scholarly journals Epigenetic Events in Ovarian Cancer

2021 ◽  
Author(s):  
Yanisa Rattanapan ◽  
Takol Chareonsirisuthigul
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Epigenetic Therapy ◽  
Dna Mutations ◽  
Epigenetic Events ◽  
Pharmacodynamic Biomarkers ◽  
Dna Methylation Inhibitors ◽  
Microrna Dysregulation ◽  
Aberrant Gene ◽  
Progressive Accumulation

Epigenetic aberrations are now well established in the development and progression of ovarian cancer, including DNA methylation, histone modifications, and microRNA dysregulation, and their progressive accumulation is correlated with the progression of the stage grade of disease. Epigenetic aberrations are relatively stable, linked to various subtypes of the disease, and present in circulating serum, representing promising diagnostic, prognostic, and pharmacodynamic biomarkers. Unlike DNA mutations and deletions, aberrant gene-repressive epigenetic changes, including DNA methylation inhibitors or histone-modifying enzymes, are theoretically reversible by epigenetic therapies. While no action against solid tumors, including ovarian cancer, has been shown in epigenetic monotherapies, preclinical studies indicate that they may be successful when used in conjunction with one another or with conventional chemotherapy, and combinatorial epigenetic therapy regiments are being investigated in cancer clinical trials. Improved interventions against this debilitating malignancy will provide a greater understanding of epigenetics’ role in ovarian cancer.

scholarly journals Minireview: Epigenetic Changes in Ovarian Cancer

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4003-4011 ◽  
Author(s):  
Curt Balch ◽  
Fang Fang ◽  
Daniela E. Matei ◽  
Tim H.-M. Huang ◽  
Kenneth P. Nephew
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Micro Rna ◽  
Disease Stage ◽  
Epigenetic Therapy ◽  
Dna Mutations ◽  
Distinct Disease ◽  
Ovarian Neoplasia ◽  
Pharmacodynamic Biomarkers ◽  
Aberrant Gene

Abstract Epigenetic aberrations, including DNA methylation, histone modifications, and micro-RNA dysregulation, are now well established in the development and progression of ovarian cancer, and their gradual accumulation is associated with advancing disease stage and grade. Epigenetic aberrations are relatively stable, associated with distinct disease subtypes, and present in circulating serum, representing promising diagnostic, prognostic, and pharmacodynamic biomarkers. In contrast to DNA mutations and deletions, aberrant gene-repressive epigenetic modifications are potentially reversible by epigenetic therapies, including inhibitors of DNA methylation or histone-modifying enzymes. Although epigenetic monotherapies have not shown activity against solid tumors, including ovarian cancer, preclinical studies suggest they will be effective when used in combination with one another or with conventional chemotherapeutics, and combinatorial epigenetic therapy regiments are being examined in cancer clinical trials. A greater understanding of the role of epigenetics in ovarian neoplasia will provide for improved interventions against this devastating malignancy.

scholarly journals Minireview: Epigenetic Changes in Ovarian Cancer

2009 ◽  
Vol 94 (9) ◽  
pp. 3617-3617
Author(s):  
Curt Balch ◽  
Fang Fang ◽  
Daniela E. Matei ◽  
Tim H.-M. Huang ◽  
Kenneth P. Nephew
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Micro Rna ◽  
Disease Stage ◽  
Epigenetic Therapy ◽  
Dna Mutations ◽  
Distinct Disease ◽  
Ovarian Neoplasia ◽  
Pharmacodynamic Biomarkers ◽  
Aberrant Gene

Epigenetic aberrations, including DNA methylation, histone modifications, and micro-RNA dysregulation, are now well established in the development and progression of ovarian cancer, and their gradual accumulation is associated with advancing disease stage and grade. Epigenetic aberrations are relatively stable, associated with distinct disease subtypes, and present in circulating serum, representing promising diagnostic, prognostic, and pharmacodynamic biomarkers. In contrast to DNA mutations and deletions, aberrant gene-repressive epigenetic modifications are potentially reversible by epigenetic therapies, including inhibitors of DNA methylation or histone-modifying enzymes. Although epigenetic monotherapies have not shown activity against solid tumors, including ovarian cancer, preclinical studies suggest they will be effective when used in combination with one another or with conventional chemotherapeutics, and combinatorial epigenetic therapy regiments are being examined in cancer clinical trials. A greater understanding of the role of epigenetics in ovarian neoplasia will provide for improved interventions against this devastating malignancy.

scholarly journals Minireview: Epigenetic Changes in Ovarian Cancer

2009 ◽  
Vol 94 (8) ◽  
pp. 3098-3098
Author(s):  
Curt Balch ◽  
Fang Fang ◽  
Daniela E. Matei ◽  
Tim H.-M. Huang ◽  
Kenneth P. Nephew
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Micro Rna ◽  
Disease Stage ◽  
Epigenetic Therapy ◽  
Dna Mutations ◽  
Distinct Disease ◽  
Ovarian Neoplasia ◽  
Pharmacodynamic Biomarkers ◽  
Aberrant Gene

Epigenetic aberrations, including DNA methylation, histone modifications, and micro-RNA dysregulation, are now well established in the development and progression of ovarian cancer, and their gradual accumulation is associated with advancing disease stage and grade. Epigenetic aberrations are relatively stable, associated with distinct disease subtypes, and present in circulating serum, representing promising diagnostic, prognostic, and pharmacodynamic biomarkers. In contrast to DNA mutations and deletions, aberrant gene-repressive epigenetic modifications are potentially reversible by epigenetic therapies, including inhibitors of DNA methylation or histone-modifying enzymes. Although epigenetic monotherapies have not shown activity against solid tumors, including ovarian cancer, preclinical studies suggest they will be effective when used in combination with one another or with conventional chemotherapeutics, and combinatorial epigenetic therapy regiments are being examined in cancer clinical trials. A greater understanding of the role of epigenetics in ovarian neoplasia will provide for improved interventions against this devastating malignancy.

Zebularine: a new drug for epigenetic therapy

2004 ◽  
Vol 32 (6) ◽  
pp. 910-912 ◽  
Author(s):  
C.B. Yoo ◽  
J.C. Cheng ◽  
P.A. Jones
Keyword(s):  
Dna Methylation ◽  
Regulatory Genes ◽  
Epigenetic Therapy ◽  
Clinical Use ◽  
Novel Therapies ◽  
New Drug ◽  
Dna Methylation Inhibitors

Regulatory genes are often hypermethylated at their promoter 5′ regions and silenced in cancer. Epigenetic therapy with DNA methylation inhibitors have been shown to result in the demethylation and reactivation of these genes. Zebularine is a recently discovered mechanism-based inhibitor of DNA methylation, and has received much attention for its potential in clinical use. Further studies exploring the effectiveness of zebularine in a variety of settings could allow the development of novel therapies for cancer.

scholarly journals Aberrant DNA Methylation in Cholangiocarcinoma

2017 ◽  
Author(s):  
Toshiaki Nakaoka ◽  
Yoshimasa Saito ◽  
Hidetsugu Saito
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Ampulla Of Vater ◽  
Endogenous Retroviruses ◽  
Epigenetic Therapy ◽  
Suppressor Genes ◽  
Aberrant Dna Methylation ◽  
Dna Methylation Inhibitors

Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. The effect of current chemotherapy regimens against cholangiocarcinoma is limited, and the prognosis of patients with cholangiocarcinoma is poor. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability during carcinogenesis. Studies have shown that the tumor suppressor genes and microRNAs (miRNAs) including MLH1, p14, p16, DAPK, miR-370 and miR-376c are frequently methylated in cholangiocarcinoma. Silencing of these tumor suppressor genes and miRNAs plays critical roles in the initiation and progression of cholangiocarcinoma. In addition, recent studies have demonstrated that DNA methylation inhibitors induce expression of endogenous retroviruses and exert the anti-tumor effect of via an anti-viral immune response. Aberrant DNA methylation of tumor suppressor genes and miRNAs could be a powerful biomarker for diagnosis and treatment of cholangiocarcinoma. Epigenetic therapy with DNA methylation inhibitors hold considerable promise for the treatment of cholangiocarcinoma through re-activation of tumor suppressor genes and miRNAs as well as induction of an anti-viral immune response.

scholarly journals Hypermethylation of mismatch repair gene hMSH2 associates with platinum-resistant disease in epithelial ovarian cancer

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Hua Tian ◽  
Li Yan ◽  
Li Xiao-fei ◽  
Sun Hai-yan ◽  
Chen Juan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ovarian Cancer ◽  
Dna Methylation ◽  
Epithelial Ovarian Cancer ◽  
Upstream Region ◽  
Platinum Resistance ◽  
Maldi Tof Mass Spectrometry ◽  
Platinum Resistant ◽  
Aberrant Dna Methylation ◽  
Low Expression

Abstract Purpose One major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of platinum resistance in EOC. The purpose of this study is to discover potential aberrant DNA methylation that contributes to drug resistance. Methods By initially screening of 16 platinum-sensitive/resistant samples from EOC patients with reduced representation bisulfite sequencing (RRBS), the upstream region of the hMSH2 gene was discovered hypermethylated in the platinum-resistant group. The effect of hMSH2 methylation on the cellular response to cisplatin was explored by demethylation and knockdown assays in ovarian cancer cell line A2780. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was employed to examine the methylation levels of hMSH2 upstream region in additional 40 EOC patient samples. RT-qPCR and IHC assay was used to detect the hMSH2 mRNA and protein expression in extended 150 patients. Results RRBS assay discovered an upstream region from − 1193 to − 1125 of hMSH2 was significant hypermethylated in resistant EOC patients (P = 1.06 × 10−14). In vitro analysis demonstrated that global demethylation increased cisplatin sensitivity along with a higher expression of the hMSH2 mRNA and protein. Knockdown hMSH2 reduced the cell sensitivity to cisplatin. MALDI-TOF mass spectrometry assay validated the strong association of hypermethylation of hMSH2 upstream region with platinum resistance. Spearman’s correlation analysis revealed a significantly negative connection between methylation level of hMSH2 upstream region and its expression. The Kaplan-Meier analyses showed the high methylation of hMSH2 promoter region, and its low expressions are associated with worse survival. In multivariable models, hMSH2 low expression was an independent factor predicting poor outcome (P = 0.03, HR = 1.91, 95%CI = 1.85–2.31). Conclusion The hypermethylation of hMSH2 upstream region is associated with platinum resistant in EOC, and low expression of hMSH2 may be an index for the poor prognosis.

scholarly journals Curcumin from Turmeric Rhizome: A Potential Modulator of DNA Methylation Machinery in Breast Cancer Inhibition

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 332
Author(s):  
Krystyna Fabianowska-Majewska ◽  
Agnieszka Kaufman-Szymczyk ◽  
Aldona Szymanska-Kolba ◽  
Jagoda Jakubik ◽  
Grzegorz Majewski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Curcuma Longa ◽  
Cancer Chemoprevention ◽  
Methylation Pattern ◽  
Dna Demethylation ◽  
Perennial Herb ◽  
Epigenetic Events ◽  
Epigenetic Machinery ◽  
Breast Cancer Inhibition

One of the most systematically studied bioactive nutraceuticals for its benefits in the management of various diseases is the turmeric-derived compounds: curcumin. Turmeric obtained from the rhizome of a perennial herb Curcuma longa L. is a condiment commonly used in our diet. Curcumin is well known for its potential role in inhibiting cancer by targeting epigenetic machinery, with DNA methylation at the forefront. The dynamic DNA methylation processes serve as an adaptive mechanism to a wide variety of environmental factors, including diet. Every healthy tissue has a precise DNA methylation pattern that changes during cancer development, forming a cancer-specific design. Hypermethylation of tumor suppressor genes, global DNA demethylation, and promoter hypomethylation of oncogenes and prometastatic genes are hallmarks of nearly all types of cancer, including breast cancer. Curcumin has been shown to modulate epigenetic events that are dysregulated in cancer cells and possess the potential to prevent cancer or enhance the effects of conventional anti-cancer therapy. Although mechanisms underlying curcumin-mediated changes in the epigenome remain to be fully elucidated, the mode of action targeting both hypermethylated and hypomethylated genes in cancer is promising for cancer chemoprevention. This review provides a comprehensive discussion of potential epigenetic mechanisms of curcumin in reversing altered patterns of DNA methylation in breast cancer that is the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide. Insight into the other bioactive components of turmeric rhizome as potential epigenetic modifiers has been indicated as well.

scholarly journals Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden

2017 ◽  
Vol 114 (51) ◽  
pp. E10981-E10990 ◽  
Author(s):  
Meredith L. Stone ◽  
Katherine B. Chiappinelli ◽  
Huili Li ◽  
Lauren M. Murphy ◽  
Meghan E. Travers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Histone Deacetylase Inhibitors ◽  
Unmet Need ◽  
Tumor Burden ◽  
Epigenetic Therapy ◽  
Type I ◽  
Type I Ifn

Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy. These data indicate that the type I IFN response is required for effective in vivo antitumorigenic actions of the DNMTi 5-azacytidine (AZA). Through type I IFN signaling, AZA increases the numbers of CD45+ immune cells and the percentage of active CD8+ T and natural killer (NK) cells in the tumor microenvironment, while reducing tumor burden and extending survival. AZA also increases viral defense gene expression in both tumor and immune cells, and reduces the percentage of macrophages and myeloid-derived suppressor cells in the tumor microenvironment. The addition of an HDACi to AZA enhances the modulation of the immune microenvironment, specifically increasing T and NK cell activation and reducing macrophages over AZA treatment alone, while further increasing the survival of the mice. Finally, a triple combination of DNMTi/HDACi plus the immune checkpoint inhibitor α-PD-1 provides the best antitumor effect and longest overall survival, and may be an attractive candidate for future clinical trials in ovarian cancer.

scholarly journals HOXA11 DNA methylation-A novel prognostic biomarker in ovarian cancer

2008 ◽  
Vol 123 (3) ◽  
pp. 725-729 ◽  
Author(s):  
Heidi Fiegl ◽  
Gudrun Windbichler ◽  
Elisabeth Mueller-Holzner ◽  
Georg Goebel ◽  
Matthias Lechner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Prognostic Biomarker
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