PURPOSE:Deregulation of apoptotic pathways in cutaneous malignant melanoma appears to be correlated with chemoresistance and poor prognosis. Furthermore, telomerase (especially h-TERT) expression induces proliferation and also represents a potential target for vaccination regarding some types of malignancies.MATERIALS AND METHODS:Using tissue microarrays (TMA) technology, 25 paraffin-embedded tissue samples of histologically confirmed malignant melanomas were cored at a diameter of 2 mm and re-embedded into one recipient block (final TMA density 24/25-96%). Immunohistochemistry (IHC) was performed by the use of anti-bcl-2, anti-caspase 3, anti-caspase 8 and anti- h-TERT antibodies. Protein expression levels were evaluated using a computerized image analysis system (CIA). SPSS (chi square test and inter-rater kappa) was used for statistical analysis.RESULTS:Strong protein expression was observed in 1/24 (4.1%), 1/24 (4.1%), 2/24 (8.2%), and 4/24 (16.4%) cases regarding h-TERT, caspase 3, caspase 8 and bcl-2, respectively. Moderate was observed in 7/24 (29.1%), 8/24 (32.2%), 5/24 (20.2%), and 8/24(32.2%) cases, whereas reduced or absent expression demonstrated 16/24 (65%), 15/24 (60.2%), 17/24 (68.5%), and 12/24 (50 %) cases. Statistical significance was assessed correlating age to caspase 3 (p=0.05), Breslow's thickness to telomerase (p=0.013) and to bcl-2 (p=0.053), Clark's level to telomerase (p=0.008) and to bcl-2 (p=0.022), and finally ulceration to telomerase expression (p=0.007).CONCLUSION:bcl-2 and telomerase expression are correlated to critical parameters of malignant melanoma, affecting its biological behavior. Furthermore, downregulation of proteins such as caspases 3/8, which normally induce apoptosis, is perhaps associated with resistance of the applied chemotherapeutic strategies in this type of malignancy.

Nonalcoholic fatty liver disease (NAFLD) may be the most common cause of chronic liver disease in Western countries, with an estimated prevalence of up to 24% in the general population. NAFLD is considered the hepatic manifestation of the metabolic syndrome and has been etiologically correlated with insulin resistance. The histopathological spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), with or without fibrosis, and cirrhosis. Liver biopsy is the “gold standard” for diagnosing NASH in a patient with clinical features of NAFLD, image detected steatosis and chronically elevated liver enzymes. This review discusses the histopathological findings of NAFLD in adults and children, including features representing resolution of NASH following treatment and features of prognostic information. Additionally, current systems of semiquantitative assessment in NAFLD and NASH are reviewed and the concurrence of NAFLD and NASH with other chronic liver diseases, mainly hepatitis C, is discussed. Key words: steatosis, steatohepatitis, nonalcoholic, liver, pathology

ACE-inhibitors prevent the development of left ventricular hypertrophy (LVH). The tumor suppressor gene p53 up-regulates the cellular renin-angiotensin system, resulting in ANG II synthesis, which activates p53 creating a positive feedback loop. One hundred and fourteen rabbits were separated into groups A (control), B (sham-operated), C and D. In groups C and D, an aortic stenosis was performed, and in group D the animals were treated with enalapril. For p53 determination, LV specimens were examined by Western blot analysis and an immunohistochemical study was performed, except for samples from group D. In conclusion, LVH was significantly induced at 7 and 28 days after aortic stenosis with no difference between the two periods, while enalapril prevented hypertrophy in these two groups. p53 was transcriptionally activated and immunoreactively present after acute pressure overload as well as in the sham-operated group. Enalapril decreased the p53 expression at 180 min, 7 and 28 days following aortic stenosis.

BACKGROUND:Recent in vitro studies provide evidence that the cell cycle molecules pRb, p53 and MDM2 form a tightly regulated protein network. In this study, we examined the relationship of this protein network in a series of non-small cell lung carcinomas (NSCLCs), with the kinetic parameters, including proliferative activity or proliferation index (PI) and apoptotic index (AI), and ploidy status of the tumors.MATERIAL AND METHODS:A total of 87 NSCLCs were examined using immunohistochemical and molecular methods in order to estimate the status of the pRb-p53-MDM2 network. The kinetic parameters and the ploidy status of the tumors were assessed by in situ assays. The possible associations between alterations of the network, kinetic parameters and ploidy status of the carcinomas were assessed with a series of statistical methods.RESULTS:Aberrant expression of pRb (Ab) and overexpression of p53 (P) and MDM2 (P) proteins were observed in 39%, 57%, and 68% of the carcinomas, respectively. The comprehensive analysis revealed that concurrent alterations in all three cell cycle regulatory molecules were the most frequent pattern, pRb(Ab)/p53(P)/MDM2(P); this "full abnormal" phenotype represented approximately 27% of the cases. This immunoprofile obtained the highest PI/AI value; whereas, the "normal" phenotype was the lowest one (p = 0.004). Furthermore, the pattern pRb(Ab)/p53(P)/MDM2(P) acquired the highest PI (p < 0.001) and lowest AI (p < 0.001) scores. Interestingly, the groups of carcinomas with impaired expression of one or two molecules attained PI/AI ratio values clustered in a narrow range placed in the middle of the scores exhibited by the "normal" and "full abnormal" phenotypes. These tumors had significantly lower AI, but similar PI values, compared with those noticed in the normal pattern. In addition, it was observed that the pRb(Ab)/p53(P)/MDM2(P) phenotype was also significantly associated with aneuploidy (p = 0.002) and a tendency was observed when the expression of two components was altered (p = 0.055).CONCLUSIONS:Our findings suggest that simultaneous deregulation of all members of the pRb-p53-MDM2 network confers an additive effect on tumor growth. The apoptotic pathway seems to be more susceptible to its defects than the cell proliferation machinery. The findings of the ploidy analysis, which are in parallel with those regarding the proliferative activity and the apoptotic rate study, further support the concept that these molecules constitute a tightly regulated network participating in cell cycle control and chromosomal stability.

Prednisolone administration in guinea pigs for 20 days induces significant hypergastrinemia and duodenal G-cell hyperplasia. Hypergastrinemia and duodenal G-cell hyperplasia are less prominent following 40 days of prednisolone administration and this could be partly attributed to the duodenal D-cell increased activity, which represents an adaptive response to the alterations of gastric secretory functions induced by corticosteroids.

The International Prognostic Score (IPS) was described by Hasenclever and Diehl, based on the analysis of 5023 patients with advanced Hodgkin's lymphoma (HL). In this study, we examined the prognostic efficacy of IPS in a medium sized population of patients with advanced HL. We analyzed 333 patients with advanced HL, defined as Ann Arbor stage IIB/III/IV. Anthracycline-containing regimens were administered to 75% and MOPP or similar regimens in 24% of the patients. Radiotherapy was given to 38% of the patients. Complete data on all variables of IPS were available in 229 patients (69%). More than half of the patients with missing data were eligible for grouped IPS analysis (for example 0-2 vs ‡3 etc). The distri- bution of IPS in our patients was similar to that described by Hasenclever and Diehl. the performance of IPS in the prediction of failure free (FFS) and overall survival (OS) of our patients was good. At 5 years, FFS was 100%, 68%, 72%, 52%, 56% and 83% for patients with IPS of 0, 1, 2, 3, 4 and ‡5 respectively (p=0.02). The corresponding figures for OS were 100%, 90%, 83%, 75%, 79% and 93% (p=0.16). The best discriminating cutoff for IPS was 3. At 5 years, FFS was 74% vs 55% (p=0.0004) and OS was 87% vs 72% (p=0.006) for patients with IPS 0-2 and ‡3 respectively. In conclusion, as compared to the original patient series, IPS performed well in an independent medium-sized population of similarly treated patients with advanced HL. However, IPS did not identify a sizeable distinct subgroup of patients with sufficiently low FFS, in order to be considered for first line intensified treatment.