Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present paper concerns two multicenter studies on adjuvant therapy with medroxyprogesterone acetate (MAP) for operable N+ breast cancer. The patients entered the study between April 1979 and March 1986. One hundred and fifty-one premenopausal patients were randomly assigned to receive either polychemotherapy (CMF) or CMF + MAP. One hundred and thirty-eight postmenopausal patients were randomized to receive either MAP h.d. or no treatment. CMF was administered according the following schedule: cyclophosphamide mg 100/ms p.o. 1-4 days; methotrexate mg 40/ms i.v. and fluorouracil mg 600/ms i.v. 1st and 8th days. The cycle was repeated six times every 28 days. MAP was administered at 1000 mg X 2/daily p.o. for 30 days and afterwards 500 mg X 2/daily for 5 months. In the premenopausal study after a median follow-up of 36 months no difference was observed in the incidence of recurrence, site of recurrence, actuarial 5-year disease-free survival (DFS) or overall survival (OS). In the postmenopausal study a statistically significant lower number of recurrences was observed in MAP-treatment patients after a median follow-up of 37 months. The effect of MAP was limited to patients with less than or equal to 3 metastatic axillary lymph nodes. In addition, there are suggestions that only patients with ER+ tumors draw some advantage from the treatment. On the other hand, no difference exists in the OS. The treatments were substantially well tolerated. The MAP + CMF regimen induces lower vomiting compared to the CMF alone. The most frequent MAP side-effects were vaginal spotting (16%) and tremors (12%). We conclude that MAP h.d., like tamoxifen and aminoglutethimide, can improve the DFS of operable N+ breast cancer in postmenopausal patients.
Eur J Cancer Clin Oncol 1988 Mar
PMID:Adjuvant therapy for operable breast cancer with medroxyprogesterone acetate alone in postmenopausal patients or in combination with CMF in premenopausal patients. 296 62

The effects of the enzyme-activated irreversible inhibitors of ornithine decarboxylase, alpha-difluoromethylornithine, alpha-(fluoromethyl)dehydroornithine, alpha-(fluoromethyl)dehydroornithine methyl ester, and (2R,5R)-6-heptyne-2,5-diamine (RR-MAP), on cell growth and parameters related to polyamine biosynthesis were compared in L5178Y and L1210 cells under identical culture conditions. The two lines are murine lymphocytic leukemia cells which differ in their ability to metabolize 5'-methylthioadenosine, the by-product of polyamine biosynthesis: L5178Y cells contain a specific 5'-methylthioadenosine phosphorylase; L1210 cells do not. In L1210 cells, the 50% inhibitory concentrations (lC50S) of the various analogues were 3.0 mM for alpha-difluoromethylornithine, 0.2 mM for alpha-(fluoromethyl)dehydroornithine, 0.1 mM for alpha-(fluoromethyl)dehydroornithine methyl ester, and 0.01 mM for RR-MAP. L5178Y cells were somewhat more sensitive to the inhibitors with lC50 values of 0.5 mM for alpha-difluoromethylornithine, 0.06 mM for alpha-(fluoromethyl)dehydroornithine, 0.03 mM for alpha-(fluoromethyl)dehydroornithine methyl ester, and 0.002 mM for RR-MAP. In all cases, growth inhibition was fully prevented by exogenous putrescine. The effects of the inhibitors on parameters related to polyamine metabolism were compared at drug concentrations approximating the average of lC50 values for the two cell lines. Under these treatment conditions, polyamine pools were similarly affected by the various inhibitors. Typically, putrescine and spermidine were depleted, but effects on spermine pools differed according to the cell line, increasing slightly in L1210 cells and decreasing by about 50% in L5178Y cells. Spermine pools in L1210 cells could be reduced by RR-MAP at concentrations higher than the lC50 (i.e., 0.1 mM). Clonogenicity in soft agar was decreased about 50% by putrescine and spermidine depletion and was not further affected by spermine depletion. The inhibitors elevated S-adenosylmethionine decarboxylase activity in both cell lines with a 2-fold greater increase in L5178Y cells than in L1210 cells. Finally, the inhibitors decreased S-adenosylmethionine pools in L1210 cells by about 50% but had little effect on these pools in L5178Y cells with the exception of RR-MAP, which decreased S-adenosylmethionine pools by about 40%. Whether the different polyamine responses of the two cell lines are related to their ability to metabolize 5'-methylthioadenosine is uncertain. It is apparent, however, that the presence or absence of methylthioadenosine phosphorylase does not substantially modulate the antiproliferative activity of ornithine decarboxylase inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Res 1986 Mar
PMID:Comparison of the biological effects of four irreversible inhibitors of ornithine decarboxylase in two murine lymphocytic leukemia cell lines. 308 Feb 34

Plasma levels of medroxyprogesterone acetate (MAP), tamoxifen (TMX) and its major metabolites, 4-hydroxy TMX and desmethyl TMX, were determined in five patients with advanced breast cancer following simultaneous MAP (2,000 mg/day) and TMX (20 mg/day) oral therapy. The interindividual variance in MAP plasma levels was wide; the mean plasma levels of both drugs were nearly identical, despite the large difference in the administered doses.
Cancer Chemother Pharmacol 1985
PMID:Medroxyprogesterone acetate (MAP) and tamoxifen (TMX) plasma levels after simultaneous treatment with 'low' TMX and 'high' MAP doses. 315 48

One hundred seventeen postmenopausal advanced breast cancer patients previously untreated with chemotherapy were randomized to receive: cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), CMF and tamoxifen (TMX), and CMF and medroxyprogesterone (MAP). Treatments B and C induced a greater proportion of responses than treatment A. No effect was identified on the number of complete responses. After treatment failure, patients from groups A and C received Adriamycin (doxorubicin) (ADX) vincristine (VCR), and TMX and patients from group B received ADM, VCR, and MAP. No differences were found between the branches in the response rates to the second protocol. Responders to both treatments had a longer survival experience than nonresponders or responders to only one of the treatments. Survival was independent of the treatment group.
Cancer 1985 Dec 15
PMID:Chemotherapy versus chemotherapy plus hormonotherapy in postmenopausal advanced breast cancer patients. A randomized trial. 390

The effects of hexestrol (HXS), medroxyprogesterone acetate (MAP) and chlormadinone acetate (CMA) on 7, 12-dimethylbenz [a] anthracene-induced mammary cancer in rats were evaluated. As a result of successive intramuscular injections of HXS at dosages of 2 or 10 mg/kg or MAP at dosages of 24 or 120 mg/Kg, tumors were markedly reduced in size in all groups on day 7 approximately 14. These effects were the same regardless of the presence or absence of cytoplasmic estrogen receptors (ER) in tumors as determined by the dextran-coated charcoal method. Although such an effect was also seen with CMA, it was much less marked than the effects seen with HXS and MAP. The body weights of HXS-administered groups decreased considerably, whereas those of MAP-administered groups increased. These results may suggest that there is another endocrinological tumor-suppressing mechanism besides the mechanism involving the estrogen-ER system in large-dose administration of HXS and MAP.
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PMID:Effects of hexestrol, medroxyprogesterone acetate and chlormadinone acetate on 7, 12-dimethylbenz [a] anthracene-induced rat mammary cancer in relation to estrogen receptor. 617 73

After simultaneous administration of medroxyprogesterone acetate (MAP) 1,000 mg PO and 1,000 mg IM to ten cancer patients, we observed mean plasma MAP profiles that could be exactly superimposed on the two absorption/decay curves obtained after administration of single doses IM or PO. Treatment with MAP given simultaneously by the IM and PO routes may be effective in overcoming the drawbacks of both routes, and can also more reliably guarantee plasma levels in the therapeutic range.
Cancer Chemother Pharmacol 1982
PMID:Medroxyprogesterone acetate (MAP) plasma levels after simultaneous oral and intramuscular administration in cancer patients. 621 87

Ten advanced cancer patients not amendable to conventional therapy were treated with high dose (greater than 500 mg/day, for 30 days) Medroxyprogesterone Acetate (MAP) both orally and intramuscularly, in order to evaluate a possible anabolic effect of this hormone. During the treatment, mean protein intake increased from 37.2 gr/day to 58.8 gr/day (p less than 0.01), nitrogen intake from 5.8 to 9.4 gr/day (p less than 0.01) and caloric intake from 1407.9 to 2075 Kcal/day (p less than 0.01). Nitrogen balance also showed a significant increase (p less than 0.05), as well as elementary strength (p less than 0.02). Lean body mass and body weight did not show significant variations. The above data confirms what was already been documented by us in animals and proposed in man-that MAP has an anabolic effect.
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PMID:The anabolic effect of high dose medroxyprogesterone acetate in oncology. 622 31

In mature male and female SD rats, the anti-weight gain effect of durabolin plus vitamin C or vitamin C alone was statistically significant compared to durabolin-treated and control rats. The anti-tumor and anti-weight gain effects of MAP plus vitamin C on DMBA-induced rat mammary cancer were compared with those of MAP and vitamin C in relation to ER. An anti-tumor effect was noted in the MAP treated groups, irrespective of the ER status; it was more pronounced in the MAP (100 mg/kg) plus vitamin C treated group with ER+tumors. Among the ER+tumor groups, weight gain was remarkable in the MAP-treated (20 mg/kg) animals; an anti-weight gain effect was seen in the MAP (20 mg/kg) plus vitamin C group.
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PMID:[Effect of medroxyprogesterone acetate (MAP) and vitamin C on DMBA induced rat mammary cancer in relation to estrogen receptor(ER)]. 622 84

Ten advanced cancer patients (both with hormone-sensitive and non-hormone sensitive tumors) were treated with high dose medroxyprogesterone acetate (MAP, greater than 500 mg/day). We determined body weight, lean body mass, blood pressure, sodium blood level, urinary excretion, and exchangeable sodium pool by the 22Na method before and after treatment. These data seem to exclude a fluid retentive effect for high-dose MAP.
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PMID:The effect of high dose medroxyprogesterone acetate on water and salt metabolism in advanced cancer patients. 624 49

We have examined aspects of the interaction of cycled microtubule protein preparations with 35S-labeled mouse DNA tracer in a competition system with unlabelled competitor E. coli or mouse DNA. The nitrocellulose filter binding assay was used to measure interaction by scintillation counting. DNA molecular weight affected the levels of filter retained 35S-labelled mouse tracer DNA. Filter retention levels increased if 35S-labelled mouse DNA tracer size was increased, and the filter binding level decreased if competitor DNA size was increased. There was a sizeable, reproducible difference in the 35S-labelled mouse DNA tracer binding level of about 1% when E. coli or mouse DNA competitors were compared. Mouse DNA more effectively competed with 35S-labelled mouse DNA for microtubule protein binding than did E. coli DNA, suggesting that a small class of higher-organism DNA sequences interacts very strongly with microtubule protein. From other studies we know this to be the MAP fraction (Marx, K.A. and Denial, T. (1984) in The Molecular Basis of Cancer (Rein, R., ed.), Alan R. Liss, New York, in the press; and Villasante, E., Corces, V.G., Manso-Martinez, R. and Avila, J. (1981) Nucleic Acids Res. 9, 895-908). We find that this difference in competitor DNA strength is qualitatively similar under high-stringency conditions (0.5 M NaCl, high competitor [DNA]) we developed for examining high-affinity complexes. Under high-stringency conditions we isolated 1.2% and 0.6% of 35S-labelled mouse DNA at 4200 and 350 bp respective sizes as nitrocellulose filter bound DNA-protein complexes. At both molecular weights these high-affinity DNA sequences, isolated from the filters, were shown to be significantly enriched in repetitive DNA sequences by S1 nuclease solution reassociation kinetics. The kinetics are consistent with about a 4-fold mouse satellite DNA enrichment as well as enrichment in other repetitious DNA sequence classes. The high molecular weight filter-bound DNA samples were sedimented to equilibrium in CsCl buoyant density gradients and found to contain primarily mouse satellite DNA density sequences (1.691 g/cm3) with some minor fractions at other density positions (1.670, 1.682, 1.705, 1.740, 1.760 g/cm3) similar to those observed by our laboratory in previous investigations of micrococcal nuclease-resistant chromatin (Marx, K.A. (1977) Biochem. Biophys. Res. Commun. 78, 777-784). That the high-affinity microtubule-bound DNA was some 3-5-fold enriched in mouse satellite sequences was demonstrated by its characteristic BstNI restriction enzyme cleavage pattern.
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PMID:High-affinity microtubule protein-higher organism DNA complexes. Many-fold enrichment in repetitive mouse DNA sequences comprised of satellite DNAs. 639 51


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