Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Canada depot medroxyprogesterone acetate (DMPA) (Depo-Provera, Upjohn Company of Canada) has been cleared for use in the management of endometriosis in the nonpregnant woman and for palliation of advanced endometrial cancer. There remains some question as to whether physicians are authorized to use this drug for other clinical conditions. The health protection branch of the Department of National Health and Welfare, after a review of the world literature and data on the clinical use of this drug for indications other than those mentioned, has concluded that the available clinical experience with DMPA shows a favorable risk/benefit ratio and that the drug does not present an undue health hazard. Since the 1st clinical studies began in the early 1960s experience with DMPA for contraception has totalled more than 10 million women years. It is estimated that over 1.2 million women in various countries are currently using DMPA for contraception and that several thousand women have used it for 10 years or longer. Available data indicate that the risk/benefit ratio for DMPA in a appropriately selected population is as favorable as that for oral contraceptives (OCs) or IUDs. These statements have been supported by many international organizations concerned with family planning. The special advisory committee on reproductive physiology of the health protection branch reviewed the October 1981 publication concerning the use of DMPA in the Ontario government facilities for the mentally retarded. Its authors considered "of borderline significance" the finding of 3 deaths from carcinoma of the breast in 533 women treated with DMPA at some time during their lives. The evidence for a causal relationship was very tenuous. The composition of the study cohort and the control group as well as the incomplete data collection made the statistical evaluation questionable. Also the higher prevalence of carcinoma of the breast in mentally retarded individuals and in patients with epilepsy and the fact that the other medications many of these patients must have taken were not reported or commented upon further confuse the issue and invalidate the inferences. From a review of the world literature it was learned that among 11,500 DMPA users in the US there have been only 4 reported cases of carcinoma of the breast, for a rate that is lower than that expected in a Canadian control population. The committee reaffirms its opinion tha DMPA is safe in the management of specific clinical problems. It is believed that there is no undue health hazard when DMPA is used to produce amenorrhea in physically or mentally handicapped individuals unable to cope satisfactorily with menstrual hygiene.
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PMID:Should depot medroxyprogesterone acetate be considered for additional uses? 713 35

The impact of three gestagens, hydroxyprogesterone caproate, norethisterone acetate, and D-norgestrel, on in vitro cell cultures was tested in 40 test tubes and ten cover glasses. All tested cultures were of endometrial carcinomas. Cytomorphological changes were recordable from more than half of all cultures and interpreted as sensitivity to gestagens of the carcinoma concerned. No differences were safely established regarding effectiveness of different gestagens and different concentrations. In vitro gestagen action was clearly demonstrated by determination of nuclear overlap indexes of the cover glass cultures. No answer has yet been found as to whether reduction in nuclear overlap index, following addition of gestagens, had been caused by cellular modification. - Sensitivity of endometrial carcinoma to gestagens in vitro depended clearly on the degree of morphological differentiation.
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PMID:[Use of gestagens to control in vitro growth of endometrial carcinoma (author's transl)]. 722 73

A 44 year old woman, multipara and healthy, started contraception with injectable medroxyprogesterone acetate in January 1978; in July 1980 severe metrorrhagia appeared and continued until December 1980 when an exploratory curettage revealed the existence of endometrial carcinoma. This diagnosis was confirmed by hysterectomy. Cases such as the one presented here are extremely rare, since medroxyprogesterone is commonly used to cure endometrial cancer. It is possible, that the adenocarcinoma was not hormone dependent since the patient was not yet menopausal, obese, or diabetic, and the dose of medroxyprogesterone used was insufficient to stop the evolution of the endometrial carcinoma. In the published literature there are no cases similar to the one presented here. In case of persistent metrorrhagia in patients treated with medroxyprogesterone acetate, an exploratory curettage is absolutely necessary.
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PMID:[Adenocarcinoma of the endometrium while undergoing contraceptive treatment with medroxyprogesterone]. 732 68

A reappraisal of endometrial cancer over the past decade reveals: 1) new concepts in its pathologic nature; 2) increase in incidence; 3) acceptance of the theory of hormonal relation; and 4) acceptance of individualization of treatment. Although endometrial carcinoma is still thought of as a predominantly well-differentiated adenocarcinoma, an increase in more virulent tumors has been seen in recent years. These include: adenosquamous carcinoma; adenoacanthoma; mesodermal sarcomas; and adenometous hyperplasia. Women at high risk for these tumors include those suffering from obesity, infertility, failure of ovulation, dysfunctional uterine bleeding, and those on long-term estrogen therapy. These women can be recognized and monitored by means of endometrial biopsy of the aspiration-curettage type. Adenomatous hyperplasia, the precursor of cancer, requires treatment with progestin or hysterectomy according to patient's age and reproductive status. Estrogens should be used only when indications are clear and in the smallest possible dose for the shortest period of time until the therapeutic goal is achieved. Aggressiveness of treatment should correspond to virulence of tumor. Dilatation and curettage under anesthesia should be used for clinical staging of endometrial cancer. Other means of treating endometrial cancers' include: total hysterectomy; bilateral salpingo-oophorectomy; iliac-aortic lymphadenectomy; pelvic irradiation; radical hysterectomy; chemotherapy, and a drug regimen (including cyclophosphamide, doxorubicin, fluorouracil, megestrol acetate).
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PMID:Current concepts in cancer: The changing nature of endometrial cancer. 735 80

The purpose of this study was to evaluate therapy with melphalan, 5-fluorouracil (5-FU), and medroxyprogesterone acetate combination (MFP) in women with metastatic or recurrent endometrial carcinoma not amenable to surgery or radiation therapy, as compared to progesterone therapy alone. Previously, the authors have treated 114 women with progesterone therapy and achieved a 15.8% objective response rate; 7.0% were complete responders. Thirteen women with documented recurrent or metastatic endometrial carcinoma were entered into the MFP study. Thirteen were evaluable for toxicity and 11 for response (2 had no measureable parameter). Treatment consisted of melphalan 0.2 mg/kg/day for 4 days every 4 weeks; 5-FU 15 mg/kg/day for 4 days every 4 weeks; and medroxyprogesterone acetate 1.0 g intramuscularly weekly. Two of the first 3 patients who were treated with this regimen developed severe thrombocytopenia (platelets, 25,000 and 17,000/mm3). Therefore, the remaining 10 patients received 5-FU at a dose of 10 mg/kg/day for 4 days every 4 weeks. Except for 1 patient who devloped thrombophlebitis, there was no other significant toxicity in the 90 courses of therapy received by the 13 women. Of the 11 women evaluable for respone, 6 (54.5%) responded (2 complete responders, 4 partial responders), 2 for stationary disease, and 3 progressed after having had stationary disease for 3, 6, and 9 months, respectively. Of special interest was that the 2 women with adenosquamous carcinoma responded and 1 additional patient with adenocarcinoma maintained a complete response with 5-FU therapy alone.
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PMID:Melphalan, 5-fluorouracil, and medroxyprogesterone acetate in metastatic or recurrent endometrial carcinoma. Preliminary report. 742 77

30 patients with advanced breast carcinoma, and 20 patients with advanced endometrial carcinoma were treated with high doses, 500 mg./day, of MPA (medroxyprogesterone acetate) administered orally for 3 months. Evaluation of results showed responses in only 30% of women treated, independently of the type of carcinoma. In the breast carcinoma group median duration of response was 10 months, and median survival time 15 months; in the second group of patients median duration of response was 15 months, and median survival time was not yet reached after 28 months of follow-up. Negative side effects were gain of body weight and hypertension; oral MPA administration seems to have a lower response rate than parenteral administration; it is, however, easier to handle, and could present a useful alternative in maintenance therapy.
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PMID:[Oral high doses of medroxyprogesterone acetate (MPA) in the treatment of advanced phases of breast and endometrial cancer]. 745 90

The migration potential through a basement membrane in an endometrial cancer cell line, such as Ishikawa, HEC-1-A or HHUA cell, in terms of strength, was enhanced by estradiol, but not modified by progesterone, medroxyprogesterone acetate (MPA), danazol or tamoxifen alone, by which estradiol-enhanced migration potential was inhibited. The order of the level of estrogen receptor was Ishikawa > HEC-1-A > HHUA cells. Therefore, it is suggested that the invasiveness of endometrial cancer cells might be activated by estradiol via estrogen receptors, but inactivated by progesterone, MPA, danazol or tamoxifen as an antiestrogen action, and that endometrial cancer cells could become invasive in the estrogen-predominant milieu, and the antiestrogenic agents could protect it.
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PMID:Estrogen activates migration potential of endometrial cancer cells through basement membrane. 750 72

We investigated the synthesis and biological effects of platelet-activating factor (PAF) in the human endometrial cancer cell line HEC-1A. We found that HEC-1A cells actively synthesize and release PAF, as demonstrated by both [3H]acetate incorporation into PAF and gas chromatography-mass spectrometry studies. HEC-1A cells not only synthesize but also respond to PAF. Indeed, in fura-2-loaded cells, PAF stimulates [Ca2+]i increase with a median effective concentration of 5.6 nM. Furthermore, PAF induces a time-dependent expression increase of the nuclear protooncogene c-fos with a median effective concentration of 130 nM and stimulates DNA synthesis (median effective concentration, 700 nM). All of these effects are inhibited by the PAF receptor antagonist L659,989. Radioligand binding studies indicated the presence of two populations of PAF receptors with affinity constants in the nanomolar and micromolar range. Since the PAF antagonist per se inhibits DNA synthesis and cell proliferation, we suggest that PAF supports an autocrine growth circuit in HEC-1A cells. On the contrary, in the uterine leiomyosarcoma cell line SK-UT-1, which does not express specific binding sites for PAF, neither this phospholipid nor its receptor antagonist affect DNA synthesis. Our results provide evidence for the existence of an autocrine proliferative loop involving PAF in the endometrial cancer cell line HEC-1A.
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PMID:Platelet-activating factor mediates an autocrine proliferative loop in the endometrial adenocarcinoma cell line HEC-1A. 752 Mar 61

To investigate the effects of progesterone on endometrial carcinoma, sulfated carbohydrate antigen was studied using a monoclonal antibody, termed E8, that reacts with sulfatide. The reactivity of monoclonal antibody (MAb) E8 with endometrial carcinoma tissues decreased when patients were treated with medroxyprogesterone acetate (MPA). A reduction of reactivity of MAb E8 with endometrial carcinoma cells was also observed in in vitro examinations using an endometrial carcinoma cell line, Ishikawa cells incubated in MPA-containing medium. Sulfated carbohydrate, such as sulfatide, is the site of binding with laminin. The binding of cell surface components with laminin is thought to be an initial step in the invasion and metastasis of carcinoma cells. The MPA-treated Ishikawa cells bound to laminin-coated dishes less [corrected] efficiently than nontreated cells. MPA treatment of endometrial carcinoma reduces the sulfatide carbohydrate on the carcinoma cell surface and may be clinically more effective in reducing cell binding to laminin.
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PMID:Progesterone treatment decreases sulfate carbohydrate antigen on endometrial carcinoma cells and inhibits the cell binding to laminin. 753 73

Estrogen receptors of human endometrial cancer Ishikawa cells were found to be present in moderate amounts (160-200 fmol/mg protein), and to specifically bind moxestrol (R2858) with a very high affinity characterized by a Kd around 60 pM, when measured under equilibrium conditions. The binding specificity respected a decreasing order as follows: estradiol (E2: 100%) > 4-hydroxy-tamoxifen (4OHTAM: 52.7%) > estriol (E3: 5.7%) > estrone (E1: 2.1%) > TAM (0.2%). The induction of alkaline phosphatase activity (APase) used as an estrogen-specific response, confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT): norethindrone (NOR), norethynodrel and levonorgestrel, at concentrations ranging from 10(-8) to 10(-6) M. The effect of NOR was partially blocked by the antiestrogen 4OHTAM, which was also partially agonistic in this model, but neither by the antiprogestin mifepristone (RU486) nor by the aromatase inhibitor aminoglutethimide. A simulatory effect was also detected at 10(-7) or 10(-6) M with ethindrone, the testosterone- (T) derived progestin homologous to NOR, and with both androgenic parent-compounds, i.e. T and 19NT themselves. In contrast, progesterone (P) derivatives like medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) remained totally inactive, as well as 19-nor-progesterone (19NP) itself or its progestagenic derivatives: ORG 2058 and nomegestrol acetate (NOM). Structure-activity relationships deduced from these studies suggest that it is not the absence of the 19-methyl group which can account for the estrogenic potential of the so-called "19-norprogestins", but rather their steroid structure derived from T in a broad sense (including the 19NT derivatives), as opposed to the non-estrogenic therapeutic progestins derived from P like MPA or CMA, or from 19NP like NOM.
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PMID:Lack of estrogenic potential of progesterone- or 19-nor-progesterone-derived progestins as opposed to testosterone or 19-nor-testosterone derivatives on endometrial Ishikawa cells. 757 23


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