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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neoplasms result from the uncontrolled proliferation of abnormal or transformed cells. The early stages of this process are difficult to study because of the lack of sensitive and specific markers of clonal evolution in an experimental system. We have developed a cat model using cellular mosaicism for glucose-6-phosphate dehydrogenase (G-6-PD). Our findings confirm that the structural locus for feline G-6-PD is on the X-chromosome and demonstrate that it is randomly inactivated in somatic cells. Heterozygous cats have balanced ratios of G-6-PD enzyme types in peripheral blood cells and hematopoietic progenitors that remain stable over time. In our initial studies, we used the model to analyze the events surrounding marrow failure experimentally induced by selected strains of feline leukemia virus (FeLV). Two G-6-PD heterozygous cats, one F1 male hybrid and one domestic cat were infected with FeLV (C or KT) and developed pure red cell aplasia (PRCA). Colonies arising from the more mature erythroid colony-forming cell were not detected in marrow culture of anemic animals although erythroid bursts persisted, suggesting that the differentiation of early erythroid progenitors (BFU-E) was inhibited in vivo. The ratio of G-6-PD types in hematopoietic progenitors and peripheral blood cells from the heterozygous cats did not change when the animals developed PRCA. Thus, the anemia did not result from the clonal expansion of a transformed myeloid stem cell. With this experimental approach, one may prospectively assess clonal evolution and cellular interactions in other FeLV-induced diseases.
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PMID:Feline glucose-6-phosphate dehydrogenase cellular mosaicism. Application to the study of retrovirus-induced pure red cell aplasia. 298 Dec 48

The naturally occurring adrenal steroid, dehydroepiandrosterone (DHEA), is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Oral administration of DHEA to mice inhibits spontaneous breast cancer and chemically induced tumors of the lung and colon. Topical application of DHEA to mouse skin inhibits 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and DMBA-induced carcinomas at both the initiation and promotion phase. Evidence is presented that critical steps in the initiation process (mixed-function oxidase activation of a carcinogen) and promotion process (enhanced rates of cell proliferation and superoxide formation) all require NADPH and may be inhibited by DHEA and structural analogs as a result of a lowering of the NADPH cellular pool. Results obtained by others with fibroblasts and lymphocytes from individuals with the Mediterranean variant of G6PDH deficiency also indicate that a reduction in the NADPH cellular pool confers resistance to benzo(a)pyrene. Preliminary data suggest that food restriction may depress G6PDH levels and this may contribute to the tumor preventive effect of underfeeding.
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PMID:Inhibition of tumor development by dehydroepiandrosterone and related steroids. 302 2

Caloric restriction reduces the incidence and progression of a broad spectrum of neoplastic diseases, yet little is known about the biochemical and molecular mechanisms involved. Profiles of enzyme activities of importance in cellular energy utilization were examined in 7,12-dimethylbenz[a]anthracene-induced (DMBA) mammary adenocarcinomas from rats fed ad libitum or calorically restricted diets. The diets provided equal nutrients except for fewer carbohydrate-derived calories; graded caloric restriction was 10, 20, 30 and 40%. The specific activities of hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, malic enzyme and fructose-1,6-bisphosphatase were all elevated to varying degrees in both large palpable and small, non-palpable tumors from calorically restricted hosts compared to activities in tumors from ad libitum-fed rats. Phosphofructokinase activity was increased in palpable tumors from calorically restricted hosts but markedly reduced in non-palpable tumors. These results suggest adaptive or compensatory alterations in tumor enzyme profiles in response to the altered nutritional state of the host.
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PMID:Biochemical alterations in 7,12-dimethylbenz[a]anthracene-induced mammary tumors from rats subjected to caloric restriction. 303 94

It has been known for many years that reducing the food intake of laboratory mice and rats inhibits the development of a broad spectrum of chemically induced and spontaneous tumors, but the mechanism of this effect is poorly understood. Food restriction of A/J mice for two weeks is now shown to inhibit the binding of topically applied [3H]7,12-dimethylbenz(a)anthracene (DMBA) to skin DNA by 50% and to abolish the stimulation of [3H]-thymidine incorporation in the epidermis produced by topical application of the tumor promoter tetradecanoylphorbol-13-acetate (TPA). Similar effects on the actions of DMBA and TPA are observed following topical application of the adrenal steroid, dehydroepiandrosterone (DHEA), a potent glucose-6-phosphate dehydrogenase (G6PDH) inhibitor, while food restriction for two weeks depresses epidermal G6PDH activity by 60%. It is suggested that both the inhibition of [3H]DMBA binding to skin DNA and the TPA stimulation in epidermal [3H]thymidine incorporation result from a reduction in the NADPH cellular pool as a result of G6PDH inhibition.
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PMID:Food restriction inhibits [3H] 7,12-dimethylbenz(a)anthracene binding to mouse skin DNA and tetradecanoylphorbol-13-acetate stimulation of epidermal [3H] thymidine incorporation. 310 76

Using 19-fluorine (19F) as nuclear magnetic resonance (NMR) signal probe and 2-fluoro-2-deoxy-D-glucose (2-FDG) as metabolic probe, one dimensional "imaging" (metabolite mapping) of pathway specific glucose metabolism in the pentose monophosphate shunt (PMS) and aldose reductase sorbitol (ARS) pathways were performed in situ in rat brain utilizing one dimensional rotating frame zeugmatography. Normal brain showed highest PMS activities in the brainstem consonant with known spatially heterogeneous concentration of glucose-6-phosphate dehydrogenase, the rate limiting enzyme for the PMS. The brain harboring sufficiently large gliosarcoma in the cerebrum showed a higher PMS/ARS area ratio indicating higher PMS activities in tumor which was localized by zeugmatography. The present study demonstrated the feasibility of studying regional glucose metabolism in the PMS and ARS utilizing 2-FDG.
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PMID:Heterogeneity of regional cerebral glucose metabolism demonstrated in situ in rat brain by 19F NMR rotating frame zeugmatography: one dimensional chemical shift imaging of normal and gliosarcoma implanted brain. 311 61

In an effort to identify enzymatic activities in primary prostatic carcinomas that might be complementary to histological and other clinical techniques for the prediction of prognosis, we have assayed several enzymatic activities extracted from prostatic carcinomas. We reported previously that, for each of the studied enzymes, tissues with benign prostatic hyperplasia and prostatic carcinoma showed significantly different activities. With additional patients now included and a longer interval since resection of these tumors, we have found that the histological grade (Gleason's system for grading) of the sample (prostate chip) analyzed is related to several activities extracted from the cancers including arginase (r = -0.81, p less than 0.0001), glucose-6-phosphate dehydrogenase (r = 0.72, p less than 0.0001), and the B isoenzyme of N-acetyl-beta-D-glucosaminidase (r = -0.58, p = 0.0369). Acid phosphatase (r = 0.15, p = 0.5530) and the BB isoenzyme of creatine kinase (r = -0.13, p = 0.5221) are not significantly related to histological grade. In a large series, Gleason grade is related to survival. In our series of 27 patients followed for 20 to 46 months, the Gleason grade (p = 0.22) is not related to survival, but arginase activity is related (p = 0.0392) to survival. In this small series, arginase is more valuable than the best currently proven predictor of survival, Gleason grade. Hexosaminidase B activity approaches being significantly (p = 0.0575) related to survival. Of the 11 patients whose tumors contained the lowest arginase activities, eight are dead. Of the 11 with the highest activities, only one is dead. Several of the enzyme activities in this series of 27 patients complemented each other for the prediction of Gleason grade; for example, glucose-6-phosphate dehydrogenase, arginase, and the BB isoenzyme of creatine kinase were more closely correlated (multiple correlation coefficient, r = 0.77) with the Gleason grade for all chips than was any single enzyme: arginase, r = -0.67; glucose-6-phosphate dehydrogenase, r = 0.67; creatine kinase, r = -0.16. It seems likely that enzymatic analysis may provide an approach that is qualitatively different from and complementary to histological evaluation for the prediction of prognosis in prostatic carcinoma. Verification of this hypothesis will require more patients followed over a longer period of time and will probably be facilitated by analysis of several samples from different locations in each tumor.
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PMID:Enzyme activities in prostatic carcinoma related to Gleason grades. 315 94

The active ingredient in the tumor-promoting croton oil, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), was shown to increase the activity of mouse skin epidermal glucose-6-phosphate dehydrogenase (+84%), hexokinase (+100%), phosphofructokinase (+158%), and pyruvate kinase (+101%). This increase in activity of these key enzymes of glucose metabolism occurred 2-8 h after TPA application and was due to a net increase in the enzyme content. This increase in the activity of the glycolytic enzymes, as well as the reported TPA-induced increase in the synthesis of RNA and DNA and cell proliferation, suggest that activation of the glycolytic pathway may be involved in the carcinogenic effects of tumor promoters.
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PMID:Enhancement in the activities of mouse epidermal glucose-6-phosphate dehydrogenase, hexokinase, phosphofructokinase, and pyruvate kinase by 12-O-tetradecanoyl-phorbol-13-acetate. 315 44

We report here the first demonstration in normal, as opposed to chimaeric mice, of the clonal architecture of the small intestine, oesophagus, breast, and thyroid, using polymorphism of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) as a clonal marker. Reproducible results using X-linked histochemistry were found to depend upon the simultaneous study of tissue from normal mice, mice homozygous for abnormal enzyme levels, and heterozygous mice. In tissues from homozygous animals where levels of enzyme activity normally vary, the use of a physiological stimulus to reduce this metabolic heterogeneity allowed interpretation of clonality in the heterozygotes. The details of the histochemical technique used require modification for each of the different tissues studied. A dual population of cells was seen in the heterozygous animals in all tissues studied. Oesophageal epithelium showed sharply separated alternating patches of positive and negative cells. Small intestinal crypts were always monophenotypic, while villi were polyphenotypic, indicating that crypts are monoclonal and villi derive from more than one crypt, confirming work in allophenic animals. In contrast, thyroid follicles and breast acini showed a mixture of mono- and polyphenotypia, consistent with a polyclonal origin. These results, which have important implications for the study of the clonal origins of normal and neoplastic growth, require the direct in situ demonstration of the cellular phenotype.
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PMID:The demonstration of tissue clonality by X-linked enzyme histochemistry. 316 72

The in vivo effects of hyperoxia were studied in lung colonies formed by B16-F10 melanoma cells in C57BL/6 mice. Several antioxidant defenses were found to change with in vivo exposure: glutathione reductase and glucose-6-phosphate dehydrogenase activities decreased as compared with levels in the cultured cells, glutathione peroxidase activity dramatically increased, and Mn-superoxide dismutase activity and levels of total glutathione were similar in vivo and in vitro. Exposure of tumor-bearing animals to 70%, O2 for 3 weeks did not alter the antioxidant defenses measured in the tumors. One hundred percent O2 exposure did not affect either initial arrest or subsequent retention of radiolabeled B16-F10 cells in the lung. Likewise, hyperoxia did not appear to alter cell division in B16-F10 cells growing in the lung. These results are consistent with our previous studies indicating that the B16-F10 cell line is resistant to levels of O2 in vivo that adversely affect other tumor cell lines.
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PMID:Effects of hyperoxia on B16-F10 cells in vivo. 318 29

Previous work based on the relative tissue content of glucose-6-phosphate dehydrogenase isoenzymes suggested that parathyroid adenomas, like primary hyperplasia, may be multicellular (not clonal) in origin. We have reexamined this issue by using two independent molecular genetic methods. We report tumor-cell-specific restriction-fragment-length alterations involving the parathyroid hormone gene from two human parathyroid adenomas. These abnormal restriction fragments indicate that in each case a clonal proliferation of cells was present and also suggest that DNA alterations involving the parathyroid hormone locus may be important in the tumorigenesis or clonal evolution of some parathyroid adenomas. In addition, we used a restriction-fragment-length polymorphism in an X-linked gene (hypoxanthine phosphoribosyltransferase) to examine the clonality of eight parathyroid adenomas in women. Of these eight adenomas, six had the DNA hybridization pattern of monoclonality, and two had an equivocal pattern. None of five hyperplastic parathyroid glands had a monoclonal pattern. We conclude that some (and perhaps many) single parathyroid adenomas are monoclonal neoplasms. Our observations suggest that there is a fundamental biologic difference between parathyroid adenomas and primary hyperplasia--a difference that could prove useful in distinguishing these entities clinically.
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PMID:Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. 334 17


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