Publications (49) View all
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Article: Hepatic angiogenesis and fibrosis are common features in morbidly obese patients.
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ABSTRACT: A mass of visceral adipose tissue is one of the most important determinants of progressive liver injury in nonalcoholic fatty liver disease (NAFLD). In accordance, nonalcoholic steatohepatitis (NASH) and fibrosis are believed to occur more commonly in morbidly obese patients compared with nonobese NAFLD patients. Comparative analysis of NAFLD histopathologic features and angiogenesis activity in morbidly obese and nonobese subjects. Biopsy samples from 40 severely obese (BMI ≥40 kg m(-2)) and 30 nonobese (BMI ≤30 kg m(-2)) NAFLD patients were examined. Kleiner's classification was used to diagnose NASH by grading steatosis, cytoplasmatic ballooning of hepatocytes, and lobular inflammation. The severity of fibrosis was evaluated according to the liver fibrosis staging system. Qualitative and quantitative immunohistochemical analyses of VEGF A, Flk-1, and CD34 were performed to study angiogenesis and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method was used to study hepatocyte apoptosis. Severely obese patients did not differ from nonobese patients with respect to age and sex distribution. NASH was diagnosed in nine (22.5%) severely obese patients and in seven (23.3%) nonobese patients. Fibrosis was more common in morbidly obese patients (82.5 vs. 43.5%, χ(²) = 11.71, p = 0.003) and was not associated with NASH. Moreover, the severity of fibrosis was greater in obese patients, as advanced fibrosis (bridging fibrosis and cirrhosis) occurred in six (15%) severely obese patients and in two (6.7%) nonobese patients. In morbidly obese individuals, angiogenesis was independent of NASH and was activated at the stage of simple steatosis. In severe obesity, there was a positive relationship between the stage of fibrosis and angiogenic activity. In severely obese patients, fibrosis is probably promoted by mechanisms independent of NASH. In these patients, angiogenesis is activated early in the natural history of NAFLD and correlates with the severity of fibrosis.Hepatology International 03/2013; 7(1):233-240. · 2.64 Impact Factor -
Article: PTEN expression profiles in colorectal adenocarcinoma and its precancerous lesions.
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ABSTRACT: The aim of the study was to determine expression of the PTEN suppressor gene in colorectal adenocarcinoma and its precancerous lesions (adenomatous polyps) in correlation with common clinical and histopathological features. Forty-four patients with adenomatous polyps and 32 with primary adenocarcinoma of the colon or rectum were enrolled in the study. They underwent endoscopic removal of polyps or major surgery and postoperative adjuvant chemo- and radiotherapy depending on staging of the disease. No patient had received chemotherapy and/or radiotherapy before the surgery. PTEN expression was evaluated using immunohistochemical staining on paraffin-embedded specimens and compared to clinicopathological features of tumors. In colorectal cancers, PTEN expression was found to be significantly lower than in normal intestinal mucosa and adenomatous polyps. That was associated with complete loss of PTEN expression observed more frequently in colorectal cancer, contrary to reduction of PTEN expression occurring mostly in polyps. A correlation between polyp diameter and loss of PTEN was demonstrated as well as between tumor size and TNM advanced stage and PTEN expression. The obtained results suggest that the PTEN/PI3K/Akt pathway may play an important role in early stages of sporadic colorectal carcinogenesis and reduced PTEN expression in late oncogenesis is associated with some adverse clinical and pathological features.Polish journal of pathology: official journal of the Polish Society of Pathologists 03/2013; 64(1):15-20. · 0.35 Impact Factor -
Article: JARID1B expression in human melanoma and benign melanocytic skin lesions.
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ABSTRACT: It has been suggested that dynamically regulated expression of the JARID1B protein is required for the continuous growth of tumors and at the same time downregulated in melanoma. The majority of the data on a role of JARID1B in maintaining tumor growth has come from in-vitro and xenografting experiments, with only one immunohistochemical study involving human tissues. We compared JARID1B expression levels in human melanomas and benign nevi and analyzed patterns of spatial distributions of positive cells among different skin layers of the lesions. The expression of JARID1B was evaluated by immunohistochemistry in formalin-fixed paraffin-embedded samples of 30 nevi, 27 primary melanomas, four lymph node metastases, and one local recurrence of melanoma. Staining for JARID1B protein was stronger in melanomas compared with nevi. We also found a significant difference in the spatial distribution of positive cells in individual skin layers of nevi and melanomas. Staining of melanocytes located in granular and spinous layers of nevi was observed very rarely, whereas for melanomas, the mean percentage fractions of positive cells present in these layers exceeded the maximum values found for nevi. The spatial patterns and expression levels of JARID1B did not change significantly with melanoma progression and were similar for primary, metastatic, and recurrent melanomas. Contrary to earlier reports, this study shows enhanced expression of JARID1B by melanoma cells and indicates that such an enhancement may be an early event in the disease progression, is not correlated with melanoma invasiveness, and therefore may not be a suitable candidate as a prognostic marker.Melanoma research 02/2013; 23(1):8-12. · 2.06 Impact Factor -
Article: Advanced glycation end products and lipofuscin deposits share the same location in cardiocytes of the failing heart.
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ABSTRACT: BACKGROUND: Disturbed glucose metabolism, particularly in diabetes type 2 (DM2), may result in advanced glycation end product (AGE) formation. One of the possible targets for this reaction is lipofuscin (LF), an intracytoplasmic garbage presumed to be a marker of physiologic and preterm aging of cells. The study was performed to seek for a relationship between AGE and LF in cardiocytes of the failing hearts. MATERIAL AND METHODS: Archived tissue samples from 136 hearts explanted before transplantation (in 14 pts. with ischemic cardiomyopathy (CM) and DM2; 8 pts. with dilated CM and DM2; 67 non-diabetic pts. with ischemic CM; 47 non-diabetic pts. with dilated CM), 14 autopsy cases with DM2, and 20 heart donors (control group) were involved in the study. Immunohistochemical localization of AGE was applied. The coexistence of lipofuscin and AGE was studied by LF autofluorescence in AGE-positive slides. RESULTS: LF granules inside AGE deposits were present in all studied groups with varying frequencies, but the differences were non-significant. LF granules joined significantly with dispersed patterns of AGE i.e. diffuse and mixed, whereas coincidence of LF and AGE forming granular pattern was rare. CONCLUSIONS: We demonstrate that LF may belong to the components of the AGE deposits. The frequency of this phenomenon is dependent on the AGE dispersion grade, but neither on diabetes nor cardiomyopathy presence.Experimental gerontology 09/2012; · 3.34 Impact Factor -
Article: Advanced glycation end product accumulation in the cardiomyocytes of heart failure patients with and without diabetes.
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ABSTRACT: Non-enzymatic coupling of protein and lipid cellular structures with glucose leading to the formation of advanced glycation end products (AGE) plays a role in aging and the development of diabetic complications, but its contribution to myocardial pathology is unclear. We aimed to assess the role of heart failure on AGE formation in patients with or without diabetes mellitus type 2 (DM2). Heart tissue specimens from 136 patients undergoing transplantation were grouped as follows: 14 cases of ischemic cardiomyopathy (ICM) and DM2, 8 cases of dilated cardiomyopathy (DCM) and DM2, 67 cases of ICM without DM2, and 47 cases of DCM without DM2. Fourteen heart samples were from the autopsies of patients with DM2 without heart disease, and 20 heart samples were from organ donors in whom the heart was wasted. AGE deposits were localized immunohistochemically counted using a semiquantitative scale and characterized by their staining pattern. Positive staining was present in all samples from both cardiomyopathy groups with DM2, in 71% of healthy hearts from the DM2 subjects, in 51% of ICM non-diabetic hearts, and in 38% of DCM non-diabetic hearts, and in only 15% of the organ donors. Mixed-diffuse and granular AGE patterns were characteristic for DM2, while a diffuse pattern was more frequently observed in heart failure patients without diabetes. The semiquantitative results supported increased AGE accumulation in patients with DM2 and/or cardiomyopathy. The amount of AGE in cardiomyocytes increases significantly in both diabetes and heart failure, with a staining pattern typical for each condition.Annals of transplantation: quarterly of the Polish Transplantation Society 06/2012; 17(2):53-61. · 2.02 Impact Factor
