Activation of mTOR in renal cell carcinoma is due to increased phosphorylation rather than protein overexpression.

The altered expression and activation of the mammalian target of rapamycin (mTOR) promotes the invasiveness and metastatic potential in a variety of malignancies. The aim of the present pilot study was to determine mTOR expression in clear cell renal cell carcinoma (RCC) and to evaluate mTOR activation and phosphorylation at Ser2448. Tissue microarray immunohistochemistry and Western blot analysis of tumor and benign tissue from 10 patients subjected to tumor nephrectomy were investigated.

PTEN and p27Kip1 are not downregulated in the majority of renal cell carcinomas--implications for Akt activation.

Activation of the PKB/Akt pathway is supposed to substantially contribute to the pathogenesis and progression of malignant disease. The present study aimed at determining the occurrence of an impaired PTEN and p27Kip1 expression alone or in combination in a renal cell carcinoma to further clarify the role of Akt-pathway-associated proteins for the development and/or progression of this malignant disease. By using tissue microarray analysis, tissue samples from renal cell cancers and the corresponding benign tissue samples were investigated for expression of the PTEN, pAkt and p27Kip1 protein by immunohistochemistry.

Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair: a COX-2 independent mechanism.

Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib.

Methods And Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by gammaH(2)AX foci assay.

Inhibition of cyclooxygenase-2 activity by celecoxib does not lead to radiosensitization of human prostate cancer cells in vitro.

Purpose: To evaluate the potential radiosensitizing effect of the specific COX-2 inhibitor celecoxib (Celebrex) on prostate carcinoma cells in vitro.

Materials And Methods: The influence of celecoxib (concentration range 5 to 75 microM) on radiation-induced cellular and clonogenic survival was investigated in prostate carcinoma cell lines PC-3, DU145, LNCaP and normal prostate epithelial cells (PrEC). Western blot analysis and ELISA were used to determine the impact of radiation alone or radiation combined with celecoxib treatment on COX-2 expression and prostaglandin E2 synthesis.

Cathepsin D expression in renal cell cancer-clinical implications.

Background: Whereas the expression of Cathepsin D (Cath D) is suggested to enhance the biological aggressiveness of human malignancies, its role in renal cell carcinoma (RCC), however, has not been investigated.

Methods: By tissue microarray analysis, tumor and benign tissue samples from 176 RCC patients were investigated for Cath D expression by immunohistochemistry and Western blots. Expression levels were correlated to clinical variables and to the postoperative outcome.

Cell cycle effects of topotecan alone and in combination with irradiation.

Background And Purpose: To elucidate the role of TP53 on differential effects of topoisomerase I inhibitor topotecan (Hycamtin on radiation sensitivity.

Materials And Methods: Cell cycle distribution and protein expression of TP53, p21(WAF1/CIP1) and cyclin B was studied in CCD32 lung fibroblasts, glioblastoma cell lines U118 (mutant TP53), and U87 (wildtype TP53) after treatment with topotecan (0.05 and 1 microM) and/or ionizing radiation (2 Gy).