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

In vivo magnetic resonance imaging (MRI) has employed almost exclusively the proton because of its high gyromagnetic ratio and natural abundance relative to other nuclei. Recent research has focused on imaging using nuclei other than 1H, but has been limited by the decreased sensitivity and/or low biologic concentrations of the nuclei. Fluorine (19F), with a gyromagnetic ratio second only to that of hydrogen, is a theoretically attractive nucleus for MRI, but fluorine is present in only minute amounts in most tissues. Perfluorochemical emulsions (PFC), developed as blood replacement agents, appear to be safe vehicles for fluorine administration. We report our initial results of in vivo 19F magnetic resonance imaging of liver, tumor, and abscess in rats given exogenous fluorine.
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PMID:In vivo 19F NMR imaging of liver, tumor, and abscess in rats. Preliminary results. 398 65

The metabolism of 9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-phosphate (F-araAMP), a soluble nucleoside analog with promising antitumor activity, has been studied in mice bearing P388 leukemia. Upon i.p. injection of an LD10 dose (1485 mg/kg) in tumor-bearing mice, F-araAMP disappeared from the ascitic fluid with a T1/2 of 1.2 h. This was accompanied by the appearance of 9-beta-D-arabinofuranosyl-2-fluoroadenine and lesser amounts of 9-beta-D-arabinofuranosyl-2-fluorohypoxanthine in both the ascitic fluid and plasma. The principal active metabolite, 9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-triphosphate, accumulated to approximately 1 mM in P388 cells, a concentration nearly 20-fold greater than that of the bone marrow or intestinal mucosa. DNA synthesis was inhibited to a similar extent in tumor and host tissues, but the duration of maximum inhibition was twice as long in P388 cells. 2-Fluoro-ATP, a second toxic metabolite, accumulated to 27 microM in P388 cells and was eliminated with a T1/2 of 3.7 h. The contributions of both 9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-triphosphate and 2-fluoro-ATP to the cytotoxicity and therapeutic action of F-araAMP should be considered in evaluations of the biochemical bases for these activities.
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PMID:Metabolism of 9-beta-D-arabinosyl-2-fluoroadenine-5'-phosphate by mice bearing P388 leukemia. 608 54

The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid phosphatases tested from potato, wheat germ, milk, and bovine prostate did not show this degree of specificity. The plasma membrane activity also dephosphorylated phosphotyrosine histone at a much greater rate than did the other acid phosphatases. pH profiles for free O-phosphotyrosine and phosphotyrosine histone showed a shift toward physiological pH, indicating possible physiological significance. Phosphotyrosine histone dephosphorylation activity was nearly 10 times greater than that seen for phosphoserine histone dephosphorylation, and Km values were much lower for phosphotyrosine histone dephosphorylation (0.5 microM vs. 10 microM). Fluoride and zinc significantly inhibited phosphoserine histone dephosphorylation. Vanadate, on the other hand, was a potent inhibitor of phosphotyrosine histone dephosphorylation (50% inhibition at 0.5 microM) but not of phosphoserine histone. ATP stimulated phosphotyrosine histone dephosphorylation (160-250%) but inhibited phosphoserine histone dephosphorylation (95%). These results suggest the existence of a highly specific phosphotyrosine protein phosphatase activity associated with the plasma membrane of human astrocytoma.
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PMID:An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein. 618 63

We have synthesized as potential imaging agents for human breast tumors a series of hexestrol analogues bearing the halogens fluorine, chlorine, bromine, and iodine at the terminus of the hexane chain. The binding affinity of these compounds for the estrogen receptor from uterine tissues forms a monotonically decreasing series, starting at 129% of that of estradiol for the fluoro analogue and decreasing to 60% for the iodo analogue. Such a modest decrease in binding affinity is thought to reflect the preference of the receptor for lipophilic groups and for substituents of moderate steric size at this site, parameters which change in opposite directions in the halogen sequence going from fluorine to iodine. Three estrogenic bis(trifluoromethyl)diphenylethylenes, prepared by DuPont, also showed substantial binding affinities for the estrogen receptor. In terms of ease of radiolabeling and high receptor binding selectivity, the compound that appears to be the most promising candidate for a breast tumor imaging agent in these series is the chain terminal fluorohexestrol.
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PMID:Estrogen receptor based imaging agents. 2. Synthesis and receptor binding affinity of side-chain halogenated hexestrol derivatives. 625 Dec 18

The skin tumor-initiating activities of 7-, 8-, 9-, and 10-fluorobenzo(a)pyrenes have been compared to that of benzo(a)pyrene in female Sencar mice after 16 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Single initiating doses of 200 or 400 nmol of each hydrocarbon were tested, and the mice were treated twice weekly with 3.2 nmol of the promoter. Under these conditions, benzo(a)pyrene caused an average of 2.9 and 5.7 papillomas/mouse, respectively, whereas none of the four fluorinated hydrocarbons had significant tumor-initiating activity. Examination of the hepatic metabolism of 7- and 8-fluorobenzo(a)pyrene revealed that a 7,8-dihydrodiol was not detected as a metabolite; thus, the bay-region diol-epoxide pathway known to be responsible for the tumorigenic activity of benzo(a)pyrene is blocked. Although 7,8-dihydrodiols are formed from 9- and 10-fluorobenzo(a)pyrene, these dihydrodiols with fluorine substituted on the 9,10-double bond may not be converted to diol-epoxides by the cytochrome P-450 system, or such fluorinated 7,8-diol-9,10-epoxides may not be tumorigenic.
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PMID:Metabolism and tumorigenicity of 7-, 8-, 9-, and 10-fluorobenzo(a)pyrenes. 629 47

Over 150 cases of central nervous system tumors have been studied with positron emission tomography using fluorine-18-labeled fluorodeoxyglucose (18FDG) as a tracer. From this material 100 consecutive cases of cerebral glioma have been reviewed and analyzed. The results show a strong correlation of tumor grade with glycolytic rate, with visual "hot spots" present in all high-grade neoplasms and in only four low-grade tumors. The quantitative accuracy is limited by three basic factors. First, the measurement of tissue uptake, as compared with the parent technique, autoradiography, is more difficult because detection must be done outside the body. Effects such as scattered radiation and self-attenuation introduce errors unless properly corrected. A more serious problem when measuring small structures, such as a rim-shaped high-grade glioma, is the limited spatial resolution. The most advanced scanner, the Neuro-PET, has a resolution of 6 to 7 mm. Second, corrections are needed for backflow, including free tracer at the time of the scan that will return to the blood and "trapped" tracer that will backflow because of the presence of phosphatase. These corrections are calculated from the blood activity using nominal rate constants for 18FDG. Our study found no significant alteration in rate constants between normal and tumoral tissue. Finally, a lumped constant is needed to correct for kinetic differences between 18FDG and glucose. If there is a change in the mechanism of either membrane transport or the hexokinase reaction, the lumped constant may change. However, measurements of actual glucose utilization in tissue culture lines from six patients support the 18FDG results.
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PMID:Issues in the in vivo measurement of glucose metabolism of human central nervous system tumors. 633 Dec 82

Etiologic and pathologic factors in clinical osteoporosis are reviewed. Techniques were developed to determine total skeletal calcium content with in vivo neutron activation analysis and to induce osteoporosis (in about three months) with low calcium diet, corticosteroid or heparin treatment in experimental animals. Genetic influence was demonstrated: C3H/St (Ha) mice were more susceptible to osteoporosis by all three modalities than C57B1/6 (J) mice. Fluoride was ineffective in preventing osteoporosis induced by either of these three modalities. Heparin induced osteoporosis was prevented by conjugated estrogens, progestins or their combinations. Progestins were shown in other studies to inhibit estrogen induced metaplasia and neoplasia. Combining estrogens with progestin may result in an increased therapeutic index for the prevention of postmenopausal osteoporosis. Human and salmon calcitonin, Deca - Durabolin, an anabolic steroid, Mopidamole, a pyrimidopyrimidine derivative, Trental, a methylxanthine derivative, certain 2-thiophene carboxylic acid derivatives and imidazoquinazolines exhibited anti-osteoporotic effects.
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PMID:Studies on the pathophysiology and therapy of osteoporosis. 639 59

We have determined the skin tumor initiating activity in SENCAR mice of 6 monofluoro derivatives of 7,12-dimethylbenz[a]anthracene (DMBA). 9-Fluoro-DMBA (9-F-DMBA) was approximately as active, and 10-F-DMBA was more active than the parent hydrocarbon, DMBA. The difference between DMBA and 10-F-DMBA was most dramatic at the highest initiating doses of 10-F-DMBA tested. 4-F-DMBA, which was only weakly active as an initiator, was also tested as a complete carcinogen on mouse skin; after 30 weeks of treatment, 50- and 100-nmol weekly doses failed to elicit papillomas or carcinomas. Animals treated with 50 nmol of DMBA weekly exhibited a 100% papilloma incidence and a 42% carcinoma incidence. Pretreatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) effectively inhibited tumor initiation with all of the monofluoro derivatives of DMBA tested. The ED50 (dose of TCDD producing half-maximal inhibition) for the inhibition of DMBA initiation in SENCAR mice was determined to be 1.8 X 10(-3) micrograms/mouse (5.6 pmol). The results indicate that the introduction of a fluorine atom in ring D of DMBA has no effect (positions 9 and 11) or enhances (position 10) tumor initiating activity. We believe 10-F-DMBA to be the first example of a hydrocarbon with a fluoro substituent giving rise to increased tumor initiating activity. The results also indicate that structural modifications that alter tumor initiating activity do not alter the ability of TCDD to inhibit tumorigenesis by DMBA.
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PMID:Tumor initiating activity of 9- and 10-fluoro-7,12-dimethylbenz[a]-anthracene (DMBA) and the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on tumor initiation by monofluoro derivatives of DMBA in SENCAR mice. 640 43

Fluorinated anesthetics such as halothane preferentially partition into hydrophobic environments such as cell membranes. The 19F-NMR spectrum of halothane in a rat adenocarcinoma (with known altered lipid metabolism and membrane composition) shows an altered chemical shift pattern compared to the anesthetic in normal tissue. In eight tumor samples examined, the 19F-NMR spectra exhibit two distinct resonances, compared to a single resonance observed in normal tissues. This is explained by an enhanced or altered hydrophobic component in the tumor tissue giving rise to two discrete halothane environments. Another fluorinated anesthetic, isoflurane, shows similar behavior in distinguishing normal from diseased tissue. Given the large chemical shift range of fluorine and the inherent sensitivity of this nucleus, 19F-NMR spectra of fluorinated anesthetics can also be used to follow anesthetic degradation by the liver. The ability of fluorinated anesthetics to discriminate tissues and to monitor metabolic processes is potentially useful for in vivo 19F-NMR surface coil and imaging studies.
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PMID:The fluorinated anesthetic halothane as a potential NMR biologic probe. 650 92

Forskolin is an activator of adenylate cyclase in many cell types. In order to determine the mechanism of forskolin's action and to determine if this mechanism is shared by hormones and other agonists of the adenylate cyclase system, we isolated and partially characterized several spontaneous, forskolin-resistant mutants from the Y1 mouse adrenocortical tumor cell line. Forskolin increased adenylate cyclase activity in Y1 cell homogenates approximately 30-fold. By virtue of its effect on cAMP accumulation, forskolin (10 microM) also inhibited the growth of Y1 cells in monolayer culture. Using forskolin as a selective agent, spontaneous mutants capable of growth in the presence of 10 microM forskolin were isolated from the Y1 cell line at a frequency of 1-2/10(6) cells. In these mutants, resistance was stable, resulting from a defect in cAMP accumulation rather than cAMP action, and was associated with a reduced ability of forskolin to stimulate adenylate cyclase activity in cell homogenates. Whereas corticotropin stimulated adenylate cyclase activity over 35-fold in cell homogenates from the Y1 parent, ACTH had only marginal effects on the enzyme's activity in the mutant clones. Fluoride-stimulated adenylate cyclase activity seemed unimpaired. These results suggest that the resistance to forskolin resulted from a mutation in the adenylate cyclase system, not in the catalytic subunit, but at a locus related to the ACTH.
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PMID:Isolation of forskolin-resistant adrenal cells defective in the adenylate cyclase system. 653 78


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