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)

A multicenter, randomized, controlled trial was conducted comparing active treatment with placebo in 227 patients with breast, colorectal, lung and other solid forms of cancer. Combination therapy, (CT) conventionally employed for the various types of tumor involved, was associated with MPA (117 patients) or placebo (110 patients). MPA was given orally as tablets, as a dose of 500 mg b.i.d. for 6 months. The results were, briefly, as follows: The incidence of leukopenia was significantly lower in the groups receiving MPA in patients with breast and colorectal cancer (P less than 0.02). Tumors of the lung and other solid forms showed no such difference. The incidence of thrombocytopenia was the same in all disease groups. Objective responses (CR + PR) were observed in 23/46 (50%) of breast cancer patients treated with CT + MPA, and in 13/47 (28%) of those given CT + placebo. The difference was significant (P less than 0.02). Subjective parameters also showed more improvement in the MPA group than in the patients given CT alone. No significant differences were found for the other types of tumor, but the numbers in this population were very limited. In a group of 45 patients, antithrombin III a (%), antithrombin III R: Ag (%), plasminogen (mg/dl), alpha-2 macroglobulin (%), factor VIII C (%), factor VIII R: Ag (%) and factor IX C (%) were determined. The most interesting post-treatment findings were an increase in anti-thrombin III (activity and antigen level) and in plasminogen. This suggests that MPA does not increase the risk of thrombosis, and might even, to some extent, impede tumor-induced thrombophilia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of high-dose medroxyprogesterone acetate (HD-MPA) on hematological toxicity induced by chemotherapy for advanced solid tumors: a multicentric controlled clinical trial. MPA-Hematology Italian Cooperative Group. 287 45

This short-term study of the relative importance of estrogen and progesterone receptors shows that progesterone receptor correlates better than estrogen receptor with tumor recurrence regardless of lymph-node status. Life-table analysis has effectively identified only two groups of patients that may be classified by progesterone receptor status alone. Progesterone-receptor negativity correlated well with tumors of histological Grade III; estrogen-receptor positivity correlated with Grade I and II tumors. The earlier recurrence of Grade III breast tumors may explain why progesterone receptor is a better prognostic indicator than estrogen receptor in short-term studies.
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PMID:Relative importance of estrogen and progesterone receptor assays as prognostic indicators in primary breast cancer: a short-term study. 291 67

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

Medroxyprogesterone acetate (MPA) has been used in high doses as hormone treatment for metastatic breast cancer. We treated five intracranial meningiomas with MPA expecting that MPA would reduce the volume or decrease the growth rate. All five patients were postmenopausal women, aged 47 to 73 years. Before treatment, the growth rate of each tumour was assessed by two consecutive CT scans (CT 1 and CT 2). Tumours 1 to 4, histologically benign meningiomas, grew slowly as the tumour volumes were not found to increase in 21 to 45 months between CT 1 and CT 2. Tumour 5 was an anaplastic meningioma the rapid growth of which was evident in 8 weeks between CT 1 and CT 2. After CT 2, MPA was given 1,000 mg intramusculary once weekly for 17 to 29 weeks until CT 3 which showed the response. Tumours 1 to 4 had neither reduced in volume nor developed necroses, and tumour 5 continued its fast growth at the same rate as before.
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PMID:Hormone treatment of meningiomas: lack of response to medroxyprogesterone acetate (MPA). A pilot study of five cases. 293 93

The biologic effect of estrogen and progesterone in human uterine sarcoma is poorly understood in comparison to that of endometrial adenocarcinoma. In an attempt to elucidate the endocrine status of these tumors, we have investigated the ability of these tumors to synthesize estrogen by measuring the aromatase activity and studied the effect of aromatase inhibitors on the activity. In addition, the effect of estrogen and progesterone on aromatase activity and the growth pattern of these tumors were studied in cell culture and athymic mice systems. Aromatase activities in eight uterine sarcomas ranged from 0.7 to 37 fmol/hr X mg protein, which were within the range or higher than the activity found in normal proliferative endometrium (0.5 to 3 fmol/hr X mg of protein, means = 1.6, n = 10). These results indicate that uterine sarcomas are capable of producing estrogen. However, the enzyme activity showed no correlation with the morphology of tumors or the age of patients. Results from the kinetic studies of aromatase activity in one of the uterine sarcomas indicated that 19-nortestosterone, testolactone, and aminoglutethimide (the most effective one) inhibited aromatase activity. In addition, induction of aromatase activity in two uterine sarcomas was investigated in cell cultures. Progesterone caused an eightfold increase in activity in a sarcoma that was estrogen and progesterone receptor positive but had no effect in a tumor that was estrogen and progesterone receptor negative. The growth rate of two estrogen/progesterone receptor-negative uterine sarcomas was studied in cell culture and in athymic mice. Progestin, but not estrogen, reduced the growth rate in both systems; 30 nmol/L of estrogen had no effect on the growth rate. In summary, we have found that human uterine sarcoma is able to synthesize estrogen. Progesterone is able to induce the aromatase activity in estrogen/progesterone receptor-positive tumors, and progesterone also suppresses the tumor growth rate in estrogen/progesterone receptor-negative tumors. These results suggest that a select group of uterine sarcomas is sensitive to steroid hormone and that progesterone may be potentially beneficial for therapeutic treatment of select uterine sarcomas.
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PMID:Endocrine aspects of human uterine sarcoma: a preliminary study. 294 37

Fifteen patients with intracranial or spinal meningiomas have been treated with the semisynthetic progestational agent medroxyprogesterone acetate (MPA, Depo-Provera) prior to surgical removal of the tumors in order to investigate the influence of MPA on the progesterone receptor (PR) status of meningioma cytosols. MPA acted as a competitive binder to meningioma-PR: The mean PR values were 15.6 fmol/mg protein (range 0-69) and 338.3 fmol/g tumor (range 0-1190), respectively. In comparison, mean PR values of our untreated meningioma series (n = 58) were 54.9 fmol/mg protein (range 0-586) and 2813 fmol/g tumor (range 0-17,168), respectively. In cases of two-stage resection of meningiomas MPA significantly decreased PR activity in the cytoplasm of meningioma cells. We conclude that MPA binds to meningioma PRs, however, its effect on the growth rate of meningiomas has still to be elucidated.
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PMID:Endocrine manipulation of meningiomas with medroxyprogesterone acetate. Effect of MPA on receptor status of meningioma cytosols. 295 42

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

Because of its rare occurrence in the human, the endocrinologic and receptor-related aspects of an uterine leiomyosarcoma (LMS) are poorly understood when compared to what is known of, say, human endometrial cancer. Thus, to increase our understanding, we have succeeded, by the string method, in inducing an uterine LMS in the mouse and have studied the possibility of hormonal therapy as a method of treatment. The findings of our study are enumerated as follows: 1. The induced uterine LMS had an estrogen receptor, which was confirmed by a biochemical assay and, morphologically, by a PAP (the peroxidase anti-peroxidase technique); 2. The growth of this tumor was significantly inhibited by MPA (medroxyprogesterone acetate) therapy (100 mg/kg); 3. After MPA therapy, the estrogen receptor levels were increased, especially in the nucleus; and, 4. The growth of a secondary tumor, transplanted after the initial hormone therapy, was not inhibited by the readministration of MPA. Our results suggest that this experimentally-induced uterine LMS in the mouse provides a useful means to study therapeutic treatment, and may assist in furthering our understanding of human uterine LMS and lead to finding an effective therapy.
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PMID:[Experimental study of the treatment of uterine leiomyosarcoma in the mouse with progestogen]. 297 92

The influence of oral high-dose (HD) medroxyprogesterone acetate (MPA) and megestrol acetate (MA) treatment on steroid hormone receptor levels in metastatic breast tumor tissue was investigated. In ten postmenopausal women with advanced breast cancer, receptor biopsies were obtained from the same tumor before the start, and one and eight weeks after the start of oral HD progestin treatment. Endocrine treatment had been stopped in all patients at least five weeks before the start of progestin treatment. Estradiol receptor (ER) levels were reduced by 26.9% and 20.0% respectively after one and eight weeks of treatment. Progesterone receptors (PgR) were significantly reduced to undetectable levels, possibly due to MPA and MA binding to PgR. A stepwise decrease in androgen receptors (AR) was observed, indicating that the two progestins (MPA and MA) may also act through AR, and/or interfere with the replenishment of AR.
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PMID:The influence of progestins on receptor levels in breast cancer metastasis. 303 71

Progesterone receptors (PR) from human breast tumors were assayed by a new method using monoclonal antibodies immobilized on beads (PR-EIA, Abbott Laboratories). EIA results were compared to those obtained with the dextran-coated charcoal method using a tritiated ligand (ORG 2058). The precision and reproducibility of the EIA method were studied over a 3-month period: intra-assay coefficients of variation were less than 6% for the range of the assay (between 5-250 fmol/ml), and inter-assay coefficients of variation calculated on 13 consecutive standard curves were less than 10%, except for standard 0 (33%). PR assays performed on 78 tumors both by EIA and radioligand (RLA) were compared. The linear regression obtained was: PR-EIA = 0.81 RLA+1 fmol/mg protein (r = 0.88). For reproducibility studies, cytosols were assayed twice during a period ranging from 1 week-3 months, both by EIA and RLA. The linear regression obtained between the second assay (B) and the first assay (A) was: B = 0.98 A + 11 fmol/mg protein for RLA (r = 0.98), and B = 0.99 A-7 fmol/mg protein for EIA (r = 0.98). To study the effect of KCl on PR-EIA, 26 tumors were homogenized in 0.4 M KCl Tris buffer and assayed both by EIA and RLA. A good correlation was obtained between the 2 methods, but higher values were obtained with PR-EIA (P = 1.6) in comparison with RLA. The addition of KCl to the cytosol showed that KCl had no effect on EIA results, but significantly lowered RLA results. To study the effect of KCl on progesterone receptor isoforms, cytosols were analyzed by chromatography on TSK G3000 SW columns, and the presence of PR was detected in each fraction by both EIA and RLA. In the absence of KCl, only the oligomeric form of PR was observed; however with both techniques, detection of this form different from tumor to tumor, emphasizing the inter-tumoral molecular heterogeneity of PR. After PR isoform dissociation by KCl (0.4 M) and chromatographic analysis of the forms obtained, monoclonal antibodies detected PR molecular forms different from those observed by radioligand; furthermore, chromatographic patterns obtained were different from one tumor to another and confirmed the inter-tumoral molecular heterogeneity of the progesterone receptor.
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PMID:Monoclonal antibodies for progesterone receptor assays and polymorphism studies in breast cancer. Comparison with radioligand assays. 305 54


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