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Abstract Details

Response of Connexin-43 to Estradiol: A Predictive Factor for the Therapy of Glioma?
Neuro-oncology
P02 - (-)
163
BACKGROUND: Glioma is more common in males (male:female=2:1) and Es antagonist (Tamoxifen) is used in its treatment, with less than half of the patients being responsive. Gap junction (GJ) regulations have impact on tumor cell proliferation. Besides, few studies have addressed the sex steroid hormone effects in glioma prognosis. Therefore, we evaluated the impact of Es on Cx43, the main GJ of astrocytes, in a model of astrocyte-microglia culture plus two different glioma cell lines.
DESIGN/METHODS: Primary astrocyte-microglia was obtained from P0-P1 Wistar rats. Based on the microglial yield, cultures were subjected to M5 (5%) and M30 (30%). F98 and C6 rat glioma cell lines were added to each of the M5/M30. Immunocytochemistry and western blotting (WB) for quantitative Cx43 were performed after 24h incubation with 100 nM of Es. All experiments were repeated at least 4 times with separate cultures. The data were tested by two-tailed Mann-Whitney test (Median卤SEM) and they were considered significant with Pvalue<0.05.
RESULTS: Cx43 expression was differently modulated by Es in C6 (58.7%卤5.0, P=0.009) and F98 (118.3%卤11.1, P=0.01) in comparison to controls (100%). M30+F98 showed reduced expression (86.8%卤6.4, P=0.02) of Cx43; however, Cx43 was over-expressed in M30+C6 cultures (140.0卤9.3, P=0.03). There were no changes over C6/F98 cells with M5 cultures.
CONCLUSIONS: Over-expression of Cx43 has inverse association with the grade of glioma. Therefore, increasing the expression of Cx43 can be beneficial for the treatment of glioma. We showed that, Cx43 is differentially modulated in two different glioma cell lines in response to Es. We also showed that microglia has critical impact in this regulation. In conclusion, we suggest Cx43 as a predictive factor for the response to Es antagonist. We recommend further in vivo investigation of the role of Es and its antagonist on Cx43.
Authors/Disclosures
Zahra Moinfar
PRESENTER
No disclosure on file
No disclosure on file
No disclosure on file
Volker Limmroth, MD, PhD (City of Cologne / Cologne General Hospital (Merheim)) No disclosure on file
Ralf Gold, MD (Neurologische Universitaetsklinik) Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Gold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer Vital. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharamaceuticals. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishers. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Novartis. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Biogen. The institution of Dr. Gold has received research support from Novartis. The institution of Dr. Gold has received research support from Biogen.
No disclosure on file
No disclosure on file