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Biomedical subjects

L Chyczewski

Publications and source records attributed to L Chyczewski.

At least 91 records · Page 5Linked to original sources

Angiogenesis in cancer.

The concept of angiogenesis and consecutive stages of the neovascularization processes under physiological and pathological conditions have been described. Angiogenesis is regulated by the different mechanisms which are in dynamic balance. The regulating components of these processes are the stimulating and inhibiting factors, the mediators of these reactions under influence of the host cell-tumor cell interaction. The role of angiogenesis in cancer development is connected with obtaining the angiogenic phenotype by tumor when the transformation from prevascular to vascular phase of neoplasm goes on. The further tumor growth and metastasis processes depend on neovascularization. Actual research trends in the field of angiogenesis have been presented in this paper. We need to know such markers of angiogenesis would be the most useful for doing research work and monitoring neoplasm diseases in clinics. Antiangiogenic management seems to be a new promising therapeutic concept in oncology.

Antineoplastic Agents↗

Immunohistochemical analysis of tissue localization of cytokeratin 19 in lung cancer.

Cytokeratins (CK) are one of the main families of intermediate filaments which make up the cytoskeleton. CK19 is strongly expressed by normal simple bronchial and respiratory epithelium as well as by their malignant counterpart. Although CK19 is a part of the cytoskeleton, a soluble fragment of this polypeptide can be released and assayed in the blood as CYFRA 21-1, new sensitive and valuable marker of non small cell lung cancer. In some cases, however, discrepancies between the serum level of CYFRA 21-1 and presence of tumor and its histological type have been observed. We studied immunohistochemically tissue localization of CK19 in tumors and non invaded lung parenchyma in a series of 34 patients surgically treated due to lung cancer. CK 19 was detected in cancer cells as well as in non neoplastic epithelium covering bronchial tree and alveolar surfaces. We found a different expression of CK19 in different histological type of tumors. The most intensive expression revealed squamous cell carcinomas and adenocarcinomas. Small cell cancer revealed poor expression of CK19. In non invaded parts of the resected lungs we found the strong expression of CK19 in the cytoplasm of regenerative II type pneumocytes occurring in large quantity in the cases of interstitial lung fibrosis concomitant with some tumors. We suggest it may be a cause of unexpectedly elevated serum levels of CYFRA 19-21 in some not oncological patients or patients with small cell lung cancer.

Adenocarcinoma↗

Activity and tissue localization of cathepsin G in non small cell lung cancer.

Activity and tissue localization of cathepsin G were examined in tumors deriving from 73 patients with non small cell lung cancer. Activity of cathepsin G was highest in adenocarcinoma, lower in planoepitheliale cancer, the lowest in macrocellular cancer. In all histological types of tumors cathepsin G activity in supernatants was lower than in sediments. The enzyme immunohistochemically was localized in neutrophils. There is evident correlation between neutrophil numbers and cathepsin G activity in examined cancer types. Result of our examinations indicate a relationship between cathepsin G activity, grade of tumor differentiation and particular clinical stages of disease.

Adenocarcinoma↗

Activity and tissue localization of cathepsin D in non small cell lung cancer.

Activity and tissue localization of cathepsin D were examined in tumors deriving from 80 patients with non small cell lung cancer. Activity of the enzyme was higher in sediments and supernatants of tumors than in non invaded lung parenchyma. In all histological types of tumors cathepsin D activity in sediments was three times lower and in lung parenchyma five times lower than in supernatants. The immunohistochemical technique was used for enzyme localization. We observed seemingly the lack of correlation between activity of cathepsin D examined in tumors and immunohistochemical reaction intensity in neoplasm cells. Different numbers of macrophages and quantity of tumor stroma could explain this effect in examined histological types of cancer. Results of our explanations indicates for relations between cathepsin D activity versus histological type and degree of tumor differentiation. We did not observe correlation between cathepsin D activity versus lymph node metastases and clinical stages.

Adenocarcinoma↗

Prolidase and prolinase activities in moderately and poorly differentiated lung adenocarcinoma.

Prolidase (E.C.3.4.13.9) and prolinase (E.C.3.4.13.8) activities were determined in normal human lung and human lung adenocarcinomas of various degree of histologic differentiation. Since these dipeptidases were found to be enzymes catabolizing mainly collagen and simultaneously involved in the recycling of proline for collagen biosynthesis, the measurement of this protein and its degradation products in studied tissues (by hydroxyproline determination) was performed. It has been found that the activity of prolinase in G2-moderately and G3-poorly differentiated lung adenocarcinoma groups, was elevated compared to lung parenchyma and that the increase was proportional to the degree of adenocarcinoma differentiation. Prolidase activity was elevated only in G3 lung adenocarcinoma. The increase of prolidase and prolinase activities were accompanied by an increase of tissue collagen content. Collagen degradation products (CDP) represented one third of total collagen in control lung tissues while in lung adenocarcinomas the CDP represented significantly lower percentage of total tissue collagen. The results suggest that prolidase and prolinase activities may reflect: (i) degree of differentiation of lung adenocarcinoma and (ii) disturbances in tissue collagen metabolism.

Adenocarcinoma↗

Prolidase activity and beta 1 integrin expression in moderately and poorly differentiated lung adenocarcinomas.

Primary human lung adenocarcinomas were divided into two groups according to the degree of histologic differentiation: G2-moderately and G3-poorly differentiated tumors. Each group was compared with normal lung tissue in respect to prolidase activity, its ability to interact with specific antibody, free proline and beta 1 integrin subunit content as well as ability of beta 1 integrin subunit to interact with specific antibody. It was found that prolidase activity in lung adenocarcinomas G3, was significantly elevated in comparison to normal lung tissue. In lung adenocarcinoma G2 no significant changes in the enzyme activity were observed. Increase in the enzyme activity was accompanied by increase of free proline content in the tissues. The western blot analysis revealed that prolidase of lung adenocarcinomas is identical to prolidase originated in control lung tissue. It was noticed that elevated activity of prolidase in adenocarcinomas G3 was accompanied by its high expression. In respect to beta 1 integrin expression, known to play an important role in metastasis, no difference was found between adenocarcinoma groups and the control lung tissue. The presented data suggest that the level of prolidase activity in lung adenocarcinoma may serve as a more sensitive marker for the histologic degree of malignancy, than the level of beta 1 integrin expression.

Adenocarcinoma↗

Studies on angiogenesis intensity in lung cancer in aspect of its correlation with histological type of tumor and clinical stage.

Angiogenesis intensity in lung cancer, in compliance with histological types, tumor differentiation and different clinical stage of disease, was evaluated. The group of 65 patients, 34-73 years old (average 58), who have been operated, were examined. Microvessels were highlighted by immunohistochemical method staining of endothelial cells for factor VIII-von Willebrand. Microvessel and single endothelial cell count per 1 mm2 in each section was determined using light microscope, synchronized with camera and IBM-AT computer (LUCIA-NIKON program for morphometric studies). All cases were divided into three groups depending on angiogenesis intensity: Io-0-200, IIo-201-400, IIIo-400 angiogenic objects/mm2 (microvessels-MV plus endothelial cells-EC). Majority (57%) of examined cases were found in IIo group. The results of studies on angiogenic objects number (MV+EC) per 1 mm2 in different histological type of cancer were following: 248.97 +/- 114.72 in squamous cell, 253.18 +/- 81.32 in adenocarcinoma, 284.04 +/- 114.27 in large cell, 388.02 +/- 117.73 in small cell, 385.27 +/- 210.92 in combined cancer. In each group of lung cancer with different TNM and clinical stages was found that the angiogenic objects number depends on T tumor feature, mainly in EC count analysis (T1-148.61 +/- 113.21, T2-179.38 +/- 100.57, T3-199.52 +/- 137.70, T4-253.18 +/- 108.60). Obtained data were analyzed with of t Student's test. The differences between angiogenic objects number in the groups with different histological type of lung cancer were no statistically significant, although were near threshold value in pairs squamous cell versus small cell (p = 0.0545) and adenocarcinoma versus small cell (p = 0.0611). The differences of EC counts in the same pairs were statistically significant: p = 0.0247 (squamous cell versus small cell) and p = 0.0380 (adenocarcinoma versus small cell). The correlation between angiogenic objects number and grade of tumor differentiation was statistically significant for G1 group versus G2 (p = 0.0380) and G1 versus G4 (p = 0.0008), in comparison to G2 versus G4-p = 0.0688. The remaining results were not statistically significant. Obtained data are no final because the examined groups of cases were not numerous enough. The dependences should be examined in large series of cases.

Adenocarcinoma↗

Ultrastructural analysis of the pneumocyte-interstitium boundary line in the course of enzymatic lung injury.

The studies were performed basing on the experimental model of acute pulmonary tissue injury. Papain in a dose of 2 mg/ml PBS/100 g b.w. was administered once, intratracheally, on the 21st day of the experiment. Besides, female Wistar rats were injected twice with BCG vaccine in a dose of 4 x 10(8) microorganisms. BCG vaccine was administered intraperitoneally on the 1st and 14th day of the experiment to activate the system of mononuclear phagocytes. Control rats were intratracheally or/and intraperitoneally given PBS solution. All the animals were killed on the 28th, 35th and 42nd day of the experiment. A single intratracheal papain injection induced emphysematous changes in the animal lungs. The changes were accompanied by basement membrane rebuilding and focal collagen and elastin cumulation. An increase in the number of type II alveolar epithelial cells was observed. Anchorage of collagen fibres and microfibrillary structures in the cytoplasm of type II pneumocytes was observed in the BCG- and papain-treated animals. There, the cytoplasmic membrane of type II cells was completely indistinct and the cytoplasm formed processes to penetrate into the connective tissue fibres. The results obtained indicate possible contribution of type II pneumocytes to fibroplasia processes during lung parenchyma rebuilding and suggest the necessity to include fibroplasia elements in the existing definition of emphysema.

Animals↗

Surfactant system in lung cancer. Endogenous lipid pneumonia.

The aim of the study was the evaluation of endogenous lipid pneumonia-type changes developing in the vicinity of primary tumors of the lungs. The postoperative material collected from 56 patients operated for non-small cell lung cancer was examined. The coexistence of endogenous lipid pneumonia-type changes with squamous cell carcinoma and large cell carcinoma of the lung was most common. Patients with these histopathological types of carcinoma had lower percentage of metastases to the lymph nodes. Endogenous lipid pneumonia was found to accompany most frequently the tumors 3 < or = 6 cm in diameter and it was slightly more common in the vicinity of peripheral tumors.

Carcinoma, Non-Small-Cell Lung↗

Collagen and glycosaminoglycans of Wharton's jelly and their alterations in EPH-gestosis.

Some prenatal pathological processes may be caused by biochemical and morphological alterations in the umbilical cord (UC). EPH-gestosis is the most common pregnancy-associated pathological process. For these reasons the role of collagen and glycos-aminoglycans (GAGs) of UC in pathobiochemistry of this syndrome seems to be important. We studied histology of extracellular matrix components, quantity, solubility and molecular polymorphism of collagen, proportional relationships between various types of collagen, the amounts of GAGs and proportional relationships between them in Wharton's jelly of control newborns delivered by healthy mothers and those delivered by mothers with EPH-gestosis. We found that Wharton's jelly is abundant in collagen and GAGs. This collagen is very insoluble and resistant to the action of depolymerizing agents (4% EDTA-Na2, pepsin). Types I, III and V collagens were isolated and quantified. Hyaluronic acid constitutes about 70%, whereas sulphated GAGs constitute about 30% of total GAGs. EPH-gestosis is accompanied by significant increase in sulphated GAGs: hyaluronic acid ratio. The EPH-gestosis-associated alterations in Wharton's jelly correspond to 'premature ageing' of this tissue.

Adult↗

Peripheral blood megakaryocytes in experimental hemorrhagic shock.

The number and morphological types of megakaryocytes (MK) in the rat inferior cava vein blood were evaluated in untreated hemorrhagic shock lasting 60 min and in 6 to 48 hours after treatment with a standard polyelectrolyte solution (PES). The rats were bled through carotid artery. MK were isolated using the 5 microns filters. The results were compared with those found in the control animals not subjected to surgical manipulation and subjected to sham operation (cervical incision only, and cervical incision + carotid artery cannulation). The most considerable increase in the circulating MK occurred in 12 hours after the PES treatment. The slight increase in the number of MK was also observed in rats with carotid artery cannulation without hemorrhage. Increase in the MK number was accompanied by a shift in their morphological types.

Animals↗

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

The CYFRA 21-1 assay is a test that has been developed recently for detection of a cytokeratin 19 fragment in serum. A diagnostic role for CYFRA 21-1 has already been proposed. The question of whether this marker is prognostically significant is important in clarifying the role of CYFRA 21-1 in clinical practice. The aim of this study was to evaluate the prognostic significance of elevated preoperative CYFRA 21-1 levels in patients with resected primary squamous-cell lung cancer (SqCC). Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 91 patients with operable SqCC. Survival and disease-free survival curves related to initial levels of this marker were estimated using the Kaplan-Meier method. In the univariate analysis the log-rank test and the log-rank test for trend were used. In the multivariate analysis the stratified log-rank test and the proportional hazard model were used. Elevated preoperative CYFRA 21-1 levels were identified in 55% of patients with SqCC. The number of patients with elevated levels of this marker increased with TNM stage (P = 0.0001). In univariate analysis elevated levels of CYFRA 21-1 were significantly associated with poor overall survival (P < 0.00005) and with disease-free survival (P < 0.00005). In multivariate analysis elevated levels of this marker were also found to be associated with poor overall and disease-free survival (P = 0.01 and P = 0.003 respectively). In conclusion, CYFRA 21-1 may be an independent prognostic parameter of survival and tumour relapse in SqCC and may be useful in identifying resected SqCC patients at high risk of treatment failure.

Adult↗

Alterations in glycosaminoglycan composition of methylcholanthrene-induced sarcoma at various stages of the tumour growth.

The methylcholanthrene-induced sarcoma contains several types of glycosaminoglycans, hyaluronic acid being the major component. Furthermore it contains all sulphated glycosaminoglycans present in the skin: chondroitin-4-sulphate, chondroitin-6-sulphate, keratan sulphate, dermatan sulphate, heparan sulphate and heparin. It was found that the amount of all glycosaminoglycans distinctly increased during tumour growth. At the same time the amount of collagen significantly decreased. It is suggested that some of the GAGs participate in the creation of a storage depot for biologically active molecules (growth factors, enzymes) which are thereby stabilized and protected. Hydrolytic degradation of some GAGs may result in the release of some cytokines which may stimulate or inhibit the tumour growth. The changes in the quantities of various glycosaminoglycans during the tumour growth may be responsible for a dual-phase growth of this tumour.

Animals↗

[Multiorgan changes in AIDS in a reported case].

The clinical course of HIV infection and results of autopsy examination in 49 years old patient was shown. The attention was paid to difficulties of diagnosis of opportunistic infections in a patients with advanced HIV disease. Variety of infectious factors, that could affect a patient with significant immunodeficiency was outlined.

AIDS-Related Opportunistic Infections↗

The effect of platelet activating factor antagonist (BN 52021) on acute experimental pancreatitis with reference to multiorgan oxidative stress.

Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were treated with platelet-activating factor receptor (PAF) antagonist--BN 52021 (5 mg/kg) and sacrificed at 1 and 3 h after induction of acute pancreatitis. Malondialdehyde and sulfhydryl groups concentration were measured in pancreatic, lung, and liver tissue as a parameter of oxidant-antioxidant balance. We have shown that BN 52021 exerts only partial protecting effect against Na-TC-induced AP in rats. The positive effects of BN 52021 were expressed by: (1) Significant reduction of hyperamylasemia accompanied by lower malondialdehyde accumulation in pancreatic tissue; (2) Prevention of sulflhydryl groups depletion in lung tissue; (3) Diminution of necrotic and inflammatory changes in pancreatic tissue; and (4) Improvement of survival rate. We suggest that these effects may depend on the inhibition of PAF-mediated activation and oxidant generation by phagocytes.

Acute Disease↗

Diagnostic and prognostic value of the new tumour marker CYFRA 21-1 in patients with squamous cell lung cancer.

We wanted to investigate the diagnostic and prognostic significance of serum CYFRA 21-1, especially in predicting the risk of recurrence in patients with operable squamous cell lung cancer. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 76 patients with squamous cell lung cancer (64 operable and 12 with unresectable tumours), 22 with other non-small-cell type (12 with adenocarcinoma and 10 with large-cell type) and 45 with nonmalignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified in 63% of patients with squamous cell type (SqCC), 33% with adenocarcinoma, and 30% with large-cell carcinoma type. The diagnostic specificity of the assay was 96%. Positive CYFRA 21-1 levels were observed in 33% of stage I, 52% of stage II, 76% of stage IIIa and 83% of stage IIIb patients with SqCC type. Statistically significant differences were obtained between stages I and II and between II and IIIa, but not between stages IIIa and IIIb. Recurrence-free survival probability for patients with elevated serum CYFRA 21-1 levels before surgery was 63% (24/38) versus 92% (24/26) for patients with normal serum CYFRA 21-1 levels. However, the difference was not statistically significant when adjusted for the TNM stage (primary tumour, regional lymph node involvement, occurrence of distant metastasis). In 9 of the 10 patients with increased trend for CYFRA 21-1 during follow-up, elevated serum CYFRA 21-1 levels preceded (7) or coincided (2) with the clinical detection of tumour recurrence, providing a predictive value of an increased trend of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

CYFRA 21-1 as a tumour marker for bronchogenic carcinoma.

Despite extensive research, the role of the commonly employed tumour markers in the diagnosis of lung carcinoma is yet to be clarified. The utility of a new marker, CYFRA 21-1, in the preoperative evaluation of patients with bronchogenic carcinoma was investigated. CYFRA 21-1 was determined with a radiometric assay in serum of 280 patients with lung cancer and 208 patients with various nonmalignant lung diseases. The levels of the marker were significantly higher in lung cancer patients. Among benign lung diseases, elevated CYFRA 21-1 levels were found in pulmonary fibrosis. Using a cut-off of 3.2 ng.ml-1 (95th percentile of levels obtained in benign lung disease), the total sensitivity of the marker was 48%. The best sensitivity was obtained in squamous cell lung cancer (60%). The highest values of CYFRA 21-1 were found in metastatic lung cancer, and the marker sensitivity was more elevated in stage IIIb and IV. On the other hand, 40% of patients with surgically resectable lung cancer had CYFRA 21-1 levels above the cut-off. We conclude that CYFRA 21-1 may be satisfactorily employed in the differential diagnosis between malignant and benign lung diseases in association with other clinical and radiological data.

Biomarkers, Tumor↗