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Hai-De Qin,
Yin Yao Shugart,
Jin-Xin Bei,
Qing-Hua Pan,
Lina Chen,
Qi-Sheng Feng,
Li-Zhen Chen, Wei Huang,
Jian Jun Liu,
Timothy J Jorgensen,
Yi-Xin Zeng,
Wei-Hua Jia
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ABSTRACT: DNA repair plays a central role in protecting against environmental carcinogenesis, and genetic variants of DNA repair genes have been reported to be associated with several human malignancies. To assess whether DNA gene variants were associated with nasopharyngeal carcinoma (NPC) risk, a candidate gene association study was conducted among the Cantonese population within the Guangdong Province, China, the ethnic group with the highest risk for NPC. A 2-stage study design was utilized. In the discovery stage, 676 tagging SNPs covering 88 DNA repair genes were genotyped in a matched case-control study (cases/controls = 755/755). Eleven SNPs with P(trend) < 0.01 were identified. Seven of these SNPs were located within 3 genes, RAD51L1, BRCA2, and TP53BP1. In the validation stage, these 11 SNPs were genotyped in a separate Cantonese population (cases/controls = 1,568/1,297). Two of the SNPs (rs927220 and rs11158728), both in RAD51L1, remained strongly associated with NPC. The SNP rs927220 had a significant P(combined) of 5.55 × 10(-5), with OR = 1.20 (95% CI = 1.10-1.30), Bonferroni corrected P = 0.0381. The other SNP (rs11158728), which is in strong linkage disequilibrium with rs927220 (r(2) = 0.7), had a significant P(combined) of 2.0 × 10(-4), Bonferroni corrected P = 0.1372. Gene-environment interaction analysis suggested that the exposures of salted fish consumption and cigarette smoking had potential interactions with DNA repair gene variations, but need to be further investigated. Our findings support the notion that DNA repair genes, in particular RAD51L1, play a role in NPC etiology and development.
Cancer Research 03/2011; 71(8):3000-8. · 7.86 Impact Factor
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Ke Pan,
Hui Wang,
Wan-li Liu,
Hua-kun Zhang,
Jun Zhou,
Jian-jun Li,
De-sheng Weng, Wei Huang,
Jian-cong Sun,
Xiao-ting Liang,
Jian-chuan Xia
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ABSTRACT: OK-432, a streptococcal preparation, has been shown as an effective activator to induce human monocyte-derived dendritic cells maturation. During this process, the activation of Toll-like receptor 4 plays an important role. However, the signaling pathway involved in has not been fully understood. In the present study, we investigated the underlying mechanisms, by which OK-432 induced maturation of human monocyte-derived DCs (MoDCs). We observed that exposure of immature MoDCs to OK-432 activated the p38 MAPK and NF-kappaB pathway, accompanied up-regulated the surface expression of maturation markers CD80, CD83, CD86 and HLA-DR, increased secretion of TNF-alpha, IL-12 and chemokine, IP-10. In addition, T cells stimulatory capacity was also enhanced. The maturation of MoDCs stimulated by OK-432 was inhibited by treatment with p38 pathway inhibitor, SB203580, or NF-kappaB pathway inhibitor, BAY-117082. Whereas, blocking of JNK pathway with SP600125 or ERK pathway with PD98059 did not influence OK-432-induced DCs maturation. Taken together, our data indicated that OK-432-induced DCs maturation was due, at least partly to the activation of p38 and NF-kappaB pathway.
Immunobiology 02/2009; 214(5):350-8. · 3.20 Impact Factor
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ABSTRACT: Previously, we identified frequent loss of heterozygosity (LOH) at D7S486 of chromosome 7q31 in gastric carcinoma. The TESTIN (TES) gene is a candidate tumor suppressor gene at 7q31.2. This study aimed to investigate the expression of TES in gastric carcinomas, and explore its correlations to clinicopathologic features and prognosis of gastric cancer.
Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to investigate the expression of TES in 140 specimens of primary gastric carcinomas and corresponding adjacent normal tissues; Western blot was performed to evaluate the expression of TES protein in 50 specimens of gastric carcinomas and adjacent normal tissues. The correlations of TES to clinicopathologic features and prognosis of gastric carcinoma were analyzed.
The mRNA level of TES was down-regulated in 96 (68.6%) of the 140 carcinomas as compared with that in matched normal tissues. The positive rate of TES protein was significantly lower in gastric cancer than in normal tissues (22.9% vs. 85.7%, P<0.001). The protein level of TES was down-regulated in 36 (72.0%) of 50 carcinomas as compared with corresponding normal tissues. TES expression was positively correlated with the differentiation of gastric carcinoma (r=0.178, P=0.035). The median survival was significantly shorter in TES-negative patients than in TES-positive patients (P=0.035).
The expression level of TES is significantly down-regulated in primary gastric cancer. TES may be a valuable marker for assessing the prognosis of gastric carcinoma.
Ai zheng = Aizheng = Chinese journal of cancer 10/2008; 27(9):984-8.
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ABSTRACT: Recent studies have identified polycomb-group gene Bmi-1 as oncogene in the generation of mouse pre-cell lymphomas, and overexpression of Bmi-1 has been found in several human tumor with the disease progress and poor prognosis of the cancer patients.
In present study, we investigated Bmi-1 expression and its prognostic significance in hepatocellular carcinoma (HCC) by performing immunohistochemical analysis, using a total of 137 HCC clinical tissue samples.
High Bmi-1 expression (Bmi-1 2+ or 3+) was shown in 29.9% cases. The positive immuno-staining of Bmi-1 was not only in well/moderately-differentiated tumor cells, but also in surrounding noncancerous or cirrhotic liver tissue. Bmi-1 expression level did not correlate with any clinicopathological parameters. However, survival analysis showed that the high-Bmi-1 group had a significantly shorter overall survival time than the low-Bmi-1 group (P=0.047). Multivariate analysis after 24 months revealed that Bmi-1 expression was a significant and independent prognostic parameter (P=0.002) for HCC patients.
Our study indicated that Bmi-1 could be a candidate biomarker for long-term survival in HCC.
Journal of Cancer Research and Clinical Oncology 06/2008; 134(5):535-41. · 2.56 Impact Factor
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ABSTRACT: Immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) plays an important role in immune tolerance. In some malignancies, the evidences were given to show that overexpression of IDO was related to poor prognosis of cancer patients.
In this study, we investigated IDO expression in hepatocellular carcinoma (HCC) cell lines and 138 primary HCC clinical surgical specimens, and correlation of IDO expression with clinical outcomes and prognosis of HCC patients.
Reverse transcription-PCR analysis showed that in vitro IDO expression in HCC cell lines and non-cancerous liver cell line were dependent on IFN-gamma. Immunohistochemical detection revealed that IDO was overexpressed in 49 of 138 (35.5%) tumor resection samples, whereas 89 of 138 (64.5%) cases showed weak immunostaining. IDO overexpression was significantly correlated with high metastasis rates (P = 0.049). Kaplan-Meier survival curves showed that overexpression of IDO resulted in significantly poor prognosis (P = 0.017, log-rank test). Multivariate Cox's analysis showed that IDO expression was an independent prognostic factor for overall survival of HCC patients (P = 0.010).
Our data indicated that IDO may be a novel favorable prognostic indicator and candidate adjuvant therapeutic target for HCC.
Journal of Cancer Research and Clinical Oncology 05/2008; 134(11):1247-53. · 2.56 Impact Factor
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ABSTRACT: The inhibitor of growth (ING) family member 2 (ING2) is a newly discovered member of ING family that can regulate a wide range of cellular processes including cell growth arrest, apoptosis, and DNA repair. Researches have shown that ING2 can activate p53 and p53-mediated apoptotic pathway involved in the hepatocarcinogenesis. To investigate the role of ING2 in hepatocellular carcinoma (HCC) pathogenesis, we analyzed the correlations between the ING2 expression level and clinicopathologic factors and studied its prognostic role in primary HCC. Using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, ING2 transcription and post-transcription level was found to be downregulated in the majority of tumors compared with matched non-tumors liver tissues (p=0.004 and p=0.014, respectively). The immunohistochemistry data indicated significant reduction of ING2 expression level in 44 of 84 (52.4%) HCC cases. In addition, the expression level of ING2 correlated with tumor size, histopathologic classification, serum AFP (p<0.05). Kaplan-Meier curves demonstrated that patients with reduced ING2 expression were at significantly increased risk for shortened survival time (p=0.009). Using multivariate analysis, ING2 expression was found to be an independent prognostic factor. Our data suggest that ING2 is involved in the progression of HCC, therefore it is considered to be a candidate tumor suppressor gene and its significantly decreased expression in HCC may lead to an unfavorable prognosis.
Cancer Letters 04/2008; 261(2):183-92. · 4.24 Impact Factor
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Ri-Cheng Jiang,
Hai-De Qin,
Mu-Sheng Zeng, Wei Huang,
Bing-Jian Feng,
Feng Zhang,
Han-Kui Chen,
Wei-Hua Jia,
Li-Zhen Chen,
Qi-Sheng Feng,
Ru-Hua Zhang,
Xing-Juan Yu,
Mei-Zhen Zheng,
Yi-Xin Zeng
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ABSTRACT: Nasopharyngeal carcinoma is a common malignancy in Southeast Asian countries, and genetic background is a well-known component of the complexity underlying its tumorigenic process. We have mapped a nasopharyngeal carcinoma susceptibility locus to chromosome 4p15.1-q12 in a previous linkage study on nasopharyngeal carcinoma pedigrees. In this study provided in this communication, we screened all the genes in this region, with a focus on exons, promoters, and the exon-intron boundary to identify nasopharyngeal carcinoma-associated mutations or functional variants. Importantly, we found a novel gene (LOC344967) with a single nucleotide polymorphism -32G/A in the promoter region. This gene is a member of the acyl CoA thioesterase family that plays an important role in fatty acid metabolism and is involved in the progression of various types of tumors. The -32A variant was found cosegregated with the disease phenotype in the nasopharyngeal carcinoma pedigrees that we previously used for the linkage study. Moreover, this -32A variant creates an activator protein (AP-1)-binding site in the transcriptional regulatory region of LOC344967, which significantly enhanced the binding of AP-1 to the promoter region and the transcription activity of the promoter in vivo. Furthermore, the expression of LOC344967 was significantly up-regulated at both mRNA and protein levels in nasopharyngeal carcinoma cells sharing the -32G/A genotype compared with nasopharyngeal carcinoma cells with the -32G/G genotype. Collectively, these results provide evidence that the -32A variant is a functional sequence change and may be related to nasopharyngeal carcinoma susceptibility in the families studied.
Cancer Research 02/2006; 66(2):693-700. · 7.86 Impact Factor
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Bing-Jian Feng, Wei Huang,
Yin Yao Shugart,
Ming K Lee,
Feng Zhang,
Jian-Chuan Xia,
Hui-Yun Wang,
Teng-Bo Huang,
Shao-Wen Jian,
Ping Huang, [......],
Yan Zhao,
Wang-Qing Liu,
Mang-Quan Deng,
Wei-Han Hu,
Shao-Xiong Wu,
Hao-Yuan Mo,
Ming-Fang Hong,
Mary Claire King,
Zhu Chen,
Yi-Xin Zeng
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ABSTRACT: Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 x 10(-5)) and 4.2 at D4S3002 (P = 1.1 x 10(-5)), which is positioned 4.5 cM away from D4S405. When Epstein Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 x 10(-5)) and 5.36 (P = 4.36 x 10(-6)) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.
Nature Genetics 09/2002; 31(4):395-9. · 35.53 Impact Factor
