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)

Different subcellular fractions (purity checked by electron microscopy and respective marker enzymes) were incubated with 0.1 muCi 14C-progesterone (10 muM) in 0.15 M phosphate buffer at pH 7.4 and 37 C under air for varying periods of time in the presence of NAD(P)H (500 muM). By the preparation of chromic acid oxidation products and acetates, thin-layer chromatography, and crystallisation to constant specific activity, the following metabolites were identified: 20alpha-hydroxypregn-4-en-3-one, 20alpha-hydroxy-5alpha-pregnan-3-one, 20alpha-hydroxy-5beta-pregnan-3-one, 5alpha-pregnane-3,20-dione, and 5beta-pregnane-3,20-dione, indicating the presence of a 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) and 5alpha- and 5beta-reductases. Most of the 20alpha-HSD activity was located in mitochondria (associated mainly with outer membranes) and microsomes. Purified nuclei and cytosol contained 1/6 to 1/18 of the activity of mitochondria and microsomes, respectively. SUBFRACTIONS OF ENDOMETRIAL CELLS ONLY CONTAINED EITHER 5ALPHA- OR 5BETA-REDUCTASE ACTIVITY. 5alpha-reductase activity was mainly associated with microsomes, 5beta-reductase activity was found only in the cytosol. While in normal endometrium specific enzyme activities in subcellular fractions depended on the phase of the cycle, in endometrial carcinoma it depended on the degree of tumour differentiation. The highest values of 5alpha-reductase activity were found in the early proliferative phase. 20alpha-HSD activity was highest in the middle of the secretory phase. The specific activity of the 5alpha-reductase increased with decreasing differentiation of the tumour while the specific activity of the 20alpha-HSD decreased. Kinetic parameters (Km-values, coenzyme requirements and maximum velocities) were determined. The Km-value for progesterone of the 20alpha-HSD in proliferative endometrium was significantly higher than in secretory endometrium, while the Km-values of the 5alpha- and 5beta-reductases were considerably lower during the proliferative than secretory phase.
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PMID:Progesterone metabolism in normal human endometrium during the menstrual cycle and in endometrial carcinoma. 24 Aug 67

Metastatic serosal and omental implants from a primary papillary endometrial carcinoma were well demonstrated by radionuclide uptake on a bone scan utilizing 99mTc-methylene diphosphonate. Imaging of an endometrial malignancy by a 99mTc-labeled phosphate compound has not previously been reported. While the exact mechanism of accumulation in such soft-tissue neoplastic foci is not known, several possibilities have been suggested. In this particular case, the mechanism appears related in some way to the presence of dystrophic calcifications within the metastatic deposits.
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PMID:Metastatic abdominal implants of endometrial carcinoma demonstrated on 99mtc-methylene diphosphonate bone scan. 69 48

Nineteen evaluable patients with advanced endometrial cancer refractory to one prior chemotherapeutic regimen were treated with a 5-day schedule of fludarabine phosphate. No responses were noted. The major toxicity was grade 2 or greater leukopenia in 45% of patients. Fludarabine phosphate at this dose and schedule does not appear to be an active agent for patients with refractory endometrial cancer.
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PMID:Phase II study of fludarabine phosphate (NSC-312887) in patients with advanced endometrial cancer. A Southwest Oncology Group Study. 170 56

This updated literature review on heterosteroids and drug research has information on chemical structure, pharmacology, and effects. It first discusses the anti-inflammatory heterosteroids, such as mometasone furoate and cortivazol. It also covers heterosteroidal antimineralocorticoids and anabolic hetero derivatives. The review discusses at length the 19-norsteroid, mifepristone (RU-486), which exhibits antiprogestational activity and is being used for fertility control in women. It also has antiglucocorticoid activity and shows promise as a treatment of diseases characterized by muscle atrophy. In vitro studies indicate that mifepristone inhibits growth of breast cancer cell lines and of endometrial cancer cell lines. It has already exhibited growth inhibitory effects in some breast cancer patients. Discussions of mifepristone's pharmacokinetics and structural modifications of mifepristone follow. Danazol is an antigonadotropin and is used to treat endometriosis, benign breast disease, precocious puberty, hereditary angioneurotic edema, menorrhagia, some types of infertility, and gynecomastia. Danazol effects considerable changes in lipid metabolism. Other hormonal, antihormonal, and/or antifertility heterosteroids and/or aspects include androgen antagonists (e.g., cyproterone acetate), estrogen activity, antiestrogens, STS-557, and oximinosteroids. Heterosteroidal inhibitors of steroid hormone biosynthesis discussed are aromatase inhibitors, 5 alpha-reductase inhibitors, and 3 beta-hydroxysteroid dehydrogenase inhibitors (trilostane, epostane, and azastene). Heterosteroids affect the cardiovascular system, including the cardiac glycosides, antiarrhythmic agents, and antilipemic agents. Some heterosteroids affect central nervous system activity (e.g., RU-5135 causes convulsions in rodents). Pancuronium analogues and chandonium and analogues are neuromuscular blocking azasteroids. In addition to danazol and RU-486, several other antineoplastic heterosteroids exist (e.g., estramustine phosphate sodium, a prostate cancer drug).
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PMID:Heterosteroids and drug research. 184 48

Incubation with estramustine phosphate for 24 h inhibited DNA, RNA and protein synthesis in primary cultures of human kidney, mammary, prostatic, cervical and endometrial carcinoma. Not only the presence, but also the concentration of oestrogen receptors correlated with estramustine phosphate effects on tumour cell proliferation.
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PMID:Presence of oestrogen receptors on target cells and antiproliferative activity of estramustine phosphate: positive correlation for human tumours in vitro. 203 92

The ultimate role played by peritoneal cytologic evaluation in endometrial cancer remains somewhat ill-defined. Proper assessment of peritoneal cytology as an independent risk factor awaits a prospective study in which patients with malignant peritoneal cytology and surgical Stage I lesions are not treated and survival is compared to controls with negative cytology. Such a study is unlikely to be done, given results available from retrospective analyses and the large number of patients needed to complete such a trial. Whether therapy is needed and which type to use in patients with malignant cytology remain uncertain. Half of these patients will presumably require pelvic radiotherapy for adnexal, nodal, or other pelvic spread. Potish et al. have advocated the use of whole-abdominal radiotherapy in such patients, with favorable results. In patients without extrauterine spread, Creasman et al. have championed the postoperative use of intraperitoneal radioactive phosphate. They based their recommendation on survival results in a group of 23 patients with positive washings who were treated with intraperitoneal radioactive chromic phosphate. In this group, the recurrence rate was reduced, when compared to historic controls, to 13% (3/23), all of whom had extra-abdominal recurrences. Soper et al. confirmed the safety of postoperative radioactive chromic phosphate in doses of approximately 15 millicuries in patients with endometrial cancer. In their study of 65 patients, 56 had percutaneous catheter placement under local anesthesia after laparotomy. In one patient, the catheter could not be used because of poor distribution of the technetium Tc 99m sulfur colloid tracer, and in a second subject, fever and peritoneal signs suggesting bowel perforation led to removal of the insertion catheter. No other significant problems were encountered in 48 patients treated with radioactive chromic phosphate without other therapy. In contrast, five of seventeen patients who received external pelvic radiotherapy in addition to radioactive chromic phosphate suffered bowel complications requiring surgical intervention. Two of these patients died of operative complications, suggesting that radioactive chromic phosphate cannot be safely combined with standard dose external radiotherapy. In a retrospective series, Mazurka et al. intimated that adjunctive chemotherapy might be useful in patients with malignant cytology, but such an approach is untested. A prospective randomized study of radioactive chromic phosphate, whole abdomen radiotherapy, or adjunctive chemotherapy versus no treatment in patients with malignant peritoneal cytology is clearly needed.
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PMID:Peritoneal cytology in endometrial carcinoma. 257 1

Previously we demonstrated the polymorphism of estrogen receptors (ER) in cytosol of various tissues based upon properties of size, shape and surface charge. This study describes the application of a multidimensional approach utilizing HPLC for characterization of ER. Cytosols from human uterus and endometrial carcinomas were characterized sequentially by high performance size exclusion chromatography (HPSEC) on Spherogel TSK-3000 SW, and high performance ion-exchange chromatography (HPIEC) using SynChropak AX-1000 anion exchange columns. Using HPSEC, specific estrogen binding was exhibited by a 30 A isoform and by one appearing after the V0 (approximately 60 A) in human uterus. However, in endometrial carcinoma other smaller binding components with Stoke's radii of less than 20 A were observed also. In buffers containing 400 mM KCl, predominantly a 28-30 A species was observed by HPSEC. Further characterization of the 28-30 A isoform from low and high salt elution from HPSEC was accomplished with an AX-1000 column. With either condition, 2 forms were eluted on HPIEC, 1 in the column wash (retention time 8-9 min), and the other at 50-70 mM phosphate. The elution profile of the larger species (approximately 60 A by HPSEC) on the ion-exchange column was time dependent. Immediate analysis (within 15 min) showed a profile similar to that of the original cytosol which contained minor components eluting in wash buffer and at 50-70 mM phosphate and a major isoform at 180 mM phosphate. However delayed analysis (after 2 h) of the 60 A isoform showed a similar profile (components in buffer wash and at 50-70 mM phosphate) obtained with the 30 A species. This time dependent change was not observed for the 30 A species or for the original cytosol. Estrogen receptors in cytosol sedimented at 10S and 4S in low ionic strength gradients and at 4S in sucrose gradients containing 400 mM KCl. The 28-30 A and 60 A species recovered from HPSEC sedimented at 3.5S. This multidimensional approach indicates that native estrogen receptors dissociated into a number of smaller molecular isoforms, which were distinguishable by different surface charge properties.
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PMID:HPLC analysis of estrogen receptor by a multidimensional approach. 373 41

Malignant peritoneal cytology in patients with endometrial carcinoma is a poor prognostic feature, identifying patients at high risk for early intra-abdominal recurrence. Between 1977 and January, 1983, 65 women with endometrial carcinoma who had malignant peritoneal cytology were treated with adjuvant intraperitoneal radioactive chromic phosphate P 32 suspension. Fifty-three patients (80%) were clinical Stage I, nine (14%) were Stage II, and three (7%) were clinical Stage III. Life-table estimates of disease-free survival were 89% for clinical Stage I patients and 94% for surgical Stage I patients beyond 24 months. One patient developed an intraperitoneal recurrence, four had simultaneous intraperitoneal and extraperitoneal recurrences, and six developed recurrences outside of the peritoneal cavity. Few significant acute complications occurred after therapy with radioactive chromic phosphate P 32 suspension. Chronic intestinal morbidity that required surgical correction was encountered in five of 17 patients (29%) who received adjuvant pelvic radiation, compared to none of the 48 patients (0%) who received only radioactive chromic phosphate P 32 suspension (p less than 0.001). Intraperitoneal instillation of radioactive chromic phosphate P 32 suspension is effective therapy for patients with malignant peritoneal cytology from endometrial carcinoma. Caution should be exercised when radioactive chromic phosphate P 32 suspension and external radiation therapy are combined.
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PMID:Intraperitoneal chromic phosphate P 32 suspension therapy of malignant peritoneal cytology in endometrial carcinoma. 403 13

One hundred sixty-seven patients with clinical State I carcinoma of the endometrium were treated primarily by operation consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and para-aortic lymphadenectomy, and cytologic testing of peritoneal washings. Twenty-six (15.5%) of the 167 patients had malignant cells identified on cytologic examinations of peritoneal washings. Recurrence developed in 10 of these 26 (34.0%) compared to 14/141 (9.9%) patients with negative cytologic testing. Of the 26 patients, 13 (50%) had disease outside of the uterus at operation and seven have died of disease (54%). Thirteen patients had malignant cells in the peritoneal washings but no disease outside of the uterus and six (46%) of these have died of disseminated intra-abdominal carcinomatosis. On the basis of the poor outcome of those patients who had malignant cells in the peritoneal washings in the 167 patients studied, a plan of treating such patients with intraperitoneal radioactive chromic phosphate suspension (P-32) was instituted. Twenty-three subsequent patients with clinical Stage I carcinoma of the endometrium were found to have malignant cells in the peritoneal fluid. All 23 received intra-abdominal P-32 suspension instillation after operation. There have been three recurrences with two patients dying of disease. All of the three recurrences appeared at sites distant from the abdominal cavity. Peritoneal cytologic examination appears to be an important factor in the prognosis of endometrial cancer and, when the washings are positive for malignant cells, intraperitoneal chronic phosphate therapy appears to be efficacious.
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PMID:Prognostic significance of peritoneal cytology in patients with endometrial cancer and preliminary data concerning therapy with intraperitoneal radiopharmaceuticals. 731 22

Certain malignant tumors synthesize and secrete a putative peptide mitogen, which elicits a potent proliferative response in their supporting stromal cells. We recently demonstrated that prolactin (PRL) binds to human endometrial fibroblasts and inhibits mitogenicity of an endometrial carcinoma extract (Imai A, et al. Proc Soc Exp Biol Med 203:117-122, 1993). In this report, we have studied inhibitory regulation by PRL of phosphatidylinositol (PtdIns) kinase activity associated with plasma membranes isolated from human endometrial fibroblasts. Incubation of the isolated plasma membrane with [gamma-32P]ATP and exogenous PtdIns caused [32P]phosphate incorporation into PtdIns phosphate (PtdInsP); 95% of the 32P-labeled PtnInsP was accounted for by PtdIns 4-P. The PtdIns phosphorylation by membrane preparations was selectively stimulated in a dose-dependent manner by vanadate, in parallel with an elevated autophosphorylation of endogenous membrane proteins. Concomitant exposure of the membrane preparations to PRL led to a remarkable inhibition of the vanadate-responsive PtdIns phosphorylation and protein autophosphorylation. This inhibition was dependent on PRL dose, and half-maximal effect occurred at a concentration 1-10 nM of PRL. Degradation of the produced PtdInsP in the plasma membranes was not affected by PRL. Similar inhibition of PtdIns kinase activities were observed in membranes prepared from cells that had been pretreated in vivo with PRL prior to assay in vitro. These findings demonstrate that PtdIns kinase activity associated with protein autophosphorylation is suppressed by PRL in plasma membrane isolated from endometrial fibroblasts. The inhibition of vanadate-responsive PtdIns kinase by PRL suggests an involvement of this enzyme in the antimitogenic action of the hormone on human endometrial fibroblasts.
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PMID:Inhibition by prolactin of membrane-associated phosphatidylinositol kinase of human endometrial fibroblast. 810 63


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