Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Episialin, which is found on the apical membrane of human endometrial epithelium, has been postulated to act as an antiadhesive factor through the steric hindrance generated by its extensively glycosylated structure. The present studies were designed to test this hypothesis in an in vitro model of endometrial-blastocyst attachment. Episialin was expressed in human endometrial carcinoma cells (HEC-1A > RL95-2), and attachment of JAr choriocarcinoma cells to the endometrial cell monolayers was inversely related to episialin expression. Treatment of endometrial monolayers with type III sialidase increased JAr binding, and this increase was suppressed by HMFG1, a monoclonal antibody specific for episialin. The effects of sialidase appear to have resulted from a contaminant protease rather than from a loss of sialic acid residues, because sialidase preparations other than type III were ineffective. After sialidase treatment, conditioned medium from cells treated with type III sialidase contained more episialin than medium from cells treated with other sialidase preparations. Similar attachment-assay results were obtained using O-sialoglycoprotein endopeptidase; after treatment, the increase in JAr binding (>50%) was suppressed by the antiepisialin antibody. These results demonstrate for the first time that episialin acts as an antiadhesive agent in a model of human endometrial-blastocyst attachment.
 ...
PMID:Episialin acts as an antiadhesive factor in an in vitro model of human endometrial-blastocyst attachment. 1085 71

Fertility and gynaecological malignancies have an important relationship. A clear inverse relationship exists between family size and the incidence of ovarian and endometrial cancer. Current methods of fertility control have an influence on subsequent development of various gynaecological malignancies. A slightly increased risk of breast cancer has been reported in current users and those who had used hormonal contraceptives (OCs) within 10 years; this risk declined with time and disappeared after 10 years. Women who started OC before age 20 had a higher relative risk; the disease did not spread beyond the breast in the majority. Most studies found OC to reduce the risk of ovarian and endometrial cancer. The relative risks of squamous cell carcinoma and adenomatous carcinoma of the cervix have been reported to be 1.3 and 1.5, respectively in ever-users of OCs; however, the aetiology of cervical cancer is multifactoral. Several reports suggest the beneficial effect of tubal ligation and breast feeding in reducing the risk of ovarian cancer. Therapy of gynaecological malignancies may have an influence on subsequent fertility. Amenorrhoea developing after treatment of hydatidiform mole may be due to choriocarcinoma, recurrent mole or a normal pregnancy. Choriocarcinoma can also develop after a partial mole. The risk of fetal teratogenicity from chemotherapy is present only if conception occurs during or immediately following the treatment cycles. Fertility is not impaired following chemotherapy. Successful pregnancies have occurred in women who have had widespread GTD including cerebral metastases. In the young patient with gynaecological malignancy preservation of fertility is possible. Fertility-sparing surgery may be safe in early ovarian epithelial cancers and even in advanced germ cell tumours. Recently, the fertility-sparing surgery of radical trachelectomy and pelvic lymphadenectomy has been carried out for early invasive cervical cancer in young women. Gynaecological cancer occurring in pregnancy is uncommon; it presents the clinician with a difficult situation to manage. In most instances the cancer is treated as though the patient is not pregnant; the timing and mode of delivery needs individualization. The overall prognosis for breast cancer complicating pregnancy is poor. Survival in cervical cancers diagnosed antepartum is similar to the non-pregnant patient. Ovarian cancer in pregnancy has a good prognosis because of the early stage at diagnosis.
 ...
PMID:Chien-Tien Hsu Memorial Lecture. Fertility and gynaecologic malignancies. 1133 Jul 24

Serum tumor markers are useful in diagnosis and follow-up for patients with gynecological malignancy or breast cancer. In epithelial ovarian cancer, CA125 has been identified as the most sensitive marker. Unfortunately, CA125 detection in the serum of patients with minimal malignant tumor has not been possible. Many nonmalignant conditions including endometriosis, menstruation and massive ascites may elevate the CA125, and almost 50% of patients with clear cell adenocarcinoma do not show CA125 elevated above 100 U/ml. To improve sensitivity and specificity in the diagnosis of ovarian cancer, the use of multiple tumor markers and the simultaneous use of image diagnosis should be employed. The value of tumor markers in the screening for cervical cancer and endometrial cancer has received little attention. However, the utility of serum SCC as a marker for monitoring cervical squamous cell carcinoma has been established. Since hCG is produced by gestational trophoblastic neoplasia and is a sensitive marker of trophoblastic cells in the body, patients with choriocarcinoma or invasive mole must be followed closely for this parameter. The improvement of the hCG detection technique has reduced the mortality rate from trophoblastic neoplasia. In breast cancer, many markers including CEA and CA15-3 are used, and they are reported to be useful as markers for monitoring.
 ...
PMID:[Tumor markers in gynecological and breast cancer]. 1474 42

Membrane-bound peptidases play a key role in the control of growth, differentiation, and signal transduction of many cellular systems by degrading bioactive peptides. Thus, abnormal changes in their expression pattern and catalytic function result in altered peptide activation, which contributes to neoplastic transformation or progression. In this review, we describe our recent findings along with work from other groups on the expression and biological functions of membrane-bound peptidases in cancer, focusing on the regulatory roles of three peptidases, aminopeptidase A (APA), neutral endopeptidase (NEP) and placental leucine aminopeptidase (P-LAP), in the progression of gynecologic malignancies. APA, NEP and P-LAP are differentially expressed and localized in various gynecologic malignancies including cervical cancer, endometrial cancer, ovarian cancer and choriocarcinoma in a tumor-type specific pattern. The expression levels are up- or down-regulated depending on histological grade or disease progression. These peptidases play regulatory roles in tumor cell proliferation, invasion or angiogenesis via degradation/inactivation of target peptides such as angiotensin II, endothelin-1 and oxytocin, which act on cancer cells as stimulatory or inhibitory factors. Thus, membrane-bound peptidases may become not only a new diagnostic/prognostic marker, but also a novel molecular target for the treatment of gynecologic malignancies.
 ...
PMID:Regulatory role of membrane-bound peptidases in the progression of gynecologic malignancies. 1544 4

The endometrial cavity may demonstrate various imaging manifestations such as normal, reactive, inflammatory, and benign and malignant neoplasms. We evaluated usual and unusual magnetic resonance imaging (MRI) findings of the uterine endometrial cavity, and described the diagnostic clues to differential diagnoses. Surgically proven pathologies of the uterine endometrial cavity were evaluated retrospectively with pathologic correlation. The pathologies included benign endometrial neoplasms such as endometrial hyperplasia and polyp, malignant endometrial neoplasms such as endometrial carcinoma and carcinosarcoma, endometrial-myometrial neoplasm such as endometrial stromal sarcoma, pregnancy-related lesions in the endometrial cavity such as gestational trophoblastic diseases (hydatidiform mole, invasive mole and choriocarcinoma) and placental polyp, myometrial lesions simulating endometrial lesions such as submucosal leiomyoma and some adenomyosis, endometrial neoplasms simulating myometrial lesions such as adenomyomatous polyp and endometrial lesions arising in the hemicavity of a septate/bicornate uterus, and fluid collections in the uterine cavity (hydro/hemato/pyometra). It is important to recognize various imaging findings in these diseases, in order to make a correct preoperative diagnosis.
 ...
PMID:Pathologies of the uterine endometrial cavity: usual and unusual manifestations and pitfalls on magnetic resonance imaging. 1622 15

Nongestational choriocarcinomas rarely occur outside the gonads or teratomas. We report a serous carcinoma of the endometrium with a choriocarcinomatous component and review of the literature. A 61-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy for a serous carcinoma with choriocarcinomatous component. Immunohistochemistry showed a strong p53 staining of the serous component and the cytotrophoblastic cells of the choriocarcinomatous component; the syncytiotrophoblast was negative. The initial serum human chorionic gonadotropin (hCG) was 225,000 IU/L. Postoperatively, the patient developed diffuse pulmonary metastatic disease. Despite chemotherapy, the patient died 2 months after initial diagnosis. Abstracting the data from the reported cases and from the literature, it can be assumed that 2 different tumor types exist. The first one is morphologically and clinically more related to the gestational choriocarcinoma with strongly elevated serum hCG levels, early onset of (distant) metastatic disease, and consecutively rapid and often fatal clinical course. The second type presents as an endometrial carcinoma with single syncytiotrophoblast-like cells, associated with low serum hCG, no distant metastatic disease, and, consequently, a better prognosis. The prognostically relevant component for long-time survival in the latter variant is the nontrophoblastic component.
 ...
PMID:Serous carcinoma of the endometrium with choriocarcinomatous differentiation: a case report and review of the literature indicate the existence of 2 prognostically relevant tumor types. 1681 62

This article reports a uterine gestational choriocarcinoma arising in a 57-year-old woman with a long latent period of 22 years from the last known pregnancy. Diagnosis was made on an endometrial biopsy specimen, and given the age of the patient, the long latent period, and the limited sample, trophoblastic differentiation within an endometrial carcinoma was considered. The results of DNA polymorphism studies illustrated both paternal and maternal alleles within the tumor in equal amounts, confirming the neoplasm to be gestational in origin and to have originated from a nonmolar gestation. The report discusses the value of DNA polymorphism studies in distinguishing gestational from nongestational choriocarcinoma and from trophoblastic differentiation within a carcinoma.
 ...
PMID:Uterine gestational choriocarcinoma developing after a long latent period in a postmenopausal woman: the value of DNA polymorphism studies. 1841 87

Estrogen action is regulated at the receptor level by regulation of expression of estrogen receptors, and at the pre-receptor level by interconversions between the active hormone (estradiol) and its inactive counterparts (estrone, estrone-sulfate). In peripheral tissues, estrogens can be produced via the aromatase or the sulfatase pathways. Aromatase converts androstenedione and testosterone to estrone and estradiol, respectively, and sulfatase releases estrogens from inactive sulfates, while sulfotransferase catalyzes the reverse reaction. In both pathways, 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are of paramount importance as they catalyze activation of estrone to estradiol and inactivation of estradiol to estrone. These enzymes belong to either the short-chain dehydrogenase/reductase (SDR) or the aldo-keto reductase (AKR) protein superfamilies. Differential expression of these pre-receptor regulatory enzymes can lead to high estradiol concentrations, which have been implicated in the development of different diseases. Here, we have examined gene expression levels of estrogen-metabolizing enzymes, as six SDRs (17beta-HSD types 1, 2, 4, 7, 8, 12) and one AKR (17beta-HSD type 5; AKR1C3), of aromatase, steroid sulfatase (STS) and estrogen sulfotransferase (SULT1E1), and of the alpha and beta estrogen receptors (ERs), in breast cancer (MCF-7), endometrial cancer (Ishikawa), choriocarcinoma (JEG3) and liver cancer (HepG2) cell lines. After RNA isolation and cDNA synthesis, real-time PCR analyses were performed. The expression of AKR1C3 was examined also at the protein level. Our data show that in all four cancer cell lines, estradiol can be synthesized from estrone by the action of 17beta-HSD type 12, or from estrone-sulfate by sulfatase. In JEG3 and HepG2 cells, estradiol can be formed from androgens by aromatase and 17beta-HSD type 1. Also in HepG2 cells, AKR1C3, which converts androstenedione to testosterone, in concert with aromatase might be responsible for estradiol formation. In MCF7 and Ishikawa cells, estradiol exerts its actions through ERalpha, while in JEG3 and HepG2 cells, it may act through non-ER-mediated pathways.
 ...
PMID:Expression of 17beta-hydroxysteroid dehydrogenases and other estrogen-metabolizing enzymes in different cancer cell lines. 1902 35

Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that estrogen signaling is mediated not only by ERalpha and ERbeta nuclear receptors, but also by GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report that primary human endometriotic H-38 cells express high levels of GPR30 with no detectable ERalpha or ERbeta. Using a novel tamoxifen analogue, STX, which activates GPR30 but not ERs, significant stimulation of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was observed in H-38 cells and in Ishikawa endometrial cancer cells expressing GPR30; a similar effect was observed in JEG3 choriocarcinoma cells. STX treatment also increased cellular pools of phosphatidylinositol (3,4,5) triphosphate, a proposed ligand for the nuclear hormone receptor SF-1 (NR5A1). Consistent with these findings, STX, tamoxifen, and the phytoestrogen genistein were able to increase SF-1 transcription, promote Ishikawa cell proliferation, and induce the SF-1 target gene aromatase in a GPR30-dependent manner. Our findings suggest a novel signaling paradigm that is initiated by estrogen activation of the 7TM receptor GPR30, with signal transduction cascades (PI3K and MAPK) converging on nuclear hormone receptors (SF-1/LRH-1) to modulate their transcriptional output. We propose that this novel GPR30/SF-1 pathway increases local concentrations of estrogen, and together with classic ER signaling, mediate the proliferative effects of synthetic estrogens such as tamoxifen, in promoting endometriosis and endometrial cancers.
 ...
PMID:Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation. 1954 22

Recent studies have shown an activation of the local renin-angiotensin system (RAS) in various tumor tissues, including the abundant generation of angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) and the upregulation of angiotensin II type 1 receptor (AT1R) expression. Thus, considerable attention has been paid not only to the role of the RAS in cancer progression, but also to the blockade of RAS as a new approach to the treatment of human cancer. There is increasing evidence that the Ang II-AT1R pathway is involved in tumor growth, angiogenesis and metastasis in various experimental animal models, suggesting the therapeutic potential of an ACE inhibitor and AT1R blocker. In addition, specific Ang II-degrading enzymes are also expressed in tumors and play a regulatory role in tumor cell proliferation and invasion. This review focuses on the role of the RAS in the progression of gynecologic cancers, such as cervical cancer, endometrial cancer, ovarian cancer, and gestational choriocarcinoma. We present here the clinical potential of blocking the RAS as a novel and promising strategy for the treatment of gynecologic cancers.
 ...
PMID:Role of the renin-angiotensin system in gynecologic cancers. 2139 51


<< Previous 1 2 3 4 Next >>