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)

Seventeen patients with endometrial cancer were studied. Tissues of primary (P) and metastatic (M) lesions were obtained from 8 patients and complete sets of P, M and Recurrent (R) lesions were obtained from 9 patients during a follow-up period of 1-10 years. Expressions of estrogen receptors, progesterone receptors, multidrug resistance protein-1, multidrug resistance-related protein, c-erbB-2, membrane-type metalloproteinase, human telomerase RNA, human telomerase reverse transcriptase RNA, E-cadherin and autocrine motility factor receptor were studied by RT-PCR. Also, telomeric restriction fragment length (TRFL) and microsatellite instability were determined between P, M and R. The results indicate that there are significant differences in the gene expression frequency during tumor progression. The mismatch rate ranged from 0 to 47.1% between P and M and from 14.3% to 66.7% between P and R, respectively. The TRFL analysis showed a marked reduction in P and M (P vs. M: 8.2 +/- 0.9 vs. 5.6 +/- 0.4 kb, mean +/-SEM, n = 9, p = 0.002 by paired Student's t test). The length further decreased in R (P vs. R: 8.2 +/- 0.9 vs. 3.2 +/- 0.7, p = 0.01, M vs. R: 5.6 +/- 0.4 vs. 3.2 +/- 0.7, p = 0.005). The genomic instability/replication error was tested by AluI arbitrary primed polymerase chain reaction (AP-PCR). Five out of 17 patients showed an altered replication error pattern (29.4%). The mean number of abnormal AluI AP-PCR patterns in M and R compared to the P was 1.5 (M) and 4 (R). The difference between the P and R was statistically significant (p < 0.04). The present data indicate that biological behavior of cancer cells in P, M and R may differ significantly.
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PMID:Gene expression in primary, metastatic and recurrent lesions of endometrial cancer. 1054 51

Age is the most important risk factor for the development of breast cancer. The risk of breast cancer continues to increase in American women until the age of 80 years. A family history of breast cancer helps identify those who possibly have the highest risk of developing breast cancer; however, most women who develop breast cancer do not have a first-degree relative with a history of breast cancer. Currently, the Gail model is a commonly used model to identify risk, and this model has now been validated in several populations of women undergoing screening for breast cancer. The first large-scale breast cancer prevention trial investigating the preventive effects of tamoxifen has demonstrated a decrease in the development of breast cancer by almost 50% in the women in the tamoxifen treatment arm as compared with those receiving placebo. The NSABP P-1 trial was the largest of the three tamoxifen breast cancer prevention trials and had the greatest power to detect a difference between the two treatment groups in breast cancer events. This trial also included the largest percentage of postmenopausal women. It is unclear why the Italian and Royal Marsden Hospital trials had negative results regarding the preventive effects of tamoxifen. These two trials were strikingly different from the NSABP P-1 trial, however, and they included a different population of women. The issues surrounding the use of HRT for treatment of hot flashes in the Italian and Royal Marsden Hospital trials adds to the controversy concerning the negative results of these trials. The new SERM, raloxifene, has shown promise in preliminary studies as a preventive agent for breast cancer. The STAR trial will open soon and will evaluate the efficacy of raloxifene in preventing breast cancer in a prospective fashion, comparing its efficacy with tamoxifen treatment. Other endpoints will evaluate side effects such as menopausal symptoms, endometrial cancer, thromboembolic events, and benefits regarding serum lipids and incidence of osteoporotic bone fractures. The development of SERMs results from an understanding of novel mechanisms of ER modulation and allows targeting for favorable effects in specific tissues. The challenge is to develop an ideal SERM that is effective in preventing breast cancer and does not increase the risk of endometrial cancer, while providing beneficial estrogenic effects on serum lipids and bone mineral density changes. Estrogen receptor-mediated intracellular processes are complex. There are at least two different types of estrogen receptors. The alpha receptors predominate in the breast and uterus, and the beta receptors predominate in the bone and blood vessels. Many proteins also interact with these receptors as co-activators or co-repressors. Transcription-activating factors modulate the effects of estrogen on its target genes. Future prevention strategies may use a combined targeted approach to inhibit ER-mediated cancer progression pathways. The retinoids are under investigation in prevention studies for a multitude of cancers, because they have been shown to inhibit cellular proliferation and to induce cellular differentiation. The retinoid 4HPR was selected for use in breast cancer prevention studies because of its low toxicity profile and prevention efficacy in preclinical studies. It is now being used in combination with tamoxifin in a phase II breast cancer prevention trial. Multiple surrogate endpoint biomarkers are being measured before and after treatment, including measurement of serum IGF-I levels. Future directions in breast cancer prevention include the development of more potent hormonal therapies that completely inhibit ER-mediated cancer progression and, ultimately, multitargeted therapies involving agents that work synergistically.
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PMID:Chemoprevention of breast cancer in the older patient. 1068 75

Loss of heterozygosity (LOH) in the region of 10q23.3 has been associated with multiple tumors, including glioblastoma multiforme, melanoma, endometrial carcinoma, and prostate carcinoma. The tumor suppressor gene, PTEN/MMAC1, is also located in this region, and, in addition to other tumor types (eg, glioblastoma multiforme, endometrial, and melanoma), PTEN/MMAC1 mutations have been found in prostate cancer cell lines, xenografts, and hormone refractory prostate cancer tissue specimens. The aim of this study was to evaluate LOH at 10q23.3 as a marker of cancer progression in node-positive prostate cancer. Genetic alterations in the region of 10q23.3 were assessed in 23 node-positive (pT2-3, N+) and 44 node-negative prostate (pT2-3, N0) cancers with D10S532, D10S1687, D10S541, and D10S583 flanking polymorphic genetic markers; PTENCA, a genetic marker within PTEN/MMAC1, was also tested. Using DNA from paired normal and microdissected tumor samples, LOH at microsatellite loci was determined after polymerase chain reaction amplification. LOH in at least 1 marker was identified in 14% (6 of 44) of lymph node-negative and 43% (10 of 23) of lymph node-positive prostate cancers (chi-square test, P = .007). This increase in genetic alterations in node-positive prostate cancer suggests that 10q23.3 is a marker for metastatic progression.
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PMID:10q23.3 loss of heterozygosity is higher in lymph node-positive (pT2-3,N+) versus lymph node-negative (pT2-3,N0) prostate cancer. 1082 99

In cancer patients impaired blood rheology in the presence of coagulation activation may reduce blood flow in the vascular microcirculation that favors thrombosis but may also support tumor progression and metastasis. In 451 patients with gynecological cancer and 177 patients with corresponding benign tumor disease preoperatively, during adjuvant treatment, when venous thrombosis (VT) or cancer progression was diagnosed hematocrit (micro centrifuge), hemoglobin, leukocytes, platelets (Coulter Counter); red blood cell (RBC) aggregation (aggr.) during stasis and low shear conditions (MA 1, Myrenne), plasma viscosity (viscosimeter KSPV 1 Fresenius), and fibrinogen (Multifibren Behring Dade) were investigated. One hundred and twelve healthy women served as controls. Preoperatively, mean plasma viscosity (pv) was significantly higher in cancer patients as compared to patients with the corresponding benign tumor disease (breast cancer: n = 261; pv = 1.32 vs. 1.27 mPa s; p = 0.023; ovarian cancer: n = 68; pv = 1.39 vs. 1.31 mPa s; p < 0.001; endometrial cancer: n = 70; pv = 1.37 vs. 1.25 mPa s; p < 0.001; cervical cancer: n = 52; pv = 1.33 vs. 1.26 mPa s; p = 0.004). RBC aggr. was significantly lower in controls compared to the preoperative values in cancer patients but mean (median) values (RBC aggr. stasis < 21) were within the normal range in all. Preoperatively, plasma viscosity was a significant risk factor for the overall survival in ovarian cancer patients (p = 0.02) and for subsequent thrombosis in ovarian (p = 0.02) and cervical cancer patients (p = 0.007). In the multivariate analysis plasma viscosity was an independent prognostic marker for the overall survival of breast cancer patients (r = 99.45; 95% CI: 7.32-980.2; p < 0.0001). An optimized preoperative cut-off value above 1.40 mPa s (Log-Rank-test) was significantly associated with poor outcome in the Kaplan-Mayer survival estimates, even in node-negative breast cancer. In gynecologic cancer patients the combination of an increase in RBC aggregation and plasma viscosity impairs blood-flow-properties and may induce hypoxia in the microcirculation that favors thrombosis, settlement of tumor-cells and thus metastasis. Improvement of blood fluidity and thus oxygen transfer in the tumor-vascular-microcirculation may increase susceptibility of systemic anti-cancer therapy.
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PMID:Association between blood rheology, thrombosis and cancer survival in patients with gynecologic malignancy. 1083 Oct 62

The recently developed cDNA expression array technique can be used to generate gene-expression fingerprints of tumour specimens. To gain insight into molecular mechanisms involved in the development and progression of cancer, this cDNA expression array technique could be a useful tool, however, no established methods for interpreting the results are yet available. We used the Atlas cancer cDNA expression array (Clontech, USA) for analysing total RNA isolated from four human endometrial carcinoma samples (two cell-lines and two tissue samples), one benign endometrial tissue sample and a human breast cancer cell-line, in order to develop a method for analysing the array data. The obtained gene-expression profiles were highly reproducible. XY-scatterplots and regression analysis of the logarithmic transformed data provided a practical method to analyse the data without the need of preceding normalization. Three genes (Decorin, TIMP3 and Cyclin D1) were identified to be differentially expressed between the benign endometrial tissue sample and the endometrial carcinoma samples (tissue and cell-lines). These three genes may potentially be involved in cancer progression. A higher degree of similarity in gene-expression profile was found between the endometrial samples (tissue and cell-lines) than between the endometrial samples and the breast cancer cell-line, which is indicative for an endometrial tissue-specific gene-expression profile.
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PMID:Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method. 1090 78

The nuclear receptor for the female hormone progesterone (PR) is widely expressed in uterine cancer. PR is expressed as two proteins (PRA and PRB) with different functions, and in vitro evidence reveals PRA to inhibit PRB function, so the cellular ratio of PRA:PRB is likely to be an important determinant of progesterone action. The relative expression of PRA and B and their involvement in the pathogenesis of endometrial cancer is not known. The aims of this study were to determine PRA and B expression by dual immunofluorescent histochemistry in endometrial adenocarcinomas compared with expression in normal and hyperplastic glands, and to correlate expression in tumors with clinical features including grade. Significantly lower PR levels were found in tumors compared with normal glands and areas of complex atypical hyperplasia within the same specimen. The normal glands expressed both of the isoforms at similar levels, whereas there was increased predominance of one isoform in hyperplastic areas and in tumors, which suggested that the loss of coordinated expression of PR isoforms was an early event in tumor progression. The majority of tumors [27 (58%) of 46] expressed only one PR isoform, and the proportion expressing either PRA or B was the same [14 (30%) of 46, and 13 (28%) of 46, respectively]. One-half of all tumors ([23 (50%) of 46] expressed either PRA only or a predominance of PRA, and a few tumors [10 (22%) of 46] expressed comparable levels of PRA and B. Similar levels of PRA and B were noted only in FIGO grade 1 tumors, whereas higher grades (2 and 3) were associated with a predominance of one isoform. In summary, expression of only one PR isoform was common in endometrial cancers, which indicates that the decreased PR levels observed in these cancers arise from the loss of one PR isoform. Expression of a single PR isoform was associated with higher clinical grade, which suggests a relationship between the loss of PR isoform expression and features of poorer prognosis. Disruption of relative PR isoform expression was observed in complex atypical hyperplasia, which suggests that early alterations in the ratio of PRA:PRB may precede and/or be implicated in the development of endometrial adenocarcinoma. Alterations in the ratio of PR isoform expression are likely to cause disordered regulation of target genes, resulting in altered progestin action in the uterus, and this may be involved in the pathogenesis of endometrial cancer.
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PMID:Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium. 1138 93

Prospective multicenter evaluation of the WHO classification and the morphometric D-score to predict endometrial hyperplasia cancer progression. In 132 endometrial hyperplasias WHO classification was performed by two experienced gynecologic pathologists. The D-score was assessed blindly by technicians in a routine diagnostic setting. Development of endometrial carcinoma during a 1-10-year follow-up was used as the end point. Eleven of 132 patients (8%), 10 of 61 (16%) atypical hyperplasias, and 1 of 71 (1%) nonatypical hyperplasias developed cancer. Twenty-six curettings had a D-score < or = 0 ("unfavorable" or endometrial intraepithelial neoplasia) of which 10 (38%) developed cancer. None of the 86 cases with a D-score > 1 ("favorable") and one of the 20 (5%) cases with 0 < D-score < or = 1 ("uncertain") developed cancer. Sensitivity of the D-score was 100%, specificity 82%, the positive and negative predictive values were 38% and 100%, respectively. These values are similar to those in three prior retrospective D-score studies but higher than the WHO values (which are 91%, 58%, 16%, and 99%, respectively). The D-score in endometrial hyperplasias is a more sensitive and specific marker for cancer prediction than the WHO classification, can be assessed in a routine clinical setting on standard hematoxylin and eosin sections (15-30 minutes per case), and is highly reproducible and cost-effective (U.S. $50 per case).
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PMID:Prospective multicenter evaluation of the morphometric D-score for prediction of the outcome of endometrial hyperplasias. 1142 Apr 65

Previous studies indicated that a new member of the human kallikrein (KLK) gene family, KLK4, was expressed in prostate, breast, and endometrial carcinoma cell lines and may have potential as a tumor marker. The aim of this study was to examine the expression of KLK4 in the normal ovary and ovarian tumors of different histology, stage, and differentiation and to determine its association with ovarian tumor progression. Using reverse transcription-PCR, Southern blot, and densitometry analyses, we found the level of KLK4 expression was higher in late stage serous (SER) epithelial-derived ovarian carcinomas than in normal ovaries, mucinous epithelial tumors, and granulosa cell tumors. KLK4 was highly expressed in all of the SER ovarian carcinoma cell lines (eight of eight), SER epithelial carcinomas (11 of 11), and two adenomas, whereas it was expressed at a lower level (or not at all) in normal ovaries (four of six), mucinous epithelial tumors (three of four), endometrioid carcinomas (four of five), clear cell carcinomas (two of three), or granulosa cell tumors (three of six). Of particular interest, KLK4 mRNA variants were detected in SER ovarian carcinoma cell lines and primary cultured ovarian tumor cells, but they were not present in normal ovaries. In situ hybridization analysis showed that KLK4 mRNA transcripts are localized to adenocarcinoma cells of ovarian tumor tissues. Similarly, immunohistochemical staining of ovarian carcinoma sections showed immunoreactivity to KLK4 protein product (hK4) antipeptide antibodies. In addition, intracellular hK4 levels, as detected on Western blot analysis, were induced by 100 nM estrogen treatment of the estrogen receptor positive ovarian carcinoma cell line OVCAR-3, >8-24 h. Our results show that the level of KLK4 expression and expression of KLK4 mRNA variants are associated with progression of ovarian cancer, particularly late stage SER adenocarcinomas. Moreover, hK4 may be a candidate marker for the diagnosis and/or monitoring of ovarian epithelial carcinomas.
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PMID:Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas. 1148 14

Serum vascular endothelial growth factor (VEGF) and endostatin were determined in postmenopausal women, including 72 with endometrial cancer, 27 with endometrial hyperplasia and 30 healthy controls. Serum VEGF levels in endometrial hyperplasia (142+/-18 ng/ml, mean +/- SE) and endometrial cancer stages I (291+/-22), II (623+/-68) and stage III-IV (1527+/-119) were significantly higher than the mean for controls (12+/-1.6). Serum endostatin levels in endometrial hyperplasia (149+/-19 ng/ml), endometrial cancer stages I (320+/-41), II (644+/-86) and stage III-IV (1253+/-114) were also significantly higher than the mean for controls (13+/-2.4). Elevated values of VEGF above the non-malignant level were encountered in 7% (stage I), 37% (stage II) and 100% (stage III-IV) of endometrial cancers. The corresponding figures for endostatin were 37%, 59 and 100%, respectively. These results demonstrate that the circulating levels of both markers correlated with tumor stage and apparently tumor burden. Serum VEGF and endostatin levels decreased significantly after treatment, followed by marked elevations at clinical relapse. The VEGF endostatin ratio was higher in the advanced stages ( > 1.0) than in the early stages of endometrial carcinoma (< 1.0). indicating that the balance of angiogenic stimulators and inhibitors may regulate metastasis and access tumor progression.
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PMID:Biomarkers of intrinsic angiogenic and anti-angiogenic activity in patients with endometrial hyperplasia and endometrial cancer. 1150 12

COX-2, the isoform of cyclooxygenase inducible by cytokines, mitogens, and growth factors, appears to play an important role in inflammation and carcinogenesis. In the colon, COX-2 overexpression results in cell cycle alterations, and NSAIDs have proven effective in cancer chemoprevention. HNPCC (hereditary nonpolyposis colon cancer) is a clinically defined cancer susceptibility syndrome in which women are also at significantly increased risk for the development of endometrial carcinoma. The purpose of this study was to evaluate expression of COX-2 in benign and malignant endometrium in the context of other cell cycle and proliferation markers, including Ki-67, cyclin D1, and the cyclin-dependent kinase inhibitor, p21. Immunostains with COX-2, Ki-67, cyclin D1, and p21 antibodies were performed on formalin-fixed and paraffin-embedded tissue sections from 40 cases: 10 benign (5 atrophic and 5 proliferative) endometria, 6 hyperplasias (complex without atypia), and 24 endometrioid carcinomas (9 well, 4 moderately, and 11 poorly differentiated). Ki-67 was positive in all proliferative and neoplastic endometria. Cyclin D1 and p21 were both overexpressed in endometrial hyperplasia and endometrioid carcinomas. COX-2 was negative in the nonneoplastic endometrium, stained minimally in the well-differentiated endometrioid carcinomas, and stained most strongly in the moderately and poorly differentiated endometrioid carcinomas. Because cyclin D1 may function as an oncogene, its effects may dominate the usual inhibitory effect of a rising p21. Alternatively, it has been shown that p21 can promote cell cycle function by stabilizing cell cycle complexes. The overexpression of COX-2 in poorly differentiated endometrioid carcinoma and lack of expression in hyperplasia and well-differentiated carcinoma suggests that in this form of cancer, COX-2 may play a role in tumor progression rather than tumor initiation.
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PMID:Expression of COX-2, Ki-67, cyclin D1, and P21 in endometrial endometrioid carcinomas. 1191 24


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