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10.1053/j.gastro.2014.08.039 http://scihub22266oqcxt.onion/10.1053/j.gastro.2014.08.039 C4253315!4253315!25181692     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25181692&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 500 Internal Server Error in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Gastroenterology 2014 ; 147 (6): 1393-404 Nephropedia Template TP {{tp|p=25181692|t=2014. Tumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT3 to Promote Expansion of Human Hepatocellular Carcinoma Stem Cells |pdf=|usr=}}{{25181692}} gab.com Text Tumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT3 to Promote Expansion of Human Hepatocellular Carcinoma Stem Cells JO: Gastroenterology http://www.kidney.de/pget.php?&tw=1&pmid=25181692 #FOAvip Background & Aims: Cancer stem cells (CSCs) can contribute to hepatocellular carcinoma (HCC) progression and recurrence following therapy. The presence of tumor-associated macrophages (TAMs) in patients with HCC is associated with poor outcomes. It is not clear whether TAMs interact with CSCs during HCC development. We investigated whether TAMs affect the activities of CSCs in the microenvironment of human HCCs. Methods: HCCs were collected from 17 patients during surgical resection and single cell suspensions were analyzed by flow cytometry. CD14+ TAMs were isolated from the HCC cell suspensions and placed into co-culture with HepG2 or Hep3B cells, and CSC functions were measured. The interleukin 6 (IL6) receptor was blocked with a monoclonal antibody (tocilizumab), and STAT3 was knocked down with small hairpin RNAs in HepG2 cells. Xenograft tumors were grown in NOD-SCID/Il2Rgnull mice from human primary HCC cells or HepG2 cells. Results: CD44+ cells from human HCCs and cell lines formed more spheres in culture and more xenograft tumors in mice than CD44? cells, indicating that CD44+ cells are CSCs. Incubation of the CD44+ cells with TAMs promoted expansion of CD44+ cells, and increased their sphere formation in culture and formation xenograft tumors in mice. In human HCC samples, numbers of TAMs correlated with numbers of CD44+ cells. Of all cytokines expressed by TAMs, IL6 was increased at the highest level in human HCC co-cultures, compared with TAMs not undergoing co-culture. IL6 was detected in the microenvironment of HCC samples and induced expansion of CD44+ cells in culture. Levels of IL6 correlated with stages of human HCCs and detection of CSC markers. Incubation of HCC cell lines with tocilizumab or knockdown of STAT3 in HCC cells reduced the ability of TAMs to promote sphere formation by CD44+ cells in culture and growth of xenograft tumors in mice. Conclusions: CD44+ cells isolated from human HCC tissues and cell lines have CSC activities in vitro and form a larger number of xenograft tumors in mice than CD44? cells. TAMs produce IL6, which promotes expansion of these CSCs and tumorigenesis. Levels of IL6 in human HCC samples correlate with tumor stage and markers of CSCs. Blockade of IL6 signaling with tocilizumab, a drug approved by the Food and Drug Administration for treatment of rheumatoid arthritis, inhibits TAM-stimulated activity of CD44+ cells. This drug might be used to treat patients with HCC. Twit Text FOAVip Tumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT3 to Promote Expansion of Human Hepatocellular Carcinoma Stem Cells ????Gastroenterology http://www.kidney.de/pget.php?&tw=1&pmid=25181692 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25181692 #FOAvip English Wikipedia <ref>{{Cite pmid|25181692}}</ref> Tumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT3 to Promote Expansion of Human Hepatocellular Carcinoma Stem Cells #MMPMID25181692 Wan S; Zhao E; Kryczek I; Vatan L; Sadovskaya A; Ludema G; Simeone DM; Zou W; Welling TH Gastroenterology 2014[Dec]; 147 (6): 1393-404 PMID25181692show ga Background & Aims: Cancer stem cells (CSCs) can contribute to hepatocellular carcinoma (HCC) progression and recurrence following therapy. The presence of tumor-associated macrophages (TAMs) in patients with HCC is associated with poor outcomes. It is not clear whether TAMs interact with CSCs during HCC development. We investigated whether TAMs affect the activities of CSCs in the microenvironment of human HCCs. Methods: HCCs were collected from 17 patients during surgical resection and single cell suspensions were analyzed by flow cytometry. CD14+ TAMs were isolated from the HCC cell suspensions and placed into co-culture with HepG2 or Hep3B cells, and CSC functions were measured. The interleukin 6 (IL6) receptor was blocked with a monoclonal antibody (tocilizumab), and STAT3 was knocked down with small hairpin RNAs in HepG2 cells. Xenograft tumors were grown in NOD-SCID/Il2Rgnull mice from human primary HCC cells or HepG2 cells. Results: CD44+ cells from human HCCs and cell lines formed more spheres in culture and more xenograft tumors in mice than CD44? cells, indicating that CD44+ cells are CSCs. Incubation of the CD44+ cells with TAMs promoted expansion of CD44+ cells, and increased their sphere formation in culture and formation xenograft tumors in mice. In human HCC samples, numbers of TAMs correlated with numbers of CD44+ cells. Of all cytokines expressed by TAMs, IL6 was increased at the highest level in human HCC co-cultures, compared with TAMs not undergoing co-culture. IL6 was detected in the microenvironment of HCC samples and induced expansion of CD44+ cells in culture. Levels of IL6 correlated with stages of human HCCs and detection of CSC markers. Incubation of HCC cell lines with tocilizumab or knockdown of STAT3 in HCC cells reduced the ability of TAMs to promote sphere formation by CD44+ cells in culture and growth of xenograft tumors in mice. Conclusions: CD44+ cells isolated from human HCC tissues and cell lines have CSC activities in vitro and form a larger number of xenograft tumors in mice than CD44? cells. TAMs produce IL6, which promotes expansion of these CSCs and tumorigenesis. Levels of IL6 in human HCC samples correlate with tumor stage and markers of CSCs. Blockade of IL6 signaling with tocilizumab, a drug approved by the Food and Drug Administration for treatment of rheumatoid arthritis, inhibits TAM-stimulated activity of CD44+ cells. This drug might be used to treat patients with HCC. äTumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT(epmc).pdf DeepDyve Pubget Overpricing