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)

Effects of prostaglandin F2 alpha, E2, D2 and J2 on the DNA and RNA contents of a human endometrial cancer cell lines (SNG and Ishikawa) were studied using flow cytometry. Cytotoxic effects of various prostaglandins on SNG and Ishikawa cell lines were examined and PG J2 and PG D2 were found most active. Among other prostaglandins PG E2 showed a comparable inhibitory activity to cellular growth but PG F2 alpha didn't. In SNG and Ishikawa cell lines after RNase treatment, PG J2, PG D2 and PG E2 caused a decrease of the S-phase and G2 + M-phase cell population in cell cycle. On the other hand, PG F2 alpha caused a increase of the S-phase cell population in cell cycle PG J2, PG D2 and PG E2 after DNase treatment caused a decrease of the relative RNA content in both of cell lines. On the other hand, PG F2 alpha caused a increase of the relative RNA content. It is a noteworthy that PG J2 and PG D2 were remarkably recognized delay of doubling time and decrease of survival fraction under the time and dose dependence. These effects occur not only by direct lethal influence of the prostaglandins, but also by substantially inhibit RNA and DNA synthesis with a delay of the cell cycle. These results might be suggested a role for prostaglandin J2 and D2 in the regulation of growth of endometrial adenocarcinoma cells.
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PMID:[Inhibition of growth of human endometrial adenocarcinoma cells in vitro treated with prostaglandin F2 alpha, E2, D2 and J2]. 346 9

Plasma RNase activity was studied in normal and females with gynecological malignancies. Basic experimental data of RNase showed linear regression to the incubation period up to 20 min., optimal pH at 8.0, maximal absorption at 260 nm and sufficient substrate concentration with 120 microgram/0.02 ml. Coefficient of variation was 6.2% (n = 15) intra-assay study. Mean plasma RNase of 32 normal subjects was 0.24 +/- 0.04 (mean +/- SD) delta OD/0.01 ml/20 min. Values deviating mean + 2SD (0.32) were regarded as abnormal. Mean value at pre-treatment was 0.27 +/- 0.04 for benign tumor and abnormal value rate was 11% (2/19). The values in cervical cancer patients were 0.29 +/- 0.06 [91.7% (11/12)] for recurrent cases. The values and abnormal rates raised as clinical stage advanced. The values were also high in advanced ovarian and endometrial cancer patients. It came into normal range with the complete surgery in early stage. Pre- and post-treatment RNase value were analysed on 29 advanced cervical, endometrial and ovarian cancer patients. Abnormal value rate was lowered from 60% (9/15) to 26.6% (4/15) in therapy-responding group, but were kept high in 14 therapy-resistant group. The value was raised again as the disease recurred. Evaluation of plasma RNase value is useful means in biochemical diagnosis and in prognosing gynecological malignancies.
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PMID:[Changes of plasma ribonuclease activities according to the method of treatment in gynecologic cancer patients (author's transl)]. 731 Jan 99

Estrogen receptor-like 1a (ESRL1a; same as estrogen receptor-related orphan receptors, ERR1) belongs to a subfamily of the nuclear receptor superfamily. We have previously shown that human ESRL1a modulates estrogen responsiveness of the lactoferrin gene promoter in transiently transfected endometrial carcinoma RL95-2 cells. In this study, we cloned and characterized the human ESRL1 gene. Through the fluorescence in situ hybridization method, the ESRL1 gene was localized to the centromere region of chromosome 11q12. Partial sequencing, restriction mapping, and PCR analysis revealed that the ESRL1 gene consists of seven exons and is approximately 20 kb in length. We found that the smallest exon (exon 3) contains 117 bp and the largest exon (exon 7) has 1032 bp. The smallest intron (intron 5) is only 88 bp long and the largest intron (intron 2) is 8 kb long. All introns have the conserved GT and AG dinucleotides present at the donor and acceptor sites, respectively. Like the estrogen receptor, the highly conserved DNA-binding domain of hESRL1a is encoded by exon 2 and exon 3, and the intron/exon junctions (2 and 3) are well conserved between the two genes. Primer extension analysis revealed multiple transcription initiation start sites in human uterine (HeLa, HEC, and RL95-2) cell lines. However, one major initiation start site was found by RNase protection assay. The hESRL1a mRNA is differentially expressed in various human tissues. The nucleotide sequence adjacent to the transcription start sites of the ESRL1 lacks the typical TATA and CAAT boxes but is GC rich and contains 10 consensus Sp1-binding elements and two E boxes. The region that contains these transcription factor-binding elements showed a high level of promoter activity when transiently transfected into RL95-2 cells.
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PMID:Human estrogen receptor-like 1 (ESRL1) gene: genomic organization, chromosomal localization, and promoter characterization. 928

It is well known that the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) acts synergistically with the DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (ADC) to reactivate DNA methylation-silenced genes. Moreover, in several studies, TSA was capable of inducing DNA demethylation even in the absence of ADC. Here we describe a mechanism by which HDAC inhibitors affect DNA methylation through their regulation on DNMT3B, a methyltransferase responsible for de novo DNA methylation. Using quantitative real-time PCR and Western blot analysis, we show that TSA down-regulates DNMT3B mRNA and protein expression in human endometrial cancer cells. This decrease in DNMT3B mRNA results in a significant reduction in de novo methylation activities. Further experiments indicated that TSA decreases DNMT3B mRNA stability and reduces its half-life from approximately 4 to 2.5 hours. We established that protein synthesis is required for posttranscriptional regulation, suggesting the involvement of an RNase and/or key mRNA stabilization factor(s) controlling the DNMT3B mRNA stability. Therefore, TSA may not only modify histone acetylation, but also potentially alter DNA methylation. Since the HDAC inhibitors are frequently used in epigenetic studies and are considered to be promising anticancer drugs, these new findings will have implications in both laboratory and clinical settings.
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PMID:Histone deacetylase inhibitors decrease DNA methyltransferase-3B messenger RNA stability and down-regulate de novo DNA methyltransferase activity in human endometrial cells. 1580 66

Laser capture microdissection of frozen tissue sections allows homogeneous cell populations to be isolated for expression profiling. However, this requires striking a balance between retaining adequate morphology for accurate microdissection and maintaining RNA integrity. Various staining protocols were applied to frozen endometrial carcinoma tissue sections. Although alcohol-based methods were superior to aqueous stains for maintaining RNA integrity, they suffered from irreproducible staining intensity. We developed a modified alcohol-based, buffered cresyl violet staining protocol that provides reproducible staining with minimal RNA degradation suitable for tissues with moderate to high levels of intrinsic RNase activity.
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PMID:A robust RNA integrity-preserving staining protocol for laser capture microdissection of endometrial cancer tissue. 2162 43

Laser capture microdissection (LCM) allows expression profiling of specific cell populations within tissues. However, isolation of high-quality RNA from laser capture microdissected frozen tissue is beset by problems arising from intrinsic tissue RNase activity. Herein, we describe an optimized staining/LCM/RNA extraction protocol developed for the isolation of epithelial RNA from frozen tissue sections using human endometrial cancer as a model tissue. This method combines excellent, reproducible visualization of tissue morphology with the isolation of high-integrity RNA suitable for downstream applications such as expression microarray analysis. We present quantitative and qualitative RNA data obtained from >200 endometrial epithelial samples (normal, hyperplastic, and cancerous), where 92% of samples had RIN values of 7 and above and highlight common pitfalls faced by investigators. This method should also be broadly applicable to a range of other tissue types.
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PMID:Laser Capture Microdissection and Isolation of High-Quality RNA from Frozen Endometrial Tissue. 2934 59

As one of the most recently (re)discovered types of non-coding RNAs (ncRNA), circular RNAs (circRNAs) differentiate from other ncRNAs by a specific biogenesis, high stability, and distinct functions. The biogenesis of circRNAs can be categorized into three mechanisms that permit the back-splicing reaction: exon-skipping, pairing of neighboring introns, and dimerization of RNA-binding proteins. Regarding their stability, circRNAs have no free ends, specific to linear RNA molecules, prompting a longer half-life and resistance to exonuclease-mediated activity by RNase R, bypassing the common RNA turnover process. Regarding their functions, circular transcripts can be categorized into four broad roles: miRNA sponging, protein binding, regulation of transcription, and coding for proteins and peptides. Female reproductive system (including mainly ovarian, corpus, and cervix uteri cancers) and breast cancers are the primary causes of death in women worldwide, accounting for over 1,212,772 deaths in 2018. We consider that a better understanding of the molecular pathophysiology through the study of coding and non-coding RNA regulators could improve the diagnosis and therapeutics of these cancers. Developments in the field of circRNA in regard to breast or gynecological cancers are recent, with most circRNA-related discoveries having been made in the last 2 years. Therefore, in this review we summarize the newly detected roles of circRNAs in female reproductive system (cervical cancer, ovarian cancer, and endometrial cancer) and breast cancers. We argue that circRNAs can become essential elements of the diagnostic and therapeutic tools for female reproductive system cancers in the future.
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PMID:A New World of Biomarkers and Therapeutics for Female Reproductive System and Breast Cancers: Circular RNAs. 3221

Dedifferentiated endometrial carcinoma (DDEC) is a rare but highly aggressive type of endometrial cancer, in which an undifferentiated carcinoma arises from a low-grade endometrioid endometrial carcinoma. The low-grade component is often eclipsed, likely due to an outgrowth of the undifferentiated component, and the tumor may appear as a pure undifferentiated endometrial carcinoma (UEC). We and others have recently identified inactivating mutations of SMARCA4, SMARCB1 or ARID1B, subunits of the SWI/SNF chromatin-remodeling complex, that are unique to the undifferentiated component and are present in a large portion of DDEC and UEC. However, the understanding of whether and how these mutations drive cancer progression and histologic dedifferentiation is hindered by lack of cell line models of DDEC or UEC. Here, we established the first UEC cell line, VOA1066, which is highly tumorigenic in vivo. This cell line has a stable genome with very few somatic mutations, which do include inactivating mutations of ARID1A and ARID1B (2 mutations each), and a heterozygous hotspot DICER1 mutation in its RNase IIIb domain. Immunohistochemistry staining confirmed the loss of ARID1B, but ARID1A staining was retained due to the presence of a truncating non-functional ARID1A protein. The heterozygous DICER1 hotspot mutation has little effect on microRNA biogenesis. No additional DICER1 hotspot mutations have been identified in a cohort of 33 primary tumors. Therefore, we have established the first UEC cell line with dual inactivation of both ARID1A and ARID1B as the main genomic feature. This cell line will be useful for studying the roles of ARID1A and ARID1B mutations in the development of UEC.
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PMID:Establishment and characterization of VOA1066 cells: An undifferentiated endometrial carcinoma cell line. 3305 29