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

Although an underlying endocrine-metabolic disorder has been implicated as causally related to the development of endometrial carcinoma, data to support such an association are ambiguous and/or contradictory. In this prospective study of 16 consecutive nonobese postmenopausal women with endometrial carcinoma and 16 cancer-free postmenopausal women matched for age and weight, fasting values for growth hormone (GH), insulin, prolactin, follicle-stimulating hormone, luteinizing hormone, estrone (E1), and estradiol (E2) were measured on 3 consecutive days. Intravenous glucose tolerance, pituitary GH release in response to arginine infusion, hyperglycemia, and hypoglycemia, and insulin secretion in response to arginine infusion and to hyperglycemia were analyzed. Our data show that these endocrine-metabolic profiles were not significantly different between the cancer patients and control subjects, suggesting that the postmenopausal women with endometrial cancer who is not obese exhibits no accountable endocrine or metabolic disorders.
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PMID:A study of endocrine and metabolic variables in postmenopausal women with endometrial carcinoma. 45 45

Plasma levels of estrone (E1), estradiol-17beta (E2), and estriol (E3), as well as follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were measured in 30 control subjects and in 20 postmenopausal patients with adenocarcinoma of the endometrium. Within the sensitivity of the assay (5 to 10 pg.), no E3 was found. Mean levels of E1 and E2 in the patients with carcinoma (42.64+/-3.8 (S.E.M.) and 17.3+/-1.7 (S.E.M.) pg. per mililiter) were significantly higher than those measured in the control subjects (E1=26.97+/-2.4 (S.E.M.) pg. per mililiter, p less than 0.001; E2=12.08+/-1.2 (S.E.M.) pg. per milliliter, p less than 0.02). Effects of age, diabetic status, and obesity were taken into consideration. Significant differences in FSH and marginally significant differences in prolactin levels were observed between the two groups. Mean levels of FSH, LH, and prolactin in the control group and the group with adenocarcinoma, respectively, were as follows: FSH=152.3+/-7.0 (S.E.M.) versus 98.1+/-8.9 (S.E.M.) mI.U. per milliliter, p less than 0.001; LH=64.7+/-3.1 (S.E.M.) versus 66.5+/-5.2 mI.U. per milliliter, difference not significant; and prolactin=14.3+/-0.9 (S.E.M.) versus 17.8+/1.7 (S.E.M.) ng. per milliliter, p less than 0.06. These results, as well as previously reported alterations in human growth hormone secretion, suggest aberrations in hypothalamic function in endometrial carcinoma.
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PMID:Plasma levels of fractionated estrogens and pituitary hormones in endometrial carcinoma. 98 36

As is obvious from the previous discussions, obesity is associated with a wide variety of changes in endocrine parameters (Table 1). Some of these changes, such as the reduction in SHBG without change in serum free testosterone levels, reflect merely laboratory abnormalities that may influence interpretation of diagnostic tests but have no important physiologic relevance. Other abnormalities have major clinical impact, such as hyperestrogenemia-endometrial carcinoma and hyperlipidemia-coronary artery disease. In some cases, endocrine changes in obesity are beneficial--that is, hyperestrogenemia leading to lower incidence of osteoporosis. In other cases, such as the profound suppression of growth hormone output in obesity, the physiologic relevance is unknown. Several endocrine changes in obesity, such as the impaired response of many hormones (growth hormone, prolactin, vasopressin, corticotropin) to insulin-induced hypoglycemia and elevated endorphin levels, suggest hypothalamic dysfunction. Furthermore, the failure of all of these abnormalities to be normalized after weight reduction raises the possibility of an underlying disorder leading to both endocrine dysfunction and obesity, rather than the endocrine dysfunction being simply a consequence of the obesity. Successful elucidation of the pathogenesis of obesity, which might then lead to much needed specific treatment modalities, may be advanced if we can solve some of these puzzles.
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PMID:Endocrine aspects of obesity. 264 1

Paradoxical hypersecretion of human growth hormone (HGH) followed a glucose load in patients with endometrial cancer and atypical hyperplasia of the endometrium. All patients had normal fasting plasma glucose and serum HGH concentration with a normal glucose tolerance curve. Their urinary estrogen concentrations were within the normal postmenopausal range. 6 months after abdominal total hysterectomy and bilateral oophorectomy, the glucose load was repeated. Following surgery all patients showed a normal suppression of HGH secretion during the hyperglycemic period. These findings suggest the existence of a HGH-releasing factor in the neoplastic and preneoplastic endometrial tissue. This factor might be related to the abnormal HGH responses observed.
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PMID:Paradoxical hypersecretion of growth hormone in patients with endometrial atypical hyperplasia and carcinoma. Effect of hysterectomy. 705 4

Existing evidence indicates that, in addition to its neuroendocrine action, growth hormone-releasing hormone (GHRH) acts directly on several nonpituitary tissues, especially neoplasms, and stimulates cell proliferation. We have recently reported that a splice variant of the receptor (SV1) is expressed in various normal tissues and particularly in tumor tissues, producing mitogenic effects on GHRH binding. By using HEC-1A human endometrial carcinoma cells, which express endogenous SV1, we show that, in addition to its ability to mediate the mitogenic effects of GHRH, SV1 also possesses relatively high intrinsic, ligand-independent activity. By using an antisense RNA-based approach we found that SV1 ablation reduces the efficacy of colony formation and the rate of cell proliferation of HEC-1A cells in the absence of exogenous GHRH, and decreases their sensitivity to GHRH when the neurohormone is added to the culture media. This ligand-independent stimulation of cell proliferation appears to be a characteristic property of the truncated form of the receptor, because the expression of SV1 and not of the full-length GHRH receptor stimulated the proliferation of 3T3 fibroblasts in the absence of exogenous GHRH, whereas both forms mediated the proliferative effects of GHRH. Evaluation of 21 specimens of human primary endometrial carcinoma for expression of SV1 by immunohistochemistry indicated that in contrast to the GHRH receptor, which is absent, SV1 is expressed in approximately 43% of the specimens. These findings indicate that SV1 can operate in a ligand-independent as well as a ligand-dependent manner. The overexpression of this form of GHRH receptor may be associated with carcinogenesis.
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PMID:Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor. 1286 92

The incidence of colon, pancreatic, and kidney cancers, as well as aggressive prostate cancer in men, and breast and endometrial cancer in women is invariably high in Western countries. Nutritional and related factors have been typically implicated. This review presents a model integrating nutrition, insulin and IGF-1 physiology ("bioactive" IGF-1), and carcinogenesis based on the following: (1) insulin and the IGF-1 axis function in an integrated fashion to promote cell growth and survival; (2) chronic exposure to these growth properties enhances carcinogenesis; (3) factors that influence bioactive IGF-1 will affect cancer risk. The model presented here summarizes the data that chronic exposure to high levels of insulin and IGF-1 may mediate many of the risk factors for some cancers that are high in Western populations. This hypothesis may help explain some of the epidemiologic patterns observed for these cancers, both from a cross-national perspective and within populations. Of particular importance is that some of relevant factors are modifiable through nutritional and lifestyle interventions. Out of a variety of perspectives presented, nutritional manipulation through the insulin pathway may be more feasible than attempting to influence total IGF-1 concentrations, which are determined largely by growth hormone. Further study is required to test these conclusions.
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PMID:Nutrition, insulin, insulin-like growth factors and cancer. 1471 Mar 48

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.
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PMID:A perspective on the hormonal abnormalities of obesity: are they cause or effect? 1635 9

In this retrospective and quantitated study on banked tissue we found that, compared to normal uterine epithelial cells, growth hormone (GH) is increased 3.4-fold in endometriosis and 3.8-fold in endometrial adenocarcinoma. Similarly, interleukin-6 (IL-6) is increased 2.4-fold in endometriosis and 4.4-fold in endometrial adenocarcinoma. These proteins appear to be involved in the progression of both these conditions. GH is particularly interesting in this context since it is known to not only promote cellular proliferation but also reduces cell-cell adhesion, thus allowing individual cells to break away from their parent architecture. Our results suggest that both IL-6 and GH may play a role in the progression of both endometriosis and endometrial carcinoma.
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PMID:Human growth hormone and interleukin-6 are upregulated in endometriosis and endometrioid adenocarcinoma. 1656 64

The expression of growth hormone-releasing hormone (GHRH) and its receptors has been demonstrated in peripheral tissues as well as CNS. Recently, the functional splice variant SV1 of GHRH receptor was identified in various human cancers and cancer cell lines. Although antineoplastic activity of GHRH antagonists has been clearly demonstrated, the mechanism of action is incompletely understood. The objective of this study was the investigation of direct anti-proliferative effect of GHRH antagonist MZ-5-156 on HEC-1A human endometrial cancer cell line and the elucidation of underlying mechanisms. RT-PCR revealed the expression of mRNA for GHRH and SV1 of GHRH receptor in HEC-1A cells. MZ-5-156, at concentrations between 10(-7) and 10(-5) M, had a dose-dependent antiproliferative effect on HEC-1A cells, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, (MTS) assay. Hoechst 33342 staining and flow cytometric analysis indicated that MZ-5-156, at 10(-6) M, induced apoptosis in HEC-1A cells after 48 h of treatment. Western blot analysis of apoptosis-related proteins demonstrated that treatment with MZ-5-156 (10(-6) M) for 48 h significantly increased the protein levels of Fas, phospho-p53 (Ser46), p53AIP1 (p53-regulated Apoptosis-Inducing Protein 1), and caspase-8, -9, and -3, and decreased the protein level of Bcl-2. These results demonstrate that MZ-5-156 can directly inhibit the proliferation of human endometrial cancer cells, which express mRNA for GHRH and SV1 of GHRH receptor, presumably through the induction of p53-dependent apoptosis coupled with the up-regulation of Fas, phospho-p53 (Ser46), p53AIP1, and caspase-8, -9, and -3, and the down-regulation of Bcl-2.
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PMID:Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormone. 1829 36

The discovery of hypothalamic hormones was briefly reviewed. The development of new hormonal methods for the therapy of various cancers based on analogues of hypothalmic hormones is then presented. My group isolated luteininzing hormone-releasing hormone (LH-RH), also known as Gn-RH, from pig hypothalmi, elucidated its amino acid sequence, and synthesized it in 1971. The interest in medical applications of LH-RH led to the synthesis of LH-RH analogues by various groups. LH-RH agonists substituted in positions 6 or 10 including Decapeptyl, Leuprolide and Zoladex are much more active than LH-RH and on continuous administration produce inhibition of pituitary and gonads. Chronic administration of LH-RH agonists is being utilized for the treatment of prostate and breast cancer. Octapeptide analogues of somatostatin have various applications in Oncology. In 1980 we developed a new endocrine therapy for advanced prostate cancer based on agonists of LH-RH, which is now preferred by 70-90% of prostate cancer patients for primary treatment. LH-RH antagonists such as Cetrorelix can be used for therapy of BPH. On the basis of the presence of specific receptors for hypothalamic peptides on human cancers, we developed targeted cytotoxic analogues of LH-RH, somatostatin, and bombesin/GRP linked to doxorubicin or 2-pyrrolinodoxorubicin. These analogues inhibit the growth of experimental human prostate, breast, ovarian and endometrial cancer, renal cell carcinoma, pancreatic, colorectal and gastric cancers, small cell lung carcinoma (SCLC) and non-SCLC, brain tumors, melanomas, and lymphomas. Cytotoxic LH-RH analogues are now in clinical trials. Recently we demonstrated that growth hormone-releasing hormone (GH-RH) also serves as an autocrine growth factor in many cancers. Antagonistic analogues of GH-RH synthesized in our laboratory inhibit the growth of diverse tumors. The discovery of LH-RH and somatostatin has led to clinical use of their analogues in the field of cancer treatment and GH-RH antagonists also show a great promise.
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PMID:New approaches to the therapy of various tumors based on peptide analogues. 1849 Dec 50


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