Stratified prokaryote network in the oxic-anoxic transition of a deep-sea halocline.

The chemical composition of the Bannock basin has been studied in some detail. We recently showed that unusual microbial populations, including a new division of Archaea (MSBL1), inhabit the NaCl-rich hypersaline brine. High salinities tend to reduce biodiversity, but when brines come into contact with fresher water the natural haloclines formed frequently contain gradients of other chemicals, including permutations of electron donors and acceptors, that may enhance microbial diversity, activity and biogeochemical cycling. Here we report a 2.5-m-thick chemocline with a steep NaCl gradient at 3.3 km within the water column betweeen Bannock anoxic hypersaline brine and overlying sea water. The chemocline supports some of the most biomass-rich and active microbial communities in the deep sea, dominated by Bacteria rather than Archaea, and including four major new divisions of Bacteria. Significantly higher metabolic activities were measured in the chemocline than in the overlying sea water and underlying brine; functional analyses indicate that a range of biological processes is likely to occur in the chemocline. Many prokaryotic taxa, including the phylogenetically new groups, were confined to defined salinities, and collectively formed a diverse, sharply stratified, deep-sea ecosystem with sufficient biomass to potentially contribute to organic geological deposits.

LHRH sparing therapy in patients with chemotherapy-naïve, mCRPC treated with abiraterone acetate plus prednisone: results of the randomized phase II SPARE trial.

BACKGROUND: Although the benefit of androgen deprivation therapy (ADT) continuation in metastatic castration-resistant prostate cancer (mCRPC) remains controversial, clinical evidence is lacking. Recent results indicated that treatment with abiraterone acetate (AA) plus prednisone (P) further suppresses serum testosterone levels over ADT alone, suggesting that continuation of ADT in the treatment of mCRPC may not be necessary. METHODS: In this exploratory phase 2 study, mCRPC patients were randomized with a 1:1 ratio to receive either continued ADT plus AA + P (Arm A) or AA + P alone (Arm B). The primary endpoint was the rate of radiographic progression-free survival (rPFS) at month 12. Secondary endpoints included PSA-response rate, objective response, time to PSA progression and safety. RESULTS: A total of 68 patients were equally randomized between the two study arms. Median testosterone-levels remained below castrate-levels throughout treatment in all patients. According to the intention-to-treat analysis the rPFS rate was 0.84 in Arm A and 0.89 in Arm B. Moderate and severe treatment-emergent adverse events were reported for 72% of the patients in Arm A and for 85% of the patients in Arm B. CONCLUSIONS: AA + P treatment without ADT may be effective in mCRPC patients and ADT may not be necessary in patients receiving AA + P.

Preliminary study of the specific endothelin a receptor antagonist zibotentan in combination with docetaxel in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: This two-part study assessed the safety and tolerability of combined treatment with zibotentan (ZD4054), a specific endothelin A receptor antagonist, plus docetaxel in patients with metastatic castration-resistant prostate cancer. METHODS: Part A was an open-label, dose-finding phase to determine the safety and toxicity profile of zibotentan in combination with docetaxel. Patients received once-daily oral zibotentan 10 mg (initial cohort) or 15 mg in combination with docetaxel 75 mg/m(2) (administered on day 1 of each 21-day cycle) for up to 10 cycles. Part B was a double-blind phase which evaluated the safety and preliminary activity of zibotentan plus docetaxel. Patients were randomized 2:1 to receive zibotentan (at the highest tolerated dose identified in part A) plus docetaxel or placebo plus docetaxel. RESULTS: Six patients were enrolled in part A (n = 3, zibotentan 10 mg; n = 3, zibotentan 15 mg). No dose-limiting toxicity was observed, thus zibotentan 15 mg in combination with docetaxel was evaluated in part B (n = 20, zibotentan plus docetaxel; n = 11, placebo plus docetaxel). CTCAE grade ≥3, most commonly neutropenia or leucopenia, were reported in 10 (50%) and nine (82%) patients in the zibotentan and placebo groups, respectively. One (17%) patient receiving placebo achieved complete response, two (22%) patients receiving zibotentan achieved partial response and stable disease occurred in six (67%) and three (50%) patients receiving zibotentan and placebo, respectively. CONCLUSIONS: The tolerability of zibotentan plus docetaxel was consistent with the known profiles of each drug. Sufficient preliminary activity was seen with this combination to merit continued development.

Body mass index as independent predictor of overall survival in patients with advanced renal cell carcinoma at start of systemic treatment-Analyses from the German clinical RCC-Registry.

OBJECTIVES: A high body mass index (BMI) is associated with an increased risk for developing renal cell carcinoma (RCC), a higher complication rate after surgery, and a postoperative decline in renal function after nephrectomy. In contrast, a high preoperative BMI has been associated with increased survival in patients with localized RCC. We examined the prognostic impact of the BMI in patients treated for metastatic RCC (mRCC) in daily routine practice in Germany. PATIENTS AND METHODS: The ongoing prospective, multicenter German clinical cohort study on mRCC (RCC-Registry) has recruited patients from more than 110 oncology/urology outpatient centers and hospitals at initiation of systemic first-line treatment. Data on patients' demographics, treatment, and outcome in routine practice, so called "real world data", have been collected. For this analysis, 606 patients were stratified into a low (BMI < 24), medium (24 < BMI < 28), and high (BMI > 28) BMI group. The influence of the BMI on the overall survival (OS) was analyzed using a multivariate Cox proportional hazards model. RESULTS: Median OS was 24.5 (95% confidence interval [CI], 19.3-28.5), 17.9 (95% CI, 15.3-20.8) and 10.9 (95% CI, 7.3-13.4) months in the high, medium, and low BMI patient group, respectively. A significant correlation of BMI with OS, independent of other factors, was found (low vs. high BMI: hazard ratio (HR): 1.94, 95% CI, 1.48-2.54; medium vs. high BMI: HR: 1.40, 95% CI, 1.10-1.78). Memorial Sloan Kettering Cancer Center risk factors were independently correlated with shorter OS. CONCLUSIONS: Our analysis showed a significant and independent correlation of a high BMI with longer OS in a prospective German cohort of mRCC routine patients starting first-line systemic treatment.