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Cheng H.,Renmin University of China | Chen C.,Renmin University of China | Liu L.,Renmin University of China | Zhan N.,Renmin University of China | Li B.,Hubei Provincial Tumor Hospital
Oncology Letters | Year: 2015

Esophageal squamous cell carcinoma (SCC) possesses one of the worst prognoses out of the digestive carcinomas. Several studies have suggested that transforming growth factor β receptor type II (TGF-βRII), Smad family member 4 (Smad4) and p21 wild-type p53-activated factor 1 (p21waf1) are associated with esophageal SCC. The aim of the present study was to evaluate the effect of Smad4, TGF-βRII and p21waf1 in esophageal squamous cancer tissue and the pathological significance of the effect. An immunohistochemical method was used to evaluate the expression levels of Smad4, TGF-βRII and p21waf1 in specimens of esophageal SCC lesions obtained from 80 patients. It was found that the expression of Smad4, TGF-βRII and p21waf1 in histologically-classified grade I esophageal SCC, without invasion or lymph node metastasis, was markedly higher compared with grade III esophageal SCC that had invaded into the deep muscular or serous layer and metastasized to the lymph nodes (P<0.05). Analysis of the expression level of Smad4, TGF-βRII and p21waf1, as well as the clinical and pathological characteristics of esophageal SCC, revealed that the three proteins may be associated with the carcinogenesis, biological behavior and prognosis of esophageal SCC, parallel to the pathological stage and cell grade. © 2015, Spandidos Publications. All Rights Reserved.


Li Q.,Huazhong University of Science and Technology | Wu H.,Huazhong University of Science and Technology | Chen B.,Hubei Provincial Tumor Hospital | Hu G.,Huazhong University of Science and Technology | And 5 more authors.
PLoS ONE | Year: 2012

Purpose: Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis. Patients and Methods: We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis. Results: The median age of the 116 men and 45 women in the study was 58 years; 62 (39%) had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%). Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204-5.359, P = 0.014; and HR 1.885, 95% CI 1.086-3.273, P = 0.024), compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390-3.985, P = 0.001). Conclusions: We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to identify patients at high risk of brain metastasis. © 2012 Li et al.


Ren J.,Huazhong University of Science and Technology | Wu X.,Huazhong University of Science and Technology | He W.,Huazhong University of Science and Technology | Shao J.,Hubei Provincial Tumor Hospital | And 2 more authors.
DNA and Cell Biology | Year: 2011

Lysyl oxidase (LOX) is an extracellular enzyme critical for the cross-linking of collagens and elastin. The LOX gene has also been shown to inhibit the transforming activity of Ras oncogene signaling. Recently, a single-nucleotide polymorphism (SNP) of LOX G473A (rs1800449) has been demonstrated to be associated with increased risk of breast cancer in African American women. In this hospital-based case-control study, the association of LOX polymorphism with breast cancer susceptibility in Chinese Han population was investigated. In total, 238 female patients with breast cancer and 234 age-matched healthy controls recruited were genotyped. We found a significant difference in the frequency of the LOX G473A genotype between the breast cancer and control groups. Individuals with GA genotype showed a 2.79-fold (95% confidence interval=1.87-4.16) increased risk of breast cancer compared with subjects carrying GG genotype (p<0.001). Further statistical analysis revealed that this polymorphism was an independent parameter with regard to other variables that are significantly associated with breast cancer, that is, age, menopausal status, estrogen exposure interval, expression status of estrogen receptor, and progesterone receptor. These findings suggest that the LOX 473 GA genotype is independently associated with increased risk of breast cancer in Chinese female population. © Copyright 2011, Mary Ann Liebert, Inc.


He W.,Huazhong University of Science and Technology | Luo S.,Huazhong University of Science and Technology | Huang T.,Huazhong University of Science and Technology | Ren J.,Huazhong University of Science and Technology | And 3 more authors.
Molecular Biology Reports | Year: 2012

Ku70 plays an important role in the DSBR (DNA double-strand breaks repair) and maintenance of genomic integrity. Genetic variations within human Ku70 have been demonstrated to be associated with increased risk of several types of cancers. In this hospital-based case-control study, we aimed to investigate whether a single nucleotide polymorphism (SNP) in the promoter region (rs2267437) of Ku70 gene is associated with susceptibility to breast cancer in Chinese Han population. A total of 293 patients with breast cancer and 301 age-matched healthy controls were enrolled in this study. The Ku70 -1310C/G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A significant difference in genotype distribution and allele frequency was observed between patients and controls. The CG or GG carries were at higher risk of breast cancer compared with the CC homozygotes (OR = 1.43, 95% CI = 1.02-2.00, P = 0.038 and OR = 3.53, 95% CI = 1.60-7.80, P = 0.002, respectively). Further stratification analysis revealed that G allele was associated with an increased risk of breast cancer among premenopausal women (OR = 1.68, 95% CI = 1.21-2.33, P = 0.002), but not in postmenopausal women (OR = 1.33, 5% CI = 0.85-2.10, P = 0.216). Our study suggests that the Ku70 -1310C/G promoter polymorphism may be a susceptibility factor for breast cancer in Chinese Han population. © 2011 Springer Science+Business Media B.V.

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