Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Background: The upregulation of microsomal prostaglandin E synthase-1 (mPGES-1) and the overexpression of interleukin-8 (IL-8) have been separately linked to glioma malignancy.
Objective: To evaluate (1) the correlation between the mRNA levels of IL-8, mPGES-1, and the main transcription factors (TFs) activating the IL-8 promoter in human brain tumors of different grades; (2) the role of prostaglandin E2 (PGE2) on IL-8 activation and the expression of these TFs in tumor-derived cells; and (3) the biological impact of PGE2 treatment and mPGES-1 silencing on IL-8 synthesis and tumorigenesis.
Methods: Quantitative real-time polymerase chain reaction, transfection experiments, and cell proliferation and apoptosis assays were performed.
Results: Regardless of histological grade, a significant positive association between IL-8 expression and mPGES-1, CCAAT/enhancer-binding protein-β (C/EBP-β) and C/EBP Homologous Protein (CHOP) mRNA levels was found only in astrogliomas (P < .001). The correlation was not significant in the other brain tumors. PGE2-treated astroglioma cells showed a marked upregulation of IL-8, C/EBP-β, and CHOP, as well as increased proliferation and decreased apoptosis compared with untreated cells. mPGES-1-silenced astroglioma cells displayed decreased IL-8 synthesis, accompanied by reduced cell growth and an increased rate of apoptosis. The other brain tumor cells were unaffected either by PGE2 treatment or by mPGES-1 knockout.
Conclusion: (1) PGE2 is responsible for IL-8 overexpression, independently of the malignancy grade, in astrogliomas only. (2) C/EBP-β and CHOP may be involved in mediating PGE2-induced IL-8 activation in these tumors. (3) mPGES-1 inhibition may have potential as a form of adjuvant therapy for astrogliomas.
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Source |
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http://dx.doi.org/10.1227/NEU.0b013e31821954c6 | DOI Listing |
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