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Biomedical subjects

L Chyczewski

Publications and source records attributed to L Chyczewski.

At least 73 records · Page 4Linked to original sources
PubMed2000

p53 gene mutation and protein expression in operable non-small cell lung cancer in Poland.

We investigated the association of p53 abnormalities (gene mutations by DNA sequencing and protein over-expression by immunostaining) with clinical data and prognosis in 74 patients with resected non-small cell lung cancer (NSCLC). DNA analysis of exons 5-8 of the p53 gene showed 34 mutations in 74 resected primary NSCLC (45.9%). Immunohistochemical study of the p53 protein revealed that 41 of 74 (55.4%) samples had positive staining. We found strong agreement between the results of the p53 protein expression test (p53-PE) and the p53 gene mutation test (p53-M) (Cohen's kappa = 0.65, 95% CI 0.48-0.82). Joint distribution of the results (analysed using the bivariate Dale model) was mainly influenced by, histological type of tumour. A positive result for the p53-PE test significantly increased (estimated odds ratio 84.5; 95% CI 8.89-803.03) the odds of observing a positive result in the p53-M test. In the univariate analysis (log rank test), positive results in the p53-M test and the p53-PE test were significantly associated with overall survival (P < 0.001 and P = 0.005, respectively). In the multivariate analysis (Cox's proportional hazard model), a positive result for the p53-M test significantly increased relative risk for overall survival (RR 9.56; 95% CI 2.62-34.87; P < 0.001). When the result of the p53-M test was accounted for, a positive result for the p53-PE test did not offer any additional prognostic information due to the strong dependence of results of the tests. However, when the result of the p53-M test was removed from the model, a positive result for the p53-PE test became a significant unfavourable prognostic factor (P = 0.009). We conclude that p53 gene mutation and protein expression analyses are in a strong agreement. Joint distribution of the results depends mainly on histological type of tumour. When considered separately, both tests are unfavourable prognostic factors in NSCLC. When the result of the p53-M test is taken into account, the p53-PE test does not offer any additional prognostic information.

Adult↗
PubMed1999

Expression of bcl-2 protein in non-small cell lung cancer: correlation with clinicopathology and patient survival.

Molecular genetic studies have revealed mutations in a number of oncogenes and tumor suppressor genes in lung cancer. The bcl-2 gene product (bcl-2 protein) is implicated in oncogenesis by its ability to prolong cell death through the inhibition of apoptosis. We investigated expression of bcl-2 in 84 resected human non-small cell lung cancers (NSCLC) and correlated this phenomena with clinicopathology and survival. Immunohistochemical analysis with a monoclonal antibody specific for bcl-2 (Clone 124; Dako) was used to detect the protein in tumor samples. Overall, bcl-2 was detectable in 39 of 84 (46%) NSCLC. The percentage of bcl-2 positive cases varied according to the histological type. Positive bcl-2 immunostaining was observed in 27 of the 46 squamous cell carcinomas (59%), 7 of the 25 adenocarcinomas (28%) and 5 of the 13 large cell carcinomas (38%). The frequency of positive bcl-2 expression in squamous cell carcinomas was significantly higher than that in other histological two types (p = 0.037). Statistical comparisons between the patients' clinical characteristics and bcl-2 status revealed no significant differences in the frequency of bcl-2 expression with respect to sex, T and N factors, as well as TNM stage. The relationship between bcl-2 protein expression and postoperative survival was analyzed in 84 patients. Patients with bcl-2 negative tumors showed significantly shorter survival times than those with bcl-2 positive tumors. In univariate analysis of various potential prognostic factors only TNM stage and bcl-2 test were significant prognostic factors (p < 0.009 and p < 0.008, respectively). In multivariate analysis (Cox proportional hazard model), bcl-2 status (negative test) was independent unfavorable prognostic factor (p = 0.017). In conclusion, this set of observations suggests that assessment of the expression status of bcl-2 by tumors may provide prognostic information on the clinical behavior of NSCLC.

Antibodies, Monoclonal↗
PubMed1999

Distribution, activity and concentration of cathepsin B and cystatin C in the wall of aortic aneurysm.

Intensity of immunohistochemical reaction to cathepsin B is stronger and to cystatin C weaker in the wall of aortic aneurysm than in normal aorta. Localization of cathepsin B and cystatin C in the aneurysm wall is different from that in the control aorta, but activity and concentration of cystatin C in the aneurysmal wall is lower than in normal aorta. The parietal thrombus of aneurysm also shows high activity of cathepsin B. The obtained results point to participation of cathepsin B in degradation of aneurysmal structural proteins and in enlargement of the aneurysmal size.

Adult↗
PubMed1999

BN52021 stabilizes the oxidant-antioxidant equilibrium in peritoneal lavage fluid in experimental hemorrhagic shock.

The overproduction of highly reactive oxygen metabolites initiates and contributes to the damage to abdominal organs in hemorrhagic shock (HS). Peritoneal environment including free cells located in peritoneal cavity may interact with the inflammatory processes occurring in abdominal organs during HS. Peritoneal lavage was carried out in 48 rats divided into following groups: (1) control, (2) untreated HS for 75 minutes, (3) HS + restoration of blood volume with polyelectrolyte solution (PES) 60 minutes after blood withdrawal, and (4) HS + platelet activating factor (PAF) receptor antagonist BN52021 directly after bleeding + PES after 60 minutes of HS. Peritoneal lavage fluid (PLF) was examined for Cu-, Zn-superoxide dismutase (SOD) activity, sulfhydryl compound (-SH) concentration, and malondialdehyde (MDA) level measured as thiobarbituric acid reactive substances (TBARS). The untreated shock (group 2) as well as HS + PES (group 3), resulted in significant increase in cell numbers in PLF. In groups 2 and 3, the SOD activities were not detected while -SH group levels were significantly higher, than those in the control. The group of shocked rats after blood volume restoration with PES was the only group where the MDA in PLF was found. The highest -SH group concentrations and detectable SOD activities were recorded in shocked rats treated with BN52021 and PES. Systemic hemorrhage may cause significant alterations in the oxidant-antioxidant (O-A) balance in peritoneal cavity, accompanied by significant elevation of number of cells lavaged from peritoneal cavity. There is an escalation of disturbances in O-A balance in peritoneal lavage fluid due to restoration of blood volume. BN52021 may exert beneficial effects stabilizing peritoneal antioxidant system in the hemorrhagic shock.

Animals↗
PubMed1999

p53 protein expression in resected invasive esophageal cancer.

Many studies have reported the increased expression of p53 protein in various human malignancies and its accumulation have been considered an intermediate biomarker in multistage carcinogenesis. This study was designed to evaluate p53 expression by immunohistochemistry using Dako p53, D0-7 monoclonal antibody in 33 resected invasive squamous cell esophageal cancers (SqCC). The relationship between p53 immunoreactivity and clinicopathologic parameters was determined by the Chi-square test and Student's t test. p53 protein overexpression (more then 10% positive staining cancer cells) was found in 15 out of 33 (45%) tumors. Positive test was found in 38% cases in Stage IIA, 57% in Stage IIB, 45% in Stage III and 50% cases in Stage IV. p53 overexpression was observed in 48% of tumors with lymph nodes metastases, and 41% of tumors without lymph nodes metastases. In respect of tumor differentiation, cases graded as G1, G2 and G3 were positive in 50%, 50% and 40%, respectively. Thirteen per cent of patients with p53 protein overexpression and 16% of patients without p53 protein overexpression survived more than 3 years. There was no correlation between p53 overexpression and stage, tumor differentiation, lymph nodes metastases, and patients survival. In conclusion our results showed that p53 overexpression did not correlate with clinicopathologic feature of invasive SqCC of the esophagus and p53 protein overexpression was unsuitable for predicting the outcome of patients after surgical resection.

Aged↗
PubMed1999

Flow cytometric examination of DNA ploidy, p53 and bcl-2 expression in primary squamous epithelial pulmonary carcinoma.

The aim of this study was answering the question whether cytofluorimetric determining of DNA ploidy, p53 and bcl-2 expression in tumour cells may enhance the diagnosis of squamous epithelial lung carcinoma. Samples of neoplastic tissue were taken from 11 operated patients. DNA staining was performed with propidium iodide. p53 and bcl-2 expression was evaluated by using monoclonal antibodies. By assessing of DNA ploidy we observed increased proliferative activity and, at the same time, high rate of the cell necrosis. In the analysis of p53 protein the presence of antigen was observed on average in 7.1 +/- 2.4, 15.1 +/- 3.9, and 19.8 +/- 4.1% of normal cells of the pulmonary tissue, the peripheral part of the tumour and cells of the central part of the tumour, respectively. bcl-2 was found on average in 7.3 +/- 2.2, 9.9 +/- 3.1, and 12.4 +/- 3.19% of the above cells, respectively. These results show that the technique of cytofluorimetric evaluation of p53 and bcl-2 proteins can be useful in diagnosis of pulmonary cancer in addition to classic histological and immunohistochemical methods.

Adult↗
PubMed1999

BN52021 inhibits activation of peritoneal mast cells caused by hemorrhage and blood volume restoration.

An extensive blood loss activates generalized inflammatory response. Abdominal organs and especially intestines are very sensitive to the ischemia-reperfusion insults due to hemorrhagic shock (HS) and blood volume restoration. Previously obtained results suggest that studies on peritoneal lavage fluid (PLF) can contribute to elucidation of inflammatory processes in abdominal organs in HS. Histamine (H) levels, total cell, and mast cell (MC) numbers, and MC ultrastructure in the fluid lavaged from peritoneal cavity were compared in the following groups of rats: control (gr. 1), sham operation (gr. 2), untreated hemorrhagic shock (gr. 3), shock treated with blood volume restoration with lactated Ringer's solution (LR) (gr. 4), shock treated with platelet activating factor (PAF)-receptor antagonist Ginkgolide B (BN52021), and LR (gr. 5). A shock-related significant increase in total cell numbers, MC numbers, MC degranulation, and histamine levels in PLF were observed. The restoration of blood volume caused further elevation of the above phenomena (gr. 4) while BN52021 seemed to inhibit peritoneal MC mobilization and degranulation as well as to attenuate increase in peritoneal H level (gr. 5). The peritoneal cavity is a place of rapid and strong reaction to hemorrhage. Evaluation of peritoneal histamine levels might be helpful in the monitoring of shock dependent intra-abdominal processes. Peritoneal MC mobilization and degranulation, and increase in histamine level is inhibited by BN52021.

Animals↗
PubMed1998

Platelet-activating factor receptor-antagonist (BN 52021) stabilizes the oxidative-antioxidative balance and attenuates the morphological changes in the gastrointestinal tract in experimental hemorrhagic shock.

The influence of the platelet-activating factor receptor-antagonist (BN 52021) and polyelectrolyte solution (PES) on the morphology and oxidant-antioxidant equilibrium in the gastrointestinal wall in hemorrhagic shock was examined in rats. The animals were divided into five groups: I - control, II - sham operation, III - untreated hemorrhagic shock lasting 75 minutes, IV - shock treated with PES, and V - shock treated with BN 52021 and PES. The most expressed morphological changes were found in the small intestine in group IV (shock treated with PES) and in group III (untreated shock). Morphological changes were well correlated with the malondialdehyde (MDA) level reflecting oxidative tissue injury and with the antioxidative potential: sulfhydryl compounds (-SH) level, and superoxide dismutase (SOD) activity. The signs of morphological and biochemical injury to the gastrointestinal tract in animals from group V (treated with BN 52021 and PES) were significantly less expressed than those in groups III and IV. The results suggest an essential role of PAF in oxygen radicals-mediated gastrointestinal injury and a beneficial effect of the early application of BN 52021 in hemorrhagic shock.

Animals↗
PubMed1998

Hemorrhagic shock-induced changes in the cathepsin D activity in the intestinal wall and blood serum in rats.

Hemorrhagic shock causes release of lysosomal proteolytic enzymes which contribute to intestinal wall destruction and can be moved into the circulation as well as into the gut lumen. The aim of the study was to examine the activity of cathepsin D in relation to the intestinal wall injury after 60 minutes of untreated hemorrhagic shock in rats. The total cathepsin D activity was investigated in duodenum, jejunum, ileum, cecum and colon, as well as in systemic and mesenteric blood serum, and the biochemical results were compared with morphological changes in the respective segments including immunohistochemical expression of cathepsin D. We found an increase in cathepsin D activity in duodenum and significant decrease in other parts of the gut in shocked rats. The enzyme activity increased also in blood serum, especially systemic (p < 0.05) and insignificantly in mesenteric blood. However, sham-operated animals (one-side carotid artery occlusion) revealed a significant increase in cathepsin D activity measured in mesenteric blood. The shock resulted in lowering protein concentration in the intestinal wall and its increase in mesenteric blood. The contents of peptides and amino nitrogen, as potential proteolytic reaction products, changed in different ways in various segments of intestine. Morphologically, the most intensive destruction was observed in ileum, duodenum and jejunum. Lifting of epithelial layer from lamina propria was the most frequently observed lesion of the intestinal wall after 60 minutes of shock. More advanced lesions, such as denuded mucosa with disintegration of lamina propria, occurred rarely and were not observed in colon and rectum. By means of polyclonal antibodies against cathepsin D, we found that the strong expression of this enzyme was in epithelial layer--the part of intestinal wall which was partially detached into gut lumen due to hemorrhagic shock. The changes of cathepsin D activity after 60 minutes of hemorrhagic shock were correlated with signs of morphological damage to the intestinal wall. Cathepsin D liberation in the intestinal wall during shock indicates the lysosomal membranes impairment and can confirm involvement of proteases in the damage to the intestinal tissue. We conclude that liberation of intestinal cathepsin D is an early phenomenon during hemorrhagic shock which may contribute to the local wall disintegration and activation of systemic inflammatory response.

Animals↗
PubMed1998

Preoperative CYFRA 21-1 level as a prognostic indicator in resected nonsmall cell lung cancer.

Cytokeratin 19 is particularly abundant in carcinoma of the lung. The CYFRA 21-1 assay has recently been developed for detection of a cytokeratin 19 fragment in serum. In the current study, the prognostic information provided by the CYFRA 21-1 assay in operable nonsmall cell lung cancer (NSCLC) was analysed. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (DiaSorin) in 94 patients with operable NSCLC. Survival and disease-free survival curves related to initial levels of this marker were estimated using the Kaplan-Meier method. Elevated preoperative CYFRA 21-1 levels were identified in 42% of patients with NSCLC. The number of patients with elevated levels of this marker increased with tumour node metastasis (TNM) stage (p=0.02). In univariate analysis elevated levels of CYFRA 21-1 were significantly associated with poor overall survival (p<0.001) and with disease-free survival (p<0.001). The results remained significant when the comparisons were adjusted, using the stratified log-rank test, for patient's TNM stage (p<0.001 for both overall and disease-free survival). Elevated preoperative levels of CYFRA 21-1 decreased the probability of survival or surviving without recurrence 15 months or more after the operation. This was confirmed by the results of the multivariate analysis. In conclusion, CYFRA 21-1 may be an independent prognostic parameter of survival and tumour relapse in nonsmall cell lung cancer and may be useful in identifying resected cancer patients at high risk for treatment failure.

Aged↗
PubMed1998

Angiogenesis in endometrial cancer.

We evaluated the level of angiogenesis in endometrial adenocarcinoma and investigated the relationship between tumor vascularity and clinicopathological parameters. The level of angiogenesis in noninvaded uterine smooth muscle was also studied. Angiogenesis was studied in uteri of 29 post-menopausal women operated on for endometrial cancer. DAKO EPOS Anti-Human von Willebrand Factor/HRP antibodies were applied to mark endothelial cells. Both vessels and endothelial cells were counted on a light microscope equipped with computerized morphometric appliance. The highest density of vessels and endothelial cells was found in disease-free uterine smooth muscle tissue situated distant to the tumor. Density of vessels and endothelial cell counts were higher in the outer as compared to the central parts of the tumor. We found statistically significant differences in total angiogenic points' density between groups of various clinical FIGO staging, specifically between Ia and Ib, Ic, II. A positive correlation was found between the clinical stage of the disease (according to FIGO) and the total angiogenic points' density, density of endothelial cells and the density of vessels with viable lumen (counts/sq. mm calculated from the central parts of the tumor). These results suggest that the analysis of angiogenesis may be a useful biologic parameter and additional study of neovascularization in endometrial cancer is warranted.

Aged↗
PubMed1997

Collagen and glycosaminoglycans of Wharton's jelly.

In this study, we report quantity, solubility and molecular polymorphism of collagen, proportional relationships between various types of collagen, ultrastructure of collagen fibres, the amounts of various glycosaminoglycans (GAGs) and proportional relationships between them in Wharton's jelly of normal umbilical cords. We compare the extracellular matrix components in Wharton's jelly with those in the umbilical cord artery. Collagen of the Wharton's jelly demonstrates some specific features. It is very insoluble in neutral salt and in a slightly acidic solution and appears to be resistant to the action of depolymerizing agent (EDTA-Na2). Only 50% of total collagen may be solubilized by pepsin digestion and fractionated by differential salt precipitation. Four collagen fractions were obtained. Three of them were identified by polyacrylamide gel electrophoresis as type I, type III, and type V collagen and proportional relationship between them was calculated. Hyaluronic acid is the most abundant component of GAGs contained in Wharton's jelly. The amounts of sulphated GAGs-keratan sulphate, heparan sulphate, chondroitin-4-sulphate, chondroitin-6-sulphate, dermatan sulphate and heparin-are distinctly lower. Each of them constitutes only a few percent of total GAGs.

Adolescent↗
PubMed1997

Ultrastructural study of endogenous lipid pneumonia and pulmonary alveolar proteinosis coexistent with lung cancer.

The aim of the study was the ultrastructural analysis of endogenous lipid pneumonia (ELP)-type changes localized in the vicinity of primary neoplasms of the lungs. The analysis was carried out on the material obtained from 30 patients with non-small cell lung carcinoma (NSCLC). Routine histopathological examination was performed in light microscope, focusing mainly on the presence or lack of ELP-type changes. Ultrastructural examinations in transmission electron microscope used 12 cases classified among early (4 cases) or advanced (8 cases) ELP forms. Results of the study reveal a likely coexistence of ELP- and PAP (pulmonary alveolar proteinosis)-type changes in the vicinity of NSCLC and suggest a correlation between the processes leading to the development of ELP or/and PAP. Ethiopathogenesis of the changes observed and the role of granulocytes, macrophages and type II alveolar epithelial cells are discussed.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Proteolytic enzymes in proliferation and neoplastic metastases formation.

Metalloproteases, plasminogen urokinase activator, plasmin and cathepsins enable the expansion of neoplastic tumors, leading to metastases formation. They cause neoplastic cells to detach from tumor, facilitate cell movement, implantation and participate in tumor vascularization. The regulation of these processes is accomplished during the synthesis and activation of proenzymes. Enzyme activity control is realized by their bonds with cellular membranes, and inhibitor action.

Animals↗
PubMed1997

Plasminogen activators and plasmin in lung cancer.

Urokinase plasminogen activator and plasmin contribute to detach neoplastic cells from solid tumor and facilitate the movement of these cells through interstitium and capillary walls as well as infiltration of the surrounding structures. Plasminogen activators inhibitors fulfill a regulatory function in these processes. Determining activity and concentration, finding subcellular, cellular and zonal localization of every component of plasminogen activation system has diagnostic and prognostic importance in different lung cancer types.

Fibrinolysin↗