Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fragments with cortisone [Folkman, J., Langer, R., Linhardt, R. J., Haudenschild, C. & Taylor, S. (1983) Science 221, 719-725]. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of [35S]heparin or [3H]heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of approximately equal to 0.1 unit/ml. The radioactive material is identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion.
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PMID:Oral heparin results in the appearance of heparin fragments in the plasma of rats. 345 56

We have analyzed the CM of 20 human tumor cell lines for the presence of PA, PA-I and PC. Most of the cell lines expressed PA activity as measured by a radioiodinated fibrin plate assay. The urinary type and tissue-type PA activities were specifically quantified by means of purified inhibitory antibodies. U-PA and/or t-PA antigen, as measured by radioimmunoassays, were detected in all but 4 of the CM and were generally 10 times more concentrated than PA activity, indicating the presence of specific PA-Is. Analysis of CM by electrophoresis followed by fibrin-agarose zymography demonstrated the presence not only of free but also of inhibitor-complexed PA. Affinity purification demonstrated that 8/20 cell lines expressed detectable PA-I activity. The PA-I1 and PA-I2 inhibitors were most frequently observed, while PN was recovered only from CM of the HT1080 fibrosarcoma cell line. PC activity, as measured by the plasma recalcification time method, was found in 9/20 CM. It was of the thromboplastin tissue factor type since most of its activity was lost when assayed with a Factor VII-deficient plasma.
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PMID:Plasminogen activators, plasminogen activator inhibitors and procoagulant analyzed in twenty human tumor cell lines. 349 Apr 46

It has repeatedly been proposed that fibrin plays a role in tumor growth and metastasis. Among tumor cell products or activities which may promote clot formation, cancer procoagulant (CP), a direct activator of coagulation factor X, has been suggested to be selectively associated with the malignant phenotype. We report here the enzymatic and immunological identification of this cysteine proteinase procoagulant in extracts and cells from human melanoma. CP activity was independent of both the intrinsic and extrinsic pathways of blood coagulation, using factor IX and factor VII deficient plasmas, and was inhibited by the cysteine proteinase inhibitors iodoacetamide and HgCl2. CP activity was detectable in extracts and cell suspensions from all 32 patients studied and was higher in extracts from metastases (14.8 +/- 3.9 units/mg protein) than from the primary tumors (3.7 +/- 1.0 units/mg protein). CP activity was not affected by an anti-apoprotein III antibody or by concanavalin A, a known inhibitor of thromboplastin. In contrast, no CP activity or antigen was detected in extracts from six benign melanocytic lesions. The procoagulant activity was dependent on factor VII and was inhibited by anti-apoprotein III antibody and by concanavalin A, properties that suggest that the procoagulant was tissue thromboplastin. These data indicate that CP can be expressed by human tumor cells and that, among melanotic lesions, its presence is associated with the malignant phenotype and its activity is particularly high in metastatic cells.
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PMID:Cancer procoagulant in human tumor cells: evidence from melanoma patients. 353 81

Abnormal hemostasis is a fundamental property of malignant disease, not merely an epiphenomenon attributable to therapy or to chronic illness. Many types of tumor cells express clotting initiators such as tissue factor and act again late in the coagulation pathway by providing a surface for prothrombinase generation. Thus, entry of tumor cells into the plasma, as during metastasis, may be expected to trigger intravascular clotting. However, and perhaps of greater importance, solid tumors growing outside of the blood vasculature regularly deposit fibrin locally in the tissues. They do so by rendering the microvasculature hyperpermeable, allowing fibrinogen and other plasma-clotting proteins to leak into the extravascular space where procoagulants associated with tumor cells or with benign stromal cells initiate clotting. Both fibrin deposition and turnover in solid tumors proceed at rapid rates. Thus, whether attributable to events in the intra- or extra-vascular space, the result is the same: abnormal clotting and fibrinolysis whose consequences may include protection from host inflammatory cells, modulation of the immune response, and induction of angiogenesis.
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PMID:Thrombosis and cancer. 354 76

The purpose of this study was to purify and characterize the agent responsible for the antimetastatic activity of an extract of the salivary glands (SGE) of the Mexican leech Haementeria officinalis. When administered intravenously in mice on the same day as the intravenous inoculation of T241 sarcoma cells, SGE markedly reduces the number and size of lung tumor colonies. In designing a purification protocol for the antimetastatic agent, we postulated that the antimetastatic agent would also display anticoagulant activity. Thus, we discovered that heparin affinity chromatography followed by anion-exchange chromatography results in a fraction highly enriched in both potent anticoagulant activity and potent antimetastatic activity. Approximately, 200-300 micrograms of purified protein is isolated from 150 mg of SGE. As little as 15 micrograms of this material inhibits tumor cell metastasis to the same extent as 1.0 mg of the unfractionated SGE. When analyzed on sodium dodecyl sulfate gels the active fraction consists mainly of one polypeptide band having an apparent molecular weight of approximately 17,000 under either reducing or nonreducing conditions. The protein has a pI of approximately 9.5 and a molecular weight of approximately 17,000 under nondenaturing conditions. A specific antiserum prepared against the 17,000-dalton protein indicated that this protein is the major anticoagulant and antimetastatic agent of leech salivary gland extract. We have termed this anticoagulant, antimetastatic agent "antistasin." We hypothesize that antistatin inhibits coagulation via factor Xa, and not thrombin, since factor Xa, but not thrombin, is rapidly inactivated upon addition of antistasin. The mechanism of antistasin's antimetastatic activity is currently under investigation.
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PMID:Isolation and characterization of antistasin. An inhibitor of metastasis and coagulation. 368 95

The spontaneous metastatic spread of a suspension of PAIII prostatic adenocarcinoma cells from the tail site of implantation was analyzed over a period of 5 weeks in male Lobund-Wistar (LW) rats. Following subcutaneous injection of the PAIII cells, the tumor metastasized through the primary lymphatic drainage. PAIII microfoci were evident in the gluteal and iliac lymph nodes prior to colonization of the lungs. Growth of the primary tumor was evidenced by significant weight differences of the tails of PAIII-bearing and control rats 1 week after tumor implantation. Time-dependent sequential spread of the adenocarcinoma was quantitated. Significant differences were noted between PAIII-bearing and control animals with respect to the gluteal lymph node weights (+2 weeks), iliac lymph node weights (+3 weeks), dry lung weights, and lung colony numbers (+4 weeks) after tumor implantation. During the course of these studies, the whole blood prothrombin, activated partial thromboplastin, and recalcification times for the PAIII-bearing animals were similar to those of the control group. These findings indicate that there were no gross changes in systemic blood coagulation accompanying the metastasis of PAIII cells from the primary tumor. The tumor in LW rats produced a consistent pattern of growth and metastasis that is suitable for quantitation. The PAIII prostatic adenocarcinoma is a sensitive and reproducible system that may be useful to evaluate potential antimetastatic and cytotoxic agents for the treatment of hormone-insensitive prostatic cancer.
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PMID:Metastatic spread of the PAIII prostatic adenocarcinoma after implantation in the tail of the rat. 370 46

Platelet function following inoculation of chemically induced carcinoma was evaluated in the rat. The original line of tumor (NGW1) was obtained using N-methyl-N-nitrosoguanidine. After trypsin homogenation a cell suspension of 0.3 X 10(6) viable tumor cells was injected subserosally in the cecum of each animal. Controls received injections of equal volumes of 0.9% NaCl solution or trypsin. The animals were subjected to laparotomy 2, 4, and 6 weeks after inoculation. Platelet function was assessed in vivo by measuring bleeding time and blood loss during mesenteric vessel transection or liver resection upon laparotomy. Hemoglobin, hematocrit, platelet count, activated partial thromboplastin time, platelet aggregation, thromboxane B2, platelet factor 4, and fibrinogen levels were evaluated after sacrifice by exsanguination. Significant decrease in bleeding time and blood loss was observed in animals with local primary tumors as well as in rats with lymph node metastases. Hemoglobin and hematocrit were decreased in the presence of metastases. Platelet count was not changed. Activated partial thromboplastin time was not affected by the presence of tumor. Platelet aggregation in vitro was accelerated in the presence of primary tumor or lymph node metastases, as well as following addition of tumor cells to platelet suspensions. No changes in thromboxane B2 or platelet factor 4 could be registered. Fibrinogen levels were decreased in the presence of liver metastases. Enhancement of primary hemostasis and platelet function in the presence of colon carcinoma in the rat was demonstrated both in vivo and in vitro. Direct or indirect interaction of the tumor cell with thrombocytes may play a role in determining the metastatic potential of the neoplasm.
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PMID:Hemostasis following inoculation and during spreading of colon carcinoma in the rat. 375 13

Forty-three patients with factor XI deficiency detected by prolonged partial thromboplastin times were reviewed over an 11-year period. They were predominantly Ashkenazim--18 men and 25 women--ranging in age from 20 to 92 years. Thirteen patients had a history of bleeding, and eight had a family history of factor XI deficiency. Six patients with thyroid disease with four significant tumors were found for a 9% incidence of associated neoplasia. These consisted of two adenomas and two papillary-mixed cancers in two men distinguished by an aggressive course by virtue of extensive nodal disease, local recurrence, and systemic metastases in whom factor XI was profoundly decreased. It would appear that there is an undue association of factor XI deficiency and thyroid neoplasia suggestive of a shared genetic disturbance. These cases illustrate the benefit of routine preoperative coagulopathy screening by use of prothrombin time, partial thromboplastin time, and platelet counts. Factor XI deficiency is an infrequent cause of excessive bleeding, and the operative morbidity of surgical management of affected individuals can be avoided by the use of fresh-frozen plasma before and after surgery.
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PMID:The factor of factor XI deficiency in thyroid neoplasia. 378 61

An outline has been given of the major abnormalities of coagulation which can occur secondary to diseases in previously normal individuals. First, the disorders due to deficiency of the vitamin K-dependent clotting factors are described. Vitamin K deficiency can occur in the newborn, or at later stages in life when there is intestinal malabsorption. The malabsorption disorders, such as coeliac disease, together with major abdominal surgery or prolonged use of broad-spectrum antibiotics can give rise to vitamin K deficiency. Additionally, in obstructive jaundice the lack of secretion of bile salts into the upper intestine causes vitamin K malabsorption. The use of oral anticoagulants is associated with haemorrhage in a small proportion of patients. These patients usually have an excessively prolonged prothrombin time, due to overdosage with anticoagulants, but occasionally haemorrhage can occur from a localized bleeding site, such as a duodenal ulcer, in patients under good anticoagulant control. The large number of drugs which can interact with anticoagulants are listed, from which it can be seen that careful monitoring of all patients on oral anticoagulants must be carried out. The haemostatic defects associated with liver disease are then tabulated. In this situation abnormalities may be due to deficient synthesis of coagulation factors in hepatocellular failure, by failure of vitamin K absorption, and also by disseminated intravascular coagulation (DIC). DIC occurs in hepatocellular failure, because the liver cells are normally responsible for clearing activated products of the coagulation and fibrinolytic enzyme systems. The presence of clinical haemorrhage and haemostatic breakdown in hepatic disease usually indicates a serious prognosis, but appropriate replacement therapy is indicated in this situation. Disseminated intravascular coagulation embraces a large number of clinical haemorrhagic syndromes, where intravascular activation of the coagulation system takes place accompanied by compensatory fibrinolytic activity. DIC can be initiated by intravascular release of procoagulant substances, such as tissue thromboplastin, or by damage to vascular endothelium and platelets. The main clinical conditions associated with DIC comprise the severe infections and septicaemias, obstetric accidents, shock and trauma, neoplasia and snake-bite envenoming. In all instances, the pathophysiological disorder of haemostasis is managed by treating the underlying disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acquired coagulation disorders. 389 41

Cancer procoagulant, a proteolytic procoagulant enzyme, has been purified from rabbit V2 carcinoma extracts by two procedures. In the first, the protein was purified by benzamidine--Sepharose affinity chromatography, gel filtration chromatography, and phenyl-Sepharose hydrophobic chromatography. Antiserum was raised against the purified protein and was used to prepare an immunoadsorbent column. In the second, tumor extracts were purified by immunoaffinity chromatography followed by p-(chloromercuri)benzoate affinity chromatography. The second procedure was substantially quicker and easier. The final product of both procedures was homogeneous on the basis of analytical sodium dodecyl sulfate--polyacrylamide gel electrophoresis and isoelectric focusing. The molecular weight was 68 000 and the isoelectric point 4.8. The proteinase activity of cancer procoagulant directly activated factor X, in the absence of factor VII, and was inhibited by 1 mM iodoacetamide and 0.1 mM mercury which are classic cysteine proteinase inhibitors. A carbohydrate analysis showed less than 1 mol of hexose or sialic acid/mol of protein. The amino acid analysis showed that serine (19.1%), glycine (18.77%), and glutamic acid (12.5%) were the prevalent amino acids. The amino acid composition of cancer procoagulant was substantially different than other known factor X activating proteinases or other cysteine proteinases including cathepsin B.
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PMID:Isolation and characterization of cancer procoagulant: a cysteine proteinase from malignant tissue. 393 63


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