Aberrant Expression of the Mammalian Target of Rapamycin, Hypoxia-inducible Factor-1α, and Glucose Transporter 1 in the Development of Ovarian Clear-cell Adenocarcinoma

2012 ◽  
Vol 31 (3) ◽  
pp. 254-263 ◽  
Author(s):  
Masafumi Kato ◽  
Sohei Yamamoto ◽  
Masashi Takano ◽  
Osamu Matsubara ◽  
Kenichi Furuya
Keyword(s):  
Glucose Transporter ◽  
Clear Cell ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Target Of Rapamycin ◽  
Clear Cell Adenocarcinoma ◽  
Aberrant Expression ◽  
Glucose Transporter 1 ◽  
Ovarian Clear Cell Adenocarcinoma ◽  
Hypoxia Inducible Factor 1Α

Alterations of Hypoxia-Induced Factor Signaling Pathway Due to Mammalian Target of Rapamycin (mTOR) Suppression in Ovarian Clear Cell Adenocarcinoma: In Vivo and in Vitro Explorations for Clinical Trial

2013 ◽  
Vol 23 (7) ◽  
pp. 1210-1218 ◽  
Author(s):  
Takeshi Hirasawa ◽  
Masaki Miyazawa ◽  
Masanori Yasuda ◽  
Masako Shida ◽  
Masae Ikeda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Proliferation ◽  
Therapeutic Strategy ◽  
Mtor Inhibitor ◽  
Clear Cell ◽  
Mammalian Target Of Rapamycin ◽  
Chemotherapeutic Agents ◽  
Target Of Rapamycin ◽  
Clear Cell Adenocarcinoma ◽  
Ovarian Clear Cell Adenocarcinoma

ObjectivesBefore setting into the clinical trial using a combination of mammalian target of rapamycin (mTOR) inhibitors (rapamycin and everolimus) and other anticancer drugs, this study was conducted to confirm the efficacy of the new therapeutic strategy for ovarian clear cell adenocarcinoma (CCA), which targeted mTOR–hypoxia-induced factor (HIF) signal transduction system.Materials and MethodsUsing the cultured cells of CCA and animal models, alteration of mTOR-HIF cofactors and cell proliferation under the mTOR inhibitor–treated condition were analyzed.ResultsMammalian target of rapamycin–HIF cofactors were inhibited dependent on concentration by mTOR inhibitor, resulting in suppression of the cultured CCA proliferation. However, von Hippel-Lindau was up-regulated at the messenger RNA level. In the nude mice with subcutaneously implanted CCA cells, apoptosis and necrosis were detected especially around the center of the tumors in the mTOR inhibitor–treated group more conspicuously than in the nontreated group. In the assessment of combination therapy with other antitumor agents, a combined treatment with mTOR inhibitor and chemotherapeutic agents caused a significant decrease in tumor size compared to the chemotherapeutic agents–only group.ConclusionsTreatment by mTOR inhibitor is expected to down-regulate the cell proliferation of the CCA as a new therapeutic strategy.

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