ABSTRACT
BACKGROUND: The aim of this study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of PI3K/AKT/mTOR pathway. PATIENTS AND METHODS: In a prospective, one-arm, phase II study, patients with mRCC received everolimus (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential biomarkers of PI3K/AKT/mTOR pathway. RESULTS: The median age of the 58 patients enrolled into the study was 60 years (range 41-78 years). In multivariate analysis, it was found that the adverse independent predictors for everolimus therapy were histological grade G1/2 {hazard ratio (HR): 2.68 [95% confidence interval (CI) 1.29-5.58, P = 0.0082]}, increased lactate dehydrogenase (LDH) level before treatment [HR: 2.55 (95% CI 1.30-4.99, P = 0.0064)] and the PIK3CA gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11-3.89, P = 0.0254). In multivariate analysis, it was observed that the adverse independent prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 1.66-10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA versus CC = 1.97 (95% CI 1.02-3.79; P = 0.0421)]. CONCLUSIONS: The PI3KCA gene polymorphism, LDH, and histologic grade can predict the effects of everolimus treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may be independent prognostic factors. Further investigation is needed to confirm and validate these findings prospectively in other RCC trials.
Subject(s)
Carcinoma, Papillary/genetics , Carcinoma, Renal Cell/genetics , Everolimus/therapeutic use , Kidney Neoplasms/genetics , Phosphatidylinositol 3-Kinases/genetics , TOR Serine-Threonine Kinases/genetics , Adult , Aged , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/mortality , Carcinoma, Papillary/secondary , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Class I Phosphatidylinositol 3-Kinases , Female , Follow-Up Studies , Genotype , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Mutation/genetics , Neoplasm Grading , Phosphoinositide-3 Kinase Inhibitors , Polymerase Chain Reaction , Prognosis , Prospective Studies , Protein Kinase Inhibitors/therapeutic use , Survival Rate , TOR Serine-Threonine Kinases/antagonists & inhibitorsABSTRACT
Histochemical studies were conducted on kidney sections of white rats, which were given Rocephin, Furosemide and Rocephin with Furosemide for 7 days. The results show changes in the activity of cellular enzymes like acid phosphatase, alkaline phosphatase and in polysaccharides. Some of kidney's bodies were destroyed after the treatment with Rocephin jointly with Furosemide.
