N-BPs induce apoptosis in prostate cancer via a caspase dependent mechanism. They have effects on protein prenylation via inhibition of the mevalonate pathway and impair membrane localization of Ras in prostate cancer cells.

cells onto mineralized dentine inserts for 24 h, and counting cells after washing. RESULTSApoptosis depended on time and dose; there was significant apoptosis with higher concentrations of zoledronic acid (100 m mol/ L) after 24 h of exposure, and in DU145 cells with concentrations as low as 1 m mol/L after 72 h of exposure. The apoptotic effect was diminished by co-treating with a broadspectrum caspase inhibitor, Z-VAD-FMK. Zoledronic acid at 1 m mol/L also significantly inhibited cell adhesion to the mineralized matrix. The lipid isoprenoid analogue geranylgeraniol reduced the apoptotic and anti-adhesive effects of zoledronic acid to a greater degree than farnesol. There was also apoptosis and inhibition of adhesion with direct inhibitors of prenylation, e.g. manumycin A and GGTI-298. C3 exoenzyme, an inhibitor of RhoA, inhibited adhesion but did not cause apoptosis. CONCLUSIONZoledronic acid induces apoptosis in prostate cancer cells via a caspase-dependent mechanism, and at concentrations as low as 1 m mol/L it also inhibits adhesion of cells to mineralized matrix. These effects appear to be exerted via inhibiting G-protein prenylation and in particular geranylgeranylation .

ObjectivesTo describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis.DesignMulticentre prospective observational cohort study.Setting and participantsEleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected.OutcomesType and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival.ResultsOf 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC.ConclusionsRaising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers.

Importance: The role of cytoreductive nephrectomy in patients with metastatic renal cancer in the era of targeted therapy is uncertain. Data on targeted therapy prior to nephrectomy is lacking.Objective: To establish the safety and efficacy of upfront pazopanib prior to cytoreductive nephrectomy in previously untreated metastatic clear cell renal cancer.

No abstract