Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH daily from the time of diagnosis. Two patients withdrew shortly after receiving GSH due to intolerable side-effects. Of the six eligible patients, two had mildly advanced tumors and four moderately advanced tumors. At 1-2-month intervals the liver was CT and ultra-sound scanned to assess the growth status of the tumor (progression, stagnation or regression). All the patients, except a male with a fibrolamellar type of HCC, died within 1 year after diagnosis. Two women with moderately advanced tumors survived almost 1 year, tumor growth stopped or regressed and in one of the women an initially abnormal alfa-1-fetoprotein (AFP) returned to normal after GSH treatment. AFP remained normal throughout the treatment period in the other women. These observations indicate that GSH may have a sex-dependent effect on HCC. However, further studies involving more patients are required to pursue this hypothesis.
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PMID:Glutathione treatment of hepatocellular carcinoma. 128 Mar 15

The effects of glutamine-enriched total parenteral nutrition (TPN+GLN) were studied in tumor-bearing rats because glutamine can benefit host tissues but also may stimulate tumor growth. Rats were implanted with the methylcholanthrene-induced fibrosarcoma (MCA sarcoma) and were studied when the tumor constituted less than 5% of carcass weight (small tumor) and when the tumor constituted 10% of carcass weight (large tumor). Provision of 20% of TPN protein as glutamine produced a significant increase in the arterial glutamine level and maintained the skeletal muscle intracellular glutamine concentration (2.02 +/- 0.1 versus 1.39 +/- 0.07 mumol/g, p less than 0.01). Concurrently, hindquarter GLN fractional release increased nearly threefold (p less than 0.05) in the TPN+GLN group. Glutamine-enriched total parenteral nutrition did not affect carcass weight, tumor weight, tumor DNA content, or tumor glutaminase activity. Furthermore, DNA flow cytometric analysis did not demonstrate any difference in percentage of aneuploid tumor cells within the G1, S, or G2M cell cycles. However, the ratio of aneuploid to diploid cells within the tumor mass increased by 20% in animals receiving glutamine. Glutamine-enriched total parenteral nutrition had no effect on tumor glutathione (GSH) levels. No increase in hepatic GSH levels was observed, but gut mucosal GSH levels were 20% greater in the TPN+GLN group (p less than 0.05). The provision of glutamine-enriched TPN may be beneficial to the host by maintaining skeletal muscle glutamine stores and by supporting gut GSH biosynthesis. In this tumor model, TPN+GLN does not appear to increase tumor size, tumor DNA content, or tumor glutamine metabolism, but the ratio of tumor cells to host infiltrating cells within the tumor mass appears to be increased.
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PMID:The effects of glutamine-enriched total parenteral nutrition on tumor growth and host tissues. 154 96

Diets with partial replacement of sulfur amino acids by thiazolidine-4-carboxylate or 2-phenylthiazolidine-4-carboxylate were fed to normal and to rhabdomyosarcoma-bearing rats (methionine-dependent tumor) to evaluate their efficacy as cysteine precursors and as antitumor agents. Food intake, weight gain, food efficiency and plasma albumin and plasma sulfur amino acid concentrations were not different when these diets were compared with isosulfurous diets containing either methionine or N-acetylcysteine. 2-Phenylthiazolidine-4-carboxylate induced a lower plasma glutathione (GSH) level than the latter diets. Tumor-bearing rats had lower plasma GSH concentration. A negative linear relationship was found between plasma GSH levels and tumor weight and also the tumor weight: body weight ratio. This could mean that the tumor becomes the most important organ in the uptake of GSH. However, there was also a significant positive correlation between plasma GSH and albumin, suggesting a reduced GSH hepatic synthesis due to amino acid uptake by the tumor. There were no differences in tumor growth among rats receiving diets containing N-acetylcysteine, thiazolidine-4-carboxylate or 2-phenylthiazolidine-4-carboxylate.
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PMID:Thiazolidine-4-carboxylate and 2-phenylthiazolidine-4-carboxylate are active as cysteine precursors but have no effect on growth of a methionine-dependent tumor in rats. 172 69

The effect of dietary selenium (Se) supplementation and low dietary magnesium (Mg) on growth of cells of the human mammary tumor cell line (HTB123/DU4475) and the tissue glutathione (GSH) content in female athymic nude mice was studied. Sixty three- to four-week-old female athymic nude mice were randomly divided into six dietary groups of 10 animals. The mice were fed a modified AIN-76A diet with two levels of Mg (100 and 665 mg/kg) and three levels of Se (0.04, 0.2, and 4.0 mg/kg). At the fourth week of dietary treatment, mice were subcutaneously inoculated with 2.5 x 10(6) viable tumor cells on the dorsal lumbar region and then fed their respective diets for another four weeks. Dietary Se supplementation had no significant effect on tumor growth or tissue GSH content. Low dietary Mg limited both tumor growth and tissue GSH synthesis but raised Mg and GSH levels in tumor tissues. The growth of mice fed the diet containing 100 mg/kg Mg and 4.0 mg/kg Se was significantly retarded. This study demonstrated that neither Se deficiency nor Se supplementation had any effect on mammary tumor growth or tissue GSH content in athymic nude mice. Low dietary Mg did retard tumor growth and inhibited GSH synthesis. Low dietary Mg also resulted in an apparent increase in Se toxicity in these animals.
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PMID:Effect of dietary selenium and magnesium on human mammary tumor growth in athymic nude mice. 177 86

Glucose oxidase (GO) catalyzes the conversion of beta-D-glucose and molecular oxygen to D-glucono-delta-lactone and H2O2. H2O2 produced by GO was effective in preventing tumor growth in mice bearing not only ascites tumor but also solid tumor. The effect of GO was enhanced by the combined administration of catalase inhibitors such as 3-aminotriazole, hydroxylamine and sodium azide or the GSH synthesis inhibitor buthionine-(S,R)-sulfoximine in vivo. The cytolytic activity of GO against T-24 cultured cells in vitro was also enhanced by addition of these inhibitors together with GO. In the peritoneal cavity of mice the antitumor effect of GO seemed to be dependent on the amount of oxygen released from oxygenated fluorocarbon-43 (FC-O2), an oxygen-supplying substance. Furthermore, the combined administration of H2O2-decomposing enzyme inhibitors and FC-O2 synergistically enhanced the antitumor effect of GO. These results suggest that GO is suitable for antitumor chemotherapy and that the use of inhibitors of H2O2-decomposing enzymes and FC-O2 potentiated the GO therapy.
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PMID:Enhancement of the antitumor effect of glucose oxidase by combined administration of hydrogen peroxide decomposition inhibitors together with an oxygenated fluorocarbon. 191 30

The effect of endotoxin on colon tumors was studied in male Sprague-Dawley rats. Colon tumors were induced in weanling rats by the administration of 20 weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH). When colon tumors were detected by colonoscopy in 80% of the rats around week 24 after DMH injection, the animals were divided randomly into two groups. One group served as the control. The other group received six endotoxin (Escherichia coli) treatments every fifth day. The first dose was 50 micrograms/100 g (intraperitoneally); the remaining doses were 100 micrograms/100 g (subcutaneously). Rats were killed 2 weeks after the last endotoxin injection. Endotoxin treatments resulted in larger colon tumors. The median tumor size was 71 mm2 for endotoxin-treated and 31 mm2 for untreated rats (P less than 0.02). Endotoxin treatments also resulted in a significantly higher incidence (P less than 0.05) of ulcer development in the small intestine, that is 47% in the endotoxin-treated versus 23% in the untreated rats. After a single subcutaneous injection of endotoxin (100 micrograms/100 g), the colon mucosal reduced glutathione (GSH) level was raised by 21% at 16 hours, reached a peak on day 2, then decreased to baseline by day 4. The increased GSH level in the colon mucosa was maintained up to the third endotoxin injection. By the fifth injection, no increase in the GSH level was observed. These results suggest that the growth of colon tumors in rats induced by DMH could be enhanced by endotoxin treatments. The enhanced tumor growth may be due to an increase in the colon GSH level and/or other mediators released by macrophages as a result of endotoxin treatments.
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PMID:The effect of endotoxin on 1,2-dimethylhydrazine-induced colonic tumors in rats. 196 25

Normal Swiss Webster mice were treated with monocrotaline or high doses of three antitumor alkylating agents (BCNU, cyclophosphamide, or mitomycin C), all of which have been connected with hepatic veno-occlusive disease at our clinic. Prior administration of WR-2721 did not improve the survival of monocrotaline-treated animals. Glutathione (GSH) improved the survival of these animals to a small degree. Glutathione monoethyl ester (GSHet) almost completely protected animals from the toxicity of monocrotaline. Pretreatment with WR-2721 produced moderate increases in survival at the highest doses of BCNU, and at the lower BCNU doses none of the animals pretreated with WR-2721 died before they were killed on day 150. Pretreatment with GSHet gave good protection from BCNU toxicity at the highest dose of the drug, and there were no deaths in the groups of animals treated with GSHet 1 hour before BCNU. On a multiple dose schedule, GSH provided some protection from cyclophosphamide toxicity; GSHet gave a very good level of protection from cyclophosphamide. In none of these treatment groups were lesions suggestive of hepatic or pulmonary venoocclusive disease identified. In all three experimental protocols (monocrotaline, BCNU, and cyclophosphamide), there was a consistent decrease in hepatic toxicity after GSHet pretreatment; this was not observed in GSH- or WR-2721-pretreated animals. There was no evidence of protection of the FSaIIC fibrosarcoma growing in C3H mice as assayed by tumor growth delay or tumor cell survival in groups treated with two different doses of GSHet 1 hour before each drug injection compared to those treated with the BCNU or cyclophosphamide alone, or BCNU with cyclophosphamide. Pretreatment with GSHet did not alter the toxicity of these drugs to bone marrow. GSHet appears to be an effective protector of critical normal tissue and does not appear to protect tumor.
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PMID:Glutathione monoethyl ester can selectively protect liver from high dose BCNU or cyclophosphamide. 284 75

The response of murine EMT6 and RIF tumors to DL-buthionine-S, R-sulfoximine (BSO), a glutathione (GSH) depletor, given either as a single dose, continuous oral administration, or in multiple doses, was determined with the use of a tumor-growth-delay assay. BSO consistently caused significant tumor growth delay in EMT6 tumors, which reached 5-7 days (two doubling times) after a single BSO dose (40 mumol/kg or 4 mmol/kg), 3 days (one doubling time) with continuous oral administration (20 mM), and 9 days (three doubling times) with daily BSO administrations (4 mmol/kg) starting at the time of tumor inoculation. Growth inhibition persisted after discontinuation of BSO treatment. Some complete tumor regressions were observed. Only slight tumor growth delay (one doubling time) was observed in RIF tumors at all treatment modes. No direct correlation was observed between tumor GSH content and the effects on tumor growth. In vitro BSO pretreatment (2 mM, 24 hr) of EMT6 tumor cells prior to tumor inoculation, which reduced cellular GSH levels to 34% of controls, did not influence subsequent tumor growth. Pretreatment of mice with BSO (4 mmol/kg, 1 daily sc injection for 7 days) prior to tumor inoculation led to a reduction of tumor takes by 25% when compared to 100% tumor takes in untreated mice. These data imply a BSO-induced change in the host response to tumor development.
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PMID:Effect of DL-buthionine-S,R-sulfoximine on the growth of EMT6 and RIF mouse tumors. 346 Dec 11

The radiosensitizing effects of misonidazole (MISO) in combination with D,L-buthionine-S, R-sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, were studied in NFSa tumors of C3H/He mice. The radiation response of tumors was assayed by the tumor growth delay time. The GSH contents in tissues were assayed by high performance liquid chromatography (HPLC). GSH content in the tumors decreased to the minimum level (45% of the control), and then gradually recovered to 75% of the control, respectively, 12 and 24 hr after the intraperitoneal injection of 5 mmole/kg BSO. On the other hand, the maximum non-protein sulfhydryl (NPSH) depletion (29% of the control) in the liver of tumor bearing mice was achieved 6 hr after the administration of the same dose of BSO, but fully recovered 24 hr later. When 5 mmole/kg BSO was injected repeatedly 4 times at an interval of 6 hr, GSH content in the tumors decreased to 19% of the control 24 hr after the first injection of BSO. The radiosensitizing effect of 0.5 mmole/kg MISO was markedly increased by this BSO treatment. The enhancement ratio (ER) of this combined treatment was 1.93. On the other hand, ERs of 1.44 and 1.16 were obtained for MISO (0.5 mmole/kg) and for 4 injections of BSO (5 mmole/kg) in combination with radiation, respectively. Although a considerable increase in the radiosensitizing efficiency of MISO in vivo by the treatment with BSO was found without any notable side effects of the combination, more studies on toxicities are needed to get a definite conclusion on the clinical applicability of the combination.
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PMID:Radiosensitizing effect of misonidazole in combination with an inhibitor of glutathione synthesis in murine tumors. 375 92

Previously we found that blood glutathione (GSH) levels increase in response to tumor growth in the rat and that this increase is not prevented with zinc deficiency. We also found that zinc deficiency which inhibited tumor growth did not prevent this increase in blood GSH. Therefore, the objectives of this study were to determine the effects of another nutritional modification, namely magnesium deficiency, on blood GSH status and on tumor growth. Magnesium was selected because it is an obligatory cofactor in GSH synthesis and in all biosynthetic reactions involving ATP. To this end, magnesium- and zinc-deficient rats with and without tumors were compared to pair-fed control rats with and without tumors. After 32 days of depletion, the rats were killed, and blood samples were analyzed for nonprotein sulfhydryls (SH) and specifically for GSH. The key finding was that in magnesium-deficient rats with or without tumors, blood GSH levels were low and SH levels were normal indicating a decrease in GSH biosynthesis. In contrast, zinc deficiency affected SH and GSH in parallel. Thus, these two deficiencies must act by different mechanisms. The zinc data verified our earlier results obtained with a different tumor type and rat strain, for blood GSH levels increased in tumor-bearing rats fed control diets, and zinc deficiency did not prevent this increase. Depletion of magnesium or zinc was equally effective in inhibiting tumor growth. These results provide in vivo evidence of a magnesium requirement for GSH biosynthesis in rat erythrocytes. Further, the results suggest that magnesium deficiency may inhibit tumor growth by limiting GSH synthesis from SH precursors.
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PMID:Magnesium deficiency inhibits biosynthesis of blood glutathione and tumor growth in the rat. 394 42


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