Biomedical subjects

Nina Zidar

Publications and source records attributed to Nina Zidar.

7 recordsLinked to original sources

PubMed2006

Expression of p16 in sinonasal malignant melanoma.

The aim of this study was to investigate the expression of p16 in relation with the histopathologic features and the clinical course in patients with sinonasal melanoma. Thirty-seven sinonasal melanomas were immunostained for p16. Seventeen tumours were investigated for loss of the 9p21 region using interphase fluorescence in situ hybridization (FISH). Twenty-seven melanomas (72.9%) showed loss of p16 expression. All cases with spindle or mixed cytology showed loss of p16, whereas this was present in 50% of epithelioid tumours (p=0.01). Loss of p16 expression was more frequently seen in melanomas with alveolar architecture (87.5%) than in tumours with diffuse architecture (68.9%) (p=0.4). There was no correlation between p16 expression and presence of lymph node or distant metastases (p=0.57 and 0.24, respectively). In addition, p16 status did not influence overall survival (p=0.2). The FISH results were in good agreement with immunohistochemistry: 11 tumours out of 17 showed deletion of the 9p21 region and 10 of these showed loss of protein expression. Loss of p16 expression is a frequent event in sinonasal melanoma and it is mainly related to deletion of 9p21 region. At variance from cutaneous melanoma, loss of p16 is not correlated with the prognosis of patients affected by sinonasal melanoma.

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PubMed2005

Immunohistochemical expression of activated caspase-3 in human myocardial infarction.

There is mounting evidence that apoptosis is important in the pathogenesis of myocardial infarction (MI). One of the key events in the process of apoptosis is activation of caspase-3. Much attention has been recently paid to caspase inhibition as a potential treatment for ischemic cardiac disease. To predict the long-term effect of such treatment, it is essential to understand the significance of caspase-3 in the evolution of MI. Our aim was therefore to analyze immunohistochemical expression of activated caspase-3 in MI. Our study included autopsy samples of infarcted heart tissue from 50 patients with MI. Immunohistochemistry was performed by a sensitive peroxidase-streptavidin method on formalin-fixed, paraffin-embedded tissue, using monoclonal antibodies against activated (cleaved) caspase-3. We found caspase-3-positive myocytes in 18 MI less than 24 h old and in 3 MI that were presumably 48 h old. Their density (number of labeled myocytes/mm(2)) was greater in patients who received reperfusion treatment (mean 0.160+/-0.373 vs 0.025+/-0.037, p=0.06). In MI older than 48 h, positive reaction was observed in neutrophil granulocytes in the interstitium and, in subacute MI, it was observed in mononuclear inflammatory cells, myofibroblasts, and vascular endothelial cells. Our results suggest that apoptosis of myocytes is an important mode of cell death in the early MI, being enhanced in patients who received reperfusion treatment. After 48 h, apoptosis is an important mechanism of the clearance of neutrophil granulocytes and other inflammatory cells and of scar formation. Treatment with caspase inhibitors therefore will not only affect myocyte loss but will also interfere with the clearance of neutrophils and with the transformation of granulation tissue into a scar.

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PubMed2005

Expression of CD34, alpha-smooth muscle actin, and transforming growth factor beta1 in squamous intraepithelial lesions and squamous cell carcinoma of the larynx and hypopharynx.

AIM OF THE STUDY: There is increasing evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. Recent studies have shown that CD34-positive stromal cells and myofibroblasts may play an important role in host response to invasive cancer. The aim of our study was to analyze the expression of CD34, alpha-smooth muscle actin (SMA), and transforming growth factor beta1 (TGFbeta1) in squamous intraepithelial lesions (SILs) and squamous cell carcinoma (SCC) of the larynx and hypopharynx, to establish their significance, and to elucidate the mechanism of myofibroblast formation. METHODS: Immunohistochemistry was performed on samples of 42 resected larynges and 12 laryngeal biopsies of SILs and SCC using antibodies against SMA, CD34, CD31, TGFbeta1, and TGFbeta1 receptors. The expression of TGFbeta1 mRNA was detected with RNA in situ hybridization using specific oligonucleotides for TGFbeta1. RESULTS: The stroma in normal laryngeal mucosa and SILs contained scattered CD34-positive cells, but there were no SMA-positive myofibroblasts. In contrast, the stroma of SCC contained SMA-positive myofibroblasts, but there were no CD34-positive stromal cells. This pattern of stromal reaction was also observed in the peritumoral zone. In adjacent normal tissue, there were CD34-positive stromal cells and no myofibroblasts. We found more intense TGFbeta1 expression in carcinoma cells than in the normal laryngeal epithelium and positive staining for both TGFbeta1 receptors on stromal cells of the normal mucosa. In SCC, many myofibroblasts expressed TGFbeta1 and both receptors for TGFbeta1. Expression of TGFbeta1 mRNA was similar to expression of TGFbeta1 protein. CONCLUSION: Our study shows that disappearance of CD34-positive stromal cells and appearance of SMA-positive stromal myofibroblasts are associated with transformation of laryngeal SILs to SCC. This pattern of stromal reaction was found not only in the tumor but also in the peritumoral zone, defined as a band of host tissue between the invasive tumor front and adjacent normal tissue. Our findings also support the suggestion that overproduced TGFbeta1 in carcinoma cells mediates one of the mechanisms of transformation of stromal cells to myofibroblasts in laryngeal carcinogenesis.

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PubMed2005

Stem celltherapy for ischemic heart failure.

As the prevalence and incidence of ischemic heart disease continue to increase, so does interest in ischemic heart failure management. Limitations of current therapies have led to research aimed at regenerating and repairing ischemically damaged myocardium through stem-cell therapy. Cell types being evaluated include embryonic stem cells, fetal and neonatal cardiomyocytes, skeletal myoblasts, bone marrow stem cells, peripheral blood CD34+ cells, endothelial progenitor cells, cardiac progenitor cells, and fibroblasts. Preclinical animal studies and promising early results of clinical trials now under way suggest that stem-cell therapy may soon become an important new tool in heart failure management.

Heart Failure↗

PubMed2004

Colorectal carcinoma in endoscopic biopsies; additional histologic criteria for the diagnosis.

In endoscopic biopsies, desmoplastic stroma and/or tumor invasion of the submucosa are generally regarded as histologic features that allow for the diagnosis of colorectal carcinoma (CRC). They are not present in all endoscopic biopsies of CRC. We investigated tumor necrosis and invasion of adjacent normal mucosa for their usefulness as possible additional histologic criteria for CRC, and evaluated quantitatively the diagnostic reliability of each of the four aforementioned histologic features in routine biopsy practice. We analyzed 440 endoscopic biopsies of lesions endoscopically suspicious of CRC and compared them with 26 colorectal adenomas with malignant change and 344 colorectal adenomas. The slides were stained by H&E and the Kreyberg-Jareg trichrome method. The endoscopic histologic diagnoses were verified by histologic examination of surgically resected specimens. In endoscopic biopsies of CRC, desmoplastic stroma was found in 83.6% of the cases, tumor necrosis in 75.7%, submucosal invasion in 27.0%, and invasion of normal mucosa in 22.7%. When only one of the diagnostic features was present, there was a false positivity of 2.5-13.3%; however, the latter has fallen to 0.8% when two features were present, but disappeared when there were three or four histologic features. Adenomas with malignant change showed necrosis in 69.2% and invasion of adjacent mucosa in 15.3%. In adenomas, necrosis was present in 0.6% of the cases, desmoplastic stroma in 3.2%, and shallow erosions in 27.3%. The presence of tumor necrosis and invasion of normal mucosa were characteristic histologic features of CRC; therefore, they represent useful additional histologic criteria for the diagnosis of CRC in endoscopic biopsies. The reliability of the histologic diagnosis of CRC correlated with the number of the four aforementioned histologic features.

Adenoma↗

PubMed2002

Proliferation of myofibroblasts in the stroma of epithelial hyperplastic lesions and squamous carcinoma of the larynx.

OBJECTIVES: The immunohistochemical phenotype, distribution and significance of proliferation of myofibroblasts in laryngeal epithelial hyperplastic lesions (EHL) and squamous carcinoma (SC) were analyzed. METHODS: Samples of 42 resected larynxes and 40 laryngeal biopsies of EHL and SC were included. Immunohistochemistry was performed using antibodies against vimentin, alpha-smooth muscle actin (SMA), desmin and leukocyte common antigen. RESULTS: Myofibroblasts were vimentin- and SMA-positive, and were found exclusively in SC, indicating that invasion beyond the basement membrane is necessary to evoke a myofibroblastic stromal reaction. We observed two patterns of stromal reaction in SC: one was characterized by a marked proliferation of myofibroblasts and desmoplasia, with scarce lymphocytic infiltration; this pattern tended to be associated with well- or moderately differentiated SC. The other was characterized by few myofibroblasts, weak desmoplasia, and dense lymphocytic infiltration; the latter pattern tended to be associated with moderately or poorly differentiated SC. The degree of myofibroblast proliferation was inversely related to the density of lymphocytic infiltration. Antibodies against SMA also stained stromal blood vessels, demonstrating a gradual increase of vessel density as the grade of EHL increased. CONCLUSIONS: Immunohistochemical analysis of myofibroblasts provides useful information on the phenotypic characteristics of the stroma in laryngeal EHL and SC, and can serve as an additional marker of invasion.

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PubMedDate not supplied

Neutrophils in human myocardial infarction with rupture of the free wall.

INTRODUCTION: Experimental studies have shown that neutrophils might play an important role in the pathogenesis of ischemic and reperfusion injury in myocardial infarction (MI). Our aim was to compare histologic characteristics of MI with and without rupture of the free wall (RFW), with emphasis on the density of interstitial neutrophil infiltration. METHODS: Autopsy samples of infarcted heart tissue from 110 patients with MI (50 with and 60 without RFW) were included. On the basis of histologic changes and clinical data, all cases were divided into three groups according to the duration of MI (<or=1 day, 1--7 days, and 1--4 weeks). Neutrophils were stained immunohistochemically with antibodies against CD 15. The intensity of interstitial neutrophil infiltration was determined on the basis of percentage of the infiltrated myocardial area using an image analysis system. RESULTS: In MI that were less than 1 day or more than 7 days old, we did not observe any differences in histologic characteristics between cases with and those without RFW. In MI that were more than 1 day and less than 7 days old, we observed a significantly more intensive interstitial neutrophil infiltration in cases with RFW than in those without RFW. However, there were no significant differences in neutrophil infiltration between patients who received reperfusion treatment and those who did not. CONCLUSIONS: Our results suggest that intensive interstitial neutrophil infiltration in human MI might increase the risk of the RFW between the 2nd and the 7th days when the density of neutrophil infiltration is believed to reach a peak. We failed to confirm the hypothesis based on experimental studies that reperfusion treatment contributes significantly to the density of neutrophil infiltration.

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