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)

Cancer-associated retinopathy (CAR) is an ocular manifestation of a paraneoplastic syndrome whereby immunological reactions to retinal antigens aberrantly expressed in tumor cells lead to the degeneration of retinal photoreceptor cells. In our previous study (H. Ohguro et al., Invest. Ophthalmol. Vis. Sci., 40: 82-89, 1999), recoverin, a retina-specific calcium-binding protein, and heat shock cognate protein 70 (hsc 70) were identified as autoantigens recognized by sera from patients with CAR. Therefore, we suggested that autoimmune reactions against both recoverin and hsc 70 might be involved in the pathogenesis of CAR. To elucidate the initial step of the molecular pathology of CAR, we examined the expression of recoverin and hsc 70 by reverse transcription-PCR and Western blot using cell lines of several kinds of cancers, including lung small cell carcinoma, lung adenocarcinoma, gastric cancer, pancreatic cancer, breast cancer, uterine cervical cancer, endometrial cancer, and leukemia. Recoverin was expressed in 21 of the 31 cancer cell lines. The expression levels of hsc 70 were significantly higher in cancer cell lines than in noncancerous cell lines. However, no difference in the expression levels of hsc 70 was observed between recoverin-positive and -negative cell lines. Immunofluorescence labeling by the affinity-purified recoverin antibody revealed the immunoreactivity to recoverin as a granular pattern within the cancer cells. Lung adenocarcinoma A549 cells, which did not express recoverin, exhibited a significant reduction in cell proliferation upon transfection with human recoverin cDNA. Taken together, our present data suggest that the retina-specific calcium-binding protein recoverin is expressed in more than 50% of a variety of cancer cells and may play a significant role in the cell proliferation of these tumor cells.
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PMID:Aberrant expression of photoreceptor-specific calcium-binding protein (recoverin) in cancer cell lines. 1076 80

After endometrial cancer, gastric cancer is the second most common extracolonic cancer in cases of hereditary nonpolyposis colorectal cancer (HNPCC), where the relative risk in HNPCC familial members is known to be 4-fold. However, it is not yet clear whether HNPCC families from Korea, an endemic area for gastric cancer, have the same relative risk or whether the incidence of gastric cancer is high enough to justify familial screening. To clarify these questions, we investigated 1011 individuals from 66 Korean HNPCC families (28 families fulfilled the Amsterdam criteria and 38 did not). The overall and age-specific relative risk of gastric cancer in HNPCC families when compared with the background population was calculated. Twenty-five patients with gastric cancer were identified from among 22 HNPCC families. The calculated risk of gastric cancer in patients with HNPCC and their first-degree relatives was 2.1-fold greater than in the general population (95% confidence interval; range, 1.4-3.2). However, the relative risk of gastric cancer in the younger generations was much greater (11.3-fold in the 30s and 5.5-fold in the 40s). Additionally, the relative risk was greater in mutation carrier families than noncarrier families (3.2-fold versus 1.6-fold). This study demonstrates that the risk of gastric cancer in members of HNPCC families in a gastric cancer endemic population, particularly in younger subjects and mutation carrier families, is high enough to justify careful screening.
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PMID:Risk of gastric cancer in hereditary nonpolyposis colorectal cancer in Korea. 1095 76

1-5% of all patients presenting with colorectal cancer, have an underlying genetic predisposition with an autosomal dominant of pattern of inheritance. Recently the underlying molecular genetic pathway of this syndrome known as HNPCC (hereditary nonpolyposis colorectal cancer) has been characterized: the predisposition is due to a pathogenic mutation in one of the DNA mismatch-repair genes. Colorectal cancers are the leading characterisitic of the syndrom and are frequently encountered at a young age of onset. However, endometrial cancer, stomach cancer, small bowel cancer, urinary tract cancer and skin cancer among others are also inherent to the syndrome. Based on the identification of the underlying molecular genetic pathway, predictive testing has become an option. Once the family-specific underlying pathogenic mutation in one of the DNA mismatch-repair genes has been identified in a proband, at-risk family members may be offered DNA testing with an unequivocal answer to if or if not they have inherited the increased cancer susceptibility. Multiple facets of family DNA testing require a multidisciplinary approach integrating clinicians, geneticists, psychologists, molecular biologist and pathologists. Mutations are identified in a rate of 50-60% of families complying with the Amsterdam criteria for HNPCC. The incidence of recta cancer in HNPCC has as yet not clearly been defined, due to a lack of unequivocal data. In a retrospective analysis (submitted) rectal cancers were encountered in 30% of the HNPCC patients. Half of the patients affected developed metachronous colon cancers. It is essential to address the issue of prophylactic surgery in HNPCC patients presenting with colorectal cancer: Prospective data is required in order to decide which of the options is more beneficial for the HNPCC patient presenting with his first colorectal primary: subtotal colectomy and ileorectal anastomosis versus restorative proctocolectomy. It is evident that apart from the more clinical data quality of life data must be evaluated in this study.
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PMID:[Hereditary nonpolyposis colorectal carcinoma (HNPCC): surgical aspects]. 1132 7

Many users of oral contraceptives (OCs) and potential users misunderstand the risks and benefits of OCs. A recent poll in the US revealed that 3 out of 4 women thought the pill carried substantial health risks. Nearly 2/3 of the women surveyed believe using OCs is at least as risky as childbearing. Family Health International (FHI) recently conducted a world survey of perceptions of OCs. It shows that women in many other countries share US womens negative image of the pill. Women believe in pill-related dangers scientists have never even suspected, much less proven, such as an increased risk of stomach cancer. Yet, many women, especially women in developing countries, are unaware of problems such as cardiovascular disease that are related to OC use, and they are ignorant of the proven health benefits of OCs, such as protection against ovarian and endometrial cancer. Despite the persistence of negative perceptions of the pill, research conducted over the past 30 years has shown that the pill is safe for the great majority of women and, in fact, provides significant health benefits for many users. With the contraceptive effectiveness of the pill established through the early tests, drug companies began steadily lowering the hormone dosages. By 1983, more than half of the OCs sold in the US contained less than 0.5 mg estrogen. Many of the combination OCs now sold have only 0.2 to 0.4 mg estrogen. Eventually, pill researchers learned that OCs containing only progestogen, even in comparatively small doses, also could effectively prevent pregnancy, though not as effectively as pills containing estrogen. The first progestogen-only pills received US Food and Drug Administration approval in 1973. Continued research on OCs shows that the increased risks of cardiovascular diseases actually were almost entirely confined to specific groups women who were over 35 or who both were over 30 and smoked. For the great majority of women, studies showed, the risk of cardiovascular disease was increased little by OC use. FHI's recent study of long-term OC risks and benefits, based on previous epidemiological research, demonstrates that OC use has no net effect on life expectancy for most women. Among younger women who do not smoke, life expectancy is slightly increased by OC use, the study shows. This is because OCs provide protection against ovarian and endometrial cancer. In an effort to improve compliance with recommended OC procedures, FHI has initiated a series of studies which will examine the interaction between OC side effects, the information and support given OC users by family planning providers, and OC compliance.
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PMID:The misunderstood pill: thirty years of testing and development have reduced pill's major, minor side effects. 1234 Oct 93

DNA mismatch repair deficiency is observed in about 15% of human colorectal, gastric, and endometrial tumors and in lower frequencies in a minority of other tumors thereby causing insertion/deletion mutations at short repetitive sequences, recognized as microsatellite instability (MSI). Evolution of tumors, including those with MSI, is a continuous process of mutation and selection favoring neoplastic growth. Mutations in microsatellite-bearing genes that promote tumor cell growth in general (Real Common Target genes) are assumed to be the driving force during MSI carcinogenesis. Thus, microsatellite mutations in these genes should occur more frequently than mutations in microsatellite genes without contribution to malignancy (ByStander genes). So far, only a few Real Common Target genes have been identified by functional studies. Thus, comprehensive analysis of microsatellite mutations will provide important clues to the understanding of MSI-driven carcinogenesis. Here, we evaluated published mutation frequencies on 194 repeat tracts in 137 genes in MSI-H colorectal, endometrial, and gastric carcinomas and propose a statistical model that aims to identify Real Common Target genes. According to our model nine genes including BAX and TGFbetaRII were identified as Real Common Targets in colorectal cancer, one gene in gastric cancer, and three genes in endometrial cancer. Microsatellite mutations in five additional genes seem to be counterselected in gastrointestinal tumors. Overall, the general applicability, the capacity to unlimited data analysis, the inclusion of mutation data generated by different groups on different sets of tumors make this model a useful tool for predicting Real Common Target genes with specificity for MSI-H tumors of different organs, guiding subsequent functional studies to the most likely targets among numerous microsatellite harboring genes.
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PMID:Pathogenesis of DNA repair-deficient cancers: a statistical meta-analysis of putative Real Common Target genes. 1270 Jun 58

Deregulated centrosome duplication or maturation often results in increased centrosome size and/or centrosome number, both of which show a positive and significant correlation with aneuploidy and chromosomal instability, thus contributing to cancer formation. Given the role of Polo-like kinases (Plks) in the centrosome cycle, it is not unexpected that deregulated expression of Plks is detected in many types of cancer and is associated with oncogenesis. Extensive studies have shown that Plk1 expression is elevated in non-small-cell lung cancer, head and neck cancer, esophageal cancer, gastric cancer, melanomas, breast cancer, ovarian cancer, endometrial cancer, colorectal cancer, gliomas, and thyroid cancer. Plk1 gene and protein expression has been proposed as a new prognostic marker for many types of malignancies, and Plk1 is a potential target for cancer therapy. In contrast to Plk1, several studies have observed that Plk3 expression is negatively correlated with the development of certain cancers.
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PMID:Polo-like kinases (Plks) and cancer. 1564 Aug 44

Colorectal and endometrial cancer are the characteristic tumors of the Lynch syndrome. We reviewed the available evidence on the occurrence of other types of cancer in the syndrome, aiming to identify those types that can be included in the tumor spectrum, based on this evidence. We chose to define the tumor spectrum as comprising the cancers for which Lynch syndrome patients are at elevated risk. We found sufficiently strong and consistent evidence to include gastric cancer, small bowel cancer, hepatobiliary tract cancer, upper urologic tract cancer, ovarian cancer, and brain tumors in this spectrum, in addition to colorectal and endometrial cancer. We predict that the spectrum will expand as additional studies are reported, especially as prospective studies of mutation carriers are completed.
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PMID:The tumor spectrum in the Lynch syndrome. 1613 85

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

Germline mutations in DNA mismatch repair (DNA-MMR) genes, mainly MLH1, MSH2, and MSH6, underlie Hereditary non-polyposis colorectal cancer (HNPCC) and are mostly family-specific, with few reported founder mutations in MSH2 (Ashkenazim) MLH1 (Finnish). No mutations in colon cancer susceptibility genes have ever been reported in Druze individuals, a Moslem related faith encompassing approximately 1,000,000 individuals worldwide. A novel MSH2 mutation is described in a Druze HNPCC family: a multigenerational family with 10 members in 4 generations affected with colorectal cancer (mean age of diagnosis 46.5 years), two with gastric cancer and one--endometrial cancer. Mutational analysis of the MSH2 gene using denaturing gradient gel electrophoresis (DGGE) and direct sequencing revealed the c.702delA mutation in codon 234 of exon 4 of the MSH2 gene leading to a premature early stop in codon 245, p.Thr234fsX245. Analysis of mutation-carrying or presumed carriers individuals' offspring, revealed 11/42 asymptomatic mutation carriers, age range 17-50 years. The mutation was not present in two additional Druze HNPCC families and 20 Druze sporadic colon cancer patients. This is the first mutation ever reported in a colon cancer susceptibility gene in a Druze family and it appears not to be a founder mutation in Druze individuals with HNPCC.
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PMID:A novel MSH2 germline mutation in a Druze HNPCC family. 1766 Nov 83

Interleukin-6 (IL-6) is proinflammatory cytokine that produces multifunctional effects. It is also involved in the regulation of immune reactions, hematopoiesis and inflammatory state. Interleukin-6 has been shown to be associated with tumor progression including inhibition of cancer cells apoptosis and stimulation of angiogenesis. Anti-IL-6 therapy is a new strategy in the inflammatory autoimmune diseases and cancer. Clinical studies have shown elevated serum IL-6 concentrations in patients with endometrial cancer, non-small cell lung carcinoma, colorectal cancer, renal cell carcinoma, breast and ovarian cancer. Serum IL-6 levels correlate with tumor stage, and survival of patients. In this article we have focused on a role of IL-6 as a prognostic factor in several malignancies such as colorectal cancer, breast cancer, gastric cancer and pancreatic cancer.
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PMID:[Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease]. 1803 Aug 75


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