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  • Kofoed Davies posted an update 3 weeks, 5 days ago

    As such APTs participate in palmitoylation, a post-translational modification that can affect membrane localization, vesicular transport, and secretion. click here CLC-P has attributes of an APT. Thus, whereas CLC-P expresses inherent lysophospholipase activity, like some other lysophospholipase enzymes, it likely also functions in regulating the dynamic palmitoylation cycle, including, given its dominant subplasmalemmal location, at the human eosinophil’s plasma membrane. ©2020 Society for Leukocyte Biology.BACKGROUND Abnormalities in the KEPA1-NRF2 pathway have a role in cancer progression, metastasis, and resistance to chemo-/radio-therapies. Persistent activation of NRF2 associates with poor prognosis across different cancer types. However, the beneficial therapeutic strategy to harness this pathway in cancer remains unclear. This study aimed to investigate the clinical outcome with immunotherapy in NFE2L2/KEAP1 mutant population. MATERIALS AND METHODS We investigated the correlation between NFE2L2/KEAP1 mutations and tumor mutational burden (TMB)/ programmed death-ligand 1 (PD-L1) expression status to identify the therapeutic vulnerability. For this purpose, relevance analysis with TMB value was performed in 9040 cancer patients, and relevance analysis with PD-L1 expression was performed in 3457 patients. The MSKCC database and real-world evidence were used to assess the immunotherapy response in NFE2L2/KEAP1 mutant subsets. RESULTS NFE2L2/KEAP1 mutations occurred in various cancers, and the highest mutation analyzed the mutational characteristics of NFE2L2/KEAP1 alterations in 9243 Chinese patients. The highest mutation incidences occurred in lung squamous cell carcinoma as of 19.16% (NFE2L2) and 10.31% (KEAP1). Relevance analysis showed the NFE2L2/KEAP1 mutant subsets were associated with higher TMB value and PD-L1 expression. Clinical data further confirmed NFE2L2/KEAP1 mutations correlate with improved outcome with immunotherapy. These findings suggest the clinical application of immunotherapy in NFE2L2/KEAP1 mutant population. © AlphaMed Press 2020.T cells are crucial for the success of immune-based cancer therapy. Reinvigorating antitumor T cell activity by blocking checkpoint inhibitory receptors has provided clinical benefits for many cancer patients. However, the efficacy of these treatments varies in cancer patients and the mechanisms underlying these diverse responses remain elusive. The density and status of tumor-infiltrating T cells have been shown to positively correlate with patient response to checkpoint blockades. Therefore, further understanding of the heterogeneity, clonal expansion, migration, and effector functions of tumor-infiltrating T cells will provide fundamental insights into antitumor immune responses. To this end, recent advances in single-cell RNA sequencing technology have enabled profound and extensive characterization of intratumoral immune cells and have improved our understanding of their dynamic relationships. Here, we summarize recent progress in single-cell RNA sequencing technology and current strategies to uncover heterogeneous tumor-infiltrating T cell subsets. In particular, we discuss how the coupling of deep transcriptome information with T cell receptor (TCR)-based lineage tracing has furthered our understanding of intratumoral T cell populations. We also discuss the functional implications of various T cell subsets in tumors and highlight the identification of novel T cell markers with therapeutic or prognostic potential. © 2020 Amgen Inc. Journal of Leukocyte Biology published by Wiley Periodicals LLC on behalf of Society for Leukocyte Biology.Successful closure of large bore vascular access (≥12 Fr) is facilitated by the MANTA vascular closure device; however, it requires a critical first step of measuring “skin to arterial wall” depth of the access site using the depth locator before dilating the vessel above 8 Fr. It may be challenging at times to acquire the deployment depth at the onset of the procedure due to case urgency, delayed closure, or when large bore access is obtained at a different institution. We discuss a novel technique of measuring the deployment depth and successful delayed closure of large bore arterial access using the MANTA closure device. © 2020 Wiley Periodicals, Inc.Journal editors are gatekeepers of knowledge, and pharmaceutical industry payments to oncology editors have not been previously characterized. We performed a cross-sectional study of nonresearch industry payments to editors of 26 oncology research journals. A total of 433 editors were eligible for inclusion in the CMS Open Payments database from 2013 to 2018. A total of 80% of eligible editors had nonresearch payments, and the mean value of payments per editor was $106,778, which has increased over time. Only 5 out of 26 journals disclosed editor conflicts of interest and 3 of these journals reported at least one editor with no nonresearch industry payments but were found to have nonresearch payments. There was a positive correlation between journal impact factor and the average payment per editor for each journal. Our study shows the high prevalence and lack of transparency of nonresearch industry payments to oncology editors. Higher impact journals appear to be associated with greater nonresearch industry payments. © AlphaMed Press 2020.BACKGROUND The aim of this study was to investigate the predictive value of early changes in 18 F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) during fulvestrant 500 mg therapy in patients with estrogen receptor (ER)-positive metastatic breast cancer. MATERIALS AND METHODS Patients underwent 18 F-FES PET/CT scans at both baseline (scan 1) and day 28 (scan 2). The maximum standardized uptake value (SUVmax) of all metastatic sites was determined in each scan, and the percentage reduction in SUVmax (ΔSUVmax) was calculated as [(SUVmax on scan 1-SUVmax on scan 2)/ SUVmax on scan 1] * 100%. RESULTS In total, 294 18 F-FES-positive lesions from 36 patients were identified. The 18 F-FES SUVmax varied widely among lesions (median 5.7; range 1.8-32.4) and patients (median 5.1; range 2.5-13.2). After treatment, the median SUVmax among lesions and patients was 2.1 and 2.1, respectively. The ΔSUVmax ranged from -5.1% to 100%, with a median reduction of 61.3%. Using receiver operating characteristic analysis, the optimal cutoff point to discriminate patients who could derive clinical benefit from fulvestrant was determined to be 38.

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