scholarly journals Resveratrol-mediated apoptosis in renal cell carcinoma via the p53/AMP‑activated protein kinase/mammalian target of rapamycin autophagy signaling pathway

2017 ◽  
Author(s):  
Qingjun Liu ◽  
Qiang Fang ◽  
Shiqi Ji ◽  
Zhixing Han ◽  
Wenlong Cheng ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Protein Kinase ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Amp Activated Protein Kinase

scholarly journals Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins: a case report and review of literature

Rare Tumors ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. 164-166
Author(s):  
Jigarkumar Parikh ◽  
Teresa Coleman ◽  
Nidia Messias ◽  
James Brown
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Renal Cell ◽  
Gene Fusion ◽  
Mammalian Target Of Rapamycin ◽  
World Health ◽  
Target Of Rapamycin ◽  
Tyrosine Kinase Receptor ◽  
Xp11.2 Translocation

Xp11.2 translocation renal cell carcinomas (TRCCs) are a rare family of tumors newly recognized by the World Health Organization (WHO) in 2004. These tumors result in the fusion of partner genes to the TFE3 gene located on Xp11.2. They are most common in the pediatric population, but have been recently implicated in adult renal cell carcinoma (RCC) presenting at an early age. TFE3-mediated direct transcriptional upregulation of the Met tyrosine kinase receptor triggers dramatic activation of downstream signaling pathways including the protein kinase B (Akt)/phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways. Temsirolimus is an inhibitor of mammalian target of rapamycin (mTOR) kinase, a component of intracellular signaling pathways involved in the growth and proliferation of malignant cells. Here we present a case of a 22-year old female who has been treated with temsirolimus for her Xp11.2/ TFE3 gene fusion RCC.

Serum Lactate Dehydrogenase Predicts for Overall Survival Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Inhibition of Mammalian Target of Rapamycin

2012 ◽  
Vol 30 (27) ◽  
pp. 3402-3407 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Daniel J. George ◽  
Susan Halabi
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Lactate Dehydrogenase ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survival Benefit ◽  
Mammalian Target Of Rapamycin ◽  
Phase Iii ◽  
Target Of Rapamycin ◽  
Poor Risk

Purpose Lactate dehydrogenase (LDH) is an enzyme involved in anaerobic glycolysis and regulated by the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR)–containing complex 1 (PI3K/Akt/TORC1) pathway as well as tumor hypoxia/necrosis. High serum LDH levels are associated with poor prognosis in patients with cancer, including renal cell carcinoma (RCC). We tested whether serum LDH is prognostic and has predictive value in patients with metastatic RCC receiving an mTOR inhibitor. Patients and Methods We evaluated pretreatment and post-treatment serum LDH in 404 poor-risk patients with RCC treated with the TORC1 inhibitor temsirolimus or interferon alfa in an international phase III randomized trial. The proportional hazards model was used to test for the prognostic and predictive association of LDH in predicting overall survival (OS). Results Mean baseline serum normalized LDH was 1.23 times the upper limit of normal (ULN; range, 0.05 to 28.5 × ULN). The multivariable hazard ratio for death was 2.81 (95% CI, 2.01 to 3.94; P < .001) for patients with LDH more than 1 × ULN versus patients with LDH ≤ 1 × ULN. The LDH-treatment interaction term was statistically significant for OS (P = .016). Among 140 patients with LDH above the ULN, OS was significantly improved with temsirolimus (6.9 v 4.2 months; P < .002). Among 264 patients with normal LDH, OS was not significantly improved with temsirolimus as compared with interferon therapy (11.7 v 10.4 months; P = .514). Conclusion Serum LDH is a prognostic and a predictive biomarker for the survival benefit conferred by TORC1 inhibition in poor-risk RCC. Further investigation of the predictive role of LDH as a measure of benefit with PI3K/TORC1 pathway inhibition in other RCC risk groups and other tumor types is warranted.

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