Biomedical subjects
Publications and source records attributed to M Sulkowska.
This review describe the influence of free radicals on the protein degradation during aging. The consequences of aging are changes in susceptibility of proteins on the proteases action as well as changes in cell proteolytic systems activity in different organs.
The cancer procoagulant activity has been evaluated in homogenates of esophagal, stomach and colorectal cancer tissues and in the blood serum of patients with these neoplasms's. Activity of CP was significantly higher in examined material than in control. The correlation between CP activity and progression degree as well as histological type was affirmed. The higher activity of CP in homogenates as well as in serum was observed in cases with higher degree of clinical progression and smaller activity of this enzyme corresponded with lower degree of the cancer progression. The highest activity of CP was observed in the cases of adenocarcinoma whereas the lowest in cases of squamous cell carcinoma. Higher activity of CP in homogenates of examined tissues correlated with higher activity of this enzyme in the serum. Activity of CP depended on the tissue localisation of the cancer and the highest was in the cases of stomach cancers whereas the lowest was in the cases of esophagal cancer.
The aim of the present study was to evaluate the activity of cathepsin B in 36 colorectal adenocarcinomas at stage pT3 of clinical advancement and histological grade G2. A correlation was also analysed of cathepsin B activity with the stage of anatomo-clinical advancement and the presence of chosen anatomo-clinical features of the tumour. Statistically significantly higher activity of cathepsin B was observed both in the cytosol and homogenate of the neoplastic tissue compared to its activity in the cytosol and homogenate of the adjacent unchanged tissue. A tendency was found towards higher cathepsin B activity in homogenate than in cytosol, both in the neoplastic and normal tissue. No correlation was revealed between cathepsin B activity in neoplastic cells and other anatomo-clinical tumour parameters analysed.
To evaluate cellular immunity in children with uveitis, we used the flow cytometry method to study the T lymphocyte subpopulation in peripheral blood. Cytometric analysis of peripheral blood lymphocytes using fluorochrome-marked monoclonal antibodies was carried out in 29 children aged 6-18 years with parasitic uveitis (group A) and with uveitis of another etiology (group B). The control group consisted of 28 healthy children aged 6-15 years. A substantially higher percentage of B lymphocytes (19.0 +/- 6.03) was observed in the children with parasitic uveitis than was observed in the healthy children. Moreover, the absolute values were higher in groups A (1.60 +/- 0.53) and B (1.81 +/- 0.40) than in controls (1.50 +/- 0.38). The lowest percentage of CD4+ lymphocytes (34.25 +/- 6.06) and the highest percentage of CD8+ lymphocytes (31.14 +/- 6.50) was found in children with parasitic uveitis. The lowest index CD4+/CD8+ (1.29 +/- 0.53) in the group of children with parasitic uveitis reflected severe disorders in response regulation. However, the percentage values of natural killer cells was lower in the two groups of patients than in controls. These results suggest that quantitative changes in the subpopulation of peripheral blood lymphocytes are more pronounced in parasitic uveitis.
Cathepsin D is one of the main proteolytic enzymes involved in the neoplastic process. The aim of the study was to evaluate the activity of cathepsin D in 36 colorectal adenocarcinomas (of the colon and rectum) at stage pT3 of clinical advancement and histological grade G2. The correlation of cathepsin D activity with the stage of anatomo-clinical advancement and the presence of chosen anatomo-clinical properties of the tumour was also analysed. The activity of cathepsin D was found to be statistically significantly higher both in the neoplastic tissue cytosol and homogenate, compared to the cytosol and homogenate of adjacent healthy tissue. No correlation was noted between the activity of cathepsin D in neoplastic cells and other parameters analysed.
The purpose of this retrospective study was to determine whether the intensity of tumor angiogenesis, expressed as microvessel density (MD), is indeed an important parameter predicting lymph node metastasis and survival rate in 73 women operated on for early invasive squamous cell carcinoma of the uterine cervix in stages Ib and IIa (FIGO). Angiogenesis was quantified by light microscope (LM) using an assay for vascular endothelial growth factor (VEGF). In the study, differences were revealed by comparing the MD between both groups. The patient survival with high MD was significantly worse than for those with low MD (p<0.01). A correlation was found between MD and the incidence of lymph node metastases. Hence, quantitative analysis of MD used as the expression of VEGF in the each cervical squamous cell carcinomas could be useful as a significant prognostic indicator.
CD44 is a cell adhesion molecule involved in tumour growth and progression. This study was undertaken to evaluate the expression of CD44 standard protein in a series of 54 colorectal adenocarcinomas in correlation with cathepsin D immunoreactivity and some other clinicopathological variables. Formalin-fixed and paraffin-embedded tissues were investigated with anti-CD44 standard protein and anti-cathepsin D antibody. Immunolocalisation of CD44 protein and cathepsin D was performed using LSAB method. 13 (41.9%) out of 31 carcinomas without lymph-node metastases had positive CD44 expression, whereas only 6 (26.1%) out of 23 carcinomas with lymph-node metastases were found positive for CD44 expression. CD44 expression in carcinomas was positively correlated with tumour cells cathepsin D (p<0.01) immunostaining. statistically significant correlation was found between the expression of CD44 standard protein and the tumour site, age and sex of the patients. These results suggest that the standard-type CD44 protein lymph-node metastases, probably with cooperation of cathepsin D.
Although it has been suggested that tumour budding at the invasive edge of colorectal cancer is an important prognostic factor its biological significance for tumour progression is still to be evaluated. The aim of the study was to correlate tumour budding intensity with cathepsin D expression and some other clinicopathological variables of presumed or established prognostic value. 48 patients with colorectal cancer at pT3 stage, G2 grade of histological differentiation and tumour budding at the invasive edge were evaluated. Colorectal tumours were investigated for cathepsin D expression by immunohistochemistry of formalin-fixed and paraffin embedded tissues. There was no statistically significant relationships between tumour budding intensity grade and primary tumour cathepsin D expression, stromal cell cathepsin D expression and histochemical immunostaining of cathepsin D in rumour budding at its invasive edge. The tumour budding intensity was not associated with lymph node status, tumour site, peritumoral inflammatory response as well as the patient's age and sex. The results of this study suggest that intensity of tumour budds formation at the invasive margin of colorectal cancer is not associated with presumed or established prognostic factors such as lymph node metastases, and peritumoural inflammatory reaction as well as cathepsin D expression.
The aim of the study was the quantitative analysis of AgNORs in oral squamous cell carcinomas as well as in dysplastic epithelial changes accompanied and not accompanied by oral squamous cell carcinomas. AgNOR proteins were visualized in histological slides using silver impregnation technique according to D. Ploton. In each sample 100 cell nuclei were assessed. The study used 54 cases of proliferating oral epithelial changes divided into 3 groups: group I consisting of 13 cases of dysplastic lesions not accompanied by oral squamous cell carcinomas; group II (a total of 18 cases) containing dysplastic lesions situated in the vicinity of oral carcinomas and group III (23 cases) with oral squamous cell carcinomas. Statistically significant differences were found between groups with mild dysplasia and groups with severe dysplasia as well as squamous cell carcinomas. Statistical analysis did not show any differences in the number of AgNORs between squamous cell carcinomas and epithelial lesions with severe dysplasia. Our results demonstrate that the analysis of AgNORs expression can serve only as an additional parameter to evaluate the potential of malignant transformation.
Although papilloma is the most frequent benign epithelial tumour of oral cavity, its biological potential for malignant transformation is still to be evaluated. The aim of the study was to correlate PCNA and P53 expression in 55 oral papillomas with some clinicopathological variables. The tissue samples were stained with H+E and by immunohistochemistry for PCNA and P53 protein. Staining patterns were assessed semiquantitatively and correlated with each other and grade of tumour epithelial dysplasia, tumour size, localization well patient age and sex. PCNA immunostaining was positive 43 (78%) oral papillomas. P53 immunohistochemical reaction was positive in 38 (69%) out of 55 epithelial tumours. Positive relationship between PCNA and P53 expression was observed as well as between PCNA immunostaining and grade of epithelial dysplasia. There was no statistically significant relationships between PCNA, P53 immunohistochemical positivity and papilloma size, site, patient age and sex. The results of this study suggest that immunohistochemical P53 overexpression is valuable marker of early neoplastic transformation and together with PCNA are presumed predictors for malignant transformation of oral papillomas.
The p53, a tumour suppressor gene, is the most commonly mutated gene human cancer. In this study, we performed immunohistochemical investigations of the expression of p53 protein in hyperplastic endometrium and adenocarcinoma. Positive immunostaining was detected in 7 (30%) cases of invasive adenocarcinoma, 2 (12%) cases of simple hyperplasia with atypia and 2 (14%) cases of complex hyperplasia with atypia. In simple and complex hyperplasia without atypia staining was seen in occasional cells. The results suggested that endometrial hyperplasia is not always accompanied by p53 protein accumulation, hence its expression is not an early exponent of the neoplastic process.
The aim of the present study was the ultrastructural characteristics of mast cell (MC) involved in host antitumor responses induced by local (i.t.) administration of recombinant human tumor necrosis factor alpha (rhTNF-alpha) in the primary focus of methA fibrosarcoma. MC were involved in tumor interstitium remodeling. Numerous mitochondria, well-developed RER and Golgi apparatus, clusters of polyribosomes, considerable polymorphism of granules and differentiated lamellar structures which frequently presented myelinic forms were observed after rhTNF-alpha application. In the study numerous fibres of the fibrous tissue, richly vascularized, occurred in the peripheral and intermediate tumor zones. Cluster of MC and tumor cells were seen on the border of the necrotic foci. However, proteolytic enzymes released by MC cause interstitial lysis, ensuring the place for tumor growth, and are involved in angiogenesis. Thus, it is not clear whether MC contribute to the inhibition of tumor growth or have an adjunctive role in tumor progression.
Small cell carcinoma (SCC) of the uterine cervix represents an uncommon variant of cervical cancer with an extremely aggressive biologic behavior, minimum survival chances and rapid and fatal clinical course. This retrospective study included 73 cases of patients treated for invasive squamous carcinoma of the uterine cervix at stages Ib and IIa at the Department of Gynecology in the years 1996-2000. Six patients (8%) with SCC were identified among all cases, sharing the clinical features of young age and early failure of appropriate radical treatment in the presence of apparently low stage disease. Neuroendocrine cellular characteristics were assessed by the biotin-streptavidin-peroxidase (LSAB) method using antibodies against neuron-specific enolase (NSE; DAKO), chromogranin A (CGA; DAKO) and synaptophysin (SYN; DAKO). All tumors examined were positive for NSE and/or CGA and/or SYN. Although the presence of neuroendocrine features appears to correlate with decreased survival, the number of patients is not large enough to determine statistical significance. However, the results confirm that SCC of the uterine cervix is one of the most aggressive tumors of the female genital tract.
Free radicals participate in the development of cancer. When the antioxidant defence system is not longer capable to destroy free radicals they may cause lipid and protein oxidation. Lipid peroxidation products also modify proteins. In such a situation the proteolytic-antiproteolytic balance existing in the blood may be changed. Therefore the aim of this study was to examine the correlation between antioxidant status and activity of proteolytic enzymes and their inhibitors in cases of colorectal cancer. This study included 55 patients with colorectal cancer. The blood was taken before surgery and plasma was collected. Total antioxidant status, the levels of lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) and activity of cathepsin G, elastase and their inhibitors (alpha-1-antitrypsin and alpha-2-macroglobulin) were determined in plasma. It was shown that during the development of cancer total antioxidant status was signficantly decreased while lipid peroxidation products were increased. Activity of alpha-2-macroglobulin was decreased and activity of determined enzymes was not significantly changed. The observed changes indicate a shift in proteolytic-antiproteolytic balance which may enhance carcinogenesis.
Evaluation of lymphocyte in children with uveitis basing on the study of T lymphocyte subpopulation in the peripheral blood using the flow cytometry method is presented. Cytometric analysis of peripheral blood lymphocytes using fluorochrome-marked monoclonal antibodies was carried out in 29 children, aged 6-18, with parasitic uveitis (group A) and with uveitis of another aetiology (group B). Control group consisted of 28 healthy children aged 6-15. The absolute values of T lymphocytes were higher in groups A (x = 1.60 +/- 0.53) and B (x = 1.81 +/- 0.40) compared to controls (x = 1.50 +/- 0.38). The lowest percentage of CD4+ lymphocytes (x = 34.25 +/- 6.06) and the highest percentage of CD8+ lymphocytes (x = 31.14 +/- 6.50) were revealed in children with parasitic uveitis. The lowest index CD4+/CD8+ (x = 1.29 +/- 0.53) in the group of children with parasitic uveitis reflects severe disorders in response regulation. However, the percentage values of NK cells were lower in the two groups of patients compared to controls. The results allow for the assumption that quantitative changes in the subpopulation of peripheral blood lymphocytes are more pronounced in parasitic uveitis.
The proliferative activity of cervical carcinoma was examined using proliferating cell nuclear antigen (PCNA) staining. Labelling index (LI) have been counted in sections of routinely processed paraffin embedded tissue blocks. Significant variation in PCNA LI were observed between study groups (p < 0.0235). The results obtained indicate that the evaluation of proliferative activity of cells expressed by high PCNA LI is assessed with worse prognosis.
Nonhistone proteins associated with the nucleolar organizer regions (NORs) can be visualized by a silver-staining technique on paraffin-embedded tissues. The number of black dots (AgNORs) appearing on the nuclei are thought to reflect cell differentiation and can be used as a measurement of cellular proliferative activity. In this study we tested AgNOR staining in ovarian epithelial tumors to evaluate its diagnostic potential in distinguishing between borderline tumors and carcinomas.
Pulmonary thrombosis in the course of shock remains life-threatening, despite advances in diagnosis, prophylaxis and therapy of the disease. Tumour necrosis factor-alpha (TNF-alpha) is an important mediator of shock. The aim of this study was to analyze the morphological changes in the pulmonary capillary bed in rats after intraperitoneal administration of multiple doses of TNF-alpha (10 microg TNF-alpha/24 h for 5 days; biological activity of 2-4x10(7)U/mg of protein). Morphological investigations were undertaken by light and transmission electron microscopy with emphasis on pulmonary thrombopoiesis. The study confirmed that the lungs may be an important site of extramedullary thrombopoiesis in the course of shock. The observations also suggested that megakaryocytes shed large fragments of cytoplasm within the pulmonary capillary bed and that megakaryocytes with copious cytoplasm occlude pulmonary vessels.