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

Methionine starvation causes changes in the protein pattern of HL-60 promyelocytic leukemia cells as observed by two-dimensional electrophoresis. One group of proteins is apparently modified, appearing in new positions. A further series of proteins, including several principal nuclear polypeptides, is substantially diminished. The morphology of a fraction of the cells in the culture changes concomitantly, with condensation and fragmentation of the nucleus and eventual remolding of the cell to a "grape-cluster" appearance. Similar effects are produced by a DNA methylation inhibitor, 5-azacytidine, but not by various other toxic agents tested. A defect in DNA methylation, either by depletion of S-adenosyl-L-methionine (the methyl donor) or by inactivation of the relevant enzyme, may be responsible. The T-lymphoblastoid line CCL-119 and the histiocytic lymphoma line U-937 also show these effects, but most fibroblast, epithelial, and lymphoblastoid lines do not. These changes can be largely prevented in each of the three susceptible lines by prior treatment with the tumor promoter, phorbol myristate acetate (PMA), an agent known to cause differentiation in at least two of the lines. The results thus suggest interesting relationships between methionine metabolism, protein and structural changes in the cell nucleus, and PMA-induced cell differentiation.
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PMID:Protein-pattern changes and morphological effects due to methionine starvation or treatment with 5-azacytidine of the phorbol-ester-sensitive cell lines HL-60, CCL-119, and U-937. 620 32

Various tumor cells contain chromatographically distinct isoacceptor tRNA species. To decide whether the tumor-specific species represent an expression of a separate tRNA gene or only an undermodified form of normal tRNAPhe, nucleotide sequences of tRNAPhe isolated from neuroblastoma and normal mouse liver were determined by postlabeling techniques. The results showed identical sequences except for the changes of post-transcriptional modifications in the anticodon loop. Normal mouse liver tRNAPhe contained Cm32, Gm34, and the hypermodified YOH next to the 3' end of the anticodon. On the contrary, tRNAPhe from neuroblastoma contained C32, G34, and, instead of YOH base m1G. A small proportion of tRNAPhe species contained an undermodified YOH base. For the examination of the conditions leading to the undermodified tRNAPhe, Vero cells derived from the kidney of African green monkey in culture were used. In these cells, deprivation of methionine or lysine resulted in changes in tRNAPhe modification similar to those in tumor cells. Ehrlich ascites tumor cells were examined to determine whether the presence of altered tRNAPhe species in various tumors is also the result of starvation of some nutritional factors. Results obtained with these cells showed that tRNAPhe species lacking the Y base disappeared in tumor-bearing mice after intraperitoneal injection with a mixture of amino acids and vitamins. Thus it is concluded that tumor-specific tRNAPhe species are the products of aberrant post-transcriptional modification, not the transcripts of different, normally repressed genes.
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PMID:Alterations in post-transcriptional modification of the Y base in phenylalanine tRNA from tumor cells. 640 57

The year 1983-1984 has been a period of evaluation and examination of efficacy of nutritional support of the cancer patient. The early observation that individual patients, unable to ingest, digest, or absorb food could be nutritionally maintained by intravenous nutrition has been repeated in every cancer center. The premature application of parenteral nutrition as an adjunct to cancer care and the results of clinical trials with small numbers of patients have initiated a reevaluation of this therapy, as a routine. The most exciting advances have come from the opportunity to utilize nutritional support as a means of investigating the basic mechanisms by which the cancer patient disposes of exogenously delivered substrate. This opportunity had been initially under-appreciated and is only now receiving the full and intensive clinical and laboratory research necessary to delineate abnormalities of metabolism that occur in the cancer-bearing host. Studies have not been performed not only in intact man, but in specific organ systems in man during nutritional support. These studies, using stable and radioactive isotopes, have given us new insight into the way that the cancer patient handles glucose and amino acids. Whether these abnormalities of metabolism are due to the cancer or are due to treatment, complications of treatment, or inherent starvation accompanying progressive cancer cachexia is being examined. Such studies should indicate whether or not therapeutic interventions in limiting substrate availability for the tumor while preserving the host are possible.
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PMID:Metabolic consequences of nutritional support of the cancer patient. 643 57

The many causes of clinical magnesium deficiency can be placed into 2 categories: diminished intake of magnesium, and enhanced losses of magnesium, either through the gastrointestinal tract or through the kidneys. Examples of the first category include alcoholism, starvation, anorexia due to neoplastic disease and/or chemotherapy. Examples of the second category include severe diarrhoeal states, gastrointestinal fistulae, malabsorption, diuretic therapy and gentamicin therapy. Estimates of the prevalence of clinical hypomagnesaemia range from 6 to 11% in hospitalised patients. Serum predictors of associated clinical magnesium depletion include hypokalaemia (42%), hyponatraemia (23%), hypophosphataemia (22%) and hypocalcaemia (20%). Experimental and clinical observations strongly support the view that magnesium and potassium are closely linked at the cellular level. Magnesium has been demonstrated to be important in cell energetics (Mg++-activated ATPase), in maintenance of the integrity of cell membranes, retardation of cell loss of potassium, as well as enhancing repletion of cell potassium. While translation of these experimental observations into clinical terms encompasses a wide spectrum of illnesses, there is special relevance in considering the role of magnesium in repletion and maintenance of cell potassium in 2 clinical instances: (a) patients treated with digitalis and diuretics; and (b) hypertensive patients. In these types of patients not only potassium but also magnesium should be administered together to avoid the problem of cell potassium depletion and refractory potassium repletion associated with coexisting and uncorrected magnesium depletion.
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PMID:Magnesium deficiency. Causes and clinical implications. 649 96

This study was designed to ascertain whether the overall availability of whole-body lipids and nitrogen is a limiting factor for survival in tumor-bearing mice suffering from anorexia and cachexia. Three-month-old nongrowing mice (C57BL/6J) were given s.c. transplants of a methylcholanthrene-induced sarcoma. Freely fed, starved, and pair-fed animals were used. Body and lipid composition, tumor growth, and survival time were measured. Freely fed sarcoma-bearing mice died with profoundly altered body composition. This was not explained by the anorexia assessed in pair-feeding experiments. Starvation had caused a more severe depletion in body composition in both tumor-bearing and nontumor-bearing animals than the tumor alone did in freely fed tumor-bearing mice. Freely fed tumor-bearing animals had normal proportions of whole-body triglycerides, cholesterol, and polar lipids, but they lost palmitic acid quantitatively more than any other fatty acid. It is unlikely that any single fatty acid became limiting during tumor growth. The results show that the overall availability of lipids, nitrogen, and glucose precursors is not a limiting factor for survival in experimental tumor cachexia. Other factors considered to be more likely as determining factors for the death of tumor-bearing animals are discussed.
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PMID:Role of whole-body lipids and nitrogen as limiting factors for survival in tumor-bearing mice with anorexia and cachexia. 657 17

Protein degradation was measured as tyrosine release rate from proteins of extensor digitorum longus (EDL) muscles and as urinary excretion of 3-methylhistidine in freely fed adult nongrowing C57BL/6J mice with sarcomas, to study protein degradation in cancer-induced wasting of skeletal muscles. Whole muscle protein breakdown rate was unchanged, whereas protein synthesis was depressed, leading to an increased net degradation of skeletal muscles with loss of soluble, myofibrillar, and collagen proteins. Starvation for 24 hours elevated whole muscle protein breakdown in mice with and without sarcomas. Subsequent refeeding for 24 hours normalized the degradation. Adaptation to anorexia in pair-fed controls was achieved by a decrease in muscle protein turnover evaluated by urinary excretion of 3-methylhistidine over 5 days. The measurement of "catabolic decrease" of muscle protein breakdown protected the muscle mass in mice without tumors, but it was ineffective in tumor-bearing animals. The unchanged rate of breakdown of proteins in whole EDL muscles from tumor-bearing mice was accompanied by increased maximum cathepsin D activity and by elevated autolytic activity at acid pH in some muscles. Therefore, cathepsin D activity and net protease activities did not reflect whole muscle protein degradation in tumor-induced malnutrition. The results demonstrate that wasting of skeletal muscles in experimental cancer was not dependent on increased degradation but was dependent on depressed protein synthesis.
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PMID:Lack of evidence for elevated breakdown rate of skeletal muscles in weight-losing, tumor-bearing mice. 657 91

Starvation-refeeding, intrarectal instillation of the suspected colon tumor promoter sodium deoxycholate (NaDOC), and a combination of the treatments were compared for their effects on ornithine decarboxylase (ODC) activity in the colon of male Sprague-Dawley rats. Starvation (48 hours) and refeeding (12 hours) led to a fivefold increase in ODC levels compared to ad libitum-fed controls, while NaDOC instillation led to a threefold rise. The combination of the two treatments gave a synergistic 16-fold increase over controls. The synergism observed in colon may indicate that the two treatments used act via different mechanisms to induce ODC, possibly by an increase in general macromolecular synthesis after starvation-refeeding and a specific increase in ODC synthesis after NaDOC treatment. Since this starvation-refeeding regimen is quite similar to the "starve and gorge" feeding pattern exhibited by pair-fed control animals, the use of pair-fed controls may not be appropriate for examining either ODC levels or processes, such as tumor promotion, which may be linked to ODC levels. The synergistic enhancement of tumor promoter-related ODC induction by a dietary pattern (rather than a dietary component) suggests a new area for investigation of potential nutrition-cancer interactions.
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PMID:Ornithine decarboxylase induction in rat colon: synergistic effects of intrarectal instillation of sodium deoxycholate and starvation-refeeding. 669 99

The effects of Mg2+ and Ca2+ deprivation on survival and growth of normal and transformed cultured cells were studied. Normal fibroblast from several origins (mouse, hamster and human) did not grow in 2 microM Mg2+ medium, whereas transformed fibroblasts (mouse and rat) and tumor cells of other types (mouse adrenocortical and rat glial cells) grew optimal. All transformed or tumorogenic cells that showed low growth requirement for Mg2+ were able to develop colonies in agarose suspension cultures, i.e., were anchorage-independent fo growth. Mg2+ deprivation of normal cells did not lead to cell cycle arresting at G0/G1 and cell death accounts for the limited growth of these cells in medium containing low Mg2+ concentration. Contrary to Mg2+, starvation for serum or for Ca2+ caused normal cells to undergo cell cycle arrest at the G0/G1 phase. During the progressive spontaneous transformation of Swiss mouse 3T3 fibroblasts, the decrease in growth requirements for Mg2+ and Ca2+ do not occur at the same time. The requirement for external Ca2+ lowers before the onset of anchorage-independent growth while the Mg2+ requirement only decreases after cells become anchorage-independent. Therefore the reductions in growth requirement for Mg2+ and Ca2+ that take place in cell transformation are not linked events.
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PMID:Ca2+ and Mg2+ requirements for growth are not concomitantly reduced during cell transformation. 670 40

We investigated the effect of starvation on the course of Listeria monocytogenes infections in mice. Mice starved for 24, 48, or 72 h and then inoculated with a lethal dose of L. monocytogenes showed significantly less mortality than mice not starved (i.e., fed mice). The protective effect of 48 or 72 h of starvation began immediately after the starvation period and persisted for at least 48 h. Starved, infected mice had significantly fewer L. monocytogenes cells in their spleens 2, 3, and 4 days after infection than did fed mice. Neither changes in T-lymphocyte function nor serum factors appeared to be responsible for the protective effect. Delayed hypersensitivity responses to L. monocytogenes antigen were smaller in starved mice than in fed mice. Adoptive transfer of spleen cells from nonimmune starved mice did not protect against L. monocytogenes. Additional studies indicated that the serum of starved mice did not inhibit multiplication of L. monocytogenes in vitro, nor was it able to transfer protection against L. monocytogenes to normal mice. In contrast, peritoneal macrophages from starved mice inhibited deoxyribonucleic acid synthesis of P815 tumor cells compared with macrophages from control mice. Therefore, the resistance of starved mice to L. monocytogenes is most likely due to nonspecific factors, one of which may be activation of macrophages.
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PMID:Acute starvation protects mice against Listeria monocytogenes. 677 66

Urinary excretion of the post-translationally modified amino-acid 3-methylhistidine, derived from the contractile proteins actin and myosin, was measured in patients with conditions associated with nitrogen loss. The ratio of 3-methylhistidine:creatinine excretion, a measure of the fractional catabolic rate of myofibrillar protein was increased in severe injury, thyrotoxicosis, neoplastic disease, prednisolone administration, and sometimes Duchenne muscular dystrophy. In myxoedema, osteomalacia, and hypothermia the ratio was decreased; and starvation, elective operations, and rheumatoid arthritis had little effect. Provided that the diet is meat free, measurement of urinary 3-methylhistidine may provide useful information on the cause of protein loss.
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PMID:Clinical usefulness of urinary 3-methylhistidine excretion in indicating muscle protein breakdown. 678 20


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