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Decreased Expression of Heat Shock Protein 20 in Colorectal Cancer and Its Implication in Tumorigenesis 下载免费PDF全文
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Yuji Nishikawa Masayuki Sone Yasuharu Nagahama Eriko Kumagai Yuko Doi Yasufumi Omori Toshiaki Yoshioka Takuo Tokairin Masayuki Yoshida Yohei Yamamoto Akihiko Ito Toshihiro Sugiyama Katsuhiko Enomoto 《Journal of cellular biochemistry》2013,114(4):831-843
We previously showed that mature hepatocytes could transdifferentiate into bile ductular cells when placed in a collagen‐rich microenvironment. To explore the mechanism of transdifferentiation, we examined whether inflammatory cytokines affected the phenotype of hepatocytes in a three‐dimensional culture system. Spheroidal aggregates of rat hepatocytes were embedded within a type I collagen gel matrix and cultured in the presence of various cytokines. In the control, hepatocytes gradually lost expression of albumin, tyrosine aminotransferase, and hepatocyte nuclear factor (HNF)‐4α, while aberrantly expressed bile ductular markers, including cytokeratin 19 (CK 19) and spermatogenic immunoglobulin superfamily (SgIGSF). Among the cytokines examined, tumor necrosis factor (TNF)‐α inhibited expression of albumin and HNF‐4α, both at mRNA and protein levels. After culturing for 2 weeks with TNF‐α, hepatocytic spheroids were transformed into extensively branching tubular structures composed of CK 19‐ and SgIGSF‐positive small cuboidal cells. These cells responded to secretin with an increase in secretion and expressed functional bile duct markers. TNF‐α also induced the phosphorylation of Jun N‐terminal kinase (JNK) and c‐Jun, and the morphogenesis was inhibited by SP600125, a specific JNK inhibitor. Furthermore, in chronic rat liver injury induced by CCl4, ductular reaction in the centrilobular area demonstrated strong nuclear staining of phosphorylated c‐Jun. Our results demonstrate that TNF‐α promotes the ductular transdifferentiation of hepatocytes and suggest a role of TNF‐α in the pathogenesis of ductular reaction. J. Cell. Biochem. 114: 831–843, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
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The Therapeutic Potential of Targeting Tumor Microenvironment in Breast Cancer: Rational Strategies and Recent Progress 下载免费PDF全文
Afsane Bahrami Seyed Mahdi Hassanian Majid Khazaei Malihe Hasanzadeh Soodabeh Shahidsales Mina Maftouh Gordon A. Ferns Amir Avan 《Journal of cellular biochemistry》2018,119(1):111-122
The tumor microenvironment (TME) is cellular environment in addition to harboring carcinoma cells, consists of different components (e.g., blood vessels, immune cells, fibroblasts, bone marrow‐derived inflammatory cells, lymphocytes, signaling molecules, and the extracellular matrix) that have an essential role on drug activity and efficacy. There is growing body of evidence showing its involvement in the progression and metastasis of different cancers, including breast cancer (BC). These observations provide a proof of concept of targeting TME compartments as a novel potential therapeutic approach in treatment of this malignancy, which is the main interested for current review. J. Cell. Biochem. 119: 111–122, 2018. © 2017 Wiley Periodicals, Inc. 相似文献