Potential Therapeutic Targets for the Primary Gallbladder Carcinoma: Estrogen Receptors

Zhang, Ling-Qiang,Zhang, Xiu-De,Xu, Jia,Wan, Yong,Qu, Kai,Zhang, Jing-Yao,Wang, Zhi-Xin,Wei, Ji-Chao,Meng, Fan-Di,Tai, Ming-Hui,Zhou, Lei,Liu, Chang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

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.

Possible Epithelial Ovarian Cancer Association with HPV18 or HPV33 Infection

Zhang, Pei-Pei,Zhou, Lei,Cao, Jia-Shi,Li, Yi-Ping,Zeng, Zhi,Sun, Ni,Shen, Li,Zhu, Hao-Yue,Ruan, Yang,Zha, Wen-Ting,Wang, Xin-Yu,Zhang, Ke-Qiang,Zhang, Ran Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

The present study was conducted to investigate the prevalence of HPV infection in epithelial ovarian cancer (EOC) in Hunan province. DNA samples were collected from paraffin embedded ovarian tissue from 322 patients with EOC, 99 with ovarian benign tumors and 199 normal persons. The polymerase chain reaction and direct sequencing were used to identify the HPV types in the samples. The relationship between the infection of human papillomavirus (HPV) and the epithelial ovarian carcinoma (EOC) was investigated combined with clinical data. The prevalence of HPV18 and HPV33 in EOC group and benign group was higher than in the normal group. HPV18 and HPV33 may play a role in the development of both EOC and ovarian benign tumor and may participate in the development of EOC with traditional risk factors, family history and abortion, possibly exerting synergistic effects.

Metastasis associated genomic aberrations in stage II rectal cancer

Hong Zhao,Zhi-Zhou Shi,Rui Jiang,Dong-Bing Zhao,Hai-Tao Zhou,Jian-Wei Liang,Xin-Yu Bi,Jian-Jun Zhao,Zhi-Yu Li,Jian-Guo Zhou,Zhen Huang,Ye-Fan Zhang,Jian Wang,Xin Xu,Yan Cai,Ming-Rong Wang,Yu Zhang 한국유전학회 2016 Genes & Genomics Vol.38 No.11

Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.

Historical Long-term Exposure to Pentachlorophenol Causing Risk of Cancer - A Community Study

Zheng, Rui-Zhi,Zhang, Qing-He,He, Yi-Xin,Zhang, Qian,Yang, Lin-Shen,Zhang, Zhi-Hua,Zhang, Xiu-Jun,Hu, Jing-Ting,Huang, Fen Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Background: Pervious studies suggested occupational workers exposure to pentachlorophenol (PCP) might contribute to increased risk of cancer. However, few studies have focused on associations between PCP and cancer risk at the community level. Objective: The present study was to explore the cancer risk for the community population living long-term in a PCP contaminated area. Methods: All the cancer cases diagnosed in 2009-2011 in Tongling City were collected. The cancer patients' residencies were geo-referenced in each district. The historical PCP usage for each district of Tongling was calculated as the PCP pollution index, which was further used to divide into PCP exposure categories. Standardized rate ratios (SRRs) of cancer incidence were applied to detect the cancer risk as exposure grade elevated. Correlation analysis was performed to analyze the relationship between PCP pollution and cancer incidence. Results: A total of 5,288 cancer cases (3,451 male and 1,837 female) were identified. PCP usage was correlated with the incidence of leukemia (r=0.88, P=0.002) for males, and with cancer of the esophagus for males (r=0.83, P=0.008) and females (r=0.71, P=0.020). Compared with the low exposure category, significant SRRs for total cancer sites was obtained for high PCP exposure category (SRR=1.61, 95%CI=1.59-1.62). Most SRR values of the cancer sites were significantly increased as exposure grade elevated and exposure time extended. Conclusion: The present study found that community residents living in the PCP contaminated area had increased risk of cancers. Leukemias, lymphomas and nasopharyngeal and esophageal cancers are most possibly associated with PCP exposure.

Fotemustine, Teniposide and Dexamethasone in Treating Patients with CNS Lymphoma

Wu, Jing-Jing,Wang, Xin-Hua,Li, Ling,Li, Xin,Zhang, Lei,Sun, Zhen-Chang,Fu, Xiao-Rui,Ma, Wang,Chang, Yu,Zhang, Xu-Dong,Han, Li-Juan,Zhang, Ming-Zhi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Purpose: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. Patients and Methods: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. Results: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR: 38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. Conclusion: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.

CD4⁺, IL17 and Foxp3 Expression in Different pTNM Stages of Operable Non-small Cell Lung Cancer and Effects on Disease Prognosis

Zhang, Guo-Qing,Han, Feng,Fang, Xin-Zhi,Ma, Xiao-Mei Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

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.

Association of Polymorphisms in the Calpain I Gene with Meat Quality Traits in Yanbian Yellow Cattle of China

Xin, Jin,Zhang, Li-Chun,Li, Zhao-Zhi,Liu, Xiao-Hui,Jin, Hai-Guo,Yan, Chang-Guo Asian Australasian Association of Animal Productio 2011 Animal Bioscience Vol.24 No.1

The calpain I (CAPN1) gene is an important marker for meat tenderness and marbling score in the bovine, but there were no studies to determine whether the CAPN1 gene had an association with other meat quality traits. In this study, we examined the relation between genetic polymorphisms of the CAPN1 gene and some meat quality traits in Yanbian Yellow Cattle of China. By PCRSSCP and gene sequencing in 321 unrelated Yanbian yellow cattle, twenty seven single nucleotide polymorphisms (SNPs) were detected in CAPN1, two existed SNPs in exon 8 and exon 17 resulted in the change of AA at F311S and M599V, respectively, and the otherpolymorphisms were at intron 7, 8, 14, 16 and 17. There were different preponderant genotypes at the corresponding gene locus and all genotypes were not associated with tenderness but other meat traits. This is the first study of the relationship between CAPN1 and meat quality besides tenderness in Yanbian yellow cattle of China.

G1/S-specific Cyclin-D1 Might be a Prognostic Biomarker for Patients with Laryngeal Squamous Cell Carcinoma

Zhang, Ying-Yao,Xu, Zhi-Na,Wang, Jun-Xi,Wei, Dong-Min,Pan, Xin-Liang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: To investigate the prognostic role of antigen KI-67 (Ki-67) and G1/S-specific cyclin-D1 (cyclin-D1) in patients with laryngeal squamous cell carcinoma (LSCC). Methods: Immunohistochemical staining (IHS) was used to determine the protein expression of Ki-67 and cyclin-D1 in LSCC tissues. Kaplan-Meier survival curves was calculated with reference to Ki-67 and cyclin-D1 levels. Results: Cyclin-D1 and Ki67 were expressed in the nuclei of cancer cells. Among the total of 92 cancer tissues examined by immunohistochemistry, 60 (65.22%) had cyclin-D1 overexpression and 56 (60.87%) had Ki67 overexpression. Cyclin-D1 overexpression is associated with the advanced stage of the cancer (P=0.029), but not with gender, age, stage of cancer, histological differentiation, anatomical site, smoking history and alcohol consumption history. Ki67 overexpression is not associated with the advanced stage, gender, age, histological differentiation, anatomical site, smoking history and alcohol consumption history. A statistically significant correlation was found between lymph node status and the expression of Ki67 (p = 0.025). Overexpression of cyclin-D1 was correlated to shorter relapse-free survival period (P<0.001). Conclusions: Overexpression of cyclin-D1 can be used as a marker to predict relapse in patients with LSCC after primary curative resection.

Identification and characterization of BGL11(t), a novel gene regulating leaf-color mutation in rice (Oryza sativa L.)

Zhi-kun Wang,Yun-xiang Huang,Zheng-diao Miao,Zhi-yan Hu,Xin-zhang Song,Li Liu 한국유전학회 2013 Genes & Genomics Vol.35 No.4

A novel bright-green leaf mutant, bgl11, derived from Nipponbare (Oryza sativa L. ssp. japonica) treated by ethyl methanesulfonate (EMS), exhibited a distinct brightgreen leaf phenotype throughout development. Chlorophyll contents of bgl11 decreased significantly than that of its wild-type parent. Genetic analysis suggested that the brightgreen leaf trait was controlled by a single recessive nuclear gene, which was tentatively designed as BGL11(t). To isolate the BGL11(t) gene, a map-based cloning strategy was employed, and the gene was finally mapped in a 94.7 kb region between marker InDel11-5 and InDel11-9 on the long arm of chromosome 11, in which no gene leaded to leaf-color mutation had been mapped or cloned. Cloning and sequencing analysis revealed that, LOC_Os11g38040, which was predicted to encode an expressed protein, had a 9 bp segment deletion in the coding region of bgl11. Furthermore, the transgenic plants with wild-type gene LOC_Os11g38040were restored to normal phenotype. Accordingly, the gene (LOC_Os11g38040) was identified as the BGL11(t) gene. These results are very valuable for further study on BGL11(t)gene and illuminating the mechanism of chloroplast development in rice.