Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:APRD00627 (MAP)
 15,705 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

Hormone deprivation may cause remission in women with advanced breast cancer. Occasionally this remission may last for 15 years. However, only 30% of women respond in this way. An essential 1st step in the response of hormone-sensitive tissues is binding of the hormone to a receptor protein in or on the target cell. For steroids, receptors have been found in the cytoplasm, while for polypeptide hormones, receptors seem to be on the surface of cell membranes. Between 40-85% of human breast cancers contain estrogen receptors. If estrogen receptors are present, 43-60% of patients have responded to endocrine therapy, whereas only 8% have responded if estrogen receptors were not present. Treatment with antiestrogens has achieved 16% response rates in patients in whom estrogen receptors were not present. Progesterone receptors have been detected in 57% of breast cancers, together with estrogen receptors in 49%. The significance of this finding is not apparent. The main peptide hormone implicated in promoting growth of breast cancers is thought to be prolactin. Growth hormone and human lactogen have also been implicated in promoting breast cancer. Receptors may be detected in human breast, prostate, endometrial, and other cancers and these preferentially bind estrogen, androgen, progesterone analogue, prolactin, growth hormone, or placental lactogen. The heterogeneity of human cancers is thus shown. Most remissions are short-lived and after relapse there is less chance for antihormonal therapy. To choose the best treatment at a given time the most hopeful prospect is that investigations may determine criteria for the study of the particular cancer in each patient.
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PMID:Editorial: Hormone receptors and breast cancer. 17 60

Aldehyde-resistant, diaminobenzidine-stained endogenous peroxidases form ideal markers for the biochemical endpoints of hormone stimulation and differentiation of certain mammalian cells and tissues. The lactoperoxidase (LPO)-type of endogenous peroxidases are synthesized by the acinar cells of the salivary, Harderian, lacrimal and mammary glands and are present in their secretions. These LPO-type enzymes, that are inhibited by cyanide and aminotriazole, appear to operate extracellularly as bactericidal agents in milk and in other biological fluids. In the mammary gland, lactoperoxidase is a consistent marker enzyme for differentiated acinar cells engaged in lactogenesis. Myeloperoxidase (MPO)-type endogenous peroxidases are prominent markers for the GERL endomembrane system and differentiated lysosomes in certain cells of the reticuloendothelial system and phagocytes. MPO is prominent within eosinophils, peritoneal macrophages and in Kupffer cells. The MPO-type endogenous peroxidases function primarily within lysosomes as bactericidal agents. Thyroid peroxidase (TPO) is relegated to the cisternae of the granular endoplasmic reticulum and Golgi apparatus, to apical cytoplasmic vesicles and to the luminar cell membrane surface of acinar cells. The enzyme is probably activated at release and functions both in the organification reaction (T leads to To) and in the biosynthesis of thyroxine. Thyroid stimulating hormone (TSH) appears to play a key role in the regulation of TPO levels and activity in the thyroid gland. Certain tissues displaying growth-dependency on estrogen (i.e., uterus, cervix, vagina and the DMBA-induced rat mammary tumor) synthesize and secrete endogenous peroxidase into their lumina. These enzymes serve as important marker proteins of estrogen action, in that they occur distal to the binding of estrogen to its receptor protein. Estrogen antagonists, particularly CI-628 (Parke-Davis) and Nafoxidine (Upjohn) that appear to function through the estrogen receptor mechanism, also induce synthesis of the reproductive tract endogenous peroxidase but inhibit growth of these tissues. Progesterone antagonizes the synthesis of the reproductive tract peroxidases and inhibits growth of the tissues as well, in part, through the reduction of the cytosol estrogen receptor protein. Endogenous peroxidase activity appears to represent a reliable marker for rodent breast cancer tissues displaying dependency for estrogen and is of potential interest as a diagnostic marker protein in human breast cancer. Rat uterine peroxidase (UP) has been investigated by microelectrophoretic techniques. The molecular weight of UP has been determined in the range of 100,000 by using polyacrylamide gradient gels in the absence and presence of nonionic and anionic detergents. The isoelectric point of UP is located between pH 4.5 and 5.9. Employing the two-dimensional combination of isoelectric focusing and gel gradient electrophoresis, UP was separated into two subunits, one having a molecular weight of 70,000, the other less than 20,000.
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PMID:Mammalian endogenous peroxidases as cellular markers and as biosynthetic endpoints of hormone-mediated activity: viewpoint from cytochemistry. 22 20

An overview of the sex hormones is presented. Testosterone is a natural androgen produced in the testes, adrenal glands, and ovaries. It has anabolic as well as androgenic effects. Testosterone is used to treat inoperable breast cancer and osteoporosis, and to stimulate erythropoesis. Androgens are absolutely counterindicated in cases of prostate cancer. Estrone, estradiol, and estriol are natural estrogens produced in the ovaries, placenta, testes, and adrenal glands. These hormones also influence the production of gonadotropins by the pituitary gland. Estrogens are used to treat menopausal disorders, ovarial insufficiency, estrogen-independent breast cancer, prostate cancer, and in some cases pregnancy disorders. Estrogens and progestagens are 2 components used in oral contraceptives. Progesterone, a natural progestagen, is produced by the corpus luteum. It promotes the proliferation phase of the endometrium, fertilization, and nidation, and it works to maintain pregnancy. Progesterone is used to treat spontaneous abortion, corpus luteum insufficiency, and endometrial cancer.
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PMID:[Sex hormones]. 24 26

Drug toxicity testing is required by the U.S. Food and Drug Administration in bitches of beagle dogs for 7 years and in female rhesus monkeys for 10 years at 25-50 times the human dosage. Progesterone, medroxyprogesterone acetate, megesterol acetate, chlormadinone acetate, chloroethynl norethisterone and chloroethynyl norgestrel are some compounds which have induced tumors in beagle dogs. However, the endocrinology of the beagles is unlike that of a woman and binding affinity of synthetic progestogens to breast cytoplasmic progesterone receptors of the beagle and women have striking differences. Some progestogen compounds which do not produce neoplasia in dogs because of too low a dose are most potent in women. Both the WHO and the Committee on Safety of Medicines concluded that progestogen-induced breast tumors in beagles are unhelpful in predicting possible breast cancer in women who use oral contraceptives.
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PMID:Hounding the pill. 31 66

The results obtained with a new hormone therapy using medroxyprogesterone acetate (MAP) in previously untested single and total doses in the treatment of advanced breast cancer are reported. Fifty-two postmenopausal patients were treated with an average total dose of 40 g of MAP for a period of 30 days. Nineteen of 44 patients (43%) had complete or partial remission, while the disease remained unchanged in nine of 44 patients (20%). Disease progression occurred in 12 of 44 patients (27%). Partial or complete remission occurred in 12 of 18 (67%) and four of six (67%) of the patients with dominant osseous and soft tissue metastases respectively. Three of ten (16%) of those with visceral metastases had remission. The average duration of remission was 7 months. Average survival times were 15.5 months for patients with remission, 8 months for those with no change, and 2.5 months for those with disease progression. From a subjective standpoint, pain was reduced significantly or disappeared in 34 of 36 patients (94%); this was also the case with respect to dyspnea (13 of 16 patients [81%]), anorexia (24 of 29 [83%]), asthenia (28 of 35 [80%]), and walking impairment (15 of 24 [63%]). When relapse occurred, patients previously treated with massive doses of MAP received further treatment with higher doses of MAP; four of 22 (18%) of the patients attained partial remission once again. Positive effects were also seen in subjective performance status, body weight, and EKG. We also describe the new clinical and toxicologic features of this treatment.
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PMID:A possible new approach to the treatment of metastatic breast cancer: massive doses of medroxyprogesterone acetate. 35 Mar 87

(MPA) Medroxyprogesterone acetate when employed at high doses (5001000 mg/day intramuscularly) can produce objective remission with improved survival in about 30% of postmenopausal women with advanced breast cancer resistant to cytotoxic drugs and endocrine therapies. When administered to women not previously treated with chemotherapy, the objective remission response rate reached 40%. From available evidence, high dose MPA can be considered a useful agent in the treatment of advanced breast cancer in postmenopausal women with soft tissue, pulmonary, pleural, or osseous involvement even when patients have become refractory to prior hormone and cytotoxic therapies. Early results suggest that the response rate can be increased in patients with estrogen-and/or progesterone-positive receptors. It is noteworthy that in a study conducted on postmenopausal women resistant to cytotoxic and/or hormonal drugs, the median duration of survival was 13.5 months, while CRs and PRs did not reach the median at 24 months after beginning MPA treatment. High dose MPA is essentially devoid of major side effects. Relief of pain, increase in appetite, and body weight, and sense of wellbeing are characteristic features of the improved quality of life under MPA treatment. However, a gluteal abscess (from 2-20% dose-related) is the most frequent side effect. A promising area for future studies is combined therapy using hormonal and cytotoxic agents or alternating sequential combinations. Well-designed studies are needed to develop means for increasing the complete response rate and therefore survival. Recent studies of combined chemotherapy and hormonal (MPA) therapy have yielded objective tumor regressions of 53-80% with an increased rate of complete remissions and duration of response. (Author's modified)
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PMID:High-dose medroxyprogesterone acetate (MPA) treatment in advanced breast cancer. A review. 39 Jul 98

Estrogen receptors (ER) were measured on specimens taken from 27 patients with benign breast conditions and 109 patients with breast cancer. Using sucrose gradient assay, 15% (4/27) of benign lesions and 56% (61/109) of malignant tumors were estrogen receptor-positive (ER-positive means 8S or 8S+4S levels more than 7 fmoles/mg cytosol protein). Progesterone receptors (PR) were tested on specimens from 28 patients and 39% (10/26) of the cancers were PR-positive. ER protein activity was not correlated with stage, histology, size of primary lesions, or extent of axillary or distant metastasis. Tumors with low ER levels are more likely to recur, and recurrent tumors after longer disease-free intervals are more likely to be ER-positive. Detailed analysis showed that ER levels did correlate with age and serum albumin levels. Concentrations of serum alpha1-globulin were decreased, while IgG and IgM were significantly increased among patients with positive ERs. Eighteen evaluable patients with advanced breast cancer had endocrine therapy, 13 had objective response. Twelve of these 13 had 8S receptor above 10 fmoles/mg, or 4S above 15 moles/mg, or 8S+4S above 25 fmoles/mg. The one exceptional patient had tumor with high PR but without detectable ER.
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PMID:Steroid receptors study in breast carcinoma. 74 84

A simple method for the assay of specific progesterone receptors in breast cancer tissue is described. Progesterone receptors were detected in 63 of 74 breast cancer specimens (85%). Estrogen receptor positive tumors had a wide range of progesterone receptor concentrations, but in 77% of cases the level was above 3 fmol/mg protein. The progesterone receptor level was generally low in tumors lacking estrogen receptors, 75% of the samples having concentrations between 0 and 3 fmol/mg protein. Unlike estrogen receptors, age had no influence on the number of progesterone receptors in breast cancer tissue.
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PMID:The determination of progesterone receptors in breast cancer and their relationship to estrogen receptors. 96 95

The clinical and experimental literature on the relation of estrogen, progestins, and oral contraceptives (OCs) to breast cancer, benign breast lesions, and cervical cancer is reviewed. Experimental studies on the relation of estrogens and OCs to mammary lesions indicate a varying response that largely depends up on the species and strain of animal studied. Various clinical studies have failed to show that estrogens or OCs cause breast cancer; similar findings have been reported in animal studies. Estrogen has been found to increase the incidence of cervical cancer in certain strains of mice, although such an effect has not been demonstrated in other species and man. Most studies agree that OCs do not adversely affect the incidence of abnormal Papanicolaou smears, cervical dysplasia, cervical cancer in situ, or invasive cervical cancer. Progesterone has effectively brought about remission in cases of cervical cancer, as have progestins in cases of breast cancer.
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PMID:Oral contraceptives: relations to mammary cancer, benign breast lesions, and cervical cancer. 109 91


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