Loss of heterozygosity (LOH) at specific loci may help localize tumor suppressor genes involved in the formation of various familial and sporadic tumors. In addition, the genetic loci for a number offamilial tumor syndromes have been mapped by linkage analysis. To explore the possible role of tumor suppressor genes in endocrine tumors, we tested 41 pheochromocytomas (34 sporadic and 7 familial) and 11 medullary thyroid cancers (MTC) (10 sporadic and 1 familial) for LOH near a variety of potentially important genetic loci: (a) the multiple endocrine neoplasia type 2A (MEN 2A) locus on chromosome 10; (b) the von Hippel-Lindau locus on 3p; and (c) the p53 and neurofibromatosis 1 loci on 17. We also examined chromosomes ip and 22q because previous studies in a small number of pheochromocytomas and MTCs suggested LOH in these regions. Background rates for LOH were assessed using several "random" probes. Finally, we examined a number of clinical and histologic characteristics of these tumors for possible correlations with specific genetic alterations. LOH in the region of the MEN 2A locus was uncommon (0% for MTCs, 5% for pheochromocytomas). However, we found significant allelic losses in pheochromocytomas on chromosomes ip (42%), 3p (16%), 17p (24%), and 22q (31%). We also noted a correlation between LOH on ip and urinary excretion of metanephrine by these patients (P = 0.02). LOH on ip, 3p, and 17p also appeared to be associated with increased tumor volume. Analysis of the smaller number of MTCs demonstrated allelic losses on chromosomes lp and 22q. Our results suggest that tumor formation and/or progression in pheochromocytomas and MTCs involves multiple genes, analogous with the model proposed for colon carcinoma. (J. Clin. Invest. 1991. 87:1691-1699
Exosome-derived microRNA (miRNA) has been the focus of attention in recent years. Mainly, their role in the pathogenesis of different types of cancer has been extensively studied. The different types of exosomal miRNAs (exomiRs) act as either oncogenes or oncosupressors. They have potential prognostic and diagnostic efficacy in different types of cancer due to their high stability and easy detection in bodily fluids. This is especially true in lung cancer, colorectal cancer, ovarian cancer, and breast cancer. However, their efficacy as potential therapies has not been widely investigated. This review will discuss the structure and functions of exosomes and miRNA, as well as the role of exomiRs in the pathogenesis of different types of cancer through boosting growth, promoting progression, chemotherapy resistance, angiogenesis, metastasis, and immune system evasion. We will also discuss the application of exomiRs in diagnosing different types of cancer and their role in prognosis. Furthermore, we shed light on the challenges of developing therapeutic agents using miRNAs and how the carriage of therapeutic miRNA by exosomes can help solve these challenges. Finally, we examine recent studies exploring the potential of exomiRs in treating cancers such as neuroblastoma, glioblastoma, and melanoma.
Cancer is the second most common culprit of mortality in the United States and epithelial carcinomas are considered as one of the most predominant types of cancer. The association between epithelial cancers and paired-box gene 8 (PAX8) has been studied significantly before. PAX8 belongs to the paired-box gene family, which plays an important role in the organogenesis of different body organ systems, especially the thyroid gland, the renal system, and the Müllerian system. Immunohistochemical staining is being used to detect PAX8 expression in different epithelial cancers and differentiate them from PAX8-negative tumors. In follicular, papillary, and anaplastic thyroid carcinomas, targeting the PAX8/peroxisome proliferatoractivated receptors (PPARs) fusion protein is being considered as a potential mechanism for therapy. Moreover, because of its high expression in primary ovarian cancers, PAX8 is being considered as a target for ovarian cancer treatment as well. More studies are needed to test the possibility of using PAX8 as a possible target for managing endometrial carcinomas. In this article, we review the functions of the PAX8 gene, how its mutations lead to the development of certain epithelial carcinomas, how it can be used as a diagnostic or a prognostic marker, and its potential as a therapeutic target for these cancers.
We retrospectively evaluated 99 intensive care unit patients with methicillin-resistant Staphylococcus aureus bacteremia to determine whether having a vancomycin minimum inhibitory concentration (MIC) of 2 mg/L affected mortality. This MIC was found in 5.1% of patients and was associated with the probability of death (adjusted odds ratio, 13.9 [95% confidence interval, 1.1-171.2]) independent of other factors.
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