Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0476089 (endometrial cancer)
11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty years ago Albright contributed the following to understanding osteoporosis: (1) He recognized it as a deficiency of formation, not of mineralization of bone matrix; (2) he observed that 40 of 42 patients with osteoporosis before age 65 were women past menopause or young women postoophorectomy; (3) he concluded that estrogen stimulates osteoblasts (a conclusion later challenged); (4) he demonstrated by metabolic balance studies that estrogen causes a positive calcium balance in postmenopausal osteoporosis; (5) he introduced periodic progesterone to prevent or treat endometrial hyperplasia from prolonged estrogen therapy; and (6) he showed that long-term therapy arrested vertebral damage and height loss in postmenopausal osteoporosis and prevented them if started early. Since Albright's time, more sensitive methods of assessing bone density have replaced conventional roentgenograms. Some large scale trials of estrogen have indicated increased bone density and fewer fractures. Unopposed estrogen increases risk of endometrial cancer and decreases mortality from other cancers, myocardial infarction, stroke, and osteoporosis. Trials of calcitonin, diphosphonates, fluoride, vitamin D, and high calcium intake have not proved more effective than estrogen.
...
PMID:Fuller Albright. His concept of postmenopausal osteoporosis and what came of it. 186 30

The pathophysiology of primary osteoporosis and the various therapeutic regimens that have been used are reviewed. Osteoporosis is a major public health problem because the incidence of hip, wrist, and vertebral fractures associated with bone loss is high. Postmenopausal women are at increased risk for developing osteoporosis because bone mineral content is lower in women than in men, dietary calcium intake is frequently insufficient, intestinal absorption of calcium decreases with age, and the rate of bone loss accelerates at menopause. The efficacy of many single and combination therapies in preventing or treating osteoporosis has been studied. Differences in study design and diagnostic techniques and the heterogeneous nature of osteoporosis make evaluation of clinical trials difficult. Exercise helps to maintain skeletal mass, but amenorrhea caused by vigorous activity may be harmful. The efficacy of estrogen replacement therapy is documented best; many studies have shown that estrogens slow the rate of bone loss and reduce the incidence of fractures, but the association of estrogen use with endometrial cancer and breast cancer is of concern. Progesterones may protect against endometrial cancer, but undesirable effects of oral contraceptives have resulted in a hesitancy to use combination hormonal therapy. All adults should meet daily nutritional requirements for calcium, but this intake may be insufficient for elderly persons and is below recommended doses for treating osteoporosis. A daily intake of at least 1000-1500 mg of elemental calcium has been shown to slow the rate of bone loss. Nutritional requirements for vitamin D should be met, but benefits from pharmacologic doses have not been demonstrated. The role of fluoride, calcitonin, anabolic steroids, and vitamin D metabolites is unclear. Fluoride has the potential to increase bone mass, but effects on bone histology and fracture rates require further study. The major goals for the management of osteoporosis are maintenance of bone mass and prevention of fractures. An adequate intake of calcium and regular weight-bearing exercise are important preventive measures. Despite the documented effectiveness of estrogens, risks associated with long-term use are of concern.
...
PMID:Pathogenesis and management of primary osteoporosis. 352 28

An adequate calcium intake is important to attain peak bone mass and to oppose that component of age-related bone loss due to insufficient intestinal calcium absorption. Calcium and appropriate vitamin D supplements are particularly important for preventing cortical bone loss and associated hip fractures in the elderly (Type II osteoporosis). Within the initial 5 years following menopause, there is an accelerated loss of trabecular bone from the spine and distal radius (Type I osteoporosis). At that time, estrogen replacement is most effective for preventing the rapid trabecular bone loss that could otherwise result in vertebral or Colles' fractures. During this early period of estrogen deficiency when excessive bone turnover is releasing large amounts of calcium into the circulation, supplemental calcium is ineffective. Progesterone, often given with estrogen to prevent endometrial carcinoma, may itself have a trophic influence on bone.
...
PMID:Calcium, estrogen, and progestin in the treatment of osteoporosis. 798 85

The menopause is defined as cessation of menstruation, ending the fertile period. The hormonal changes are a decrease in progesterone level, followed by a marked decrease in estrogen production. Symptoms associated with these hormonal changes may advocate for hormonal replacement therapy. This review is based on the English-language literature on the effect of estrogen therapy and estrogen plus progestin therapy on postmenopausal women. The advantages of hormone replacement therapy are regulation of dysfunctional uterine bleeding, relief of hot flushes, and prevention of atrophic changes in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin. Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke, and there is no increased risk of venous thrombosis or hypertension. A disadvantage of hormone replacement therapy is an increased risk of forming gall-bladder stones and undergoing cholecystectomy. Unopposed estrogen therapy gives a higher incidence of endometrial cancer in women with an intact uterus, but the contribution of progestins for about 10 days every month excludes this risk. Breast cancer in relation to estrogen-progestogen therapy has been given much concern, and the problem is still not fully solved. If there is a risk, it is small, and only after prolonged use of estrogen (15-20 years). The decision whether or not to use hormone replacement therapy should, of course, be taken by the individual woman in question, but her decision should be based on the available scientific information. It is the opinion of the authors that the advantages of hormone replacement therapy far exceed the disadvantages. We suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular diseases.
...
PMID:Postmenopausal hormone replacement therapy--clinical implications. 819 55

Responses of stage III/IV endometrial adenocarcinomas to cytotoxic agents have been partial and of short duration, results which indicate a need for new agents and therapeutic strategies. This study was undertaken to determine the effects of carboplatin and the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3 (calcitriol), on the growth of RL95-2 endometrial carcinoma cells. Carboplatin is a second-generation platinum-based cytotoxic agent. Calcitriol is a biologic agent that has activity against multiple solid tumors, including ovarian carcinomas. Carboplatin inhibited the growth of RL95-2 cells in a concentration-dependent manner with maximal inhibition (78%) at 200 micrograms/ml. Calcitriol also inhibited RL95-2 growth in a concentration-dependent manner. Maximal inhibition (29%) was elicited by 80 nM calcitriol. Addition of 10-50 nM calcitriol to 5-20 micrograms/ml carboplatin resulted in improved growth inhibition. The degree of interaction between carboplatin and calcitriol was assessed using isobolographic analysis and was found to be additive at all drug concentrations and ratios examined. These results suggest that carboplatin and calcitriol each inhibit the growth of RL95-2 endometrial carcinoma cells and that the combination of these two agents acts additively to inhibit the growth of RL95-2 cells. These agents merit further investigation for their utility against endometrial carcinomas.
...
PMID:Additive inhibition of RL95-2 endometrial carcinoma cell growth by carboplatin and 1,25 dihydroxyvitamin D3. 827 88

To understand the molecular mechanisms underlying the regulation of hepatocyte growth factor (HGF) gene expression and to define the DNA sequences essential for its cell-type specific and inducible expression, we have isolated and characterized the 5'-flanking region of the HGF gene. A genomic clone containing 2.8 kilobases of the 5'-flanking region of the HGF gene has been isolated from a mouse liver genomic library. Sequence analysis showed that the promoter region of the mouse HGF gene contains a noncanonical TATA box (ATAAA). Further analysis of the 5'-flanking region revealed a number of putative regulatory elements, such as four interleukin-6 response elements (IL-6 RE), two potential binding sites for NF-IL6, a TGF-beta inhibitory element (TIE), a cAMP response element (CRE), two estrogen response elements (ERE) including one located in the first intron, a potential vitamin D response element (VDRE) which overlaps a chicken ovalbumin upstream promoter (COUP) transcription factor binding element, two liver-specific transcription factor (C/EBP) binding sites, and a B cell- and macrophage-specific transcriptional factor binding site (PU.1/ETS). To determine the location of sites that may be critical for the function of the HGF promoter, we constructed a series of chimeric genes containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT). Transient transfection of chimeric plasmids demonstrated that the mouse HGF gene promoter containing 70 base pairs of the 5'-flanking sequences were active in mouse fibroblast NIH 3T3 cells and in human endometrial carcinoma RL95-2 cells. This basal transcription activity of the HGF promoter was modulated in NIH 3T3 and RL95-2 cells by multiple upstream elements. Three positive elements were identified at positions -2848 to -2674, -1386 to -1231, and -699 to -274, and three negative candidate elements were mapped to positions -1652 to -1386, -964 to -699, and -274 to -70, respectively. By the combination of a series of 5'-end deletion and internal deletion, a cell type-specific negative regulatory element in RL95-2 cells was localized to the nucleotide position -964 to -699. Moreover, the reporter plasmid containing interleukin 6 (IL-6) response element was responsive to IL-6 stimulation in stably transfected NIH 3T3 cells. Our findings revealed a complex pattern of transcriptional regulation of the mouse HGF gene expression.
...
PMID:Structural and functional characterization of the mouse hepatocyte growth factor gene promoter. 830 76

The term "SERM" stands for "Selective Estrogen Receptor Modulators", substances which act on certain organs as oestrogen agonists and on other organs as oestrogen antagonists. They can exert the known oestrogen-like effects on bone and lipids without exerting any action on the endometrium and the breast, a potentially ideal profile for postmenopausal hormone replacement treatment. Long known are clomifen, an ovulation stimulator, and tamoxifen, used for secondary prevention in breast cancer. Tamoxifen prevents postmenopausal bone loss as efficiently as hormone replacement treatment, and lowers blood lipids and the coronary risk, but increases the risk of endometrial cancer; for this reason it cannot be used in the prevention of postmenopausal osteoporosis. Raloxifen stimulates neither the endometrium nor the mammary gland, and probably even lowers the risk of breast cancer. Its relatively mild but significant effect on BMD (+ 2-3%/2 years) is sufficient for prevention, and in osteoporotics goes along with a substantial decrease in vertebral fracture incidence (by about 50%) comparable to the effect of other treatments. As in hormone replacement treatment, thromboembolism and leg cramps occur more frequently. Therefore, raloxifen can be used in women free of climacteric symptoms for the prevention and treatment of postmenopausal osteoporosis with no increased risk of phlebitis, alone or in combination with calcium, vitamin D, bisphosphonates and calcitonin; in future it may also be useful in male osteoporosis.
...
PMID:[Selective estrogen receptor modulators (SERM): new substances for hormone replacement therapy]. 1063 85

It is well known that estrogen deficiency is the major determinant of bone loss in postmenopausal women. Estrogen is important to the bone remodeling process through direct and indirect actions on bone cells. The largest clinical experience exists with estrogen therapy, demonstrating its successful prevention of osteoporosis as well as its positive influence on oral bone health, vasomotor and urogenital symptoms, and cardiovascular risk factors, which may not occur with other nonestrogen-based treatments. Compliance with HRT, however, is typically poor because of the potential side effects and possible increased risk of breast or endometrial cancer. Nevertheless, there is now evidence that lower doses of estrogens in elderly women may prevent bone loss while minimizing the side effects seen with higher doses of estrogen. Additionally, when adequate calcium, vitamin D, and exercise are used in combination with estrogen-based treatments, more positive increases occur in bone density. The benefits and risks of HRT must be assessed on a case-by-case basis, and the decision to use HRT is a matter for each patient in consultation with her physician. Estrogen-based therapy remains the treatment of choice for the prevention of osteoporosis in most postmenopausal women, and there may be a role for estrogen to play in the prevention of corticosteroid osteoporosis. Combination therapies using estrogen should probably be reserved for patients who continue to fracture on single therapy or should be used in patients who present initially with severe osteoporosis.
...
PMID:Role of estrogens in the management of postmenopausal bone loss. 1128 92

Daily diet factors that could potentially be related to endometrial cancer (EC) in Mexico are still unknown. This study aims to evaluate the association between EC and Mexican dietary factors. A case-control study in Mexico City was conducted during 1995-1997 in a social security hospital, using 85 incident cases of EC and 629 controls. A validated questionnaire with 116 items about the frequency and type of food intake was used. The analysis of nutrients was performed using the residual method, adjusting by predictor variables through logistic regression methods. In addition, partitional models estimated total caloric intake for other sources. We found no association between EC risk and consumption of animal or vegetable proteins, saturated, monounsaturated, or polyunsaturated fat, although high intake of nutrients such as lactose (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.21-1.01, P for trend = 0.004), vitamin D (OR, 0.38; 95% CI, 0.18-0.82, P= 0.003), and calcium (OR, 0.39; 95% CI, 0.17-0.89, P= 0.02) were inversely associated with EC. Our results suggest that dietary vitamin D and calcium play an important role in the development of EC, although the mechanisms postulated should be explained with additional studies with large populations.
...
PMID:Dietary factors and endometrial cancer risk. Results of a case-control study in Mexico. 1617 49

1,25(OH)(2)D(3) (calcitriol) has been shown to play an important role in cell proliferation, differentiation and immune responsiveness. The enzyme responsible for calcitriol synthesis 25 hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-OHase) has been reported in many human tissues. The aim of this study was to investigate the expression of 1alpha-OHase in gynaecological tissues. Using a highly specific nested touchdown PCR we examined the expression of 1alpha-OHase in normal and malignant endometrial tissue and in human endometrial Ishikawa cells. In addition, we analyzed the protein expression of 1alpha-OHase by Western blot. The expression of 1alpha-OHase in normal and malignant endometrial tissue and Ishikawa cells was detected and splice variants of the enzyme in Ishikawa cells were identified. These data suggest an alternative splicing of 1alpha-OHase in malignant endometrial tissue and cells. We postulate that the expression of 1alpha-OHase gene variants may contribute to the antiproliferative effects of calcitriol. In conclusion, the modulation of the 1alpha-OHase opens up a new target for vitamin D(3) related therapies in endometrial cancer.
...
PMID:Expression of 25 hydroxyvitamin D3-1alpha-hydroxylase in human endometrial tissue. 1723 59


1 2 3 Next >>

---