Diagnostic mesothelioma biomarkers in effusion cytology

Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1-associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.     

Monocyte to HDL ratio: a novel marker of resistant hypertension in CKD patients

International Urology and Nephrology - Inflammation, oxidative stress (OS), atherosclerosis and resistant hypertension (RH) are common features of chronic kidney disease (CKD) leading to a higher...     

IL-17 and its role in inflammatory,autoimmune, and oncological skin diseases: state of art

Recent data support the theory of the involvement of IL-17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases). Even if the role of IL-17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumor is still controversial. Some reports show that Th17 cells eradicate tumors, while others reveal that they promote the initiation and early growth of tumors. Herein, we review the role of IL-17 in the involvement of some common dermatologic diseases: psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, vitiligo, melanoma, and nonmelanoma skin cancers.     

Cytoskeleton reorganization and ultrastructural damage induced by gliadin in a three-dimensional in vitro model

AIM: To evaluate the interplay between gliadin and LoVo cells and the direct effect of gliadin on cytoskeletal patterns. METHODS: We treated LoVo multicellular spheroids with digested bread wheat gliadin in order to investigate their morphology and ultrastructure (by means of light microscopy and scanning electron microscopy), and the effect of gliadin on actin (phalloidin fluorescence) and the tight-junction protein occludin and zonula occluden-1. RESULTS: The treated spheroids had deep holes and surface blebs, whereas the controls were smoothly surfaced ovoids. The incubation of LoVo spheroids with gliadin decreased the number of intracellular actin filaments, impaired and disassembled the integrity of the tight-junction system. CONCLUSION: Our data obtained from an "in vivo-like" polarized culture system confirm the direct noxious effect of gliadin on the cytoskeleton and tight junctions of epithelial cells. Unlike two-dimensional cell culture systems, the use of multicellular spheroids seems to provide a suitable model for studying cell-cell interactions.     

Homocysteine metabolism in renal failure

PURPOSE OF REVIEW: This review focuses on recent findings (June 2002-July 2003) on the topic of homocysteine, a sulfur amino acid associated with cardiovascular disease, and its metabolism in renal failure, a condition with a high prevalence of both hyperhomocysteinemia and cardiovascular disease. RECENT FINDINGS: A large meta-analysis of prospective studies in the general population established that hyperhomocysteinemia is a risk factor for cardiovascular disease. The results of intervention trials, once available, will also have to be tested in a meta-analysis, because of predicted problems with their statistical power. In kidney patients, intervention trials, still in the recruiting stage, target transplant patients, because of their unique characteristics related to folate responsiveness. As for the cause of hyperhomocysteinemia, new findings show that in humans, renal metabolic extraction depends on renal plasma flow in the post-absorptive state. Folate absorption or interconversion seems not to be affected. Riboflavin is a determinant of plasma homocysteine levels in uraemia. The consequences of hyperhomocysteinemia in uraemia are DNA hypomethylation and altered gene expression. SUMMARY: The causes of hyperhomocysteinemia in renal failure are still not clear. However, the possibilities include defective renal or extrarenal metabolism as a result of uraemic toxicity. Renal plasma flow is important in homocysteine renal metabolism. Among the consequences of hyperhomocysteinemia in renal failure are impaired protein and DNA methylation, with an alteration in the allelic expression of genes regulated through methylation. Intervention trials are under way to test whether hyperhomocysteinemia is causally related to cardiovascular disease in this patient population.