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Biomedical subjects

S Terlikowski

Publications and source records attributed to S Terlikowski.

At least 19 recordsLinked to original sources

Evaluation of tumor angiogenesis and thymidine phosphorylase tissue expression in patients with endometrial cancer.

The formation of new blood vessels in endometrial cancer tissue is a main process, which leads to tumor progression, and is connected with tumor expansion and invasiveness. The aim of the study was evaluation of thymidine phosphorylase protein (TP) expression in human endometrial cancer cells by immunohistochemistry and comparison obtained data with intensity of angiogenesis process and clinicopathological factors as FIGO stage of disease and histopathologic grade. Endometrial cancer specimens were obtained from 55 postmenopausal patients (aged 52 to 74 years) underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. None of patients received preoperative pelvic irradiation. Histopathological typing and grading of the endometrial tumors (G-1, G-2, G-3) as well as myometrial invasion (<1/2, >1/2) were assessed using standard criteria, on hematoxylin-eosin sections. At the surgery, FIGO clinical stage of disease was determined. Thymidine phosphorylase overexpression was observed in 23 of 55 (41.8%) cases of endometrial cancer. Although we found no statistically significant differences in TP expression between histopathologic grades, particular FIGO stages showed a significant trend of increase TP tumor overexpression. Thymidine phosphorylase overexpression cases demonstrate higher intensity of angiogenesis in comparison to negative samples and results are statistically significant for t-test (p<0.0001). The most intensive new blood vessel formation was observed in G-2 of tumor differentiation grade (p=0.013 for ANOVA test) Mean angiogenic points density (APD) values in cases of G-1 histopathologic grade reached 135.7; values of G-2 and G-3 grades reached 213.8 and 162.8, respectively. Mean intensity of angiogenesis in the first FIGO stage of disease reached 160.0 APD, in stage II 205.6 APD, and in the third 286.9, respectively. Angiogenesis was more intensive in cases of advanced tumors - analysis of variance (ANOVA) confirmed statistically significant differences in APD values between FIGO stage groups (p=0.0007). In conclusion, thymidine phosphorylase expression correlates with increased microvessel density in endometrial cancer. The intensity of angiogenesis process increases according to FIGO stage of disease, which is connected with progressing of cancer disease. Thymidine phosphorylase can play an important role in endometrial cancer progression and could offer additional information about advance of disease.

Aged↗

Evaluation of angiogenesis, p-53 tissue protein expression and serum VEGF in patients with endometrial cancer.

Endometrial carcinoma occurs mostly in post-menopausal women. Classical methods of prognostication, as FIGO stage and histopathologic grade, could be improved by applying additional techniques, utilizing molecular biology and immunochemistry. p-53 tumor suppressor gene, the most commonly mutated gene in human cancers has been shown to play an important role in the biology of gynecologic carcinomas. Angiogenesis, a process of formation of new vessels, being connected to tumors progression and metastatic potential was shown to be linked with tumor suppressor genes expression. The aim of the study was to evaluate relationships between intensity of tumor angiogenesis, serum levels of Vascular Endothelial Growth Factor (VEGF) and tissue p-53 protein expression in endometrial adenocarcinoma. Angiogenic Point's Density (APD) was calculated in hot spots areas using the morphometric appliance. For detection of p53 protein in tumor samples, LSAB + Kit Alkaline Phosphatase (DAKO) was used. VEGF levels were assessed in patient's blood sampled before the operation. Overexpression of p53 protein was found in tumor tissue in 35.2% of cases and mean angiogenic points density was greater in p53 positive cases. Serum levels of VEGF were above the cut off level in 54.5% of patients, in those cases angiogenesis was also elevated. In cases of p53 overexpression, VEGF levels tended to be greater as compared with p53 negative cases. In conclusion, our study demonstrated that angiogenesis was more intensive in p53 positive cases, confirming the hypothesis of tumor suppressor-gene regulation of the process of neovascularization. Serum levels of VEGF were borderline-significantly higher in cases of p53 overexpression, they were also correlated to the angiogenesis. Joint assessment of angiogenesis and tumor suppressor genes expression may contribute to reliable evaluation of the biology of endometrial carcinoma.

Adenocarcinoma↗

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↗

Expression of nucleolar organizer regions (NORs) in ovarian epithelial tumors.

AgNOR staining technique was tested in ovarian epithelial tumors to evaluate its diagnostic potential in distinguishing between borderline tumors and well-differentiated carcinomas. In our opinion, the AgNOR count appears useful for assessing differences only between borderline and well-differentiated serous ovarian tumors at stage I of FIGO clinical advancement.

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↗

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↗

Patterns of immunohistochemical staining for p53 expression in hyperplastic endometrium and adenocarcinoma.

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.

Adenocarcinoma↗

Small cell carcinoma of the uterine cervix--an uncommon variant of cervical cancer with neuroendocrine features.

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.

Adult↗

The antitumor effect of intraperitoneal treatment with rhTNF-alpha muteins on Ehrlich ascites tumor growth.

The intraperitoneal (i.p.) treatment with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) is one of the possible therapies for tumors that are confined to the abdominal cavity. Clinical trials aiming at the exploitation of the antitumor effects of rhTNF-alpha have been largely disappointing. In this model the activity of some rhTNF-alpha derivatives was studied. Ehrlich's ascites tumor (EAT) bearing Swiss albino male mice were treated i.p. three times a week with 10 micrograms/mice of rhTNF-alpha, mutein V or mutein VI for two weeks, starting on the 4th day after tumor inoculation. Control mice received PBS. The effect of the rhTNF-alpha derivatives on the course of EAT was evaluated basing on: total ascites volume (TAV); packed cell volume (PCV); total packed cell volume (TPCV); inhibitory growth rate (IGR); cellular population of EAT fluid; morphological EAT cell changes and mean survival time (MST). In the study mutein VI had only a slight effect on MST but significant on TAV- and TPCV-IGR (p < 0.001). In mice treated with rhTNF-alpha and mutein V the enhancement of MST (p < 0.01) was accompanied by TAV- and TPCV-IGR (p < 0.001). The number of EAT cells in ascites decreased after rhTNF-alpha and mutein V administration (p < 0.001). We conclude that treatment with high-dose of this modified molecule lacking the possibility of binding with p75R and not producing so intensified side effects is likely to find wider application in therapy and prevent the ascites growth just as rhTNF-alpha dosage.

Animals↗

[Expression of PCNA antigen in cellular proliferative activity of cervical carcinoma].

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.

Carcinoma↗

[Heterogeneity of ovarian epithelial tumors in analysis of nucleolar organizer regions (NORs) expression].

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.

Adult↗

Study of borderline and invasive mucinous ovarian tumors using Ki-67 (MIB 1) antibodies and nucleolar organizer region (NOR) staining.

Extensive application of new methods in histopathology has resulted in large quantities of data on molecular markers in different types of human tumors. The main purpose has been to obtain additional parameters for the characterization of various types of malignancy to give more precise information on their biological behavior. In this study we tested AgNOR and Ki-67 (MIB 1) staining in 39 ovarian mucinous tumors to evaluate its diagnostic potential in distinguishing between borderline tumors and well-differentiated carcinomas at stage I of FIGO classification. In general, there was an increase in AgNOR median values from benign (1.83 +/- 0.8) to well-differentiated carcinomas (2.91 +/- 1.3) with an intermediate value in borderline (2.3 +/- 1.6). The lowest Ki-67 labeling index (LI) was found in benign cystadenomas (5.7% +/- 3.4%) and papillary mucinous cystadenomas (7.9 +/- 5.8%). In borderline tumors mean LI was 12.2 +/- 10.9% whereas well-differentiated carcinomas had higher LI (16.8 +/- 10.2%). There were no statistically significant differences between the evaluated tumors and techniques applied. In our opinion the AgNOR count and Ki-67 LI do not appear useful for assessing differences between borderline and well-differentiated mucinous ovarian tumors at stage I of clinical advancement.

Adenocarcinoma, Mucinous↗

Occlusion of pulmonary vessels by megakaryocytes after treatment with tumour necrosis factor-alpha (TNF-alpha).

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.

Animals↗

Nucleolar organizer regions in differentiated preneoplastic and neoplastic endometrial lesions.

The aim of the study was the quantitative assessment of nucleolar organizer regions (NORs) in the cells of preneoplastic and neoplastic endometrial lesions. Retrospective analysis included tissue material obtained from 87 patients with simple and complex hyperplasia with or without atypia and well-differentiated stage-I endometrial adenocarcinoma. Sections were made from routine paraffin blocks and stained with AgNO3. The mean number of AgNORs per cell was determined. The results obtained indicate that the evaluation of proliferative activity of cells expressed by AgNOR count can help in the distinction between atypical hyperplasia and well-differentiated adenocarcinoma, and thus can serve as a useful pathological criterion.

Adenocarcinoma↗

Comparative studies on the ultrastructure of the rat lungs after intratumor treatment of Morris hepatoma with rhTNF-alpha and its muteins.

The aim of the present study was the comparative analysis of morphological changes found in the lungs of Buffalo rats in the course of Morris hepatoma 5123 after i.t. treatment with recombinant human TNF-alpha (rhTNF-alpha) and its muteins. Modification of the native TNF-alpha molecule and synthesis of mutagenized analogues can prevent undesirable symptoms observed in the case of therapeutic administration of rhTNF-alpha. TNF-alpha has been shown to interact with two distinct membrane receptors (TNF-R): p55R and p75R. Mutagenized mutein V binds selectively with p55R. Mutein VI fails to recognize either TNF-R. The cytokines were applied in a dose of 10 micrograms protein in a cycle of 8 days. The control group consisted of tumor-bearing animals which were given PBS. Ultrastructural examinations were based on transmission electron microscope (TEM). Mutein VI-receiving animals showed enhanced changes of cytotoxic nature. Severe damage to endothelial cells (necrosis inclusive) was observed. Blood vascular lumen showed accumulation of neutrophils and monocytes. Features of enhanced activity of endothelial cells were noted. Focally, within pulmonary alveoli conglomerates of fibrin and fragments of damaged cells were found, with erythrocytes, neutrophils and macrophages in their vicinity. The epithelium of pulmonary alveoli showed signs of considerable damage, including necrosis. The lumen of pulmonary capillaries in rhTNF-alpha-treated animals showed a predominance of eosinophils and monocytic cells. Features of endothelial stimulation were observed, although without a tendency to form microthrombi. Much less pronounced changes both in the lung capillary bed and in the alveolar epithelial cells were noted in the mutein V-given animals. Our findings confirm the possibility of peripheral activation of cells involved in the cytokine-induced antitumor response. Mutein V with the smallest effect on the lung tissue rebuilding seems to be a rhTNF-alpha derivative which can delimit the undesirable symptoms in the course of antitumor therapy reduced to i.t. injections.

Animals↗