Johnsoncheek4941

By regulating the levels of multiple cell cycle- and apoptosis-related proteins, the combination therapy induced G1 cell cycle arrest in GBM cells. In vivo studies showed that S109 combined with radiotherapy significantly inhibited the growth of intracranial GBM and prolonged survival. Importantly, we found that S109 combined with radiotherapy promoted the nuclear accumulation of IκΒα, and inhibited phosphorylation of p65 and the transcriptional activation of NF-κΒ. read more Conclusion Our findings provide a new therapeutic regimen for improving GBM radiosensitivity as well as a scientific basis for further clinical trials to evaluate this combination therapy. © The Author(s) 2020.Background Programmed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a meta-analysis to identify the prognostic role of PD-L1 in melanoma. Methods A thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg's test and Egger's test. Results Thirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57-1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43-1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22-0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90-1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51-1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06-4.83, P = 0.592). Conclusions This meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients. © The Author(s) 2020.Background Colitis-associated cancer (CAC) is a complication of inflammatory bowel disease (IBD) with a poor prognosis because it is often diagnosed in advanced stages with local progression or metastasis. Compared with the more common polyp-induced sporadic colorectal cancer (sCRC), CAC has different molecular mechanisms. Toll-like receptor 2 (TLR2) expression is not limited to cells related to inflammation and immune function. High levels of TLR2 expression in tumor tissues of colorectal cancer (CRC) patients have been reported. This report is to investigate the effects of knockout and knockdown of the TLR2 gene on the proliferation of CAC and sCRC. Methods Twelve C57BL/6 J wild-type mice (WT) and 12 TLR2 knockout mice (TLR2-/-) were used to rapidly establish a colitis-associated cancer (CAC) model via the 1,2-dimethylhydrazine-dextran sodium sulfate (DMH-DSS) method and were divided into the normal WT control group (NC), TLR2 knockout control group (KC), normal wild-type tumor modeling group (NT), and TLR2out and knockdown of TLR2 can inhibit the proliferation of inflammation-related colorectal cancer and sporadic colorectal cancer. © The Author(s) 2020.Since Saul Kripke's influential work in the 1970s, the revisionary approach to semantic paradox-the idea that semantic paradoxes must be solved by weakening classical logic-has been increasingly popular. In this paper, we present a new revenge argument to the effect that the main revisionary approaches breed new paradoxes that they are unable to block. © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.In this paper I examine how the promissory value of genetics is constituted through processes of scale and scaling, focussing on the relationship between "rare" and "common" forms of disease. I highlight the bodies and spaces involved in the production of post-genomic knowledge and technologies of Alzheimer's disease and the development of new disease-modifying drugs. I focus on the example of the development of a monoclonal antibody therapy for Alzheimer's disease. I argue that the process of therapeutic innovation, from genetic studies and animal models to phase III clinical trials, reflects the persistent importance of a genetic imaginary and a mutually constitutive relationship between the rare and the common in in shaping visions of Alzheimer's disease medicine. Approaching this relationship as a question of scale, I suggest the importance of attending to how and where genomic knowledge is "scaled" or proves resistant to scaling. © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.This paper provides a comparison of how genetic biomarkers are used (or not) in three contexts clinic-based diagnostic work with people; lab-based research on mice and their marbles; and lab-based research on thrashing nematodes. For all the worldwide drive to find biomarkers that can be used in the detection of early, presymptomatic dementia, there is little research on how or when the association between biomarkers and a definitive disease are being made to "hold." First, we show the disjuncture between the animal modeling that underpins laboratory attempts to stabilize genetic biomarkers and the paradigms that inform clinical diagnosis. Secondly, we develop this theme to show how in our third site, an epigenetics "worm" laboratory, neurodegenerative changes are explored as located in specific gene-environment interactions over time. We speculate whether such an enactment brings us closer to a notion of "situated biology," to undercut possibilities of making genetic biomarkers of preclinical dementia hold. © 2019 The Author(s).