Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Downregulates the Expression of Protumor Factors Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in a GM-CSF Receptor-Independent Manner in Cervical Cancer Cells
Jiang N.,Wenzhou University |
Tian Z.,Chongqing Medical University |
Tang J.,105th Hospital of PLA |
Ou R.,Wenzhou University |
Xu Y.,Wenzhou University
Mediators of Inflammation | Year: 2015
Enhanced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) is associated with the pathogenic processes of various tumor types. COX-2 and iNOS expression in the immunomodulatory dendritic cells is mediated by the granulocyte macrophage-colony stimulating factor (GM-CSF), which is also expressed by cervical cancer cells; however, whether and how GM-CSF regulates COX-2 and iNOS expression in clinical cervical cancer cells remain unknown. In this study, we found that the COX-2 and iNOS expression was upregulated in the cervical cancer tissues and positively correlated with cancer metastasis and stage. About one-half of the cervical cancer tissues showed strong/moderate GM-CSF expression, while the normal cervical tissues showed >80% positive rate; no GM-CSFR protein was detectable on the cervical cancer cells. The GM-CSF expression was negatively correlated with the COX-2 and iNOS expression in the cervical cancer tissues and the functional negative regulatory effect of GM-CSF on COX-2/iNOS expression was demonstrated in various cervical cancer cell lines. Therefore, in cervical cancer cells, GM-CSF might contribute an antitumor response by inhibiting iNOS and COX-2 expression in a GM-CSFR independent manner. © 2015 Nanyan Jiang et al.
Ding Z.,Wenzhou Medical College |
Ou R.,Wenzhou Medical College |
Ni B.,Chongqing Medical University |
Tang J.,105th Hospital of PLA |
Xu Y.,Wenzhou Medical College
Clinical and Vaccine Immunology | Year: 2013
Heat shock proteins (HSPs) have been successfully applied to a broad range of vaccines as biological adjuvants to enhance the immune response. The recently defined HSP110, in particular, exhibits strong protein binding affinity and is capable of enhancing the immunogenicity of protein antigens remarkably more than other HSP family members. In our previous study, we verified that murine HSP110 (mHSP110) significantly enhanced the immune response of a C57BL/6 mouse model to the H-2d-restricted human papillomavirus (HPV) E749-57 epitope (short peptide spanning the 49th to 57th amino acid residues in the E7 protein). To determine whether HSP110 similarly enhances the immunogenicity of human epitope peptides, we used the HLA-A2 transgenic mouse model to investigate the efficacy of the mHSP110 chaperone molecule as an immunoadjuvant of the human HLA-A2-restricted HPV16 E711-20 epitope vaccine. Results showed that mHSP110 efficiently formed a noncovalently bound complex with the E7 11-20 epitope. The mHSP110-E711-20 complex induced epitope-specific splenocyte proliferation and E711-20-specific gamma interferon (IFN-γ) secretion. Importantly, cytotoxic T lymphocytes primed by the mHSP110-E711-20 complex exerted strong cytolytic effects on target T2 cells pulsed with the E711-20 peptide or TC-1 cells transfected with the HLA-A2 gene. In addition, the mHSP110-E7 11-20 complex elicited stronger ex vivo and in vivo antitumor responses than either emulsified complete Freund's adjuvant or HSP70-chaperoned E711-20 peptide. These collective data suggest that HSP110 is a promising immunomodulator candidate for peptide-based human cancer vaccines, such as for the HLA-A2-restricted E711-20 epitope. Copyright © 2013, American Society for Microbiology. All Rights Reserved.
Wang H.,Anhui Medical University |
Guan W.,105th Hospital of PLA |
Yang W.,First Hospital of Anqing |
Wang Q.,Anhui Medical University |
And 4 more authors.
PLoS ONE | Year: 2014
Hepatic stellate cell (HSC) activation is an essential event during alcoholic liver fibrosis. Evidence suggests that adenosine aggravates liver fibrosis via the adenosine A2A receptor (A2AR). Caffeine, which is being widely consumed during daily life, inhibits the action of adenosine. In this study, we attempted to validate the hypothesis that caffeine influences acetaldehyde-induced HSC activation by acting on A2AR. Acetaldehyde at 50, 100, 200, and 400 μM significantly increased HSC-T6 cells proliferation, and cell proliferation reached a maximum at 48 h after exposure to 200 μM acetaldehyde. Caffeine and the A2AR antagonist ZM241385 decreased the cell viability and inhibited the expression of procollagen type I and type III in acetaldehyde-induced HSC-T6 cells. In addition, the inhibitory effect of caffeine on the expression of procollagen type I was regulated by A2AR-mediated signal pathway involving cAMP, PKA, SRC, and ERK1/2. Interestingly, caffeine's inhibitory effect on the expression of procollagen type III may depend upon the A2AR-mediated P38 MAPK-dependent pathway. Conclusions: Caffeine significantly inhibited acetaldehyde-induced HSC-T6 cells activation by distinct A2AR mediated signal pathway via inhibition of cAMP-PKA-SRC-ERK1/2 for procollagen type I and via P38 MAPK for procollagen type III. © 2014 Wang et al.
Hu F.,Anhui Medical University |
Lv D.,105th Hospital of PLA |
Zhu J.,105th Hospital of PLA |
Fang J.,105th Hospital of PLA
Traffic Injury Prevention | Year: 2014
Objective: To explore the related risk factors of injuries caused by e-bike and bicycle crashes in Hefei, Anhui. Methods: Between June 2009 and June 2011, the records of injuries were triggered by e-bike and bicycle crashes in Hefei maintained by 105th Hospital of PLA. A form was designed to document patient age, gender, road user category (driver, passenger, pedestrian), safety factors (safety devices present, speed, traffic violations), environmental factors (time of trauma, light conditions, road surface), crash mode, impact type, and vehicle type. Results: Of the 205 cases, 108 were female and 97 were male. One hundred forty-six patients suffered injuries due to e-bike accidents and 59 due to bicycle accident. The chi-squared test compared distribution of categorical variables suggested that age (P =.0250), road user category (P =.0278), traffic rule violations (P =.0132), crash mode (P =.0027), impact type (P =.0019), and vehicle type (P =.0219) are related to the severity of injuries caused by e-bike/bicycle crashes in Hefei. The multiple-factor nonconditional logistic regression analysis showed that injury severity is the most commonly sustained within the vehicle type (odds ratio [OR] = 14.418; 95% confidence interval [CI], 4.680-44.418), followed by crash mode (OR = 11.556; 95% CI, 4.430-30.142), traffic rule violations (OR = 4.735; 95% CI, 1.934-11.594), and age (OR = 2.910; 95% CI, 1.213-6.979). Conclusions: With the study of e-bike/bicycle crashes in Hefei, primary identification of the risk factors for the traffic injuries is obtained. These findings are important in decision making regarding preventive measures. © 2014 Copyright Taylor and Francis Group, LLC.
Li B.,Shanghai University |
He H.,Shanghai University |
Tao B.-B.,Shanghai University |
Zhao Z.-Y.,105th Hospital of PLA |
And 8 more authors.
Oncology Reports | Year: 2012
Chemotherapy is widely used for the treatment of glioma. Given the high resistance of brain neoplasm tissues to chemotherapy, it is important to find new methods to improve the effects of chemotherapy. However, the molecular mechanisms underlying glioma resistance to chemotherapy are largely unknown. Here, we demonstrate that CDK6, a cell cycle regulator, is significantly upregulated in glioma cells, and the increasing expression of CDK6 correlates well with the grades of glioma malignancy. Using shRNA-mediated CDK6 knockdown, we found that the proliferation and survival of tumor cells were dramatically inhibited. Moreover, CDK6 knockdown in the U251 glioma cell line caused significant increase in the apoptosis of U251 cells treated with temozolomide (TMZ). Furthermore, CDK6 knockdown reduced the expression level of drug resistance genes such as MRP and MDR. These data indicate that CDK6 is an important mediator of glioma resistance to chemotherapy. Our findings provide a new strategy for the development of chemotherapy sensitizer.