Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous evidence has indicated that either purine starvation or incorporation into DNA may be the dominant biochemical effect of the antileukemic agent 6-thioguanine (TG), depending on exposure conditions. Furthermore, it has been suggested that the paradoxical decrease in TG-induced cytotoxicity at high drug concentrations may be due to an antagonistic interaction between these two mechanisms, in which purine starvation inhibits DNA synthesis and, therefore, incorporation of TG into DNA. In this report we test the hypothesis that by concurrent treatment of L1210 cells with TG and the purine precursor 4-amino-5-imidazolecarboxamide (AIC) it is possible to alleviate DNA synthesis inhibition caused by high concentrations of TG, thus enhancing TG incorporation into DNA and TG-induced cell kill. Both the cytotoxic and cytokinetic results presented support this hypothesis. However, gross incorporation of TG into DNA was not increased by AIC under conditions in which a significant enhancement of cytotoxicity (i.e., 1 log) was observed. These findings suggest that the potentiating effect of AIC may be most prominent on the subpopulation of cells that are resistant to treatment with TG alone, and they demonstrate that the cytotoxic effects of TG treatments are more accurately reflected by observing specific cytokinetic changes (delayed late S/G2 arrest) than by measuring the average extent of TG incorporation into DNA within a given population. Finally, we propose that it may be possible to select conditions for administration of TG that favor one or the other cytotoxic mechanism, depending on whether the clinical objective is induction of remission (where rapid cell lysis due to purine starvation would be desired) or eradication of subclinical disease during remission (where proliferation-dependent cytotoxicity due to DNA incorporation should be more effective.
Cancer Chemother Pharmacol 1990
PMID:Modulation of the cytotoxic mechanism of 6-thioguanine by 4-amino-5-imidazolecarboxamide. 235 62

The synthesis and release of the tumor marker carcinoembryonic antigen (CEA) from the colon cancer cell line LS180 has previously been reported to be enhanced during the later stages of in vitro culture after growth has stopped. It has been suggested that CEA expression was inversely related to the growth rate for these cells (Kahan, B.D.; Rutzky, L.P.; Legrue, S.J.; Tom, B.H. Methods Cancer Res. 18:197-275; 1979 and Shi, Z.R.; Tsao, D.; Kim, Y.S. Cancer Res. 43:4045-4049; 1983). Our studies indicate, however, that while certain environmental perturbations that halt growth (e.g., glucose starvation and elevated temperatures) do indeed stimulate CEA expression and release; other growth-arresting conditions, such as oxygen starvation, have no effect. Replacement of spent or conditioned medium with fresh medium during the later culture stages resulted in a 10-fold decrease in CEA release, indicating that either depleted nutrients or accumulating cellular products (such as lactate or ammonium) trigger enhanced CEA production.
Cancer Commun 1990
PMID:The effects of adverse growth conditions on the shedding of carcinoembryonic antigen from cultured LS180 colon cancer cells. 237 72

The cheek pouch of the Syrian hamster is an excellent model for the experimental study of oral carcinogenesis. The carcinogenic chemical 7,12-dimethylbenz[a]anthracene consistently produces epidermoid carcinomas in the cheek pouch of the Syrian hamster, giving rise to characteristic histopathological lesions in a time-dependent manner. We now present experimental evidence that c-Ki-ras mRNA can be detected in all 7,12-dimethylbenz[a]anthracene-induced tumors examined (in vivo and in vitro) in this experimental oral cancer model while no detectable c-Ki-ras mRNA can be found in the normal hamster cheek pouch epithelium. Cellular synchronization experiments using a cell line (hamster cheek pouch carcinoma cell line 1) derived from one of these 7,12-dimethylbenz[a]anthracene-induced hamster oral tumors revealed that the c-Ki-ras protooncogene is expressed during the G1 phase of the cell cycle (proliferation dependent). Serum starvation and RNA synthesis inhibition experiments using hamster cheek pouch carcinoma cell line 1 cells suggest that the c-Ki-ras protooncogene is indeed quiescent in the normal hamster cheek pouch epithelium and that failure to detect its mRNA is not related to the slower proliferation of the normal epithelial cells. These results suggest that the transcription of the c-Ki-ras protooncogene is associated with malignant transformation in the cheek pouch of the Syrian hamster.
Cancer Res 1989 Aug 15
PMID:Detection of Ki-ras messenger RNA in normal and chemically transformed hamster oral keratinocytes. 250 Oct 28

Malnutrition has a direct relationship to complications associated with ineffective wound and fracture healing, inadequate immune responses, decreased tolerance to cancer therapy, muscle weakness, and certain organ dysfunctions (heart and liver). Malnutrition combined with disease, injury, or stress increases the metabolic rate in patients above that of resting. These patients are undergoing an accelerated form of starvation, which is more common than presently recognized in veterinary medicine and may be responsible for the less than optimal responses to proper therapies. Diseased or injured patients unable to digest or absorb nutrients from the gastrointestinal tract require additional medical support in the form of parenteral nutrition. Advances in parenteral solutions, products, and delivery systems make parenteral nutritional support possible in veterinary medicine, although not possible in all small animal practices. Proper patient selection, well-informed clients, dedicated technicians, and knowledgeable veterinarians are all essential in the successful implementation of parenteral nutritional support.
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PMID:Parenteral nutritional support in the small animal patient. 251 12

The influence of 3 and 7 days of preoperative intravenous nutrition (IVN) on the capacity for protein synthesis in liver and on concentrations of plasma proteins and amino acids were investigated in patients with gastrointestinal malignancy. Thirty patients with gastrointestinal neoplasms who had lost more than 5 kg of weight over 3 months were randomized into three groups to receive preoperatively: (a) no IVN, (b) IVN for 3 days (0.18 gN/kg/day as amino acid; 30 kcal/kg/day as glucose), or (c) IVN for 7 days. Free access to a hospital diet was available to all patients including 10 patients who had not lost weight who served as controls. In the three groups of patients who had lost weight, median transferrin and fibronectin were lower than for controls, whereas other proteins and amino acids were comparable. After feeding, samples of liver were obtained peroperatively and the potential rates of protein synthesis were calculated from the in vitro incorporation of (14C)-leucine, into protein. Preoperative IVN significantly increased the potential rate of protein synthesis in liver after 3 days. Plasma amino acids were comparable with controls whereas in the unfed-group concentrations suggested utilization of alanine and breakdown of muscle. Three days of IVN also increased plasma fibronectin and IgA but increases of prealbumin, IgM, and complement C3 were only significant in the group fed for 7 days. On the 7th postoperative day plasma proteins were decreased similarly in each group. This study shows that concentrations of several plasma proteins, in preoperative patients reflect net rates of hepatic protein synthesis and are susceptible to depletion during starvation and repletion by 3 or 7 days of IVN.
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PMID:Influence of preoperative intravenous nutrition upon hepatic protein synthesis and plasma proteins and amino acids. 251 6

Lectins purified by affinity chromatography on immobilized asialofetuin from extracts of mouse K-1735P melanoma cells appeared as two polypeptides [L-14.5 (Mr 14,500) and L-34 (Mr 34,000)] in one-dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. However, in two-dimensional electrophoresis (isoelectric focusing followed by sodium dodecyl sulfate:polyacrylamide gel electrophoresis) the L-14.5 polypeptide was resolved into three acidic forms of pI 4.6, 4.9, and 5.8, whereas the L-34 was resolved into two polypeptides of pI 4.9 and 5.3. Antibodies directed against galactoside-binding lectins from rat and bovine lungs, mouse 3T3 fibroblasts, and mouse UV-2237 fibrosarcoma cells reacted with the K-1735P lectins in immunoblots, and normal mouse lung extracts were found to contain cross-reactive proteins that comigrated with the two melanoma lectins. Indirect immunofluorescence staining using the above antibodies demonstrated that both L-14.5 and L-34 were expressed on the surface of viable K-1735P cells. Treatment of these cells with 1 microM beta-all-trans-retinoic acid or 1 mM N6,O2'-dibutyryl cyclic AMP for 5 days induced morphological differentiation, inhibition of anchorage-dependent and anchorage-independent growths, and a selective decrease in the L-34 lectin level. Growth inhibition by starvation for serum factors, which did not induce differentiation, had no effect on the level of L-34. These results demonstrate that the melanoma lectins are immunologically related to normal cell lectins and that the two polypeptide species are expressed on the cell surface. Further, they demonstrate that the L-34 lectin level can be modulated by agents that suppress the transformed phenotype by enhancing differentiation.
Cancer Res 1989 Mar 01
PMID:Biochemical and immunological characterization of K-1735P melanoma galactoside-binding lectins and their modulation by differentiation inducers. 253 46

Malnutrition, as well as malignancy, induces alterations in heart metabolism and performance. Previous studies have implicated adrenergic mechanisms as the cause. The present study was undertaken to investigate if the adenylate cyclase system in the rat heart was affected by malnutrition. Three different animal groups with malnutrition were compared with a control group: rats with acute starvation for 14-96 hours, rats with protein-calorie malnutrition for 2 weeks, and rats with tumors. Stimulation by beta-adrenergic receptors and inhibition by muscarinic receptors of adenylate cyclase activity were not altered by malnutrition. However, conditions used for in vitro adenylate cyclase determinations were, of necessity, not physiological. Neither did the number of beta-adrenergic and muscarinic receptors change. When competition-binding experiments were performed, differences comprising agonist affinity and affinity state distribution were noted among the groups. The myocardial beta-adrenergic receptors formed a reduced number of high-affinity sites in all groups as compared with the control rats. All high-affinity sites displayed a more than 10-fold increase in affinity toward isoproterenol and an impaired sensitivity to guanine nucleotides except in heart membranes derived from rats starved less than 48 hours. While the protein-calorie restricted and the tumor-bearing rats had myocardial beta-adrenergic receptors that were unresponsive to guanine nucleotides, after 48 hours of starvation the rats exhibited an attenuated guanine-nucleotide-induced affinity shift. No changes associated with malnutrition in myocardial membrane levels of the of the stimulatory guanine-nucleotide-binding protein were detected by cholera-toxin-induced ADP-ribosylation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of malnutrition on rat myocardial beta-adrenergic and muscarinic receptors. 253 24

Exploiting the immunomasking method, a polyclonal antibody has been developed in mice for identification of a novel 80 kDa antigen (P80) in KB cells. The P80 was not detected in normal resting cells but was present in appreciable amount in malignant cells. In a comparative Western transfer the antisera to the immune complexes identified a 80 kDa peptide absent in normal cell extracts. When growth of KB cells were arrested by 48 h of serum starvation the P80 was not detected but after refeeding with serum containing medium, the P80 reappeared within 1 h. This result indicates that the P80 is associated with cell proliferation and appears early in the GI-S phase of the cell cycle.
Cancer Lett 1989 Oct
PMID:Identification of a novel 80 kDa antigen associated with cell proliferation. 269 24

1. Indirect calorimetry has been used to measure resting energy expenditure (REE) and the thermogenic response to a test meal (diet-induced thermogenesis) in groups of weight-stable and weight-losing patients with gastrointestinal adenocarcinoma. Average daily intakes of energy and protein were computed from dietary assessment for the week before hospitalization. Results were compared with a control group of patients with benign gastrointestinal disease. 2. Weight-losing cancer patients had a significantly reduced mean total energy and protein intake. 3. There was no significant difference in REE between the groups when results were normalized in terms of metabolic body size (kJ/kg 0.75) and lean body mass (kJ/kg). 4. Diet-induced thermogenesis was reduced in weight-losing cancer patients. 5. It is suggested that the reduction of diet-induced thermogenesis in weight-losing cancer patients is another element of starvation adaptation, subsequent to their weight loss, and that altered thermogenesis does not contribute to the weight loss seen in cancer cachexia.
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PMID:Diet-induced thermogenesis in patients with gastrointestinal cancer cachexia. 276 53

From this review of the natural history of EBV infection in humans, it is clear that the virus has evolved to a symbiotic state with humans. Once individuals are infected, EBV establishes a permanent infection that is maintained at a low level by replication of the virus in the oropharyngeal region with subsequent seeding of circulating B-lymphocytes. Individuals with normal immune systems are able to control the pronounced proliferative potential of EBV-infected cells and thus prevent the emergence of lymphoproliferations. Disease states result when the immune system is altered by other infections, developmental conditions, immunosuppressive agents, or debilitating circumstances such as cancer or starvation. In some cases, localized lymphoproliferations resembling large-cell non-Hodgkin's lymphomas can result that are monoclonal by immunoglobulin gene rearrangement studies. Remarkably, many of the localized masses will regress if the immunosuppressive agents or condition can be ameliorated in these individuals. In patients with hereditary immune deficiencies, these localized masses can progress to a fatal disease without further cytogenetic events. Burkitt's lymphoma, which is associated with EBV infection, appears to result when EBV-driven lymphoproliferations undergo cytogenetic translocations involving predominantly chromosome 8. Most of the conditions that are associated with EBV can be diagnosed by accurate application of EBV-serology, examination of peripheral blood films, a careful history and physical examination, and, in some cases, more sophisticated techniques such as the establishment of lymphoblastoid cell lines, EBNA staining, DNA probes, and pedigree analysis.
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PMID:Epstein-Barr virus--associated lymphoproliferative lesions. 283 36


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