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Biomedical subjects

R Wierzbicki

Publications and source records attributed to R Wierzbicki.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Plasminogen activator inhibitors from neoplastic tissues].

This article contains a survey of works, published in the last few years on plasminogen activators inhibitors in neoplastic tissues. These inhibitors belong to a heterogenous group of proteins, having different molecular weights and specific ways of acting. They exemplify immunological relationship to known inhibitors of fibrinolysis from normal tissues--i.e. the inhibitors from endothelial cells--(PAI-1) and placental inhibitor--(PAI-2). To PAI-1 type belong: acid-stabile inhibitor of fibrinolysis with Mr 50,000 from HTC hepatoma cells in rats, acid-labile inhibitor Mr 42,770 produced by HepG2 human hepatoma cells; the inhibitor with Mr 54,000 from HT 1080 human cells from fibrosarcoma and single-chain acid-stabile inhibitor with Mr 50,000 from MJZJ melanoma cells. In PAI-2 type we can mention the inhibitor with Mr 47,000 from U-937 histiocytic lymphoma cells.

Animals↗
PubMed1990

Cancer procoagulant in serum of rats during development of experimental epithelioma.

The activity of cancer procoagulant (CP) during the development of Guérin epithelioma was studied in the blood of Wistar rats. Blood was collected from the carotid artery and, after clotting, proteins adsorbing on aluminum hydroxide were removed from the serum. Then procoagulant activity was determined in the test system without factor VII by means of substrate S-2222 specific for factor Xa. A statistically significant increase in the activity of CP in serum was detected, coinciding with the period of intensive tumor growth (15th-25th day of disease).

Animals↗
PubMed1990

Fibrinolytic activity of rat plasma during development of Guerin epithelioma.

Fibrinolytic activity in the blood of rats during the development of Guerin epithelioma was studied. It was measured by means of radiometric method, based on the amount of plasmin degradation products released from 125I-fibrin, as well as by means of amidolytic technique with the use of Chromozym PL. During the initial phase of epithelioma development the fibrinolytic activity of plasma, determined after inactivating plasma proteinase inhibitors, increases. It also increases in the euglobulin fraction. Simultaneously, the content of fibrin(ogen) degradation products (FDP) increases in the blood. During the stage of the intensive development of neoplastic disease fibrinolytic activity as well as plasminogen activator activity become inhibited, whereas the concentration of FDP retains the level observed in healthy animals. Inhibition of fibrinolytic activity in the later phase of the disease coincides with the appearance of low-molecular weight antifibrinolytic factor in the blood of rats loaded with epithelioma.

Animals↗
PubMed1990

Procoagulant activity of human stomach and colon cancers.

Procoagulant activity in extracts from human stomach and colon cancers was examined, using chromogenic substrate S-2222. The activity of direct activator of factor X varied between 6 and 96% of total procoagulant activity of the tested extracts. The direct activator of factor X from stomach cancer was sensitive to heating and was inhibited by phenylmethylsulphonylfluoride and also by iodoacetic acid and HgCl2. Such results lead to the assumption that investigated activator is of enzymatic nature.

Blood Coagulation Factors↗
PubMed1990

Epirubicin in extensive small-cell lung cancer: a phase II study in previously untreated patients: a National Cancer Institute of Canada Clinical Trials Group Study.

The Clinical Trials Group of the National Cancer Institute of Canada (NCIC) studied single-agent epirubicin in 40 previously untreated patients with extensive small-cell lung cancer (SCLC). The starting dose of epirubicin was 100 (eight patients) or 120 (32 patients) mg/m2 administered intravenously every 3 weeks. Twenty patients (50%) achieved an objective response (95% confidence limits, 33% to 66%) and three of the 20 had complete responses (CRs). The median survival of all 40 patients was 8.3 months (35.4 weeks). Myelosuppression, mild or moderate nausea and vomiting, and hair loss were commonly seen. There was one chemotherapy-related death. This drug is active and well tolerated in SCLC and the use of it as first-line therapy did not appear to compromise survival in this group of patients.

Carcinoma, Small Cell↗
PubMed1990

Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer.

Thirteen previously untreated patients with extensive small-cell lung cancer (SCLC) were treated with the investigational agent amonafide in a dose of 300 mg/m2 intravenously (IV) over 1 hour daily for 5 consecutive days. No responses were seen in 12 eligible patients. Myelosuppression was only occasionally seen. Other toxicities included diaphoresis, chest pain, local irritation at the injection site, arthralgias, nausea and vomiting, and neuromuscular problems. There were two early deaths, both attributable to tumor progression with resultant obstruction of a vital structure. Ten patients crossed over to alternate active therapy (etoposide [VP-16]-cisplatin) and five responded. The median survival time (MST) of the whole group of treated patients was 31 weeks. In future trials of investigational new drugs in previously untreated SCLC, we recommend that patients with the following characteristics be excluded: Eastern Cooperative Oncology Group (ECOG) performance status 2, 3, and 4; superior vena cava (SVC) obstruction; any major paraneoplastic syndrome; serious comorbid illness; and extensive hepatic involvement by tumor. The trial design should include prompt crossover to active alternative therapy, such as VP-16 and cisplatin, for disease progression or for failure to respond after two treatment cycles. Also, the trial design should use an early stopping rule based on interest in identifying only very active agents with a minimum response rate of 30%.

Adenine↗
PubMed1990

5-Fluorouracil with folinic acid is not effective against metastatic adenocarcinoma of the lung.

Thirty patients with a diagnosis of metastatic adenocarcinoma of the lung were entered on a trial to evaluate the antitumor efficacy of 5-fluorouracil 370 mg/m2 daily for 5 days every four weeks in combination with folinic acid 200 mg/m2, 60 min prior to 5FU. All patients had a good performance status, bidimensionally measurable disease, and weight loss less than or equal to 5% of preillness weight. Of the 29 evaluable patients, only two (7%) had partial responses (95% confidence limits 1-24%). Eleven (38%) had stable disease and 16 (55%) progressed. The two responding patients survived 12 and 60+ weeks. The median survival of all evaluable patients was 25 weeks (range 7-60+) and that of the stable patients was 26 weeks. The principal toxicities observed were diarrhea and stomatitis. Myelosuppression was rarely dose limiting. In contrast to the results of treatment with 5FU and folinic acid in metastatic colorectal cancer and breast cancer, the results of treatment with this combination of agents have been much less encouraging in adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1990

Plasminogen activator (PA) in Guerin epithelioma. Additional PA inhibitor in plasma of rats bearing the epithelioma.

The presence of plasminogen activator (PA) with a Mr of about 35,000 was detected by SDS-PAGE in extract from Guerin epithelioma. The activator, which is a serine proteinase, was partially purified on Sephadex G-50 followed by Lys-Sepharose. Rat plasma, both of healthy and epithelioma-bearing animals, inhibited the activity of such isolated PA. However, the difference between these plasmas in their antiactivator action was observed after inactivation of plasma proteinase inhibitors. In such conditions, the control plasma lost the ability to inhibit the examined PA, whereas the plasma of epithelioma bearing rats retained this ability.

Aniline Compounds↗
PubMed1989

Low molecular weight fibrinolytic inhibitor from Guerin epithelioma.

Antifibrinolytic activity of the extract from Guerin epithelioma, a highly metastatic tumour implanted to rats, was determined by fibrinolytic and zymographic methods. The extract exhibits antifibrinolytic activity which is thermostable (60-100 degrees C) and pH-stable (pH 2.7-12). It contains a fibrinolytic inhibitor, with Mr about 7000, with antiplasmin properties, bound to lys-Sepharose and heparin-Sepharose. The molecular weight, physicochemical properties and antiplasmin action of the epithelioma inhibitor prove its identity with the low molecular weight antifibrinolytic factor appearing in the plasma of rats during the development of this tumour.

Animals↗
PubMed1989

Fibrinolytic inhibitors from the experimental rat epithelioma.

Guerin epithelioma, a highly metastatic tumour implanted to Wistar rats contains two inhibitors of fibrinolysis which can be detected with the use of zymographic techniques. The first one--with Mr about 48000 forms SDS-stable complex with urokinase. The second--with Mr about 7000 inhibits fibrinolytic and amidolytic activity of plasmin.

Aniline Compounds↗
PubMed1989

[Fast-acting plasminogen activator inhibitor in the plasma].

This study contains a survey of papers published in the last few years on the specific inhibitor of plasminogen activation (PA-inhibitor, or antiactivator) discovered in plasma in 1983. Molecular weight of the PA-inhibitor is ranging from 40,000 to 50,000; the antiactivator is present in very small concentration in plasma. Most probably it originates from the endothelial cells. The antiactivator inhibits both tissue plasminogen activator and urokinase, forming complexes in molar ratio 1:1 with them. Possibly, it is the main plasmic inhibitor of plasminogen activators. Its increased content in plasma of patients with tendency to develop thromboembolic disease points to a relationship between lowered fibrinolytic activity and increased concentration of the PA-inhibitor in blood.

Blood Coagulation↗
PubMed1989

Blood coagulation changes in rats during development of epithelioma.

Coagulation activity in the blood of rats during the development of Guerin epithelioma was studied. Clotting time, level of fibrinogen and some coagulation factors (II, V, VII + X) in the plasma were determined and thromboelastographic studies were performed. Two periods of blood hypercoagulability were observed in the process of epithelioma development. The first a short-term period, was noticed during the first days following the implantation of the neoplastic tissue. The second took place during the intensive growth of the primary tumor and metastases.

Animals↗
PubMed1988

A phase II study of VP-16 and cisplatin in patients with unresectable malignant mesothelioma. An NCI Canada Clinical Trials Group Study.

The National Cancer Institute of Canada (NCIC) Clinical Trials Group has carried out a phase II study of VP-16 100 mg/m2 daily x 3 and cisplatin 25 mg/m2 daily x 3 in untreated patients with malignant mesothelioma. Twenty-seven eligible patients were entered on the trial and the majority had pleural and/or soft tissue disease. Myelosuppression and gastrointestinal symptoms were the most common toxicities, and were usually mild or moderate in severity. Only 3 partial responses were seen in the 26 patients evaluable (12%). We conclude that the combination of VP-16 and cisplatin when used in this fashion has only minimal activity in mesothelioma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Factor X-activating activity from Guerin epithelioma.

The procoagulant activity (PCA) was examined in extracts from primary tumor and metastases of experimental Guerin epithelioma transplanted into Wistar rats. PCA was evaluated by measurement of the level of activation of coagulation factor X using specific chromogenic substrate S-2222. We observed that extracts from both primary tumor and metastases were able to activate factor X in vitro. This activity was not factor VII-dependent, it was inhibited by phenylmethylsulfonyl fluoride (PMSF) and mercuric chloride, and in a smaller degree by p-chloromercuric benzoate (p-CMB) and iodoacetic acid (IAA). No difference between procoagulant activity in extracts from primary tumor and from metastases was observed.

Animals↗
PubMed1983

Interaction of fibrinogen with mercury.

The interaction of bovine fibrinogen with mercuric chloride was studied. Gel filtration on Sephadex G-25 revealed that fibrinogen bound twice the amount of mercury such as fibrin or fibrin monomers (8.8, 4.5, and 3.4 micrograms Hg2+ ions/mg protein, respectively). Fibrinogen complexed with mercury or in the presence of Hg2+ ions at concentration above 10-6 M was clotted by thrombin more effectively than in the control system which was devoid of this metal. Reaggregation of the purified fibrin monomers was not affected by mercury.

Animals↗