Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 77-year-old male presented at our Department of Urology in August 1990 with a gradually enlarging swelling in the right scrotum. On August 21, right high orchietomy was performed. This was diagnosed histologically as non-Hodgkin's lymphoma (diffuse large cell type), and the patient was transferred to our department on September 11 for further examination and treatment. As enlargement of the lymph nodes around the abdominal aorta was evident, it was diagnosed as stage IIA according to the Ann Arbor Classification. Beginning on September 21, three courses of COP-BLAM therapy (CPM, VCR, PDN, BLM, ADR, PCZ) were administered (the third course started on November 8) to achieve complete remission. Hepatic dysfunction appeared, however, from November 16, and by November 19, GOT and GPT increased to 6700 and 2120, respectively, with aggravation of jaundice. PDN therapy was instituted, and GOT and GPT improved gradually, but jaundice did not improve. On December 22, laparoscopy was performed, and liver biopsy produced histologic findings of drug-induced hepatitis. Further, lymphoblastic response was positive for CPM. Hepatic failure occurred on December 29, and plasma exchange was performed, but it failed to improve the condition, and the patient died on January 15. We described a case of non-Hodgkin's lymphoma complicated by hepatic dysfunction, probably induced by CPM, in an elderly patient who died to hepatic failure.
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PMID:[Non-Hodgkin's lymphoma in an elderly patient complicated by cyclophosphamide-induced allergic hepatic dysfunction]. 143 65

Degradable starch microspheres (DSM) have a mean diameter of 45 micron and temporarily obstruct blood flow at the arteriolar (micro-circulatory) level. A new approach was attempted to improve the anticancer effect on non-resectable liver cancer with simultaneous administration of DSM and MMC (mitomycin C) or ADR (adriamycin) into hepatic artery. Three patients with primary liver cancer were treated with DSM (600-1200 mg) and ADR (20-60 mg), and five with metastatic liver cancer were treated with DSM and MMC (10-20 mg). The treatment was repeated two to ten times. Partial or minor responses were observed in 1 out of 3 cases of primary liver cancer and 3 out of 5 metastatic cases. Side effects of DSM were temporary and mild epigastric or chest pain, vomiting, fever, slight dyspnea, etc. A temporary change in the liver functional data (GOT, GPT) was noted in 3 patients. Selective intra-hepatic arterial chemo-embolization therapy with DSM would appear to be beneficial for the treatment of liver cancers with appropriate indications. Cases in which DSM and anticancer drugs were effected were presented in detail.
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PMID:[Hepatic arterial infusion of degradable starch microspheres (DSM) with adriamycin or mitomycin C in liver cancer]. 313 87

As a novel method for the medical application of liposomes, we have tried hepatic artery chemoembolization using temperature-sensitive liposomes with hyperthermia for the treatment of hepatic tumors. In this study, the effect of temperature-sensitive liposomes was compared with that of Lipiodol emulsion, which has been used clinically. The temperature-sensitive liposomes, consisting of dipalmitoylphosphatidylcholine or Lipiodol emulsions entrapping doxorubicin, were administered into the hepatic artery of hepatic tumor-bearing rats via a cannula. Doxorubicin administered in a liposomal form showed a high accumulative property toward tumors, with heating, while that in the emulsion form showed a slow release property toward tumors. Not only was tumor growth inhibited, but also, an actual diminishing of the tumor was observed in each form. Side effects were also examined: an abnormal rise in GPT, or necrosis of the normal tissues in liver, which was often observed in hepatic artery chemoembolization using Lipiodol emulsion, was remarkably reduced in the liposomal chemoembolization.
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PMID:Study on hepatic artery chemoembolization using temperature-sensitive liposome or lipiodol emulsion. 774 98

Our working hypothesis states that DNA damage is a critical step in toxic cell death. The DNA hypothesis was tested in cultured mouse hepatocytes by examining whether inhibitors of DNA repair would increase dimethylnitrosamine toxicity and DNA damage in parallel. Inhibitors were chosen for selectivity toward DNA polymerase alpha (aphidicolin, myricetin), DNA ligase (ethidium bromide), or multiple repair enzymes (ara-C, doxorubicin). Dimethylnitrosamine caused concentration-dependent DNA damage at 6 hr and cell death at 24 hr (35% ALT release vs. 8.8% in control cultured hepatocytes). Each repair inhibitor increased dimethylnitrosamine-induced DNA damage and toxic cell death in parallel. Doxorubicin maximally elevated DNA fragmentation and toxicity (57% ALT release). Repair inhibitors alone failed to damage DNA or cause cell death in this model system. These data support the hypothesis that DNA damage is an early causal event in toxic cell death caused by alkylating hepatotoxicants.
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PMID:DNA as a critical target in toxic cell death: enhancement of dimethylnitrosamine cytotoxicity by DNA repair inhibitors. 799 86

An 87-year-old woman, who had been suffering from hypothyroidism and had been treated as an outpatient at our department since 1982, noticed left cervical swelling toward the end of November 1992. Because ultrasonic examination revealed a mass in her thyroid gland, she was admitted for a closer examination and additional treatment. Biopsy of thyroid gland revealed non-Hodgkin's lymphoma (NHL; the diffuse small cell type, B-cell origin). A part from the swelling of thyroid gland and the left cervical lymph node, performance of various examinations did not detected any other NHL lesions. Therefore, it was classified as stage II NHL according to the Ann Arbor classification. Laboratory data on admission were as follows; WBC 4,400/microliters, Hb 13.6 g/dl, platelet count 10.1 x 10(4)/microliters, GOT 51 IU/l, GPT 31 IU/l, TSH 1.17, free-T4 1.03, free-T3 2.04, and microsome test 1,600 x. Those data indicated marked hypothyroidism. In addition, stage IIa and IIc gastric cancers were detected by the examination with gastric endoscopy performed for stage classification. Both were adenocarcinomas. Because polyps were found in her sigmoid colon with colonoscopy, polypectomy was performed. The polyps were diagnose histologically as moderately differentiated adenocarcinoma. On July 20, COP-BLAM therapy was started (CPM 600 mg div, VCR 1.2 mg iv, ADR 30 mg iv on day 1, PDN 40 mg p.o and PCZ 100 mg p.o. on days 1-10, BLM 7.5 mg div on day 14). Subsequently, the left cervical lymph node swelling disappeared, and shrinkage of the mass in the thyroid gland was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of elderly Hashimoto disease presenting malignant lymphoma, gastric cancer and colon cancer]. 829 59

We investigated the anticancer effect and pharmacokinetics of doxorubicin hydrochloride(ADR, 1 mg/kg) and mitomycin C (MMC, 0.2 mg/kg) given intra-arterially in combination with a temporary embolizing material, degradable starch microspheres (DSM, 5 mg/kg), to rabbits in which VX2 tumors had been implanted into the liver. The results revealed that the anticancer effect of ADR and MMC was potentiated by concomitant treatment with DSM in comparison to intra-arterial drug therapy alone. The tumor growth inhibition rate in both groups was about 87%. There was a tendency of higher intra-tumour ADR concentrations after ADR and DSM than after ADR alone. When we measured the serum levels of ADR and MMC over 45 min., it was indicated that exposure of the drugs to the systemic circulation was inhibited by the combination with DSM. In these experiments, GOT and GPT values increased temporarily after intra-arterial chemotherapy combined with DSM, but decreased gradually later to normal or close to the normal levels. These results indicate that intra-arterial chemotherapy combined with DSM causes a temporary blood flow blockade and the resulting regional retention of the cytotoxic agents, provides a more potent anticancer effect than drug therapy alone.
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PMID:[Effect of intra-arterial chemotherapy combined with degradable starch microspheres against liver cancer--a study by experimental VX2 liver tumor model]. 837 73

Doxorubicin produces clinically useful responses in a variety of human cancers. However, the toxicity of doxorubicin has limited its usefulness. This side effect is mainly due to the doxorubicin-mediated free radical formation. Administration of doxorubicin (10 mg/kg body weight) to rats intravenously induces heme oxygenase-1 (HO-1) in the liver. The levels of HO-1 protein were first detected at 6 hours and peaked at about 18 to 24 hours after the injection. It is known that HO-1 plays a protective role against the oxidative injury. Therefore, we have examined the protective effect of doxorubicin preconditioning against the hepatic ischemia-reperfusion injury. Partial hepatic ischemia was produced in the left and medium lobes for 45 minutes followed by 120 minutes reperfusion. When low doses of doxorubicin (1 mg/kg body weight) was intravenously administered to rats 2 days before the ischemia, the serum alanine transaminase (ALT) levels in the preconditioning rat were clearly improved compared with those in the rat without preconditioning. Under this situation, zinc-protoporphyrin IX, a specific inhibitor of HO-1, was injected subcutaneously to rats at 3 and 16 hours before the ischemia, the ALT levels were not improved by doxorubicin preconditioning. Histopathologic examination also supported these results. Although the HO-1 protein level was fairly low 2 days after the doxorubicin administration, significant amounts of HO-1 protein were detected. Our results indicated that the induction of HO-1 played a protective role against hepatic ischemia-reperfusion injury and that doxorubicin preconditioning is more clinically useful than other preconditioning methods.
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PMID:Doxorubicin preconditioning: a protection against rat hepatic ischemia-reperfusion injury. 1065 83

Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme into biliverdin, carbon monoxide, and iron. HO-1, an inducible form, is thought to contribute to resistance to various types of oxidative stress. Doxorubicin (DOX) produces clinically useful responses in a variety of human cancers. We reported previously that prior administration of DOX ameliorated subsequent hepatic ischemia and reperfusion injury. The aim of this study was to examine whether this pharmacological preconditioning was useful for another type of hepatic injury induced by a non-surgical method. When a high dose of DOX (10 mg/kg body weight) was administered directly to rat liver via the portal vein, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels increased markedly 24 hr after the injection. Under this condition, zinc-protoporphyrin IX, a specific inhibitor of HO-1, caused both serum AST and ALT levels to be elevated further. When a low dose of DOX (5 mg/kg body weight) was administered to rats via the tail vein as pharmacological preconditioning 3 days before the injection of a high dose of DOX via the portal vein, the levels of serum AST and ALT in rats clearly were improved as compared with rats without the preconditioning. Expression of HO-1 in the liver was confirmed 3 days after the administration of a low dose of DOX. In addition, prior administration of zinc-protoporphyrin IX abolished the effect of DOX preconditioning. Immunohistochemical analysis showed that the positive staining of HO-1 protein induced by a low dose of DOX was localized to histiocytes infiltrating periportal areas. These results strongly suggest that pharmacological preconditioning with DOX may generally help to attenuate subsequent oxidant-induced hepatic injury.
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PMID:Pharmacological preconditioning with doxorubicin. Implications of heme oxygenase-1 induction in doxorubicin-induced hepatic injury in rats. 1170 58

Oleuropein (oleu) is a natural phenolic antioxidant, which is present in elevated concentration in olives, olive oil and olive tree leaves. Doxorubicin (DXR) induced cardiotoxicity is mainly induced by oxidative stress but the precise mechanism remains obscure. However, there is evidence that high concentration of nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite formation may be involved in DXR cardiotoxicity. The aim of the present study was to evaluate a possible protective role of oleu in DXR induced cardiotoxicity in vivo. Fifty rats were divided into 6 groups and treated as follows: control group with a single injection of 2 ml normal saline intraperitoneally (i.p.), DXR group with a single dose of 20 mg/kg i.p, and DXR plus oleu groups with 20 mg/kg DXR i.p. and 100 or 200 mg/kg/BW of oleu i.p. for 5 or 3 consecutive days starting either 2 days before or on the day of DXR administration. Seventy-two hours after DXR treatment blood samples were collected for creatine phosphokinase (CPK), creatine phosphokinase-MB (CPK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) assessments and the rats were then sacrificed. Hearts were used for general histology, iNOS immunohistochemical and Western blot analysis, and for determination of tissue concentrations of lipid peroxidation products, protein carbonyls (PCs), and nitrotyrosine (NT). DXR treated animals demonstrated very extensive cytoplasmic vacuolisation whereas much less vacuolisation was found in oleu treated groups. They also revealed a significant elevation of cardiac enzymes release into systemic circulation (P<0.05 vs saline). Both doses of Oleu tested and both treatment protocols reduced DXR elevated serum levels of CPK, CPK-MB, LDH, AST and ALT (P<0.05). Furthermore, it reduced DXR induced lipid peroxidation, PCs content, NT concentration and iNOS induction in myocardial tissue (P<0.05). Oleu exerts a protective effect by eliminating DXR induced cardiotoxicity expressed by the alteration of intracellular and peripheral markers. Combined oleu and DXR treatment improves the therapeutic outcome by preventing undesirable toxicity.
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PMID:Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress. 1722 28

1. Doxorubicin is an anti-cancer drug with well-described effects against a wide range of tumours. However, doxorubicin also exhibits dose-dependent cytotoxicity. The purpose of the present study was to determine whether chronic supplementation of creatine or a mix of vitamins C and E could increase survival and improve plasma parameters 48 h after doxorubicin treatment. 2. Rats were divided into four groups: (i) saline (control); (ii) doxorubicin treated; (iii) a creatine (0.2 g/kg per day)-supplemented group; and (iv) a vitamin C (250 mg/kg per day) and E (400 IU/kg per day)-supplemented group. After 30 days supplementation of rats with either creatine or the vitamins, one dose of doxorubicin (15 mg/kg, i.p.) was administered. 3. There was no difference in weight loss among the groups until the 3rd day after doxorubicin treatment, but the creatine- and vitamin-supplemented groups lived longer compared with the doxorubicin only treated group (6, 7 and 3 days, respectively). The doxorubicin-treated group lost 13.4% bodyweight over 3 days, whereas the creatine- and vitamin-supplemented groups lost approximately 35% 3 days after the administration of doxorubicin. Doxorubicin treatment resulted in an increase in alanine aminotransferase (ALT; P < 0.05), lactate dehydrogenase (LDH; P < 0.05), urea (P < 0.05) and creatinine (P < 0.05) compared with levels observed in the control group. Conversely, creatine supplementation promoted a partial return to control values for LDH (P < 0.05) and creatinine (P < 0.05), whereas the vitamin mix reversed the changes in ALT (P < 0.05), LDH (P < 0.05), urea (P < 0.05) and creatinine (P < 0.05). 4. In conclusion, the results of the present study indicate that the two supplementation protocols decreased the cytotoxic effects of doxorubicin and that a protective effect was more noticeable in animals supplemented with the mixture of vitamins C and E.
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PMID:Chronic supplementation of creatine and vitamins C and E increases survival and improves biochemical parameters after Doxorubicin treatment in rats. 1797 71


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