Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four compounds having a molecular structure analogous to that of tilorone and tilorone itself, taken as a reference compound, were examined for complex formation ability with DNA. While the association constants of the various complexes were almost the same, the r values in saturation conditions (that is the highest number of molecules bound per nucleotide of DNA) increased with the size of the planar moiety or with the length of the two basic side chains of the molecules. Concerning the structure of the complexes, it was evidenced by means of flow dichroism measurements that the non-covalent binding to DNA occurs via an intercalative mode. Moreover, it was observed that by decreasing the ionic strength, the affinity of the drugs for the macromolecule increases, indicating that in complex formation, electrostatic forces exerted between the DNA phosphate residues and the positively charged nitrogen of the side chains of the drugs are involved. It seems also possible that, in this condition, and in the presence of high concentrations of the drug, a secondary binding consisting only of electrostatic interactions outside of the helix takes place. In connection with the complexing ability with DNA, the examined compounds proved able to inhibit DNA and RNA synthesis in Ehrlich ascites tumor cells. A correlation was found between complexing ability and inhibitory activity on nucleic acid synthesis.
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PMID:Interaction between DNA and some congeners of tilorone. 55 95

Concentrations of intracellular orthophosphate were determined in Ehrlich ascites tumor cells incubated with glucose, inosine, or uridine in media of different orthophosphate concentration. The effects of orthophosphate concentration on the accumulation of lactate and of phosphoribosyl pyrophosphate and on concentrations of ribose 1-phosphate and ribose 5-phosphate in tumor cells incubated with glucose were also determined. Both the phosphorolysis of inosine and the rate of catabolism of ATP in cells incubated with 2-deoxyglucose were also influenced by the orthophosphate concentration of the medium.
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PMID:Role of orthophosphate concentration in the regulation of ribose phosphate synthesis and purine metabolism in Ehrlich ascites tumor cells. 56 Sep 2

A regulatory function of the cell membrane in controlling the cytoplasmic level of Pi has been proposed, and in Ehrlich ascites tumor cells an active influx of primary phosphate has been reported in the literature. In the present study, Ehrlich cells were incubated at 1.5--50 mM extracellular Pi at pH 7.4 (Pi mainly secondary phosphate) and at pH 6.0 (mainly primary phosphate), and the measured cell Pi was compared with the value expected from a passive distribution of Pi. At a low extracellular Pi concentration the cell Pi was 3--6 mumol/g or even more. It is suggested that a major part of this cell Pi can be accounted for by enzymic release of Pi during the sampling procedure. If this interpretation is correct, the present results show that both ionic species of Pi are in electrochemical equilibrium across the cell membrane at steady state. Moreover, in vivo the concentration of free Pi in the cytosol will presumably be maintained at a steady-state level of about 0.4 mM, one order of magnitude below the directly measured values. This implies that the ratio [ATP]/[ADP][Pi] which is important in the regulation of energy metabolism, is higher than reported in the literature.
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PMID:Inorganic phosphate in Ehrlich ascites tumor cells and its distribution across the cell membrane. 56 66

High-resolution 31P NMR spectra of normal and malignant muscle tissue from mice were obtained at 100 MHz. The spectrum of normal muscle was found to resemble that obtained by Hoult et al. for normal rat skeletal muscle. But the spectrum of malignant muscle tumor (rhabdomyosarcoma) was found to comprise only the inorganic phosphate and sugar phosphate peaks, which indicates potential usefulness of this NMR method for diagnosis. Moreover, the inorganic phosphate peak was observed to be shifted downfield 70 Hz from the location seen in normal muscle. This identification of an NMR absorption frequency different in cancer tissue than in normal, singles out what may be the first of many absorption frequencies that could be utilized as target frequencies for delivery of cancer-destructive radiation.
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PMID:Spectral differences in the 31P NMR of normal and malignant tissue. 60 Nov 9

An unusual finding of systemic calcinosis in a patient with a nonparathyroid malignant neoplasm stimulated us to do a sclinicopathologic review of similar cases at our institution in the past seven years. Of 3,268 autopsies performed from 1968 to 1975, a total of 17 cases of calcinosis were found, 11 with solid tumors and 6 with hematopoietic neoplasms. Calcinosis was most prominent in the lung, kidney, heart, and stomach and was rarely discovered prior to death. Eighty-two percent of the patients had hypercalcemia and 53% had associated bony metastatic disease. Corticosteroid or phosphate treatment for the hypercalcemia may have contributed to the tissue deposition of calcium. Significant hepatic, renal, metabolic, and pulmonary dysfunctions were also associated with this disorder. Thirty-six percent of the patients had hypercalcemia without skeletal involvement; tumor-produced parathormone-like substances may be responsible for these calcium abnormalities. Calcinosis was a significant complication of neoplastic disease in these patients and contributed to morbidity and mortality.
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PMID:Calcinosis in nonparathyroid malignant disease: an unusual case report and clinicopathologic review of 17 cases. 62 63

With radioactive compounds of high specific activity, the binding of carcinogens to DNA can be measured with doses that are ineffective in long-term studies. The binding of tritiated benzo(a)pyrene to liver DNA of adult male rats has been determined 50 hr after a single i.p. injection of doses between 40 microgram/kg and 4 mg/kg. The dose-response relationship is linear up to 1 mg/kg, shows a step towards 2 mg/kg, and gives a shallow linear slope above that value. The observed binding ranges from 1.7 to 180 nmoles benzo(a)pyrene per mole DNA phosphate. The nonlinearity could be due to an induction of metabolizing enzymes. The microsomal aryl hydrocarbon hydroxylase activity increases significantly 24 hr after a single dose of 4 mg/kg and 48 hr after doses of 2 and 4 mg/kg, but no induction is found with 1 mg/kg. The binding from an equimolar dose is 35 times lower than the one found on mouse skin DNA and 300 times lower than that of N,N-dimethylnitrosamine in rat liver. A good correlation exists to the respective tumor formation in long-term studies.
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PMID:Nonlinear dose-response relationship for the binding of the carcinogen benzo(a)pyrene to rat liver DNA in vivo. 62 63

Snell adrenocortical tumor 494 was implanted into male Sprague-Dawley rats and recovered 7, 14, 21, 28 or 35 days following initial detection by palpation (7-10 days following transplantation). Electron microscopic, stereological and biochemical analyses of the tumor were compared to adrenals of normal animals to serve as a baseline for further studies of the effects of chemotherapeutic agents on tumor cells. Tumor cells possessed oval or elongated mitochondrial profiles with tubular cristae, one or two very large (greater than 5 micrometer) lipid droplets, abundant ribosomes and coated vesicles, and sparse rough and smooth endoplasmic reticulum. Stereologic evaluation revealed that tumor lipid volume was 41% and mitochondrial volume 29% that of the normal adrenal controls. Tumor nuclei were 2.5 times larger than adrenocortical nuclei while cellular volumes were similar. On a net weight basis, tumor cholesterol was 55%, cholesterol ester 2.2%, and lipid phosphate 25% of respective mean values for normal adrenal glands. The tumor cholesterol: cholesterol ester ratio progressively decreased with time but remained 18-fold greater than the normal adrenal. Plasma corticosterone levels in tumor-bearing rats were elevated 3-fold by 14 days and initial detection. The adrenals of the tumor-bearing host exhibited marked involution, the extent of which was directly related to tumor size.
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PMID:Rat adrenocortical carcinoma 494: an integrated structural, stereological, and biochemical analysis. 63 20

Electron microscopy of two osteoblastomas revealed the existence of three distinct types of cells in this tumor: osteoblast like, macrophage like, and multinucleated giant cells. In addition to the lysosomes, most Golgi cisternae and vesicles in the osteoblast like cells showed evidence of acid phosphatase activity. Deposits of lead phosphate indicating the site of this enzyme in the macrophage like cells were confined to the large and abundant lysosomes. Wide spread deposition of final product was noted in the cytoplasm of the multinucleated giant cells, both in conventional lysosomes, Golgi regions and special organelles probably corresponding to GERL. With regard to nonspecific alkaline phosphatase, final product indicating the location of enzyme activity was confined to the plasma membranes and associated vesicular and vacuolar structures in the osteoblast like cells. The findings suggest that the giant cells in osteoblastomas participate in lytic bone destructive and resorptive processes while osteoblast like cells appear to be osteoid and bone forming carriers of the neoplastic properties of the tumor.
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PMID:Studies on the fine structure of osteoblastoma with notes on the localization of nonspecific acid and alkaline phosphatase. 64 29

A patient with a benign condroblastoma of the talus bone is described. A review of the pathogenesis and more common sites of predilection of this unusual tumor is presented. This is the first case, to our knowlege, shown by labeled phosphate scanning.
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PMID:Benign chondroblastoma of talus demonstrated by skeletal scanning. 65 55

A binary logistic model is used for predicting response to cytotoxic chemotherapy for a breast cancer patient on the basis of her tumor enzyme activity profile. The enzymes used in the model are lactate dehydrogenase, nicotinamide adenine dinucleotide phosphate-isocitrate dehydrogenase, and phosphoglucomutase, all of which were measured on primary tumor specimens from each patient. The statistical model provides an estimate of the probability that an individual will respond to treatment. Chemotherapeutic treatment consisting of combination cytotoxic drugs and subsequent evaluation of patient response followed cooperative group protocol guidelines, including outside review to confirm the patient evaluation. The model based on this study, which represents 5 years of patient follow-up, correctly predicts clinical outcome in 32 of the 37 cases available.
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PMID:A statistical model for predicting response of breast cancer patients to cytotoxic chemotherapy. 66 49


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