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Liu T.,Shanghai University | Zhou W.,Shanghai University | Cai B.,Ningbo Development Zone Center Hospital | Chu J.,First Peoples Hospital of Hefei | And 5 more authors.
Molecular Medicine Reports | Year: 2015

Osteosarcoma (OS) is the most frequent type of primitive malignant bone tumor with a poor prognosis due to distant metastasis. Our previous studies have demonstrated that IRX2 is overexpressed and is important in cell proliferation and invasion. However, the molecular mechanisms underlying the IRX2-dependent regulation of OS progression remains to be elucidated. In the present study, the effects of IRX2 on the upregulation of MMP2 and VEGF in OS were determined by western blotting, and the underlying molecular mechanisms were elucidated. These findings provided data suggesting that IRX2 modulates the expression levels of MMP2 and VEGF in an AKT-dependent manner. The overexpression of IRX2 promoted the activation of PI3K/Akt and increased the proliferation and invasiveness of the OS cell lines as shown by CCK8 and invasion assays. Notably, interruption of the AKT pathway by treatment with LY294002, a specific PI3K inhibitor, attenuated IRX2-induced cell proliferation and invasive ability, and the upregulation of MMP2 and VEGF. The results of the present study suggested that inhibition of the IRX2-mediated AKT signaling pathway may be a suitable therapeutic target for the treatment of OS.

Zheng X.,Anhui University of Science and Technology | Cheng M.,Anhui University of Science and Technology | Cheng M.,Anhui Medical University | Fu B.,Anhui University of Science and Technology | And 6 more authors.
Cancer Research | Year: 2015

There remains a great need for effective therapies for lung cancer, the majority of which are non-small cell lung cancers (NSCLC). Here, we report the identification of a novel candidate therapeutic target, LUNX, as a molecule overexpressed in primary NSCLC and lymph node metastases that is associated with reduced postoperative survival. Functional studies demonstrated that LUNX overexpression promoted lung cancer cell migration and proliferation by interactions with the chaperone protein 14-3-3. Conversely, LUNX silencing disrupted primary tumor growth, local invasion, and metastatic colonization. The finding that LUNX was expressed on cell membranes prompted us to generate and characterize LUNX antibodies as a candidate therapeutic. Anti-LUNX could down-regulate LUNX and reduce lung cancer cell proliferation and migration in vitro. Administered in vivo to mice bearing lung cancer xenografts, anti-LUNX could slow tumor growth and metastasis and improve mouse survival. Together, our work provides a preclinical proof of concept for LUNX as a novel candidate target for immunotherapy in lung cancer. ©2015 AACR.

Ju X.-A.,Shenyang University | Ju X.-A.,Liaoning Cardiac Center | Chen J.,Beijing Institute of Radiation Medicine | Ding L.,General Hospital of Air Force | And 6 more authors.
In Vitro Cellular and Developmental Biology - Animal | Year: 2013

In this report, a slow-growing subpopulation of human umbilical cord mesenchymal stromal cells (MSCs) was identified. These cells were around 5 μm in diameter and their relative gravity was between 1.031 and 1.043 g/ml. In sharp contrast to the parent MSCs, they expressed highly CD271 and poorly the receptor for platelet-derived growth factor. Quantitative PCR with the identification of the products by DNA sequencing proved that these cells expressed Nanog at a higher level than cells from the other subpopulation (approximately 30-fold), which was further confirmed by western blotting. Furthermore, they did not grow at clonal density and depletion of these cells from the population had little effect on the colony formation of the parent MSCs. The results here indicate that a subpopulation of cells with special biological features exist in human cord MSCs in culture. © 2013 The Society for In Vitro Biology.

Li Y.,Nanjing University | Tian Y.,Nanjing Medical University | Zhu W.,Nanjing University | Gong J.,Nanjing University | And 5 more authors.
International Immunopharmacology | Year: 2013

Background IL-6/STAT3/SOCS3 signaling pathway plays an important role in the pathogenesis of Crohn's disease by induction of the antiapoptotic factors Bcl-2 and Bcl-xl in lamina propria mononuclear cells (LPMCs). We previously reported that triptolide showed therapeutic activity in mouse colitis by mechanisms involving suppression of IL-6 trans-signaling. IL-10 gene-deficient mice with established colitis were used for the experiments with triptolide administration. Methods This study further investigates the mechanism by which triptolide attenuates Crohn's colitis. IL-10 gene-deficient mice (IL-10 -/-) of 10-12 weeks with established colitis were used for the experiments with chronic triptolide administration. Apoptosis of lamina propria mononuclear cells (LPMCs) were measured by flow cytometry. SOCS, Bcl-2, Bcl-xl and Bax were determined by Western blot. Furthermore, an in vitro study was performed by using cultured intestine from CD patients to observe the direct effects of triptolide. Results Our data indicated triptolide promoted apoptosis in LPMCs in vivo. Interestingly, triptolide significantly induced the apoptosis of LP-CD4-positive but not LP-CD4-negative cells. Triptolide significantly induced SOCS3 protein and reduced STAT3 target anti-apoptotic genes Bcl-2 and Bcl-xl in LPMCs. The results were confirmed by an in vitro study using colonic explants cultured with triptolide. Conclusions Our results indicated that triptolide therapy may restore the homeostatic balance of LP-T cell apoptosis within the gut, and demonstrate a novel mechanism of action of triptolide therapy mediated through regulation IL-6/STAT3/SOCS3 signaling pathway. © 2013 Elsevier B.V.

Pan J.,Anhui Medical University | Chen M.,Anhui Medical University | Zhang X.,First Peoples Hospital of Hefei | Chen Y.,First Peoples Hospital of Hangzhou | And 2 more authors.
Indian Journal of Dermatology | Year: 2012

Objectives: This study sought to determine the high risk factors for severe hand, foot, and mouth disease (HFMD). Materials and Methods: Retrospective 229 severe HFMD cases from four hospitals in FuYang, HeFei, and BoZhou (Anhui Provincial Hospital, Fuyang City People's Hospital, No. 2 People's Hospital of Fuyang and Bozhou city People's Hospital) in 2008-2009 were studied, with 140 mild HFMD cases in the same area. Using univariate and multivariate logistic regression analyses, the high risk factors of HFMD were identified by comparing clinical and laboratory findings between severe cases and mild cases. Results: There was a significant difference in age, total duration of fever, rate of respiratory and heart, shake of limbs, white blood cell count, blood sugar, and CK-MB between the two groups. Univariate logistic regression analysis showed that severe cases were associated with age (<3 years), withdrawnness and lethargy, shake of limbs, tachycardia, total leukocyte count (1710 9 /l), blood sugar (7 mmol/l), and CK-MB (16 mmol/l). Furthermore, age (<3 years), withdrawnness, and lethargy, shake of limbs, WBC (1710 9 /l), and CK-MB (16 mmol/l) were found to be high risk factors for severe cases after multivariate logistic regression analysis. Conclusions: Clinicians should give importance to these risk factors. Early recognition of children at risk and timely intervention is the key to reduce acute mortality and morbidity.

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