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Liu G.-Y.,Hubei University | Liu G.-Y.,Hubei Cancer Clinical Study Center | Liu G.-Y.,Hubei Key Laboratory of Tumor Biological Behaviors | Liu G.-Y.,Sun Yat Sen University | And 13 more authors.
World Journal of Surgical Oncology | Year: 2012

Background: The histopathological and molecular heterogeneity of normal tissue adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue (NTAB), and the availability of limited specimens make deciphering the mechanisms of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers that could be reliably used to define a transforming fingerprint using RNA in situ hybridization.Methods: We evaluated 15 tumor-related RNA in situ hybridization biomarkers using tumor microarray and samples of seven tumor-adjacent normal tissues from 314 patients. Biomarkers were determined using comprehensive statistical methods (significance of support vector machine-based artificial intelligence and area under curve scoring of classification distribution).Results: TP53 was found to be a most reliable index (P <10-7; area under curve >87%) for distinguishing NTAC from NTAB, according to the results of a significance panel (BCL10, BECN1, BRCA2, FITH, PTCH11 and TP53).Conclusions: The genetic alterations in TP53 between NTAC and NTAB may provide new insight into the field of cancerization and tumor transformation. © 2012 Liu et al.; licensee BioMed Central Ltd.


Zhou F.-X.,Wuhan University | Xiong J.,Hubei Key Laboratory of Tumor Biological Behaviors | Luo Z.-G.,Hubei Key Laboratory of Tumor Biological Behaviors | Dai J.,Wuhan University | And 5 more authors.
Radiation Research | Year: 2010

To achieve a more complete understanding of the molecular mechanisms underlying tumor radioresistance, we established a radioresistant cell line from the human larynx squamous cell carcinoma cell line Hep-2 after long-term radiation induction. The biological features of the resulting cell lines were characterized. cDNA microarray technology was used to measure the alterations of gene expression in the radioresistant cells. We found that certain genes associated with DNA repair, cell cycle, apoptosis, etc. were significantly changed. In particular, genes related to telomeres, such as POT1, were significantly altered. Radioresistant cells had higher telomerase activity and longer telomeres than their parental cells. Our research suggests that telomere function is a novel hallmark of cellular radiosensitivity, and the mechanistic link between telomere maintenance and radiosensitivity may involve the genes and pathways we implicated in this study. © 2010 by Radiation Research Society.


Zhang H.,Hubei University | Zhang H.,Hubei Key Laboratory of Tumor Biological Behaviors | Zhang H.,The Fifth Hospital of Wuhan | Zeng L.,Hubei University | And 11 more authors.
Japanese Journal of Clinical Oncology | Year: 2012

A 36-year-old man was found to have Hurthle cell carcinoma, as diagnosed with surgical pathology after a lobectomy of the thyroid. A post-operative magnetic resonance imaging scan revealed a small mass in the lower pole of the right thyroid and a computed tomography scan showed bilateral nodules in the lungs and the neck, and multi-focal disease in the liver. He was treated with a docetaxel and cisplatin chemotherapy regimen. After six cycles of the docetaxel and cisplatin regimen, we could hardly find the lesions in the lungs and the liver, and the patient presented a complete tumor response lasting 17 months and has not shown any tumor recurrence till now. The docetaxel and cisplatin regimen may be an effective chemotherapy regimen for multi-metastases of Hurthle cell cancer. © The Author 2012. Published by Oxford University Press. All rights reserved.


Zhong Y.H.,Wuhan University | Zhong Y.H.,Hubei Clinical Cancer Study Center | Dai J.,Wuhan University | Dai J.,Hubei Clinical Cancer Study Center | And 9 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2013

Purpose: To evaluate the feasibility and efficacy of neoadjuvant chemotherapy involving docetaxel and cisplatin followed by intensity-modulated radiotherapy (IMRT) with concurrent cisplatin in patients with newly diagnosed stage III to IVB nasopharyngeal carcinoma (NPC). Methods: Docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1) were administered on a 3-week cycle for 2 courses, followed by radical IMRT (72 Gy/33F/6.5-7 W) with concurrent cisplatin (75 mg/m2, on day 1) every 3 weeks for 2 cycles. Results: From June 2008 to October 2010, forty-six patients were recruited in this trial. Forty-five patients completed neoadjuvant setting, and all patients completed planned concurrent chemoradiotherapy (CCRT). The complete and partial response rates were 28.3 and 56.5 % after neoadjuvant chemotherapy, and 91.3, 8.7 % after CCRT, respectively. After median follow-up of 26 months (range 12-39 months), one patient experienced local recurrence and 4 patients developed distant metastasis. The 3-year overall survival and progression-free survival rate were 94.1 and 72.7 %, respectively. Neutropenia (37.0 %) and vomiting (28.3 %) were the most common Grade 3-4 adverse effects during neoadjuvant course, while mucositis (30.4 %), xerostomia (30.4 %) and radiodermatitis (21.7 %) were the most common Grades 3 acute toxicities during CCRT. Xerostomia (73.9 %), dysphagia (56.5 %), hear loss (30.4 %) and skin reaction (21.7 %) were the common Grade 1-2 late effects. There were no Grades 3-4 late toxicities. Conclusions: The protocol of neoadjuvant docetaxel and cisplatin followed by IMRT with concurrent cisplatin was well tolerated, with outstanding compliance and efficacy in locally advanced NPC, which deserved further follow-up. © 2013 Springer-Verlag Berlin Heidelberg.


Xu Y.,Wuhan University | Xu Y.,Hubei Key Laboratory of Tumor Biological Behaviors | Hou J.,Hubei Key Laboratory of Tumor Biological Behaviors | Hou J.,Wuhan University | And 16 more authors.
Journal of Translational Medicine | Year: 2011

Background: Gene therapy is a promising therapeutic approach for cancer. Targeted expression of desired therapeutic proteins within the tumor is the best approach to reduce toxicity and improve survival. This study is to establish a more effective and less toxic gene therapy of cancer.Methods: Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase (HRP) mediated by human telomerase reverse transcriptase (hTERT) promoter (AdhTERTHRP) and murine interleukin-12 (mIL-12) under the control of Cytomegalovirus (CMV) promoter (AdCMVmIL-12) was developed and evaluated against Lewis lung carcinoma (LLC) both in vivo and in vitro. The mechanism of action and systemic toxicities were also investigated.Results: The combination of AdhTERTHRP/indole-3-acetic acid (IAA) treatment and AdCMVmIL-12 resulted in significant tumor growth inhibition and survival improvement compared with AdhTERTHRP/IAA alone (tumor volume, 427.4 ± 48.7 mm3vs 581.9 ± 46.9 mm3, p = 0.005 on day 15; median overall survival (OS), 51 d vs 33 d) or AdCMVmIL-12 alone (tumor volume, 362.2 ± 33.8 mm3vs 494.4 ± 70.2 mm3, p = 0.046 on day 12; median OS, 51 d vs 36 d). The combination treatment stimulated more CD4+and CD8+T lymphocyte infiltration in tumors, compared with either AdCMVmIL-12 alone (1.3-fold increase for CD4+T cells and 1.2-fold increase for CD8+T cells, P < 0.01) or AdhTERTHRP alone (2.1-fold increase for CD4+T cells and 2.2-fold increase for CD8+T cells, P < 0.01). The apoptotic cells in combination group were significantly increased in comparison with AdCMVmIL-12 alone group (2.8-fold increase, P < 0.01) or AdhTERTHRP alone group (1.6-fold increase, P < 0.01). No significant systematic toxicities were observed.Conclusions: Combination gene therapy with AdhTERTHRP/IAA and AdCMVmIL-12 could significantly inhibit tumor growth and improve host survival in LLC model, without significant systemic adverse effects. © 2011 Xu et al; licensee BioMed Central Ltd.


Xu Y.,Wuhan University | Xu Y.,Hubei Key Laboratory of Tumor Biological Behaviors | Zhou Y.-F.,Wuhan University | Zhou Y.-F.,Hubei Key Laboratory of Tumor Biological Behaviors | And 10 more authors.
Chinese Journal of Cancer Prevention and Treatment | Year: 2011

OBJECTIVE: To investigate the antitumor effect of horseradish peroxidase (HRP)/indole-3-acetic acid (IAA) system driven by human telomerase reverse transcriptase (hTERT) promoter in combination with interleukin-12 (IL-12) gene in a murine model of Lewis lung carcinoma. METHODS: Murine models of Lewis lung carcinoma were established and randomized into 4 groups: control, HRP group, IL-12 group and combination group, which were treated with AdCMVGFP, AdhTERTHRP and AdCMVmIL-12 alone or in combination followed by IAA administration, respectively. Tumor growth and animal survival was monitored to evaluate the antitumor effect. The expression of HRP and IL-12 was determined using the western blot and enzyme-linked immunosorbant assay, respectively. Lymphocyte infiltration was evaluated by immunohistochemistry. RESULTS: Tumor growth in combination group was significantly inhibited compared with other groups (combination vs control: P=0.000, 9 d; combination vs HRP: P=0.005, 15 d; combination vs IL-12: P=0.046, 12 d). The survival in combination group was statistically prolonged in comparison to other groups (combination vs control: χ 2 = 9.529, P=0.002; combination vs HRP: χ 2= 9.039, P=0.003; combination vs IL-12: χ 2 = 8.595, P=0.003). The combination group showed larger areas of necrosis and more CD4 + or CD8 + lymphocyte infiltration than any other group. CONCLUSION: HRP/IAA suicide gene system mediated by hTERT promoter in combination with IL-12 gene is more effective than either single treatment, which can provide a novel therapeutic strategy for lung cancer.

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