Asian Pacific Journal of Cancer Prevention
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
- 월간
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
과학기술표준분류
- 보건의료 > 의약품/의약품개발
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
KSCI제13권8호
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Prabhu, V. Vinod;Siddikuzzaman, Siddikuzzaman;Grace, V.M. Berlin;Guruvayoorappan, C. 3539
The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy. -
Chhabra, Sarabjeet;Hegde, Padmaraj;Singhal, Paras 3549
Primary small cell carcinoma of urinary bladder is a rare but aggressive disease with poor prognosis and a high mortality rate. It accounts for less than 1 % of all the primary cancers seen in the urinary bladder. Diagnosis and management of this entity poses a challenge to the clinician due to the lack of a standardized protocol for its treatment. Herein we discuss primary small cell carcinoma of the urinary bladder in its entirety. -
Mika, Denish;Ahmad, Sabrina;Guruvayoorappan, C. 3555
The tumour lysis syndrome (TLS) is a group of metabolic abnormalities caused by rapid and unexpected release of cellular components into the circulation as a result of massive destruction of rapidly proliferating malignant cells. It usually develops in patients with hematologic malignancies like acute lymphoid leukemia, non-Hodgkin and Burkitt's lymphoma after initiation of chemotherapy or may, rarely, occur spontaneously. Though TLS is seldom observed in relation to solid tumours, there have been reports of connections with examples such as lung, liver, breast, gastric carcinomas. The clinical manifestations of TLS include hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These indications if untreated lead to life-threatening complications such as acute renal failure, cardiac arrhythmias, seizures, and eventually death due to multiorgan failure. Therefore early detection of TLS is of vital importance. This can be accomplished by identification of high risk patients, implementation of suitable prophylactic measures andmonitoring of the electrolyte levels in patients undergoing chemotherapy. -
The calcium sensing receptor (CaSR) is a member of the largest family of cell surface receptors, the G protein-coupled receptors involved in calcium homeostasis. The role of the CaSR in neoplasia appears to be homeostatic; loss of normal CaSR-induced response to extracellular calcium is observed in cancers of the colon and ovary, while increased release of PTHrP is observed in cancers of the breast, prostate and Leydig cells. Currently CaSR can be considered as a molecule that can either promote or prevent tumor growth depending on the type of cancer. Therefore, recognition of the multifaceted role of CaSR in gliomas and other malignant tumors in general is fundamental to elucidating the mechanisms of tumor progression and the development of novel therapeutic agents. Emphasis should be placed on development of drug-targeting methods to modulate CaSR activity in cancer cells.
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Social support is regarded as a complex construct which has long been suggested to have direct and buffering effects on patients' wellbeing and emotional adjustment to cancer. Cross-sectional and prospective studies show a positive association between perceived social support and psychological adjustment following cancer treatment. Research findings suggest that the evidence for the relationship between social support and cancer progression is sufficiently strong. This report points out the importance of social support in cancer and provides recommendations for health care professionals.
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Masthan, K.M.K.;Babu, N. Aravindha;Dash, Kailash Chandra;Elumalai, M. 3573
Oral cancers are one of the most common cancers worldwide today. They are usually neglected by the common population when compared to systemic cancers such as the lung cancer, colon cancer etc. However, they also may be extremely fatal if left untreated even at a very initial stage of the lesion. Early detection and treatment gives the best chance for its cure. The five-year survival rate of oral cancer still remains low and delayed diagnosis is suggested to be one of the major reasons. The detection and diagnosis are currently based on clinical examination, histopathological evaluation of the biopsy material and molecular methods. Several diagnostic aids have been developed over the years for early detection of oral cancer. The purpose of this article is to review the advanced available diagnostic adjuncts for the detection of oral cancer. -
Small cell lung cancer (SCLC) is characterized by a short cell doubling time, rapid progression and early occurrence of blood-borne and lymph metastasis. The malignancy is the highest of all lung cancer types. Although SCLC has a relatively good initial response to chemotherapy as well as radiotherapy, relapse or disease progression may occur quickly after the initial treatment. Drug resistance, especially multi-drug resistance, is the most important cause of failure of SCLC chemotherapy. This article provides a brief update of research on mechanisms of drug resistance in SCLC and reversal strategies.
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Shen, Huo-Jian;Zhu, Hong-Yi;Yang, Chao;Ji, Fu 3583
SUMOylation has emerged as an important post-translational modification that modulates the localization, stability and activity of a broad spectrum of proteins. A dynamic process, it can be reversed by a family of SUMO-specific proteases (SENPs). However, the biological roles of SENPs in mammalian development and pathogenesis remain largely elusive. Here, we demonstrated that SENP2 plays a critical role in the control of hepatocellular carcinoma cell growth. SENP2 was found to be down-regulated in hepatocellular carcinoma (HCC) tissues and over-expression suppressed the growth and colony formation of HCC cells. In contrast, silencing of SENP2 by siRNAs promoted cancer cell growth. We further found that stability of${\beta}$ -catenin was markedly decreased when SENP2 was over-expressed. Interestingly, the decrease was dependent on the de-SUMOylation activity of SENP2, because over-expression of a SENP2 catalytic mutant form had no obviously effects on${\beta}$ -catenin. Our results suggest that SENP2 might play a role in hepatocellular carcinoma cell growth control by modulating the stability of${\beta}$ -catenin. -
Bano, Nusrat;Najam, Rahila;Mateen, Ahmed;Qazi, Faaiza 3589
Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients and Methods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid ($200mg/m^2$ ), glucose 5%, 5-FU ($400mg/m^2$ ) and 22 hr. CIV ($600mg/m^2$ ) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid ($20mg/m^2$ )for five days, 5FU($425mg/m^2$ ) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria. Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade${\geq}2$ events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status. -
Objective: The objective of this study was to determine the practice and barriers of mammography and associated factors among Malaysian women in the general population. Methodology: A cross-sectional study was conducted among 200 women in Shah Alam, Selangor; Malaysia. The questionnaire contained 27 questions and was comprised of two sections; socio-demographic characteristics and practices, knowledge and barriers of mammography. All the data were analyzed using the Statistical Package for the Social Sciences (SPSS) 13.0. Results: Of the 200 Malaysian women who participated in this study, the majority were under the age of 50 years (65.5%), Malay (86%), and married (94.5%). Regarding any family history of cancer in general, the majority of the participants had none (78%). However, some did report a close relative with breast cancer (16.5%). While the majority of them knew about mammography (68%), 15% had had a mammogram once in their life and only 2% had the procedure every two or three years. Univariate analysis showed that age, family history of cancer, family history of breast cancer, regular supplement intake, regular medical check-up and knowledge about mammogram were significantly associated with mammogram practice among the general population (p=0.007, p=0.043, P=0.015, p=0.01, p=0.001, p<0.001; respectively). Multivariate analysis using multiple linear regression test showed that age, regular medical check-up and knowledge about mammography testing were statistically associated with the practice of mammography among the general population in Malaysia (p=0.035, p=0.015 and p<0.001; respectively). Lack of time, lack of knowledge, not knowing where to go for the test and a fear of the test result were the most important barriers (42.5%, 32%, 21%, 20%; respectively). Conclusion: The practice of mammogram screening is low among Malaysian women.
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Duan, Wei-Hong;Zhu, Zhen-Yu;Liu, Jun-Gui;Dong, Mao-Sheng;Chen, Jun-Zhou;Liu, Quan-Dda;Xie, Yu;Sun, Ti-Ye;Gao, Ze-Feng;Zhou, Ning-Xin 3601
Purpose: Numerous studies have evaluated the association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Chinese Han population. However, the results have been inconsistent. We therefore here examined whether the XRCC1 Arg399Gln gene polymorphism confers hepatocellular carcinoma risk by conducting a meta-analysis. Methods: PubMed, Google scholar and China National Knowledge Infrastructure databases were searched for eligible articles in English and Chinese that were published before April 2012. Results: 6 studies involving 1,246 patients with hepatocellular carcinoma and 1,953 controls were included. The association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma in the Chinese Han population was significant under GG vs AA (OR = 1.48, 95% CI = 1.13 to 1.94). Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. Conclusions: In the Chinese Han population, the XRCC1 Arg399Gln gene polymorphism is associated with an increased hepatocellular carcinoma risk. -
Cheng, Peng;Cheng, You;Li, Yan;Zhao, Zhenguo;Gao, Hui;Li, Dong;Li, Hua;Zhang, Tao 3605
Lung cancer seriously threatens human health, so it is important to investigate gene expression changes in affected individuals in comparison with healthy people. Here we compared the gene expression profiles between smokers with and without lung cancer. We found that the majority of the expressed genes (threshold was set as 0.1 RPKM) were the same in the two samples, with a small portion of the remainder being unique to smokers with and without lung cancer. Expression distribution patterns showed that most of the genes in smokers with and without lung cancer are expressed at low or moderate levels. We also found that the expression levels of the genes in smokers with lung cancer were lower than in smokers without lung cancer in general. Then we detected 27 differentially expressed genes in smokers with versus without lung cancer, and these differentially expressed genes were foudn to be involved in diverse processes. Our study provided detail expression profiles and expression changes between smokers with and without lung cancer. -
Gillani, Munazza;Akhtar, Farhan;Ali, Zafar;Naz, Irum;Atique, Muhammad;Khadim, Muhammad Tahir 3611
Objective: The objective of this study was to establish the diagnostic accuracy, specificity and sensitivity of fine needle aspiration cytology(FNAC) for intra-oral tumors, comparing with histopathology as the gold standard. Materials and methods: Forty cases of FNA cytology from intraoral tumors was performed in AFID along with the demographic data and clinical information and then diagnosed at AFIP, Rawalpindi. Then the cytology results obtained per FNAC were compared with the histopathological biopsy results of the same lesions. The following variables were recorded for each patient: Age, gender, site of biopsy, diagnosis. The data were entered and analyzed using Open-epi version 2.0. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Cohen Kappa was further applied to compare the agreement between the biopsy and FNAC diagnoses. A p-value of < 0.05 was considered as statistically significant. Results: Among the total patients included in the study there were 24 males and 16 females, with a ratio of 1.5:1. Age of the patients ranged from 24 to 80 years with a mean of 52 years. A total of six sites were aspirated from the oral cavity with maximum (11) aspirates taken from alveolar ridge. The results of FNAC revealed that there were 32 malignant and 8 benign aspirates. Confirmation through histopathological analysis came for 31/32 malignant cases while one was falsely given positive for malignancy on FNAC. Among a total of 40 cases, 31(77%) cases diagnosed were found to be malignant and remaining 9(23%) were benign. The FNAC results revealed 32 malignant and 8 benign lesions. Histopathology of the subsequent surgically excised specimen showed malignant lesions in 31(77%) and benign in 9(23%) patients. As a whole, it was found that the absolute sensitivity for introral FNAC was 100% and specificity 89% with positive predictive value of 97% and negative predictive value of 100%. Conclusion: Cytological diagnosis was almost corroborative with final histopathological diagnosis in all cases, with very few exceptions, exhibiting high diagnostic accuracy. -
Aghaei, Abbas;Najafi, Farid;Mosavi-Jarrahi, Alireza;Ahmadi-Jouibari, Toraj 3617
Background: The completeness of cancer registration is a major validity index of any reported cancer incidence. The present study aimed to evaluate the esophageal cancer incidence registered in the Tehran Metropolitan Area Cancer Registry. Materials and methods: The data on esophageal cancer abstracted from three sources of 1) pathology departments, 2) medical records, and 3) death certificates during 2003 till 2007 were utilized. The completeness of the data sources were evaluated using coverage (defined as the proportion of a community population with esophageal cancer identified by the source) and density (defined as the proportion of non-empty fields of the data by source). Results: A total 1,404 cases of esophageal cancer were reported for the duration of the study. Pathology provided 771, medical records 432, and death certificates 609. The coverage was 0.55 for pathology, 0.31 for medical records, and 0.43 for death certificates. The respective density values were 0.82, 0.96 and 0.98, respectively. Pathology (0.45) was the most complete source followed by medical records (0.42), and death certificates (0.29). Discussion: A low degree of completeness dictates putting more effort into case finding plus abstracting data more thoroughly. -
Qadri, Sumyra Khurshid;Hamdani, Nissar Hussain;Shah, Parveen;Lone, Mohammad Iqbal;Baba, Khalil Mohammad 3621
Lymphadenopathy is one of the commonest and significant manifestations of local as well as systemic ailments, especially malignancies. Fine needle aspiration cytology (FNAC) helps in diagnosing the disease itself, in general, but more importantly ruling out malignancy, in particular. Hence it saves much of the cost and use of resources incurred with excision biopsy of such lymph nodes. This prompted us to study the cytologic patterns of lymphadenopathy in our setting and the diagnostic utility of FNAC in the evaluation of lymphadenopathy. In this retrospective observational study, 1,579 patients (953 males and 626 females) with lymphadenopathy who were subjected to FNAC over a period of three years (January 2009 to December 2011) were studied. The cervical region was involved in most of the cases (76%) followed by the axillary region (17.5%). Metastatic malignancy (38.2%) was the commonest cause of lymphadenopathy followed by reactive lymphoid hyperplasia (36.9%), tuberculosis (9.1%) and lymphomas (8.6%). Squamous cell carcinoma (32.2%) followed by adenocarcinoma (21.9%) were the most frequent metastatic tumors. FNAC is a useful diagnostic tool in the management of patients presenting with lymphadenopathy and should be considered before more invasive and costly procedures are performed, particularly in developing countries. -
The epithelial cell adhesion molecule (EpCAM) is a pan-epithelial differentiation antigen that is expressed on almost all carcinomas. However, a role in rat liver carcinogenesis has never been reported previously. Thus, its expression was investigated herein in rat liver tumors induced by diethylnitrosamine (DEN). Twenty male 5-week-old F344 rats were used in this experiment. Mini-osmotic pumps containing doses of 47.5 mg of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. All animals were sacrificed at 26 weeks after DEN treatment. At necropsy, hepatic masses were processed for histopathological examination, which revealed forty-four hepatocellular adenomas (HCAs) and twenty hepatocellular carcinomas (HCC). Tumors were immunohistochemically analyzed for EpCAM, proliferating cell nuclear antigen (PCNA) and co-localization of the two. EpCAM expression was mainly detected in hepatic tumor cells, showing a cytoplasmic staining pattern. However, expression was also slightly observed in normally-appearing surrounding hepatic cells. PCNA expression was highly detected in tumor cells, showing nuclear staining. Double staining of EpCAM and PCNA in tumors showed many cells with co-localization. Taken together, EpCAM and PCNA expression were increased in DEN-induced tumors and many tumor cells showed co-expression. It is suggested that EpCAM may increase during DEN-induced tumors, possibly associated with cell proliferation.
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Zhao, Li-Jun;Xu, Heng;Qu, Jun-Wei;Zhao, Wan-Zhou;Zhao, Yi-Bing;Wang, Jin-Hua 3631
Objective: To determine whether silence of$PKC-{\alpha}$ expression by small interference RNA (siRNA) might regulate MDR1 expression and reverse chemoresistance of ovarian cancer. Methods: We measured gene and protein expression of MDR1 and$PKC-{\alpha}$ in ovarian cancer cells and assessed their correlation with cell drug resistance. We also examined whether blocking$PKC-{\alpha}$ by RNA interference (RNAi) affected MDR1 expression and reversed drug resistance in drug sensitivity tests. Results: The drug resistance cell lines, OV1228/DDP and OV1228/Taxol, had higher gene and protein expression of MDR1 and$PKC-{\alpha}$ than their counterpart sensitive cell line, OV1228. SiRNA depressed$PKC-{\alpha}$ gene protein expression, as well as MDR1 and protein expression and improved the drug sensitivity in OV1228/DDP and OV1228/Taxol cells. Conclusion: These results indicated that decreasing$PKC-{\alpha}$ expression with siRNA might be an effective method to improve drug sensitivity in drug resistant cells with elevated levels of$PKC-{\alpha}$ and MDR1. A new siRNA-based therapeutic strategy targeting$PKC-{\alpha}$ gene could be designed to overcome the chemoresistance of ovarian cancer. -
Zhou, Li-Ping;Luan, Hong;Dong, Xi-Hua;Jin, Guo-Jiang;Man, Dong-Liang;Shang, Hong 3637
Objective: Non-homologous end joining (NHEJ) is a pathway for repairing DNA double-strand breaks. Recent publications indicated that XRCC5, XRCC6 and XRCC7 genes may participate in the pathogenesis of breast cancer. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate associations between XRCC5, XRCC6 and XRCC7 genetic polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between genetic polymorphisms in XRCC5, XRCC6 and XRCC7 genes and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers. The meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated based on the extracted data. Results: According to the inclusion criteria, we final included seven studies with a total of 2,864 breast cancer cases and 3,060 healthy controls. Meta-analysis results showed that rs3835 (G>A) and rs828907 (G>T) in XRCC5 gene, and rs132793 (G>A) in XRCC6 gene might increase the risk of breast cancer, while rs132788 G>T and rs6002421 (A>G) might be protective factors. However, there was no relationship between XRCC7 genetic polymorphisms and the risk of breast cancer. Conclusion: This meta-analysis suggests that the rs3835 G>A and rs828907 G>T in XRCC5 gene, rs6002421 (A>G), rs132788 (G>T) and rs132793 (G>A) in XRCC6 gene might be risk factors for breast cancer, while the rs132788 (G>T) and rs6002421 (A>G) in XRCC6 gene might be protective. -
Nandini, N.M.;Nandish, S.M.;Pallavi, P.;Akshatha, S.K.;Chandrashekhar, A.P.;Anjali, S.;Dhar, Murali 3645
Conventional pap smear (CPS) examination has been the mainstay for early detection of cervical cancer. However, its widespread use has not been possible due to the inherent limitations, like presence of obscuring blood and inflammation, reducing its sensitivity considerably. Automated methods in use in developed countries may not be affordable in the developing countries due to paucity of resources. On the other hand, manual liquid based cytology (MLBC) is a technique that is cost effective and improves detection of precursor lesions and specimen adequacy. Therefore the aim of the study was to compare the utility of MLBC with that of CPS in cervical cancer screening. A prospective study of 100 cases through MLBC and CPS was conducted from October 2009 to July 2010, in a Medical College in India, by two independent pathologists and correlated with histopathology (22 cases). Morphological features as seen through MLBC and CPS were compared. Subsequently, all the cases were grouped based on cytological diagnosis according to two methods into 10 groups and a subjective comparison was made. In order to compare the validity of MLBC with CPS in case of major diagnoses, sensitivity and specificity of the two methods were estimated considering histological examination as the gold standard. Increased detection rate with MLBC was 150%. The concordance rate by LBC/histopathology v/s CPS/histopathology was also improved (86% vs 77%) The percentage agreement by the two methods was 68%. MLBC was more sensitive in diagnosis of LSIL and more specific in the diagnosis of inflammation. Thus, MLBC was found to be better than CPS in diagnosis of precursor lesions. It provided better morphology with increased detection of abnormalities and preservation of specimen for cell block and ancillary studies like immunocytochemistry and HPV detection. Therefore, it can be used as alternative strategy for cervical cancer prevention in limited resource settings. -
Li, Fu-Rong;Yu, Feng-Xiu;Yao, Shu-Tong;Si, Yan-Hong;Zhang, Wei;Gao, Lin-Lin 3653
Background: A number of effective prevention measures have been introduced in attempts to substantially reduce both the incidence and mortality due to many kinds of cancer. The search for new anti-cancer compounds in foods or in plant medicines is one realistic and promising approach to prevention. Chinese medicines provide a rich pool of novel and efficacious agents for cancer prevention and treatment. Previously it was demonstratrated that hyperin extracted from the Manchurian rhododendron leaf reduces the proliferation of many cancer cells. The present study was carried out to evaluate its effects on human endometrial cancer cell viability and apoptosis and to investigate its mechanisms of action in RL952 cells. Methods: Cell viability was measured using the MTT assay. Intracellular calcium ions were detected using laser-scanning confocal microscopy. The effects of hyperin on apoptosis related proteins in RL952 cells were examined using Western blot analysis. Results: The growth of RL952 cells was inhibited by treatment with hyperin. OD values of caspase-3 and caspase-9 were increased and expression of bcl-2 was increased and bax was decreased in protein levels in RL952 cells after 24 h of hyperin treatment, Moreover, intracellular calcium accumulation occurred in hyperin-treated cells. Conclusion: These results suggest that hyperin may play an important role in tumor growth suppression by inducing apoptosis in human endometrial cells via a$Ca^{2+}$ -related mitochondrion apoptotic pathway in RL952 cells. -
Afshar, Reza Malekpour;Mollaie, Hamid Reza 3657
HBV infection is contagious and may be transmitted vertically or horizontally by blood products and body secretions. Over 50% of Iranian carriers have contracted the infection prenatally, making this the most likely route of transmission of HBV in Iran. This study assesses the resistance to Lamivudine in patients with chronic hepatitis B infection using a new ZNA probe Real Time PCR method. To evaluate the effectiveness of Lamivudine therapy for chronic hepatitis B infection, a study was conducted on 70 patients (63 men and 7women), who had received the drug first line. All patients were tested for the presence of HBsAg and HBeAg, the serum ALT level and the HBV DNA load before and after treatment. In all samples resistance to Lamivudine was tested with the ZNA Probe. Our results showed that ZNA Probe Real Time PCR method could detect wild type,YMDD, and its mutants, tyrosine-isoleucine-aspartate-aspartate and tyrosine-valine-aspartate-Aspartate. Among an estimated seventy patients with chronic hepatitis B infection, 18 (25.7%) were resistant to lamivudine. Only one patient was negative for presence of HBS-Ag (5.6%) and two patients were negative for HBe-Ag (11.1%). Real-time PCR with Zip nucleic acid probes is a sensitive, specific and rapid detection method for mutations in the YMDD motif, which will be essential for monitoring patients undergoing Lamivudine antiviral therapy. -
Saeed, Nadeem Mohammed;Bawazir, Amen Ahmed;Al-Zuraiqi, Masuod;Al-Negri, Fadhel;Yunus, Faisel 3663
The hepatitis B virus (HBV) and the hepatitis C virus (HCV) are still public health problems in Yemen, with older individuals having much higher prevalence than younger generations. However, research on the prevalence of viral hepatitis in association with hepatocellular cancer (HCC) has not yet been undertaken in Yemen. The aim of this study was to determine the prevalence of HBV and HCV infection among HCC patients and to estimate the risk of these infections being associated with the development of HCC. A cross-sectional study was conducted on patients attending oncology outpatient in Sana'a, Yemen, through the period 2008-mid 2010 with confirmed diagnosis of HCC. A total of 88 cases were studied thoroughly with different investigations such as CT-scan, ultrasound, tumour marker, alpha-feto-protein and histopathological biopsy. A structured questionnaire was also applied and physical examination done to assess the general condition of the patients. Statistical package (SPSS version 16) was used for analysis of the data. The mean age of the cases was 61.2 years (${\pm}12.6$ ) with half over 60 years. There were fewer male patients (36%) compared to females and most (97%) only had basic /no formal education. Seventy nine (89%) were diagnosed as HCC cases with histopathological biopsy while the rest were diagnosed by ultrasound, CT scan, tumour marker, and alpha-feto-protein. Around one-third of the subjects were positive for HBsAg and HCV antibodies. Multivariate analysis showed infection with HCV and use of smoking was associated with HCC diagnosis. Although an association was observed between the occurrence of HCC and viral hepatitis (either HBV or HCV) and cigarette smoking, but the rate of viral infection was lower than what has been reported elsewhere. -
Reza, Malekpour Afshar;Fahimeh, Gadari;Reza, Mollaie Hamid 3669
A role for the xenotropic murine leukemia virus (XMRV) in prostate cancer development has been postulated. To answer questions regarding the prevalence of XMRV in Iranian patients with prostate cancer and its association with the RNASEL R462Q polymorphism, we here investigated a series of cases in Kerman, in the Southeast of Iran, and sought to verify the association with the R462Q using Real Time PCR Method. Prostate tissue specimens of 200 patients with prostate cancer were genotyped for R462Q by real time polymerase chain reaction allelic discrimination and were screened for XMRV proviral DNA by real time polymerase chain reaction specific for the envelope gene. Of 200 patients in this study 8 (4%) cases were positive for XMRV, the QQ allele being the most frequenct regarding the R426Q polymorphism while in negative patients it was the RQ allele. There was significant correlation between high pathological scores and XMRV positive samples. No significant relationship was found between age groups and XMRV results. XMRV was only found in patients with QQ and RQ alleles, not RR. XMRV is detectable in tumor prostate tissue from some patients with prostate cancer, independent of R462Q. -
Li, Yu-Zhu;Li, Shu-Ling;Li, Xia;Wang, Li-Jie;Wang, Jiu-Ling;Xu, Jia-Wen;Wu, Zhi-Hong;Gong, Li;Zhang, Xiao-Dan 3675
Objective: To investigate the expression of endogenous hypoxia-related markers identified as being involved in vulvar squamous cell carcinoma (VSCC). Methods: We performed immunohistochemical staining of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$ ), glucose transporter-1 (GLUT-1), carbonic anhydrase 9 (CA-9) and vascular endothelial growth factor (VEGF), on tissue sections of 25 VSCC patients, 10 vulvar intraepithelial neoplasia (VIN) patients and 12 healthy controls. Results: HIF-$1{\alpha}$ expression was found in all sections, with no significant difference between controls, VIN and VSCC sections (all P<0.05). Glut-1 expression was found in 25% of control, 90% of VIN and 100% of VSCC sections. A significant difference between control and VIN or VSCC was observed (all P<0.05), while no difference was found between VIN and VSCC sections (P>0.05). CA-9 expression was negative in control sections, but it was found in 30% of VIN sections and 52% of VSCC sections with strong staining. Similarly, CA-9 expression also showed obvious differences between controls and VIN or VSCC sections (all P<0.05). However, there was no significant difference between VIN and VSCC (P>0.05). There were only 25% of control sections with weak VEGF expression, while strong staining was found in about 60% of VIN sections and 25% of VSCC sections (all P<0.05). In addition, a difference was also found between VIN and VSCC sections (P<0.05). Conclusion: Expression of endogenous hypoxia markers (HIF-$1{\alpha}$ , GLUT-1, CA-9 and VEGF) might be involved in the malignant progression of VSCC. -
Wu, Jun-Zhao;Lu, Peng;Liu, Rong;Yang, Tie-Jian 3681
Background: In breast cancer, estrogen receptors have been demonstrated to interact with transcription factors to regulate target gene expression. However, high-throughput identification of the transcription regulation relationship between transcription factors and their target genes in response to estradiol is still in its infancy. Purpose: Thus, the objective of our study was to interpret the transcription regulation network of MCF7 breast cancer cells exposed to estradiol. Methods: In this work, GSE11352 microarray data were used to identify differentially expressed genes (DEGs). Results: Our results showed that the MYB (v-myb myeloblastosis viral oncogene homolog [avian]), PGR (progesterone receptor), and MYC (v-myc myelocytomatosis viral oncogene homolog [avian]) were hub nodes in our transcriptome network, which may interact with ER and, in turn, regulate target gene expression. MYB can up-regulate MCM3 (minichromosome maintenance 3) and MCM7 expression; PGR can suppress BCL2 (B-cell lymphoma 2) expression; MYC can inhibit TGFB2 (transforming growth factor, beta 2) expression. These genes are associated with breast cancer progression via cell cycling and the$TGF{\beta}$ signaling pathway. Conclusion: Analysis of transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of breast cancer. -
Bao, Li-Dao;Niu, Jian-Xiang;Song, Hui;Wang, Yi;Ma, Rui-Lian;Ren, Xian-Hua;Wu, Xin-Lin 3687
Objective: The current meta-analysis was performed to address a more accurate estimation of the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and risk of gastric cancer (GC), which has been widely reported with conflicting results. Methods: A comprehensive literature search was conducted to identify all the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Results: A total of 20 studies containing 2,821 GC cases and 6,240 controls were finally included in the analyses. Overall, no significant association between GSTP1 polymorphism and GC risk was observed in worldwide populations. However, subgroup analysis stratified by ethnicity showed that GSTP1 polymorphism was significantly associated with increased risk of GC in Asians (G vs. A, OR = 1.273, 95%CI=1.011-1.605; GG vs. AA, OR=2.103, 95%CI=1.197-3.387; GG vs. AA+AG, OR =2.103, 95%CI=1.186-3.414). In contrast, no significant association was found in Caucasians in any genetic models, except for with AG vs. AA (OR=0.791, 95%CI=0.669-0.936). Furthermore, the GSTP1 polymorphism was found to be significantly associated with GC in patients with H. pylori infection and in those with a cardiac GC. Subgroup analysis stratified by Lauren's classification and smoking status showed no significant association with any genetic model. No studies were found to significantly influence the pooled effects in each genetic mode, and no potential publication bias was detected. Conclusion: This meta-analysis suggested that the GSTP1 polymorphism might be associated with increased risk of GC in Asians, while GSTP1 heterozygote genotype seemed to be associated with reduced risk of GC. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results. -
Xu, Lu-Lu;Guo, Shu-Liang;Ma, Su-Ren;Luo, Yong-Ai 3695
Mammalian mediator (MED) is a multi-protein coactivator that has been identified by several research goups. The involvement of the MED complex subunit 19 (MED 19) in the metastasis of lung adenocarcinoma cell line (H1299), which expresses the MED 19 subunit, was here investigated. When MED 19 expression was decreased by RNA interference H1299 cells demonstrated reduced clone formation, arrest in the S phase of the cell cycle, and lowered metastatic capacity. Thus, MED 19 appears to play important roles in the biological behavior of non-small cell lung carcinoma cells. These findings may be important for the development of novel lung carcinoma treatments. -
Background: Cervical cancer is one of the most common cancers in developing countries and the second most common type of cancer in women globally. Several recent studies suggested a co factor role for Chlamydia trachomatis in pathogenesis of cervical cancer. This study aimed to evaluate existence of C. trachomatis DNA in pathologic blocks of patients with cervical cancer. Materials and methods: Seventy-six formaldehyde fixed paraffin embedded tissue specimens from patients with histologically proven history of cervical cancer as well as 150 blocks from healthy peoples were included in the present study. Thin slices were prepared from selected blocks followed by deparaffinization and DNA extraction; the presence of C. trachomatis DNA was examined by Taq Man real-time PCR. Results: Our TaqMan real time PCR assay with cervical specimens of patients with cervical cancer showed that there was no C. trachomatis DNA. Also, we found three positive specimens among our control group. Conclusion: It seems that based on results obtained from the specimens examined in the present study, there is no association between the presence of C. trachomatis DNA in cervical specimens and cervical cancer.
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Liu, Bin;Gao, Hai-Cheng;Xu, Jing-Wei;Cao, Hong;Fang, Xue-Dong;Gao, Hai-Mei;Qiao, Shi-Xing 3705
Effects of Cantharidinate on apoptosis of human colorectal cancer UTC-116 cells were investigated by means of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, H and E staining, flow cytometry, and Raman Spectra analysis. The results showed Cantharidinate to exert inhibitory action on proliferation of human colorectal cancer UTC-116 cells, inducing apoptosis, arresting cells in G1 phase, with decline of S and G2 phases. In addition, the results of Raman spectrum showed significant changes in the UTC-116 cells chemical structure with stretching after the application of Cantharidinate. Taken together, these results suggest that the treatment of human colorectal cancer with Cantharidinate may be associated with multiple molecular mechanisms for apoptosis. Furthermore, similar to fluorouracil, Cantharidinate should be considered as novel assistant drug for controlling the growth of human colorectal cancer UTC-116 cells. -
Dai, Xin;Zhao, Hong-Qiang;Liu, Run-Hao;Xu, Chang-Tao;Zheng, Fang;Yu, Li-Bao;Li, Wei-Min 3709
This study evaluated the advantages and applications of contrast-enhanced ultrasound (CEUS)-supported percutaneous radiofrequency ablation (RFA) in the treatment of metastatic hepatocellular carcinoma after liver transplantation, based on clinical details. CEUS-supported percutaneous RFA was adopted to treat 12 patients with hepatic metastatic carcinomas after liver transplantation. The diameters of the metastatic carcinomas varied from 1 cm to 5 cm, and the foci were discovered after 3 months to 12 months. Each focus was diagnosed and localised by CEUS for RFA once or twice. Curative effects were evaluated by CEUS or contrast-enhanced CT after the treatment. The re-examination results at 2 weeks post-treatment showed that the foci of 11 patients were ablated completely, whereas one patient with the largest focus required retreatment by RFA because of a partial residue. No local recurrence was found one month later in the re-examination. CEUS-supported percutaneous RFA in the treatment of hepatic metastatic carcinoma after liver transplantation has the advantages of accurate localisation, good efficacy, easy operation, and minimal invasion without any complications. Therefore, it can be recommended as the preferred therapy for hepatic metastatic carcinoma after liver transplantation. -
Sun, Wei;Ma, Xiu-Min;Bai, Jing-Ping;Zhang, Guo-Qing;Zhu, Yue-Jie;Ma, Hai-Mei;Guo, Hui;Chen, Ying-Yu;Ding, Jian-Bing 3713
Objective: Transmembrane protein 166 (TMEM166) expression in esophageal squamous cell carcinoma (ESCC) and remote normal esophageal tissues was examined to assess any role in tumour biology. Methods: TMEM166 mRNA expression in 36 cases with ESCC (36 tumour samples, 36 remote normal esophageal tissue samples) was detected by RT-PCR. TMEM166 protein expression was analysed in paraffin-embedded tissue samples from the same cases by immunohistochemistry. Results: Semi-quantitative analysis showed TMEM166 mRNA expression in ESCCs to be significantly lower than in remote normal esophageal tissues ($0.759{\pm}0.713$ vs.$2.622{\pm}1.690$ , P=0.014). TMEM166 protein expression was also significantly reduced (69.4% vs. 94.4%, P<0.01). Conclusion: TMEM166 mRNA and protein expression demonstrated significant reduction in ESCCs compared with remote esophageal tissues, albeit with no correlation with tumour size, differentiation, stage, and lymph node metastasis, suggesting a role in regulating autophagic and apoptotic processes in the ESCC. -
Wang, Xi-Wen;Zhong, Tian-Yu;Xiong, Yun-Hui;Lin, Hai-Bo;Liu, Qing-Yi 3717
Purpose: Any association between the CYP1A1 Ile462Val polymorphism and endometrial cancer risk remains inconclusive. For a more precise estimate, we performed the present meta-analysis. Methods: PUBMED, OVID and EMBASE were searched for the studies which met inclusion criteria. Data in all eligible studies were evaluated and extracted by two authors independently. The meta-analysis estimated pooled odds ratio (OR) with 95% confidence interval (CI) for endometrial cancer risk attributable to the CYP1A1 Ile462Val polymorphism. Results: A total of 7 studies were included in this meta-analysis. The results indicated no association between endometrial cancer risk and the CYP1A1 Ile462Val polymorphism (for Val vs Ile allele model [OR 1.09, 95% CI 0.73-1.62]; for Val.Val vs Ile.Ile genotype model [OR 1.54, 95% CI 0.56-4.23]; for (Ile.Val + Val.Val) vs Ile.Ile genotpye model [OR 1.08, 95% CI 0.71-1.63]; for Val.Val vs (Ile.Ile + Ile.Val) genotype model [OR 1.46, 95% CI 0.53-4.04]). Conclusions: This meta-analysis suggests that there is no association between endometrial cancer risk and the CYP1A1 Ile462Val polymorphism. -
Norsa'adah, Bachok;Rahmah, Mohd Amin;Rampal, Krishna Gopal;Knight, Aishah 3723
Delay in help-seeking behaviour which is potentially preventable has a major effect on the prognosis and survival of patients with breast cancer. The objective of this study was to explore reasons for delay in seeking help among patients with breast cancer from the East Coast of peninsular Malaysia. A qualitative study using face-to-face in-depth interview was carried out involving 12 breast cancer patients who had been histo-pathologically confirmed and were symptomatic on presentation. Respondents were selected purposely based on their history of delayed consultation, diagnosis or treatment. All were of Malay ethnicity and the age range was 26-67 years. Three were in stage ll, seven in stage lll and two in stage lV. At the time of interview, all except one respondent had accepted treatment. The range of consultation time was 0.2-72.2 months with a median of 1.7 months, diagnosis time was 1.4-95.8 months( median 5.4 months )and treatment time was 0-33.3 months (median 1.2 months). The themes derived from the study were poor knowledge or awareness of breast cancer, fear of cancer consequences, beliefs in complementary alternative medicine, sanction by others, other priorities, denial of disease, attitude of wait and see and health care system weakness. Help-seeking behaviour was influenced by a complex interaction of cognitive, environmental, beliefs, culture and psycho-social factors. Breast cancer awareness and psychological counselling are recommended for all patients with breast symptoms to prevent delay in seeking clinical help. -
Ma, Seung Hyun;Kim, Byoung-Gie;Choi, Ji-Yeob;Kim, Tae-Joong;Kim, Yong-Man;Kim, Jae Weon;Kang, Sokbom;Kang, Daehee;Yoo, Keun-Young;Park, Sue K. 3731
Background: There have been few studies of Asian ovarian cancer and benign tumors. The primary aim of this paper was to report the protocol of the Ko-EVE study to examine epidemiological and molecular factors for ovarian cancer and benign neoplasms and to ascertain the major risk factors for ovarian cancer control in Korea. Methods: This case-control study covers incident epithelial ovarian cancers and benign neoplasms, four major centers participating in enrolling incident cases and 3 hospitals enrolling healthy controls among health examinees. Standardized questionnaires were administered by trained interviewers, including sections on socio-demographics characteristics, past medical history, medication usage, family history, lifetime consumption of alcohol and tobacco, diet, physical activity, and reproductive factors for women. Various biological specimens were collected in the biorepository according to the standardized protocol. Annual follow-up for cancer cases and follow-up at the 1st year for benign tumor cases are performing to evaluate treatment effect and progression. Passive follow to see long-term survival will be conducting using record linkage with national data. Results: The total number recruited in 2010-2011 was 246 epithelial ovarian cancer cases, 362 benign epithelial tumors and 345 controls. We are planning to collect subjects for at least 1,500 sets of ovarian cancer, 2,000 benign tumors and 1,500 controls till 2018. Conclusions: The Ko-EVE will provide unique and important data to probe the etiology and natural history of Korean epithelial ovarian cancer. It will be continued by genomic and proteomic epidemiological analyses and future intervention studies for the prevention of ovarian cancer among Koreans. -
Cheng, Peng;Cheng, You;Su, Mei X.;Li, Dong;Zhao, Guo Z.;Gao, Hui;Li, Yan;Zhu, Jie Y.;Li, Hua;Zhang, Tao 3741
Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the most common form of liver cancer. However, while it is associated frequently with hepatitis C virus (HCV) there is only an elementary understanding of its molecular pathogenesis. Methods: To gain insight into the molecular mechanisms of HCV-induced hepatocarcinogenesis, we performed microarray analysis on 75 surgical liver samples from 48 HCV-infected patients. Results: There were 395 differentially expressed geness between cirrhotic samples and HCC samples. Of these, 125 genes were up-regulated and 270 genes were down-regulated. We performed pathway enrichment analysis and screened as described previously. Conclusions: The differentially expressed genes might be involved in hepatocarcinogenesis through upregulating the pathways of ECM-receptor interaction, focal adhesion, cell adhesion molecules and other cancer-related pathways, and downregulating the pathways of "complement and coagulation cascades". We hope our results could aid in seeking of therapeutic targets for HCV-induced hepatocellular carcinoma. -
Shen, Fang-Rong;Liu, Ming;Zhang, Xia;Feng, Ya-Hong;Zhou, Long-Shu;Chen, You-Guo 3747
Aim: The aim of this study was to investigate the quality of life (QOL) of breast cancer patients by using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaires. Methods: A total of 522 adult patients who were admitted to our hospital with breast cancer were collected during the period of Jun. 2007 to Dec. 2009. Results: Our FACT-B questionnaire study suggested that women below 50 years old, employed, higher education and annual income, lower TNM stage and receiving modified radical mastectomy manifested significantly better QOL using the assessment tool of the FACT-B subscale. Moreover, regression analysis indicated patients with young age, low stage cancer, high education and income were more likely to have high score of QOL, with ORs (95% CI) of 2.8 (1.52-4.56), 2.1 (1.15-3.95), 3.1 (1.45-5.12) and 3.54 (1.54-5.43), respectively. Conclusions: Our study showed younger age, lower stage of cancer, higher education and income could influence the QOL of breast cancer patients in our Chinese population. Further large sample studies are still needed for confirmation. -
Zheng, Feng-Jin;Shi, Lin;Yang, Jun;Deng, Xiao-Hui;Wu, Yu-Quan;Yan, Xi-Qing;Huang, Ning 3751
Aim: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis. For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted to investigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelial cells (EC cells) and adhesion molecule expression in vitro. Methods: The expression of CD44 or CD54 in the PG cells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopy double fluorescence staining. Results: The results showed that tea polyphenols: (1) inhibited the expression of CD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantly blocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influenced CD44 and CD54 expression during the adhesion process of PG cells to EC cells. Conclusions: The data indicated that the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54. The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibiting adhesion molecule expression to block cancer cell adhesion. -
Li, Cai-Yan;Huang, Wen-Feng;Wang, Qun-Li;Wang, Fan;Cai, E.;Hu, Bing;Du, Jia-Cheng;Wang, Jing;Chen, Rong;Cai, Xiao-Jing;Feng, Jing;Li, Hui-Hui 3757
Objective: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro. Methods: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using fow cytometric analysis after propidium iodide staining. Apoptosis was detected using theTUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclinA and P21 were examined by Western blot analysis. Results: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h signifcantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) signifcantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner. Conclusions: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug. -
Liu, Xiang-Ming;Liu, Feng-Hua;Tang, Yong;Li, Qiang 3763
Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of the MTHFR C677T polymorphism in pancreatic carcinogenesis is still controversial. Methods: A literature search was performed using Pubmed and CNKI databases for published studies through May 2012. We performed a meta-analysis of all relevant case-control studies that examined the association between MTHFR C677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a total of 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysis showed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancer risk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI 1.40-5.48; for recessive model, OR = 1.96, 95%CI 1.54-2.50; for dominant model, OR = 2.11, 95%CI 1.01-4.41). However, no significant association was found in Caucasians. Conclusions: The MTHFR C677T polymorphism is associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studies with a larger sample size are needed to further clarify this association. -
Shin, Ji-Yeon;Kim, So Young;Lee, Kun-Sei;Lee, Sang-Il;Ko, Young;Choi, Young-Soon;Seo, Hong Gwan;Lee, Joo-Hyuk;Park, Jong-Hyock 3767
Objective: We estimated the total medical costs incurred during the 5 years following a cancer diagnosis and annual medical use status for the six most prevalent cancers in Korea. Methods: From January 1 to December 31, 2006, new patients registered with the six most prevalent cancers (stomach, liver, lung, breast, colon, and thyroid) were randomly selected from the Korea Central Cancer Registry, with 30% of patients being drawn from each cancer group. For the selected patients, cost data were generated using National Health Insurance claims data from the time of cancer diagnosis in 2006 to December 31, 2010. The total number of patients selected was 28,509. Five-year total medical costs by tumor site and Surveillance, Epidemiology, and End Results (SEER) stage at the time of diagnosis, and annual total medical costs from diagnosis, were estimated. All costs were calculated as per-patient net costs. Results: Mean 5-year net costs per patient varied widely, from $5,647 for thyroid cancer to $20,217 for lung cancer. Advanced stage at diagnosis was associated with a 1.8-2.5-fold higher total cost, and the total medical cost was highest during the first year following diagnosis and decreased by the third or fourth year. Conclusions: The costs of cancer care were substantial and varied by tumor site, annual phase, and stage at diagnosis. This indicates the need for increased prevention, earlier diagnosis, and new therapies that may assist in reducing medical costs. -
Objective: Despite government efforts to increase participation in gastric cancer screening, the rate is still suboptimal in Korea. Therefore, we explored barriers to and predictors of gastric cancer screening participation among a nationally representative sample. Methods: We used the Health Interview Survey sub-dataset derived from the Fourth Korean National Health and Nutrition Examination Survey 2008 (KNHANES IV) to evaluate participation in gastric cancer screening and factors associated with attendance in individuals age
${\geq}40$ years. We enrolled 4,464 subjects who completed the questionnaire and were not previously diagnosed with gastric cancer. Four groups of factors were considered potential predictors of gastric cancer screening in a multivariate analysis: sociodemographic, health behavior, psychological and cognitive, and dietary factors. Results: Overall, 41.3% complied with the gastric cancer screening recommendations. Younger age, lower education level, living without a spouse, frequent binge drinker, and current smoker were significantly associated with less participation in gastric cancer screening. Conclusions: To improve participation in gastric cancer screening, more focused interventions should be directed to vulnerable populations, such as groups with low socioeconomic status or unhealthy behavior. In addition, there should be new promotional campaigns and health education to provide information targeting these vulnerable populations. -
Zhong, Zhi-Qiang;Song, Mao-Min;He, Ying;Cheng, Shi;Yuan, Hui-Sheng 3781
Background: Pancreatic cancer is one of the most aggressive tumors with a dismal prognosis. The membrane cytoskeletal crosslinker Ezrin participates in several functions including cell proliferation, adhesion, motility and survival. There is increasing evidence that Ezrin is overexpressed in vast majority of malignant tumors and regulates tumor progression. However, its roles in pancreatic cancer remain elusive. Methods: Three pairs of specific Ezrin siRNAs were designed and synthetized and screened to determine the most efficient one for construction of a hairpin RNA plasmid targeting Ezrin. After transfection into the Panc-1 pancreatic cancer cell line, real-time quantitative PCR and Western blotting were performed to examine the expression of mRNA and protein. The MTT method was applied to examine the proliferation and the drug sensibility to Gemcitabine. Flow cytometry was used to assess the cycle and apoptosis, while capacity for invasion was determined with transwell chambers. Furthermore, we detected phosphorylated-Erk1/2 protein and phosphorylated-Akt protein by Western blotting. Results: Real-time quantitative PCR and Western blotting revealed that Ezrin expression was notably down-regulated at both mRNA and protein levels by RNA interference (P< 0.01). Proliferation was inhibited and drug resistance to gemcitabine was improved (P< 0.05). Flow cytometry showed that the proportion of cells in the G1/G0 phase increased (P< 0.01), and in G2/M and S phases decreased (P< 0.05), with no apparent differences in apoptosis (P> 0.05). The capacity for invasion was markedly reduced (P< 0.01). In addition, down-regulating Ezrin expression had no effect on phosphorylated-Akt protein (P>0.05), but could decrease the level of phosphorylated-Erk1/2 protein (P< 0.05). Conclusions: RNA interference of Ezrin could inhibit its expression in the pancreatic cancer cells line Panc-1, leading to a potent suppression of malignant behavior in vitro. Assessment of potential as a target for pancreatic cancer treatment is clearly warranted. -
Chen, Ping;Huang, Hui-Fang;Lu, Rong;Wu, Yong;Chen, Yuan-Zhong 3791
CD44v, especially splice variants containing exon v6, has been shown to be related closely to development of different tumors. High levels of CD44v6/v7 have been reported to be associated with invasiveness and metastasis of many malignancies. The objective of this study was to detect expression of CD44v6-containing variants in patients with acute promyelocytic leukemia (APL) and evaluate the potential of CD44v6/v7 for risk stratification. Reverse transcription polymerase chain reaction (RT-PCR) followed by PCR product purification, ligation into T vectors and positive clone sequencing were used to detect CD44 v6-containing variant isoforms in 23 APL patients. Real-time quantitative PCR of the CD44v6/v7 gene was performed in patients with APL and in NB4 cells that were treated with all-trans retinoic acid (ATRA) or arsenic trioxide ($As_2O_3$ ). Sequencing results identified four isoforms (CD44v6/v7, CD44v6/v8/v10, CD44v6/v8/v9/v10, and CD44v6/v7/v8/v9/v10) in bone marrow mononuclear cells of 23 patients with APL. The level of CD44v6/v7 in high-risk cases was significantly higher than those with low-risk. Higher levels of CD44v6/v7 were found in three patients with central nervous system relapse than in other patients inthe same risk group. Furthermore, in contrast to ATRA, only$As_2O_3$ could significantly down-regulate CD44v6/v7 expression in NB4 cells. Our data suggest that CD44v6/v7 expression may be a prognostic indicator for APL. -
Zhao, Lian-Mei;Han, Li-Na;Ren, Feng-Zhi;Chen, Shu-Hong;Liu, Li-Hua;Wang, Ming-Xia;Sang, Mei-Xiang;Shan, Bao-En 3795
Cochinchina momordica seeds (CMS) have been widely used due to antitumor activity by Mongolian tribes of China. However, the details of the underlying mechanisms remain unknown. In the present study, we found that an EtOAc (ethyl ester) extract of CMS (CMSEE) induced differentiation and caused growth inhibition of melanoma B16 F1 cells. CMSEE at the concentration of$5-200{\mu}g/ml$ exhibited strongest anti-proliferative effects on B16 F1 cells among other CMS fractions (water or petroleum ether). Moreover, CMSEE induced melanoma B16 F1 cell differentiation, characterized by dendrite-like outgrowth, increasing melanogenesis production, as well as enhancing tyrosinase activity. Western blot analysis showed that sustained phosphorylation of p38 MAP accompanied by decrease in ERK1/2 and JNK dephosphorylation were involved in CMSEE-induced B16 F1 cell differentiation. Notably, 6 compounds that were isolated and identified may be responsible for inducing differentiation of CMSEE. These results indicated that CMSEE contributes to the differentiation of B16 F1 cells through modulating MAPKs activity, which may throw some light on the development of potentially therapeutic strategies for melanoma treatment. -
Zhang, Long;Ji, Qing;Ni, Zhen-Hua;Sun, Jian 3803
Prohibitin (PHB), an evolutionarily-conserved protein, has been found to be over-expressed in gastric cancer and be closely related with tumor malignancy. In this study, to investigate the relationship between PHB expression and cell apoptosis in the BGC823 gastric cancer cell line, low and high expression PHB in BGC823 cells was accomplished using RNA interference technology and gene transfer techniques. Cell proliferation, cell cycling, apoptosis, Bax, Bcl-2 and Cyt.c protein expression and the activation of Caspase-3,9 were assessed after 48h. Over-expression of PHB gene in BGC823 cells resulted in slow cell growth, cell arrest in G2 phase, and an increased apoptosis ratio while the opposite was found for PHB under-expressing cells. In PHB over-expressing cells, the expression of Bax gene was increased, the expression of Bcl-2 was decreased, the activation level of Caspase-3, 9 was increased, but the activation level of Caspase-8 demonstrated no change. These results indicate that PHB induced apoptosis through the mitochondrial pathway. -
Background and Objectives: Colorectal cancer (CRC) is a major health problem in the Kingdom of Saudi Arabia (KSA). Our aim was to characterize the epidemiology of CRC in the Saudi population. Design and Setting: Retrospective analysis of all cases of CRC recorded in the Saudi Cancer Registry (SCR) between January 2001 and December 2006 amongst Saudi citizens in KSA. Patients and Methods: Data were retrieved from the database of the SCR. Descriptive statistics was performed using SPSS. Results: A total of 4,201 cases of CRC were registered in the SCR. The incidence of CRC increased between 2001 and 2006. The mean age of patients at the time of diagnosis was 58 years; most patients were above 45 years of age (n=3322; 79.1%). At the time of diagnosis, 977 patients (23.0%) presented with localized disease and 1,018 (24.0%) had distant metastasis. The most frequent pathological variant was adenocarcinoma (73%), with grade 2 (moderately differentiated) being the most common grade among all variants (61%). For all cancer grades, the frequency of CRC was significantly higher among patients >45 years (P=0.004), who presented with more advanced disease (stages III and IV) (P=0.012). Based on logistic regression, age >45 years was associated with advanced regional presentation (P=0.001). Tumor grade was associated with advanced regional presentation and metastasis. Conclusions: There was an increase in the incidence of CRC between 2001 and 2006. The age at the time of diagnosis was low when compared with reports from developed countries. A nationwide approach is needed to encourage and illustrate the importance of screening programs.
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Du, Yong;Chen, Xin;Huang, Zhi-Ming;Ye, Xiao-Hua;Niu, Qing 3815
The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ($18.8%{\pm}1.26%$ ) was found to be significantly higher than that in normal mice ($9.99%{\pm}1.90%$ ) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed, and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer. -
Hao, Ting;Feng, Wei;Zhang, Jie;Sun, Yong-Jian;Wang, Gang 3821
Aim: SNPs of ERCC1 and ERCC2 genes have been found to be associated with response to platinum therapy in different clinical settings. In the current study, we investigated the relationship of SNPs in ERCC1 and ERCC2 to cisplain response and survival in osteosarcoma patients. Methods: 267 consecutive patients diagnosed with osteosarcoma between January 2003 to January 2005 were followed up until the end of January 2010. ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln polymorphisms were detected based upon the Sequenom MassARRAY platform.Results: For ERCC1 Asn118Asn, the variant genotype T/T was strongly significantly associated with a higher event free survival when compared with the wild-type C/C, with an adjusted OR (95% CI) of 0.39 (0.14-0.95). ERCC2 751 A/A genotype showed increased event free survival of osteosarcoma (HR=0.44; 95%CI=0.10-0.87). However, we did not find significant association of ERCC1 Gln504Lys and ERCC2 Asp312Asn polymorphisms with prognosis of osteosarcoma. Conclusions: We first report associations of four SNPs, ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln, with risk of death from osteosarcoma in a Chinese population, indicating ERCC1 118T/T and ERCC2 A/A may be used as surrogate markers for clinical outcome of osteosarcoma treatmetn with cisplain. -
Mazloumi, Seyed Hashem Mir;Madhumathi, D.S.;Appaji, L.;Prasannakumari, Prasannakumari 3825
FISH is one of the most sensitive molecular methods to detect genetic abnormalities with DNA probes. When cytogenetic studies are normal or insufficient, FISH may detect cryptic rearrangements, rare or slowly proliferative abnormal populations in non-mitotic cells. We cytogenetically evaluated 70 childhood ALL - 67.1% were found to have an abnormal karyotype. The 23 patients (32.9%) with a normal karyotype were analyzed by FISH applying two probes; TEL/AML1 and MYB which detect cryptic rearrangements of t(12;21)(p13;q22) and deletion of (6q) respectively, associated with a good prognosis. Out of 23 patients, one was positive for t(12;21)(p13;q22) (4.3%). None of our patients were positive for MYB del(6q). Two patients showed an extra signal for MYB on chromosomes other than 6 (8.6 %) indicating amplification or duplication. Findings were compared with the available literature. Our study clearly indicated the integrated FISH screening method to increase the abnormality detection rate in a narrow range. FISH is less useful for diagnostic study of patients with suspected del(6q) but it helps in detecting known cryptic rearrangements as well as identification of new abnormalities(translocation , duplication and amplification) at the gene level. -
Al-Naggar, Redhwan Ahmed;Bobryshev, Yuri V.;Al-Jashamy, Karim 3829
Objective: The objective of this study was to examine the practice and associated factors of breast self-examination (BSE) among Malaysian women. Methods: For this cross-sectional study 250 women were selected by a simple random sampling technique. The questionnaire was consisted of three parts: socio-demographic characteristics, knowledge about BSE, and practice of BSE. Obtained data was analyzed using SPSS version 13. T-test and ANOVA test were used to explore the relation between socio-demographic characteristics and the practice of BSE. Results: About 32% of the participants reported that they have had family history of cancer and about 20% of the participants reported that they have had family history of breast cancer. The majority of the participants (88.8%) have heard about breast cancer and 78.4% of the participants have heard about BSE. Race, marital status, residency, regular exercise, awareness about breast cancer, belief that breast cancer can be detected early, belief that early detection improves the chance of survival, family history of cancer, family history of breast cancer, awareness about BSE, and belief that BSE is necessary, significantly influenced the practice of BSE among women. Practice of BSE on monthly basis was found to be 47.2% among the study participants. Conclusions: The socio-demographic characteristics significantly influence the practice of BSA among women in Malaysia. The findings of this study might not only influence the planning of specific screening interventions and strategies in Malaysia but might also be important for the relevant international communities, interested in the peculiarities of BSE incidence in different countries. -
Al-Naggar, Redhwan Ahmed;Bobryshev, Yuri V.;Al-Jashamy, Karim;Al-Musli, Mahfoudh 3835
Objective: The objective of this study is to determine the practice and associated factors of HPV vaccine among school girls in Melaka, Malaysia. Methodology: A total number of 612 secondary school girls participated in this study. The questionnaire consists of 38 questions which included 3 sections. The first section is about socio-demography. The Second section is about knowledge and awareness of HPV vaccines. The third section is about practices with associated barriers of HPV vaccination. Verbal consent was obtained from all participants, and data were analyzed using SPSS 13. Results: A total number of 612 secondary school girl students participated in this study. The mean age was$13.93{\pm}SD$ (1.09); minimum age was 13 years old and maximum was 17 years old. The majority of them was Malay, from rural areas and had a family monthly income of RM 3000 or less (91.8%, 53.1%, 69.6%; respectively). The majority of the parents of the school girls were with secondary education level (56.4%). The majority of the participants did not have a family history of cervical cancer (99.0%). The prevalence of HPV vaccination was 77.9% among school girls in Melaka. The majority of the participants were vaccinated in their schools (77.0%). About 69% knew about cervical cancer and 77.6% had ever heard about HPV vaccine. Regarding the factors that influence the practice of uptake HPV vaccine, they were age, race, income, parents' education, knowledge about cervical cancer, heard about HPV vaccine and place of getting the vaccine (p<0.001). Conclusions: The prevalence of HPV vaccine among school girls is high. Age, race, income, parents' education, knowledge about cervical cancer, heard about HPV vaccine and place of getting the vaccine were the significant factors that influence the practice of uptake HPV vaccine among school girls. -
Al-Naggar, Redhwan A.;Bobryshev, Yuri V.;Abdulghani, Mahfoudh Al-Musali Mohammed;Rammohan, Subramanian;Al-Jashamy, Karim 3841
Objective: The objective of this study was to explore the knowledge and perceptions of Malaysian tradition healers towards cancer and cancer prevention. Methodology: A total of 25 participants agreed to participate in this qualitative study during the period from$20^{th}$ July 2011 until$24^{th}$ of September 2011. The proposal of this study was approved by the Ethics Committee of Management and Science University (MSU). Once the participant agreed to be interviewed, date, time and place of the interviews were determined. Consent form was obtained from participants before the interview began. Participants were briefed about the study and its purpose, and after asking their permissions, their replies were recorded. The data was organized into themes and analyzed manually. Results: Twenty-five Malaysian traditional healers participated in this qualitative study. The age of participants ranged between 26 to 78 years old. The majority were in the age group of 31-60 years old, male, Chinese, degree holders with a monthly income ranging from 1,000-5,000 Ringgit Malaysia (RM) and were married (56%, 80%, 48%, 52%, 68%, 84% respectively). The majority defined cancer as having high cholesterol or abscess accumulation. A few of them defined cancer as a type of cell growth. The majority mentioned that food and unhealthy lifestyles are the primary causes of cancer. Surprisingly some of them mentioned that cancer is caused by interference by ghosts. Regarding the diagnosis of cancer, the majority mentioned that they refer their patients to modern physicians' medical report when it comes to diagnosing or treating patients with cancer. The most common cancers that many patients came to seek treatment were breast cancers, followed by colon cancers, liver and lung cancers. Conclusions: Despite good knowledgeabout the causes of cancer among traditional healers, misconceptions still exist. Insufficient knowledge about the definition of cancer was noted among the traditional healers. This urges immediate action by the Ministry of Health of Malaysia to set up a strict regulation and regular monitoring of the traditional healers nationally. Traditional and Complementary Medicine may be integrated into the healthcare system and need to have sustained cooperation for the benefit of patients since about 80% of patients use traditional medicines. -
Jana, Debarshi;Mandal, Syamsundar;Mukhopadhyay, Madhumita;Mitra, Debabrata;Mukhopadhyay, Sunit K.;Sarkar, Diptendra Kumar 3851
Introduction: The worldwide incidence of breast cancer has increased rapidly in recent years. The scenario of Eastern India is also showing the same trend. It is necessary to study the utility of HER-2/neu as a prognostic factor in breast cancer survival. However, there have not been detailed studies in this respect with the breast cancer patients of Eastern India. Thus this study was conducted. Materials and Methods: In this hospital-based study 86 breast cancer patients attending a breast clinic of a reputed institute of Eastern India and having invasive ductal carcinomas were observed for a period of 5 years after surgery. Associations between 5 years observed survival and status of ER, PR and HER-2/neu of the patients were critically evaluated. Results: There was statistically significant association between survival pattern for 5 years and the HER-2/neu status (p=0.00001). Better survival was observed for the patients with HER-2/neu negative tumors 67(100%) compared to HER-2/neu positive tumors 7(36.8%). Conclusions: There is strong interaction between survival and HER-2/neu expression of breast cancer patients. Thus the patients with HER-2/neu positive tumors need to be treated aggressively. -
Jaafar, Hasnan;Abdullah, Suhaila;Murtey, Mogana Das;Idris, Fauziah M. 3857
A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity. -
Ashtiani, Zahra Ousati;Heidari, Mansour;Hasheminasab, Sayed-Mohammad;Ayati, Mohsen;Rakhshani, Naser 3863
In this study mitochondrial D-Loop variations in Iranian prostate cancer and benign prostatic hyperplasia (BPH) patients were investigated. Tumour samples and corresponding non-cancerous prostate tissue from 40 prostate cancer patients and 40 age-matched BPH patients were collected. The entire mtD-loop region (16024-576) was amplified using the PCR method and products were gel-purified and subjected to direct nucleotide sequencing. A total of 129 variations were found, the most frequent being 263A${\rightarrow}$ G and 310T${\rightarrow}$ C among both BPH and prostate cancer patients. Variation of 309 C${\rightarrow}$ T was significantly more frequent in prostate cancer patients (P value<0.05). Four novel variations were observed on comparison with the MITOMAP database. Novel variations were np16154delT, np366G${\rightarrow}$ A, np389G${\rightarrow}$ A and 56insT. There was no correspondence between the different variations and the age of subjects. Considering that D-loop variations were frequent in both BPH and prostate cancer patients in our study, the fact that both groups had high average age can be a possible contributing factor. D-loop polymorphisms and microsatellite instability can influence cell physiology and result in a benign or malignant phenotype. Significantly higher frequency of 309 C${\rightarrow}$ T variation in cancer patients is a notable finding and must be a focus of attention in future studies. -
Inal, Ali;Kaplan, M. Ali;Kucukoner, Mehmet;Urakci, Zuhat;Guven, Mehmet;Nas, Necip;Yunce, Muharrem;Isikdogan, Abdurrahman 3869
Background: The majority of patients with gastric cancer in developing countries present with advanced disease. Systemic chemotherapy therefore has limited impact on overall survival. Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyze prognostic factors for survival in advanced gastric cancer patients undergoing first-line palliative chemotherapy. Methods: We retrospectively reviewed 107 locally advanced or metastatic gastric cancer patients who were treated with docetaxel and cisplatin plus fluorouracil (DCF) as first-line treatment between June 2007 and August 2011. Twenty-eight potential prognostic variables were chosen for univariate and multivariate analyses. Results: Among the 28 variables of univariate analysis, nine variables were identified to have prognostic significance: performance status, histology, location of primary tumor, lung metastasis, peritoneum metastasis, ascites, hemoglobin, albumin, weight loss and bone metastasis. Multivariate analysis by Cox proportional hazard model, including nine prognostic significance factors evident in univariate analysis, revealed weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level to be independent variables. Conclusion: Performance status, weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level were identified as important prognostic factors in advanced gastric cancer patients. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for treatment. -
Ulaganathan, V.;Kandiah, M.;Zalilah, M.S.;Faizal, J.A.;Fijeraid, H.;Normayah, K.;Gooi, B.H.;Othman, R. 3873
Objective: Colorectal cancer (CRC) and the metabolic syndrome (MetS) are both on the rise in Malaysia. A multi-centric case-control study was conducted from December 2009 to January 2011 to determine any relationship between the two. Methods: Patients with confirmed CRC based on colonoscopy findings and cancer free controls from five local hospitals were assessed for MetS according to the International Diabetes Federation (IDF) definition. Each index case was matched for age, gender and ethnicity with two controls (140: 280). Results: MetS among cases was highly prevalent (70.7%), especially among women (68.7%). MetS as an entity increased CRC risk by almost three fold independently (OR=2.61, 95%CI=1.53-4.47). In men MetS increased the risk of CRC by two fold (OR=2.01, 95%CI, 1.43-4.56), demonstrating an increasing trend in risk with the number of Mets components observed. Conclusion: This study provides evidence fora positive association between the metabolic syndrome and colorectal cancer. A prospective study on the Malaysian population is a high priority to confirm these findings. -
Amin, Tarek Tawfik;Al-Wadaani, Hamed Abdullah;Al-Quaimi, Manal Mubarak;Aldairi, Nedaa' Abdullah;Alkhateeb, Jawaher Mohammed;Al-Jaafari, Azzam Abdul Lateef 3879
Background: Development of effective educational strategies should accompany increases in public awareness and the availability of genetic testing for breast cancer (BC). These educational strategies should be designed to fulfill the knowledge gap while considering factors that influence women's interest in order to facilitate decision making. Objective: To determine the possible correlates of Saudi women's interest in BC genes testing including socio-demographics, the level of awareness towards BC genes, the family history of BC and the perceived personal risk among adult Saudi women in Al Hassa, Saudi Arabia. Subjects and methods: This cross-sectional study was carried out during the second BC community-based campaign in Al Hassa, Saudi Arabia. All Saudi women aged${\geq}18$ years (n=781) attending the educational components of the campaign were invited to a personal interview. Data collection included gathering information about sociodemographics, family history of BC, the perceived personal risk for BC, awareness and attitude towards BC genes and the women's interest in BC genes testing. Results: Of the included women (n=599), 19.5% perceived higher risk for BC development, significantly more among < 40 years of age, and with positive family history of BC before 50 years of age. The participants demonstrated a poor level of awareness regarding the inheritance, risk, and availability of BC genetic testing. The median summated knowledge score was 1.0 (out of 7 points) with a knowledge deficit of 87.8%. The level of knowledge showed significant decline with age (> 40 years). Of the included women 54.7% expressed an interest in BC genetic testing for assessing their BC risk. Multivariate regression model showed that being middle aged (Odds Ratio 'OR'=1.88, confidence intervals 'C.I'=1.14-3.11), with higher knowledge level (OR=1.67, C.I=1.08-2.57) and perceiving higher risk for BC (OR=2.11, C.I=1.61-2.76) were the significant positive correlates for Saudi women interest in BC genetic testing. Conclusion: Saudi women express high interest in genetic testing for BC risk despite their poor awareness. This great interest may reflect the presence of inappropriate information regarding BC genetic testing and its role in risk analysis. -
Aims: The purposes of this study were to (1) to identify the causes of cancer in breast cancer survivors in Taiwan; and (2) to investigate the influence of demographic characteristics and breast cancer-related factors on the cause of cancer. Materials and method: This study details the related investigative results on survivors with breast cancer using a descriptive and correlational design. A convenience sampling approach was employed. A structured questionnaire was used to assess the participants. Results: A total of 230 breast cancer survivors completed the questionnaire. Low-scoring cause of cancer participants were older adults (OR = 2.49, p<0.05) who were already of menopausal status (OR = 2.28, p < 0.05). Around 72% of particpants agreed high responsibility. Our breast cancer survivors felt stress had caused their breast cancer. Conclusion: These findings are helpful in understanding the relationship between cause of cancer and related factors in breast cancer survivors.
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Utada, Mai;Ohno, Yuko;Shimizu, Sachiko;Ito, Yuri;Tsukuma, Hideaki 3893
In previous studies we predicted future trends in cancer incidence for each prefecture in order to plan cancer control. Those predictions, however, did not take into account the characteristics of each prefecture. We therefore used the results of age-period-cohort analysis of incidence and mortality data of Osaka, and estimated the incidence and mortality of cancers at all sites and selected sites. The results reflect the characteristics of Osaka, which has and is expected to have large number of patients with liver cancer. We believe our results to be useful for planning and evaluating cancer control activities in Osaka. It would be worthwhile to base the estimation of cancer incidence and mortality in each prefecture on each population-based cancer registry. -
Lu, Peng;Liu, Rong;Ma, Er-Min;Yang, Tie-Jian;Liu, Jia-Lin 3899
B7-H3 is a newly discovered member of the B7/CD28 superfamily which functions as an important T-cell immune molecule. It has been reported recently that B7-H3 is highly expressed in many cancer cells, the data indicating that it may be a regulation factor contributing to tumor-resistance. In our study, we used bioinformatics to identify differentially expressed genes between colonic cancer cells and normal colonic cells, aiming to analyze mechanisms and identify sub-pathways closely related to progression, with the final aim of finding small molecule drugs which might interfere this progression. We found that ajmaline is one related factor which may enhance self-immunity in colon carcinoma therapy and B7-H3 plays important roles with regard to immunoreactions of colonic cancer cells. All the results indicate that H7-B3 is a favorable prognostic biomarker for colon carcinomas, providing novel information regarding likely targets for intervention. -
Ovarian cancer is the fifth leading cause of cancer death in women aged 35 to 74 years. Although there are several popular hypothesis of ovarian cancer pathogenesis, the genetic mechanisms are far from being clear. Recently, systems biology approaches such as network-based methods have been successfully applied to elucidate the mechanisms of diseases. In this study, we constructed a crosstalk network among ovarian cancer related pathways by integrating protein-protein interactions and KEGG pathway information. Several significant pathways were identified to crosstalk with each other in ovarian cancer, such as the chemokine, Notch, Wnt and NOD-like receptor signaling pathways. Results from these studies will provide the groundwork for a combination therapy approach targeting multiple pathways which will likely be more effective than targeting one pathway alone.
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Xie, Wen-Chuan;Chan, Man-Him;Mak, Kei-Choi;Chan, Wai-Tin;He, Miao 3911
Background: The objective of this study WAS to describe cancer incidence rates and trends among THE Hong Kong population for the period 1983-2008. Methods: Incident cases and population data from 1983 to 2008 were obtained from the Hong Kong Cancer Registry and the Census and Statistics Department, respectively. Agestandardized incidence rates (ASIR) were estimated and joinpoint regression was applied to detect significant changes in cancer morbidity. Results: For all cancers combined, the ASIR showed declining trends (1.37% in men, 0.94% in women), this also being the case for cancers of lung, liver, nasopharynx, stomach, bladder, oesophagus for both genders and cervix cancer for women. With cancer of thyroid, prostate, male colorectal, corpus uteri, ovary and female breast cancer an increase was evident throughout the period. The incidence for leukemia showed a stable trend since early 1990s, following an earlier decrease. Conclusion: Although overall cancer incidence rates and certain cancers showed declining trends, incidence trends for colorectal, thyroid and sex-related cancers continue to rise. These trends in cancer morbidity can be used as an important resource to plan and develop effective programs aimed at the control and prevention of the spread of cancer amongst the Hong Kong population. It is particularly useful in allowing projection of future burdens on the society with the increase in certain cancer incidences. -
Ni, Xiao-Jian;Xia, Tian-Song;Zhao, Ying-Chun;Ma, Jing-Jing;Zhao, Jie;Liu, Xiao-An;Ding, Qiang;Zha, Xiao-Ming;Wang, Shui 3917
Background: The relationship between postmenopausal hormone therapy (HT) and invasive breast cancer has been extensively investigated, but that with breast carcinoma in situ (BCIS) has received relatively little attention. The aim of our present study was to review and summarize the evidence provided by longitudinal studies on the association between postmenopausal HT use and BCIS risk. Methods: A comprehensive literature search for articles published up to May 2012 was performed. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Relative risk (RR) or odds ratio (OR) values were calculated using 14 reports (8 case-control studies and 6 cohort studies), published between 1986 and 2012. Results: There was evidence of an association between ever postmenopausal estrogen use and BCIS based on a random-effects model (RR = 1.25, 95% confidence interval (CI) = 1.01, 1.55). However, we found no strong evidence of an association between ever postmenopausal estrogen combined with progesterone use and BCIS using a randomeffects model (RR = 1.55, 95% CI = 0.95, 2.51). Furthermore, our analysis showed a strong association between "> 5 years duration" of estrogen or estrogen combined with progesterone use and BCIS. Furthermore, current use of any HT is associated with increased risk of BCIS in cohort studies. Additional well-designed large studies are now required to validate this association in different populations. -
Harirchi, Iraj;Azary, Saeedeh;Montazeri, Ali;Mousavi, Seyed Mohsen;Sedighi, Zahra;Keshtmand, Gelavizh;Zarinkolah, Zahra;Soltani, S.M. Amin Khalifeh 3927
Breast cancer is the most common cancer in women worldwide and the leading cause of death from cancer among women. Evidence suggests that early diagnosis and screening interventions might help to improve outcomes. This population-based study was conducted to determine breast cancer awareness and screening behavior among Iranian women and to examine its association with women's literacy. The study was carried out in two provinces, with 1,477,045 population, located in central and eastern part of Iran. Overall, 770 women were studied. Of these, 482 (62.7%) were literate and 287 (37.3%) were not. The results obtained from the data analysis indicated that there was a significant difference between literate and illiterate women. Further analysis of the data using logistic regression showed that literacy was an important contributing factor for breast cancer prevention behavior. The findings suggest that in order to improve women's health and breast cancer outcomes providing equal educational opportunities for women seems necessary. -
Ding, Xiang;Cui, Feng-Mei;Xu, Song-Tao;Pu, Jin-Xian;Huang, Yu-Hua;Zhang, Jiang-Lei;Wei, Xue-Dong;Hou, Jian-Quan;Yan, Chun-Yin 3931
Background: Epidemiological studies evaluating the association of two variants rs9340799 and rs2234693 on estrogen receptor 1 (ESR1) with prostate risk have generated inconsistent results. Methods: A meta-analysis was here conducted to systematically evaluate the relationship of these two variants with prostate cancer susceptibility. Results: For rs9340799, heterozygosity of T/C carriers showed a significant increased prostate cancer risk with a pooled odds ratio (OR) of 1.34 (95% CI = 1.06-1.69) while homozygote C/C carriers showed an increased but not statistically significant association with prostate cancer risk (pooled OR = 1.29, 95% CI = 0.94-1.79). Compared to the homozygous TT carriers, the allele C carriers showed a 31% increased risk for prostate cancer (pooled OR = 1.31, 95% CI = 1.06-1.63). No significant association between the rs2234693 and prostate cancer risk was found with the pooled OR of 1.15 (95% CI = 0.97-1.39, T/C and C/C vs. T/T) under the dominant genetic model. Compared to the homozygote T/T carriers, the heterozygous T/C carriers did not show any significantly different risk of prostate cancer (pooled OR = 1.13, 95% CI = 0.94-1.36) and the homozygous C/C carriers also did not show a significant change for prostate cancer risk compared to the wide-type T/T carriers (pooled OR = 1.26, 95% CI = 0.98-1.62). Conclusion: These data suggested that variant rs9340799, but not rs2234693, on ESR1 confers an elevated risk of prostate cancer. -
Background: Many studies have investigated possible association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and ovarian cancer risk, but the impact is still unclear owing to the obvious inconsistencies. This study was performed to quantify the strength of the association with a metaanalysis. Methods: We searched the PubMed, Embase, and CNKI databases for studies relating the association between MTHFR C677T polymorphism and ovarian cancer risk and estimated summary odds ratios (ORs) with confidence intervals (CIs) for assessment. Results: Finally, eight studies with a total of 3,379 ovarian cancer cases and 4,078 controls were included into this meta-analysis. Overall the showed that MTHFR C677T polymorphism was not associated with ovarian cancer risk under all genetic models (
$OR_{T\;versus\;C}$ = 1.03, 95%CI 0.90-1.18;$OR_{TT\;versus\;CC}$ = 1.08, 95%CI 0.79-1.47;$OR_{TT\;versus\;TC+CC}$ = 1.05, 95%CI 0.80-1.37;$OR_{TT+TC\;versus\;CC}$ = 1.05, 95%CI 0.86-1.21). Meta-analyses of studies with confirmation of HWE also showed no significant association. Subgroup analyses by ethnicity showed there was no significant association in the Caucasians but MTHFR C677T polymorphic variant T contributed to increased risk of ovarian cancer in East Asians. No evidence of publication bias was observed. Conclusion: Meta-analyses of available data show that MTHFR C677T polymorphism is not associated with ovarian cancer risk in Caucasians, but the MTHFR polymorphic variant T may contribute to increased risk in East Asians. -
Niu, Yu-Ming;Shen, Ming;Li, Hui;Ni, Xiao-Bing;Zhou, Juan;Zeng, Xian-Tao;Leng, Wei-Dong;Wu, Ming-Yue 3943
Objective: Findings for associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and head and neck cancer risk have been conflicting. We therefore performed a meta-analysis to derive a more precise relationship. Methods: Ten published case-control studies were collected and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR A1298C polymorphism and head and neck cancer risk. Sensitivity analysis and publication bias assessment also were performed to guarantee the statistical power. Results: Overall, no significant association between MTHFR A1298C polymorphism and head and neck cancer risk was found in this meta-analysis (C vs. A: OR=1.04, 95%CI=0.87-1.25, P=0.668, Pheterogeneity<0.001; CC vs. AA: OR=1.07, 95%CI=0.70-1.65, P=0.748,$P_{heterogeneity} < 0.001$ ; AC vs. AA: OR=1.06, 95%CI=0.88-1.27, P=0.565,$P_{heterogeneity} < 0.001$ ; CC+AC vs. AA: OR=1.06, 95%CI=0.86-1.30, P=0.571,$P_{heterogeneity} < 0.001$ ; CC vs. AA+AC: OR=1.02, 95%CI=0.69-1.52, P=0.910,$P_{heterogeneity} < 0.001$ ). Similar results were also been found in succeeding analysis of HWE and stratified analysis of ethnicity. Conclusion: In conclusion, our meta-analysis demonstrates that MTHFR A1298C polymorphism may not be a risk factor for developing head and neck cancer. -
Siddiqui, Md. Salahuddin;Chandra, Rajeev;Aziz, Abdul;Suman, Saurav 3949
Head and neck cancers are amongst the commonest malignancies, accounting for approximately 20% of the cancer burden in India. The major risk factors are tobacco chewing, smoking and alcohol consumption, which are all preventable. This retrospective study presents data from the histopathology register for a five year period from 2002-2006 at Patna Medical College and Hospital, a tertiary care hospital drawing patients from the entire Bihar state, the 3rd most populous state of India with the majority of the population residing in rural areas. Incidence rates based on sex, age, site of lesion, including age standardized incidence rates for males and females, with mean age of presentation, distribution of histological variants and year wise trend were calculated. Out of 455 head and neck neoplasias, 241 were benign while 214 were malignant. The most common age group for all malignant biopsies was 7th decade for males and the 5th decade for females. Malignant cases were commoner in males than females with the male:female ratio of 3.1:1, which was found to be statistically significant by the chi-square (${\chi}^2$ ) test. The crude rate and age standardized incidence rate was 0.05 and 0.06 per 100,000 population respectively. Squamous cell carcinoma (SCC) contributed about 96% of all cases, with grade I being the most common. Larynx was the most common site for malignancy, the supraglottic region being its most commonly affected sub-site. This observed incidence patterns in the region are a reminder of widespread unawareness, low healthcare utilization with virtually non-existent cancer programs. It also underlines the need to advocate for reliable cost-effective programs to create awareness, for early detection and plan appropriate management strategies. There is a compelling demand for a cancer registry in this region as well as proper implementation of preventive measures to combat this growing threat of cancer, many of whose risk factors are preventable. -
Zhang, Guo-Qing;Han, Feng;Fang, Xin-Zhi;Ma, Xiao-Mei 3955
Objective: To investigate the effects of$CD4^+$ , IL17 and Foxp3 expression on prognosis of operable non-small cell lung cancer (NSCLC) with different pTNM stages. Methods: Expression of$CD4^+$ , IL17 and Foxp3 in 102 cases of NSCLC tissues and adjacent cancer tissues was detected by immunohistochemistry and associations with prognosis with different pTNM stages were analyzed. The Chi-square test was used to compare count data. Survival differences were evaluated by Kaplan-Meier single factor analysis and the COX regression model was used to analyze the relationship between influential factors and the disease prognosis. The significance level was${\alpha}$ =0.05. Results: Expression of CD4, IL-17 and Foxp3 significantly varied in different pTNM stages of NSCLC tissues (P < 0.05). The same was true for CD4 expression (P < 0.05). The median survival time (MST) in the positive CD4 expression group was evidently higher than that in the negative group (25.8/23.9 months). Compared with stage III, the MST difference of stages I and II in the positive CD4 expression group were statistically significant (P < 0.05). The MST in positive IL-17 and Foxp3 expression groups was obviously lower than that in the corresponding negative group (P < 0.05) (25.6/35.1 months and 24/35.3 months, respectively). There was a significant difference of MST between any two of three stages of positive IL-17 expression group (P < 0.05), and it was the same with positive Foxp3 expression group. TNM stage, negative CD4 expression, and positive IL-17 and Foxp3 expression were the main risk factors for the prognosis of NSCLC. Conclusion: Surgical prognosis of NSCLC can be better assessed by the combination of clinical staging and expression of IL17 and Foxp3. -
Yu, Hong-Sheng;Wang, Xin;Song, Ai-Qin;Liu, Ning;Zhang, Wei;Yu, Li 3961
Objective: To compare the clinical effects of concurrent radiochemotherapy with those of radiotherapy in treating locally advanced nasopharyngeal carcinoma (Stage III~IVa). Methods: A total of 95 patients suffering from nasopharyngeal carcinoma (Stage III~IVa) were divided into two groups: concurrent radiochemotherapy (Group CCRT, n=49) and radiotherapy (Group RT, n=46). The two groups were both delivered conventional fractionated radiotherapy, while Group CCRT also received three cycles of PF (DDP+5-Fu) or PLF (DDP+5-Fu+CF) chemotherapy. Results: The complete remission rate and total remission rate of Group CCRT were higher than those of Group RT ($X^2$ =4.72~7.19, P<0.05). The one-year overall survival (OS) rate calculated by the life table method, was also higher than that of Group RT ($X^2$ =4.24, P<0.05) as well as the 3-year OS rate, nasopharyngeal control rate and cervical lymph nodes' control rate ($X^2$ =4.28~4.40, P<0.05). In addition, the 5-year OS and metastasis-free rates of Group CCRT were higher than those of Group RT and the differences were of statistical importance ($X^2$ =3.96~8.26, P<0.05). However, acute toxicity was also obviously higher, the difference in gastrointestinal reactions being statistically significant ($X^2$ =11.70, P<0.05). Conclusion: This study demonstrated that concurrent radiochemotherapy could improve the remission rate, overall survival rate and locally control rate. The toxicity of concurrent radiochemotherapy could be tolerated by the patients. -
Qian, Li-Yuan;Li, Ping;Li, Xiao-Rong;Chen, Dao-Jin;Zhu, Shai-Hong 3967
Aims: To explore the relationship between various molecular makers and liver metastasis of colorectal cancer (CRC). Method: Using immunohistochemistry, protein expression of CEA, nm23, c-met, MMP2, COX-2, VEGF, EGFR, and CD44 was assessed in 80 CRC cases. The Chi-square test and logistic regression were performed to analyze the relationship between these indicators and CRC liver metastasis. Results: There were significant differences in expression of CEA, MMP2, CD44, VEGF and EGFR between the liver metastasis and non metastasis groups (P < 0.05); no significant differences were noted for nm23, c-met, and COX-2 expression. Logistic regression analysis showed that only CEA, VEGF, and EGFR entered into the regression equation, and had significant correlations with CRC liver metastasis (${\alpha}$ inclusion= 0.10,${\alpha}$ elimination = 0.15, R2 = 0.718). Conclusions: Combination detection of CEA, VEGF, and EGFR may be an effective means to predict CRC liver metastasis. Nm23, c-met, MMP2, COX-2, and CD44, in contrast, are not suitable as prognostic markers. -
Kucukoner, Mehmet;Isikdogan, Abdurrahman;Yaman, Sebnem;Gumusay, Ozge;Unal, Olcun;Ulas, Arife;Elkiran, Emir T.;Kaplan, Muhammed A.;Ozdemir, Nuriye;Inal, Ali;Urakci, Zuhat;Buyukberber, Suleyman 3973
Background: The aim of this study was to evaluate the efficacy and toxicity of long-term, low-dose oral etoposide as an advanced treatment option in patients with platinum resistant epithelial ovarian cancer. Materials and Methods: For the purposes of this study, 51 patients with histologically-confirmed, recurrent or metastatic platinum-resistant epithelial ovarian cancer (EOC) treated at six different centers between January 2006 and January 2011 were retrospectively evaluated. Patients were treated with oral etoposide (50 mg/day for a cycle of 14 days, repeated every 21 days). Results: Among the 51 platinum-resistant patients, 17.6% demonstrated a partial response and 25.5% a stable response. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.1-5.7), while the median overall survival was 16.4 months (11.8.20.9). No significant relationship was observed between the pre-treatment CA 125 levels, post-treatment CA-125 levels and the treatment response rates (p=0.21). Among the 51 patients who were evaluated in terms of toxicity, grade 1 or 4 hematologic toxicity was observed in 19 (37.3%); and grade 1-4 gastrointestinal toxicity occurred in 15 patients (29.4%). Conclusions: Chronic low-dose oral etoposide treatment is generally effective and well-tolerated in platinum-resistant ovarian cancer patients. -
Shan, Zhao;Feng-Nian, Rong;Jie, Geng;Ting, Zhou 3977
Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer. -
Yusoff, Harmy Mohamed;Daud, Norwati;Noor, Norhayati Mohd;Rahim, Amry Abdul 3983
In Malaysia, colorectal cancer is the most common cancer in males and the third most common in females. Mortality due to colorectal cancer can be effectively reduced with early diagnosis. This study was designed to look into colorectal cancer screening participation and its barriers among average risk individuals in Malaysia. A cross sectional study was conducted from August 2009 till April 2010 involving average risk individuals from 44 primary care clinics in West Malaysia. Each individual was asked whether they have performed any of the colorectal cancer screening methods in the past five years. The barrier questions had three domains: patient factors, test factors and health care provider factors. Descriptive analysis was achieved using Statistical Program for Social Sciences (SPSS) version 12.0. A total of 1,905 average risk individuals responded making a response rate of 93.8%. Only 13 (0.7%) respondents had undergone any of the colorectal cancer screening methods in the past five years. The main patient and test factors for not participating were embarrassment (35.2%) and feeling uncomfortable (30.0%), respectively. There were 11.2% of respondents who never received any advice to do screening. The main reason for them to undergo screening was being advised by health care providers (84.6%). The study showed that participation in colorectal cancer screening in Malaysia is extremely low and multiple factors contribute to this situation. Given the importance of the disease, efforts should be made to increase colorectal cancer screening activities in Malaysia. -
Sakthive, K.M.;Kannan, N.;Angeline, A.;Guruvayoorappan, C. 3989
The aim of the present investigation was to evaluate the effect of A.nilotica extract against Dalton's ascitic lymphoma (DAL) induced solid and ascitic tumors in BALB/c mice. Experimental animals received A.nilotica extract (10 mg/kg.bw) intraperitoneally for 10 and 14 consecutive days before induction of solid and ascitic tumors, respectively. Treatment with A.nilotica extract significantly decreased the development of tumor and percentage increase in body weight when compared to DAL induced solid tumor control group, also increasing the life span, restoring the total white blood cell count and hemoglobin content and significantly decreasing the levels of serum aspartate transaminase (SGPT), alanine transaminase (SGOT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and nitric oxide (NO) when compared to DAL induced ascitic tumor controls. The treatment also reduced significantly the cellular glutathione (GSH) and nitric oxide levels in treated animals. Histopathological studies also confirmed protective influence. The outcome of the present work indicates that A.nilotica extract could be used as natural anticancer agent for human health. -
MicroRNAs (miRNAs) play roles in the clinic, both as diagnostic and therapeutic tools. The identification of relevant microRNAs is critically required for ovarian cancer because of the prevalence of late diagnosis and poor treatment options currently. To identify miRNAs involved in the development or progression of ovarian cancer, we analyzed gene expression profiles downloaded from Gene Expression Omnibus. Comparison of expression patterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 508 genes that were commonly up-regulated and 1331 genes that were down-regulated in the cancer specimens. Function annotation of these genes showed that most of the up-regulated genes were related to cell cycling, and most of the down-regulated genes were associated with the immune response. When these differentially expressed genes were mapped to MiRTarBase, we obtained a total of 18 key miRNAs which may play important regulatory roles in ovarian cancer. Investigation of these genes and microRNAs should help to disclose the molecular mechanisms of ovarian carcinogenesis and facilitate development of new approaches to therapeutic intervention.
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Ding, Yin-Lu;Wang, Qi-San;Zhao, Wei-Min;Xiang, Lei 4001
Backgrouds: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. Methods: To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. Results: IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression ($48.7{\pm}8.02$ months vs$28.0{\pm}6.86$ months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). Conclusions: Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression. -
Khaenam, Prasong;Niibori, Akiko;Okada, Seiji;Jearanaikoon, Patcharee;Araki, Norie;Limpaiboon, Temduang 4007
Purpose: Retinoblastoma-interacting zinc finger gene (RIZ1) is a tumor suppressor gene which is highly inactivated by promoter hypermethylation in patients with liver fluke-related cholangiocarcinoma (CCA). Epigenetic aberration of this gene might withdraw the ability to restrain tumor cell proliferation and migration. We aimed to define the role of RIZ1 on cell proliferation and migration in CCA cell line. Materials and methods: Small interference RNA (siRNA) was used to knock down the expression of RIZ1 in a CCA-derived cell line in which cell proliferation and cell migration were performed. Results: A predominant nuclear localization of RIZ1 was observed. Reduction of RIZ1 by siRNA augmented cell proliferation and migration. Conclusion: The result suggested that RIZ1 might play a role in regulating cell proliferation and migration in CCA. Reduction of RIZ1 expression may aggravate the progression of CCA. -
Baloch, Abdul Hameed;Shuja, Jameela;Daud, Shakeela;Ahmed, Muneer;Ahmad, Adeel;Tareen, Mehrullah;Khan, Farah;Kakar, Muhammad Azam;Baloch, Dost Mohammad;Kakar, Naseebullah;Naseeb, Hafiz Khush;Ahmad, Jamil 4013
Purpose: Breast cancer is the commonest malignancy of females throughout the world with one million new cases each year. In Pakistan, the burden of breast cancer disease is high with late stage presentation being a common feature, more than half being stage III or stage IV. The objective of this study was to study various aspects, patterns and risk factors in breast cancer patients of Balochistan. Method: Present study was performed on 134 patients of breast cancer who were registered in CENAR. The patients were interviewed by providing a questionnaire. Informed consent was taken from all the patients who took part in this study after explanation of the study aims. Body mass index (BMI) was calculated andbiopsy reports were obtained from patients files. All the cases were classified with respect to age, gender, ethnic group (Baloch, Pashtoon, Punjabi, Afghani, Hazara) BMI, cancer type, cancer grade, hormonal status, side of the cancer, fertility and marital status. Results: Out of 134 patients, the most common ethnic group was Pashtoon with a total of 42 and the common age group was 41-50 years with a total of 51. Invasive ductal carcinoma (IDC) was the most common type, accounting for in 128 patients (95.5%) followed by invasive lobular carcinoma (ILC). Conclusion: Pashtoon was the most common ethnic group, IDC was common type and most of the patients had an ER/PR positive hormonal status. -
Promthet, Supannee;Pientong, Chamsai;Ekalaksananan, Tipaya;Songserm, Nopparat;Poomphakwaen, Kirati;Chopjitt, Peechanika;Wiangnon, Surapon;Tokudome, Shinkan 4017
Background and Aim: Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) are known to be associated with predisposition for certain cancers. This study aimed to evaluate the effects of lifestyle factors, family history and genetic polymorphisms in MTHFR C677T and A1298C on rectal cancer risk and possible interactions with lifestyle factors in Northeast Thailand. Methods: A hospital-based case-control study was conducted during 2002-2006 with recruitment of 112 rectal cancer cases and 242 non-rectal cancer patient controls. Information was collected using a structured-questionnaire. Blood samples were obtained for assay of MTHFR C677T and A1298C genotypes by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) techniques. Associations between lifestyle factors, family history and genetic polymorphisms v.s. rectal cancer risk were assessed using logistic regression analysis. Results: Subjects with frequent and occasional constipation had a higher risk ($OR_{adj.}$ =14.64; 95%CI=4.28-50.04 and$OR_{adj.}$ =2.15; 95%CI=1.14-4.06), along with those who reported ever having hemorrhoids ($OR_{adj.}$ =2.82; 95%CI=1.36-5.84) or a family history of cancer ($OR_{adj.}$ =1.90; 95%CI=1.06-3.39). Consumption of a high level of pork was also associated with risk ($OR_{adj.}$ =1.82; 95%CI=1.05-3.15). Interactions were not observed between MTHFR and other risk factors. Conclusions: This study suggested that the risk factors for rectal cancer in the Thai population are bowel habits, having had hemorrhoids, a family history of cancer and pork consumption. -
Background and Objective: Cardiotoxicity and oxidative stress is a life-threatening side effect of doxorubicin (DOX). We investigate the effects of short-term exercise as therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity in the rat. Methods: Wistar males (weighing
$257{\pm}28g$ ) were divided into six groups: (1) control+placebo (2) control+DOX$10mg.kg^{-1}$ (3) control+DOX$20mg.kg^{-1}$ (4) training+placebo (5) training+ DOX$10mg.kg^{-1}$ (6) training+DOX$20mg.kg^{-1}$ . Cardiotoxicity was induced by DOX (10 and$20mg.kg^{-1}$ ). The rats in groups 4, 5 and 6 experienced treadmill running of 25 to$39min.day^{-1}$ and 15 to$17m.min^{-1}$ , 5 days/wk for 3 wk. At the end of the endurance training program, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, DOX$10mg.kg^{-1}$ and DOX$20mg.kg^{-1}$ , respectively. Result: DOX administration (10 and$20mg.kg^{-1}$ ) caused significant increase in MDA and Apelin, an insignificant increase in NO and a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment endurance exercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificant decrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOX treatment with$10mg.kg^{-1}$ and$20mg.kg^{-1}$ , a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant difference between DOX$10mg.kg^{-1}$ and DOX$20mg.kg^{-1}$ treatments in MDA levels only. Conclusion: Pretreatment exercise may improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and up-regulation of antioxidants in heart tissue. -
Elhag, Osama A.O.;Hu, Xiao-Jing;Wen-Ying, Zhang;Li, Xiong;Yuan, Yong-Ze;Deng, Ling-Feng;Liu, De-Li;Liu, Ying-Le;Hui, Geng 4031
Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies. -
Zhou, Rui;Huang, Wen-Jun;Ma, Cong;Zhou, Yan;Yao, Yu-Qin;Wang, Yu-Xi;Gou, Lan-Tu;Yi, Chen;Yang, Jin-Liang 4037
Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer. -
Balasundram, Sathesh;Mustafa, Wan Mahadzir Wan;Ip, Jolene;Adnan, Tassha Hilda;Supramaniam, Premaa 4045
Objective: The impact of ablative oral cancer surgery was studied, with particular reference to recurrence and nodal metastasis, to assess survival probability and prognostic indicators and to elucidate if ethnicity influences the survival of patients. Methods: Patients who underwent major ablative surgery of the head and neck region with neck dissection were identified and clinical records were assessed. Inclusion criteria were stage I-IV oral and oropharyngeal malignancies necessitating resection with or without radiotherapy from 2004 to 2009. All individuals had a pre-operative assessment prior to the surgery. The post operative assessment period ranged from 1 year to 5 years. Survival distributions were analyzed using Kaplan-Meier curves. Results: 87 patients (males:38%; females:62%) were included in this study, with an age range of 21-85 years. Some 78% underwent neck dissections while 63% had surgery and radiotherapy. Nodal recurrence was detected in 5.7% while 20.5% had primary site recurrence within the study period. Kaplan-Meier survival analysis revealed that the median survival time was 57 months. One year overall survival (OS) rate was 72.7% and three year overall survival rate dropped to 61.5%. On OS analysis, the log-rank test showed a significant difference of survival between Malay and Chinese patients (Bonferroni correction p=0.033). Recurrence-free survival (RFS) analysis revealed that 25% of the patients have reached the event of recurrence at 46 months. One year RFS rate was 85.2% and the three year survival rate was 76.1%. In the RFS analysis, the log-rank test showed a significant difference in the event of recurrence and nodal metastasis (p<0.001). Conclusion: Conservative neck is effective, in conjunction with postoperative radiotherapy, for control of neck metastases. Ethnicity appears to influence the survival of the patients, but a prospective trial is required to validate this. -
Waly, Mostafa I.;Ali, Amanat;Guizani, Nejib;Al-Rawahi, Amani S.;Farooq, Sardar A.;Rahman, Mohammad S. 4051
Functional foods include antioxidant nutrients which may protect against many human chronic diseases by combating reactive oxygen species (ROS) generation. The purpose of the present study was to investigate the protective effect of pomegranate peel extract (PPE) on azoxymethane (AOM)-induced colon tumors in rats as an in vivo experimental model. Forty Sprague-Dawley rats (4 weeks old) were randomly divided into 4 groups containing 10 rats per group, and were treated with either AOM, PPE, or PPE plus AOM or injected with 0.9% physiological saline solution as a control. At 8 weeks of age, the rats in the AOM and PPE plus AOM groups were injected with 15 mg AOM/kg body weight, once a week for two weeks. After the last AOM injection, the rats were continuously fed ad-libitum their specific diets for another 6 weeks. At the end of the experiment (i.e. at the age of 4 months), all rats were killed and the colon tissues were examined microscopically for lesions suspected of being preneoplastic lesions or tumors as well as for biochemical measurement of oxidative stress indices. The results revealed a lower incidence of aberrant crypt foci in the PPE plus AOM administered group as compared to the AOM group. In addition, PPE blocked the AOM-induced impairment of biochemical indicators of oxidative stress in the examined colonic tissue homogenates. The results suggest that PPE can partially inhibit the development of colonic premalignant lesions in an AOM-induced colorectal carcinogenesis model, by abrogating oxidative stress and improving the redox status of colonic cells. -
Raj, Sherin;Piang, Lam Khan;Nair, K.S.;Tiwari, V.K.;Kaur, Harneet;Singh, Bacchu 4057
Objective: To study the level of awareness and knowledge about cancers and associated risk factors among households in selected states of India. Methods: In the study 3070 households were interviewed from six states viz, West Bengal, Kerala, Madhya Pradesh, Rajasthan and Mizoram. Results: Knowledge of cancers other than those related to tobacco was very low (prostate 8%, colon 11% ) among the communities, with a poor awareness of warning signs and symptoms. The knowledge varied from state to state. It is found that the major source of information related to cancers was television (38%) followed by friends and relatives (36%). Only about 15 % of respondents had knowledge about cancer awareness camps organized in their districts but they did not have knowledge about the organizers of the camp. Findings suggested a strong need for strengthening of DCCP. Conclusion: It is important to create awareness among community through educational programs on cancer prevention, preventable cancer risk factors, benefits of early diagnosis, and availability of screening facilities. Integration of District Cancer Control activities with NRHM could be the most cost-effective strategy to prevent cancers and rural population. -
Chaiwerawattana, Arkom;Thanasitthichai, Somchai;Boonlikit, Sarawan;Apiwanich, Chanin;Worawattanakul, Suvipapan;Intakawin, Anothai;Rakiad, Supattra;Thongkham, Kanchana 4063
To determine the clinical outcome of breast cancer BI-RADS 4 lesions and seek a more effective management guideline, we conducted a retrospective study of all BI-RADS4 patients diagnosed between 2003-2008 with follow up time not less than 2 years. A total of 392 cases of BI-RADS 4 were identified and 320 could be sub-categorised as 4a, 4b and 4c. Overall malignant positive results were 7.65, 38.7 and 58.percent, respectively. In all cases assigned to the close follow up group, no malignancy was detectable (P<0.02). The results of the study suggested that BI-RADS sub-categories have benefit for cancer diagnosis and treatment decisions of clinicians and it might be possible to set up a safe follow-up guideline in selected groups of patients to minimize un-necessary tissue biopsy for breast cancer detection. -
Ueno, Toshiya;Teraoka, Naoya;Takasu, Shinji;Nakano, Katsuya;Takahashi, Mami;Yamamoto, Masafumi;Fujii, Gen;Komiya, Masami;Yanaka, Akinori;Wakabayashi, Keiji;Mutoh, Michihiro 4067
Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator activated receptor$receptor{\gamma}$ ($PPAR{\gamma}$ ) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-$A^{\mathcal{Y}}$ obesity and diabetes model mice, and tried to clarify mechanisms by which the$PPAR{\gamma}$ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF/mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-$A^{\mathcal{Y}}$ mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer. -
Al-Douh, Mohammed Hadi;Sahib, Hayder B.;Osman, Hasnah;Hamid, Shafida Abd;Salhimi, Salizawati M. 4075
Benzimidazoles 1-4 were obtained using modified synthesis methods and studied for their ability to inhibit cell proliferation of colon cancer cell HCT-116 and breast cancer cell MCF-7 using MTT assays. In the HCT-116 cell line, benzimidazole 2 was found to have an$IC_{50}$ value of$16.2{\pm}3.85{\mu}g/mL$ and benzimidazole 1 a value of$28.5{\pm}2.91{\mu}g/mL$ , while that for benzimidazole 4 was$24.08{\pm}0.31{\mu}g/mL$ . In the MCF-7 cell line, benzimidazole 4 had an$IC_{50}$ value of$8.86{\pm}1.10{\mu}g/mL$ , benzimidazole 2 a value of$30.29{\pm}6.39{\mu}g/mL$ , and benzimidazole 1 a value of$31.2{\pm}4.49{\mu}g/mL$ . Benzimidazole 3 exerted no cytotoxity in either of the cell lines, with$IC_{50}$ values$ > 50{\mu}g/mL$ . The results suggest that benzimidazoles derivatives may have chemotherapeutic potential for treatment of both colon and breast cancers. -
Saibul, Nurfaizah;Shariff, Zalilah Mohd;Rahmat, Asmah;Sulaiman, Suhaina;Yaw, Yong Heng 4081
Complementary and alternative medicine (CAM) use is prevalent among individuals with cancer, especially breast cancer survivors. This study was conducted among 394 breast cancer survivors in selected regions of Peninsular Malaysia to identify the pattern and factors associated with CAM use. About 51% of the respondents reported CAM use as complementary treatment. Vitamins (47.2%), spiritual activities (33.2%) and other dietary supplements (30.7%) were the most commonly used CAM therapies. Common reasons for CAM use were to increase the body's ability to perform daily activities (70.9%), enhance immune function (58.3%) and improve emotional well-being (31.7%). Users obtained CAM information mainly from friends and family members (62.5%), physicians (25.0%) and mass media (13.9%). Ethnicity and years of education were significantly associated with CAM use. Although no adverse effects of CAM were reported, breast cancer survivors should discuss their CAM use with health professionals to prevent potential adverse effects of these therapies. -
Gao, Chang-Ming;Ding, Jian-Hua;Li, Su-Ping;Liu, Yan-Ting;Cao, Hai-Xia;Wu, Jian-Zhong;Tajima, Kazuo 4087
To evaluate the relationship between polymorphisms (28 bp repeated sequences in 5'-UTR and 6-bp ins/del in 3'-UTR) in then thymidylate synthetase gene (TS) and risk of colorectal, colon and rectal cancers, we conducted a case-control study with 315 cases of colorectal cancer and 439 population-based controls in Jiangsu province, China. TS genotypes were identified using PCR.RFLP (restriction fragment length polymorphism) methods. Odds ratios (ORs) were estimated with an unconditional logistic regression model. We found that the distributions of 5'-UTR genotypes in TS were significantly different between controls and male colon cases (${\chi}^2$ =8.25, P = 0.016). Compared with 3R/3R genotype, individuals with the 2R allele were at an increased risk of colon cancer (age-, BMI-, smoking- and alcohol drinking-adjusted OR=1.98, 95%CI: 1.11-3.53) among men. In ccontrast, the 6-bp ins/del polymorphism at the TS 3'- UTR did not influence risk of the colorectal, colon and rectal cancers. When combined genotypes for both TS 5'-UTR and 3'-UTR polymorphisms were evaluated, individuals with the 5'-UTR 2R allele had a OR of 3.61 (95%CI: 1.38-9.49) for colon cancer among men with the 3'-UTR .6bp/-6bp genotype. These results show that the polymorphism of the 28 bp repeated sequences in TS 5'-UTR could influence susceptibility to colon cancer and that there was a coordinated effect between TS 3'-UTR and 5'-UTR polymorphisms in increasing risk of colon cancer among Chinese men. -
Zhou, Kai-Yu;Jin, Hang-Huang;Bai, Zhi-Qiang;Liu, Chi-Bo 4093
Objective: To determine whether pituitary adenomas can be diagnosed by identifying protein biomarkers in the serum. Methods: We compared serum proteins from 65 pituitary adenoma patients and 90 healthy donors using proteomic fingerprint technology combining magnetic beads with matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Results: A total of 42 M/Z peaks were identified as related to pituitary adenoma (P<0.01). A diagnostic model established based on three biomarkers (3382.0, 4601.9, 9191.2) showed that the sensitivity of diagnosing pituitary adenoma was 90.0% and the specificity was 88.3%. The model was further tested by blind analysis showing that the sensitivity was 88.0% and the specificity was 83.3%. Conclusions: These results suggest that proteomic fingerprint technology can be used to identify pituitary adenoma biomarkers and the model based on three biomarkers (3382.0, 4601.9, 9191.2) provides a powerful and reliable method for diagnosing pituitary adenoma. -
Long, Xiang-Ju;Lin, Shan;Sun, Ya-Nan;Zheng, Zhen-Feng 4097
Background/Aims: Diabetes mellitus (DM) is widely considered to be associated with risk of cancer, but studies investigating the association between DM and prostate cancer in Asian countries have reported inconsistent findings. We examined this association by conducting a detailed meta-analysis of studies published on the subject. Methods: Cohort or case-control studies were identified by searching Pubmed, Embase and Wanfang databases through May 30, 2012. Pooled relative risk (RR) with its corresponding 95% confidence interval (95% CI) were calculated using the random-effects model. Subgroup analyses were performed by the study type. Results: Finally, we identified 7 studies (four cohort studies and three case-control studies) with a total of 1,751,274 subjects from Asians. DM was associated with an increased risk of prostate cancer in Asians (unadjusted RR= 2.82, 95% CI 1.73.4.58, P < 0.001; adjusted RR= 1.31, 95% CI 1.12.1.54, P = 0.001). Subgroup analyses by study design further confirmed an obvious association. Conclusion: Findings from this meta-analysis strongly support that diabetes is associated with an increased risk of prostate cancer in Asians. -
Kucuktulu, Eda;Yavuz, Aydin Ali;Cobanoglu, Umit;Yenilmez, Engin;Eminagaoglu, Selcuk;Karahan, Caner;Topbas, Murat;Kucuktulu, Uzer 4101
Purpose: The degree of radiation injury to kidneys which are located within the limits of radiotherapy area is determined by the volume and the dose of radiation to which the organ is exposed. When the tolerance dose of the kidney is exceeded after a latent period of 6 months acute nephritis develops and after 18 months chronic nephritis ensues. Melatonin is known to prevent the oxidative injury of toxins and radiotherapy with its free radical scavenging capacity. Methods and Materials: In this study 8 weeks old 24 Sprague -Dawley rats were allocated into 4 groups: Control group; Radiotherapy group (20 Gy bilaterally in 5 fractions); Melatonin group (10 mg/kg intraperitoneally), and Melatonin+radiotherapy group (20 Gy Radiotherapy in 5 fractions+ melatonin 10 mg/kg intraperitoneally). After a follow-up period of 6 months BUN was determined in all groups. After rats were euthanized the kidneys were removed for histopathological examination under both light and electron microscopes. Results: After 6 months follow-up, both at light and electron microscopy levels, the rats in radiotherapy+melatonin group were significantly protected against the radiation injury comparing to radiotherapy group (p<0.05). Conclusion: It was shown in this experimental model that melatonin has protective effects against radiation injury to kidneys. -
Pandurangan, Ashok Kumar;Periasamy, Srinivasan;Anandasadagopan, Suresh Kumar;Ganapasam, Sudhandiran;Srinivasalu, Shyamala Devi Chennam 4107
4-Nitroquinoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, has been found to induce lipid peroxidation in vivo and in vitro. Green tea contains a high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GTP) might be expected play a protective role against 4-NQO induced lipid peroxidation and bone marrow toxicity. In the present study, a dose of 200 mg of GTP/kg b.wt/day was given orally for a week, simultaneously animals received 0.2 ml of 0.5% 4-NQO in propylene glycol (5 mg/ml) injected intramuscularly for three times/week. Oxidants and antioxidants such as malendialdehyde (MDA) and thiols, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were significantly decreased in 4-NQO induced animals except MDA, and these parameters were brought back to near normalcy on treatment with GTP. The results suggest that GTP treatment offers significant protection against 4-NQO induced lipid peroxidation and bone marrow toxicity and might be a promising potential candidate for prevention of mutations leading to cancer. -
Izadi, Pantea;Noruzinia, Mehrdad;Fereidooni, Foruzandeh;Nateghi, Mohammad Reza 4113
Breast cancer is a prevalent heterogeneous malignant disease. Gene expression profiling by DNA microarray can classify breast tumors into five different molecular subtypes: luminal A, luminal B, HER-2, basal and normal-like which have differing prognosis. Recently it has been shown that immunohistochemistry (IHC) markers including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2), can divide tumors to main subtypes: luminal A (ER+; PR+/-; HER-2-), luminal B (ER+;PR+/-; HER-2+), basal-like (ER-;PR-;HER2-) and Her2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype have been characterized by poor prognosis and reduced overall survival. Due to the importance of the ER signaling pathway in mammary cell proliferation; it appears that epigenetic changes in the$ER{\alpha}$ gene as a central component of this pathway, may contribute to prognostic prediction. Thus this study aimed to clarify the correlation of different IHC-based subtypes of breast tumors with$ER{\alpha}$ methylation in Iranian breast cancer patients. For this purpose one hundred fresh breast tumors obtained by surgical resection underwent DNA extraction for assessment of their ER methylation status by methylation specific PCR (MSP). These tumors were classified into main subtypes according to IHC markers and data were collected on pathological features of the patients.$ER{\alpha}$ methylation was found in 25 of 28 (89.3%) basal tumors, 21 of 24 (87.5%) Her2+ tumors, 18 of 34 (52.9%) luminal A tumors and 7 of 14 (50%) luminal B tumors. A strong correlation was found between$ER{\alpha}$ methylation and poor prognosis tumor subtypes (basal and Her2+) in patients (P<0.001). Our findings show that$ER{\alpha}$ methylation is correlated with poor prognosis subtypes of breast tumors in Iranian patients and may play an important role in pathogenesis of the more aggressive breast tumors. -
Duman, Berna Bozkurt;Afsar, Cigdem Usul;Gunaldi, Meral;Sahin, Berksoy;Kara, I. Oguz;Erkisi, Melek;Ercolak, Vehbi 4119
Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression. -
Duman, Berna Bozkurt;Gunaldi, Meral;Ercolak, Vehbi;Afsar, Cigdem Usul;Sahin, Berksoy;Erkisi, I. Melek Koksal;Kara, Oguz;Paydas, Semra;Gonlusen, Gulfiliz;Sertdemir, Yasar 4125
Background: Soft tissue sarcomas (STS) must be managed with a team involving pathologists, radiologists, surgeons, radiation therapists and medical oncologists. Treatment modalities and demographic charasteristics of Turkish STS were analysed in the current study. Material-Methods: Primary adult STS followed between 1999-2010 in Cukurova University Medical Faculty Department of Medical Oncology were analzied retrospectively Results: Of the total of 498 patients, 238 were male and 260 female. The most seen adult sarcomas were leomyosarcoma (23%). Localization of disease was upper extremity (8.8%), lower extremity (24.7%), head-neck 8.2%, thoracic 8%, retroperitoneal 5.6%, uterine 12.4%, abdominal 10%, pelvic region 3.6 and other regions 10%. Some 13.1% were early stage, 10.2% locally advanced, 8.2% metastatic and 12.2% recurrent disease. Patients were treated with neoadjuvant/adjuvant (12%) or palliative chemotherapy (7.2%) and 11.4% patients did not receive chemotherapy. Surgery was performed as radical or conservative. The most preferred regimen was MAID combination chemotherapy in the rate of 17.6%. The most common metastatic site was lung (18.1%). The overall survival was 45 months (95%CI 30-59), 36 months in men and 55 months in women, with no statistically significant difference (p=0.5). The survival rates were not different between the group of adjuvant and palliative chemotherapy (respectively 28 versus 18 months) (p=0.06), but radical surgery at 37 months was better than 22 months for conservative surgery (p=0.0001). No differences were evident for localization (p=0.152). Locally advanced group had higher overall survival rates (72 months) than other stages (p=0.0001). Conclusion: STS can be treated successfully with surgery, chemotherapy and radiotherapy. The survival rates of Turkish people were higher in locally advanced group; these results show the importance of multimodality treatment approach and radical surgery. -
Urun, Yuksel;Utkan, Gungor;Yalcin, Suayib;CosKun, Hasan Senol;Kocer, Murat;Ozdemir, Nuriye Yildirim;Kaplan, Mehmet Ali;Arslan, Ulku Yalcintas;Ozdemir, Feyyaz;Oztuna, Derya;Akbulut, Hakan;Icli, Fikri 4129
Background: An association between the ABO blood group and the risk of certain malignancies, including pancreatic and gastric cancer, has been reported previously. However, it is unclear whether this association is valid for gastrointestinal stromal tumors (GIST). In this study, ABO blood groups and the Rh factor were investigated in a series of GIST cases. Material and Methods: In 162 patients with GIST, blood group and Rh factor were examined and compared with a control group of 3,022,883 healthy volunteer blood donors of the Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with tumor size, mitotic activity, and age were also evaluated. Results: Overall, the ABO blood group and Rh factor distributions of the 162 patients with GIST were similar to those of the general population. There were no significant differences between both ABO blood types and Rh factor in terms of tumor size, mitotic activity, and age. Conclusion: This is the first study reported on this issue. In our study, we didn't find any relationship between GIST and ABO blood group and Rh factor. However further studies with larger number of patients are needed to establish the role of blood groups in this population. -
Larizadeh, Mohammad Hasan;Shabani, Mohammad 4133
Aim: To report the results of radiotherapy with or without chemotherapy in the patients with oral cancer. Methods: Over the 2003-2009 periods, a total number of 69 patients with squamous cell carcinoma of the oral cavity that refused surgery or had unresectable tumor were enrolled in this study. A total dose of 60 to 70 Gy (2 Gy per day) was given to the primary tumor and clinically positive nodes. In the patients with locoregionally advanced disease (57 patients with$T_3$ ,$T_4$ lesions and/ or$N^+$ ) induction chemotherapy following by concomitant chemoradiation was used. Induction chemotherapy consisted of 3 cycles of Cisplatin and 5-Flourouracil with or without Docetaxel. Weekly cisplatin was used in concomitant protocol. Kaplan-Meier method was used to calculate overall survival. Log-rank test and Cox regression model were used for comparison purposes. Results: Median follow-up was 32 months. The mean age of the patients was 59.2 years. The overall response rate after induction chemotherapy was 68.4%. Actuarial overall survival rates after 2 and 3 years were 38% and 26%, respectively. Clinical stage emerged as the only independent predictor of survival. Conclusion: Outcome of the patients with oral cancer is poor. Presenting with an advanced stage lesion contributed to this result. The role of chemotherapy in advanced cases remains to be defined. -
Jung, Hwi-Dong;Nam, Woong;Cha, In-Ho;Kim, Hyung Jun 4137
The authors present five cases of combined oral mucosa-mandible defects reconstructed with the vascularized internal oblique-iliac crest myoosseous free flap. This technique has many advantages compared to other conventional methods such as the radial flap, scapula flap, and fibula flap. Vascularized iliac crest flaps provide sufficient high-quality bone suitable for reconstructing segmental madibular defects. Although fibular flaps allow longer donor bone tissue to be harvested, the iliac crest can provide an esthetic shape for mandibular body reconstruction and also provides sufficient bone height for dental implants. Conventional vascularized iliac crest myoosseous flaps have excessive soft tissue bulk for reconstruction of intraoral soft tissue defects. The modification discussed in the present article can reduce soft tissue volume, resulting in better functional reconstruction of the oral mucosa. Another advantage is that complete replacement of the oral mucosa is observed in as early as one month post-operation. The final mucosal texture is much better than that obtained with other skin paddle flaps, which is especially beneficial for the placement of dental implant prostheses. Donor site morbidity looks to be similar to, if not less than that observed for other modalities in terms of function and esthetics. For combined oral mucosa-mandible defects, the vascularized internal oblique-iliac crest myoosseous free flap shows good results with respect to hard and soft tissue reconstruction. -
In this study, the aim was to examine the effects of caring burdens of family caregivers of cancer patients on their quality of life in the east of Turkey. Data were collected at the Chemotherapy unit of Yakutiye Research Hospital of Ataturk University. Participants were 18 years old and older. The sample included 190 family caregivers who were living in the same flats with the patients during caregiving. Data were collected using a questionnaire that included socio-demographic questions for family caregivers and the Burden Interview, and the Caregiver Quality of Life Index-Cancer (CQOLC) Scale. SPSS version 14.0 was used to analyse the data. Descriptive statistics were computed for demographic variables of family caregivers. Pearson correlation analysis was used to analyze the relationship between the care burden and quality of life, linear logistic regression analysis was applied to determine the effect care burdens have on the quality of life, and logistic regression analysis was employed to determine the effect descriptive characteristics and care-related properties have on the quality of life. The score mean of the burden interview of caregivers was
$36.6{\pm}11.2$ ; and their score mean of CQOLC was$81.4{\pm}17.3$ . This study concluded that there was a negative relationship between caring burdens and the quality of life (p<0.001); descriptive characteristics, caring-related properties, and caring burden variables were all significant predictors of the quality of life. It is recommended that caregivers are given support by being offered training about providing care. -
Yu, Jing;Chen, Kui-Sheng;Li, Ya-Nan;Yang, Juan;Zhao, Lu 4147
The current study was conducted to explore the inhibitory effects of a small interfering RNA (siRNA) on 3-phosphoinositide-dependent protein kinase 1 (PDK1) expression in esophageal cancer 9706 (EC9706) cells and the influence on their biological behavior. After transfection of a synthesized PDK1 siRNA, PDK1 mRNA and protein expression and the phosphorylation level of the downstream Akt protein were assessed using RT-PCR and Western blot analysis. Proliferation, apoptosis, cell invasion and in vivo tumor formation capacity were also investigated using MTT, flow cytometry, Transwell invasion trials, and nude mouse tumor transplantion, respectively. PDK1 siRNA effectively suppressed PDK1 mRNA and protein expression, and down-regulated the phosphorylation level of the Akt protein in the EC9706 cells (P < 0.05). It also inhibited cell proliferation and invasion, and promoted apoptosis; such effects were particularly obvious at 48 h and 72 h after transfection (P < 0.05). Growth of transplanted tumors was inhibited in nude mice, with decreased PDK1 expression in tumor tissues. PDK1 may be closely correlated with proliferation, apoptosis and invasion of esophageal cancer cells and thus may serve as an effective target for gene therapy. -
Wang, Mei;Gu, Jun;Wang, Hai-Xing;Wu, Mei-Hong;Li, Yong-Mei;Wang, Ya-Jie 4153
Purpose: To investigate the efficacy and toxicity of a combination of gemcitabine with nedaplatin (GN) or cisplatin (GC) for patients with unresectable or recurrent esophagus squamous cell carcinoma. Methods: Gemcitabine was administered at 1 g/m2 intravenously on days 1 and 8; and nedaplatin or cisplatin were administered at 80 mg/m2 intravenously on day 1. We analyzed the response rate, overall survival time, progression-free survival time, and toxicity in 21 patients treated with GN and 27 patients treated with GC. Results: In patients treated with gemcitabine plus nedaplatin, the ORR was 47.6%, the median progression-free survival time was 4.1 months, and the median survival time was 9.3 months. In patients treated with gemcitabine plus cisplatin, the ORR was 48.2%, the median progression-free survival time was 3.9 months, and the median survival time was 9.1 months, respectively. There were no statistically significant differences in ORR, PFS and OS between the two groups. In both, the most commonly observed toxicities were thrombocytopenia and fatigue. Nausea and vomiting was more frequent in the GC group than in the GN group. Conclusion: Gemcitabine based chemotherapy was effective and tolerable for patients with unresectable or recurrent esophagus squamous cell carcinoma refractory to first line chemotherapy. -
Guo, Wei;Li, Guo-Jun;Xu, Hong-Bo;Xie, Jie-Shi;Shi, Tai-Ping;Zhang, Sheng-Zhong;Chen, Xiao-Hong;Huang, Zhi-Gang 4157
Background: Novel prognostic biomarkers or therapeutic molecular targets for laryngeal squamous cell carcinoma (LSCC) are an urgent priority. We here sought to identify multiple novel LSCC-associated genes. Methods: Using high-density microarray expression profiling, we identified multiple genes that were significantly altered between human LSCCs and paired normal tissues. Potential oncogenic functions of one such gene, DCUN1D5, were further characterized in vitro. Results: Our results demonstrated that DCUN1D5 was highly expressed in LSCCs. Overexpression of DCUN1D5 in vitro resulted in 2.7-fold increased cellular migration, 67.5% increased invasive capacity, and 2.6-fold increased proliferation. Endogenous DCUN1D5 expression was decreased in a time-dependent manner after genotoxic stress, and silencing of DCUN1D5 by siRNA decreased the number of cells in the S phase by 10.2% and increased apoptosis by 11.7%. Conclusion: Our data suggest that DCUN1D5 in vitro might have vital roles in DNA damage response, but further studies are warranted to assess its significance in vivo. -
Ma, Jin-Bo;Wei, Lin;Chen, Er-Cheng;Qin, Guang;Song, Yi-Peng;Chen, Xiang-Ming;Hao, Chuan-Guo 4163
Aims: To prospectively assess the efficacy and safety of moderately hypofractionated conformal radiotherapy in patients with thoracic esophageal cancer. Methods and Materials: From Sept. 2002 to Oct, 2005, 150 eligible patients with T2-4N0-1M0 stage thoracic esophageal squamous cell cancers were enrolled to receive either conventional fractionated radiation (CFR) or moderately hypofractionated radiation (MHR) with a three-dimensional conformal radiation technique. Of the total, 74 received moderately hypofractionated radiation with total dose of 54-60Gy/18-20fractions for 3.5-4 weeks in the MHR arm, and 76 received conventional radiation with total dose of 60Gy/30 fractions for 6 weeks in the CFR arm. Concurrent chemotherapy comprised of paclitaxel and cisplatin. Safety was evaluated, and local control and overall survival rates were calculated. Results: Statistically significant differences between the CFR versus MHR arms were observed in local/regional failure rate (47.3% v 27.0%, P=0.034) and the percentage of patients with persistent local disease (26.3% v 10.8%, P=0.012). But 3 and 5-year overall survival rates (43.2%, 38.8% v 38.2%, 28.0%, respectively) were not different between the two arms (P=0.268). There were no significant differences in the incidences of grade 3 or higher acute toxicities (66.3% v 50.0%) and late complications rates (27.0% v 22.4%) between the MHR and CFR arms. Conclusions: Moderately hypofractionated, three-dimensional radiation treatment could improve the local control rate of esophageal cancer and potentially increase patients' survival. -
Isaac, Rita;Finkel, Madelon;Olver, Ian;Annie, I.K.;Prashanth, H.R.;Subhashini, J.;Viswanathan, P.N.;Trevena, Lyndal J. 4169
Background: The majority of women in rural India have poor or no access to cervical cancer screening services, although one.quarter of all cervical cancers in the world occur there. Several large trials have proven the efficacy of low-tech cervical cancer screening methods in the Indian context but none have documented the necessary components and processes of implementing this evidence in a low-resource setting. Methods: This paper discusses a feasible model of implementation of cervical cancer screening programme in low-resource settings developed through a pilot research project carried out in rural Tamilnadu, India. The programme used visual inspection of cervix after acetic acid application (VIA) as a screening tool, nurses in the primary care centres as the primary screeners and peer educators within Self-Help Women groups to raise community awareness. Results: The uptake of screening was initially low despite the access to a screening programme. However, the programme witnessed an incremental increase in the number of women accessing screening with increasing community awareness. Conclusions: The investigators recommend 4 key components to programme implementation in low-resource setting: 1) Evidence-based, cost-effective test and treatment available within the reach of the community; 2) Appropriate referral pathways; 3) Skilled health workers and necessary equipment; and 4) Optimisation of health literacy, beliefs, attitudes of the community. -
Background: Adolescent tobacco use is a major public health problem. However, there is little information about the impact of tobacco advertising and availability near schools on adolescent tobacco use in India. Methods: The various tobacco products and brands available in outlets within 100 meters of two high schools in an Indian town were identified. A stratified random sample of 172 participants from these two schools completed a questionnaire on tobacco use and socioeconomic status. Results: Eighteen outlets selling tobacco products were identified. In the two schools the current use of smoked and smokeless tobacco was 9.1% and 17.4% respectively. School location and low socio-economic status of adolescents were associated with tobacco awareness of advertisements (p=0.001) and the receipt of a free sample (p= 0.032). Advertisements on billboards, posters and the receipt of a free tobacco sample were significant factors (p=0.031, p=0.016, p=0.017 respectively) in current tobacco use. Conclusion: In this study a significant proportion of adolescents used tobacco. Tobacco-promotion activities (advertising, the receipt of a free sample), school location and economic status were found to be associated with adolescent tobacco initiation. The local environment should be included in the prevention of adolescent tobacco initiation.
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Wani, Majid;Afroze, Dil;Makhdoomi, Muzamil;Hamid, Iqra;Wani, Bilal;Bhat, Gulzar;Wani, Rauf;Wani, Khursheed 4177
Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in the capacity to repair mismatches in the genome, is an important factor in the development of gastric cancer (GC), for example. Epigenetic changes, including aberrant methylation of 5/CpG islands in the promoter regions of mismatch repair (MMR) genes like hMLH1, have been implicated in the development of various types of GC. In the present study we evaluated the role of hMLH1 promoter hypermethylation in Kashmiri GC patients and controls, and assessed correlations with various dietary and lifestyle factors. The study included 70 GC patients (56 males and 14 females; age ($mean{\pm}S.D$ )$50{\pm}11.4$ years). Distinction between methylated and unmethylated was achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due to promoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC cases than in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001).We also observed a statistically significant association between methylated hMLH1 gene promoter and smoking, consumption of sundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylation is strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in the Kashmir valley. -
Khanra, Kalyani;Panda, Kakali;Mitra, A.K.;Sarkar, Ranu;Bhattacharya, Chandan;Bhattacharyya, Nandan 4183
Background: Ovarian cancer is the number one killer among all the gynecological cancers. We undertook association study to identify potential alterations in the genomic DNA of a DNA repair gene, DNA polymerase beta ($pol{\beta}$ ), involved in base excision repair (BER), in ovarian carcinomas of patients from Haldia, India. Mutations, splice variants have been reported earlier in different tumors other than ovarian tumors. Aim: In this study we explored the possibility of association of any mutation of$pol{\beta}$ (Exon 8) with prognosis in 152 ovarian cancer samples. Results: Alteration in the exon 8 region (Exon 8:468,$A{\rightarrow}C$ ; 15.1%) was noted among fifty seven polymorphism positive samples. Alteration in the intervening sequence 8 (IVS8, -25,$A{\rightarrow}C$ ; 3.9%) was also noted. All alterations are heterozygous in nature. Conclusions: We found no significant association among the samples from serous type, stage IV, and the$pol{\beta}$ mutations ($P{\leq}0.01$ ). Only a slight tendency of association was evident between IVS8, -25, A to C; and stage III. Further analysis with a larger number of samples is needed. -
Uchino, Junji;Hirano, Ryosuke;Tashiro, Naoki;Yoshida, Yuji;Ushijima, Shinichiro;Matsumoto, Takemasa;Ohta, Keiichi;Nakatomi, Keita;Takayama, Koichi;Fujita, Masaki;Nakanishi, Yoichi;Watanabe, Kentaro 4187
Aims and Background: To evaluate the efficacy of a combination of aprepitant and conventional antiemetic therapy in patients with advanced or recurrent lung cancer receiving moderately emetogenic chemotherapy (MEC). Methods: Patients with advanced or recurrent lung cancer who were treated with MEC regimens at the Department of Respiratory Medicine, Fukuoka University Hospital, were included and classified into the following groups: control group (treatment: 5-HT3 receptor antagonists + dexamethasone) and aprepitant group (treatment: 5-HT3 receptor antagonists + dexamethasone + aprepitant). The presence or absence of chemotherapy-induced nausea and vomiting (CINV) was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0; patients with grade 1 or above were considered positive for CINV. Food intake per day, completion of planned chemotherapy, and progression-free survival (PFS) achieved by chemotherapy were investigated. Results: The complete suppression rate of nausea in the aprepitant group was significantly higher than that in the control group (p = 0.0043). Throughout the study, the food intake in the aprepitant group was greater than that in the control group, with the rate being significantly higher, in particular, on day 5 (p = 0.003). The completion rate of planned chemotherapy was also higher in the aprepitant group (p = 0.042). PFS did not differ significantly, but tended to be improved in the aprepitant group. Conclusions: The aprepitant group showed significantly higher complete suppression of nausea, food intake on day 5, and completion of planned chemotherapy than the control group. -
Identifying Women's Knowledge about Risk Factors of Breast Cancer and Reasons for Having MammographyGuvenc, Inanc;Guvenc, Gulten;Tastan, Sevinc;Akyuz, Aygul 4191
The aim of this study was to identify breast cancer risk factors and reasons for having mammography of the women who applied for mammography, as well as to determine their level of knowledge about risk factors and level of risk perception, and anxiety concerning breast cancer. This cross-sectional descriptive study was conducted from June 15, 2010 through September 10, 2010, in a university hospital in Ankara, Turkey. A questionnaire prepared by the researchers was used to collect the data. The mean age of the women was$52.1{\pm}9.98$ years. Sixteen percent of the women had a family history of breast cancer. The majority of participants had mammograms (75.8%) before and had gained knowledge about breast cancer and its screening (73.7%). The leading source of information about breast cancer was physicians (46.2%). Physician recommendations, having breast-related complaints, and family history of breast cancer were important reasons to obtain mammography. The mean knowledge score about risk factors of breast cancer was$4.15{\pm}2.73$ and the mean anxiety score was$1.65{\pm}1.61$ . It was found that some socio-demographic and obstetrical characteristics of women, their family history, and risk perceptions about breast cancer affect their knowledge and anxiety scores about breast cancer. In conclusion, the present study identified a number of factors affecting mammography participation for women. The results of this study can be helpful in promoting screening for breast cancer. -
Arab, Maliheh;Yaseri, Mehdi;Ashrafganjoi, Tahereh;Maktabi, Maryam;Noghabaee, Giti;Sheibani, Kourosh 4199
Objective: The aim of our study is to compare an ovarian malignancy prediction model based on age and four sonographic findings (OMPS1) with a new model called OMPS2 which differs just by adding serum CA125 measurement to (OMPS1). Methods: In a cross sectional comparative study OMPS1 was validated in 830 operated ovarian masses within a 3 years period (2006-2009). Logistic regression analysis was used to construct OMPS2 based on OMPS1 adding serum CA125 findings. The area under the curve for two models was compared in 411 patients. Results: OMPS2 was calculated as follows: OMPS1 + 1.444 (if serum CA125= 36-200) or 3.842 (if serum CA125 is more than 200). AUC of OMPS2 was increased to 84.3% (CI 95% 78.1- 89.8) in comparison to OMPS1 with AUC of 78.1% (CI 95% 71.8-84.5). Conclusion: Our second model is more accurate in prediction of ovarian malignancy, compared with our first model. -
Sritara, Chanika;Charoenphun, Putthiporn;Ponglikitmongkol, Mathurose;Musikarat, Suchawadee;Utamakul, Chirawat;Chokesuwattanasakul, Payap;Thakkinstian, Ammarin 4203
Aim: This study assessed if onfFN mRNA in the peripheral blood of patients with DTC can identify individuals with metastatic disease. Methods: Comparison of onfFN mRNA was made among 3 groups: disease-free, lymph node metastasis, and distant metastasis using real-time RT-PCR on 5 ml blood samples from each DTC patient. Results: Fifty-one patients were included: 30 (59%) were disease-free; 7 (13.7%) had lymph node metastasis; and 14 (27.5%) had distant metastasis. OnfFN mRNA levels in the 3 groups were significantly different (P=0.001) but with a large overlap and the expression being highest in the disease-free group. Subgroup analysis of the metastatic groups did not show any effect of age, cell type, and serum TSH, Tg, and antiTg on onfFN mRNA. The within-run and between-run root mean square coefficients of variations were <2%. Conclusion: OnfFN mRNA in patients with DTC cannot identify those with metastatic disease. -
Wei, Kuang-Rong;Chen, Wan-Qing;Zhang, Si-Wei;Liang, Zhi-Heng;Zheng, Rong-Shou;Ou, Zhi-Xiong 4209
The current situation of cancer registration in China was systematically reviewed. So far, cancer registration in China has been making a great progress in the following aspects: the number of cancer registries and covered population have increased dramatically; a registration network has been established and completed gradually; regulations and rules improved remarkably; more attention is being paid by every level of government; a lot of registration software has been created and financial support ensured. However, we are still facing some problems and challenges, such as no stable groups of registrars, shortage of training opportunities, poor data quality, insufficient utilization and lack of multidisciplinary mechanisms, so that the cancer registration system still needs to be enhanced and improved. Along with the development of economy, science and information technology, methods and patterns of cancer registration is changing. It is to be expected that cancer registration will be automatic, nationwide and integrated with community healthcare in the near future.