Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma-GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis.
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PMID:[The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases]. 151 41

We investigated the relationship between the growth of HCC and nutrition, especially amino acids, and reconsidered the clinical application of amino acid imbalance. At first, rat chemical hepato-carcinogenesis was performed to investigate whether Aminoleban EN stimulates or restrains the occurrence of HCC. 2-Acetyl-amino-fluorene containing diet was administered intermittently according to Epstein's method. Rats were divided into two groups; group 1 was fed on Aminoleban EN containing diet and group 2 on a basal diet. There was no significant difference between the survival rate in the two groups. The average body weight of group 1 was significantly higher than that of group 2. The rats were sacrificed at the 25th week. All 11 rats of group 1 had no liver tumor, but 2 of 17 rats of group 2 had liver tumors, including a HCC and cholangiocellular carcinoma. The incidence of the liver tumor was significantly different between the two groups. Aminoleban EN could inhibit rat liver carcinogenesis, so it is considered to be a desirable nutritional product for LC patients from the stand point of cancer prevention. Secondly, the composition of amino acid was studied on HCC and surrounding tissue. There was no significant difference of Val, Leu, Leu, Phe, Tyr, Met and Fischer ratio between HCC and surrounding tissue.
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PMID:[Nutritional treatment of hepatocellular carcinoma]. 158 Jun 35

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing doxorubicin (DOX) and galactosamine can be targeted to the hepatocyte galactose receptor for organ-specific chemotherapy of primary and metastatic liver cancer. Here we report the dose-dependent pharmacokinetics of this macromolecular conjugate. Following intravenous administration to mice most efficient liver targeting was seen at low dose (0.05 mg DOX kg-1), with receptor saturation observed using higher bolus doses. Repeated low dose bolus injections did not cause down-regulation of the galactose receptor and targeted drug delivery rates of greater than or equal to 2 micrograms DOX g-1 liver h-1 were achieved. DOX is released from such conjugates intracellularly via action of lysosomal proteinases. It was shown that isolated rat liver lysosomal enzymes (Tritosomes) can release unmodified DOX from the peptidyl side chain Gly-Phe-Leu-Gly at a rate greater than or equal to 3 micrograms DOX g-1 liver h-1 i.e. the hydrolytic capacity is greater than the observed rate of drug delivery to the liver lysosomes in vivo. Although most conjugate would be captured by normal hepatocytes following intravenous administration, it was shown that the human hepatoma cell line HepG2 retains the galactose receptor, accumulating and processing the conjugate efficiently. Potential dose limiting toxicities of such drug conjugates could include cardio- or hepatotoxicity. Administration of conjugate reduced the 15 min heart level of DOX approximately 100-fold compared with that observed for an equivalent dose of free drug. Preliminary experiments showed that plasma levels of alkaline phosphatase, alanine transaminase and asparate transaminase did not change following administration of HPMA copolymer-daunorubicin (DNR) (10 mg DNR kg-1) indicating no significant heptatoxicity.
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PMID:N-(2-hydroxypropyl)methacrylamide copolymers targeted to the hepatocyte galactose-receptor: pharmacokinetics in DBA2 mice. 164 46

Two enzyme forms of alkaline phosphatase have been partially purified from the medium spent for the culture of HUH-6 clone 5 cells, which were originally derived from hepatoblastoma tissue. The purification methods used are ammonium sulfate precipitation, ethanol precipitation, diethylaminoethyl cellulose chromatography, Affi-Gel Blue chromatography, and Sephadex G-200 gel filtration. These alkaline phosphatases have been characterized by thermostability, inhibition, and immunological and electrophoretic studies. Both are L-phenylalanine and L-tryptophan sensitive and L-homoarginine and L-leucylglycylglycine insensitive, and both react with an antiserum against intestinal alkaline phosphatase. The major enzyme form is a neuraminidase-cleavable, moderately thermostable isoenzyme which on polyacrylamide gel shows an electrophoretic mobility similar to that of liver alkaline phosphatase. The minor enzyme form is a neuraminidase-uncleavable, thermolabile isoenzyme which shows an intermediate electrophoretic mobility between liver and hepatoma alkaline phosphatases. The molecular weights of the major and minor enzymes have been estimated by gel filtration to be 170,000 and 110,000, respectively. These results support the conclusion that the two enzyme forms of HUH-6 alkaline phosphatase are intestinal in type, with the major enzyme form closely resembling hepatoma and oncoamnionic alkaline phosphatases, and the minor enzyme form resembling "intestine-like liver alkaline phosphatase." HUH-6 clone 5 cell line may be a useful in vitro model to study the regulatory mechanism for phenotypic expression of intestinal-type alkaline phosphatase isoenzymes in liver cancer cells.
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PMID:Intestinal-type alkaline phosphatase produced by human hepatoblastoma cell line HUH-6 clone 5. 631 71

We have developed a useful strategy for identifying amino acid spin systems and side-chain carbon resonance assignments in small 15N-, 13C-enriched proteins. Multidimensional constant-time pulsed field gradient (PFG) HCC(CO)NH-TOCSY experiments provide side-chain resonance frequency information and establish connectivities between sequential amino acid spin systems. In PFG HCC(CO)NH-TOCSY experiments recorded with a properly tuned constant-time period for frequency labeling of aliphatic 13C resonances, phases of cross peaks provide information that is useful for identifying spin system types. When combined with 13C chemical shift information, these patterns allow identification of the following spin system types: Gly, Ala, Thr, Val, Leu, Ile, Lys, Arg, Pro, long-type (i.e., Gln, Glu and Met), Ser, and AMX-type (i.e., Asp, Asn, Cys, His, Phe, Trp and Tyr).
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PMID:Classification of amino acid spin systems using PFG HCC(CO)NH-TOCSY with constant-time aliphatic 13C frequency labeling. 858 9

Hereditary tyrosinaemia type I is the most common of the diseases caused by defects in tyrosine metabolism. The underlying genetic defect is a mutation in the gene for fumarylacetate hydrolase (FAH), and more than 30 different mutations in this gene have been identified. The main clinical consequences of this defect include hepatic involvement, with a high risk for liver cancer, and renal tubular dysfunction. Restriction of phenylalanine and tyrosine from the diet along with supportive measures can ameliorate the symptoms, but cure has so far been possible only with liver transplantation. Recent discovery of a pharmacological treatment with a peroral inhibitor of tyrosine catabolic pathway, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), offers a new promising tool for the treatment of patients with hereditary tyrosinaemia type I. Mouse models of FAH deficiency have been successfully used in experimental gene therapy, and these studies indicate that future management of tyrosinaemia with a gene therapeutic approach may become feasible.
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PMID:Hereditary tyrosinaemia type I: from basics to progress in treatment. 1112 30

Luxiancao is a new medicine for liver cancer, and is purely natural botanical It has good curative effects and few side effects. The curative mechanism of Luxiancao is unknown. In the present paper, the authors used a 514. 5 nm laser to measure the changes in the Raman spectrum of liver cancer cells (SMMC-7721) treated by Luxiancao at different concentrations. The study can help us know more about the mechanism, efficiency and side effects of Luxiancao. The results show that significant changes were observed in the cells' Raman spectra after reacting with Luxiancao. The intensities at 785 and 1 092 cm(-1), corresponding to DNA phosphate backbone vibration, were reduced; and the Raman bands for the bases A and G at 1 312 and 1585 cm(-1) also decreased, indicating that Luxiancao may be inserted in DNA bases and influence the DNA replications, resulting in the reduction in DNA content and breaking of the DNA strands. Besides, the intensity of 1 360 cm(-1), belonging to Trp, decreased gradually and disappeared in the end, indicating the Trp of cancer cells began to be exposed when adding in Luxiancao. The bands at 1 004 cm(-1) for Phe and 1 656 cm(-1) for proteins alpha-helix also decreased, suggesting that there were changes in the structure of protein and circumstance of amino acid. Moreover, the effects on cancer cells were enhanced gradually with the HCPT concentration increasing. Since a Raman spectrum is a chemical fingerprint of a sample, the different concentration dependent changes in the Raman spectra of individual cells due to reacting with Luxiancao can overcome the limitations of other detection systems used for quantitative and qualitative analysis of the drug.
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PMID:[Raman spectroscopic investigation on the interactions between liver Cancer cells (SMMC-7721) and fufang Luxiancao particles]. 1927 93

The prognosis of liver cancer remains poor, but recent advances in nanotechnology offer promising possibilities for cancer treatment. Novel adjuvant, amphiphilic nanoparticles (NPs) composed of L: -phenylalanine (Phe)-conjugated poly(gamma-glutamic acid) (gamma-PGA-Phe NPs) having excellent capacity for carrying peptides, were found to have the potential for use as a peptide vaccine against tumor models overexpressing artificial antigens, such as ovalbumin (OVA). However, the anti-tumor potential of gamma-PGA-Phe NPs vaccines using much less immunogenic tumor-associated antigen (TAA)-derived peptide needs to be clarified. In this study, we evaluated the effectiveness of immunization with EphA2, recently identified TAA, derived peptide-immobilized gamma-PGA-Phe NPs (Eph-NPs) against mouse liver tumor of MC38 cells (EphA2-positive colon cancer cells). Immunization of normal mice with Eph-NPs resulted in generation of EphA2-specific type-1 CD8+ T cells. Immunization with Eph-NPs tended to provide a degree of anti-MC38 liver tumor protection more than that observed for immunization with the mixture of EphA2-derived peptide and complete Freund's adjuvant (Eph + CFA). Neither Eph-NPs nor Eph + CFA vaccines inhibited tumor growth of BL6, EphA2-negative melanoma cells. Splenocytes isolated from MC38-bearing mice treated with Eph-NPs showed strong and specific cytotoxic activity against MC38 cells. Immunization with Eph + CFA induced liver damage as evidenced by elevation of serum alanine aminotransferase, while Eph-NPs vaccination did not exhibit any toxic damage to the liver. These results demonstrated that immunization with Eph-NPs displayed anti-tumor effects against liver tumor by generating acquired immunity equivalent to the toxic adjuvant CFA, suggesting that safe gamma-PGA-Phe NPs could be applied clinically for the vaccine treatment of liver cancer.
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PMID:EphA2-derived peptide vaccine with amphiphilic poly(gamma-glutamic acid) nanoparticles elicits an anti-tumor effect against mouse liver tumor. 1994 47

Our recent studies have revealed that among the 10 different commonly used adeno-associated virus (AAV) serotypes, AAV3 vectors transduce human liver cancer cells extremely efficiently because these cells express high levels of human hepatocyte growth factor receptor (hHGFR), and AAV3 utilizes hHGFR as a cellular co-receptor for viral entry. In this report, we provide further evidence that both extracellular as well as intracellular kinase domains of hHGFR are involved in AAV3 vector entry and AAV3-mediated transgene expression. We also document that AAV3 vectors are targeted for degradation by the host cell proteasome machinery, and that site-directed mutagenesis of surface-exposed tyrosine (Y) to phenylalanine (F) residues on AAV3 capsids significantly improves the transduction efficiency of Y701F, Y705F and Y731F mutant AAV3 vectors. The transduction efficiency of the Y705+731F double-mutant vector is significantly higher than each of the single mutants in liver cancer cells in vitro. In immunodeficient mouse xenograft models, direct intratumoral injection of AAV3 vectors also led to high-efficiency transduction of human liver tumor cells in vivo. We also document here that the optimized tyrosine-mutant AAV3 vectors lead to increased transduction efficiency following both intratumoral and tail-vein injections in vivo. The optimized tyrosine-mutant AAV3 serotype vectors containing proapoptotic genes should prove useful for the potential gene therapy of human liver cancers.
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PMID:Development of optimized AAV3 serotype vectors: mechanism of high-efficiency transduction of human liver cancer cells. 2177 25

Tyrosinemia type 1 is caused by deficiency of fumarylacetoacetate hydrolase. The enzymatic defect impairs the conversion of fumarylacetoacetate to fumarate, causing accumulation of succinylacetone which induces severe liver and kidney dysfunction along with mutagenic changes and hepatocellular carcinoma. Treatment is based on nitisinone (NTBC), an enzymatic inhibitor which suppresses succinylacetone production. NTBC, which has dramatically changed the disease course improving liver and kidney functions and reducing risk of liver cancer, causes a side effect of the increase of tyrosine levels. Treatment is therefore based on the combination of NTBC with a protein-restricted diet to prevent the potential toxicity of excessive tyrosine accumulation. Long-term therapy requires a careful monitoring in blood of NTBC levels along with other disease biomarkers, which include succinylacetone, and a selected panel of circulating aminoacids. We have developed a straightforward and fast MS/MS method for the simultaneous determination of NTBC, succinylacetone, tyrosine, phenylalanine, and methionine on a dried blood spot requiring a 2 min run. A single assay suitable for quantitative evaluation of all biochemical markers is of great advance over conventional methods, especially in pediatric patients, since it reduces laboratory costs and blood sampling, is less invasive and particularly suitable for pediatric patients, and allows easier storage and shipping.
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PMID:LC-MS/MS method for simultaneous determination on a dried blood spot of multiple analytes relevant for treatment monitoring in patients with tyrosinemia type I. 2214 91


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