PROMISE Registry: A prostate cancer registry of outcomes and germline mutations for improved survival and treatment effectiveness.

Background: Recently approved treatments and updates to genetic testing recommendations for prostate cancer have created a need for correlated analyses of patient outcomes data via germline genetic mutation status. Genetic registries address these gaps by identifying candidates for recently approved targeted treatments, expanding clinical trial data examining specific gene mutations, and understanding effects of targeted treatments in the real-world setting.

Methods: The PROMISE Registry is a 20-year (5-year recruitment, 15-year follow-up), US-wide, prospective genetic registry for prostate cancer patients.

Staurosporine increases toxicity of gemcitabine in non-small cell lung cancer cells: role of protein kinase C, deoxycytidine kinase and ribonucleotide reductase.

Gemcitabine, a deoxycytidine analog, active against non-small cell lung cancer, is phosphorylated by deoxycytidine kinase (dCK) to active nucleotides. Earlier, we found increased sensitivity to gemcitabine in P-glycoprotein (SW-2R160) and multidrug resistance-associated protein (SW-2R120), overexpressing variants of the human SW1573 non-small cell lung cancer cells. This was related to increased dCK activity.

Pharmacological aspects of the enzastaurin-pemetrexed combination in non-small cell lung cancer (NSCLC).

Conventional regimens have limited impact against NSCLC. Current research is focusing on multiple pathways as potential targets, and this review describes pharmacological aspects underlying the combination of the PKCbeta-inhibitor enzastaurin with the multitargeted antifolate pemetrexed. Pemetrexed is commonly used, alone or combined with platinum compounds, in NSCLC treatment, and ongoing studies are evaluating its target, thymidylate synthase (TS), as predictor of drug activity.

Molecular pathways involved in the synergistic interaction of the PKC beta inhibitor enzastaurin with the antifolate pemetrexed in non-small cell lung cancer cells.

Conventional regimens have limited impact against non-small cell lung cancer (NSCLC). Current research is focusing on multiple pathways as potential targets, and this study investigated molecular mechanisms underlying the combination of the PKC beta inhibitor enzastaurin with the multitargeted antifolate pemetrexed in the NSCLC cells SW1573 and A549. Pharmacologic interaction was studied using the combination-index method, while cell cycle, apoptosis induction, VEGF secretion and ERK1/2 and Akt phosphorylation were studied by flow cytometry and ELISAs.

Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer.

Glioblastoma multiforme (GBM), the most frequent malignant brain tumor, has a poor prognosis, but is relatively sensitive to radiation. Both gemcitabine and its metabolite difluorodeoxyuridine (dFdU) are potent radiosensitizers. The aim of this phase 0 study was to investigate whether gemcitabine passes the blood-tumor barrier, and is phosphorylated in the tumor by deoxycytidine kinase (dCK) to gemcitabine nucleotides in order to enable radiosensitization, and whether it is deaminated by deoxycytidine deaminase (dCDA) to dFdU.