EC:2.3.1.109 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Protein kinase C alpha (PKC-alpha) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC-alpha that reduces PKC-alphain human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this phase 2 study, aprinocarsen was administered to patients with recurrent high-grade gliomas by continuous intravenous infusion (2.0 mg/kg/day for 21 days per month). Twenty-one patients entered this trial. Their median age was 46 years (range, 28-68 years), median Karnofsky performance status was 80 (range, 60-100), median tumor volume was 58 cm3 (range, 16-254 cm3), and histology included glioblastoma multiforme (n = 16), anaplastic oligodendroglioma (n = 4), and anaplastic astrocytoma (n = 1). The number of prior chemotherapy regimens included none (n = 3), one (n = 10), and two (n = 8). No tumor responses were observed. Patients on this therapy rapidly developed symptoms of increased intracranial pressure with increased edema, enhancement, and mass effect on neuroimaging. The median time to progression was 36 days, and median survival was 3.4 months. The observed toxicities were mild, reversible, and uncommon (grade 3 thrombocytopenia [n = 3] and grade 4 AST [n = 1]), and no coagulopathy or CNS bleeding resulted from this therapy. Plasma concentrations of aprinocarsen during the infusion exhibited significant interpatient variability (mean = 1.06 mug/ml; range, 0.34-6.08 mug/ml). This is the first study to use an antisense oligonucleotide or a specific PKC-alpha inhibitor in patients with high-grade gliomas. No clinical benefit was seen. The rapid deterioration seen in these patients could result from tumor growth or an effect of aprinocarsen on bloodbrain barrier integrity.
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PMID:Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas. 1570 Dec 80

Infection with hepatitis C virus (HCV) is characterized by inflammatory liver damage and a long viral persistence associated with an increased risk of developing hepatocellular carcinoma (HCC). Intercellular adhesion molecule-1 (ICAM-1) plays a key role during liver inflammation and also expressed in HCC. Its cellular expression is associated with the release of soluble form (sICAM-1) in the peripheral blood. The process of angiogenesis plays a critical role in liver damage-associated HCV infection and in tumor growth and metastasis. Vascular Endothelial Growth Factor (VEGF) is an important angiogenic factor regulating tumor angiogenesis. This study aimed at investigating the influence of HCV infection on serum profile of sICAM-1 and VEGF in patients with hepatitis C and HCC and their diagnostic value as useful markers reflecting progressive liver damage and development of HCC. Serum levels of sICAM-1 and VEGF were determined in the serum of fifteen HCV infected patients, fifteen HCV-positive patients with superimposed HCC as well as ten healthy control subjects by enzyme linked immunosorbent assay. HCV RNA copy numbers were analyzed by Real-time polymerase chain reaction using TaqMan probe technology. Alpha-fetoprotein levels and serum aminotransferases activities were also measured. The group of patients with hepatitis C and superimposed HCC had significantly higher sICAM-1 and VEGF values than HCV infected patients (1178.113 +/- 631.87 vs. 313.67 +/- 82.72 & 320.88 +/- 117.99 vs. 132.45 +/- 91.56, p < 0.001 respectively). In comparison to healthy subjects, HCV infected patients showed dramatically elevated serum levels of VEGF (132.45 +/- 91.56 vs. 7.76 +/- 7.41, p < 0.001). On the other hand, sICAM-1 levels were elevated in patients with HCV as compared with healthy controls, but this did not reach statistical significance (313.67 +/- 82.72 vs. 230.3 +/- 47.4, p > 0.05). A highly significant correlation was found between VEGF and sICAM-1 levels in all patients (r = 0.731, p < 0.001) also between VEGF, sICAM-1 and AFP (r = 0.473, p < 0.001, r = 0.690, p < 0.001, respectively) as well as between sICAM-1 and AST activities (r = 0.367, p < 0.05). A weak correlation was found between the level of viremia and VEGF, sICAM-1 levels, yet this did not reach statistical significance (r = 0.312, p = 0.09 & r = 0.228, p > 0.05 respectively). The sensitivity of HCC detection using AFP alone was 93.3%. It yielded 100% detection sensitivity when combined with sICAM-1 and/or VEGF with diagnostic accuracy reaching 96.67%. In conclusion, HCV infection and the development of HCC on top greatly affect the serum profile of VEGF and sICAM-1. VEGF as it stimulates endothelial cell growth, it could modulate the expression of sICAM-1 and both could be considered as convenient markers of progressive liver damage, endothelial activation and therefore could improve detection and management of HCC.
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PMID:Influence of hepatitis C virus infection on circulating levels of sICAM-1 and VEGF in patients with hepatitis C and hepatocellular carcinoma (HCC) and their role in enhancing detection of HCC. 1797 48

The polymer, OEI-HD, based on beta-propionamide-cross-linked oligoethylenimine and its chemical transferrin conjugate were evaluated for siRNA delivery into murine Neuro2A neuroblastoma cells in vitro and in vivo. An 80% silencing of luciferase expression in neuroblastoma cells, stably transfected with a luciferase gene, was obtained using standard OEI-HD polyplexes or transferrin-conjugated shielded OEI-HD polyplexes. The Ras-related nuclear protein Ran was selected as a therapeutically relevant target protein. Systemic delivery of transferrin-conjugated OEI-HD/RAN siRNA formulations (three intravenous applications at 3 days interval) resulted in >80% reduced Ran protein expression, apoptosis, and a reduced tumor growth in Neuro2A tumors of treated mice. The treatment was not associated with signs of acute toxicity or significant changes in weight, hematology parameters, or liver enzymes (AST, ALT, or AP) of mice. All our results demonstrate that OEI-HD/siRNA formulations can knockdown genes in tumor cells in vitro and in vivo in mice in the absence of unspecific toxicity.
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PMID:Induction of apoptosis in murine neuroblastoma by systemic delivery of transferrin-shielded siRNA polyplexes for downregulation of Ran. 1863 33

Agaricus blazei Murrill, a native mushroom of Brazil, has been widely consumed in different parts of the world due to its anticancer potential. This effect is generally attributed to its polysaccharides; however, the precise structure of these has not been fully characterized. To better understand the relationship between polysaccharide structures and antitumor activity, we investigated the effect of the intraperitoneally (i.p.) or orally (p.o.) administered alpha-(1-->4)-glucan-beta-(1-->6)-glucan-protein complex polysaccharide from A. blazei alone or in association with 5-fluorouracil (5-FU) in tumor growth using Sarcoma 180 transplanted mice. Hematological, biochemical, and histopathological analyses were performed in order to evaluate the toxicological aspects of the polysaccharide treatment. The polysaccharide had no direct cytotoxic action on tumor cells in vitro. However, the polysaccharide showed strong in vivo antitumor effect. Thus, the tumor growth-inhibitory effect of the polysaccharide is apparently due to host-mediated mechanisms. The histopathological analysis suggests that the liver and the kidney were not affected by polysaccharide treatment. Neither enzymatic activity of transaminases (AST and ALT) nor urea levels were significantly altered. In hematological analysis, leucopeny was observed after 5-FU treatment, but this effect was prevented when the treatment was associated with the polysaccharide. In conclusion, this polysaccharide probably could explain the ethnopharmacological use of this mushroom in the treatment of cancer.
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PMID:In vivo growth-inhibition of Sarcoma 180 by an alpha-(1-->4)-glucan-beta-(1-->6)-glucan-protein complex polysaccharide obtained from Agaricus blazei Murill. 1872 68

The continuing threat to biodiversity lends urgency to the need of identification of sustainable source of natural products. This is not so much trouble if there is a microbial source of the compound. Herein, violacein, a natural indolic pigment extracted from Chromobacterium violaceum, was evaluated for its antitumoral potential against the Ehrlich ascites tumor (EAT) in vivo and in vitro. Evaluation of violacein cytotoxicity using different endpoints indicated that EAT cells were twofold (IC(50)=5.0 microM) more sensitive to the compound than normal human peripheral blood lymphocytes. In vitro studies indicated that violacein cytotoxicity to EAT cells is mediated by a rapid (8-12h) production of reactive oxygen species (ROS) and a decrease in intracellular GSH levels, probably due to oxidative stress. Additionally, apoptosis was primarily induced, as demonstrated by an increase in Annexin-V positive cells, concurrently with increased levels of DNA fragmentation and increased caspase-2, caspase-9 and caspase-3 activities up to 4.5-, 6.0- and 5.5-fold, respectively, after 72 h of treatment. Moreover, doses of 0.1 and 1.0 microg kg(-1) violacein, administered intraperitoneally (i.p.) to EAT-bearing mice throughout the lifespan of the animals significantly inhibited tumor growth and increased survival of mice. In view of these results, a 35-day toxicity study was conducted in vivo. Complete hematology, biochemistry (ALT, AST and creatinine levels) and histopathological analysis of liver and kidney indicated that daily doses of violacein up to 1000 microg kg(-1) for 35 days are well tolerated and did not cause hematotoxicity nor renal or hepatotoxicity when administered i.p. to mice. Altogether, these results indicate that violacein causes oxidative stress and an imbalance in the antioxidant defense machinery of cells culminating in apoptotic cell death. Furthermore, this is the first report of its antitumor activity in vivo, which occurs in the absence of toxicity to major organs.
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PMID:Growth inhibition and pro-apoptotic activity of violacein in Ehrlich ascites tumor. 2041 85

Influence of the antitumour rhenium-platinum system on biochemical liver characteristics in the model of tumor growth (Guerin carcinoma) was studied and possible hepatoprotective activity of rhenium cluster compounds when introducing them in different forms was shown, that was confirmed by decreasing of diagnostic enzymes activity in blood (aminotransferase--AST 6 times and ALT 5.6 times, lactatedehydrogenase 4.9 times, gamma-glutamyltranspeptidase 3.6 times) and normalization of morphological state of the liver cells. The hepatoprotective activity of the cluster rhenium compound with adamanthyl ligands was confirmed in the model of acute toxic hepatitis. Introduction of this compound led to reduction of the concentration of MDA in homogenates of liver tissue (2 times), and in blood plasma (3.8 times); to reduction of levels of diagnostic liver enzymes in blood--AST and ALT 5.8 and 5.5 times respectively in comparison with control group. Some aspects of the mechanism of hepatoprotection were discussed, that included the presence of conjugated systems around the quadrupol rhenium-rhenium bond and alkyl radicals with significant positive inductive effects.
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PMID:[Influence of antitumor system rhenium-platinum on biochemical state of the liver]. 2188 57

Herbal formulas based on the traditional Chinese medicine (TCM) syndrome (ZHENG) have been used as alternative treatments for breast cancer. However, there is a lack of the experimental animal ZHENG model for the evaluation of the herbal formulas. In this study, we have established 4T1 mouse breast cancer with Liver Fire Invading Stomach Syndrome model (4T1 LFISS mice) and investigated the effects of the herbal formula, Zuo-Jin Wan (ZJW). Our results showed that 4T1 LFISS mice have the features of LFISS including irritability, loss of appetite, yellow urine, chow, and a tail hot. Compared to untreated 4T1 LFISS mice, ZJW significantly reduced tumor weight and volume (P < 0.05), although it was weaker than Cisplatin. However, ZJW significantly increased the body weight and food intake of 4T1 LFISS mice and decreased serum ALT, AST, Cr, and BUN levels and ZHENG score (P < 0.05), while Cisplatin reduced the food intake, and body weight and increased serum ALT, AST, Cr, and BUN levels in 4T1 LFISS mice. Our study has provided a mouse breast cancer ZHENG model and showed that ZJW suppresses tumor growth and improves LFISS and kidney and liver functions in the 4T1 LFISS mice.
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PMID:Establishment of an Experimental Breast Cancer ZHENG Model and Curative Effect Evaluation of Zuo-Jin Wan. 2434 96

Under malignant growth, the alterations of blood serum biochemical parameters including activity of studied enzymes were observed. The drug "Grinization GRIN R" was shown to stabilize the tumor growth of Guerin's carcinoma as well as biochemical parameters in the range close to normal values. The changes of protein metabolism parameters appeared to be significant. Also the considerable changes of AST and ALT activities were demonstrated. In the case, there was significant difference between the groups studied (p < 0.05). Administration of rats with drug "Grinization (Grin R" in different doses led to decreasing of average tumor volume in dynamics. Increasing and normalization of total protein level in rats with Guerin's carcinoma was established under "Grinization GRIN" administration in doses 115 mg/kg and 270 mg/kg. The meaning of albumin concentration approached to physiological normal value under "Grinization GRIN" administration in dose 270 mg/kg. Meanwhile AST and ALT activities were approaching to normal values in rats with Guerin's carcinoma under "Grinization GRIN" administration in dose 270 mg/kg. Such effects were observed mainly at the 18th and 23th days after tumor inoculation in comparison with tumor control (Guerin's carcinoma) values.
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PMID:[Dynamics of rat blood serum biochemical parameters under malignant growth in condition of the antioxidant substance "greenization green R" introduction]. 2451 81

The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity.
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PMID:Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo. 2490 91

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