Workmanflores3631

The combination of panobinostat and the MICA/B antibody reduced the number of pulmonary metastases formed by a human melanoma cell line in NSG mice reconstituted with human NK cells. NK cell-mediated immunity induced by a mAb specific for MICA/B, therefore, provides an opportunity to target tumors with mutations that render them resistant to cytotoxic T cells. Copyright ©2020, American Association for Cancer Research.Natural killer (NK) cells provide a natural defense against MHC-I-negative tumors, such as melanoma. Donor lymphocyte infusion (DLI) containing NK cells, a form of adoptive immunotherapy used after allogenic bone marrow transplantation (allo-BMT), promotes antitumor immune responses, but is often associated with life-threatening complications such as graft-versus host disease (GVHD). Here, we showed that without prior allo-BMT, DLI provoked melanoma control associated with the infiltration and persistence of the transferred NK cells. This allograft acceptance did not correlate with an increase of GVHD, instead it correlated with the expansion and activation of tumor-infiltrating NK cells that expressed the cytotoxic molecules (e.g., IFN-gamma and granzyme B) and maturation signatures (e.g., CD11bhiCD27lo and KLRGhi/CD43hi). The development of beneficial tumor-infiltrating NK cells of DLI-origin required host CD4+ T cell help in part by producing IL2, as well as by limiting regulatory CD4+ T cells (Tregs). IL2 blockade impaired the NK-dependent melanoma control, which could not be rescued by IL2 administration beyond CD4+ T cell help. Our findings linked NK allograft acceptance-CD4+ T cell help crosstalk to melanoma development without the need of allo-BMT. We thereby helped define that tumor-infiltrating NK cells of DLI-origin may serve as effective therapeutic targets for controlling melanoma. Copyright ©2020, American Association for Cancer Research.Bacterial ribosomal proteins (r-proteins) encoded by non-essential genes often carry out very important tasks in translation. In particular, this is the case of a small basic bacteria-specific r-protein L31 (bL31). Recent studies revealed a crucial role of bL31 in formation of the protein-protein intersubunit bridge B1b and hence its contribution to ribosome dynamics. In addition, bL31 counteracts ribosome destabilization by certain nascent peptides, and it may facilitate translation initiation and maintaining reading frame. Our goal was to study in vivo regulation of the rpmE operon encoding bL31. We used a previously developed approach based on chromosomally integrated fusions with the lacZ reporter. E. 1-Naphthyl PP1 cost coli rpmE is transcribed from two promoter regions, and translation of both mRNA transcripts was shown to be feedback regulated by bL31, indicating that the autogenous operator is located within the shorter transcript. The bL31-mediated control of rpmE is gene-specific, as no regulation was found for rpmE-unrelated reporters. Thus, bL31, as many other r-proteins, possesses dual activity in living cells, acting both as an integral ribosome component and an autogenous repressor. Phylogenetic studies revealed the presence of a highly conserved stem-loop structure in the rpmE 5'UTR, a presumable translational operator targeted by bL31, which was further confirmed by site-directed mutagenesis. This stable operator stem-loop separates an AU-rich translational enhancer from a Shine-Dalgarno element, which is a rare case of a non-contiguous translation initiation region. Sequence/structure computational approaches classify bL31 as an RNA-binding protein, consistent with its repressor function discovered here. Mutational analysis of bL31 showed that its unstructured N-terminal part enriched in lysine is necessary for the repressor activity. Published by Cold Spring Harbor Laboratory Press for the RNA Society.OBJECTIVES Internet search engine data have been widely used to monitor and predict infectious diseases. Existing studies have found correlations between search data and HIV/AIDS epidemics. We aimed to extend the literature through exploring the feasibility of using search data to monitor and predict the number of newly diagnosed cases of HIV/AIDS, syphilis and gonorrhoea in China. METHODS This paper used vector autoregressive model to combine the number of newly diagnosed cases with Baidu search index to predict monthly newly diagnosed cases of HIV/AIDS, syphilis and gonorrhoea in China. The procedures included (1) keywords selection and filtering; (2) construction of composite search index; (3) modelling with training data from January 2011 to October 2016 and calculating the prediction performance with validation data from November 2016 to October 2017. RESULTS The analysis showed that there was a close correlation between the monthly number of newly diagnosed cases and the composite search index (the Spearman's rank correlation coefficients were 0.777 for HIV/AIDS, 0.590 for syphilis and 0.633 for gonorrhoea, p less then 0.05 for all). The R2 were all more than 85% and the mean absolute percentage errors were less than 11%, showing the good fitting effect and prediction performance of vector autoregressive model in this field. CONCLUSIONS Our study indicated the potential feasibility of using Baidu search data to monitor and predict the number of newly diagnosed cases of HIV/AIDS, syphilis and gonorrhoea in China. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES To understand, describe and analyse the experiences of women with breast cancer in Vietnam when accessing and using breast cancer services. DESIGN Descriptive qualitative study. Women were interviewed about their experiences from the first time they became aware of symptoms or changes to their body through treatment and post-treatment. This study is the first descriptive study on breast cancer in Vietnam from the perspective of women with a breast cancer diagnosis. PARTICIPANTS Women (n=13) who had completed or were still receiving treatment for breast cancer, purposively recruited from the north and south of Vietnam. RESULTS An analysis of the experiences of women with breast cancer in Vietnam revealed a lack of awareness and knowledge about breast cancer and symptoms. Family and social support were described as key factors influencing whether a woman accesses and uses breast cancer services. Cost of treatment and out-of-pocket expenditures limited access to services and resulted in significant financial challenges for women and their families.