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)

Insulin and insulin-like growth factor I are known to be mitogenic and therefore may play a role in the development of endometrial cancer. We undertook this study to investigate whether human endometrial cancer tissue has receptors for these substances. Endometrial cancer tissue samples were obtained at hysterectomy from 10 women with endometrial cancer, and control endometrial tissue was collected from normal cycling women undergoing hysterectomy for nonendocrine problems. Binding studies with iodine 125-insulin and [125I]insulin-like growth factor I revealed the presence of specific binding sites for insulin and insulin-like growth factor I in both normal endometrium and endometrial cancer tissue. The percent binding of [125I]insulin in the endometrial cancer tissue (mean +/- SE 2.4% +/- 0.5%/100 micrograms protein) was not significantly different from that in normal endometrium (3.5% +/- 1%/100 micrograms protein). On the contrary, the percent total binding of [125]insulin-like growth factor I in the endometrial cancer (5.3% +/- 1.5%/100 micrograms protein) was significantly (p less than 0.04) higher than that observed in normal endometrium (2.1% +/- 0.4%/100 micrograms protein). There was a significant positive correlation between the histologic grade of the tumor and the insulin-like growth factor I binding (r = 0.865, p less than 0.02). The affinity constants for the high-affinity receptors were similar in the normal and neoplastic endometrium. These results indicate that insulin and insulin-like growth factor I may play a role in the growth and development of endometrial cancer.
 ...
PMID:Specific binding sites for insulin and insulin-like growth factor I in human endometrial cancer. 172 87

In recent years there has been an increase in the use of parenteral oestradiol as an alternative to the conventional oral preparations used in hormone replacement treatment (HRT) in menopause, such as conjugated equine oestrogens (CEE). The latter have been subject in the past to apprehensions, partly due to misunderstanding and oversimplification but also in relation to problems that have arisen during the history of HRT, for example the increase in endometrial cancer risk deriving from the use of non-progestogen-opposed treatment. However, confidence in long-term HRT comes from the epidemiological findings, which refer mainly to the use of oral CEE unopposed by progestogen: a reduced risk of osteoporotic fractures and of cardiovascular disease, and a very limited risk of breast cancer. Oral oestrogens produce marked hepatocellular effects. These effects are, on the whole, favourable from the point of view of cardiovascular risk. In addition, it cannot be excluded that some hepatocellular effects of oral oestrogen, for example increased sex hormone binding globulin levels and reduced circulating insulin-like growth factor I activity, offer protection to the breast. As progestogen supplementation is needed in non-hysterectomized women, priority should be given to preparations, such as progesterone or dydrogesterone, that feature good endometrial activity without opposing oestrogen hepatocellular effects.
 ...
PMID:Long-term hormone replacement treatment in menopause: new choices, old apprehensions, recent findings. 810 14

Myofibroblastic invasion associated with malignant epithelial cells of endometrial cancer as well as other cancers is often found in the interstitium. To assess the myofibroblastic-epithelial interaction, frozen sections from a total of 10 endometrial cancers with or without invasive myofibroblasts were immunohistochemically examined. Interestingly, the invasive myofibroblasts adjacent to malignant epithelial cells showed frequently intensive positive staining of several growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor I, and epidermal growth factor, the cognate receptors such as Fetal liver kinase-1/Kinase Insert Domain-containing receptor/VEGF receptor-2, fms-like tyrosine kinase-1/VEGF receptor-1, and epidermal growth factor receptor, several cell cycle regulators such as cyclins and cyclin dependent kinases, and estrogen receptor alpha. Moreover, we indicated that the majority of the myofibroblasts as well as cancer epithelial cells are proliferating because of their positive staining of proliferating cell nuclear antigen and Ki-67. Furthermore, the myofibroblasts were also positive of hypoxia-inducible factor 1 alpha, which is a marker protein of hypoxia, probably followed by activation of VEGF-Flk-1 and VEGF-fms-like tyrosine kinase-1 signals, which could initiate angiogenesis. These findings suggest directly that the myofibroblasts might participate in the progression of tumor cells in terms of cancer cell growth stimulation and also activated initiation of angiogenesis.
 ...
PMID:Cancer-associated myofibroblasts possess various factors to promote endometrial tumor progression. 1159 1

Controversies are still seen in the histological differential diagnosis of hyperplasia and well-differentiated endometrial carcinoma. Prediction of endometrial cancer in patients with hyperplasia with atypia, with the available markers has not been reliable yet. Hence these patients require more attention in the clinical management. Endometrial hyperplasia is proliferation of endometrial glands resulting in a higher gland : stroma ratio. Cytological atypia, which may progress to or co-exist with endometrial cancer and other pathological changes, result from estrogen stimulation unopposed by progesterone. Biomarkers whose expression is altered in cases of endometrial hyperplasia or cancer such as progesterone receptor, insulin-like growth factor I, retinaldehyde dehydrogenase type II, and secreted frizzled-related protein 4, seem to be promising to use as early-stage tumor markers. Mutation of PTEN is present in 83% of endometrial adenocarcinoma cases, making it the most frequent early molecular genetic alteration in type 1 endometrial tumors, which are generally associated with hyperplasia. p53 gene mutation is not found in endometrial hyperplasia, but researchers have detected this mutation in 20% of cases of endometrial carcinoma and 90% of cases of serous endometrial tumors. Cyclooxygenase-2 is important in tumorogenic transformation of hyperplasia. Expression of cyclooxygenase-2 decreases apoptosis, increases angiogenesis, and is related to invasiveness. Cyclooxygenase-2 expression increases significantly in cases of well-differentiated endometrial adenocarcinoma. Prostaglandin E2 is known to regulate aromatase gene expression and is the product of cyclooxygenase-2. The data about aromatase inhibitors are promising; in breast cancer patients, treatment with tamoxifen induces uterine abnormalities as early as 3 months after the initiation of therapy. In contrast, these abnormalities are not seen in patients who receive aromatase inhibitors and switched therapy after tamoxifen withdrawal may reverse tamoxifen-associated endometrial thickening.
 ...
PMID:From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures. 1828 70