Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of cycloprodigiosin hydrochloride (cPrG-HCl), a new H(+)/Cl(-) symporter, were examined in liver cancer cell lines in vitro and in vivo. In the in vitro MTT assay, cPrG-HCl inhibited the growth of 6 liver cancer cell lines (Huh-7, HCC-M, HCC-T, dRLh-84, and H-35, hepatocellular carcinoma; HepG2, hepatoblastoma) in a dose- and time-dependent manner. The 50% inhibitory concentrations (IC(50)) at 72 hours' treatment for liver cancer cell lines were 276 to 592 nmol/L, while that for isolated normal rat hepatocyte was 8.4 micromol/L. The cPrG-HCl treatment of Huh-7 cells induced apoptosis as confirmed by the appearance of a subG(1) population, intranucleosomal DNA fragmentation, and chromatin condensation. cPrG-HCl raised the pH of acidic organelles and lowered pHi (below pH 6.8). In addition, the apoptosis in Huh-7 cells induced by cPrG-HCl was strongly suppressed when the cells were cultured with imidazole, a cell-permeable base. In the in vivo assay, nude mice bearing subcutaneous xenografted Huh-7 cells received 2 weeks of treatment with cPrG-HCl (1 or 10 mg/kg/d) subcutaneously. This treatment significantly inhibited tumor growth compared with the control after 8 days. The control mice were treated with 1% dimethylsulfoxide (DMSO) in saline (vehicle). A histopathological examination using the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) method showed apoptosis in the treated tumor cells. No pathological changes were observed in any organs, and the serum alanine transaminase levels remained within normal limits. These results suggest that cPrG-HCl may be useful for the treatment of hepatocellular carcinoma.
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PMID:Cycloprodigiosin hydrochloride, a new H(+)/Cl(-) symporter, induces apoptosis in human and rat hepatocellular cancer cell lines in vitro and inhibits the growth of hepatocellular carcinoma xenografts in nude mice. 1049 40

Some possible biological and biochemical effects of Sistrurus Malarius Barbouri (SMB) crude venom were investigated. The acute median lethal doses of the venom under investigation were found to be 14.4 and 9.72 microg/g body weight (b.w.), respectively, in rats on i.p. administration. The possible neurotoxicity of acute, subchronic and chronic doses was investigated in-vivo and in-vitro. The venom at a dose level of 2 microg/g b.w. significantly impaired motor coordination, learning and retention, spontaneous activity and produced behavioural changes, muscle weakness and loss of righting reflex in mice. The same dose also produced a significant decrease in body temperature and inhibited acetylcholine-induced contraction of the isolated smooth (rabbit intestine) and skeletal (frog rectus abdominis) muscles and impaired transmission at the nerve muscle synapse of the rat phrenic nerve diaphragm preparation. The effects of the acute sublethal and chronic doses on carbohydrate metabolism revealed a hyperglycemic effect associated with a diminution of liver and muscle glycogen, while its effects on blood electrolytes (sodium and potassium) showed a significant elevation in the blood sodium level and a significant reduction in that of potassium. Serum enzymes were also affected. Levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were moderately increased. The crude venom had an aggregatory effect on platelets and had also a phospholipase A2 activity while, on the other hand, it showed no L-amino acid oxidase activity. Testing of the effect of the venom on the plasma recalcification time showed that the venom had an anticoagulant effect in case of high dose (200 microg), while a coagulant effect was produced at a low dose of the venom (2.5 microg). SMB venom at a dose level of 1.94 microg/g b.w. (LD10) was found to exhibit no significant inhibitory effect on tumor growth when injected into mice.
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PMID:An in vitro and in vivo study of some biological and biochemical effects of Sistrurus Malarius Barbouri venom. 1052 Nov 45

DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl] -4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induce methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it does produce.
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PMID:Effect of DW2282 on the induction of methemoglobinemia, hypoglycemia or WBC count and hematological changes. 1061 61

The antitumor effects of cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) (SM-11355) were evaluated in a rat hepatic tumor model, and were compared with those of cisplatin (CDDP). A novel slowly-growing rat hepatic tumor model was established by the successive transplantation of rat AH109A tumor into the liver. The drugs, which were suspended in Lipiodol, were administered into the proper hepatic artery of tumor-bearing rats. Tumor growth was suppressed in the group that received SM-11355 suspended in Lipiodol (SM-11355/Lipiodol). Mean tumor growth rates in the groups administered 20 microl of Lipiodol containing 0, 0.02, 0.04, 0.1, 0.2, or 0.4 mg of SM-11355 were 244, 86, 110, 81, 51, and 40%, respectively, 1 week after treatment. Those in the groups administered 20 microl of Lipiodol containing 0.1, 0.2, or 0.4 mg of CDDP were 240, 110, and 45%, respectively. In the groups administered 0.2 and 0.4 mg of SM-11355 or 0.4 mg of CDDP, massive necrosis was observed in the tumor tissue 1 week after drug administration, and the tumors disappeared 4 weeks after drug administration. Serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels were measured as markers of liver damage one day after the drug was administered into the hepatic artery of rats. The minimum toxic dose, which raised serum GOT and GPT levels significantly compared with Lipiodol alone, was 0.2 mg for SM-11355/Lipiodol and 0.1 mg for CDDP/Lipiodol, respectively. The results demonstrated that SM-11355/Lipiodol exerted antitumor activity at a dose that showed no hepatic toxicity in the rat model, but CDDP/Lipiodol did not.
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PMID:Antitumor effects of a novel lipophilic platinum complex (SM-11355) against a slowly-growing rat hepatic tumor after intra-hepatic arterial administration. 1072 91

Cytotropic heterogeneous molecular lipid (CHML), which is a new anticancer agent with US patent number 5,260,067, has recently been shown to suppress tumor cell growth in multiple tumor lines and induce apoptosis in vitro (1). These results indicate that CHML may be an effective antitumor agent. In the present study, using both local injection and intravenous injection, we have investigated the suppressive effect of CHML on human breast caner cells MCF-7 xenograft in nude mice. In the local injection, CHML was introduced into nude mice implanted with human breast cancer xenograft at doses of 25 mg/tumor area (cm2), 35 mg/tumor area (cm2), or 50 mg/tumor area (cm2), once every two days, total 3 times. The inhibition of tumor growth was 81.3%, 93.8% and 100%, respectively. In the intravenous injection, the nude mice bearing MCF-7 xenografts were treated with CHML at 10 mg/kg/day, or 15 mg/kg/day, or 20 mg/kg/day, once a day, total 7 days, the growth inhibition of tumor area was 58.1%, 77.4%, and 83.9%, respectively. At the same time, the toxicity of CHML was determined through examining the number of the white blood cell (WBC) and the activity of the serum glutamic-pyruvic transaminase (SGPT). However, no evident alterations of WBC and SGPT were detected in all animals treated with CHML, suggesting that CHML has little toxicity on nude mice. Taken together, these results indicate that CHML is an effective agent that suppresses breast tumor growth and suggest the possibility of using CHML in the clinical trial in the near future.
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PMID:Antitumor activity of cytotropic heterogeneous molecular lipids (CHML) on human breast cancer xenograft in nude mice. 1172 10

Kupffer cells are involved in the pathogenesis of chemically mediated liver injury through release of biologically active mediators that promote the pathogenic process. The purpose of this study was to elucidate specific biochemical and molecular changes occurring in Kupffer cells throughout a time course of carbon tetrachloride (CCl(4))-mediated liver injury and fibrosis. Rats were administered 1 ml/kg of CCl(4) (10% v/v olive oil) twice weekly for up to 6 weeks. Plasma alanine aminotransferase values and hematoxylin-and-eosin- and trichrome-stained liver sections indicated minor liver damage at 2 weeks followed by increased damage and collagen deposition by 4 and 6 weeks. Additionally, mRNA levels in Kupffer cells isolated from CCl(4)-treated rats demonstrated significant increases in tumor necrosis factor alpha (TNF alpha); tumor growth factor beta; interleukin-6 (IL-6); interleukin 1 beta; cyclooxygenase 2; CD14, and I kappa B alpha transcripts after 2 and 4 weeks of treatment. However, the expression of these genes at 6 weeks was similar to that of controls. Increased gene expression of cytokines in Kupffer cells isolated from CCl(4)-treated rats was accompanied by increases in protein production of TNF alpha, IL-6, IL-1 beta, and interleukin 10 following lipopolysaccharide stimulation. Further, liver sections stained for ED2-positive cells demonstrated an increase in the number of resident macrophages at 2 and 4 weeks with a slight decrease in ED2-positive cells by week 6 but still significantly more than control. Analysis of reduced glutathione (GSH) and oxidized glutathione (GSSG) indicated that Kupffer cells from CCl(4)-treated animals exhibited a 50% decrease in GSH at 2 and 4 weeks, whereas no significant changes were observed for GSSG. In conclusion, these data implicate Kupffer cells as a critical mediator of the inflammatory and fibrogenic responses during CCl(4)-mediated liver damage and provide new insight into the temporal molecular and biochemical changes associated with the ability of these resident macrophages to modulate liver injury.
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PMID:Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats. 1173 48

The effects of cPrG x HCl and epirubicin on the suppression of cell growth were examined on human breast cancer cell line (MDA-MB-231). Either cPrG x HCl or epirubicin alone showed a tumor growth inhibition in a time- and dose-dependent manner, however, the combinatory use of cPrG x HCl together with epirubicin resulted in prominent synergistic effects on the breast cancer cells. In the in vitro studies, the combinatory use of these two drugs accelerated apoptotic cell death as revealed by morphological changes as well as by the appearance of subG1 population by flow cytometry. In addition, confocal microscopy revealed that the accumulation of epirubicin in nucleus increased apparently when cPrG x HCl were present. In the in vivo assay, nude mice bearing xenografted tumor cells received 4 weeks of intraperitoneal administration of cPrG-HCl and epirubicin. After 12 days, the combinatory treatment significantly suppressed the tumor growth compared to the controls. The TUNEL staining revealed that tumor cells in cPrG x HCl plus epirubicin-treated mice exhibited a higher apoptotic rate. In addition, 31P-NMR studies on the xenografted tumor revealed that cPrG x HCl lowered tumor pHi (below pH 6.9). while it did not affected muscle pHi. No pathological changes were observed in any intrinsic organs and the serum alanine aminotransferase levels remained within normal limits among the groups. These results suggest that the combinatory use of cPrG x HCl and epirubicin may be useful for breast cancer therapy.
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PMID:Synergistic effects induced by cycloprodigiosin hydrochloride and epirubicin on human breast cancer cells. 1200 Feb 16

Raf-1 protein serine threonine kinase plays an important role in cell survival and proliferation. Antisense inhibition of Raf-1 expression has been shown to enhance the cytotoxic effects of radiation and anticancer drugs. Here we have evaluated the toxicity, pharmacokinetics, and antitumor efficacy of a novel formulation of liposome-entrapped raf antisense oligodeoxyribonucleotide (LErafAON). The LErafAON preparation showed high liposome entrapment efficiency of rafAON (>85%) and stability at room temperature. In CD2F1 mice, administration of LErafAON produced no morbidity/mortality (5-35 mg/kg/dose, i.v., x12). Dose-related elevations in liver enzymes (alanine aminotransferase and aspartate aminotransferase) and histopathological changes in liver were noted in LErafAON and blank liposome groups. No morbidity/mortality and changes in clinical chemistry or histopathology were observed in New Zealand white rabbits (3.75 mg/kg/dose, i.v., x8; 6.5 mg/kg/dose, i.v., x6) or in cynomolgous monkeys (3.75 or 6.25 mg/kg/dose, i.v., x9). Transient decrease in total hemolytic complement activity (approximately 62-74%) and increases in C3a (approximately 3-fold) and Bb levels (approximately 5-12-fold) were observed in LErafAON and blank liposome groups of monkeys. A 30 mg/kg i.v. dose of LErafAON in human prostate tumor (PC-3)-bearing BALB/c athymic mice gave a terminal plasma half-life of 27 h, and intact rafAON could be detected in plasma and in normal and tumor tissues for up to at least 48 h. In monkeys, the terminal plasma half-life of 30.36 +/- 23.87 h was observed at an i.v. dose of 6.25 mg/kg. LErafAON (25 mg/kg/dose, i.v., x10) or ionizing radiation (3.8 Gy/day, x5) treatment of PC-3 tumor-bearing athymic mice led to tumor growth arrest, whereas a combination of LErafAON and ionizing radiation treatments resulted in tumor regression. LErafAON treatment caused inhibition of Raf-1 protein expression in normal and tumor tissues in these mice (>50%, versus controls). These data have formed a basis of the clinical Phase I studies of LErafAON for cancer treatment.
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PMID:Pharmacokinetics, toxicity, and efficacy of ends-modified raf antisense oligodeoxyribonucleotide encapsulated in a novel cationic liposome. 1242 53

Quantitative determination of newly reported enzymes activity in the crude skin toxin (CST) of catfish revealed highest activities of hyaluronidase and lipase, lesser activities of phospholipase A2, lactate dehydrogenase (LDH), cholinesterase (CE), alkaline phosphatase (ALP), and aspartate transaminase (AST), and least activities of proteinase and 5-nucleotidase (5'-NT). The CST has a hemolytic activity of 54% and no ichthyotoxicity up to 500 ug/ml. The chosen dose of CST (LD12.5) showed a potential cytotoxic activity against solid Ehrlich carcinoma-bearing mice demonstrated by an increase in the mean survival time (238.8%) and tumor growth inhibition ratio (T/C) of 73%. The CST ameliorated the relative weights of heart and liver after three weeks, while modulating the elevation in the relative spleen weight throughout the treatment periods (three, six, and nine weeks). The levels of serum triglyceride, total cholesterol, and liver total lipids were normalized after three weeks, whereas the serum albumin and hepatic glycogen concentrations, as well as ALT, AST, 5'-NT, and G-6-Pase activities were ameliorated after 6 weeks. Serum levels of glucose, LDH, and creatine kinase (CK) activities were significantly modulated throughout the treatment periods. Histological examinations of the tumor and liver tissues of treated tumor-bearing animals were carried out. Tumor tissues showed many cytolytic and cytopathic changes after treatment, while liver tissues showed moderate dysplastic changes after six weeks of treatment, which became more marked after nine weeks.
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PMID:Biological activities of the crude skin toxin of the Suez Gulf oriental catfish (Plotosus lineatus) and its antitumor effect in vivo (mice). 1250 71

Hepatocellular carcinoma is a major health problem worldwide. Different treatment strategies have been developed to cope with this problem. Herbal medicine is now widely studied in both Eastern and Western countries. In this study, we used both in vitro and in vivo model to illustrate the anti-tumor effect of a product, CKBM, consisting of herbal medicine and specially processed Saccharomyces cerevisiae. Dose-dependent anti-proliferation effect was observed on in vitro growth of human hepatoma HepG2 cells after 48 hours incubation with CKBM. At the 50% inhibitory concentration (IC50) no significant toxic effect was observed on normal human fibroblasts Hs68 and human liver WRL-68 cells. The results of morphological changes, detection of DNA fragmentation, flow cytometric analysis and Western blot analysis indicated that this anti-tumor effect of CKBM was mediated via the process of apoptosis. In addition, HepG2 cells- bearing nude mice model was used for in vivo anti-tumor study. Our results showed that 14-day treatment with 0.8 ml daily dosage of CKBM could inhibit 54.1% of tumor growth. The plasma activities of enzymes specific for heart and liver, namely creatine kinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase, remained at normal levels, indicated that CKBM did not produce toxicity to the host.
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PMID:Anti-cancer and pro-apoptotic effects of an herbal medicine and Saccharomyces cerevisiae product (CKBM) on human hepatocellular carcinoma HepG2 cells in vitro and in vivo. 1565 8


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