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

Common fragile sites (CFS) are large, genomically unstable regions, which are hot-spots for deletions and other alterations, especially in cancer cells. Several have been shown to contain genes that span large genomic regions, such as FHIT (1.5 Mb), WWOX (1.0 Mb), GRID2 (1.36 Mb), PARK2 (1.3 Mb), and RORA (730 kb). These genes are frequently inactivated in multiple different cancers, and FHIT and WWOX are shown to function as tumor suppressors. The disabled-1 gene (DAB1) is one of the human homologs of the Drosophila disabled locus, which in mammals is involved in neuronal migration and lamination in the developing cerebral cortex. Mice DAB1 inactivation results in the neurological mutant Scrambler, having similarities to mice with the inactivation of PARK2 (Quaker), GRID2 (Lurcher), and RORA (Staggerer). We were interested in whether DAB1 was another large CFS gene that could have cancer development importance. We demonstrated here that the human DAB1 gene (spanning 1.25 Mb) mapped within FRA1B CFS region on chromosomal band 1p32.2. Real-time RT-PCR analysis revealed that the expression level of DAB1 was decreased in many human cancer samples, including primary tumor tissues and cancer-derived cell lines, from several different cancers, especially in brain and endometrial cancer. Additionally, the introduction of an over-expression DAB1 plasmid into two different cell lines, having insignificant endogenous DAB1 expression, resulted in decreased cell growth. In summary, DAB1 is another gene that resides within an unstable CFS region and might play a role in human tumorigenesis. These data may provide further linkage between neurological development and cancer.
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PMID:Disabled-1 is a large common fragile site gene, inactivated in multiple cancers. 1800 69

Endometrial cancer is the most common gynecologic cancer in the developed world. The cell-adhesion protein E-cadherin acts as a tumor-suppressor protein and is down-regulated by the transcription factor Snail, whose expression was shown to be associated with estrogen receptor signaling. This study aimed to investigate the expression of E-cadherin, Snail, and estrogen-receptor alpha in 87 primary tumors and 26 metastases of endometroid endometrial carcinomas. Reduced E-cadherin immunoreactivity was seen in 44.8% of the primary tumors and 65.4% of the metastases with a statistical correlation to higher tumor grade (P=0.003) only in metastatic lesions. About 28.7% of primary tumor specimens showed a positive Snail immunoreactivity that was correlated with reduced estrogen-receptor alpha expression (P=0.047). Positive Snail immunoreactivity was also seen in 53.8% of the metastases where it was correlated with higher tumor grade (P=0.003) and abnormal E-cadherin expression (P=0.003). Interestingly, a Snail expressing endometrial carcinoma-cell line showed a higher migration potential than a variant of this cell line with low levels of Snail. Taken together, our data are in line with a proposed role for Snail in endometrial tumor progression.
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PMID:The E-cadherin repressor snail plays a role in tumor progression of endometrioid adenocarcinomas. 1804 86

The alpha(v)beta(6) integrin (alphavbeta6) has been shown to be up-regulated in adenocarcinoma of the breast, colon, stomach, and ovary, generally reflecting a more aggressive phenotype. Expression in endometrial cancer has not been reported. We analyzed alphavbeta6 expression in the tissue from primary endometrial carcinomas (endometrioid type) using a mouse monoclonal antibody against human alphavbeta6, and correlated the findings with grade, stage, and nodal involvement. Normal cycling endometrium was studied for comparison. alphavbeta6 was only weakly expressed in normal epithelium and infrequently expressed in precancers, but up-regulated in the majority of endometrial carcinomas, especially with high grade. Nodal metastases strongly expressed alphavbeta6, even when the primary tumor showed only focal expression. No correlation was found between expression and depth of invasion or the presence of metastases. Overexpression of alphavbeta6 in endometrial carcinoma is common. Expression is high in metastatic lesions. The level of expression of the primary tumor was not indicative of the presence of nodal metastasis; however, the number of cases with nodal metastases was limited.
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PMID:Overexpression of the alphavbeta6 integrin in endometrial cancer. 1869 61

In this article we review the current and developing roles of magnetic resonance imaging (MRI) in endometrial and cervical cancer. In endometrial cancer, the purpose of MRI is to stage the primary tumor and in particular to identify myometrial and cervical invasion and extra-uterine disease, thereby informing preoperative surgical planning. MRI is also used to safely select young patients suitable for fertility-preserving medical management. In cervical cancer, MRI has an established role in local staging and in assessing proximal extension of tumors in young women for feasibility of fertility-preserving surgery. It is used to plan radiotherapy for primary tumors in cervical cancer and particularly for conformal radiotherapy to deliver optimal doses to the tumor sites, while limiting unwanted exposure of bowel and other pelvic organs. In both cancers, MRI is used for diagnosing nodal disease, surveillance, detection of recurrence, and evaluation of complications secondary to treatment.
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PMID:Magnetic resonance imaging of endometrial and cervical cancer. 1883 2

Loss of heterozygosity (LOH) is implicated in the initiation and progression of various human neoplasia, and is observed in both early or in advanced-stage human cancers. The current study was aimed at investigating the frequency of LOH TP53 in human endometrial carcinoma (EC) metastases. LOH was analyzed using 3 intragenic polymorphisms in 38 primary ECs and corresponding metastatic lesions. Allelic loss at intron 1 was detected in 14 out of 38 (37%) primary carcinomas and in 11 out of 38 (29%) metastatic lesions. LOH at intron 1 in primary and metastatic tumors was concomitantly noted in 8 out of 38 (21%) cases. LOH at intron 4 was seen in 46% (17 out of 37) primary ECs and in 35% (13 out of 37) metastatic lesions. LOH at intron 4 in primary tumor/metastasis was concomitantly demonstrated in 27% (10 out of 33) cases. Allelic loss at exon 4 was detected in 5 out of 33 (15%) primary ECs and in one out of 33 (3%) corresponding metastases. Coexistence of LOH TP53 in primary ECs with metastases at intron 1 and intron 4 was observed in three out of 33 (9%) cases. Correlation between allelic loss at intron 1 in primary ECs and corresponding metastases was found (R = 0.475, p = 0.003). Moreover, there was correlation between LOH at intron 1 in metastastic ECs and allelic imbalance at intron 4 in primary uterine tumors (R = 0.416, p = 0.01). There was a relationship between LOH at intron 4 in primary ECs and corresponding metastatic lesions (R = 0.457, p = 0.004). LOH TP53 at intron 4 correlated with the presence of the neoplasm in the uterine cervix (R = 0.319, p = 0.049), and with the non-endometrioid type of primary tumor (R = 0.371, p = 0.024). There was a significant correlation between exon 4 LOH and patient age (less or equal to 50 years and above this age; R = -0.375, p = 0.032). p53 overexpression was present in thirteen out of 38 (34%) cases, both in primary ECs and in metastatic lesions. Overexpression of p53 was higher in non-endometrioid ECs (three out of 5; 60%) than in endometrioid-type uterine tumors (ten out of 33; 30.3%; p = 0.315). p53 overexpression correlated with the presence of cancer in the lumen of fallopian tube(s) (R = 0.032, p = 0.046), and with allelic loss at intron 1 in primary ECs (R = 0.599, p = 0.0001). In conclusion, LOH occurs not only in primary uterine tumors but also in corresponding metastases, with the higher incidence being reported at intron 4 of the TP53. A significant link existed between LOH TP53 at intron 1 and p53 overexpression in primary ECs, but not in the corresponding metastatic lesions.
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PMID:Allelic loss at TP53 in metastatic human endometrial carcinomas. 1956 39

Expression of Migration inducting gene-7 (Mig-7) is limited to tumor cells and to date not found in normal tissues. Multiple tumor microenvironment factors, such as epidermal and hepatocyte growth factors, in concert with alphavbeta5 integrin ligation, induce Mig-7 mRNA expression. Gain or loss of Mig-7 protein studies shows that Mig-7 promotes invasion of colon and endometrial carcinoma cells. These data led us to hypothesize that targeting Mig-7 through various methods could decrease invasion, enhance monocyte cell killing of tumor cells, and inhibit disease progression. To begin testing this hypothesis, an in vitro chemoinvasion assay of endometrial carcinoma cells treated with Mig-7-specific or control antibodies was used. Mig-7 antibody significantly reduced invasion by >60% compared with controls. In another approach to test this hypothesis, an in vitro analysis of peptide-stimulated human peripheral blood monocyte cells and their killing of MCF-7 breast carcinoma cells was used. Mig-7 peptide treatment increased monocyte cell tumor necrosis factor expression and killing of MCF-7 cells 30-fold over no peptide stimulation and 3-fold over MUC-1 or control peptide treatments. Furthermore, stably expressing Mig-7-specific short hairpin RNA resulted in significantly reduced Mig-7 protein levels and early primary tumor growth in a xenograft nude mouse model. Reduced phosphorylation of ERK1/2, Akt, and S6 kinase as well as decreased membrane-type 1 matrix metalloproteinase activity were mechanisms through which Mig-7 protein caused these effects. Based on these collective data, Mig-7 expression could be a potential candidate for future targeted cancer therapies.
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PMID:Targeting migration inducting gene-7 inhibits carcinoma cell invasion, early primary tumor growth, and stimulates monocyte oncolytic activity. 1967 48

Neoplastic involvement of the sternotomy incision has rarely been described after cardiac operations. We present 3 patients with sternotomy incisions that were initially suspected to be infected but were subsequently found to involve metastatic spread of a distant primary tumor. These patients presented with renal cell carcinoma, multiple myeloma, and endometrial cancer, malignancies known to invade bone, within 12 months of their cardiac operation. The immediacy of presentation after the operation suggests that these patients may have had subclinical cancer at the time of the procedure. Seeding of the surrounding tissue may therefore have occurred with the sternotomy. Neoplastic involvement should, therefore, remain part of the differential diagnosis for incisional drainage or induration, especially beyond the initial postoperative period.
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PMID:Malignant invasion of sternotomy incision after cardiac operation. 2033 65

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. In 2008, approximately 40,000 cases were newly diagnosed. Although the majority of these cancers are curable by means of hysterectomy and radiotherapy, a subset of endometrial tumors exhibits an aggressive phenotype characterized by lymphovascular invasion, high histological grade, and myometrial invasion, leading to poor prognosis. The mechanisms involved in this aggressive transformation are largely unknown, however, interactions between the primary tumor mass and the surrounding stroma likely play a role in this transformation. Despite the fact that research in other common malignancies has elucidated important associations between stromal protein expression and invasion, these mechanisms have been poorly explored in the area of endometrial cancer. In fact, few investigations have been conducted in the area of tumor microenvironment for endometrial tumors. Invasion and metastasis are two primary reasons for treatment failure related to endometrial cancer. Expression of stromal-derived proteins can potentially serve as biomarkers of aggressive disease as well as biomarkers for remission monitoring. In order to study how expression of these proteins relates to the prognosis of endometrial cancer, these proteins need to be explored in large sets of existing data and/or tissue banks. In this paper, we briefly review the role of three stromal related pathways, SDF-1alpha/CXCR4, HGF/c-Met, and VEGF-A in endometrial cancer prognosis as an overview of the literature. We report that the role of SDF-1alpha/CXCR4 and HGF/c-Met in endometrial cancer prognosis remains unclear, whereas the evidence pertaining to VEGF indicates that overexpression is involved in tumor growth and metastasis. Finally, we would like to highlight the need to explore stromal proteins as a potential tool for the detection of aggressive endometrial tumors and explore some of the molecular approaches that can be utilized in the exploration of the tumor environment.
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PMID:Future directions in the field of endometrial cancer research: the need to investigate the tumor microenvironment. 2052 27

PET-CT plays an increasing role in the diagnosis and treatment of gynaecological cancers. In cervix cancer, whilst MRI remains the best imaging technique for initial primary tumor staging, PET-CT has been showed to be a highly sensitive method to determine lymph node status, except in patients with early-stage cervical cancer where PET-CT cannot replace surgical exploration of pelvic lymph nodes. In patients with advanced cervical cancer, PET-CT has the potential of showing lymph node metastasis not only within the pelvis, but also outside the pelvis, more particularly in the para-aortic area. PET-CT has also been described as a useful tool in 3-D-based adaptative brachytherapy. In endometrial cancer, the issues are different, as the recent decade has seen a therapeutic decrease in early-stage disease, especially in postoperative radiation therapy, whilst more advanced disease have been approached with more aggressive treatments, integrating chemotherapy and external beam radiotherapy. Lymph node status is also an important issue and PET-Scan may replace lymph node surgical procedure particularly in obese patients.
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PMID:Clinical evidence on PET-CT for radiation therapy planning in cervix and endometrial cancers. 2070 17

This article reviews the role of imaging in malignant neoplasms of the uterine corpus. Endometrial cancer is the most common uterine malignancy, and diagnosis is made by histology. Staging of these tumors remain surgical-pathologic on the 2009 International Federation of Gynecology and Obstetrics staging system. However, imaging is important in treatment planning, with magnetic resonance imaging providing the best staging for the primary tumor; more advanced disease may be evaluated with computed tomography or positron emission tomography-computed tomography. Uterine sarcomas are uncommon and heterogeneous group of malignancies. International Federation of Gynecology and Obstetrics have introduced a new staging system for uterine sarcoma that is also surgical-pathologic. Imaging is used in evaluating these tumors and in defining the extent of disease. Other malignant tumors involving the uterus and discussed here include lymphoma and metastases.
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PMID:Imaging of uterine malignancies. 2097 57


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