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)

High dosage MAP (medroxyprogesterone acetate) was used in the treatment of very advanced breast cancer. 25 patients were included in the study all of whom had measurable lesions which had been unsuccessfully treated by other methods, hormonal or combination chemotherapy. Tables present information on previous treatments, results of pre-MAP therapy examinations, and results of post-MAP therapy examinations. Treatment dosage is explained. Results with this high MAP-dosage therapy compare favorably with the rate of remission obtained through other primary hormonal therapies by other researchers. Promising results without noteworthy adverse effects were obtained; remissions, however, were short. 7 of the 25 had partial remission with a median duration of 5+ months. Another 7 patients obtained a stationary status of the disease. Even some patients who had not responded previously to Tamoxifen achieved partial remission with MAP therapy, indicating that the MAP does not operate directly on the tumor cells. The incidence of partial remissions was not adversely affected by previous combination chemotherapy and hormonal treatment. Acceptability of the treatment was good.
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PMID:High dose medroxyprogesterone-acetate treatment in advanced mammary carcinoma. A phase II investigation. 16 70

Twenty-six patients with advanced renal cell carcinoma were treated with suramin administered by continuous infusion, with dosing determined by a nomogram. One patient achieved a partial response and five patients achieved a minor response or had stable disease for > 3 months. Toxicities included an immune-mediated thrombocytopenia in one patient and Staphylococcus sepsis that was not associated with neutropenia in five patients. Pharmacokinetic parameters were determined by the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit using a two-compartment open model and first-order rate elimination. This showed a wide interpatient variation in time to target level (median, 13.8 days), volume of distribution (median, 15.2 liters/m2), and t1/2-beta (median, 20.6 days). The patients who achieved a partial response, minor response, or stable disease had a slower elimination rate of suramin, compared to patients with progressive disease. Tumor specimens were obtained prior to therapy and were analyzed for the production of five different growth factor-specific RNA transcripts. These included transforming growth factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor types A and B. No difference in the pattern of growth factor expression was seen in tumors of responding and nonresponding patients. Suramin does not have significant antitumor activity in renal cell carcinoma. The wide variability in pharmacokinetics suggests that individual dosing should be used in future trials of suramin for treatment for other malignancies. Pertinent corollary studies of tumor biology and clinical pharmacology should be included whenever possible in clinical trials in patients with renal cell carcinoma.
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PMID:Phase II trial of suramin in patients with advanced renal cell carcinoma: treatment results, pharmacokinetics, and tumor growth factor expression. 139 2

The objective of the present investigation was to compare the effects of three ornithine decarboxylase inhibitors on tumoricidal macrophage and antitumor activities in vivo. alpha-Difluoromethylornithine (DFMO), (2R,5R)-6-heptyne-2,5-diamine, and alpha-(fluoromethyl)dehydroornithine methyl ester (delta MFMOme) were administered continuously in drinking water starting on Day 1 to B16F1 tumor-bearing mice. DFMO, (2R,5R)-6-heptyne-2,5-diamine, and delta MFMOme reduced B16F1 tumor growth, measured on Day 18, up to 87, 79, and 95%, respectively. Similarly, all three ornithine decarboxylase inhibitors reduced B16F1 putrescine and spermidine levels. delta MFMOme was substantially more effective both as an antitumor agent and in reducing polyamines. Both DFMO and delta MFMOme augmented macrophage tumoricidal activity directed against B16F1 target cells. MAP had no effect on macrophage tumoricidal activity. Lipopolysaccharide-stimulated macrophages from delta MFMOme-treated mice also exhibited an increase in interleukin and tumor necrosis factor levels. Furthermore, treatment with a known macrophage activator, gamma-interferon, enhanced the antitumor activity of delta MFMOme. delta MFMOme did not alter natural killer cell activity; however, cytolytic T-lymphocyte induction was reduced by 40 to 50%. These results demonstrate that, in addition to their established antitumor activity, ornithine decarboxylase inhibitors may also potentiate specific tumoricidal effector cell generation in vivo.
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PMID:Effects of three irreversible inhibitors of ornithine decarboxylase on macrophage-mediated tumoricidal activity and antitumor activity in B16F1 tumor-bearing mice. 211 41

The human tumor soft agar cloning assay has been used to assess the biological effects of cytotoxic drugs and other agents on human cancers. In this study we have examined the effects of two hormonal agents, tamoxifen (Tam) and medroxyprogesterone acetate (MPA), on colony growth of the MCF-7 human breast cancer cell line as well as fresh human breast cancer specimens. Using standard criteria for a colony (greater than 50 cells or greater than 60 microns in diameter) Tam (1.0 microM) reduced MCF-7 colony formation by only 30% to 50%, and MAP (1.0 microM) had no effect. However, both agents dramatically reduced the formation of larger colonies; less than 10% of colonies larger than 124 microns survived Tam exposure, and less than 25% survived with MPA. In vitro sensitivity (less than 30% colony survival) of fresh human breast cancer specimens was observed infrequently with either Tam (1/39 evaluable assays) or MPA (3/36 evaluable assays). Colony growth of human breast cancer was unaltered when cells were plated in charcoal-stripped serum to reduce the endogenous estrogen concentration. In vitro sensitivity to Tam or MPA was not increased under these conditions. No correlation was found between estrogen receptor (ER) concentration and inhibition of colony survival with Tam or MPA. None of 16 assays from ER-positive specimens treated with Tam and 2 of 18 ER-positive specimens treated with MPA were sensitive in vitro. In contrast, 2 of 12 ER-negative specimens tested with Tam and 3 of 7 ER-negative specimens tested with MPA were sensitive in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endocrine therapy testing of human breast cancers in the soft agar clonogenic assay. 293 13

The anti-tumor activities of steroid compounds on endometrical cancer (Ishikawa cell line) were examined in vitro by human tumor clonogenic assay (HT CA). Clinically effective progestational compounds including medroxyprogesterone acetate (MAP), and 17 alpha hydroxy-progesterone caproate were effective. Norethindrone (ENT), which is also a potent progestational compound, and RU486, which is known to be a progesterone antagonist were ineffective in this in vitro system, neither having any influence on the effect of MAP. These results indicated that the anti-tumor activity of MAP did not proceed via the so-called progesterone receptor system. Morphological changes induced by MAP in undifferentiated endometrial cancer, the effectiveness of tamoxifen, hormonochemotherapy, and the use of MAP for adjuvant therapy and prophylaxis were also discussed.
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PMID:[Hormone dependency and progestogen therapy in the treatment of endometrial cancer]. 295 4

Investigations with the fluorinated spermidine analogues show clearly that these compounds have significant potential for studying the metabolism and functions of the polyamines. However, the biochemical and biological properties of these analogues are dissimilar. This is due to the influence of the fluorine substituent(s) on the basicity of the amine function proximal to the fluoromethylene group, this effect being amplified by geminal disubstitution. The monofluorinated spermidine analogues compare well with the natural amine in their ability to regulate the expression of the decarboxylase enzymes, to be substrates of spermine synthase and to support growth of polyamine-deficient cells. It is also likely that 6-monofluorospermine, formed biochemically in situ, shares with spermine similar functions. These findings raise the possibility of using these spermidine analogues to study the metabolism and pharmacology of polyamines in vivo but also to provide more insight into the regulatory role of spermidine in ODC and SAM-DC expression. Another potential application may be the use of these analogues as probes in tumor imaging and therapy control. This indication has been inferred by studies in tumor-bearing animals, using 19F-NMR spectroscopy determination of tissue fluorospermidine and fluorospermine, formed biochemically from the precursors 2-fluoro or 2,2-difluoroputrescine, and which demonstrate preferential accumulation in tumor versus normal tissue. Finally, these monofluorinated spermidine analogues may exert beneficial effects in pathological states associated with polyamine deficiency. These diseases remain however to be identified. Among the difluorinated spermidine analogues, 7,7-difluorospermidine possesses the most interesting properties. This spermidine analogue still possesses ODC and SAM-DC repressing activities although at much higher concentration than spermidine. More importantly it is a potent inhibitor of spermine synthesis both in cultured cells and in vivo due to its efficient competition with spermidine in the spermine synthase reaction. This compound not only depletes tumor cell of its spermine content but, in addition, appears to exert by itself and/or via 6,6-difluorospermine, the product of its metabolism, polyamine antagonist effects. Combined with MAP but also with DFMO, two potent irreversible inhibitors of ODC which block the synthesis of the natural endogenous polyamines, 7,7-difluorospermidine causes an immediate decrease of viability in cultured HTC cells and promotes tumor regression and stabilization in hepatoma-bearing rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fluorine-containing polyamines: biochemistry and potential applications. 307 45

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

In the therapy of metastatic breast cancer MAP was used with different dosages and different forms of administration. Pharmacokinetics and pharmacodynamics were investigated. MAP plasma concentrations are dose dependent with great interindividual variation. The cortisol suppressive effect is dependent on plasma concentrations with only narrow interindividual variability. The oral administration of the crystal suspension is equivalent to the administration of tablets concerning plasma levels und endocrine effects. The therapy schedule for i.m. application used here leads to lower MAP plasma concentrations and correspondingly to a minor endocrine effect than in oral therapy. Tumor effective and cortisol suppressive plasma concentrations seem to have the same level.
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PMID:[High dose medroxyprogesterone acetate in metastatic breast cancer. Comparative clinical, pharmacokinetic and pharmacodynamic data of different forms of administration]. 621 99

Based upon preliminary observations that tumor response to MPA was correlated to cortisol suppression 42 patients were treated with MPA at different dose levels. 1500 mg MPA p.o. almost completely suppressed endogenous cortisol production in 23 out of 23 patients. Consequently, 51 patients with advanced stage metastatic breast cancer were treated with Medroxyprogesteroneacetate (HD-MAP) at a dosage of 1500 mg p.o. daily or 500 mg i.m. on 5 days per week. There were 5 complete and 7 partical remissions, 23 patients with no change and 10 with progressive disease. 7 patients were not evaluable. Clinical results correlated to plasma cortisol and prolactin blood levels bot not to LH, FSH, TSH, TBI, T3, T4, ACTH and aldosterone measurements. There was no patient with relapse and suppressed cortisol or normal prolactin measurements. The development of pituituary resistance to MPA is suggested. HD-MPA was equally effective in estrogen and/or progesterone receptor positive as in receptor negative patients. It is proposed that cortisol and prolactin determinations are useful to monitor for effective MPA treatment and the early detection of MPA resistance.
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PMID:[High dose medroxyprogesteroneacetate in metastasizing breast cancer: correlations between course of the disease and hormone profiles]. 622 46

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


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