Frontiers in oncology
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Frontiers in oncology · Jan 2014
ReviewDQB1*06:02-Associated Pathogenic Anti-Myelin Autoimmunity in Multiple Sclerosis-Like Disease: Potential Function of DQB1*06:02 as a Disease-Predisposing Allele.
Susceptibility to multiple sclerosis (MS) has been linked mainly to the HLA-DRB1 locus, with the HLA-DR15 haplotype (DRB1*1501-DQA1*0102-DQB1*0602-DRB5*0101) dominating MS risk in Caucasians. Although genes in the HLA-II region, particularly DRB1*1501, DQA1*0102-DQB1*0602, are in tight linkage disequilibrium, genome-wide-association, and gene candidate studies identified the DRB1*15:01 allele as the primary risk factor in MS. Many genetic and immune-functional studies have indicated DRB1*15:01 as a primary risk factor in MS, while only some functional studies suggested a disease-modifying role for the DRB5*01 or DQB1*06 alleles. ⋯ These findings not only offer a rationale for a potential role for DQB1*06:02 in predisposing susceptibility to MS, but also suggest a more complex and differential functional role for HLA-DR15 alleles, depending on the primary target myelin antigen. However, the conflict between these findings in HLA-Tg mice and the extensive genome-wide-association studies, which could not detect any significant effect from the DQB1*06:02 allele on MS risk, is rather puzzling. Functional analysis of MS PBLs for DQB1*06:02-associated anti-myelin autoimmunity may indicate whether or not DQB1*06:02 is associated with MS pathogenesis.
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Frontiers in oncology · Sep 2013
ReviewPlatinum-sensitive recurrence in ovarian cancer: the role of tumor microenvironment.
Despite several advances in the understanding of ovarian cancer pathobiology, in terms of driver genetic alterations in high-grade serous cancer, histologic heterogeneity of epithelial ovarian cancer, cell-of-origin for ovarian cancer, the survival rate from ovarian cancer is disappointingly low when compared to that of breast or prostate cancer. One of the factors contributing to the poor survival rate from ovarian cancer is the development of chemotherapy resistance following several rounds of chemotherapy. ⋯ In this review, we discuss the potential role of the tumor microenvironment in ovarian cancer recurrence and resistance to chemotherapy. Finally, we propose an alternative view of platinum-sensitive recurrence to describe a potential role of the ECM in the process.