title: Effect of Target Therapy on the Content of Transcription and Growth Factors, Protein Kinase TOR, and Activity of Intracellular Proteases in Patients with Metastatic Renal Cell Carcinoma.
abstract: We analyzed the dynamics of the expression of transcription factors, VEGF and its receptor VEGFR2, serine-threonine protein kinase mTOR and activity of proteasome and calpain in patients with metastatic renal cancer during therapy with tyrosine kinase inhibitor Votrient and mTOR blocker Afinitor. The expression of hypoxic nuclear factor HIF-1α in the tumor tissue decreased during therapy with the target preparations. The decrease of VEGF and its receptor VEGFR2 was observed only in patients treated with mTOR inhibitor. The increase in calpain activity in the tumor tissue was observed in both groups. These findings extend our understanding of the mechanism of action of target anticancer preparations as allow considering the studied markers as predictors in choosing optimal therapy.
authors.affiliation: Tomsk Research Institute of Cancer, Tomsk, Russia. spirinalvl@mail.ru.
authors.forename: L V
authors.initials: LV
authors.lastname: Spirina
authors.affiliation: Tomsk Research Institute of Cancer, Tomsk, Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Usynin
authors.affiliation: Tomsk Research Institute of Cancer, Tomsk, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Kondakova
authors.affiliation: Tomsk Research Institute of Cancer, Tomsk, Russia.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Yurmazov
authors.affiliation: Tomsk Research Institute of Cancer, Tomsk, Russia.
authors.forename: E M
authors.initials: EM
authors.lastname: Slonimskaya
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002154:Calpain / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000068338:Everolimus / Q000008:administration & dosage; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007191:Indazoles; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D009392:Nephrectomy; D011743:Pyrimidines / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; D016328:NF-kappa B; D011743:Pyrimidines; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C516667:pazopanib; D000068338:Everolimus; C546842:MTOR protein, human; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D058570:TOR Serine-Threonine Kinases; D002154:Calpain
keywords: intracellular proteases; mTOR; renal cancer; transcription and growth factor