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

The development of the luteinizing hormone-releasing hormone (LH-RH) agonists and antagonists and the principles of their clinical use were reviewed. In the 28 years that have elapsed since the elucidation of the structure of LH-RH, various applications in gynecology, reproductive medicine, and oncology have been established for LH-RH agonists and antagonists. These clinical applications are based on inhibition of the pituitary and the gonads. The advantage of the LH-RH antagonists is due to the fact that they inhibit the secretion of gonadotropins and sex steroids immediately after the first injection and thus achieve rapid therapeutic effects in contrast to the agonists, which require repeated administration. LH-RH antagonists should find applications in the treatment of benign gynecologic disorders and benign prostatic hypertrophy and in assisted reproduction programs. The primary treatment of advanced androgen-dependent prostate cancer is presently based on the use of depot preparations of LH-RH agonists, but antagonists like Cetrorelix already have been tried successfully. Antagonists of LH-RH might be more efficacious than agonists in treatment of patients with breast cancer as well as ovarian and endometrial cancer. Recently, practical cytotoxic analogs of LH-RH that can be targeted to LH-RH receptors on tumors have been synthesized and successfully tested in experimental cancer models. Targeted cytotoxic LH-RH analogs show a great promise for therapy of prostate, breast, and ovarian cancers.
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PMID:Luteinizing hormone-releasing hormone analogs: their impact on the control of tumorigenesis. 1057 98

Analogues of luteinizing hormone-releasing hormone (LH-RH) have made possible new approaches to the treatment of some hormone-dependent cancers and diseases and conditions which result from inappropriate sex hormone levels. In the fields of both gynaecology and oncology, the development of sustained delivery depot systems has played a key role in the clinical use of LH-RH agonists and will be also essential for the LH-RH antagonists. Clinical results show that therapy with agonists of LH-RH is the preferred method of treatment for men with advanced prostate cancer. For prostate cancer and other indications, the new LH-RH antagonists such as Cetrorelix may offer an advantage based on the fact that they inhibit LH, FSH and sex-steroid secretion from the start of the administration and thus reduce the time of the onset of therapeutic effects. The use of antagonists would avoid the temporary clinical "flare-up" of the disease which can occur with the agonists in men with prostate cancer. The rapid shrinkage of the prostate and improvement in urinary symptoms obtained with Cetrorelix in men with benign prostatic hyperplasia (BHP) suggests that LH-RH antagonists offer a therapeutic alternative in patients who are considered poor surgical risks. Various experimental and clinical studies suggest that analogues of LH-RH might be useful for treatment of premenopausal women with oestrogen-dependent breast cancer. LH-RH antagonists such as Cetrorelix could be also considered for hormonal therapy of epithelial ovarian cancer which responds only marginally to the agonists, and for treatment of endometrial cancer. Many investigators have reported beneficial effects of LH-RH agonists in the treatment of patients with leiomyomas. LH-RH antagonists also appear to be promising for therapy of uterine leiomyomas, and in addition might be useful for treatment of endometriosis and polycystic ovarian disease (PCOD). LH-RH agonists have been employed in in vitro fertilization and embryo transfer (IVF-ET) programs to prevent a premature rise in LH and various results suggest that the use of antagonist Cetrorelix in assisted reproduction procedures, could be even more advantageous. For most of these indications, the use of sustained release depot preparations will be required.
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PMID:Rational use of agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH) in the treatment of hormone-sensitive neoplasms and gynaecologic conditions. 1083 70

Luteinizing hormone-releasing hormone (LHRH) and its receptor are frequently expressed in human ovarian and endometrial cancers and are part of an autocrine mechanism of growth control. We have previously shown that the LHRH analog Triptorelin induces activation of nucleus factor kappa B (NFkappaB) and reduces apoptosis induced by doxorubicin in human ovarian cancer cells EFO-21 and EFO-27. The present study was performed to investigate the anti-apoptotic effects of LHRH analogs on apoptosis induced by doxorubicin, UV-light and ligation of CD95 in human endometrial and ovarian cancer cells. We further investigated the interaction of the LHRH system with the apoptotic pathway focusing on the effector-protease caspase 3. Doxorubicin (100 nM) induced apoptosis in the LHRH-receptor-positive human endometrial cancer cell line Ishikawa and in the human ovarian cancer cell lines EFO-21 and NIH:OVCAR-3. Pretreatment for 24 h with native LHRH, the LHRH agonist Triptorelin or the LHRH antagonist Cetrorelix (100 nM) significantly reduced apoptosis induced by doxorubicin in these cells. In EFO-21 cells pretreatment with 100 nM Triptorelin also reduced UV-light-induced apoptosis from 76% to 62.7% (p<0.01). EFO-21 cells express CD95. Cross-linking of CD95 with monoclonal antibody anti-APO-1 (500 ng/ml) increased apoptosis from spontaneous rate to 10.3% to 38.3% in EFO-21 cells (p<0.001). Pre-treatment with Triptorelin did not reduce CD95-mediated apoptosis in these cells. LHRH analogs protect human endometrial and ovarian cancer cells from DNA-replication-dependent cytotoxic agent and UV-light-induced apoptosis, but not from CD95-mediated apoptosis.
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PMID:Luteinizing hormone-releasing hormone (LHRH) inhibits apoptosis induced by cytotoxic agent and UV-light but not apoptosis mediated through CD95 in human ovarian and endometrial cancer cells. 1527 47

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