• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2185-2190
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• 2013

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.1015-1018
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• 2012

Objective: To improve the diagnosis of primary gallbladder carcinoma (GBC) with/without hepatic metastases by analyzing our experience of different GBC treatment in our patients. Methods: A retrospective study was carried out to analyze the clinical data of the 139 patients with GBC who underwent hepatic resection in our unit from January 2003 to December 2007. Patients were divided into two groups according to whether they demonstrated hepatic invasion. Tumor presentation, surgical modes, and prognosis of each patient were retrospectively reviewed. Kaplan-Meier curves and log-rank tests were employed to compare the survival rates of those patients undergoing different surgical procedures. Results: Of the 139 patients, 46 were men and 93 were women with the male to female ratio of 1:2.0. Their ages were ranged from 35 to 86 years with a mean age of $62.8{\pm}10.4$ years. There were 73 patients complicated with hepatic invasion (group A), and no hepatic invasion occurred in the other 66 patients (group B). Compared with the group B, the patients with hepatic invasion suffered lower differentiation of tumor (p=0.000), more advanced Nevin staging (p=0.008) and poorer prognosis (p=0.013). Radical resection were more frequently performed in group B (75.76%) than in group A (45.20%) with better outcomes (p=0.000). Conclusion: GBC patients complicated with hepatic invasion had poorer prognosis than those without invasion in long-term follow-ups. Radical resection might result in a satisfied prognosis in patients without hepatic invasion, but appears less favorable than palliative resection in those who were complicated with hepatic invasion.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.391-395
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• 2014

Background: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materials and Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. Results: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. Conclusions: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4843-4845
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• 2012

Cancer is now a worldwide problem. Although we have obtained a deeper understanding of the disease with the help of the science and technology, we still cannot reach the essence of cancer. Based on the former theory of carcinogenic and researches, we submit a new theory called "Spatial -Temporal Biphasic Carcinogenesis" to explain its development from the viewpoints of time and space.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1985-1988
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• 2013

Aim: To study any correlation of LKB1 expression with prognosis in hepatocellular carcinoma (HCC) cases. Methods: A total of 70 HCC patients and 20 primary intrahepatic stone patients in the first affiliated hospital of Wenzhou Medical College were enrolled in this study. LKB1 expression was detected by immunohistochemistry. Patients were followed-up and prognostic factors were evaluated. Result: LKB1 expression was decreased in the HCC samples. Loss of LKB1 expression in HCC was significantly related to histologic grade (P=0.010), vascular invasion (P=0.025) and TMN stage (P=0.011). Patients showing negative LKB1 expression had a significantly shorter disease-free and overall survival than those with positive expression (P = 0.001, P=0.000, respectively). Multivariate Cox regression analysis indicated that LKB1 expression level was an independent factor of survival (P = 0.033). Conclusion: HCC patients with decreased expression LKB1 have a poor prognosis. The loss of LKB1 expression is correlated with a lower survival rate.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5587-5587
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• 2015

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3509-3514
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• 2013

The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson ${\chi}^2$ test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2503-2509
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• 2012

Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3601-3604
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• 2012

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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2841-2846
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• 2012

Background: Many studies have investigated the association between the MDM2 promoter SNP309 T/G polymorphism and liver cancer risk, but inconsistencies make drawwing definitive conclusions difficult. Methods: We therefore searched main databases for articles relating MDM2 SNP309 T/G polymorphism to risk of liver cancer in humans and estimated summary odds ratio (OR) with 95% confidence intervals (95% CI) to assess the possible association in a meta-analysis. Results: The main analysis revealed no significant heterogeneity, and the pooled ORs of fixed-effects were all significant (for G versus T, OR = 1.59, 95% CI 1.42-1.78; for GG versus TT, OR = 2.45, 95% CI 1.93-3.12; for GT versus TT, OR = 1.70, 95% CI 1.38-2.09; for GG versus GT, OR = 1.49, 95% CI 1.24-1.79; for GG and GT versus TT, OR = 1.95, 95% CI 1.61-2.38; for GG versus TT and GT, OR = 1.73, 95% CI 1.46-2.07). Subgroup analyses by ethnicity and sensitivity analyses both showed associations to remain significant. Conclusion: The present meta-analysis of available data showed a significant association between the MDM2 SNP309 T/G polymorphism and liver cancer risk, the MDM2 SNP309 G allele contributing to increased risk in both Asians and Caucasians in a graded, dose-dependent fashion.