This study, to our knowledge, is the first to explore the effects of nivolumab against ovarian cancer. The encouraging safety and clinical efficacy of nivolumab in patients with platinum-resistant ovarian cancer indicate the merit of additional large-scale investigations (UMIN Clinical Trials Registry UMIN000005714).

No abstract

Hepatitis E virus (HEV) is a causative agent of acute hepatitis. The crystal structure of HEV-like particles (HEV-LP) consisting of capsid protein was determined at 3.5-Å resolution. The capsid protein exhibited a quite different folding at the protruding and middle domains from the members of the families of Caliciviridae and Tombusviridae, while the shell domain shared the common folding. Tyr-288 at the 5-fold axis plays key roles in the assembly of HEV-LP, and aromatic amino acid residues are well conserved among the structurally related viruses. Mutational analyses indicated that the protruding domain is involved in the binding to the cells susceptive to HEV infection and has some neutralization epitopes. These structural and biological findings are important for understanding the molecular mechanisms of assembly and entry of HEV and also provide clues in the development of preventive and prophylactic measures for hepatitis E.capsid ͉ HEV ͉ VLP

Natural products produced by microorganisms are important starting compounds for drug discovery. Secondary metabolites, including antibiotics, have been isolated from different Streptomyces species. The production of these metabolites depends on the culture conditions. Therefore, the development of a new culture method can facilitate the discovery of new natural products. Here, we show that mycolic acid-containing bacteria can influence the biosynthesis of cryptic natural products in Streptomyces species. The production of red pigment by Streptomyces lividans TK23 was induced by coculture with Tsukamurella pulmonis TP-B0596, which is a mycolic acid-containing bacterium. Only living cells induced this pigment production, which was not mediated by any substances. T. pulmonis could induce natural-product synthesis in other Streptomyces strains too: it altered natural-product biosynthesis in 88.4% of the Streptomyces strains isolated from soil. The other mycolic acid-containing bacteria, Rhodococcus erythropolis and Corynebacterium glutamicum, altered biosynthesis in 87.5 and 90.2% of the Streptomyces strains, respectively. The coculture broth of T. pulmonis and Streptomyces endus S-522 contained a novel antibiotic, which we named alchivemycin A. We concluded that the mycolic acid localized in the outer cell layer of the inducer bacterium influences secondary metabolism in Streptomyces, and this activity is a result of the direct interaction between the mycolic acid-containing bacteria and Streptomyces. We used these results to develop a new coculture method, called the combined-culture method, which facilitates the screening of natural products.In modern microbiology, single-strain culture is the standard method for cultivating microorganisms. However, owing to the absence of interacting microorganisms that are present in the natural environment, the growth conditions in a flask culture are significantly different from those in the natural environment.The members of the order Actinomycetales, especially the genus Streptomyces, produce a number of antibiotics and other bioactive natural products. The genomic analysis of some Streptomyces strains revealed the presence of biosynthetic gene clusters for about 30 secondary metabolites, and these data imply that a single Streptomyces strain can produce more than 30 secondary metabolites (1, 9, 12). However, some of these secondary-metabolite genes are not expressed in fermentation culture. To date, various methods (7,14,15,17) have been used to activate genes synthesizing cryptic secondary metabolites. Secondary-metabolite production is affected by environmental factors (5, 17) such as temperature, the presence of hormone-like chemicals (6), and medium composition (3). Therefore, to identify new antibiotics, the isolation of new actinomycetes should be accompanied by the study of the effects of different growth conditions on each isolated strain.Coculture is an effective method for inducing the production of cryptic metabolites. Some coculture methods have been reported ...

Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy.