, Mohammadreza;Mahdavi, Morteza;Doosti, Mohammad;Parizadeh, Amirreza 4339
Background: The purpose of this study was to evaluate the prevalence of BRCA1 (MIM: 113705) founder mutations in familial breast cancer (BC) patients with high risks in Iran. BRCA1 is among the cancer susceptibility genes best known for high penetrance mutations. BRCA1 genotyping is now used to determine patient counseling, management decisions, and prognosis of this syndrome. Materials and Method: Thirty nine patients with clinical BC and 29 high risk healthy women, related to the patients, participated in the study. DNA from blood samples was extracted and analyzed by PCR and SSCP methods in order to find 185delAG and 5382insC founder mutations. In addition, a 251bp fragment of BRCA1's exon 11 was amplified and analyzed for determination of new mutations. Results: The data indicated the presence of 185delAG and 5382insC founder mutations in both groups studied. Two out of 39 BC patients (5.1%) and one out of 29 relatives (3.4%) were suspected to be carriers of 185delAG mutations. However, we found only one patient (2.6%) to be a carrier of a 5382insC mutation. Also, 2 women (5.1%) of the patient group and 3 n (10.3%) of relatives group were identified as carriers of unclarified mutations in the 251bp fragment of the BRCA1 gene. The carriers of BRCA1 founder mutations have a high lifetime risk of breast cancer. Conclusions: Therefore, these data are useful in counseling of individuals with a significant family history of breast cancer. -
Sambantham, Shanmugam;Radha, Mahendran;Paramasivam, Arumugam;Anandan, Balakrishnan;Malathi, Ragunathan;Chandra, Samuel Rajkumar;Jayaraman, Gopalswamy 4347
Aim: To investigate the molecular mechanisms underlying triggering of apoptosis by hesperetin using in silico and in vitro methods. Methods: The mechanism of binding of hesperetin with NF-${\kappa}B$ and other apoptotic proteins like BAX, BAD,$BCL_2$ and$BCL_{XL}$ was analysed in silico using Schrodinger suite 2009. In vitro studies were also carried out to evaluate the potency of hesperetin in inducing apoptosis using the human prostate cancer PC-3 cell line. Results: Hesperetin was found to exhibit high-affinity binding resulting from greater intermolecular forces between the ligand and its receptor NF-${\kappa}B$ (-7.48 Glide score). In vitro analysis using MTT assay confirmed that hesperetin reduced cell proliferation ($IC_{50}$ values of 90 and$40{\mu}M$ at 24 and 48h respectively) in PC-3 cells. Hesperetin also downregulated expression of the anti-apoptotic gene$BCL_{XL}$ at both mRNA and protein levels and increased the expression of pro-apoptotic genes like BAD at mRNA level and BAX at mRNA as well as protein levels. Conclusion: The results suggest that hesperetin can induce apoptosis by inhibiting NF-${\kappa}B$ . -
Haroon, Saroona;Hashmi, Atif Ali;Khurshid, Amna;Kanpurwala, Muhammad Adnan;Mujtuba, Shafaq;Malik, Babar;Faridi, Naveen 4353
Introduction: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, which can be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO do not recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We therefore aimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymph node metastasis, ER, PR and HER2neu status. Methods: A total of 194 cases of newly diagnosed breast cancer were included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed by the DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated both as continuous and categorical variables. Results: Mean age of the patients was 51.7 years (24-90). Mean Ki67 index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%) and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade, PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size. There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen with HER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as compared to intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. Conclusion: Our study indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognostic markers because we found that tumors with Ki67 higher than 30% have better prognostic profile compared to tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis and HER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate and low groups when considering adjuvant chemotherapy and prognostic stratification. -
Ahmed, Hussain Gadelkarim;Elmubasher, Maysa Badawi;Salih, Rashid Awad Abdallah;Elhussein, Gamal Eldin Mohamed Osman;Ashankyty, Ibraheem Mohmmed Alamin 4359
Background: Pediatric lymphadenopathy is a challenging medical situation for the child patient, the parents, and the physician. Although the bulk of masses will be benign the fear of malignancy is omnipresent. Therefore, the objective of this study was to identify the common cytopathological patterns of lymphadenopathy among Sudanese children. Methods: One hundred pediatric patients presenting with peripheral lymphadenopathy were included in the study, their ages ranging from 2 to 14 years, with a mean age of 7 years. Demographic characteristics, clinical manifestations and FNA materials were prospectively obtained. Results: FNA was performed in 100 cases (100%). There were no technical complications. All cases confirmed adequacy of specimen. Overall, FNA demonstrated 90 (90%) benign lesions and 10 (10%) malignant diagnosis. The benign lesions were reactive lymphoid hyperplasia (n=64), followed by benign granulomatous disease (n=26). Of the 10 cases diagnosed with malignancy, 7 (7%) were cases of non-Hodgkin`s lymphoma and the remaining 3 (3%) were Hodgkin's lymphomas. Conclusion: Pediatric lymphadenopathy is common in Sudan. CLA is the common frequent site. Lymphoma represents a major challenge in this setting. -
Dirican, Nigar;Baysak, Aysegul;Cok, Gursel;Goksel, Tuncay;Aysan, Tulin 4365
Background: Bronchioloalveolar carcinoma (BAC) is considered a subtype of adenocarcinoma of the lung. Recently BAC has been variously termed adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant invasive adenocarcinoma, and invasive mucinous adenocarcinoma. The aim of the study was to analyze and detect prognostic factors of patients with BAC over a 7-year period. Materials and Methods: This retrospective single-center study included 44 patients with BAC. The impact on survival of fifteen variables (gender, age, smoking status, cough, dyspnea, hemoptysis, fever, chest pain, sputum, metastasis number, Karnofsky performance status, pT, pN, TNM stage, cytotoxic chemoterapy) were assessed. Results: Median age was 55 years (38-83). Most patients were male (63.6%) and stage IV (59.1%). Twenty-one patients (47.7%) received cytotoxic chemotherapy (platinum-based regimens) for metastatic disease. Objective response rate was 33.3% (4 partial, 3 complete responses). Stable disease was observed in nine in patients (42.8%). Disease progression was noted in 5 (23.8%). The median OS for all patients was 12 months (95%CI, 2.08-22.9 months). Independent predictors for overall survival were: Karnofsky performance status (HR:3.30, p 0.009), pN (HR:3.81, p 0.018), TNM stage (HR:6.49, p 0.012) and hemoptysis (HR:2.31, p 0.046). Conclusions: Karnofsky performance status, pN, TNM stage and hemoptysis appear to have significant impact on predicting patient survival in cases of BAC. -
Wang, Wen-Jing;Tao, Zhen;Gu, Wei;Sun, Li-Hua 4369
Objective: To evaluate the association of a diagnosis of lung cancer and combined detection of serum carcinoembryonic antigen (CEA), carbohydrateantigen 19-9 (CA19-9), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1). Methods: Serum CEA, CA19-9, NSE and CYFRA21-1 were assessed in 150 patients with lung cancer, 100 patients with benign lung disease and 100 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of lung cancer were analyzed. Results: Serum CEA, CA19-9, NSE and CYFRA21-1 in patients with lung cancer were significantly higher than those with benign lung disease and normal controls (p<0.01). It is suggested that these four tumor markers combined together could produce a positive detection rate of 90.2%, significantly higher than that of any single test. Conclusion: Combination detection of CEA, CA19-9, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be important in early detection. -
Gyenwali, Deepak;Pariyar, Jitendra;Onta, Sharad Raj 4373
Background: The majority of cervical cancers, the most prevalent cancer among Nepali women, are diagnosed in advanced stage leading to high mortality in Nepal. The present study explored factors associated with late diagnosis. Materials and Methods: A cross-sectional study was carried out in two specialized cancer hospitals of Nepal from August 12 to October 12, 2012. Randomly selected 110 cervical cancer patients were interviewed and their medical records were reviewed. Multivariate logistic regression analysis was performed to predict associations. Results: Mean age of patients was 52.7years (SD=10.6), 66% were illiterate and 77% were rural inhabitants. Medical shops (33.6%) and private hospitals (31%) were major first contact points of patients with health care providers (HCP). There was no cervical/per-speculum examination (78.2%) and symptoms misinterpretation (90%) of patients occurred in initial consultation with HCP. Four in every five cases (80.9%) of cervical cancer had late diagnosis. Literate women (adjusted OR=0.121, CI: 0.030-0.482) and women having abnormal vaginal bleeding as early symptom (adjusted OR=0.160, CI: 0.035-0.741) were less likely to suffer late diagnosis. Women who shared their symptoms late (adjusted OR=4.272, CI: 1.110-16.440) and did so with people other than their husband (adjusted OR=12.701, CI: 1.132-142.55) were more likely for late diagnosis. Conclusions: High level of illiteracy among women and their problematic health seeking behavior for gynecological symptoms are responsible for late diagnosis of cervical cancer in Nepal. In the absence of a routine screening program, prevention interventions should be focused on raising awareness of gynecological symptoms and improving health seeking behavior of women for such symptoms. -
Dsouza, Neevan D.R.;Murthy, N.S.;Aras, R.Y. 4379
Projection of cancer incidence is essential for planning cancer control actions, health care and allocation of resources. Here we project the cancer burden at the National and State level to understand the magnitude of cancer problem for the various calendar years from 2011 to 2026 at 5-yearly intervals. The age, sex and site-wise cancer incidence data along with populations covered by the registries were obtained from the report of National Cancer Registry Programme published by Indian Council of Medical Research for the period 2001-2004. Pooled age sex specific cancer incidence rates were obtained by taking weighted averages of these seventeen registries with respective registry populations as weights. The pooled incidence rates were assumed to represent the country's incidence rates. Populations of the country according to age and sex exposed to the risk of development of cancer in different calendar years were obtained from the report of Registrar General of India providing population projections for the country for the years from 2001 to 2026. Population forecasts were combined with the pooled incidence rates to estimate the projected number of cancer cases by age, sex and site of cancer at various 5-yearly periods Viz. 2011, 2016, 2021 and 2026. The projections were carried out for the various leading sites as well as for 'all sites' of cancer. In India, in 2011, nearly 1,193,000 new cancer cases were estimated; a higher load among females (603,500) than males (589,800) was noted. It is estimated that the total number of new cases in males will increased from 0.589 million in 2011 to 0.934 million by the year 2026. In females the new cases of cancer increased from 0.603 to 0.935 million. Three top most occurring cancers namely those of tobacco related cancers in both sexes, breast and cervical cancers in women account for over 50 to 60 percent of all cancers. When adjustments for increasing tobacco habits and increasing trends in many cancers are made, the estimates may further increase. The leading sites of cancers in males are lung, oesophagus, larynx, mouth, tongue and in females breast and cervix uteri. The main factors contributing to high burden of cancer over the years are increase in the population size as well as increase in proportion of elderly population, urbanization, and globalization. The cancer incidence results show an urgent need for strengthening and augmenting the existing diagnostic/treatment facilities, which are inadequate even to tackle the present load. -
Dsouza, Neevan D.R.;Murthy, N.S.;Aras, R.Y. 4387
Projection of load of cancer mortality helps in quantifying the burden of cancer and is essential for planning cancer control activities. As per our knowledge, there have not been many attempts to project the cancer mortality burden at the country level in India mainly due to lack of data on cancer mortality at the national and state level. This is an attempt to understand the magnitude of cancer mortality problem for the various calendar years from 2011 to 2026 at 5-yearly intervals. Age, sex and site-wise specific cancer mortality data along with populations covered by the registries were obtained from the report of National Cancer Registry Programme published by Indian Council of Medical Research for the period 2001-2004. Pooled age sex specific cancer mortality rates were obtained by taking weighted average of these six registries with respective registry populations as weights. The pooled mortality rates were assumed to represent the country's mortality rates. Populations of the country according to age and sex exposed to the risk of cancer mortality in different calendar years were obtained from the report of Registrar General of India providing population projections for the country for the years from 2011 to 2026. Population forecasts were combined with the pooled mortality rates to estimate the projected number of cancer mortality cases by age, sex and site of cancer at various 5-yearly periods Viz. 2011, 2016, 2021 and 2026. The projections were carried out for the various cancer-leading sites as well as for 'all sites' of cancer. The results revealed that an estimated 0.44 million died due to cancer during the year 2011, while 0.51 million and 0.60 million persons are likely to die from cancer in 2016 and 2021. In the year 2011 male mortality was estimated to be 0.23 million and female mortality to be 0.20 million. The estimated cancer mortality would increase to 0.70 million by the year 2026 as a result of change in size and composition of population. In males increase will be to 0.38 millions and in females to 0.32 millions. Among women, cancer of the breast, cervical and ovary account for 34 percent of all cancer deaths. The leading sites of cancer mortality in males are lung, oesophagus, prostrate and stomach. The above results show a need for commitment for tackling cancer by reducing risk factors and strengthening the existing screening and treatment facilities. -
Zekri, Abdel-Rahman Nabawy;Hassan, Zeinab Korany;Bahnassy, Abeer Ahmed;Eldahshan, Dina Hassan;El-Rouby, Mahmoud Nour Eldin;Kamel, Mahmoud Mohamed;Hafez, Mohamed Mahmoud 4393
Background: Chromosomal translocations are genetic aberrations associated with specific non-Hodgkin lymphoma (NHL) subtypes. This study investigated the differential gene expression profile of Egyptian NHL cases based on a microarray approach. Materials and Methods: The study included tissue samples from 40 NHL patients and 20 normal lymph nodes used as controls. Total RNA was extracted and used for cDNA microarray assays. The quantitative real time polymerase chain reaction was used to identify the aberrantly expressed genes in cancer. Results: Significant associations of 8 up-regulated and 4 down-regulated genes with NHL were observed. Aberrant expression of a new group of genes not reported previously was apparent, including down-regulated NAG14 protein, 3 beta hydroxy-delta 5-c27 steroid oxi-reductase, oxi-glutarate dehydrogenase (lipo-amide), immunoglobulin lambda like polypeptide 3, protein kinase x linked, Hmt1, and caveolin 2 Tetra protein. The up-regulated genes were Rb binding protein 5, DKFZP586J1624 protein, protein kinase inhibitor gamma, zinc finger protein 3, choline ethanolamine phospho-transferase CEPT1, protein phosphatase, and histone deacetylase-3. Conclusions: This study revealed that new differentially expressed genes that may be markers for NHL patients and individuals who are at high risk for cancer development. -
Wang, Xiao;Song, Zheng-Fang;Xie, Rui-Meng;Pei, Jiao;Xiang, Ming-Fei;Wang, Huan 4399
Objectives: To analyze underlying disease, fatality rate and the major causes of death of in-patients with malignant tumors in Sichuan Cancer Hospital. Methods: Clinical data of in-patients from 2002 to 2012 were retrospectively analyzed. Results: The top 10 tumors (82.0%of the total) of the malignant tumors of the in-patients were lung, cervical, esophagus, breast, colorectal, nasopharynx, liver and gastric cancers, lymphomas and ovarian cancers. The overall fatality rate was 2.7% during these eleven years, 3.4% and 2.0% for male and females, respectively with statistical significance for the difference (${\chi}^2$ =164.737, P<0.001). The top 10 death causes were lung cancer, liver cancer, colorectal cancer, esophagus cancer, gastric cancer, lymphoma, breast cancer, pancreatic cancer, ovarian cancer and nasopharynx cancer. In-patients with pancreatic cancer had the highest fatality rate (9.6%). There were different ranks of death causes in different sex groups and age groups. Conclusion: Prevention and control work of cancer should be enhanced not only for cancers with high incidence such as lung cancer, esophageal cancer but also for the cancers which have low incidence but high fatality rate, such as pancreatic cancer and gallbladder cancer, which would help to improve the survival rate and quality of life of cancer patients in the future. -
Bhat, Imtiyaz Ahmad;Pandith, Arshid A.;Bhat, Bashir A.;Naykoo, Niyaz A.;Qasim, Iqbal;Rasool, Roohi;Aziz, Sheik Aejaz;Shah, Zafar Amin 4403
Background: Chronic inflammation is considered as an important factor in the pathogenesis of lung cancer. The presence of inflammatory cells and higher levels of pro-inflammatory cytokines in the tumor microenvironment and their surrounding tissues is gaining much importance in research. Materials and Methods: One hundred ninety NSCLC cases and 200 age, smoking and sex matched controls were evaluated for association of IL-8 -251 (rs4073) and IL-8 -845 (rs2227532) in our population. Restriction fragment length polymorphism (RFLP) was used followed by direct sequencing for the detection of SNPs. Results: The IL-8 -845 polymorphism was not found in our population. No significant association was observed between the IL-8 -251 AT genotypes and IL-8 -25 AA genotypes and NSCLC (p=0.05) in our population. The IL-8 -251 A allele was also non-significant (p=0.05) in NSCLC patients. Conclusions: In conclusion, this report reveals lack of association between IL-8 - 251 A/T polymorphism and NSCLC in our Kashmir Valley population. -
Nakao, Makoto;Hosono, Satoyo;Ito, Hidemi;Oze, Isao;Watanabe, Miki;Mizuno, Nobumasa;Yatabe, Yasushi;Yamao, Kenji;Niimi, Akio;Tajima, Kazuo;Tanaka, Hideo;Matsuo, Keitaro 4409
Background: Cigarette smoking is a well-established risk factor of pancreatic cancer (PC). Although an association between nicotine dependence phenotype, namely time to first cigarette (TTFC) after waking, and the risk of several smoking-related cancers has been reported, an association between TTFC and PC risk has not been reported. We assessed the impact of smoking behavior, particularly TTFC, on PC risk in a Japanese population. Materials and Methods: We conducted a case-control study using 341 PC and 1,705 non-cancer patients who visited Aichi Cancer Center in Nagoya, Japan. Exposure to risk factors, including smoking behavior, was assessed from the results of a self-administered questionnaire. The impact of smoking on PC risk was assessed with multivariate logistic regression analysis adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Cigarettes per day (CPD) and/or smoking duration were significantly associated with PC risk, consistent with previous studies. For TTFC and PC risk, we found only a suggestive association: compared with a TTFC of more than 60 minutes, ORs were 1.15 (95%CI, 0.65-2.04) for a TTFC of 30-60 minutes and 1.35 (95%CI, 0.85-2.15) for that of 0-30 minutes (p trend=0.139). After adjustment for CPD or smoking duration, no association was observed between TTFC and PC. Conclusions: In this study, we found no statistically significant association between TTFC and PC risk. Further studies concerning TTFC and PC risk are warranted. -
Background: Measuring effects of cancer on family caregivers is important to develop methods which can improve their quality of life (QOL). Nevertheless, up to now, only a few tools have been developed to be used in this group. Among those, the Caregiver Quality of Life Index-Cancer Scale (CQOLC) has met minimum psychometric criteria in different populations in spite of conflicting results. The present study was conducted to evaluate reliability and validity of CQOLC among Turkish cancer family caregivers. Materials and Methods: The CQOLC was administered to 120 caregivers, along with Beck Depression Inventory (BDI), Medical Outcomes Study MOS 36- Item Short Form Health Survey (SF-36), State-Trait Anxiety Inventory (STAI), and Multidimensional Scale of Perceived Social Support (MSPSS). Internal consistency and test-retest stability were used to investigate reliability. Construct validity was examined by using known group method, convergent, and divergent validity. For the known group method, we hypothesized that CQOLC scores would differ between depressed and non-depressed subjects. We investigated convergent validity by correlating scores for CQOLC with scores for other similar measures including SF-36 and STAI. The MSPSS was completed at the same time as CQOLC to provide divergent validity. Results: The values for internal consistency and test-retest correlation were 0.88 and 0.96, respectively. The CQOLC discriminated those who were depressed from those who were not. Convergent validity supported strong correlations between CQOLC scores and two main component scores (PCS, MCS) in SF-36 although there was a weak correlation between CQOLC and STAI scores. Regarding divergent validity, the correlation between CQOLC and MSPSS was in the low range, as expected. Conclusions: The Turkish CQOLC is a reliable and valid tool and it can be utilized to determine QOL of family caregivers.
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Dong, Yong-Qiang;Liang, Jiang-Shui;Zhu, Shui-Bo;Zhang, Xiao-Ming;Ji, Tao;Xu, Jia-Hang;Yin, Gui-Lin 4421
Objective: The present study employed 5-aza-2'-deoxycytidine (5-Aza-CdR) to treat non-small cell lung cancer (NSCLC) cell line A549 to investigate the effects on proliferation and expression of the TFPI-2 gene. Methods: Proliferation was assessed by MTT assay after A549 cells were treated with 0, 1, 5, 10${\mu}mol/L$ 5-Aza-CdR, a specific demethylating agent, for 24, 48 and 72h. At the last time point cells were also analyzed by flow cytometry (FCM) to identify any change in their cell cycle profiles. Methylation-specific polymerase chain reaction (MSPCR), real time polymerase chain reaction(real-time PCR) and western blotting were carried out to determine TFPI-2 gene methylation status, mRNA expression and protein expression. Results: MTT assay showed that the growth of A549 cells which were treated with 5-Aza-CdR was significantly suppressed as compared with the control group (0${\mu}mol/L$ 5-Aza-CdR). After treatment with 0, 1, 5, 10${\mu}mol/L$ 5-Aza-CdR for 72h, FCM showed their proportion in G0/G1 was$69.7{\pm}0.99%$ ,$76.1{\pm}0.83%$ ,$83.8{\pm}0.35%$ ,$95.5{\pm}0.55%$ respectively (P<0.05), and the proportion in S was$29.8{\pm}0.43%$ ,$23.7{\pm}0.96%$ ,$15.7{\pm}0.75%$ ,$1.73{\pm}0.45%$ , respectively (P<0.05), suggesting 5-Aza-CdR treatment induced G0/G1 phase arrest. MSPCR showed that hypermethylation in the promoter region of TFPI-2 gene was detected in control group (0${\mu}mol/L$ 5-Aza-CdR), and demethylation appeared after treatment with 1, 5, 10${\mu}mol/L$ 5-Aza-CdR for 72h. Real-time PCR showed that the expression levels of TFPI-2 gene mRNA were$1{\pm}0$ ,$1.49{\pm}0.14$ ,$1.86{\pm}0.09$ and$5.80{\pm}0.15$ (P<0.05) respectively. Western blotting analysis showed the relative expression levels of TFPI-2 protein were$0.12{\pm}0.01$ ,$0.23{\pm}0.02$ ,$0.31{\pm}0.02$ ,$0.62{\pm}0.03$ (P<0.05). TFPI-2 protein expression in A549 cells was gradually increased significantly with increase in the 5-Aza-CdR concentration. Conclusions: TFPI-2 gene promoter methylation results in the loss of TFPI-2 mRNA and protein expression in the non-small cell lung cancer cell line A549, and 5-Aza-CdR treatment could induce the demethylation of TFPI-2 gene promoter and restore TFPI-2 gene expression. These findings provide theoretic evidence for clinical treatment of advanced non-small cell lung cancer with the demethylation agent 5-Aza-CdR. TFPI-2 may be one molecular marker for effective treatment of advanced non-small cell lung cancer with 5-Aza-CdR. -
Xiao, Xue;Liu, Li;Li, Wei-Jie;Liu, Juan;Chen, Dun-Jin 4427
Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphisms have been shown to be associated with cervical cancer risk, but results have varied among different populations. In this study, the HLA-A, -B, and -DRB1 alleles among 100 southern Chinese women with cervical squamous cell carcinoma (SCC) were compared to 254 controls. Our results showed that$B^*51$ :01:02 allele frequency was significantly higher in patients with SCC than in healthy controls ($P=3.17{\times}10^{-5}$ ,$P_c$ =0.005, OR=26.7). Statistical analysis also revealed a significantly decreased frequency of$B^*51$ :01:02 ($P=7.01{\times}10^{-4}$ ,$P_c$ =0.03, OR=0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-$B^*51$ :01:02 may confer susceptibility to SCC and HLA-$B^*51$ :01:02 may contribute to resistance to the development of SCC in Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in cases and controls after multiple testing corrections, indicating the individual allele associations to be independent of the identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved with susceptibility for developing SCC. -
Chihara, Takeshi;Shimpo, Kan;Beppu, Hidehiko;Tomatsu, Akiko;Kaneko, Takaaki;Tanaka, Miyuki;Yamada, Muneo;Abe, Fumiaki;Sonoda, Shigeru 4435
Aloe vera gel supercritical$CO_2$ extract (AVGE) has been shown to contain five phytosterols, reduce visceral fat accumulation, and influence the metabolism of glucose and lipids in animal model experiments. Recent epidemiologic studies have shown that obesity is an established risk factor for several cancers including colorectal cancer. Therefore, we examined the effects of AVGE on intestinal polyp formation in Apc-deficient Min mice fed a high-fat diet. Male Min mice were divided into normal diet (ND), high fat diet (HFD), low dose AVGE (HFD+LAVGE) and high dose AVGE (HFD+HAVGE) groups. The ND group received AIN-93G diet and the latter 3 groups were given modified high-fat AIN-93G diet (HFD) for 7 weeks. AVGE was suspended in 0.5% carboxymethyl cellulose (CMC) and administered orally to mice in HFD+LAVGE and HFD+HAVGE groups every day (except on Sunday) for 7 weeks at a dose of 3.75 and 12.5 mg/kg body weight, respectively. ND and HFD groups received 0.5% CMC alone. Between weeks 4 and 7, body weights in the HFD and HFD+LAVGE groups were reduced more than those in the ND group. However, body weights were not reduced in the HFD+HAVGE group. Mice were sacrificed at the end of the experiment and their intestines were scored for polyps. No significant differences were observed in either the incidence and multiplicity of intestinal polyps (${\geq}0.5$ mm in a diameter) among the three groups fed HFD. However, when intestinal polyps were categorized by their size into 0.5-1.4, 1.5-2.4, or${\geq}2.5$ mm, the incidence and multiplicity of large polyps (${\geq}2.5$ mm) in the intestine in the HFD+HAVGE group were significantly lower than those in the HFD group. We measured plasma lipid (triglycerides and total cholesterol) and adipocytokine [interleukin-6 and high molecular weight (HMW) adiponectin] levels as possible indicators of mechanisms of inhibition. The results showed that HMW adiponectin levels in the HFD group were significantly lower than those in the ND group. However, the levels in the HFD+HAVGE group were significantly higher than those in the HFD group. These results indicate that HAVGE reduced large-sized intestinal polyps and ameliorated reduction in plasma HMW adiponectin levels in Min mice fed HFD. -
Srikoon, Pattaravadee;Kariya, Ryusho;Kudo, Eriko;Goto, Hiroki;Vaeteewoottacharn, Kulthida;Taura, Manabu;Wongkham, Sopit;Okada, Seiji 4441
Cholangiocarcinoma (CCA) is a tumor of biliary ducts, which has a high mortality rate and dismal prognosis. Constitutively activation of the transcription factor nuclear factor kappa-B (NF-${\kappa}B$ ) has been previously demonstrated in CCA. It is therefore a potential target for CCA treatment. Effects of diethyldithiocarbamate (DDTC) on NF-${\kappa}B$ -dependent apoptosis induction in cancer have been reported; however, anti-metastasis has never been addressed. Therefore, here the focus was on DDTC effects on CCA migration and adhesiond. Anti-proliferation, anti-migration and anti-adhesion activities were determined in CCA cell lines, along with p65 protein levels and function. NF-${\kappa}B$ target gene expression was determined by quantitative RT-PCR. DDTC inhibited CCA cell proliferation. Suppression of migration and adhesion were observed prior to anti-CCA proliferation. These effects were related to decreased p65, reduction in NF-${\kappa}B$ DNA binding, and impaired activity. Moreover, suppression of ICAM-1 expression supported NF-${\kappa}B$ -dependent anti-metastatic effects of DDTC. Taken together, DDTC suppression of CCA migration and adhesion through inhibition of NF-${\kappa}B$ signaling pathway is suggested from the current study. This might be a promising treatment choice against CCA metastasis. -
Purpose: To investigate the risk factors for anastomotic leakage (AL) after anterior resection for rectal cancer with a double stapling technique. Patients and Methods: Between January 2004 and December 2011, 753 consecutive patients in Jiangsu Cancer Hospital and Research Institute diagnosed with rectal cancer and undergoing anterior resection with a double stapling technique were recruited. All patients experienced a total mesorectal excision (TME) operation. Additionally, decrease of postoperative tumor supplied group of factors (TSGF), which have not been reported before, was proposed as a new indicator for AL. Univariate and multivariate analysis were performed to determine risk factors for AL. Results: AL was detected in 57 (7.6%) of 753 patients with rectal cancer. The diagnosis of anastomotic leakage was confirmed between the 6th and 12th postoperative day (POD; mean 8th POD). After univariate analysis and multivariate analysis, age (p<0.001), gender (p=0.002), level of anastomosis (p<0.001), preoperative body mass index (BMI) (p=0.001) and reduction of TSGF in 5th POD was less than 10
${\mu}/ml$ (p<0.001) were selected as 5 independent risk factors for AL. It was also indicated that a temporary defunctioning transverse ileostomy (p=0.04) would decrease the occurrence of AL. Conclusion: AL after anterior resection for rectal carcinoma is related to elderly status, low level site of the tumor (below the peritoneal reflection), being male, preoperative BMI and the decrease of TSGF in$5^{th}$ POD is less than 10${\mu}/ml$ . Preventive ileostomy is advisable after TME for low rectal tumors to prevent AL. -
Mohammadzadeh, Niloofar;Safdari, Reza;Rahimi, Azin 4455
In the new millennium people are facing serious challenges in health care, especially with increasing non-communicable diseases (NCD). One of the most common NCDs is cancer which is the leading cause of death in developed countries and in developing countries is the second cause of death after heart diseases. Cancer registry can make possible the analysis, comparison and development of national and international cancer strategies and planning. Information technology has a vital role in quality improvement and facility of cancer registries. With the use of IT, in addition to gaining general benefits such as monitoring rates of cancer incidence and identifying planning priorities we can also gain specific advantages such as collecting information for a lifetime, creating tele medical records, possibility of access to information by patient, patient empowerment, and decreasing medical errors. In spite of the powerful role of IT, we confront various challenges such as general problems, like privacy of the patient, and specific problems, including possibility of violating patients rights through misrepresentation, omission of human relationships, and decrease in face to face communication between doctors and patients. By implementing appropriate strategies, such as identifying authentication levels, controlling approaches, coding data, and considering technical and content standards, we can optimize the use of IT. The aim of this paper is to emphasize the need for identifying positive and negative effects of modern IT on cancer registry in general and specific aspects as an approach to cancer care management.