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Nanjing, China

Zhu W.,Chinese PLA General Hospital | Lu L.,Jindu Hospital | Li Y.,Chinese PLA General Hospital | Yao J.,Pla No 161 Center Hospital | Xu B.,Chinese PLA General Hospital
Tumor Biology | Year: 2014

The potentially functional polymorphism Arg72Pro in p53 gene has been implicated in glioma risk, but published studies have mixed findings. The aim of current investigation was to identify whether p53 Arg72Pro polymorphism was significantly associated with the risk of glioma. By searching the databases of PubMed, EMBASE, and Web of Science, our meta-analysis included ten eligible studies consisting of 2,645 glioma cases and 3,920 control subjects. The association between p53 Arg72Pro polymorphism and glioma risk was assessed by summarizing the odds ratios (ORs) with the corresponding 95 % confidence intervals (CIs). We found that there was no overall risk of glioma in relation to any genetic model of p53 Arg72Pro polymorphism. Similar results were implicated in the analyses which are subgrouped by ethnicity and source of controls. This nonsignificant association remained stable when analyses were restrained to the studies consistent with HWE. In conclusion, our meta-analysis, based on the combined data from published papers before May 2013, reveals no evidence for significant association between p53 Arg72Pro polymorphism and glioma risk. © 2014 International Society of Oncology and BioMarkers (ISOBM).

Zhu J.,Chongqing Medical University | Lu L.,Jindu Hospital | Cheng X.,Chongqing Medical University | Xie R.,Chongqing Medical University | And 5 more authors.
Tumor Biology | Year: 2014

Several studies have assessed the association of CD95L polymorphism with cervical cancer risk, but the data lack the power to provide compelling evidence. In this study, we aimed to clarify the association through a meta-analysis. A comprehensive search was conducted in PubMed, Embase, and Web of Science. The fixed-effects model was used to calculate odds ratio (OR) with 95 % confidence intervals (CIs). A total of five papers with six case-control studies were derived and finally included in this meta-analysis. The overall estimate did not reveal any significant association between CD95L -844C/T polymorphism and cervical cancer risk. Subgroup analysis in Asian population indicated nonsignificant nevertheless potentially increased risk in CC genotype carriers in comparison with the carriers of CT+TT genotypes (OR CC vs. CT+TT=1.16, 95 % CI=0.99-1.36, P for heterogeneity=0.231). Based on current epidemiological studies, this meta-analysis suggests that CD95L polymorphism may not be a risk factor contributing to cervical cancer development. © 2014 International Society of Oncology and BioMarkers (ISOBM).

Lu L.,Jindu Hospital | Xu X.,Nanjing Medical University | Zhang B.,Jindu Hospital | Zhang R.,Jindu Hospital | And 2 more authors.
Journal of Translational Medicine | Year: 2014

Background: The coinhibitory receptor Programmed Death-1 (PD-1) inhibits effector functions of activated T cells and prevents autoimmunity, however, cancer hijack this pathway to escape from immune attack. The costimulatory receptor glucocorticoid-induced TNFR related protein (GITR) is up-regulated on activated T cells and increases their proliferation, activation and cytokine production. We hypothesize that concomitant PD-1 blockade and GITR triggering would synergistically improve the effector functions of tumor-infiltrating T cells and increase the antitumor immunity. In present study, we evaluated the antitumor effects and mechanisms of combined PD-1 blockade and GITR triggering in a clinically highly relevant murine ID8 ovarian cancer model.Methods: Mice with 7 days-established peritoneal ID8 ovarian cancer were treated intraperitoneally (i.p.) with either control, anti-PD-1, anti-GITR or anti-PD-1/GITR monoclonal antibody (mAb) and their survival was evaluated; the phenotype and function of tumor-associated immune cells in peritoneal cavity of treated mice was analyzed by flow cytometry, and systemic antigen-specific immune response was evaluated by ELISA and cytotoxicity assay.Results: Combined anti-PD-1/GITR mAb treatment remarkably inhibited peritoneal ID8 tumor growth with 20% of mice tumor free 90 days after tumor challenge while treatment with either anti-PD-1 or anti-GITR mAb alone exhibited little antitumor effect. The durable antitumor effect was associated with a memory immune response and conferred by CD4+ cells and CD8+ T cells. The treatment of anti-PD-1/GITR mAb increased the frequencies of interferon-γ-producing effector T cells and decreased immunosuppressive regulatory T cells and myeloid-derived suppressor cells, shifting an immunosuppressive tumor milieu to an immunostimulatory state in peritoneal cavity. In addition, combined treatment of anti-PD-1/GITR mAb mounted an antigen-specific immune response as evidenced by antigen-specific IFN-γ production and cytolytic activity of spleen cells from treated mice. More importantly, combined treatment of anti-PD-1/GITR mAb and chemotherapeutic drugs (cisplatin or paclitaxel) further increased the antitumor efficacy with 80% of mice obtaining tumor-free long-term survival in murine ID8 ovarian cancer and 4 T1 breast cancer models.Conclusions: Combined anti-PD-1/GITR mAb treatment induces a potent antitumor immunity, which can be further promoted by chemotherapeutic drugs. A combined strategy of anti-PD-1/GITR mAb plus cisplatin or paclitaxel should be considered translation into clinic. © 2014 Lu et al.; licensee BioMed Central Ltd.

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