Search PubMed⌕ Search

Biomedical subjects

M Sulkowska

Publications and source records attributed to M Sulkowska.

At least 19 recordsLinked to original sources

Suitability of selected markers for identification of elements of the Intestinal Nervous System (INS).

The possibility of identifying and characterising elements of the enteric nervous system based on their contents of cathepsin D, chromogranin A, neuronal specific enolase and S-100 protein was studied in colorectal specimens (operative full-thickness, seromuscular and mucosomuscular biopsies) obtained from 15 children, aged 2 days to 10 years. Nine patients suffered from Hirschsprung's disease, and two from chronic constipation. Four neonates with imperforate anus or meconium ileus composed the control group. All markers were identified immunohistochemically by antibodies against human antigens with appropriate detection methods. Chromogranin A staining was not always adequate to identify all neuronal cell bodies and other nervous elements. However, it proved superior to the other methods in the depiction of neuroendocrine cells in the intestinal mucosa. Cathepsin D antibodies stained normal and abnormal neural cells with different intensity; nerve fibres were not stained. This marker did not allow an unequivocal differentiation of ganglion cells from macrophages within the submucosa; the latter exhibited exceptionally strong marking and in some cases represented the predominant elements in this area. Neuronal specific enolase was distinctly expressed in nerve cells and fibres of the intestinal wall. Atrophic and hypoplastic features could be identified, suggesting that this method may give some insight into functional aspects. Continuous connections between ganglions were also observed. S-100 protein antibodies resulted in a negative image of unstained ganglion cells surrounded by extensively marked Schwann cells and neural fibres. With respect to clinical application, all these markers may provide supplementary information for the differential diagnosis of intestinal motility disorders.

Biomarkers↗

P53 protein expression in oral squamous cell cancer in relation to some of its clinicopathological variables.

Oral squamous cell cancer develops through a multistep process by the accumulation of genetic and phenotypic changes. Loss of P53 tumor suppressor gene function represents the most common genetic lesion in human cancer. The significance of P53 expression for the development and progression of oral squamous cell cancer has still to be evaluated. The aim of this study was to estimate relationships between P53 protein expression and some clinicopathological variables of established or presumed prognostic value. A series of 129 oral squamous cell cancers was investgated retrospectively for expression of P53 protein by immunohistochemistry of paraffin-embedded tissue sections. The slides were stained with H+E and by immunohistochemistry with anti-human P53 antibody. Positive immunohistochemical staining for P53 protein was present in 75 (58%) oral cancer cases. There were no statistically significant correlations between oral cancer P53 expression and tumor site, grading, mitotic index, invasive margin type, as well as patients age and sex. Our results suggest that immunohistochemical overexpression of P53 is an important markerof accomplished neoplastic transformation in oral cavity lesions but it does not play a crucial role in the tumor progression.

Adult↗

Prognostic significance of CD34 expression in early cervical squamous cell carcinoma.

The aim of the study was to evaluate angiogenesis as an independent prognostic factor and to determine the correlation of the microvessel density (MD) with lymph node metastases and survival rate in 73 women operated because of invasive squamous cell carcinoma (SCC) of the uterine cervix at clinical stages lb and IIa (FIGO). The patients were divided into two groups: I--25 (34.4%) with survival rate <5 years and II--48 (65.6%) with survival rate >5 years. Angiogenesis was quantified in light microscope using an assay for CD34. The CD34 antibody intensely immunostained single endothelial cells as well as larger microvessels. In the study. differences were revealed by comparing the MD between both groups. The 5-year overall survival rate for patients with high MD was significantly worse than for those with low MD (p<0.003). A correlation was found between angiogenesis intensity and vascular involvement as well as the incidence of lymph node metastases. Thus, tissue expression of CD34 in SCC appears to be a significant prognostic indicator.

Adult↗

Antioxidant status and lipid peroxidation in colorectal cancer.

Colon carcinogenesis is a multistep process where oxygen radicals were found to enhance carcinogenesis at all stages: initiation, promotion, and progression. Since insufficient capacity of protective antioxidant system can result in cancer, the aim of this study was to examine the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and the levels of reduced glutathione, vitamin C, and vitamin E. The lipid peroxidation products were also determined by measuring malondialdehyde and 4-hydroxynonenal levels in colorectal cancer tissue collected from 55 patients. In these cases the activity of superoxide dismutase, glutathione peroxidase, and glutathione reductase was significantly increased while the activity of catalase was significantly decreased in cancer tissue. However, the level of nonenzymatic antioxidant parameters (glutathione, vitamin C, and vitamin E) was significantly decreased in cancer tissue. Further lipid peroxidation was enhanced during cancer development, manifested by a significant increase in malondialdehyde and 4-hydroxynonenal levels. The obtained results indicate significant changes in antioxidant capacity of colorectal cancer tissues, which lead to enhanced action of oxygen radicals, resulting in lipid peroxidation.

Antioxidants↗

Morphological and molecular aspects of cancerogenesis in the lung.

Morphology and some molecular aspects of hyperplastic (bronchial basal cell hyperplasia and alveolar cell hyperplasia), metaplastic (squamous metaplasia), preneoplastic and early neoplastic (dysplasia in squamous metaplasia, cancer in situ and atypical alveolar cell hyperplasia) changes were studied in 180 lungs resected due to non-small cell lung cancer: 106 cases (58.9%) of squamous cell carcinoma, 42 (23.3%) of adenocarcinoma and 32 (17.8%) of large cell carcinoma. P53 protein and PCNA expressions were detected immunohistochemically (using formalin-fixed, paraffin-embedded sections). DNA extracted from the microdissected P53-positive cells was analysed for point mutations in the P53 gene. No P53 immunostaining was observed in normal mucosa, hyperplasia of basal cells, squamous metaplasia without and with minor and moderate dysplasia of bronchial mucosa as well as alveolar cell hyperplasia. Overexpression of P53 protein occurred in 3 out of 12 (25%) cases of severe bronchial dysplasia, 5 out of 11 (45.5%) cases of intraepithelial carcinoma and 6 out of 45 (13.3%) cases of alveolar cell hyperplasia. Using direct sequencing, mutations in the P53 gene were detected in 11 out of 14 (87%) P53-immunopositive samples, including all severe dysplasias, all carcinomas in situ and 3 of 6 alveolar cell hyperplasias. A significant association was observed between PCNA expression and preinvasive as well as invasive lesions. The data clearly show that lung resected due to primary cancer ought to be treated as "field cancerization" in which one can find early morphologic events of multi-step cancerogenesis. P53 protein alterations and P53 gene mutations can occur before invasion and its frequency depends on the degree of dysplasia.

Carcinoma, Non-Small-Cell Lung↗

Immunohistochemical evaluation of cathepsin D expression in colorectal cancer.

Cathepsin D is one of the main proteolytic enzymes contributing to the development of cancer. The aim of the present study was to evaluate the expression of cathepsin D in 48 colorectal adenocarcinomas at pT3 stage of clinical advancement and G2 histologic grade. The correlation between cathepsin D expression, anatomo-clinical advancement and the presence of chosen anatomo-clinical properties of the tumours was also analysed. Formalin-fixed and paraffin-embedded tissues were investigated with anti-cathepsin D antibody. Immunolocalisation of cathepsin D was performed using Labelled Streptavidin Biotin (LSAB) method. A statistical correlation was found between high catepsin D expression in the cells of the main mass of the cancer and low cathepsin D expression in low-differentiated cancer cells which formed nests at the border of cancer invasion. There was no correlation between cathepsin D expression in the cells of colorectal cancer and other anatomo-clinical parameters of the tumours.

Adenocarcinoma↗

Correlation between chromogranin A, neuron-specific enolase and synaptophysin expression, and some clinico-pathological features of colorectal cancer.

Several studies employing various techniques have demonstrated the occurrence of neuroendocrine cells in colorectal cancers. Chromogranin A (CGA), neuron-specific enolase (NSE) and synaptophysin (SYN) are general markers of neuroendocrine cells. The aims of the present study were to evaluate the possible correlations between CGA and/or NSE and/or SYN expression in colorectal cancer and some of its clinico-pathological features. The study was conducted on 48 patients with colorectal cancer treated with surgery only at the Department of Surgical Gastroenterology, Medical Academy and District Oncology Center, Białystok. There were no statistically significant relationships between colorectal cancer CGA and/or NSE and/or SYN expression and tumor site, histopathological type, grading, lymph node metastases, age and sex of patients. However, high ratio of lymph node metastases in colorectal cancers with neuroendocrine cells suggests their more agressive clinical course.

Adult↗

Study of P53 protein expression in colorectal cancer.

Mutations of the P53 gene, strictly associated with the carcinogenesis are a commonly observed in neoplastic cells. The aim of this study was the immunohistochemical evaluation of P53 protein expression in colorectal carcinomas and analysis of its relationship to chosen anatomo-clinical and morphological parameters of the tumours. The study used the material obtained during surgical treatment of 74 colorectal carcinomas. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the antihuman P53 protein monoclonal antibody. The immunolocalization of P53 protein was performed using the Labelled Streptavidin Biotin (LSAB) method. The P53 protein expression was semiquantitatively assessed in neoplastic cells and the reaction present in more than 25% of tumour cells was accepted as the threshold of positivity. No correlation was found between P53 protein expression and tumour histologic type and site, and age and sex of patients. However, P53 protein expression in primary and metastatic tumours was found statistically significantly correlated.

Adult↗

Expression of P53 protein in primary uveal melanoma.

Malignant melanomas are the commonest intraocular tumours. The aim of the present study was the immunohistochemical analysis of P53 protein expression in 39 primary ocular melanomas treated surgically in the years 1983-1997. Expression of P53 was estimated semiquantitatively with the use of a light microscope at a magnification of x 400. At least 200 neoplastic cells per sample were analysed. The expression of P53 in 3% of melanoma cells was considered the threshold of positive reaction. The results were subjected to statistical analysis with exact Fischer's test. No statistically significant correlations were found between P53 expression and anatomoclinical properties of tumours, although increased P53 expression was observed in epithelioid-cellular melanomas and in tumours growing in women. A lack of statistically significant relationship between P53 protein level and the parameters examined, and morphological specificity of ocular melanomas hindering immunohistochemical analysis, indicate the necessity for studies on a wider group of tumours or/and use of molecular biology techniques to establish possible relations between P53 gene mutation and ocular melanoma biology.

Adult↗

Proliferative activity in endometrial hyperplasia and adenocarcinoma.

Studies on the proliferative activity of cells in endometrial hyperplasia and adenocarcinoma were performed using techniques detecting Proliferating Cell Nuclear Antigen (PCNA) and Nucleolar Organizer Regions (NORs). PCNA expression was defined as the percentage of nuclei showing reactivity in 200 cells per sample. The mean AgNOR count per cell was calculated following the analysis of at least 100 nuclei per sample at a magnification of x 400. Student-t test was used for the statistical analysis. The results obtained indicate that the evaluation of cell proliferative activity expressed by AgNOR count and PCNA index can help in the distinction between atypical hyperplasia and well-differentiated adenocarcinoma, and thus can serve as a useful pathological criterion.

Adenocarcinoma↗

Angiogenesis as a prognostic factor in invasive carcinoma of the uterine cervix.

The aim of the study was to evaluate angiogenesis as an independent prognostic factor and to determine the correlation between the angiogenic index (AI) and histologic grade of the neoplastic process in patients operated on for invasive carcinoma of the uterine cervix. Angiogenesis was assessed with immunohistochemical technique using a monoclonal antibody against human factor VIII--(F8/86 M0616, DAKO, Denmark). A positive correlation was revealed between the intensification of angiogenesis and the incidence of lymph node involvement and survival rate.

Adult↗

Evaluation of p53 and bcl-2 oncoprotein expression in precancerous lesions of the oral cavity.

The oral cavity is continually exposed to various traumas due to the effect of thermal, mechanical and chemical stimuli, which when accompanied by inflammatory states may promote the growth of neoplastic changes. Numerous studies have revealed a correlation between the expression of p53 and Bcl-2 proteins and the progression of neoplastic disease. It cannot be excluded that these proteins act as biomarkers of a neoplastic transformation threatening in precancerous states (including leukoplakia) or the already existing neoplastic transformation (e.g. in oral squamous cell carcinoma). The aim of the study was to evaluate the expression of p53 and Bcl-2 proteins in the proliferating epithelium in relation to leukoplakia degree and with regard to the lesions accompanied and not accompanied by squamous cell carcinomas. Fifty-five cases of proliferating changes in the oral epithelium (leukoplakia) were investigated. Group I contained 20 leukoplakias not accompanied by oral squamous cell carcinomas. Groups II, III and IV included 35 cases of changes in the vicinity of carcinomas on the lower lip (group II), in the front 2/3 of the tongue (group III) and in the oral floor (group IV). Staining was performed according to the immunohistochemical method with the use of monoclonal antibodies against human p53 protein (DAKO No M7001) and Bcl-2 (DAKO No M0887). A higher expression of p53 protein (54%) was found in leukoplakia changes coexisting with squamous cell carcinomas, compared with the non-accompanied ones (p53--45%). The results indicate a correlation between epithelial dysplasia degree and p53 and Bcl-2 protein expression--severe dysplasia occurred with an increase in the expression of both proteins. Leukoplakias situated in the vicinity of squamous cell carcinomas showed higher expression of p53 and Bcl-2 compared with the non-accompanied alterations. A correlation was also revealed between the location and p53 and Bcl-2 protein expression degree in the non-accompanied changes; no such correlations were found in proliferating epithelial changes adjacent to neoplastic tumors.

Carcinoma, Squamous Cell↗

[Cancer procoagulant activity in cases of esophageal, stomach and colorectal cancer considering progression degree and histological type of cancer].

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.

Adenocarcinoma↗

[The activity of cathepsin B in colorectal adenocarcinomas].

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.

Adenocarcinoma↗

Cellular immunity in pediatric uveitis.

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.

Adolescent↗

Cathepsin D activity in colorectal cancer.

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.

Adenocarcinoma↗

Tissue expression of VEGF as a prognostic factor in early cervical squamous cell carcinoma.

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.

Carcinoma, Squamous Cell↗