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

The effect of conophylline, a new vinca alkaloid that inhibits ras expression, on tumour cell adhesion and infiltration was evaluated using a human endometrial cancer cell line. When SNG-II, a highly differentiated human endometrial cancer cell line, was exposed to conophylline, the cells developed filamentous processes at concentrations which did not affect cell proliferation (0.03-0.3 microgram/ml). After exposure to conophylline (0.3 microgram/ml), cells adherent to matrigel- and type IV collagen-coated wells respectively decreased to 26.9% and 33.3% of the number in the untreated control culture (p < 0.01). In an in vitro invasion assay using a Boyden chamber, infiltration of cells exposed to conophylline decreased to 19.4% (0.3 microgram/ml) (p < 0.01) of the control. In a wound assay, conophylline inhibited the movement of cells at 24 hr after wounding. Flow cytometric analysis revealed that expression of integrin beta 1 was not altered by conophylline, but E-cadherin and CD44 were decreased. The expression of E-cadherin and CD44 could be changed by conophlline.
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PMID:Inhibition of attachment and chemotactic invasion of uterine endometrial cancer cells by a new vinca alkaloid, conophylline. 1065 93

Historical observations have suggested that endometrial carcinomas vary in histopathologic appearance and clinical features. More recent, systematic studies have provided epidemiologic, clinicopathologic, and molecular support for these observations. Specifically, studies suggest that the most common type of endometrial carcinoma, endometrioid adenocarcinoma, develops from endometrial hyperplasia in the setting of excess estrogen exposure and usually pursues an indolent clinical course. In contrast, a minority of endometrial carcinomas, best represented by serous carcinoma, do not seem to be related to estrogenic risk factors or elevated serum hormone levels, and these tumors seem to develop from atrophic rather than hyperplastic epithelium. We have proposed that serous carcinomas develop from "endometrial intraepithelial carcinoma," a lesion representing malignant transformation of the endometrial surface epithelium. Whereas endometrioid carcinoma and endometrial hyperplasia are associated with microsatellite instability and ras and PTEN mutations, serous carcinoma and endometrial intraepithelial carcinoma are associated with p53 mutations and abnormal accumulation of p53 protein. Based on these data regarding the pathogenesis of endometrioid and serous carcinoma, we have proposed a dualistic model of endometrial carcinogenesis incorporating a "classic" estrogen-driven pathway and an "alternative" pathway seemingly unrelated to hormones. It is hoped that further studies may permit the extension and modification of this model and that these advances will lead to improved diagnosis, management, and prevention.
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PMID:Theories of endometrial carcinogenesis: a multidisciplinary approach. 1075 40

Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Genes that cause cancer are of two distinct types: oncogenes and onco-suppressor genes. The normal proto-oncogene can be converted into an active oncogene by deletion or point mutation in its coding sequence, gene amplification, and by specific chromosome rearrangements. Mutations and abnormal expression in ras, myc, c-erbB-2, and other oncogenes have been reported in several types of gynecological cancer. Onco-suppressor genes are involved in gynecological cancer, their functions are localized in different phases of the cell cycle. Structural changes and deletions of these genes can cause cancer. Mutations in the p53, BRCA1, DCC, and PTEN genes have been reported in gynecological cancers such as ovarian, cervical, and endometrial cancer. Human papillomaviruses are of major interest because specific types (HPV-16, -18, and several others) have been identified as causative agents in at least 90% of cancers of the cervix. In this study we summarize the available information regarding the implication of specific oncogenes, onco-suppressor genes, and HPV in the development of female genital malignancies.
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PMID:Molecular basis of gynecological cancer. 1081 92

The AKT proteins are constitutively activated in several types of human cancers, which may play a role in carcinogenesis. In this study, we examined the activation of AKT in a panel of human endometrial cancer cell lines and tumor samples in this study. Two endometrial cancer cell lines, Ishikawa (ISK) and RL-95 and several tumor samples showed elevated levels of phosphorylated AKT PTEN, which is mutated in 45% of endometrial cancers, is a negative regulator of AKT. We examined the growth suppression activity of PTEN in ISK and KLE endometrial cancer cells. Expression of PTEN significantly suppressed the growth of both cell clines. In primary rat embryo fibroblasts, PTEN also inhibited malignant transformation mediated by ras and c-myc oncogenes. These two oncogenes are commonly mutated or amplified in endometrial cancer. These results suggest that PTEN may be a potent therapeutic agent for endometrial cancer.
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PMID:Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells. 1149 85

We set out to determine the relative timing of loss of DNA mismatch repair and KRAS2 mutation in endometrial tumorigenesis. We studied endometrial carcinoma (CA) and synchronous atypical endometrial hyperplasia (AEH), the premalignant precursor of endometrial cancer. Carcinoma and hyperplasia were investigated for loss of mismatch repair as evidenced by microsatellite instability (MSI) and for KRAS2 mutations. Endometrial cancers previously shown to be MSI-positive were evaluated for KRAS2 codon 12 and 13 mutations. DNA was isolated from foci of AEH concomitant with, but physically remote from, the cancers by use of tissues prepared by laser capture microdissection (LCM). The AEH DNAs were then assessed for MSI and KRAS2 mutations. Of 210 endometrial CAs investigated, 51 (26%) were MSI-positive, and among those, 21 (41%) arose concomitantly with AEH. Of 41 foci of AEH (mean, two foci per patient) investigated, 34 (83%) were MSI-positive. KRAS2 mutations were seen in 5/51 (10%) MSI-positive carcinomas. From the five patients informative for both KRAS2 mutation and MSI, 10 foci of AEH were available for investigation. All 10 AEH specimens (100%) were MSI-positive, and six (60%) had the KRAS2 mutation present in the coexisting CA. The observation that some MSI-positive AEH specimens lack the KRAS2 mutation seen in the coexisting CA supports a model in which loss of DNA mismatch repair precedes KRAS2 mutation. However, in addition to the absence of KRAS2 mutations in AEH, we discovered mutations in LCM hyperplasia and carcinoma specimens that were not present in the portion of the cancers originally investigated. These discordant genotypes suggest genetic heterogeneity in endometrial hyperplasia and concomitant cancer.
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PMID:Genotypic and phenotypic progression in endometrial tumorigenesis: determining when defects in DNA mismatch repair and KRAS2 occur. 1174 70

Endometrial cancer is a common gynaecological malignancy in the industrialised world. Unopposed stimulation of the endometrium by oestrogens is the classic aetiological factor associated with the development of this malignancy. However, not all are associated with oestrogen exposure and two different clinicopathological types can be distinguished: the oestrogen-related of endometrioid type (type I) and the non-oestrogen-related of non-endometrioid type (mainly papillary serous or clear cell carcinomas) (type II). Recent advances in the knowledge on the molecular genetics of endometrial cancer have shown that the molecular changes involved in its the development differ in oestrogen-dependent type I and non-oestrogen-dependent type II. Type I carcinomas frequently show mutations of DNA-mismatch repair genes (MLH1, MSH2, MSH6), PTEN, k-ras and beta-catenin genes whereas type II malignancies are characterised by aneuploidy, p53 mutations and her2/neu amplification. This article reviews the latest findings concerning common gene mutations involved in the development and progression of endometrial cancer.
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PMID:Molecular genetics and endometrial cancer. 1280 10

The recently described gene, RAB32, is a ras proto-oncogene family member that encodes an A-kinase-anchoring protein. RAB32 has been found to be frequently hypermethylated in microsatellite instability-high (MSI-H) colon cancers. We sought to determine the prevalence of RAB32 hypermethylation in gastric and endometrial adenocarcinomas, the 2 other major tumor types in which MSI-H is common. Moreover, we delineated the association of RAB32 hypermethylation with microsatellite instability (MSI) and hMLH1 hypermethylation. MSI status and hypermethylation of the RAB32 and hMLH1 genes were studied in paired primary normal and tumor tissues from 48 patients with gastric cancer. An additional 80 endometrial cancer patients were studied for RAB32 methylation and MSI status. Thirteen (27%) of 48 gastric cancers demonstrated evidence of RAB32 hypermethylation. MSI status was determined in 46 of the tumors, with 7 (100%) of 7 MSI-H tumors, 1 (33%) of 3 MSI-low (MSI-L) tumors and 4 (11%) of 36 microsatellite-stable (MSS) tumors found to harbor RAB32 hypermethylation. RAB32 methylation was significantly associated with intestinal type histology and concomitant hMLH1 hypermethylation in gastric cancer. In contrast, RAB32 methylation occurred in only 1 of 80 endometrial cancers, including 20 MSI-H, 8 MSI-L and 52 MSS tumors. Hypermethylation of hMLH1 was noted in 16 (20%) of 80 endometrial tumors. We conclude that although RAB32 methylation is rare in endometrial cancers, it is strongly associated with hMLH1 hypermethylation and MSI in gastric adenocarcinomas. Given its similar involvement in colon cancer, RAB32 inactivation may represent a component of the oncogenic pathway of microsatellite-unstable gastrointestinal adenocarcinomas.
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PMID:RAB32 hypermethylation and microsatellite instability in gastric and endometrial adenocarcinomas. 1655 77

Molecular genetic evidence indicates that endometrial carcinoma likely develops as the result of a multistep process of oncogene activation and tumor suppressor gene inactivation. These molecular alterations appear to be specific for Type I (endometrioid) and Type II (non endometrioid) cancers. Type I cancers are characterized by mutation of PTEN, KRAS2, defects in DNA mismatch repair, as evidenced by the microsatellite instability phenotype, and a near diploid karyotype. Type II cancers often contain mutations of TP53 and Her-2/neu and are usually nondiploid. The clinical value of many of these molecular markers is now being tested and it may help to refine diagnosis and establish an accurate prognosis. Furthermore, some of these tumor biomarkers constitute the targets for emerging therapies. Transtuzumab against Her-2/neu and bevacizumab against VEGF overexpressing carcinomas are among the promising novel treatments. Additional translational research is needed to identify molecular and genetic alterations with potential for therapeutic interventions.
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PMID:Molecular alterations in the pathogenesis of endometrial adenocarcinoma. Therapeutic implications. 1664 98

Tamoxifen remains a frontline treatment for hormone-responsive breast cancer despite its use being associated with a 2-7-fold elevated risk of developing endometrial carcinoma. Several groups have investigated whether tamoxifen induces DNA-damaging (genotoxic) versus non-genotoxic mechanisms. Some studies point to the presence of tamoxifen-DNA adducts while others suggest otherwise. In many of these studies, the histological sub-type has not been considered; as type 1 carcinomas are associated with PTEN and KRAS2 mutations whereas type 2 carcinomas exhibit TP53 and ERBB-2 mutations, the absence of this information makes comparisons between such independent investigations difficult. An examination of the sub-types of endometrial carcinoma points to histological and mechanistic distinctions between sporadic and tamoxifen-associated disease; this could suggest differing aetiologies. On this basis, we propose a dual mechanism of action highlighted by the different patterns of endometrial carcinoma sub-types. Tamoxifen may initially be pro-oestrogenic in the endometrium giving rise to elevated type 1 endometrioid carcinoma occurrence whereas after long-term use, there is an increase of type 2 disease or malignant mixed mullerian tumours associated with a hormone-independent mechanism of action. Despite these associated risk factors, and the introduction of new selective oestrogen receptor modulators (SERMs), we suggest that the organ-specific pleiotrophic effects of tamoxifen mean that this effective therapeutic agent for breast cancer will continue to have significant usage. The focus of future research should concentrate on the different aetiologies of tamoxifen-associated endometrial carcinomas while efforts continue to develop future SERMs.
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PMID:Tamoxifen: important considerations of a multi-functional compound with organ-specific properties. 1717 95

Endometrial carcinoma is one of the most common cancers in women. A limited number of endometrial carcinoma cell lines are available for studies of signal transduction pathways and experimental therapeutics in vitro. However, these cell lines have not been comprehensively characterized. In this study, we used genome-wide microarray-based comparative genomic hybridization (aCGH) technology to characterize five of the more commonly used endometrial cancer cell lines. We detected DNA copy-number gains in chromosomal regions 2q, 3p, 3q, 5q, 7p, 17q, and 19q in all five cell lines. Other common sites of copy-number gains, which were detected in four of five cell lines, included segments of chromosomes 1, 6, 8, 9, 11, 12, and 16. In all five cell lines, we found DNA copy-number losses in regions 3p, 10p, 10q, 11q, 11p, 14q, 15q, 18p, and 21q. Other common sites of genetic aberrations included segments of chromosomes 1, 2, 4, 5, 6, 16, 20, and 22. The genes involved in the copy-number alterations included the oncogenes PIK3CA (3q26.3), K-ras (12p12.1), R-ras (19q13.3-qter), Raf-1 (3p25), EGFR (7p12), Akt1 (14q32.32), and Akt2 (19q13.1-q13.2). A pathway analysis showed that genes in the PI3K and Wnt pathways are commonly affected. Our characterization of genomic alterations in these five commonly used endometrial cancer cell lines provides valuable genomic information for research that focuses on these key oncogenic pathways in endometrial cancer.
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PMID:Genomic characterization of gene copy-number aberrations in endometrial carcinoma cell lines derived from endometrioid-type endometrial adenocarcinoma. 2021 40


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