Tianjin Medical University was founded in 1951; was the first medical institution approved by the State Council of the People's Republic of China. Hsien-I Chu, a renowned endocrinologist, was the first president of the university. The current president is Yongfeng Shang.In December 1993, with the approval of the State Education Council, the Tianjin Medical College and the Tianjin Second Medical College were integrated into the Tianjin Medical University. In December 1996, the university was accepted into Project 211, so it became one of the 97 key institutions in which there are 9 medical institutions that will be constructed emphatically by the State.In 1981, the university was approved by the Academic Degree Committee of State Council to confer the Doctorate Degree, Master's Degree and Bachelor's Degree and in 1988, was permitted to set up seven-year medical program.It is listed in International Medical Education Directory . Wikipedia.
Wang X.-D.,Tianjin Medical University
Oncogene | Year: 2017
Tumors consistently mimic wound-generating chronic inflammation; however, why they do not heal like wounds with fibrotic scars remains unknown. The components of the tumor microenvironment, such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGFs), may account for this phenomenon. Tumor formation involves continuous activation of the FGF pathway, whereas the repair of tissue injury is a self-limiting process accompanied with controlled activation of the FGF pathway. In the tumor microenvironment TGF-β increases the secretion of FGFs, further promoting the malignant biological properties of tumors. However, during wound healing, sufficient TGF-β together with moderate FGFs lead to matrix deposition and the formation of fibrotic scars. In the present study, TGF-β1 combined with AZD4547, an FGF receptor (FGFR) inhibitor, transformed hepatoma cells into less malignant fibroblast-like cells with respect to morphology, physiological properties, and gene expression profiles. In vivo experiments showed that TGF-β1 combined with AZD4547 not only inhibited tumor growth but also promoted tumor parenchyma fibrosis. Our results indicate that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression.Oncogene advance online publication, 6 March 2017; doi:10.1038/onc.2016.512. © 2017 Macmillan Publishers Limited, part of Springer Nature.
Chen D.,Tianjin Medical University
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2017
OBJECTIVEW—: Angiogenesis is a hallmark of embryonic development and various ischemic and inflammatory diseases. Prostaglandin E2 receptor subtype 3 (EP3) plays an important role in pathophysiologic angiogenesis; however, the precise mechanisms remain unknown. Here, we investigated the role of EP3 in zebra fish embryo and mouse retina angiogenesis and evaluated the underlying mechanisms. APPROACH AND RESULTS—: The EP3 receptor was highly expressed in the vasculature in both zebra fish embryos and murine fetal retinas. Pharmacological inhibition or genetic deletion of EP3 significantly reduced vasculature formation in zebra fish embryos and mouse retinas. Further characterization revealed reduced filopodia extension of tip cells in embryonic retinas in EP3-deficient mice. EP3 deletion activated Notch activity by upregulation of delta-like ligand 4 expression in endothelial cells (ECs). Inhibition of Notch signaling rescued the angiogenic defects in EP3-deficient mouse retinas. Moreover, EP3 deficiency led to a significant increase in β-catenin phosphorylation at Ser675 and nuclear accumulation of β-catenin in ECs. Knockdown or inhibition of β-catenin restored the impaired sprouting angiogenesis resulting from EP3 deficiency in ECs. The EP3 receptor depressed protein kinase A activity in ECs by coupling to Gαi. Inhibition of protein kinase A activity significantly reduced Ser675 phosphorylation and nuclear translocation of β-catenin, abolished the increased delta-like ligand 4 expression, and subsequently restored the impaired angiogenic capacity of EP3-deficient ECs both in vitro and in vivo. CONCLUSIONS—: Activation of the EP3 receptor facilitates sprouting angiogenesis through protein kinase A–dependent Notch signaling, suggesting that EP3 and its downstream pathways maybe potential therapeutic targets in the treatment of ischemic diseases. © 2017 American Heart Association, Inc.
Gao Y.,Tianjin Medical University
International Journal of Obesity | Year: 2017
Background:Recent studies suggest that Embelin, a natural plant extract might have the potential to prevent body weight gain in rats. However, the mechanisms involved remain to be elucidated.Methods:Effects of Embelin on adipocyte differentiation and lipogenesis were studied in murine ST2 stromal cells and C3H10T1/2 mesenchymal cells. The mechanisms through which Embelin regulates adipogenic differentiation and lipogenesis were explored. The in vivo anti-obesity effects of Embelin in high-fat diet (HFD)-induced obesity mice and possible transcriptional impact were investigated.Results:Embelin treatment suppressed ST2 and C3H10T1/2 cells to proliferate, and differentiate into mature adipocytes, along with the inhibition of adipogenic factors peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein-α, adipocyte protein 2 and adipsin. Embelin treatment also decreased the expression levels of lipogenic factors sterol regulatory element-binding protein 1, fatty acid synthase, acetyl-CoA carboxylase 1 and stearoyl-Coenzyme A desaturase 1. Embelin promoted the translocation of β-catenin from the cytoplasm into the nucleus in C3H10T1/2. The nuclear protein levels of β-catenin and TCF-4 were increased following Embelin treatment. Furthermore, Dickkopf-1 (Dkk1) expression was downregulated by Embelin, and overexpression of Dkk1 in C3H10T1/2 reversed the inhibition of adipogenesis and lipogenesis by Embelin. In vivo studies showed that Embelin treatment reduced the gain of body weight and fat, decreased the serum level of triglycerides, free fatty acid and total cholesterol, and improved glucose tolerance and insulin resistance in HFD-fed mice. Moreover, Embelin blocked induction of adipogenic and lipogenic factors and Dkk1 in adipose tissue in HFD-fed mice.Conclusions:The present work provides evidences that Embelin is effective in inhibiting adipogenesis and lipogenesis in vitro and the mechanisms may involve canonical Wnt signaling. Embelin has the potential to prevent body weight gain and fat accumulation, and to improve obesity-related glucose tolerance impairment and insulin resistance in the HFD-fed mice.International Journal of Obesity advance online publication, 28 February 2017; doi:10.1038/ijo.2017.35. © 2017 Macmillan Publishers Limited, part of Springer Nature.
Yang J.,Tianjin Medical University |
Zhang W.,University of Houston
Current Opinion in Oncology | Year: 2013
PURPOSE OF REVIEW: Recent translational studies in osteosarcoma are discussed with the purpose to shed light on the new molecular therapeutic targets. RECENT FINDINGS: The genetic aberrations of vascular endothelial growth factor (VEGF), mammalian target of rapamycin, Wnt signaling pathway, the inactivation of p53, Rb, WWOX genes, and amplification of APEX1, c-myc, RECQL4, RPL8, MDM2, VEGFA might be involved in the pathogenesis of osteosarcoma. The promising therapeutic targets for osteosarcoma patients include: integrin, ezrin, statin, NOTCH/HES1, matrix metalloproteinases (MMPs), m-calpain, and Src, which are involved in tumor cell invasion and metastasis; aldolase A, fructose-bisphosphate, sulfotransferase family 3A, member 1, BCL2-associated athanogene 3, heat shock protein 70 (HSP70), B-cell lymphoma 2-interacting mediator (BIM), polo-like kinase 1, hypoxia inducible factor 1, alpha subunit, minibrain-related kinase, Bcl-xl, caspase-3, midkine, high mobility group box 1 protein (HMGB1), and Beclin1, which are involved in tumor proliferation and apoptosis; met proto-oncogene (hepatocyte growth factor receptor), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, insulin-like growth factor (IGF)-1R, fms-related tyrosine kinase 4, platelet-derived growth factor receptor, beta polypeptide, IGF-I/II, and c-kit, which are involved in tumor growth; endosialin, VEGF, thrombin, and MMPs, which are involved in tumor angiogenesis; transforming growth factor-α/β, parathyroid hormone-like hormone, interleukin-6, interleukin-11, receptor activator of nuclear factor-κB ligand, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1, and cathepsin, which are involved in osteoclast function; Myc, HSP90, p-Met, p-Akt, p-STAT3, and cyclin D1, which are transcriptional factors; p-GP, hydroxysteroid (17-beta) dehydrogenase 10, HMGB1, BIM, inorganic phosphate, Bcl-2, PARP, mdm2, p21, Bax, and mitogen-activated protein kinase 1, which are involved in drug sensitivity. Furthermore, microRNAs such as miR-215 are also therapeutic targets. SUMMARY: These translational studies in osteosarcoma have identified new molecular targets for osteosarcoma. Copyright © Lippincott Williams & Wilkins.
Zhang C.,Tianjin Medical University |
Zhang C.,CAS Research Center for Eco Environmental Sciences
Oncogene | Year: 2014
Rho-associated kinase (ROCK) has an essential role in governing cell morphology and motility, and increased ROCK activity contributes to cancer cell invasion and metastasis. Burgeoning data suggest that ROCK is also involved in the growth regulation of tumor cells. However, thus far, the molecular mechanisms responsible for ROCK-governed tumor cell growth have not been clearly elucidated. Here we showed that inhibition of ROCK kinase activity, either by a selective ROCK inhibitor Y27632 or by specific ROCK small interfering RNA (siRNA) molecules, attenuated not only motility but also the proliferation of PC3 prostate cancer cells in vitro and in vivo. Importantly, mechanistic investigation revealed that ROCK endowed cancer cells with tumorigenic capability, mainly by targeting c-Myc. ROCK could increase the transcriptional activity of c-Myc by promoting c-Myc protein stability, and ROCK inhibition reduced c-Myc-mediated expression of mRNA targets (such as HSPC111) and microRNA targets (such as miR-17-92 cluster). We provided evidence demonstrating that ROCK1 directly interacted with and phosphorylated c-Myc, resulting in stabilization of the protein and activation of its transcriptional activity. Suppression of ROCK-c-Myc downstream molecules, such as c-Myc-regulated miR-17, also impaired tumor cell growth in vitro and in vivo. In addition, c-Myc was shown to exert a positive feedback regulation on ROCK by increasing RhoA mRNA expression. Therefore, inhibition of ROCK and its stimulated signaling might prove to be a promising strategy for restraining tumor progression in prostate cancer.
Li Y.,Tianjin Medical University
Journal of neurosurgery | Year: 2012
The goal of this study was to assess neuroimaging and clinical outcomes in patients harboring brainstem metastases that were treated with the Leksell Gamma Knife. Twenty-eight patients with brainstem metastases (32 lesions: 8 midbrain, 21 pontine, and 3 medullary) were consecutively treated with GKS. The primary cancer diagnoses in this group included 22 cases of lung cancer, 5 cases of breast cancer, and 1 case of rectal cancer. The median age of the patients was 61 years (range 45-83 years). The median treated lesion volume was 0.78 cm(3) (range 0.03-5.6 cm(3)), and the median GKS margin dose was 16 Gy (range 12-20 Gy). Overall survival in these patients was calculated using the Kaplan-Meier method. The median survival time was 9 months after GKS (range 2-32 months). Survival was 39.3% at 1 year and 10.7% at 2 years. The tumor control rate in the series was 90.6% (29 of 32 lesions). Development of peritumoral edema occurred in 1 patient after GKS; 4 months after GKS, the edema disappeared. Gamma Knife surgery using a median margin dose of 16 Gy is a safe and effective local therapy for patients with brainstem metastases.
Wang X.,Tianjin Medical University
British Journal of Cancer | Year: 2014
Background:Syndecan-1 (Sdc-1) shedding induced by matrix metalloproteinase-7 (MMP-7) and additional proteases has an important role in cancer development. However, the impact of Sdc-1 shedding on chemotherapeutic resistance has not been reported.Methods:We examined Sdc-1 shedding in colorectal cancer by enzyme-linked immunosorbent assay (ELISA), Dot blot, reverse transcription-PCR (RT-PCR), immunohistochemistry and so on, its impact on chemotherapeutic sensitivity by collagen gel droplet embedded culture-drug sensitivity test (CD-DST) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), and potential mechanisms of action by Dot blot, western blot and immunofluorescence.Results:Sdc-1 shedding was increased in colorectal cancer patients, Sdc-1 serum levels in postoperative patients were lower than in preoperative patients, but still higher than those observed in healthy adults. Patients with high preoperative Sdc-1 serum levels were less responsive to 5-Fluorouracil, Oxaliplatin, Irintecan, Cisplatin or Paclitaxel chemotherapy. Moreover, the disease-free survival of patients with high preoperative Sdc-1 serum levels was significantly poorer. The possible mechanism of chemotherapy resistance in colorectal cancer can be attributed to Sdc-1 shedding, which enhances EGFR phosphorylation and downstream signalling.Conclusions:Shed Sdc-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer, and Sdc-1 serum levels could be a new prognostic marker in colorectal cancer.British Journal of Cancer advance online publication, 16 October 2014; doi:10.1038/bjc.2014.493 www.bjcancer.com. © 2014 Cancer Research UK
Gao Y.,Tianjin Medical University
International journal of nanomedicine | Year: 2011
RNA interference is a powerful method for the knockdown of pathologically relevant genes. Small interfering RNAs (siRNAs) have been widely demonstrated as effective biomedical genetic-therapy applications for many diseases. Unfortunately, siRNA duplexes are not ideal drug-like molecules. Problems hindering their effective application fundamentally lie in their delivery, stability, and off-target effects. Delivery systems provide solutions to many of the challenges facing siRNA therapeutics. Due to some fatal disadvantages of viral vectors, nonviral carriers have been studied extensively. Aside from liposomes, nanoparticles and cationic polymer carriers have exhibited improved in vivo stability, better biocompatibility, and efficiency for gene silencing with less cellular toxicity. They may represent a promising strategy for siRNA-based therapies, especially as nanomaterials. The present review also summarizes other methods of siRNA delivery and the side effects of the nanoparticles.
Wang Y.,Tianjin Medical University |
Shang Y.,Tianjin Medical University
Experimental Cell Research | Year: 2013
Epithelial-mesenchymal transition (EMT) is vital for morphogenesis during embryonic development and is also critical for the conversion of early stage tumors into invasive malignancies. Several key inducers of EMT are transcription factors that repress the expression of E-cadherin, whose loss is a hallmark of EMT. Epigenetic regulation encompasses three types of changes: DNA methylation, histone modifications, and microRNAs, each of which has been shown to play a key role in controlling epithelial-mesenchymal transition and cancer metastasis. As we gain deeper understanding of epigenetic mechanisms controlling EMT processes and orchestrating all the metastatic steps, we broaden the therapeutic potentials of epigenetic drugs, such as DNA demethylating drugs and histone deacetylase/demethylase inhibitors, which can act upon metastasis-related genes, restoring their expression and biological functions. © 2012 Elsevier Inc.
Hao J.,Tianjin Medical University
OncoImmunology | Year: 2015
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal digestive tract malignancies. Hypoxia-inducible factor (HIF-1) is over-expressed in pancreatic cancer and associated with poor prognosis. During the past several years, we focused on identifying the function of HIF-1 and the antitumor effect of HIF-1 inhibitors on PDAC, especially in regards to immunogenic cell death. © 2015 Taylor & Francis Group, LLC.