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Yuan J.M.,Zhejiang Cancer Research Institute
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To study the expression of miRNA-106a gene in esophageal squamous cell carcinoma (ESCC) and its association with clinicopathological features and prognosis of ESCC patients. Real-time fluorescence quantitative polymerase chain reaction (PCR) assay was used to determine the expression of miRNA-106a gene in esophageal cancer tissue and corresponding normal mucosa of 81 cases. Immunohistochemical technique was applied to detect the expression of p53, human epidermal growth factor receptor 2 (HER-2), DNA topoisomerase II (Topo II) and multidrug resistance-associated protein (MRP). The association of miRNA-106a expression with clinicopathological features, expression of related proteins, and prognosis of the patients was analyzed. Among the 81 cases, under-expression of miRNA-106a gene was found in 48 cases (59.3%), normal expression in 22 cases (27.2%), and overexpression in 11 cases (13.6%). The expression of miRNA-106 gene was significantly associated with lymph node metastasis, pathological stage, and nerve invasion (all P < 0.05), significantly associated with expression of p53 (P = 0.006), and not significantly associated with expressions of HER-2, Topo II and MRP proteins (all P > 0.05). The expression of miRNA-106a gene was also significantly associated with progression-free survival (PFS, P = 0.032), but not significantly with overall survival (OS, P = 0.486). The results of Cox multivariate regression analysis showed that the PFS of ESCC patients was significantly correlated with lymph node metastasis (P = 0.029), but not correlated with the age, gender, tumor length, T stage, degree of differentiation, nerve invasion, and miRNA-106a expression (all P > 0.05). In esophageal squamous cell carcinomas, the miRNA-106a gene is under-expressed, with tumor suppressor function, and may be regarded as a biological marker to assess the prognosis in patients with esophageal squamous cell carcinoma.

Chen Z.,Zhejiang Cancer Research Institute | Chen Z.,Zhejiang Province Key Laboratory of Anti cancer Drug Research | Zheng S.,Zhejiang Province Key Laboratory of Anti cancer Drug Research | Li L.,Zhejiang Province Key Laboratory of Anti cancer Drug Research | Jiang H.,Zhejiang Province Key Laboratory of Anti cancer Drug Research
Current Drug Metabolism | Year: 2014

Flavonoids are naturally occurring polyphenols, which are widely taken in diets, supplements and herbal medicines. Epidemiological studies have shown a flavonoid-rich diet is associated with the decrease in incidence of a range of diseases. Pharmacological evidences also reveal flavonoids display anti-oxidant, anti-allergic, anti-cancer, anti-inflammatory, anti-microbial and anti-diarrheal activities. Therefore, it is critical to study the biotransformation and disposition of flavonoids in human. This review summarizes the major metabolism pathways of flavonoids in human. First, lactase-phlorizin hydrolase (LPH) and human intestinal microflora mediate the hydrolysis of flavonoid glycosides, which is recognized as the first and determinant step in the absorption of flavonoids. Second, phase II metabolic enzymes (UGTs, SULTs and COMT) dominate the metabolism of flavonoids in vivo. UGTs are the most major contributors, followed by SULTs and COMT. By contrast, phase I metabolism pathway mediated by CYPs only plays a minor role. Third, the coupling of transporters (such as BCRP and MRPs) and phase II enzymes (UGTs and SULTs) plays an important role in the disposition of flavonoids, especially in the enteroenteric and enterohepatic circulations. Thus, all the above factors should be taken into consideration when studying pharmacokinetics of flavonoids. Here we describe a comprehensive metabolism profile of flavonoids, which will enhance our understanding of the mechanisms underlying the disposition and pharmacological effects of flavonoids in vivo. © 2014 Bentham Science Publishers.

Xu S.H.,Zhejiang Cancer Research Institute
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2012

To investigate the expression of protein peak (3144 m/z) in serum and of its association with clinical pathological characteristics and prognosis in patients with gastric cancer. Three hundred and twenty seven pathologically confirmed gastric cancer patients were recruited from February 2006 to October 2008 in the Zhejiang Cancer Hospital. SELDI-TOF-MS was employed to detect the expression of protein peak (3144 m/z) in preoperative serum. The positive rate of 3144 m/z protein peak was 33.9% (111/327), significantly higher than that of CEA (21.1%,69/327), and the difference was statistically significant (P<0.01). The positive rate of combined detection of protein peak (3144 m/z)and CEA was 45.6% (149/327). The expression of protein peak (3144 m/z) was associated with clinical staging (P<0.01), nervous invasion (P<0.01), tumor size (P<0.01), vascular invasion (P<0.05), lymph node metastasis (P<0.05), expression of CEA (P<0.05), and depth of infiltration (P<0.05). Significant difference was observed in 3-year survival rate between the patients with protein peak and patients without protein peak (44.7% vs. 64.4%, P<0.01). However, 3144 m/z protein peak was not an independent prognostic factor on multivariate Cox regression analysis (P=0.057). Protein peak (3144 m/z) may be used as a diagnostic or prognostic marker of gastric cancer.

Wang F.,Zhejiang Sci-Tech University | Zheng Z.,Zhejiang Cancer Research Institute | Guo J.,Zhejiang Sci-Tech University | Ding X.,Zhejiang Sci-Tech University
Gynecologic Oncology | Year: 2010

Objectives: MicroRNAs (miRNAs) have been underlined as a promising potential biomarker for breast cancer but are limited to tissue specimens. Clinical specimens of sera are more abundant and more conveniently collected than tissues. This work was designed to investigate the expression and correlation of a selected panel of miRNAs associated with breast tumor in tissues and matching serum samples. Methods: Tumor tissues, adjacent non-tumor tissues and matching serum samples were collected from 68 patients with newly diagnosed breast tumors. Normal control sera were collected from 40 healthy subjects. A panel of 6 miRNAs (miRNA-21, 106a, 126, 155, 199a and 335) were selected and their aberrant expression levels were quantified by using real-time PCR technique. Results: A high correlation of miRNA expression level was found between breast tumor tissues and sera. MiR-21, miR-106a and miR-155 were significantly over-expressed in the tumor specimens compared with those in normal controls (P < 0.05), whereas miR-126, miR-199a and miR-335 were significantly under-expressed (P < 0.05). Furthermore, the relative expression of miR-21, miR-126, miR-155, miR-199a and miR-335 was closely associated with clinicopathologic features of breast cancer (P < 0.05), such as histological tumor grades and sex hormone receptor expression. Conclusions: Selective expression and modulation of miRNAs could be potential blood-based biomarkers for breast cancer diagnosis, grading and prognosis. Our results should encourage further studies on the use of miRNAs in serum samples as an easy and convenient method of breast cancer screening. © 2010 Elsevier Inc. All rights reserved.

Yang H.,Fudan University | Liu Y.,Fudan University | Bai F.,University of North Carolina at Chapel Hill | Zhang J.-Y.,Fudan University | And 10 more authors.
Oncogene | Year: 2013

The TET (ten-eleven translocation) family of -ketoglutarate (-KG)-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of -KG, linking 5mC oxidation to cancer development. We report here that the levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic and prostate cancers when compared with the matched surrounding normal tissues. Associated with the 5hmC decrease is the substantial reduction of the expression of all three TET genes, revealing a possible mechanism for the reduced 5hmC in cancer cells. The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development. © 2013 Macmillan Publishers Limited All rights reserved.

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