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)

-It has been shown that ovarian steroid hormones can reduce the incidence of cardiovascular disease in postmenopausal women. As hormone replacement therapy for postmenopausal women, progestins are added to estrogens to eliminate the increased risk of endometrial cancer. However, the effects of progestins on the atherogenic process have not been well understood. In the present study, we examined the effects of progestins on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Immunocytochemical analysis revealed the presence of progesterone receptors in HUVECs. Progesterone clearly inhibited tumor necrosis factor-alpha-activated expression of VCAM-1 protein and its mRNA in HUVECs. Synthetic progesterone receptor agonist R5020 also inhibited the tumor necrosis factor-alpha-activated VCAM-1 expression, whereas medroxyprogesterone acetate (MPA) failed to do so. Electrophoretic mobility shift assays demonstrated that progesterone, but not MPA, inhibited DNA binding of the transcription nuclear factor-kappaB, which is critical for the inducible expression of VCAM-1. Because the expression of VCAM-1 is one of the earliest events that occurs in the atherogenic process, this adhesion molecule might be a target molecule for progesterone on vascular walls. The contrasting effects of progesterone and MPA seem clinically important, inasmuch as MPA is a widely used progestin in the regimen of hormone replacement therapy.
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PMID:Progesterone, but not medroxyprogesterone, inhibits vascular cell adhesion molecule-1 expression in human vascular endothelial cells. 1115 60

Fifteen cases of endometrial cancer were administered daily doses of 600 mg of MPA after surgery to prevent the recurrence of cancer. The initiation times of coagulation (time necessary for fibrin network formation) were measured with a highly sensitive damped oscillation rheometer and compared with those of 15 control patients who were not administered MPA. Biochemical studies of blood coagulation and fibrinolysis were also done. The initiation times of coagulation were 19.0+/-1.8 minutes (min mean +/- standard deviation) after 3-6 months and 16.0+/-2.0 min after 9-12 months of MPA administration, both times being significantly shorter compared with the controls (24.0+/-2.5 min). Hematocrit values, platelet counts and fibrinogen levels were similar between the two groups. Activated partial thromboplastin time (APTT) was significantly decreased and antithrombin III activity (AT III), thrombin-antithrombin complex (TAT), plasminogen level, plasmin-alpha(2) plasmin inhibitor complex level (PIC) and the fibrin degradation product level (FDP) were significantly increased in the MPA group compared with the control group. Accelerated coagulation of blood was definitely induced by high-dose MPA but antithrombin and fibrinolytic activities were also induced, and, thus, thromboembolic complications were prevented.
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PMID:Effect of high-dose progestogen on hemostatic properties of blood in patients with endometrial cancer. 1138 Nov 84

Recently, the number of cases of endometrial cancer has increased in Japan. Most of the increase are accounted for by premenopausal cases, which are frequently positive for ER or PR. Hormonal treatment using progestins such as MPA has been widely applied to endometrial cancer patients under 40 years old under the conditions of grade 1 well-differentiated endometrioid adenocarcinoma without myometrial invasion. In our hospital, we applied high-dose (600 mg/day) MPA for over 8 weeks in 14 cases of endometrial cancer, of which adenocarcinoma disappeared in 12 cases (86%), followed by cyclic administrations of low-dose MPA, with 7 subsequent recurrences. We think that a protocol for improving ovarian function, such as active induction of ovulation, should be established to induce intrinsic progesterone sufficient for the prevention of the recurrence of endometrial cancers. In the 2 cases, in which adenocarcinoma remained even after long administrations of MPA, myometrial invasion was noted in the surgically resected specimens. For advanced or recurrent endometrial cancers, MPA has been reported to be effective in an average of 26% in several reports, and effective in 42% cases when applied with combination chemotherapy, such as CAP, by virtue of the "chemical modulator" effect, which can delay the acquired resistance against ADM or CDDP. Furthermore, MPA has resulted in a significant improvement of 5-year disease-free survival rate when used as adjuvant therapy after complete operations and whole pelvic irradiation, compared with administrations of 5-FU in a randomized controlled study in Japan. Thus, in the future, we consider that hormonal therapy will play a more important role in endometrial cancer treatment.
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PMID:[Hormonal therapy for endometrial adenocarcinoma]. 1147 42

Two injectable forms of hormonal contraception, depot medroxyprogesterone acetate (DMPA, Depo-Provera) and medroxyprogesterone acetate/estradiol cypionate (MPA/E(2)C, Lunelle), are now available to American women. Both formulations have demonstrated high degrees of efficacy, safety, and ease of use in international and U.S. trials. Data on DMPA have shown a number of noncontraceptive and therapeutic benefits, the most prominent of which is an 80% reduction in the risk of endometrial cancer. Although such benefits are less documented for MPA/E(2)C, they are expected to be similar to those seen with DMPA and oral contraceptives. Minor side effects of both formulations include menstrual irregularities in the early months of treatment and amenorrhea with DMPA. Patient counseling about the potential for these side effects, as well as possible risks, is important to long-term successful use of these contraceptive methods.
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PMID:Current options for injectable contraception in the United States. 1172 75

The median survival of women with advanced or recurrent endometrial cancer is less than one year. Only half the women with early stage endometrial cancer and poor prognostic factors such as high grade or deep myometrial invasion will survive for 5 years. Over the past decade, incredible strides have been taken in evaluating systemic therapy for this disease. However, survival rates remain poor. A literature search was conducted using CANCERLIT, EMBASE, Medline, Investigational Drug database (Current Drug Ltd.) and R&D Focus (IMSworld Publications). The references of the articles were also explored. Search terms included: endometrial cancer, chemotherapy, endocrine/hormonal therapies, molecular biologics, and specific drug names. Progestin therapy offers a 10-20% response rate and survival of less than 1 year. Progestins are most effective in women with well-differentiated tumours and a long disease-free interval. There is no role for adjuvant progestin therapy in early stage disease. Single-agent chemotherapy with the most activity includes ifosfamide, cisplatin/carboplatin, doxorubicin and paclitaxel. Combination chemotherapy provides a response rate of 40-60%; however, median survival is still less than a year. New areas of research include the identification and evaluation of new active endocrine therapies (i.e. LY353381.HCl and letrozole), chemotherapeutics (i.e. herceptin), evaluating chemotherapeutic agents in combination (i.e. paclitaxel, doxorubicin and platinum), in addition to radiation or instead of radiation. New avenues under development involve the specific molecules and pathways responsible for the initiation and growth of endometrial carcinoma, including: tumour suppressor genes, DNA mismatch repair genes, oncogenes, molecules involved in adhesion and invasion and angiogenesis. Further significant advances in radiotherapy, hormonal therapy and chemotherapy are unlikely. Exciting developments in understanding the molecules involved in tumour development and metastasis will allow the development of specific and selective inhibitors.
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PMID:Current status and future innovations of hormonal agents, chemotherapy and investigational agents in endometrial cancer. 1180 79

Progesterone is a critical steroid hormone that controls cell proliferation and differentiation in the female reproductive tract. Progesterone acts through two nuclear receptor isoforms, progesterone receptors A and B (PRA and PRB, respectively), each with unique cellular effects. Loss of PRB has recently been linked to the development of poorly differentiated endometrial tumors, a lethal form of cancer. To study the molecular effects of progesterone, progesterone receptors were introduced into Hec50co endometrial cancer cells by adenoviral vectors encoding either PRA or PRB. Progesterone induced the cyclin-dependent kinase inhibitors p21 and p27, thereby significantly reducing the percentage of proliferating cells. Cancer cell invasion was also markedly inhibited as measured by Matrigel invasion studies. Similarly, a differentiated, secretory phenotype was induced by progesterone in cells expressing PRB. However, replicative senescence was induced by progesterone only in cells expressing PRA. Expression array analysis followed by confirmatory semiquantitative reverse transcription-PCR experiments demonstrated a significant progesterone-dependent inhibition of expression of a cadre of cellular adhesion molecules, including fibronectin, integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of down-regulation of adhesion molecule expression was significantly greater in the presence of the B isoform, demonstrating that progesterone acts principally through B receptors to inhibit cancer cell invasiveness modulated by adhesion molecules.
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PMID:Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. 1183 May 47

Progesterone has been used in the treatment of patients with recurrent or metastatic progesterone receptor-positive endometrial carcinoma and breast cancer. In vitro study using a breast cancer cell line, T47D, demonstrated an increase in p53 gene expression and induction of apoptosis by the administration of progesterone. Therefore, we investigated the effect of progesterone administration on the proliferation and apoptosis in a mesothelioma cell line, 211H. The expression of the progesterone receptor gene was detected in this cell line by a nested RT-PCR method. The proliferation of the cell line was suppressed after a 10-day incubation with 30 microM progesterone. In progesterone-treated 211H cells, apoptotic cells were detected by TUNEL assay and nuclear DNA fragmentation analysis. These results clearly demonstrated that progesterone administration suppressed the cell proliferation and induced apoptosis in malignant mesothelioma cells.
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PMID:Progesterone induces apoptosis in malignant mesothelioma cells. 1191 Dec 61

Progestin-only injectables are among the most effective and safe of all contraceptives, yet they are not widely used in many countries. This limited use is in part due to a lack of accurate information about health concerns, inadequate counseling for users about managing side effects, and their limited availability. Where they are available, progestin-only injectables rapidly become one of the preferred methods. Depot-medroxyprogesterone acetate (DMPA) and norethindrone enanthate (NET-EN) are the two progestin-only injectables in use worldwide. The former drug is sold under the brand name Depo-Provera, and the latter as Noristerat. DMPA is delivered in a water-based, crystalline suspension and absorbed gradually by the body. The normal injection of 150 mg is intended to be administered every three months, but contraceptive protection continues for an additional two weeks to provide a grace period for women who are late receiving their next injection. NET-EN is an oily solution which requires a larger needle than DMPA for injection. A 200 mg injection of NET-EN is usually administered every two months. Both of these safe, highly effective drugs are injected in either the upper arm or buttocks. DMPA and NET-EN can be distributed easily in nonclinical settings where nonphysicians can provide them to clients. The main disadvantage of the method is the disruption of the menstrual cycle, but that is generally not a serious medical problem. Focusing mainly upon DMPA, this article includes discussion of menstrual irregularity, the reduced risk of endometrial cancer among DMPA users, and method availability.
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PMID:Progestin-only injectables offer many advantages. 1228 28

Among 30-40 year old women, 40% of pregnancies are unplanned, which is indicative of the unreliability of the birth control methods they are using. The 1992 Ortho Birth Control Study interviewed almost 7000 women, of whom 8% listed withdrawal and 4% listed the rhythm method. These two methods have failure rates of 24% and 19%, respectively. Birth control methods often disappoint the users and increasingly they turn to sterilization. 48% of married women aged 15-44 had themselves been sterilized or had a sterilized partner in the Ortho survey. Although reversal of tubal ligation succeeds in 43-88% of cases, conception cannot be guaranteed. For women over the age of 30 who are healthy and do not smoke, low-estrogen or no-estrogen oral contraceptive pills are considered safe. Taking the pill also helps prevent ovarian and endometrial cancer. The failure rate is 6%. Barrier methods also offer protection from sexually transmitted diseases including HIV. Condoms are favored by 33% of unmarried women and 19% of married women. Sexually active 40-44 year old unmarried women run a 14-19% risk of contracting a sexually transmitted disease (STD) in a 12-month period. Diaphragms offer some protection against STDs, but their failure rate is 18%. IUDs are regaining popularity, but only 1% of women use them (ParaGard T380A or Progestasert). Pelvic inflammatory disease is the reason: a 1992 study showed that 0.97% of women developed it within 20 days of use. Norplant is a long-term implant containing levonorgestrel with a failure rate of 0.5%. A 1993 study followed 1253 implant users over 12 months and found a very low rate of pregnancy, but 75% experienced some side effects during the first year. About half of the women using Norplant removed it after 2.5 years because of irregular bleeding. Depo-Provera is an injectable administered every 3 months, but after removal it can take up to a year for ovulation to return. Side effects may include hair loss and weight gain; and links to breast cancer have also been suggested.
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PMID:Birth control over 30. 1229 85

The steroid hormones are recognized and fixed by special cytoplasmic proteins in the target tissue called receptors. Most circulating natural steroids are tied to transport proteins. Estradiol and progesterone are active as such in the receptor cells, but testosterone is transformed into dihydrotestosterone in situ under the influence of the enzyme 5 alpha reductase before combining with the receptor. Receptivity may be exacerbated or reduced. Exacerbation is particularly likely when physiological control mechanisms are deficient. Testosterone has a biological effect at the level of the Wolfian apparatus in the embryo and in the muscle and bone of the adult. The activity of perineal 5 alpha reductase implicated in these phenomena and the hepatic 5 alpha reductase activity implicated in the degradation of testosterone are found in both sexes and are under genetic influence independent of the male hormone. Problems in receptivity to the male hormone are well known to clinicians. Hirsutism, whatever its cause, is always associated with great cutaneous 5 alpha reductase activity. The use of antiandrogens derived from synthetic progestagens has transformed treatment of hirsutism. Male pseudohermaphrodism may be secondary to an insufficient testosterone production or to primary resistence to the male hormone, in which case the plasma concentration of testosterone is always greater than normal. The characteristic case is of a deficit of 5 alpha reductase and feminization of the testicle. 5 alpha reductase deficiency causes sexual ambiguity at birth. Absence of the testosterone receptor at both the perineal and public levels explains why attempts to treat these disorders with high doses of testosterone or dihydrotestosterone always fail. Problems in receptivity to the male hormone have been found to cause other pathologies, such as severe oligospermia. The quantity of estradiol and progesterone receptors varies according to the volume of circulating estradiol and of progesterone. Progesterone is a natural antiestrogen; it limits the activity of estradiol by favoring the transformation of estradiol into estrone and decreases the synthesis of estradiol receptors. The normal endometrium may become hyperplasic after menopause, the 1st stage in development of endometrial cancer. Continuous estrogen stimulation not countebalanced by progesterone permits the transformation. Study of estradiol and progesterone receptors in mammary fibroadenomas has shown that estradiol receptors increase to a maximum in the preovulatory period and diminish in the luteal phase. The increase in estradiol is followed by an increase in progesterone receptors. Since 1971 it has been apparent that breast cancer susceptible to improvement by hormonal treatment were rich in estrogen receptors.
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PMID:[Receptivity to the sex steroids, physiopathological aspects]. 1231 77


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