Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma.
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PMID:Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule. 20 86

We previously studied fibrinolysis and fibrinogenolysis by analyzing fragments of fibrin/fibrinogen degradation products (FDP) employing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In this report, we characterized the fragments of FDP in four patients with disseminated intravascular coagulation (DIC), that were caused by various diseases. In the patients suffering from acute lymphoblastic leukemia (case 1) and acute suppurative cholangitis (case 3), DD and DY/X fragments resulting from fibrinolysis accounted for the most part of the FDP fragments. In case 3, D fragments resulting from fibrinogenolysis were also observed to much less extent. In a DIC associated with acute myeloblastic leukemia (case 2), both fibrinolysis and fibrinogenolysis were increased and resulted in high levels of D, Y and DY/X fragments, concomitant with moderate levels of DD and high molecular weight (HMW) fragments in the patient's sera. The increased fibrinogenolysis in this case was attributed to accelerated activation of plasmin. In a DIC patient of case 4, who underwent an operation due to hepatocellular carcinoma, marked increase in DY/X and HMW fragments and slight increase in DD fragment were observed on the day of operation. Hyperfibrinolysis documented in case 4 was explained by both increased production of thrombin and moderately accelerated activation of plasmin. Both qualitative and quantitative changes in the fragments of FDP during the courses of treatment in two cases of DIC were also noted. In summary, each underlying disease expresses characteristic pattern of FDP fragments in DIC.
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PMID:[Studies on the fragments of FDP in 4 patients with DIC]. 130 14

The efficacy of transarterial immuno-embolization therapy (TIE) was investigated in 7 patients with multiple hepatocellular carcinoma (HCC). We administered OK-432 (10 KE), fibrinogen (30 mg/ml) and thrombin (1 U/ml) as a new treatment for HCC with intrahepatic metastasis. In all patients with a high level of AFP, the AFP level decreased promptly less than the pretreatment level after TIE therapy. High fever in all cases, epigastralgia in 6 cases and appetite loss in 3 cases were observed after TIE therapy. Our results indicate that this therapy may be a safe and effective method in HCC patients with intrahepatic metastasis.
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PMID:[The efficacy of transarterial immuno-embolization therapy in patients with hepatocellular carcinoma]. 132 9

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5 U/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on s-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC50, 0.02 microM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC50, 0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E3 and 10 E5) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.
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PMID:Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line. 151 27

The ability of normal and malignant blood-borne cells to extravasate correlates with the activity of an endo-beta-D-glucuronidase (heparanase) which degrades heparan sulfate (HS) in the subendothelial extracellular matrix (ECM). The association of malignancy with different types of coagulopathies prompted us to study the effect of thrombin (EC 3.4.21.5), a serine protease elaborated during activation of the clotting cascade, on the ability of heparanase to degrade the ECM-HS. The circulating zymogen form of thrombin, prothrombin, was converted to proteolytically active thrombin during incubation with ECM. Thrombin generation by the ECM was time and dose dependent, reaching maximal conversion by 6 h incubation at 3 U/ml of prothrombin. Heparanase-mediated release of low Mr HS cleavage products from sulfate-labeled ECM was stimulated four- to sixfold in the presence of alpha-thrombin, but there was no effect on degradation of soluble HS. Similar results were obtained with heparanase preparations derived from mouse lymphoma and human hepatoma cell lines and from human placenta. Incubation of ECM with alpha-thrombin alone resulted in release of nearly intact high-Mr labeled proteoglycans. Thrombin stimulation of heparanase action was dose and time dependent, reaching a maximal value at 24 h incubation with 1 microM alpha-thrombin. The effect of modified thrombin preparations correlated with their proteolytic activity. Catalytically blocked preparations of thrombin (e.g., DIP-alpha-thrombin, MeSO2-alpha-thrombin) failed to facilitate heparanase action, while catalytically modified preparations (e.g., gamma-thrombin, NO2-alpha-thrombin) exerted only a slight enhancement. Antithrombin III (ATIII) and hirudin both inhibited thrombin-stimulated heparanase degradation of ECM-bound HS. Heparanase action was also facilitated by ECM-immobilized thrombin to an extent which was similar to that induced by soluble thrombin. This result implies that thrombin sequestered by the subendothelial ECM and protected from interaction with its natural inhibitor ATIII (Bar-Shavit et al., 1989, J. Clin. Invest. 84, 1096-1104) may participate locally in cellular invasion during tumor metastasis, inflammation, and autoimmunity.
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PMID:Thrombin enhances degradation of heparan sulfate in the extracellular matrix by tumor cell heparanase. 161 23

The changes in coagulation and fibrinolysis were studied in cases of hepatocellular carcinoma with (n = 20) and without (n = 8) transcatheter hepatic arterial embolization (TAE). The plasma levels of thrombin-antithrombin III complex (TAT) and alpha 2 plasmin inhibitor complex (PIC) were significantly elevated after TAE, concurrently with a decrease in antithrombin III and antiplasmin (alpha 2-plasmin inhibitor) levels. The elevation of TAT was most significant (2.4-fold of the pre-TAE level) on day 3, whereas that of PIC was relatively less (1.3-fold on day 3). Tissue plasminogen activator in blood was also significantly increased on day 1, but it was decreased thereafter, although plasminogen activator inhibitor (PAI) remained high for at least 7 days after TAE. In contrast, such hematological changes were not observed in patients without TAE. Thus, both coagulation and fibrinolysis were activated after TAE, but its effect on fibrinolysis was less prominent, due probably to the increased synthesis of PAI.
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PMID:Effects of transcatheter hepatic arterial embolization on coagulation and fibrinolysis in patients with hepatocellular carcinoma. 166 Feb 19

To clarify the effects on blood coagulation-fibrinolytic system after transcatheter hepatic arterial therapy for cases of hepatocellular carcinoma (HCC), plasma levels of Plasmin-alpha 2PI complex (PIC), Ddimer and Thrombin-ATIII (TAT) before and after therapy were measured by EIA, in addition to other conventional coagulofibrinolytic parameters. In the group (9 cases) treated with intra-arterial injection of adriamycin, there were no significant changes of coagulofibrinolytic parameters except for Ddimer (P less than 0.05) which was elevated 1-2 days after therapy. However, only two cases in whom plasma PIC, Ddimer and TAT levels were clearly elevated before therapy, showed further marked elevation of those parameters after therapy. In the group (29 cases) treated with intra-arterial injection of adriamycin-lipiodol suspension, whether or not embolized with gelfoam, plasma PIC, Ddimer and TAT levels were significantly elevated (P less than 0.01) after therapy, as well as other conventional coagulofibrinolytic parameters. These results indicate that hypercoagulable and hyperfibrinolytic states were induced by treatment. Moreover, the secondary hyperfibrinolytic state tended to persist longer than the hypercoagulable state. The 14 cases embolized with gelfoam seemed to have more apparent effects on blood coagulation-fibrinolytic system than cases not treated with gelfoam. Therefore, we conclude that caution and prophylaxis for the occurrence of disseminated intravascular coagulation are necessary for transcatheter arterial therapy for cases of HCC.
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PMID:[Effects on blood coagulation-fibrinolytic system after transcatheter hepatic arterial therapy in cases of hepatocellular carcinoma analyzed by plasma levels of plasmin-alpha 2-PI complex, D dimer and thrombin-ATIII complex]. 169

Detection of hypercoagulable state might be helpful in the diagnosis of primary hepatocellular carcinoma (HCC) complicating liver cirrhosis (LC). Plasma levels of thrombin-antithrombin III complex (TAT) were determined in 50 patients of LC with or without HCC. The levels were above 2 ng/ml in 80% of 25 HCC patients, but only in 12% of 25 non-HCC patients (P less than 0.01). The levels over 2 ng/ml occurred even in five of six HCC patients whose serum alpha-fetoprotein levels were below 20 ng/ml as well as in two of three patients with HCC less than 2 cm in diameter. Those levels in HCC patients were significantly decreased within 8 days after treatment with transcatheter arterial embolization or infusion of antitumor agents, without affecting plasma antithrombin III levels. These results suggest that plasma TAT levels may be useful in the diagnosis of HCC complicating LC.
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PMID:Plasma thrombin-antithrombin III complexes in the diagnosis of primary hepatocellular carcinoma complicating liver cirrhosis. 184 49

Thrombin-antithrombin III complex (TAT) and Plasmin-alpha 2 plasmin inhibitor complex (PIC) were examined in fifty two cases of various chronic liver diseases. TAT was significantly elevated in cases of hepatocellular carcinoma (HCC), but PIC did not show significant changes in any chronic liver diseases. Elevations of TAT and PIC were seen in cases of HCC accompanied by tumor enlargement and extensive tumor thrombosis. In cases of HCC undergoing transcatheter arterial embolization (TAE), TAT and PIC increased on the next day after TAE, and tended to recover with time, returning to almost normal at fourth week. Prolongation of prothrombin time, elevation of FDP and positive FM test were noted more often in liver cirrhosis with disseminated intravascular coagulation (DIC) than in severe liver dysfunction without DIC. Of five cases confirmed as DIC, only three cases were diagnosed as DIC by DIC score. On the other hand, TAT and PIC were significantly elevated in DIC cases. Especially, TAT exceeded 30 ng/ml in all DIC cases. TAT was regarded to be useful for the diagnosis of DIC in severe liver dysfunction.
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PMID:[Clinical significance of thrombin-antithrombin III complex and plasmin-alpha 2 plasmin inhibitor complex in chronic liver diseases]. 214 51

To clarify the meaning of increased serum fibrin/fibrinogen degradation products (FDP) in the postoperative period of hepatectomy, blood coagulation and fibrinolysis were studied using recently devised laboratory assays of a group of 30 patients with hepatocellular carcinoma. Twenty of these cases were associated with liver cirrhosis. As a control group, 15 patients with colorectal carcinoma without liver diseases were also selected. In the early postoperative period following hepatectomy, a hypercoagulable state designated as intravascular thrombin generation was confirmed from the finding of increased plasma levels of fibrinopeptide A (FPA). Fibrinopeptide B beta 15-42 (B beta 15-42) in the plasma also increased immediately after the peak of FPA, followed by a gradual decline in B beta 15-42 levels. On the other hand, FDP in the serum increased significantly rather late in the postoperative period following hepatectomy without increased levels of plasmin-alpha 2-plasmin inhibitor complex. However, postoperative increase of fibrin/fibrinogen degradation products-D (FDP-D) was modest and not different from the colectomy group. Therefore, the relevance of intravascular coagulation in the hepatectomy for the patients with liver cirrhosis seems not to be significant, and then such an increase of FDP in the serum seems to be related to other mechanisms.
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PMID:Increased fibrin/fibrinogen degradation products without increase of plasmin-alpha 2-plasmin inhibitor complex after hepatectomy for hepatocellular carcinoma. 215 47


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