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DNA microarrays are now able to measure the expressions of thousands of genes simultaneously. These measurements or gene profiling provides a snapshot?of life that maps to a cross section of ge-netic activities in a four-dimension space of time and the biological entity. Although recent microarray ex-periments[1, 2] hold the promise of the innovative tech-nology to cast new insights onto discovery of secrets of life, development of powerful and efficient analysis strategies for microarray dat… 相似文献
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HIF‐2α regulates non‐canonical glutamine metabolism via activation of PI3K/mTORC2 pathway in human pancreatic ductal adenocarcinoma
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Huilin Ye Yue Zhao Zhiqiang Fu Wenwei Pan Shangyou Zheng Lusheng Wei Tianwen Nong Zhihua Li Rufu Chen 《Journal of cellular and molecular medicine》2017,21(11):2896-2908
Hypoxia‐inducible factor‐2α (HIF‐2α) plays an important role in increasing cancer progression and distant metastasis in a variety of tumour types. We aimed to investigate its biological function and clinical significance in human pancreatic ductal adenocarcinoma (PDAC). A total of 283 paired PDAC tissues and adjacent normal tissues were collected from patients who underwent surgery or biopsy at Sun Yat‐sen Memorial Hospital between February 2004 and October 2016. In this study, we noted that HIF‐2α expression was significantly up‐regulated in PDAC, positively associated with disease stage, lymph‐node metastasis and patient survival, and identified as an independent prognostic factor of PDAC patients. We demonstrated that HIF‐2α silencing could reduce proliferation, migration and invasion of PDAC cells in vitro. The similar effect on growth was demonstrated in vivo. Furthermore, we noted that knock‐down of HIF‐2α significantly decreased the expression of glutamate oxaloacetate transaminase 1 (GOT1). Importantly, we confirmed that the PI3K/mTORC2 pathway promoted GOT1 expression by targeting HIF‐2α. Our study validated HIF‐2α was an important factor in PDAC progression and poor prognosis and may promote non‐canonical glutamine metabolism via activation of PI3K/mTORC2 pathway. Targeting HIF‐2α represents a novel prognostic biomarker and therapeutic target for patients with PDAC. 相似文献
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Tianwen Li Yongchong Yang Changmei Cheng Amit K. Tiwari Kamlesh Sodani Yufen Zhao Ioana Abraham Zhe-Sheng Chen 《Bioorganic & medicinal chemistry letters》2012,22(23):7268-7271
Our earlier research has shown that N-phenyl-2,2-dichloroacetamide analogues had much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this current study, a variety of N-arylphenyl-2,2-dichloroacetamide analogues were synthesized via Suzuki coupling reaction and their anti-cancer activity was evaluated. The results showed that N-terphenyl-2,2-dichloroacetamide analogues had satisfactory anti-cancer activity. Among them, N-(3,5-bis(benzo[d][1,3]dioxol-5-yl)phenyl)-2,2-dichloroacetamide (6 k) had an IC50 of 2.40 μM against KB-3-1 cells, 1.04 μM against H460 cells and 1.73 μM against A549 cells. 相似文献
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The Escherichia coli heat-labile enterotoxin B subunit (HLT-B) is one of the most powerful mucosal immunogens and known mucosal adjuvants. However, the induction of high levels of HLT-B expression in E. coli has proven a difficult proposition. Therefore, in this study, the HLT-B gene was cloned from pathogenic E. coli and expressed as a fusion protein with GST (glutathione S-transferase) in E. coli BL21 (DE3), in an attempt to harvest a large quantity of soluble HLT-B. The culture conditions, including the culture media used, temperature, pH and the presence of lactose as an inducer, were all optimized in order to obtain an increase in the expression of soluble GST-rHLT-B. The biological activity of the purified rHLT-B was assayed in a series of GM1-ELISA experiments. The findings of these trials indicated that the yield of soluble recombinant GST-rHLT-B could be increased by up to 3-fold, as compared with that seen prior to the optimization, and that lactose was a more efficient alternative inducer than IPTG. The production of rHLT-B, at 92% purity, reached an optimal level of 96 mg/l in a 3.7 L fermentor. The specific GM1 binding ability of the purified rHLT-B was determined to be almost identical to that of standard CTB. 相似文献
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This review focuses on the structure, function and pathological role of leukocyte function-associated antigen-1 (LFA-1) which is a heterodimeric protein consisting of two subunits. LFA-1 plays a most important role in the immune system including adhesion, extravasation, migration, apoptosis, cytotoxicity, cytokine production, and proliferation of lymphocytes. Therefore, T-cell activation can be suppressed by blocking ICAM-1/LFA-1 interaction in autoimmune diseases and organ transplantation. Many different inhibitors (i.e. antibodies, peptides, small molecules) have been demonstrated to block ICAM-1/LFA-1 interaction, and some of them are promising for medical treatment or have reached clinical trials. 相似文献
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Structure-based stabilization of an enzyme: the case of penicillin acylase from Alcaligenes faecalis
The modeled structure of penicillin acylase from Alcaligenes faecali (AFPGA) was constructed by comparative modeling with the Modeller program. Candidate positions that could be replaced with cysteine were estimated by scanning the modeled structure of AFPGA with the program MODIP (modeling disulfide bond in protein). The mutant Q3C/P751C had a higher optimum temperature by three degrees than that of the wild type AFPGA. The half life of the double mutant Q3C/P751C at 55 degrees C was increased by 50%. To our knowledge, this was the first structure-based genetic modification of AFPGA. 相似文献
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