Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Interleukin-6 (IL-6), one of the proinflammatory cytokines, is considered to be one of the factors associated with poor prognosis of patients with renal cell carcinoma (RCC). Suppressor of cytokine signalling-3 (SOCS3) is rapidly up-regulated by IL-6 and a negative regulator of cytokine signalling. SOCS3 not only suppresses cytokine-mediated JAK/STAT signalling, but also sustains MAPK pathways. In our study, among the RCC cell lines, IL-6 mRNA expression was the highest in the 786-O cells, which also showed the highest level of SOCS3 mRNA expression under the condition of interferon stimulation. In contrast, ACHN cells had the lowest expression of both IL-6 and SOCS3 mRNA under the same condition. Our study is undertaken to evaluate the effect of humanised antihuman IL-6 receptor (IL-6R) antibody, which completely neutralises IL-6 activity, in RCC cell proliferation and its effect on signalling pathways. IL-6R antibody, tocilizumab, significantly suppressed cell proliferation in 786-O cells with interferon stimulation. Western blot analysis revealed that the tocilizumab enhanced the interferon-induced phosphorylation of STAT1 and inhibited SOCS3 expression and the phosphorylation of both STAT3 and ERK. In contrast, the IL-6 inhibited STAT1 phosphorylation, enhanced STAT3 phosphorylation and accelerated cell proliferation in ACHN cells. The in vivo effects of combination therapy with tocilizumab and interferon showed significant suppression of 786-O tumour growth in a xenograft model. Morphological observation of the tumours revealed the apoptosis, invasion of inflammatory cells and fibrosis. These findings suggest that combination therapy using an antihuman IL-6R antibody with interferon may represent a novel therapeutic approach for the treatment of RCC.
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Source |
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http://dx.doi.org/10.1016/j.ejca.2012.11.038 | DOI Listing |
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