Time-gated luminescence assay using nonmetal probes for determination of protein kinase activity-based disease markers.

A novel nonmetal optical probe ARC-1063 whose long-lifetime luminescence is induced by association with the target protein kinase is used for the measurement of the concentration of catalytic subunit of protein kinase A (PKAc) in complicated biological solutions. High affinity (K(D) = 10 pM toward PKAc) and unique optical properties of the probe enable its application for the measurement of picomolar concentrations of PKAc in the presence of high concentrations of other proteins. The described assay is applicable in the high-throughput format with the instrument setups designed for lanthanide-based time-gated (time-resolved) luminescence methods. The assay is used for demonstration that extracellular PKAc (ECPKA) is present in plasma samples of all healthy persons and cancer patients but great care must be taken for procedures of treatment of blood samples to avoid disruption, damage, or activation of platelets in the course of plasma (or serum) preparation and conservation.

Testicular cancer survival in Estonia: improving but still relatively low.

BACKGROUND: international comparisons have pointed to very low survival of patients diagnosed with testicular cancer (TC) in Estonia. METHODS: using population based data from the Estonian Cancer Registry and period analysis, we examined trends in TC survival between 1985 and 2004. Additional results from a review of clinical records to ascertain patterns of disease management (1990-2003) were used to explain the changes and identify the areas for potential improvement. RESULTS: age-adjusted 5-year period relative survival increased from 47.9% in 1985-1989 to 74.5% in 2000-2004 (p for trend <0.01). A marked improvement was seen for the patients younger than 30, with the 5-year survival reaching 93.3%, while the improvement remained modest among patients aged 30 and above. Although substantial advances occurred in staging and treatment techniques since 1990, deficiencies remained evident in disease management, including not referring patients to an oncologist after their orchiectomy and less careful diagnostic workup for patients above 30 years of age. Low use of radiotherapy suggests poor access to contemporary equipment. Delays in seeking medical consultation, but also in starting adjuvant therapy, could have contributed to poorer outcomes. CONCLUSIONS: survival in TC increased markedly in Estonia by the 21(st) century, but is still notably lower than in the more developed countries. Multidisciplinary efforts may help to achieve further improvement. The provision of TC care should be coordinated by specialised cancer centres.

Combination therapy with capecitabine and interferon alfa-2A in patients with advanced renal cell carcinoma: a phase II study.

Capecitabine is a fluoropyrimidine carbamate capable of exploiting the high concentrations of thymidine phosphorylase in tumor tissue to achieve activation preferentially at the tumor site. Thymidine phosphorylase activity is high in renal cell carcinoma tissue. Interferon alfa has been proved to be the agent for standard therapy in metastatic renal cell carcinoma. The purpose of the study was to assess the efficacy and toxicity of combining capecitabine and interferon alfa-2A in patients with advanced renal cell carcinoma. Twenty-five patients with advanced renal cell carcinoma and no prior systemic therapy were treated with the combination of capecitabine at a dose of 1,250 mg/m2 twice daily for 2 weeks after every 21 days and interferon alfa-2A 6 million U three times a week. The overall response rate was 24.0% (95% CI, 9.4-45.1%), from 6 responded patients 5 had partial responses and 1 complete response. Stable disease status was achieved in 9 patients (36.0% with 95% CI 18.0-57.5%). The median survival time was 248 days (95% CI, 173-265 days). The median time to progression was 126 days (95% CI, 49-165 days). Grade 3-4 toxicities occurred in 12 patients and included fatigue (33.3%), nausea, hand-foot syndrome (both 12.5%), anorexia (8.3%), vomiting, anemia and neutropenia (all 4.2%). The capecitabine and interferon alfa-2A combination has clinical activity and an acceptable toxicity profile in patients with metastatic renal cell carcinoma. The importance of adding capecitabine to interferon alfa needs to be confirmed in a randomized trial.