Santanu Dutta

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported . CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.

The ethanol extract of Cyperus rotundus (EECR) was tested for possible pharmacological effects on experimental animals. EECR significantly potentiated the sleeping time of mice induced by standard hypnotics, viz. pentobarbitone sodium, diazepam, and meprobamate in a dose dependent manner. EECR showed significant analgesic properties as evidenced by the significant reduction in the number of writhes and stretches induced in mice by 1.2% acetic acid solution. It also potentiated analgesia induced by morphine and pethidine in mice. Pretreatment with EECR caused significant protection against strychnine and leptazol-induced convulsions. The behavioral studies on mice indicate CNS depressant activity of the ethanol extract of C. rotundus.

beta-D-Galactosidase (EC 3.2.1.23) was extracted from Streptococcus thermophilus grown in deproteinized cheese whey. Cultural conditions optimum for maximum enzyme production were pH 7.0, 40 degrees C, and 24 h. Proteose peptone (2.0%, wt/vol) and corn steep liquor (2.8%, wt/vol) were highly stimulatory, increasing the enzyme units available in their absence from 660 U/liter of medium to 18,200 and 10,000 U/liter of medium, respectively, in their presence. There was an insignificant increase in the production of enzyme in the presence of added inorganic nitrogen and phosphorus sources. Enzymatic hydrolysis for recuction of lactose content in aqueous solution and in skim milk was studied.

ABSTRACT A β‐galactosidase from Streptococcus thermophilus was purified to homogeneity by ammonium sulfate and acetone fractionation, gel filtration on Sephadex G‐200, and ion exchange chromatography on DEAE‐Sephadex A‐50. The purified enzyme preparation exhibited an optimum pH at 6.6–7.0 and an optimum temperature of 57°C. The enzyme was stable at pH 6.8–7.0. Km and V max for the enzyme, using ortho‐nitrophenyl β‐D‐galactopyranoside as the substrate, were 0.25 mM and 83 μmoles/mg protein/min, respectively. It was strongly inhibited by Hg ++ , Ag + , and Cu ++ as well as pchloro‐mercuri benzoate. The enzyme had a molecular weight of about 6 × 10 5 and was highly specific for β‐galactoside bonds.