Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitomycin C microcapsules (MMC-mc), which were developed as a novel drug carrier, have proved to exert a potential therapeutic effect due to both microinfarction and sustained drug action (chemo-embolization), when infused into a tumor supplying arteries. Experimental studies have demonstrated that chemo-embolization with MMC-mc produces a definitely marked and extensive cytotoxicity in target tissues as compared with traditional arterial chemotherapy, embolization or combination of both. Sixty-seven patients with advanced hepatoma were treated with intra-arterial MMC-mc during the period from 1978 to 1982. Since the majority of patients were in far advanced stages, 56 patients received only single or two infusions of an average dose of 20 mg MMC-mc. Objective tumor reduction greater than 25% in area was observed in 22 (40%) of measurable 55 tumors. Elevated serum alpha-fetoprotein in 26 patients improved in 22 (85%). Relative survival rates of 59 patients without distant metastasis were 64% at 3 months, 49% at 6 months and 26% at 12 months. Side effects such as bone marrow depression, decreased liver function, fever, anorexia, pain and infection were experienced in 9 to 39%, but the majority of them were mild and controllable. Our preliminary experience suggests that MMC-mc can be effectively used in treatment of liver tumors as a palliative but also as a preoperative measure. Further clinical trials including controlled study may well demonstrate the advantages of MMC-mc.
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PMID:[Chemo-embolization with mitomycin C microcapsules for hepatoma]. 620 39

Spleen cells obtained from ACI rats bearing a syngeneic hepatoma (9098) (TBR spleen cells) showed a strongly depressed mitogen responses to concanavalin A (Con A) and to phytohaemagglutinin-P (PHA) at various concentrations of the tested mitogens. The activity of suppressor cells in TBR spleens was demonstrated in mixtures with normal spleen cells where a marked depression of the mitogen response was observed. The properties of tumour-induced suppressor cells were adherent to plastic or nylon wool, phagocytic, and radioresistant (maybe macrophages). The Con A response of TBR spleen cells was more completely restored than was the PHA response after the removal of adherent or phagocytic cells. The suppression when TBR spleen cells (2,000 rad) were added to normal spleen cells at 0, 24, and 45 h after culture initiation was greater in the PHA response than in the Con A response. The PHA assay appeared to be more sensitive method than the Con A assay for the detection of suppressor cell activity in tumour bearing rats.
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PMID:Tumour-induced suppressor macrophages in rats: differences in their suppressive effects on the Con A and PHA responses. 623 88

Subacute and chronic oral toxicities of trinotroglycerin (TNG) were studied in beagle dogs, CD rats, and CD-1 mice. No adverse effects were seen in dogs given up to 1 mg/kd/day of TNG for 4 weeks, then 5 mg/kg/day for 9 more weeks. Dogs given 25 to 200 mg/kg/day for 5 days had transient and dose-related severe methemoglobinemia, while 200 mg/kg/day produced depression; dogs given 1, 5, or 25 mg/kg/day for 12 months had transient and dose-related mild methemoglobinemia. Rats fed 0.1% TNG for 5 weeks, then 0.5% (230-234 mg/kd/day) for 8 more weeks had decreases in feed consumption and weight gain after the increase in dosage; rats fed 2.5% TNG (1406 or 1416 mg/kg/day for males and females, respectively) for 13 weeks suffered adverse effects, including weight loss, compensated anemia, and testicular degeneration, but they resumed gaining weight as feeding continued. Rats fed 1% TNG (363 or 434 mg/kg/day for males and females, respectively) for 2 years had decreased weight gain, decreased grooming, methemoglobinemia and its sequelae, cholangiofibrosis , hepatocellular carcinoma, and interstitial cell tumors of the testis. A decrease in the naturally occurring pituitary chromophobe adenoma and mammary tumors increased the life span of the females. Some rats fed 0.1% TNG (31.5 or 38.1 mg/kg/day for males and females, respectively) had mild hepatic lesions similar to those seen in rats fed the larger doses. No adverse effects were seen in mice fed up to 0.1% TNG for 3 weeks, then 0.5% for 10 more weeks. Mice fed 1% TNG (1022 or 1058 mg/kg/day for males and females, respectively) for 2 years had decreased weight gain, decreased grooming, and methemoglobinemia and its sequelae, but no obvious cellular changes as found in the rats.
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PMID:Subacute and chronic toxicity studies of trinitroglycerin in dogs, rats, and mice. 642 46

Treatment of Ehrlich ascites tumor cells with the alkylating antitumor agents triaziquonum, N-mustard and cyclophosphamide leads to a reduction in the posttranslational incorporation of 3H-acetate into histones and the extent of histone acetylation in Ehrlich ascites tumor cells. All core histones are affected. The depression of histone acetylation is not the result of a decrease in acetyl-CoA. Evidence is presented for an activation of histone deacetylase by alkylating agents. A reduction of histone deacetylation is observed after exposure to all concentrations of alkylating agents which inhibit cell proliferation. In order to evaluate the biological consequences of a reduction of histone acetylation, the extent of acetylation was modulated by either chemical acetylation or treatment with butyrate. In all cases an increase in histone acetylation leads to an enhancement of the rate of transcription. In accord with previous reports from our laboratory (1), it is concluded that the reduction of histone acetylation affects RNA synthesis. It is emphasized, however, that besides a regulation of transcription, histone acetylation may be involved in other cell functions. Thus, the complete biological consequences of the reduction of histone acetylation remain to be elucidated. In view of the antitumor activity of the alkylating agents it seems noteworthy that hepatoma AS30D cells are characterized by a remarkably higher extent of histone H4-acetylation compared to normal, adult, fetal, or regenerating liver.
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PMID:Depression of histone acetylation by alkylating antitumor agents: significance for antitumor activity and possible biological consequences. 647 41

A comparative study of the transport of pyruvate in mitochondria isolated from normal rat liver and from three tumors has been carried out. The Km for net pyruvate uptake in mitochondria isolated from Ehrlich ascites tumor cells is practically equal to that measured in normal rat liver mitochondria while, on the other hand, it is higher in Morris hepatomas 44 and 3924A. The Vmax of pyruvate uptake is depressed in all three types of tumor mitochondria as compared to that in the rat liver mitochondria, with the depression being higher in Morris hepatoma 3924A mitochondria. The lower activity of pyruvate translocator in mitochondria isolated from tumor cells as compared to that in rat liver mitochondria is also shown by depression of the rate of pyruvate-supported oxygen uptake. The results document a decreased activity of the pyruvate translocator in tumor mitochondria which seems to be correlated with the growth rate of the tumor cells.
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PMID:Transport of pyruvate in mitochondria from different tumor cells. 661 43

Experiments in vivo were made to examine the action of hydrazine sulfate on the gluconeogenesis in the liver and kidneys of rats with Zajdela's hepatoma and mice with lymphoma NK/Ly. The intensity of the gluconeogenesis in the liver descended and in the kidneys increased. These alterations did not affect blood glucose content in the test animals. The data obtained do not support the hypothesis that the mechanism of hydrazine sulfate action by an abrupt depression of the gluconeogenesis during malignant growth is the sole mechanism.
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PMID:[Gluconeogenesis during therapy of experimental tumors with hydrazine sulfate]. 669 28

Trout were fed a range of dietary components which altered their carcinogenic response to aflatoxin B1 (AFB1). Dietary protein at levels substantially exceeding nutritional requirements were synergistic with AFB1. Cyclopropene fatty acids (CPFA) were carcinogenic when fed alone at 20 or 55 ppm, and synergistic when fed with AFB1. In contrast, several flavonoid and indole compounds, especially beta-naphthoflavone (beta-NF) and indole-3-carbinol, inhibited the carcinogenic response when fed prior to and along with AFB1. The mechanisms by which some of these dietary factors modulate AFB1 carcinogenesis were investigated. Dietary beta-naphthoflavone was shown to substantially induce the levels of mixed function oxidase (MFO) activities assayed in vitro. These changes were accompanied by alterations in AFB1 metabolism and binding in freshly isolated hepatocytes. AFB1 incubated in hepatocytes freshly isolated from fish fed beta-NF diet was metabolized more rapidly, showed enhanced rates of detoxication reactions, and decreased accumulation of AFB1-DNA adducts compared to control hepatocytes. These results suggest that beta-NF inhibits AFB1 carcinogenesis at least in part by altering MFO activities such that detoxication is enhanced and initial DNA damage by AFB1 is reduced. In contrast, high dietary protein is a synergist for AFB1 carcinogenesis, and this appears to occur primarily by enhancing the transformation probability for AFB1-initiated genome damage. Fish treated with AFB1 as embryos and then reared on high protein diets had substantially higher incidences of hepatocellular carcinoma (86%) than similarly treated fish fed normal protein diet (44%) or high protein controls without AFB1 exposure (0-2%). The synergistic behavior of dietary CPFAs also appears to partially involve enhanced transformation following DNA damage by AFB1. Fish exposed as embryos to AFB1 and then fed CPFA-containing diets are known to show promotion effects similar to the high protein results (Hendricks, J.D., Proc. 11th Int. Symp. of the Princess Takamatsu Cancer Research Fund, in press.) However, factors other than promotion are involved in the synergism between CPFA and AFB1. Preliminary studies indicate that dietary CPFAs repress MFO activities and depress DNA damage by AFB1 in vitro. If this occurs in vivo, then the net synergistic effect of dietary CPFAs would involve depression of initial AFB1-induced DNA damage, but highly efficient promotion of transformation from the remaining lesions.
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PMID:Mechanisms of dietary modification of aflatoxin B1 carcinogenesis. 681 11

The Walker 256 carcinosarcoma growing in Sprague-Dawley rats and the Morris 5123 hepatoma growing in Buffalo rats both produce cachexia but have widely differing patterns of host metabolism and tumor growth. Both organisms respond to exogenous insulin with increased food intake and rate of weight gain of host. The insulin treatment response of food intake was 1.5 to 2 times and of body weight gain was 2 to 3 times that of tumor-free controls. Insulin does not accelerate tumor growth. On withdrawal of insulin, the reactive hypophagia seen in tumor-free rats does not occur in tumor bearers, and the host weight does not return to the expected untreated value as it does in tumor-free rats. Most of the weight gained during insulin treatment of tumor bearers above that gained by tumor-free rats is retained after withdrawal of insulin. A computer model based on the inference from these results, that the tumor-bearing host is blind to body weight error, indicates that this abnormality of feeding control could account for only about one-third of the observed depression of host weight and food intake.
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PMID:Feeding response of tumor-bearing rats to insulin and insulin withdrawal and the contribution of autonomous tumor drain to cachectic depletion. 704 59

Until now it was unknown, whether 5-fluorouracil (5-FU) would be absorbed sufficiently after oral application, so that therapeutical effects could be expected. For this reason a comparative pharmacokinetic study of intravenous versus oral application was performed on six patients, as well as a pilot study on 13 patients with adenocarcinomas of different origins. The results show that 5-FU is absorbed rapidly. The biological availability increases with higher dose, which would indicate a saturation of the "first pass" in the liver. The clinical study shows partial remission in seven patients, with hepatoma and tolerable signs of bone marrow depression, decrease of hemoglobin, leukocytes and platelets after oral application of 5-FU in doses of 1,000-1,250 mg on days 1, 3, 5, 8, 10, and 12. 5-FU can therefore be given successfully at an adequate dose by the oral route.
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PMID:5-Fluorouracil: a comparative pharmacokinetic study and preliminary results of a clinical phase I study. 730 55

Hepatocellular carcinomas 1 cm in diameter with high or low echogenicity can be detected on ultrasonography and confirmed on fine-needle biopsy, but it is still very difficult to detect small hepatocellular carcinomas with isoechogenicity. In this study, we assessed lymphokine-activated killer cell activity and interferon-gamma production prospectively every 1 to 3 mo for 23 +/- 4 mo (mean +/- 1 S.D.) in 227 patients with cirrhosis. Transient depression of lymphokine-activated killer activity was detected in 43 patients (defective lymphokine-activated killer group), and hepatocellular carcinoma was detected in 24 cases before the end of the 18-mo follow-up. Twenty-one (87.5%) of the 24 hepatocellular carcinoma patients were included in the defective lymphokine-activated killer group. Defective lymphokine-activated killer activity was detected more than 6 mo before detection of a space occupying lesion in the liver or elevation of alpha-fetoprotein level above 400 ng/ml. Serum alpha-fetoprotein level was elevated above 400 ng/ml in only five cases in which hepatocellular carcinoma was detected as a space-occupying lesion. Our results indicate that sequential assessment of lymphokine-activated killer activity may be a predictor of hepatocellular carcinoma and that the depression of immune function in cirrhotic patients is a serious risk factor for hepatocellular carcinoma emergence.
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PMID:Depressed immune function in patients with cirrhosis before emergence of hepatocellular carcinoma. 768 81


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