Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood was obtained on 414 occasions from 106 children with acute lymphocytic leukemia (ALL) or solid tumors. Resting and stimulated hexose monophosphate shunt (HMPS) activity and unstimulated and stimulated nitroblue tetrazolium (NBT) dye reduction were assessed on each sample. The values obtained were compared to similar determinations made on blood obtained from 178 healthy children. Resting HMPS activity of all patients with malignant diseases was significantly (p smaller than 0.01) greater, and ability to stimulate HMPSP activity significantly (p smaller than 0.01) less than that noted in healthy control patients. Unstimulated NBT dye reduction of leukocytes obtained from patients with malignant disorders was significantly (p smaller than 0.01) less than that observed in healthy control children. No significant differences were noted in HMPS activity or NBT dye reduction in patients with ALL, rhabdomyosarcoma, or other solid tumors who had bacterial infection when compared to uninfected patients, or when patients were categorized according to the type of chemotherapy provided. HMPS activity and NBT dye reduction of patients with ALL prior to treatment, in remission, and during episodes of relapse did not differ from each other. Thus, a functional impairment in leukocyte function was noted in patients with ALL even when their peripheral blood and bone marrow cells exhibited normal morphology.
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PMID:Leukocyte function in children with malignancies. 105 20

Preclinical investigations were performed with glucose administration in WAG/Rij rats carrying the rhabdomyosarcoma BA1112 in two sites per animal: one in the subcutis of the flank (for pH measurements in the tumour tissue) and one in the transparent "sandwich" chamber for measuring the erythrocyte flux in the tumour tissue as an indication for changes in tumour blood flow. A glucose solution (20%) was slowly infused intravenously in a range of dose levels, similar to those reported for inducing long-term hyperglycaemia in man. The eventual aim of such investigations is to sensitise tumours for hyperthermic treatment. This approach is not new, but the present experiments were performed with the aim to explore the level of the minimal amount of glucose which would nonetheless yield a likely therapeutic effect. Endpoints in this study were the blood glucose level and pH and the relative erythrocyte flux in the tumour tissue. Obviously, as one would expect, many significant changes in the various parameters were found as a response to administration of glucose. However, the changes in the blood glucose level, the induced decrease in tumour pH and the influence of the tumour volume did not show a well-defined relationship which was reliable enough to predict the exact influence of the various parameters on the magnitude of the desired changes in individual animals and/or tumours. This was probably caused by interfering differences in physiological feedback mechanisms. Nonetheless, the data indicate that the optimal effect was not obtained with the highest treatment level, but with moderate doses of glucose, i.e. 2.4-3 g.kg/h which induced a satisfactory tumour acidification of 0.25 pH units. This may turn out to a clinically useful pH drop for enhancing the cytotoxic effect of hyperthermia. The erythrocyte flux through the tumour tissue does not appear to be influenced to a sizeable extent by such a treatment.
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PMID:Dose-effect relationships for glucose-induced tumour acidification and its erythrocyte flux. 183 27

Pancreatic tumors are rare in children. Over a 20-year period we have treated 13 children with pancreatic neoplasms. There were eight boys and five girls (age range, 4 months to 12 years). Seven tumors were benign, including five insulinomas, and two cystadenomas. Six lesions were malignant (rhabdomyosarcoma, 2; pancreatic carcinoma, 4). Children with insulinoma presented with hypoglycemia and irrational behavior. Three had abnormal insulin:glucose ratios ( greater than 1.0). The tumor was detected by computed tomography scan in three cases, at the time of surgery in one, and with intraoperative ultrasound in one. Surgical treatment included tumor enucleation in four cases and 80% pancreatectomy in one. Mucinous cystadenomas were observed in two patients, ages 4 months and 10 months. Tha latter infant underwent cyst excision alone, resulting in malignant recurrence at 18 months of age and death. The 4-month-old child had a distal pancreatectomy and is alive at 6 years. Two of the four children with pancreatic cancer had unresectable tumors at diagnosis, and were treated by biopsy (ductal adenocarcinoma), irradiation, and chemotherapy. Length of survival was 6 months and 9 months. Two others (ages 4 and 12 years) underwent 85% distal pancreatic resection for pancreatoblastoma and a pancreatoduodenectomy for papillary carcinoma, respectively. The latter is alive and tumor-free at 20 years of follow-up. The former underwent hepatic lobectomy for a 3.0 x 3.0 cm solitary liver metastases and is alive at 6 years with no evidence of disease. One child with rhabdomyosarcoma died of progressive disease, the other is alive with residual disease despite resection and chemotherapy. Most insulinomas can be treated by enucleation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pancreatic tumors in childhood: analysis of 13 cases. 226 58

Rhabdomyosarcoma tumors in rats made hyperglycemic by multiple injections of glucose exhibited a transient decrease in pH and an increased ability to accumulate derivatives of hematoporphyrin (HPD). Photoradiation of tumors in glucose/HPD-treated animals produced a greater cell kill than in galactose/HPD-treated controls. A therapeutic benefit of glucose administration in conjunction with HPD-phototherapy is suggested.
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PMID:Glucose administration augments in vivo uptake and phototoxicity of the tumor-localizing fraction of hematoporphyrin derivative. 252 59

The effects of nutritional manipulation and subsequent chemotherapeutic treatment upon growth and metabolism of a transplanted rat rhabdomyosarcoma were investigated by in vivo 31P NMR spectroscopy. Nutritional manipulation was accomplished by administration of a protein deprived diet containing no protein and 75.5% glucose. After 5 days the protein deprived rats (PD rats) were nutritionally replenished with a normal protein diet containing 27% protein and 47.3% glucose. Twenty-four hours after nutritional replenishment the PD rats and continuously well-fed controls (NP rats) received methotrexate (MTX, 30 mg/kg, i.p.). 31P NMR spectroscopy of the tumors 24 h after MTX administration showed a decreased ratio of nucleoside triphosphates to inorganic phosphate (referred to as 'ATP/Pi ratio') in PD rats in contrast to an unchanged ATP/Pi ratio in the NP controls. At the time of MTX administration the PD rats had a significantly lower tumor pH than the NP group (6.75 +/- 0.03 [SEM] vs 6.95 +/- 0.04; p less than 0.02). Tumor response in the PD group was significantly (p less than 0.01) enhanced compared to the NP group. These findings indicate that a period of dietary protein deprivation combined with a high glucose load and followed by nutritional replenishment impairs tumor metabolism. The altered metabolic status is expressed by acidification of the tumor and distinct changes in ATP/Pi ratio and appears to relate to an enhanced susceptibility to MTX chemotherapy.
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PMID:31P NMR study of the impact of dietary manipulation on tumor metabolism and response to methotrexate. 264 Dec 88

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.
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PMID:Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions. 311 66

Children undergoing ABMT, a procedure which entails massive doses of chemotherapy along with total-body irradiation, are candidate to develop severe gastrointestinal toxicity and prolonged anorexia requiring administration of Parenteral Nutrition (PN) for variable periods. We report a series of 35 consecutive children affected by malignancies who underwent 37 courses of PN after ablative therapy followed by ABMT. Age ranged from 8 months to 17 years; 16 were females, 19 males. There were 23 cases of neuroblastoma, 5 of Wilms' tumor, 3 of acute myelogenous leukemia, 2 of Ewing's sarcoma, 1 case each of rhabdomyosarcoma and acute lymphoblastic leukemia. All patients developed severe neutropenia for 9-42 days (median 18 d). Fever occurred in all patients; sepsis was documented in 10. Duration of PN ranged from 10 to 64 days (23 +/- 9; mean +/- SD). PN solution, containing crystalline L-Aminoacids (8.5%) mixed with 33% glucose, minerals, trace elements and vitamins provided for children a caloric intake of 49.8 +/- 17.3 Kcal/Kg/day with a nitrogen intake of 0.26 +/- 0.27 g/Kg/day. Nutritional assessment, utilizing percent ideal body weight, serum protein electrophoresis, C3, pseudocholinesterase and fibrinogen, was performed at the beginning and at the completion of each course of PN. Mean percent ideal body weight was 95.8 before PN, 98.5 on last day of PN (p less than 0.0005). Other parameters did not change significantly. No metabolic complication nor severe electrolyte imbalance were observed except for 5 patients who developed hypokalemia in coincidence with administration of Amphotericin B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Autologous bone marrow transplantation in children. Use of parenteral nutrition]. 311 38

In studying the bioenergetics of living cells, the microfluorometric analysis of coenzyme (NAD(P)H) responses to microinjected respiratory and glycolytic substrates enables, in principle, a search for qualitative/quantitative differences in normal versus carcinogen-treated (short-term, long-term) and malignant cells. Responses are compared in L-cells, same adapted to hypertonic media (i.e. L255, L355) and highly malignant rhabdomyosarcoma (CCL 136) cells. The largest responses to respiratory substrate (malate, isocitrate) and the lowest responses to glycolytic substrate (glucose-6-P) are in the L255, 355 cells which exhibit structural rearrangement and dense packing of mitochondria possibly due to high energy requirement for ion pumping. The converse is observed in the CCl 136 where there is no lack of these organelles, but they could be functionally deficient, as suggested by a predominant response to glucose-6-P compared to malate. In the control L-cell, the malate and glucose-6-P responses are relatively well balanced. Upon addition of dimethylnitrosamine to L-cells, there is an initial acceleration in the rate of glucose-6-P-induced NAD(P) reduction (? NADPH requirement for dimethylnitrosamine metabolization), followed by an upsurge of the malate response. In L355 cells, addition of the carcinogens dimethylnitrosamine or ethionine is followed by a strong reductive response to malate, and minimal response to glucose-6-P. The dramatic intensification of the NAD(P)H response to malate in L355 cells pretreated with an ATP trap (ethionine) or an uncoupler (dinitrophenol) strongly points to a requirement for ATP depletion. Weaker enhancement of NAD(P)H response (preferentially after glucose-6-P) is observed in the CCL 136 upon treatment with ethionine. The findings indicate the need for further study on differences in respiratory/glycolytic pathways and efficiency of ATP cycle in malignant cells exhibiting graded differences of structural/functional specialization.
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PMID:The differential effects of dimethylnitrosamine and ethionine on mitochondrial and extramitochondrial dehydrogenases in single intact cells. 669 53

The relationship between duration of a period of vascular occlusion and magnitude of pH decrease in tumour and normal tissue was investigated in rats. To acidify tissue pH further, moderate dose glucose (2.4-3.0 g.kg(-1).hr(-1)) was administered intravenously through a catheter positioned in a tail vein, immediately after the clamp was released. This sequence of pH modifying modalities was chosen since it is employed in clinical regional isolation perfusion for recurrence of malignant melanoma of the limbs. Tumour pH in rat rhabdomyosarcoma BA1112 decreased more than normal tissue pH under 10, 20, 30 or 60 min of temporary vascular occlusion. Administration of glucose following any period of clamping always decreased tumour pH further. The largest pH decrease (0.29 pH units) was obtained after 30 min of clamping followed by 60 min glucose and 60 min saline infusion. In the clinic the combination of a maximum of 30 min of clamping followed by moderate dose glucose infusion, which can decrease tumour pH effectively, can be easily achieved in the setting of regional isolation perfusion. It can be used for treatment modalities that are known to be enhanced at lowered tissue pH, such as hyperthermia and certain chemotherapeutic drugs. These results form the basis for studying the therapeutic gain which can be obtained with this model.
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PMID:Temporary vascular occlusion and glucose: effects on tumour and normal tissue pH in animal experiments. 858 4

Differentiation of a tumor plays an important role in terms of biological aggressiveness. The question arises as to whether this is reflected in differences in the metabolic and energetic status of solid tumors. The aim of this study was to analyze the influence of clonal tumor cell differentiation on the microenvironment of rat rhabdomyosarcomas. Two distinct lines of a rhabdomyosarcoma (BA-HAN-1) with different histomorphological properties were used (line F1, co-existence of mononuclear stellate cells and multinuclear myotube-like giant tumor cells; G8, polygonal, mononuclear tumor cells). Solid tumors were grown s.c. on the hind food dorsum of Lewis rats. Tumor oxygenation was measured using O2-sensitive needle electrodes. For determining tumor blood flow, the 133Xe clearance method was used. Global glucose and lactate concentrations were measured enzymatically, global ATP, ADP, and AMP were analyzed by HPLC. The regional distribution of metabolic and energetic parameters within the tumors was analyzed using quantitative bioluminescence and image analysis. Tumor growth rate was significantly different between the two lines. The volume doubling time was 2.5 days for the F1 and 3.0 days for G8 tumors. No differences in blood flow were seen between the two lines investigated, oxygenation was slightly poorer, glucose and ATP levels slightly higher, and lactate concentration somewhat lower in the F1 line as compared to the G8 line. From these differences - although marginal - it is concluded that the G8 line presumably relies on glycolysis whereas the F1 line seems to prefer oxidative glucose turnover. Despite these different metabolic profiles between the two tumor lines, the histopathology of the rhabdomyosarcomas seems to be only of limited significance for the tissue oxygenation status as already postulated for various tumors in the clinical setting.
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PMID:Blood flow, oxygenation, metabolic and energetic status in different clonal subpopulations of a rat rhabdomyosarcoma. 966 12


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