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

1. Incubation of human and rat hepatoma cells with insulin (1 mU/10(6) cells) decreases their content of adenosine 3':5'-monophosphate by more than half after 1 h and by about a quarter after 4 h. 2. The activities of the ATP-metabolising enzymes, adenylate kinase and Mg2+-adenosine triphosphatase are significantly increased by insulin within 1 h and after 4 h. Activity of succinate dehydrogenase and lactic dehydrogenase showed no change at either time interval. 3. Insulin markedly stimulated glucose 6-phosphate dehydrogenase activity within 1 h but by 4 h the increase was less apparent. Glutamate dehydrogenase activity by contrast was not increased by 1 h but was elevated at 4 h.
 ...
PMID:The influence of insulin on various enzyme activities in human and rat hepatoma cells. 17 8

1. Mitochondrial and microsomal fractions were prepared from normal rat liver and the Morris 7777 hepatoma and characterized by the use of the marker enzymes, succinate dehydrogenase and rotenone-insensitive NADPH-cytochrome c reductase. 2. The phospholipid content per mg membrane protein of Morris 7777 hepatoma mitochondria was increased by 75% as compared with mitochondria from normal rat liver. Microsomes from this poorly-differentiated tumor were found to have a 45% decrease in the content of phospholipid. These abnormalities were independent of tumor size or age. 3. The percent phospholipid content of the subcellular fractions was determined, and revealed an increase in the percent sphingomyelin in both the microsomal and mitochondrial fractions of the tumor. Decreases in the percent phosphatidylcholine and phosphatidylethanolamine were noted in tumor microsomes as compared with normal liver. Diphosphatidylglycerol was not found in significant quantities in the microsomal fraction of this hepatoma line. 4. The content of the various phospholipid classes per mg protein in the respective mitochondrial and microsomal fractions was determined. Large increases in nearly all the major phospholipid classes were found in tumor mitochondria; tumor microsomes were characterized by an increased content of sphingomyelin but the content of nearly all other phospholipids was significantly decreased. These findings suggest the presence of disturbances in the regulation of phospholipid metabolism in subcellular organelle membranes of the Morris 7777 hepatoma.
 ...
PMID:Abnormal membrane phospholipid content in subcellular fractions from the Morris 7777 hepatoma. 18 53

Well-coupled mitochondria were isolated from a HuH13 line of human hepatoma cells and human liver tissue. The liver mitochondria showed a feeble glutamine oxidation activity in contrast to the hepatoma mitochondria, whereas they utilized glutamate well for the oxidative phosphorylation. In the liver mitochondria, glutamate was oxidized via the routes of transamination and deamination. On the other hand, glutamate oxidation was initiated preferentially via transamination pathway in the tumor mitochondria. In the liver mitochondria, bicarbonate nearly at a physiological concentration inhibited oxygen uptake with glutamate as substrate. The interaction of bicarbonate with the pathway of glutamate oxidation occurred primarily at the level of succinate dehydrogenase, due to competitive inhibition of the enzyme by the compound. In contrast to the liver mitochondria, glutamate oxidation was not affected by bicarbonate in the tumor mitochondria. These results indicate that the aberrations in the glutamate metabolism and its regulation observed in the hepatoma mitochondria may be favorable to the respiration utilizing glutamine and/or glutamate as an energy source.
 ...
PMID:Pathway of glutamate oxidation and its regulation in the HuH13 line of human hepatoma cells. 167 60

Interleukin 6 (IL-6) was established as a transcriptional inducer of the rat alpha 2-macroglobulin gene, a prototype liver acute-phase gene. Maximum induction occurred when the 5' flanking sequences of this gene (position -209 to -43) directed expression from the gene's own TATA box and transcription start site. Removal of the hexanucleotide CTGGGA (position -164 to -159) abolished 60-70% of the hormonal induction in FAO1 rat hepatoma cells. This hexanucleotide was defined as the IL-6 response element (IL-6-RE). The IL-6-RE is well conserved in the cytokine-responsive regions of other acute-phase genes and serves as a binding site for nuclear proteins. A characteristic DNA-protein complex (complex I) was formed with nuclear proteins from normal rat livers. A different, hormone-inducible complex (complex II) was assembled specifically with nuclear proteins from acute-phase rat livers or from IL-6-treated human Hep 3B hepatoma cells. Complex II was competitively inhibited by oligonucleotides representing the conserved IL-6-RE sequence from other acute-phase genes. Thus, the proteins building complex II likely participate in a general signal transduction mechanism mediating the transcriptional activation by IL-6 of several acute-phase genes.
 ...
PMID:Acute-phase reaction induces a specific complex between hepatic nuclear proteins and the interleukin 6 response element of the rat alpha 2-macroglobulin gene. 169 Apr 31

Chemosensitivity of hepatocellular carcinoma tissues from 72 patients to 6 antitumor agents was assayed using the succinate dehydrogenase inhibition test. Sensitivity was positive in 47.2% of tissues exposed to adriamycin, 53.5% to mitomycin C, 10.3% to 5-fluorouracil, 51.5% to cisplatin and aclacinomycin A. respectively, and 52.9% to carboquone. Eight percent of the tissues were sensitive to all 6 drugs, while the resistance rate to all drugs was 36.5%. The remaining 55.5% were sensitive to only some of the drugs. When a comparison of the sensitivity to the 6 drugs was made between two different areas of tumors in 16 patients, positive or negative sensitivity was in a range of 76.9-92.9%. The hypovascular masses seen on the angiography and the histologically well differentiated tumors were resistant to adriamycin, a drug most commonly prescribed to treat patients with liver cancer. For some of these tumors, mitomycin C or carboquone may be effective. Our observation shows that the succinate dehydrogenase inhibition test is useful for determining which drugs will be effective for a particular tumor.
 ...
PMID:Human hepatocellular carcinoma sensitivity to antitumor drugs assayed using the succinate dehydrogenase inhibition test. 184 32

The chemosensitivity was evaluated by the in vitro succinate dehydrogenase inhibition (SDI) test in 1,000 human tumors including 237 gastric cancers, 116 colorectal cancers, 113 hepatoma and 534 others. These tumor cells were exposed to 5 kinds of antitumor drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cis-platinum (DDP). After exposure to the antitumor drugs, cell viability was assessed with colorimetric assay, based on the ability of succinate dehydrogenase (SD) in living tumor cells to reduced a tetrazolium (MTT) to a formazan. The chemosensitivity was determined to be positive when the SD activity of drug exposed cells decreased to below 50% of that of control cells, on day 3 of exposure. The chemosensitivity varied in the tumor tissues. The chemosensitivity of metastatic lesions of lymph nodes were higher than that of the primary lesions, while metastatic liver tumors had lower sensitivity than the primary lesions. The intra-tumorous distribution of SD activity in 12 human gastric cancers were compared with normal adjacent tissues using histochemistry. Seventy-five % (9/12) of gastric cancer tissues had higher SD activity than normal adjacent tissues. The SDI test is rapid and simple method to predict the sensitivity test of various human tumors to antitumor drugs.
 ...
PMID:[The sensitivity of 1,000 human tumors to antitumor drugs using the succinate dehydrogenase inhibition (SDI) test]. 227 70

The different distribution of cytochemically demonstrable enzymes: lactate dehydrogenase (LDH, 1.1.1.27), succinate dehydrogenase (SDH, 1.3.99.1), dihydrofolate reductase (DHFR, 1.5.1.3), acid phosphatase (AcP, 3.1.3.2) and alkaline phosphatase (ALP, 3.1.3.1), has been documented in Yoshida ascites hepatoma cells in vivo or stored at 80 degrees C. The dehydrogenase activities (LDH, SDH, DHFR) show a strong reaction in all samples. An increased level of these enzyme activities has been observed in the malignant cells spreading through the organs of tumor bearing rats. On the contrary, in the same samples, acid and alkaline phosphatase activities are very low. The strong dehydrogenase activities observed in Yoshida ascite cells stress the rapid turnover of tumor cells. Our results indicate that the histochemical method may be a useful tool to detect the scattered tumor cells. Furthermore, the cytochemical methods allow the characterization of the metabolic pathways employed by the primary and disseminated tumor cells.
 ...
PMID:[Cytochemical study of cells of primary and disseminated ascite Yoshida tumor cells]. 276 51

To determine whether or not the cytotoxic effects of hyperthermia are directed primarily to malignant cells, we examined changes in thermosensitivity during hepatocarcinogenesis in rats, as induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The findings were compared with those in livers of rats fed a commercial diet. The cell viability was determined using the succinate dehydrogenase inhibition (SDI) test. The succinate dehydrogenase (SD) activity of liver cells, when exposed to heat (43 degrees C) for 2, 5, or 10 hr, decreased in a time-dependent manner, in each tissue. The decrease in SD activity was evident in 3'-Me-DAB liver for 5 hr of heat treatment on day 57, compared with findings in the normal liver. Significant differences were present for 2, 5, and 10 hr on days 93 and 136. Thus a chemically induced hepatoma is more sensitive to heat than are the normal cells. As this thermosensitivity gradually increased during the hepatocarcinogenesis, the malignant cells are particularly vulnerable to hyperthermia.
 ...
PMID:Azo-dye-induced primary hepatoma and a gradual increase in thermosensitivity. 279 54

The precursor polypeptides of a large subunit of succinate dehydrogenase and ornithine aminotransferase (the enzymes which are located in the mitochondrial inner membrane and matrix respectively) were synthesized as a larger molecular mass than their mature subunits, when rat liver RNA was translated in vitro. These precursor polypeptides were also detected in vivo in ascites hepatoma cells (AH-130 cells). When the 35S-labeled precursor polypeptides were incubated with isolated rat liver mitochondria at 30 degrees C in the presence of an energy-generating system, these two precursors were converted to their mature size and the 35S-labeled mature-size polypeptides associated with mitochondria. Furthermore, these mature-size polypeptides were recovered from their own locations, the inner mitochondrial membrane and the matrix. The precursor of ornithine aminotransferase incubated with rat liver mitochondria at 0 degree C was specifically and tightly bound to the surface of the mitochondria even in the presence of an uncoupler of oxidative phosphorylation. This precursor, bound to the mitochondria, was imported into the matrix when the mitochondria were reisolated and incubated at 30 degrees C in the presence of an energy-generating system, suggesting that a specific receptor may be involved in the binding of the precursor. The processing enzyme for both precursor polypeptides seemed to be located in the mitochondrial matrix and was partially purified from the mitochondria. A metal-chelating agent strongly inhibited the processing enzyme and the inhibition was recovered by the addition of Mn2+ or Co2+.
 ...
PMID:Translocation of proteins into rat liver mitochondria. The precursor polypeptides of a large subunit of succinate dehydrogenase and ornithine aminotransferase and their imports into their own locations of mitochondria. 395 98

In vitro chemosensitivity was evaluated by SDI test in various human tumors including 1 lymph node metastasis of esophageal cancer, 10 gastric cancers, 4 colo-rectal cancers, 1 hepatoma, 2 lung cancers, 2 breast cancers and 1 gallbladder cancer. Tumor fragments cut with scissors were exposed to twelve kinds of antitumor drugs at five to ten times peak plasma concentration. After 3 days at 37 degrees C, each tumor fragment suspension was washed with phosphate-buffered saline and assayed for succinate dehydrogenase (SD) activity using 3-(4,5- dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) as a hydrogen acceptor. When the SD activity of the drug-treated cells was reduced to below 50% that of control cells, the chemosensitivity to the antitumor drug was considered positive. The chemosensitivity of each tumor varied individually. Mitomycin C or 5-fluorouracil are regularly used to treat gastric cancer patients, but, some specimens of gastric cancer in this study showed a resistance to these drugs and an unexpected sensitivity to other drugs. Our results show that the SDI test is a convenient method for clinical use and gives significant information about drug sensitivity.
 ...
PMID:[In vitro chemosensitivity of various human tumors evaluated by the SDI (succinate dehydrogenase inhibition) test]. 405 18


1 2 3 4 5 Next >>