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

Adenomyosis is a nonneoplastic condition, characterized by benign invasion of ectopic endometrium into the myometrium with hyperplasia of adjacent smooth muscle. The common symptoms include dysmenorrhea, menorrhagia, and abnormal uterine bleeding, but these do not allow diagnosis. Therefore, imaging plays an important role because establishment of the correct preoperative diagnosis is critical to avoid unnecessary intervention. Magnetic resonance (MR) imaging is a highly accurate noninvasive modality for diagnosis of adenomyosis, differentiation of adenomyosis from other gynecologic disorders, and planning of appropriate treatment. Although the typical MR imaging findings are well established, adenomyosis actually varies widely in terms of histopathologic features (adenomyosis with sparse glands), growth patterns (polypoid adenomyoma, adenomyotic cyst, and miniature uterus), responses to hormonal activity (tamoxifen, decidual changes), and responses to treatment (gonadotropin-releasing hormone agonist). The MR imaging findings of adenomyosis occasionally mimic those of uterine malignancy or ovarian cancer. Furthermore, malignancy occasionally develops in otherwise benign adenomyosis. Pitfalls in diagnosis of adenomyosis include myometrial contractions, leiomyoma, adenomatoid tumor, metastases, endometrial carcinoma, and endometrial stromal sarcoma. Knowledge of the various appearances of adenomyosis and the possible pitfalls in differential diagnosis help guide the determination of appropriate treatment options.
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PMID:MR imaging findings of adenomyosis: correlation with histopathologic features and diagnostic pitfalls. 1565 84

The majority of ovarian, endometrial, and breast cancers express gonadotropin-releasing hormone (GnRH) receptors. Apart from reproductive organs (ovaries, fallopian tubes, and uterus) that are normally removed during surgical therapy of ovarian or endometrial cancer, pituitary gonadotrophs also express GnRH receptors. The signal transduction pathway in tumor cells is basically different from the classic GnRH receptor signal transduction, which is known to operate in the pituitary gonadotrophs and can therefore be considered tumor specific. Other organs and hematopoetic stem cells do not express GnRH receptors. We have recently shown specific activation of nucleus factor kappaB in ovarian, endometrial, and breast cancers after treatment with GnRH agonists. Based on this tumor-specific signaling pathway and the distribution pattern of GnRH receptors, we have developed and successfully tested a gene therapy concept by using a GnRH analogue as an inducer for the transcription of a therapeutic gene in cell culture and in nude mice.
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PMID:Gonadotropin-releasing hormone receptor-targeted gene therapy of gynecologic cancers. 1571 94

The expression of LHRH and its receptor has been demonstrated in a number of human malignant tumors, including cancers of the breast, ovary, endometrium, and prostate. These findings suggest the presence of an autocrine regulatory system based on LHRH. Dose-dependent antiproliferative effects of LHRH agonists in cell lines derived from these cancers have been observed by various investigators. LHRH antagonists also have marked antiproliferative activity in most of the ovarian, breast, and endometrial cancer cell lines tested, indicating that the dichotomy of LHRH agonists and antagonists might not apply to the LHRH system in cancer cells. Findings from our laboratories suggest that the classical LHRH receptor signal-transduction mechanisms, known to operate in the pituitary, are not involved in the mediation of antiproliferative effects of LHRH analogues in cancer cells. Results obtained by several groups, including ours, instead suggest that LHRH analogues interfere with the mitogenic signal transduction of growth-factor receptors and related oncogene products associated with tyrosine kinase activity. The pharmacological exploitation of these direct antiproliferative actions of LHRH analogues might provide new therapeutic approaches to these cancers.
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PMID:Growth-inhibitory actions of analogues of Luteinizing Hormone Releasing Hormone on tumor cells. 1840 25

Several studies have previously reported the expression of the gonadotropin-releasing hormone receptor (GnRHr) in cases of endometrial cancer. However, the relationship between GnRHr expression and a variety of clinicopathologic parameters remains unclear. This study was conducted with 141 endometrial cancer patients, all of whom had undergone operations between 1993 and 2002. Paraffin-embedded tissue blocks were sectioned and immunostained with monoclonal anti-GnRHr antibody. Clinicopathologic variables were also evaluated, with 10% cutoff values for GnRHr positivity. Seventy specimens (49.6%) stained as GnRHr-positive. Mean parity was higher in the patients with GnRHr-positive tumors than those with GnRHr-negative tumors (2.50+/-1.92 versus 1.82+/-1.37, P=0.016). Body mass indices were also higher in the patients with GnRHr-positive tumors (26.6+/-4.6 versus 24.7+/-4.2, P=0.010). However, GnRHr positivity was not determined to be statistically significantly associated with any other clinicopathologic characteristics, including age, menopausal status, histotype, disease stage, tumor differentiation, lymph node metastasis, and myometrial invasion. The results of this study, although they may require further investigation, suggested that obese and multiparous women with endometrial cancer might be greatly influenced by endogenous gonadotropin-releasing hormone and/or exogenous gonadotropin-releasing hormone analogs.
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PMID:Gonadotropin-releasing hormone receptor expression in endometrial cancer. 1904 13

Type I GnRH (GnRH-I, GNRH1) and type II GnRH (GnRH-II, GNRH2), each encoded by separate genes, have been identified in humans. The tissue distribution and functional regulation of GnRH-I and GnRH-II clearly differ despite their comparable cDNA and genomic structures. These hormones exert their effects by binding to cell surface transmembrane G protein coupled receptors and stimulating the Gq/11 subfamily of G proteins. The hypothalamus and pituitary are the main origin and target sites of GnRH, but numerous studies have demonstrated that extra-hypothalamic GnRH and extra-pituitary GnRH receptors exist in different reproductive tissues such as the ovary, endometrium, placenta, and endometrial cancer cells. In addition to endocrine regulation, GnRH is also known to act in an autocrine and paracrine manner to suppress cell proliferation and activate apoptosis in the endometrium and endometrial cancer cells through several mechanisms. Both GnRH-I and GnRH-II exhibit regulatory roles in tissue remodelling during embryo implantation and placentation, which suggests that these hormones may have important roles in embryo implantation and early pregnancy. The presence of varied GnRH and GnRH receptor systems demonstrate their different roles in distinct tissues using dissimilar mechanisms. These may result in the generation of new GnRH analogues used for several hormone-related diseases.
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PMID:GnRH signaling in intrauterine tissues. 1920 50

Gonadotropin-releasing hormone type II (GnRH-II) has an antiproliferative effect on human endometrial cancer cells. Apoptosis in cancer cells may play a critical role in regulating cell proliferation. However, more studies are necessary to elucidate the underlying molecular mechanisms and develop potential applications of GnRH-II. Therefore, we explored the mechanisms of GnRH-II-induced apoptosis and the effects of GnRH-II on GADD45alpha activation in human endometrial cancer cell lines. GnRH-II decreased cell viability in a dose- and time-dependent manner. Apoptosis was induced with increased terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling apoptotic cells after GnRH-II treatment. Knockdown of the endogenous GnRH-I receptor with small interfering RNA (siRNA) rescued the cells from GnRH-II-mediated cell growth inhibition and abolished the induction of apoptosis. GnRH-II activated extracellular signal-regulated kinase (ERK)-1/2 and p38 mitogen-activated protein kinase (MAPK) in a time-dependent manner, and the activation was abolished by GnRH-I receptor siRNA and MAPK inhibitors. Cells pretreated with MAPK inhibitors were rescued from GnRH-II-mediated cell growth inhibition. Moreover, both inhibitors abolished GnRH-II-induced apoptosis. GnRH-II induced GADD45alpha expression, which was abolished by knockdown of endogenous GnRH-I receptors and MAPK inhibitors. GnRH-II-stimulated cell growth inhibition was rescued by knockdown of endogenous GADD45alpha with siRNA. Cells treated with GADD45alpha siRNA were refractory to GnRH-II-induced apoptosis. Thus, GnRH-II inhibits cell growth by inducing apoptosis through binding of the GnRH-I receptor, activation of the ERK1/2 and p38 MAPK pathways, and induction of GADD45alpha signaling. This finding may provide a new concept relating to the mechanism of GnRH-II-induced antiproliferation and apoptosis in endometrial cancer cells, indicating the possibility of GnRH-II as a promising therapeutic intervention for human endometrial cancer.
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PMID:Gonadotropin-releasing hormone type II induces apoptosis of human endometrial cancer cells by activating GADD45alpha. 1936 94

Endometrial carcinoma is the most common neoplasm of the female genital tract, accounting for nearly one half of all gynecologic cancers in the Western world. Although intensive research on pathological phenomena of endometrial cancer is currently going on, but exact cause and biological aspects of this disease are not well described yet. In addition to well-documented roles of gonadotropin-releasing hormone (GnRH) in hypopituitary ovarian (HPO) axis, the agonistic or antagonistic analogs (or both) of GnRH have been shown to inhibit the proliferation of a variety of human gynecologic cancers. Thus, in the present study, we further examined the possibility that GnRH induces integrin beta3 and activation of focal adhesion kinase (FAK) through mitogen-activated protein kinases (MAPKs), ERK1/2 and p38, to inhibit the growth of HEC1A endometrial cancer cell line. As a result, both GnRH-I and GnRH-II resulted in a significant increase in integrin beta3 expression and evoked the activation of FAK in a time-dependent manner in these cells. In addition, these analogs induced an activation of ERK1/2 and p38 MAPK in a time-dependent manner as downstream pathways of FAK. It appears that GnRH-II has much greater effect on the activation of FAK, ERK1/2 and p38 compared to GnRH-I in these cells. Further, we demonstrated that the growth inhibition of HEC1A cells by GnRH-I or GnRH-II is involved in the activation of integrin-FAK and ERK1/2 and p38 MAPK pathways. Taken together, these results suggest that GnRH may be involved in the inhibition of endometrial cancer cell growth via activation of integrin beta3 and FAK as a direct effect. This knowledge could contribute to a better understanding of the mechanisms implicated in the therapeutic action of GnRH and its biomedical application for the treatment against endometrial cancer.
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PMID:Gonadotropin-releasing hormone (GnRH)-I and GnRH-II induce cell growth inhibition in human endometrial cancer cells: involvement of integrin beta3 and focal adhesion kinase. 1965 90

Uterine fibroids are the most common benign tumor of the uterus in women of reproductive age. However, most of them are asymptomatic and do not require any treatment. Menorrhagia and pelvic pain are the most usual symptoms, and some women may present with infertility or pregnancy-related complications. In those with abnormal uterine bleeding, one should exclude other causes of abnormal vaginal bleeding including endometrial cancer. Diagnosis of uterine fibroid is established by pelvic ultrasonography with or without saline infusion hysterosonography. Management options depend on the patient's fertility potential and desire for future pregnancy. Submucous myoma should be treated by a hysteroscopic approach. Intramural and subserous myomas in women who opt for nonsurgical treatment could be treated with uterine artery embolization (UAE), high-intensity focused ultrasound (HIFU), or medical treatment such as selective gonadotropin-releasing hormone agonists, progesterone receptor modulators, or aromatase inhibitors. All interventions aside from hysterectomy provide temporary relief, although myomectomy, UAE, and HIFU provides more durable symptom relief relative to current medical management. Patients wishing to preserve their fertility are best treated by myomectomy, which can be done by laparoscopy. A laparoscopic approach is more advantageous than laparotomy, but laparoscopic suturing is more demanding. This can be overcome by robotic-assisted laparoscopic myomectomy.
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PMID:Minimally invasive approach for myomectomy. 2041 45

This study was designed to elucidate the signal transduction mechanisms, mediating the antiproliferative effects of analogs of luteinizing hormone releasing hormone (LHRH) on cell lines derived from human cancers of the ovary (EFO-21, EFO-27) and the endometrium (HEC-1A, Ishikawa). The LHRH agonist triptorelin had no measurable effects on the activity of phospholipase C, protein kinase C, or adenylate cyclase in all 4 cell lines, though these enzymes could be activated through pharmacological stimuli. The proliferation of EFO-21, EFO-27 and HEC-1A cells in serum/phenol red-free medium was significantly stimulated by epidermal growth factor (EGF). This mitogenic effect of EGF was dose dependently antagonized by triptorelin, without affecting the concentrations of EGF receptors. Net tyrosine phosphorylation induced by 1 nM EGF was nearly completely suppressed by simultaneous addition of 10 mu M triptorelin or preincubation for 48 h with 100 nM triptorelin. This inhibitory effect of the LHRH agonist on EGF-induced net tyrosine phosphorylation was partly antagonized by exposure to 100 mu M sodium vandate, an inhibitor of phosphotyrosine phosphatase. In EFO-21, EFO-27, and HEC-1A cells exposure to 100 nM EGF for 5 min induced an approximately 5-fold increase in activity of mitogen activated protein kinase (MAP-kinase)/extracellular signal regulated kinase (ERK) which was virtually nullified, when the cells were exposed for 15 min to 10 mu M triptorelin. These data suggest that LHRH signal transduction mechanisms based on the activation of phospholipase C, protein kinase C, and adenylate cyclase, which operate in the pituitary gonadotroph, are not necessarily involved in the mediation of the antiproliferative effects of triptorelin in these ovarian and endometrial cancer cell lines. Instead our findings support the hypothesis that triptorelin interferes with mitogenic signal transduction, probably through antagonizing tyrosine kinase activity of the EGF receptor.
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PMID:Luteinizing hormone-releasing hormone agonist triptorelin antagonizes signal transduction and mitogenic activity of epidermal growth factor in human ovarian and endometrial cancer cell lines. 2154 21

With increase in the marriage age some women experience gynecological cancers before giving birth. Thus fertility sparing in these patients is an important point and much work has been done on conservative management. We here report our experience on fertility sparing with cervical, endometrial and ovarian cancers and include a review of the literature. With cervical cancer, radical trachelectomy with para-aortic and pelvic lymphadenectomy can be performed in patients with early stage IA1-IB cancers, because they have low recurrence rates. The complications are fewer than with radical hysterectomy. For endometrial cancer, the accepted treatment is total abdominal hysterectomy+bilateral salpango-oopherectomy (TAH+BSO), but in young patients with early stage 1 lesions, we can suggest use of hormonal therapy in place of radical surgery if we evaluate with MRI and the result is early stage disease without the other site involvement and the grade of tumor is well differentiated. GNRH analog, oral medroxyprogestrone acetate (MPA), 100-800 mg/day, megestrol acetate 40-160 mg/day and combination of tamoxifen and a progestin have been applied, but we must remember, they should underwent repeated curettage for investigating medical outcome after 3 months. With normal pathology we follow medical therapy for 3 months and can evaluate for infertility treatment. The best option for patients who treated by medical therapy is TAH+BSO after normal term pregnancy. With ovarian cancer, there is much experience on fertility sparing surgery and in Iran conservative surgical management in young patients with stage I (grade 1,2) of epithelial ovarian tumor and sex cord-stromal tumor and patients with borderline and germ cell ovarian tumors is being successfully performed.
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PMID:Fertility sparing treatments in young patients with gynecological cancers: Iranian experience and literature review. 2229 20


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