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Decreased levels of the serum inflammatory biomarkers, sGP130, IL-6, sCRP and BAFF, are associated with increased likelihood of AIDS related Kaposi's sarcoma in men who have sex with men. 血清炎症生物标志物sGP130、IL-6、sCRP和BAFF水平的降低与男男性行为者患艾滋病相关卡波西肉瘤的可能性增加有关。

Cancer research frontiers Pub Date : 2018-01-01 DOI: 10.17980/2018.45

Rachel Bolanos, Otoniel Martinez-Maza, Zuo-Feng Zhang, Shehnaz Hussain, Mary Sehl, Janet S Sinsheimer, Gypsyarn D'Souza, Frank Jenkins, Steven Wolinsky, Roger Detels

{"title":"Decreased levels of the serum inflammatory biomarkers, sGP130, IL-6, sCRP and BAFF, are associated with increased likelihood of AIDS related Kaposi's sarcoma in men who have sex with men.","authors":"Rachel Bolanos, Otoniel Martinez-Maza, Zuo-Feng Zhang, Shehnaz Hussain, Mary Sehl, Janet S Sinsheimer, Gypsyarn D'Souza, Frank Jenkins, Steven Wolinsky, Roger Detels","doi":"10.17980/2018.45","DOIUrl":"https://doi.org/10.17980/2018.45","url":null,"abstract":"AIDS-related Kaposi's sarcoma (AIDS-KS) risk remains substantially elevated compared with the general population, even among patients who receive effective combination antiretroviral therapy. This study investigated the role of inflammatory and immune activating biomarkers in AIDS-KS in men who have sex with men in the Multicenter AIDS Cohort study between 1984 and 2010. Concentrations of 24 serum biomarkers; IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, sGP130, sIL-2Rα, sIL-6R, eotaxin, MCP-1, MCP4, MIP 1β, TARC, BLC-BCA1, IP-10, GM-CSF, IFN-γ, BAFF, sCD14, CD27, sTNFR-2, sCRP, and TNF-α were tested longitudinally in 1,501 men. The concentrations of each biomarker were compared between AIDS-KS cases and controls at multiple time points, 0-1 years, 1-2 years, 2-3 year, 3-5 years and over 5 years, prior to KS diagnosis or study termination, using univariate non-parametric Kruskal-Wallis tests and logistic regression, adjusted for HBV and HCV co-infection, race/ethnicity, age at last visit, education, smoking and CD4+ cell count. In univariate analyses, concentrations of four markers were consistently higher in cases; sIL-2Rα, IP-10, sTNFR-2, MCP-1, and five were higher in controls; GM-CSF, IL-6, MIP-1β, sCRP, sGP130. In the adjusted models concentrations of four markers were significantly inversely associated with AIDS-KS risk including sGP130 (OR=0.14, 95% CI = 0.03-0.73, BAFF (OR=0.60, 95% CI =0.16-0.90), sCRP (OR=0.61, 95% CI = 0.43-0.87) and IL-6 (OR=0.51, 95% CI = 0.35-0.76). These results support a role for markers of immune activation and inflammation in AIDS-KS and may highlight pathways to be targeted for risk stratification or therapeutics.","PeriodicalId":87228,"journal":{"name":"Cancer research frontiers","volume":"4 1","pages":"45-59"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25316120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

In vitro visualization and characterization of wild type and mutant IDH homo- and heterodimers using Bimolecular Fluorescence Complementation. 利用双分子荧光互补技术对野生型和突变型 IDH 同二聚体和异二聚体进行体外可视化和表征。

Cancer research frontiers Pub Date : 2016-05-01 Epub Date: 2016-07-09 DOI: 10.17980/2016.311

Gemma L Robinson, Beatrice Philip, Matthew R Guthrie, James E Cox, James P Robinson, Matthew W VanBrocklin, Sheri L Holmen

{"title":"In vitro visualization and characterization of wild type and mutant IDH homo- and heterodimers using Bimolecular Fluorescence Complementation.","authors":"Gemma L Robinson, Beatrice Philip, Matthew R Guthrie, James E Cox, James P Robinson, Matthew W VanBrocklin, Sheri L Holmen","doi":"10.17980/2016.311","DOIUrl":"10.17980/2016.311","url":null,"abstract":"Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) were recently found in ~80% of WHO grade II-III gliomas and secondary glioblastomas. These mutations reduce the enzyme's ability to convert isocitrate to α-ketoglutarate and, instead, confer a novel gain-of-function resulting in the conversion of α-ketoglutarate to 2-hydroxglutarate (2-HG). However, IDH mutations exist in a heterozygous state such that a functional wild type allele is retained. Recent data suggest that the ability of mutant IDH1, but not mutant IDH2, to produce 2-HG is dependent on the activity of the retained wild type allele. In this study, we aimed to further our understanding of the interaction and function of wild type and mutant IDH heterodimers utilizing Bimolecular Fluorescence Complementation (BiFC). Dimerization of wild type and mutant IDH monomers conjugated to the N- and C-terminus of Venus protein, respectively, is directly proportional to the amount of fluorescence emitted and can be used as an approach to visualize and assess IDH dimerization. Thus, we utilized this method to visualize IDH homo- and heterodimers and to examine their cellular physiology based on subcellular localization, NADPH production, and 2-HG levels. Our results demonstrate that wild type and mutant IDH1 or IDH2 heterodimers display similar physiological characteristics to that of mutant IDH1 or IDH2 homodimers with the exception of their ability to generate NADPH. IDH1 heterodimers consistently generate NADPH whereas IDH2 heterodimers do not. However, the presence of mutant IDH1 or IDH2 in homo- or heterodimer configurations consistently generates equivalent levels of 2-HG. Our data suggest that the wild type protein is not required for the generation of 2-HG.","PeriodicalId":87228,"journal":{"name":"Cancer research frontiers","volume":"2 2","pages":"311-329"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34973781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanistic roles of epithelial and immune cell signaling during the development of colitis-associated cancer. 上皮细胞和免疫细胞信号在结肠炎相关癌症发展过程中的机制作用。

Cancer research frontiers Pub Date : 2016-02-01 Epub Date: 2016-01-21 DOI: 10.17980/2016.1

Renuka Subramaniam, Atsushi Mizoguchi, Emiko Mizoguchi

{"title":"Mechanistic roles of epithelial and immune cell signaling during the development of colitis-associated cancer.","authors":"Renuka Subramaniam, Atsushi Mizoguchi, Emiko Mizoguchi","doi":"10.17980/2016.1","DOIUrl":"https://doi.org/10.17980/2016.1","url":null,"abstract":"To date, substantial evidence has shown a significant association between inflammatory bowel diseases (IBD) and development of colitis-associated cancer (CAC). The incidence/prevalence of IBD is higher in western countries including the US, Australia, and the UK. Although CAC development is generally characterized by stepwise accumulation of genetic as well as epigenetic changes, precise mechanisms of how chronic inflammation leads to the development of CAC are largely unknown. Preceding intestinal inflammation is one of the major influential factors for CAC tumorigenesis. Mucosal immune responses including activation of aberrant signaling pathways both in innate and adaptive immune cells play a pivotal role in CAC. Tumor progression and metastasis are shaped by a tightly controlled tumor microenvironment which is orchestrated by several immune cells and stromal cells including macrophages, neutrophils, dendritic cells, myeloid derived suppressor cells, T cells, and myofibroblasts. In this article, we will discuss the contributing factors of epithelial as well as immune cell signaling in initiation of CAC tumorigenesis and mucosal immune regulatory factors in the colonic tumor microenvironment. In depth understanding of these factors is necessary to develop novel anti-inflammatory and anti-cancer therapies for CAC in the near future.","PeriodicalId":87228,"journal":{"name":"Cancer research frontiers","volume":"2 1","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841680/pdf/nihms751291.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34330950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 25