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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor adaptation to chronic energy starvation in vivo was studied on Ehrlich ascites carcinoma (EAC) cells. EAC cells were isolated from mice and incubated in a glucose-free medium containing blocators of mitochondrial ATP generation (rotenone, 2,4-dinitrophenol, or oligomycin). ATP level in the treated cells decreased to 3-4% of the initial during 30 min of the incubation. The aggregation of cytoskeletal proteins, blebbing, and necrotic death within 2-3 h were observed in ATP-depleted EAC which were isolated and treated in the exponential phase of growth (5 days after inoculation), whereas stationary EAC (8 days after inoculation) were considerably more resistant to ATP depletion, and actin aggregation as well as bleb formation were suppressed in these cells despite the ATP loss. In contrast to the exponentially growing cells, thermotolerance and unexpected expression of inducible HSP68 and HSP27 as well as an elevated level of HSP90 were found in stationary EAC. Since the stationary cells had decreased content of ATP, ATP/ADP ratio, and energy charge, we suggest that this energy dysbalance may be conducive to HSP induction within the ascites tumor in vivo, and, at the same time, EAC cells with elevated content of HSPs acquire resistance to chronic energy starvation occurring in late stages of the tumor growth.
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PMID:Adaptation of Ehrlich ascites carcinoma cells to energy deprivation in vivo can be associated with heat shock protein accumulation. 755 91

The extracellular pH (pHe) in solid tumors is frequently lower than the pHe in normal tissues, but the intracellular pH (pHi) is regulated to physiological levels. Cell killing can be achieved in an acidic environment in tissue culture by nigericin, which acidifies cells by transporting H+ from the extracellular space into the cytoplasm; this cell killing can be enhanced when used with 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a potent inhibitor of membrane-based Na+/H+ exchange, which plays a major role in the regulation of pHi (R. P. Maidorn; E. J. Cragoe; I. F. Tannock, Br. J. Cancer 67:297-303; 1993). We have therefore assessed the ability of nigericin and EIPA to kill cells in two murine solid tumors (the KHT fibrosarcoma and the EMT-6 sarcoma). Hydralazine, which reduces tumor blood flow, or glucose, which stimulates glycolysis leading to accumulation of lactate, were also administered to mice to lower pHe in the tumors. We observed only a small decrease in the surviving fractions of cells in the tumors when tolerated doses of nigericin and EIPA were given IP to tumor-bearing mice. When nigericin and EIPA were combined with administration of hydralazine, the surviving fraction of cells in both tumors was reduced by a factor of 0.01, but there were minimal effects on growth delay. Administration of glucose with nigericin and EIPA led to a smaller reduction in surviving fraction of the KHT tumor (by approximately 0.1), although glucose was more effective than hydralazine in lowering the mean tumor pHe. When KHT tumors were treated with 15 Gy X-rays followed immediately by nigericin, EIPA, and hydralazine, a reduced surviving fraction as well as an increase in tumor growth delay was observed compared to radiation alone; however, there was little evidence to suggest that these agents were selectively toxic to the cells that survived radiation. Nigericin and EIPA, with or without hydralazine, had minimal effects on normal tissues, as assessed by changes in body weight, number of leukocytes, and serum creatinine levels. We conclude that pharmacological effects to acidify cells and to prevent regulation of pHi under the acidic conditions that exist in solid tumors can lead to moderate levels of cell killing, if additional strategies are used to lower tumor pHe.
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PMID:Antitumor activity of nigericin and 5-(N-ethyl-N-isopropyl)amiloride: an approach to therapy based on cellular acidification and the inhibition of regulation of intracellular pH. 786 1

The bioenergetic effects of cancer cachexia on the livers of male Fischer rats inoculated with a methylcholanthrene-induced sarcoma were assessed using serial in vivo 31P magnetic resonance spectroscopy. Rats were randomized into three groups: tumor-bearing controls (n = 7); an insulin-treated group receiving 2 units/100 g body weight/day starting 21 days after implantation (n = 8); and a chronic insulin-treated group receiving insulin every day after implantation (n = 3). During the 32-day study, serial measurements of food intake, body weight, and tumor volume were taken, and 31P magnetic resonance spectroscopy analyses of the livers were conducted every 7 days after tumor implantation. Neither the short-term nor the chronic insulin treatment regimens stimulated the progress of tumor growth. However, both treatments prevented body weight loss, and the short-term insulin treatment prevented tumor-induced decrease in food intake relative to the control group. Liver bioenergetic deterioration was evaluated from the increase in the ratio of Pi to ATP obtained from the hepatic 31P magnetic resonance spectra. At day 28 postimplantation, control rats exhibited appreciable hepatic bioenergetic deterioration, i.e., a Pi/ATP ratio of 1.41 +/- 0.35 (SE), significantly higher (P < 0.05) than the Pi/ATP ratio for short-term or chronic insulin treatment groups (Pi/ATP 0.92 +/- 0.22 and 0.84 +/- 0.22, respectively) or rats before tumor implantation (Pi/ATP 0.76 +/- 0.14). This insulin-induced bioenergetic protection occurred at any given tumor burden up to at least 10%. Thus, both short-term insulin given just prior to the frank manifestations of cancer cachexia and chronic insulin treatment given throughout tumor growth ameliorated host hepatic bioenergetic deterioration without significantly stimulating tumor growth. Insulin may act by altering the host metabolism (stimulation of liver glucose uptake and utilization, decreased energy-requiring gluconeogenesis, and general protein-sparing action) at the expense of the tumor.
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PMID:Insulin protects against hepatic bioenergetic deterioration induced by cancer cachexia: an in vivo 31P magnetic resonance spectroscopy study. 798 32

The role of nutrition in cancer patients is highly important, not just in preventing development of the cancer but also in avoiding greater weight loss accompanying the cancerous cachexia in the evolution of the cancer. The different ways of treating cancer also involve increased deterioration of the nutritional state. To design a correct nutritional strategy for these patients, it is fundamental to understand the anomalies present at the metabolic level, including those affecting the cancer carrying host and those observed in the tumor itself. The results of various studies carried out on animals and neoplastic subjects using predominantly glucose as the non-protein calorie source suggest a stimulating effect on tumor growth. On the other hand, it appears that there is, at the level of the tumor, an inability to correctly oxidize fatty acids. Enhanced knowledge of the different alterations to carbohydrate and fat metabolism found in cancer patients might aid in a better grasp and design of a nutritional strategy aimed at reducing morbidity and mortality in these patients and improving their quality of life.
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PMID:[Carbohydrate and lipid metabolism in the cancer patient]. 803 51

Positron emission tomography (PET) with 2-deoxy-2 [18F] fluoro-D-glucose (18FDG), a structural analog of glucose, allows tumor images to be obtained, based on increased glycolysis in cancer cells. In the present study, in order to confirm the effectiveness of 18FDG-PET tumor images for cancer diagnosis, 18FDG tumor uptake values were measured in human gastric cancer xenografts in nude mice. Firstly, comparison of 18FDG uptake and histological grade in four gastric cancers showed that 18FDG uptake increased with loss of differentiation. Secondly, reduction of 18FDG uptake values after administration of anticancer drug was found to correlate with chemosensitivity to anticancer agent, and the values were reduced prior to suppression of tumor growth. These data suggest that 18FDG-PET tumor images may provide reliable indications for assessment of the histological grade of the tumor and the efficacy of cancer chemotherapy.
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PMID:[Experimental study on the effectiveness of PET tumor images for cancer diagnosis]. 810 93

Glucose metabolism is increased in CNS tumors and correlates with malignant grade. We have previously investigated the role of IGFs in regulating CNS tumor growth and metabolism. In the present study we examined total cellular RNA from human CNS tumors for the presence for glucose transporter (Glut) and IGF mRNA. Human meningiomas and gliomas were frozen in liquid nitrogen at the time of surgery and then stored at -80 degrees C. Total cellular RNA was prepared by acid-guanidinium phenol-chloroform extraction and 20 micrograms of RNA was loaded for agarose-formaldehyde gel electrophoresis and transfer. RNA integrity in 5 meningiomas and 2 gliomas was confirmed by ethidium bromide staining of 28S and 18S ribosomal RNA and hybridization with a cDNA probe for beta-actin. For analysis, membranes were hybridized to radioactively labeled human Glut-1, Glut-3, IGF-I, and IGF-II cDNA probes, and mRNA transcripts were identified by autoradiography. All 7 tumors expressed Glut-1 and Glut-3 mRNA and Glut-3 appeared to be more abundant in meningiomas. IGF-II mRNA was detected in 2 of 6 meningiomas and in both gliomas. IGFs may play an important role in the regulation of glucose metabolism in CNS tumors. IGFs and specific glucose transporters may prove useful as markers of malignancy and potential targets for future therapy.
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PMID:Identification of insulin-like growth factor (IGF) and glucose transporter-1 and -3 mRNA in CNS tumors. 826 14

The purpose of this study was to determine the effects of the 7288ctc Morris hepatoma on heart size and performance. Hearts from tumor bearing and control animals were perfused in the working configuration one to three weeks post implantation. As tumor growth progressed there was an inverse linear relationship between tumor size and heart weight. When intrinsic heart work (defined as the product of the cardiac output and peak systolic pressure) was assessed in vitro over a range of physiologic preloads, significant differences were found between tumor-bearing and non-tumor-bearing animals. The hearts from the tumor-bearing animals (tumor weight 10-20 grams) developed only 76% of the heart work of control animals at maximal left atrial filling pressure (25 cm H2O). Hearts excised from rats with tumor masses from 30-65 grams developed 43% of the myocardial work as controls at the same (25 cm) preload. At the time of sacrifice resting blood pressures, blood glucose, insulin, and tumor necrosis factor (TNF) levels were similar in both groups. Blood from tumor bearing animals were negative for both aerobic and anaerobic bacteria. The data suggests that the decrements in cardiac size and performance are independent of several vectors known to influence heart size and performance and occur in the absence of detectable bacteremia.
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PMID:Myocardial effects of experimental neoplastic disease. 828 90

The effects of nutritional state on tumor growth are poorly understood. Most animal studies to date suggest an inhibitory effect of nutritional depletion on tumor growth and a stimulatory effect of nutritional repletion or overfeeding. We have modified an "isolated tumor vascular pedicle" model in the nude rat to study the growth and tumor-specific nutrient utilization of the FaDu cell line of human hypopharyngeal squamous carcinoma. Two weeks after tumor implantation, rats were randomized to either a fed or fasted study group for an additional 7 days. Tumors were significantly larger in the fasted group (0.602 +/- 0.215 g vs 0.362 +/- 0.104 g; P < .02). Whole blood nutrient gradients were determined across the tumor and systemic tissues in both groups. The nutrient gradients across these tissues were significantly different in the fed animals and approached statistical significance in the fasted animals. In addition, there appeared to be a greater utilization of glucose in the fed group (-0.401 +/- 0.904 mmol/L vs -0.298 +/- 0.589 mmol/L), while there was a greater production of lactate in the fasted group (0.798 +/- 0.518 mmol/L vs 0.046 +/- 0.639 mmol/L; P < .1). Flow cytometric analysis revealed no difference in the percentage of cells in any particular stage of the cell cycle between the two groups. These results suggest that the maintenance of adequate body weight may be beneficial not only to the nutrition of the cachectic tumor-bearing host but may also prevent a ketotic state or state of lipolysis that may be preferential to the tumor.
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PMID:The effect of an acute fast on human head and neck carcinoma xenograft. Growth effects on an 'isolated tumor vascular pedicle' in the nude rat. 834 53

The present study was performed to determine the time-course for the development of peripheral and hepatic insulin resistance in rats as a result of an increasing tumor burden. Animals were inoculated with Yoshida ascites hepatoma, and studies were conducted during the early phase of tumor growth (day 4) at which time there was no change in food intake and at a later time point (day 8) when the tumor burden was increased and rats demonstrated anorexia. In vivo insulin action was accessed under euglycemic hyperinsulinemic conditions, in which insulin was infused at rates sufficient to produce arterial insulin levels that represent high physiological (3.5 ng/ml) or maximally stimulating values (180 ng/ml). On day 4, tumor-bearing (TB) rats were euglycemic, and whole body glucose turnover was elevated 32%. Insulin-mediated glucose uptake (IMGU) in TB rats was similar to control values at the low insulin infusion rate but reduced by 53% under maximally stimulating conditions. The insulin-induced suppression of glucose production was similar in TB and control animals at this time point. In contrast, on day 8, TB rats were hypoglycemic and glucose turnover was reduced 35%. The impairment in IMGU was more severe than seen earlier, with glucose uptake being reduced 39 and 61% at both levels of hyperinsulinemia. At this time point, the ability of insulin to inhibit glucose production was also impaired. These results indicate that the insulin resistance induced by the Yoshida hepatoma was manifested initially by a reduction in IMGU by peripheral tissues. As the tumor burden increased peripheral insulin resistance became more severe and an impairment in hepatic insulin action was observed.
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PMID:Impairment of insulin action on peripheral glucose uptake and hepatic glucose production in tumor-bearing rats. 836 89

In the WAG/Rij nude rat, subcutaneous (s.c.) and intracerebral (i.c.) xenografts of the human SCLC cell line GLC-28 were evaluated for their growth behavior, in vivo monoclonal antibody binding and presence of tumor infiltrating lymphocytes. For the i.c. xenografts, two models of cerebral tumor growth were studied, one in the cerebral cortex and one in the lateral ventricle of the brain. In the s.c. and both i.c. xenografts models, in vivo localization of anti-carcinoma moab MOC-31 occurred within 4 hours after i.p. injection, with a maximal binding at 24 h after injection. A pronounced tumor infiltration of predominantly NK cells was observed for s.c. and intraventricular xenografts, but not for the GLC-28 tumors xenografted in the cerebral cortex. The presented nude rat/GLC-28 xenograft models may be used for the in vivo testing of experimental imaging techniques or alternative treatment strategies relevant to brain metastases of human SCLC.
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PMID:Intracerebral and subcutaneous xenografts of human SCLC in the nude rat: comparison of monoclonal antibody localization and tumor infiltrating lymphocytes. 841 Jan 37


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