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10.21037/jtd.2016.06.47 http://scihub22266oqcxt.onion/10.21037/jtd.2016.06.47 C4999763!4999763 !27621846     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27621846 &cmd=llinks): Failed to open stream: HTTP request failed! 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Gram-negative bacteria facilitate tumor outgrowth and metastasis by promoting lipid synthesis in lung cancer patients |pdf=|usr=}}{{27621846 }} gab.com Text Gram-negative bacteria facilitate tumor outgrowth and metastasis by promoting lipid synthesis in lung cancer patients JO: J Thorac Dis http://www.kidney.de/pget.php?&tw=1&pmid=27621846 #FOAvip BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Patients with lung cancer are very frequently present with pulmonary infections, in particular with Gram-negative bacteria. Herein, we investigated the effect of the co-presence of Gram-negative bacteria on outgrowth and metastasis of lung cancer cells in clinical patients. METHODS: Lung cancer cells were isolated from clinical surgical tissues. Heat-inactivated E. coli was used as Gram-negative bacteria. Tumor outgrowth and invasion in vitro was analyzed with MTT assay and Biocoat Matrigel Invasion Chamber. Tumor growth and metastasis in vivo was evaluated in BALB/c nude mice. Lipid synthesis was evidenced by expressions of FASN and ACC1, as well as BODIPY Fluorophores staining. Block lipid synthesis was performed with C75 as a FAS inhibitor and transfection with ACC1 siRNA. Knockdown of TLR4 and TLR9 signaling was achieved by transfection with specific shRNAs and administration of specific antagonists. RESULTS: Gram-negative bacteria significantly promoted lung cancer development including growth and metastasis in dose dependent manner. Mechanistically, Gram-negative bacteria activate TLR4 and TLR9 signaling and enhance lipid synthesis in human lung cancer cells. Knockdown of TLR4 and/or TLR9 was able to block Gram-negative bacteria mediated lipid synthesis and lung cancer development. Interference with lipid synthesis efficiently abrogated Gram-negative-bacteria-induced lung cancer development. In lung cancer patients, higher expressions of innate immune receptors, TLR4 and TLR9, were observed in those with Gram-negative infections and associated with the aberrant lipid synthesis that was observed in vitro. CONCLUSIONS: Pulmonary infections with Gram-negative bacteria lead to aberrant lipid synthesis through TLR4 and TLR9 signaling in lung cancer patients and result in rapid proliferation and metastasis of lung cancer cells. These findings reveal a new mechanism for pulmonary infection-trigged caner development and provide clues for exploring therapeutics for lung cancer patients. Twit Text FOAVip Gram-negative bacteria facilitate tumor outgrowth and metastasis by promoting lipid synthesis in lung cancer patients ????J Thorac Dis http://www.kidney.de/pget.php?&tw=1&pmid=27621846 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27621846 #FOAvip English Wikipedia <ref>{{Cite pmid|27621846 }}</ref> Gram-negative bacteria facilitate tumor outgrowth and metastasis by promoting lipid synthesis in lung cancer patients #MMPMID27621846 Ye M ; Gu X ; Han Y ; Jin M ; Ren T J Thorac Dis 2016[Aug]; 8 (8 ): 1943-55 PMID27621846 show ga BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Patients with lung cancer are very frequently present with pulmonary infections, in particular with Gram-negative bacteria. Herein, we investigated the effect of the co-presence of Gram-negative bacteria on outgrowth and metastasis of lung cancer cells in clinical patients. METHODS: Lung cancer cells were isolated from clinical surgical tissues. Heat-inactivated E. coli was used as Gram-negative bacteria. Tumor outgrowth and invasion in vitro was analyzed with MTT assay and Biocoat Matrigel Invasion Chamber. Tumor growth and metastasis in vivo was evaluated in BALB/c nude mice. Lipid synthesis was evidenced by expressions of FASN and ACC1, as well as BODIPY Fluorophores staining. Block lipid synthesis was performed with C75 as a FAS inhibitor and transfection with ACC1 siRNA. Knockdown of TLR4 and TLR9 signaling was achieved by transfection with specific shRNAs and administration of specific antagonists. RESULTS: Gram-negative bacteria significantly promoted lung cancer development including growth and metastasis in dose dependent manner. Mechanistically, Gram-negative bacteria activate TLR4 and TLR9 signaling and enhance lipid synthesis in human lung cancer cells. Knockdown of TLR4 and/or TLR9 was able to block Gram-negative bacteria mediated lipid synthesis and lung cancer development. Interference with lipid synthesis efficiently abrogated Gram-negative-bacteria-induced lung cancer development. In lung cancer patients, higher expressions of innate immune receptors, TLR4 and TLR9, were observed in those with Gram-negative infections and associated with the aberrant lipid synthesis that was observed in vitro. CONCLUSIONS: Pulmonary infections with Gram-negative bacteria lead to aberrant lipid synthesis through TLR4 and TLR9 signaling in lung cancer patients and result in rapid proliferation and metastasis of lung cancer cells. These findings reveal a new mechanism for pulmonary infection-trigged caner development and provide clues for exploring therapeutics for lung cancer patients. äGram-negative bacteria facilitate tumor outgrowth and metastasis by pr(epmc).pdf DeepDyve Pubget Overpricing