Biomedical subjects

I Linkov

Publications and source records attributed to I Linkov.

21 records · Page 2Linked to original sources

PubMed1997

Glutathione S-transferase PI (GST-pi) class expression by immunohistochemistry in benign and malignant prostate tissue.

PURPOSE: Glutathione S-transferase (GST) enzymes may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Recently, it was reported that most prostate cancers fail to express GST-pi despite an abundant presence in benign prostate tissue, suggesting a common genetic alteration. To define its presence in prostate tissue, we evaluated GST-pi expression in a variety of prostate tissues. MATERIALS AND METHODS: Immunostaining with anti-GST-pi antibody was performed on 69 benign prostates, 44 malignant prostates, 12 incidental prostate carcinomas and 17 prostatic intraepithelial neoplasia (PIN) specimens. Specimens were evaluated for the presence and percent of GST-pi. Within benign tissue, GST-pi immunostaining was distinguished between basal cells and secretory acinar epithelium. RESULTS: In benign epithelium, the basal cells demonstrated intense staining in all cases. The mean percent staining among the basal cells was 67% (R 40-90%). The acinar epithelium stained weakly positive in 94% (65/69) of specimens, however the mean percent staining was only 5% (R 0-25%). GST-pi was detected in only 3.5% (2/56) of the prostate cancers. No incidental prostate cancers and only one (6%) high grade PIN stained positive. CONCLUSIONS: Our study confirms the absence of GST-pi expression in prostate cancer and high grade PIN. Furthermore, GST-pi expression correlates well with the basal cell phenotype, but not with benign epithelial cells. The lack of staining among prostate cancer cells may reflect the absence of a basal cell layer, suggesting that GST-pi is involved more in epithelial differentiation and questioning its role in the malignant transformation of prostatic acinar cells.

Epithelium↗

PubMed1996

A dynamic model for evaluating radionuclide distribution in forests from nuclear accidents.

The Chernobyl Nuclear Power Plant accident in 1986 caused radionuclide contamination in most countries in Eastern and Western Europe. A prime example is Belarus where 23% of the total land area received chronic levels; about 1.5 x 10(6) ha of forested lands were contaminated with 40--190 kBq m-2 and 2.5 x 10(4) ha received greater than 1,480 kBq m-2 of 137Cs and other long-lived radionuclides such as 90Sr and 239,240Pu. Since the radiological dose to the forest ecosystem will tend to accumulate over long time periods (decades to centuries), we need to determine what countermeasures can be taken to limit this dose so that the affected regions can, once again, safely provide habitat and natural forest products. To address some of these problems, our initial objective is to formulate a generic model, FORESTPATH, which describes the major kinetic processes and pathways of radionuclide movement in forests and natural ecosystems and which can be used to predict future radionuclide concentrations. The model calculates the time-dependent radionuclide concentrations in different compartments of the forest ecosystem based on the information available on residence half-times in two forest types: coniferous and deciduous. The results show that the model reproduces well the radionuclide cycling pattern found in the literature for deciduous and coniferous forests. Variability analysis was used to access the relative importance of specific parameter values in the generic model performance. The FORESTPASTH model can be easily adjusted for site-specific applications.

Biological Transport, Active↗

PubMed1995

Aberrant expression of p53 or the epidermal growth factor receptor is frequent in early bronchial neoplasia and coexpression precedes squamous cell carcinoma development.

New strategies are needed for the detection and treatment of lung cancer and must derive from a fuller understanding of lung carcinogenesis. Frequent molecular genetic abnormalities occur in non-small cell lung cancer (NSCLC), but little is known about which of these precede an invasive carcinoma. We examined the expression of p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha, the most common molecular genetic abnormalities in NSCLC, in preneoplastic bronchial lesions. Primary NSCLC and associated bronchial lesions were identified by retrospective review of resected tumors at this center. Expression in the invasive carcinomas, the associated bronchial lesions, and normal lung were contrasted using immunohistochemistry. Thirty-four NSCLC associated with 62 bronchial lesions were identified. The invasive tumors included 15 squamous cell carcinomas (SCCs) and 19 non-SCCs. Bronchial lesions included areas of squamous metaplasia (n = 14), inflammatory atypia (n = 19), dysplasia (n = 17), and carcinoma in situ (n = 12). Nineteen (56%) NSCLC and 10 (16%) bronchial lesions exhibited aberrant p53 immunostaining, whereas 18 (53%) NSCLC and 30 (48%) bronchial lesions showed abnormal EGFR immunostaining. Positive staining for transforming growth factor alpha was seen in 16 (47%) NSCLC but occurred inconsistently in the bronchial lesions and in normal bronchial epithelium. Only bronchial lesions associated with squamous cell carcinomas exhibited staining for p53. Aberrant EGFR expression was not associated with a specific type of invasive carcinoma or with specific preneoplastic lesions, although there was a trend toward increased expression in dysplasia and carcinoma in situ relative to metaplasia and atypia. All but one of the NSCLC simultaneously showing aberrant p53 and EGFR staining were SCC. We conclude that: (a) transforming growth factor alpha is variably expressed in normal respiratory epithelium as well as reactive and preneoplastic bronchial lesions; (b) p53 expression is seen in preneoplastic bronchial lesions but is not present in reactive or metaplastic epithelium; (c) aberrant EGFR expression occurs in both reactive and preinvasive bronchial lesions and may be an early marker of neoplastic transformation; and (d) the simultaneous aberrant expression of EGFR and p53 occurs predominantly in SCC and their associated bronchial lesions. These findings indicate that aberrant expression of p53 or the EGFR is frequent in bronchial neoplasia, and coexpression may predispose to the development of squamous cell carcinomas of the lung.

Bronchial Neoplasms↗