Analysis of Snail-1, E-Cadherin and Claudin-1 Expression in Colorectal Adenomas and Carcinomas

We report the expression of Snail-1, E-cadherin and claudin-1 by indirect immunohistochemistry in colonic neoplasia. Snail-1 is a zinc finger transcription factor expressed in cells that already have undergone almost complete epithelial-mesenchymal transition (EMT) and have already evaded from the tumor. The main mechanism by which Snail induces EMT is downregulation of E-cadherin, of which expression was shown to be frequently downregulated in many different types of tumors, where it accompanies the invasiveness and metastatic behavior of malignant cells. Moreover, Snail-1 may downregulate the expression of claudin-1, a cell-cell adhesion protein which plays a likely role in progression and dissemination during tumorigenesis. Snail-1 was expressed in both carcinoma and adenoma cells with histologically normal epithelium in the mucosa, adjacent to the tumors, without significant differences, and predominant strong intensity of staining. Statistically significant differences were revealed between normal and tumorous epithelium (p = 0.003) at the subcellular level, where the shift of the protein to the cytoplasm with combined cytoplasmic/nuclear or pure cytoplasmic expression was observed. E-cadherin expression was present in 100% of cases of both adenocarcinomas and adenomas, with prevailing strong membranous immunoreactivity and no differences between protein expression in tumors and normal mucosa. Predominating strong positivity of claudin-1 was detected in tumor cells of adenocarcinomas and adenomas. Marked differences were seen in protein localization, where membranous staining, typical for nontumorous epithelium, changed to combined membranous/cytoplasmic expression in adenocarcinomas (p = 0.0001) and adenomas (0.0002), in which cytoplasmic shift was associated with a higher degree of dysplasia. Furthermore, membranous/cytoplasmic localization was more frequent in the carcinoma group (87%) in comparison with adenomas (51%) (p = 0.0001). We conclude that dystopic subcellular localizations of Snail-1 and claudin-1 may participate in changes of cellular morphology and behavior which might be associated with altered effectory pathways of proteins and thus substantially contribute to the cancer development

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Prispevek ke studiu vyvoje patologickych lezi delozniho cipku. Lokalni bunecna reakce a HPV DNA.

The aim of this work is the examination of some chosen parameters of the local immune reaction (HLA-DR, CD 68, Ino-S) in dysplastic and neoplastic cervical lesions and the analysis of anti-apoptotic Bcl-2 protein expression and DNA content (ploidy) in cervical keratinocytes with respect to any possible relationship to human papillomavirus (HPV) infection. In the theoretical part an overview of cervical dysplastic and neoplastic lesion is presented as well as risk factors which have been shown to play a role in the process of cervical epithelium cancerogenesis. The following chapter is devoted to the problems of HPVs, their characteristics and taxonomy. This work describes in detail mechanisms of cell transformation and the morphological and molecular-biological methods of HPV detection. The work includes a review of antitumour and antivirus immune reactions and several chapters consider the function of the anti-apoptotic Bcl-2 protein and the determination of ploidy and cell DNA content.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

The Changes of Angiogenesis and Immune Cell Infiltration in the Intra- and Peri-Tumoral Melanoma Microenvironment

Malignant melanoma (MM) urgently needs identification of new markers with better predictive value than currently-used clinical and histological parameters. Cancer cells stimulate the formation of a specialized tumor microenvironment, which reciprocally affects uncontrolled proliferation and migration. However, this microenvironment is heterogeneous with different sub-compartments defined by their access to oxygen and nutrients. This study evaluated microvascular density (MVD), CD3+ lymphocytes (TILs) and FOXP3+ T-regulatory lymphocytes (Tregs) on formalin-fixed paraffin-embedded tissue sections using light microscopy. We analyzed 82 malignant melanomas, divided according to the AJCC TNM classification into four groups—pT1 (35), pT2 (17), pT3 (18) and pT4 (12)—and 25 benign pigmented nevi. All parameters were measured in both the central areas of tumors (C) and at their periphery (P). A marked increase in all parameters was found in melanomas compared to nevi (p = 0.0001). There was a positive correlation between MVD, TILs, FOXP3+ Tregs and the vertical growth phase. The results show that MVD, TILs and FOXP3+ Tregs substantially influence cutaneous melanoma microenvironment. We found significant topographic differences of the parameters between central areas of tumors and their boundaries