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Methylation ovarian cancer platinum resistance

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https://www.readbyqxmd.com/read/29436261/an-epigenomic-approach-to-identifying-differential-overlapping-and-cis-acting-lncrnas-in-cisplatin-resistant-cancer-cells
#1
Olga Vera, Carlos Rodriguez-Antolin, Javier de Castro, Florian A Karreth, Thomas A Sellers, Inmaculada Ibañez de Caceres
Long noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensitive/resistant non-small cell lung cancer and ovarian cancer cell lines. The epigenetic landscape of overlapping and cis-acting lncRNAs was determined by combining human microarray data on 30,586 lncRNAs and 20,109 protein coding mRNAs with whole-genome bisulfite sequencing...
February 13, 2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29434981/3-oxoacid-coa-transferase-1-as-a-therapeutic-target-gene-for-cisplatin-resistant-ovarian-cancer
#2
San-Duk Yang, So Hee Ahn, Jong-Il Kim
Ovarian cancer (OC) is the second leading cause of mortality from gynecological malignancies and has the highest mortality rate worldwide. As it is commonly asymptomatic during the early stages of the disease, >70% of patients with OC are diagnosed at advanced stages with metastasis. Despite treatment methods, including optimal debulking surgery and chemotherapy with the platinum-based drug cisplatin, OC recurrence is often inevitable, with an overall 5-year survival rate of 45%, mostly due to the steady development of cisplatin resistance...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29386467/alkaloids-from-stephania-venosa-as-chemo-sensitizers-in-skov3-ovarian-cancer-cells-via-akt-nf-%C3%AE%C2%BAb-signaling
#3
May Thuu Mon, Supachai Yodkeeree, Wanisa Punfa, Wilart Pompimon, Pornngarm Limtrakul
Crebanine (CN), tetrahydropalmatine (THP), O-methylbulbocapnine (OMBC) and N-methyl tetrahydropalmatine (NMTHP) are isoquinoline derived natural alkaloids isolated from tubers of Stephania venosa. We investigated chemo-sensitizing effects of these alkaloids in ovarian cancer cells and evaluated underlying molecular mechanisms involved in chemo-sensitivity. Detection of cell apoptosis was evaluated by using flow cytometry. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay...
2018: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29229600/genomic-and-epigenomic-signatures-in-ovarian-cancer-associated-with-resensitization-to-platinum-drugs
#4
Fang Fang, Horacio Cardenas, Hao Huang, Guanglong Jiang, Susan M Perkins, Chi Zhang, Harold N Keer, Yunlong Liu, Kenneth P Nephew, Daniela Matei
DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer. In this study, we elucidated an epigenetic signature associated with platinum drug resensitization that may offer utility in predicting the outcomes of patients who are coadministered a DNA methyltransferase inhibitor. The ovarian cancer specimens we analyzed were derived from a recent clinical trial that compared the responses of patients with recurrent platinum-resistant ovarian cancer who received carboplatin plus the DNA methyltransferase inhibitor guadecitabine or a standard-of-care chemotherapy regimen selected by the treating physician...
February 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29158814/dna-methylation-of-mir-7-is-a-mechanism-involved-in-platinum-response-through-mafg-overexpression-in-cancer-cells
#5
Olga Vera, Julia Jimenez, Olga Pernia, Carlos Rodriguez-Antolin, Carmen Rodriguez, Fatima Sanchez Cabo, Javier Soto, Rocio Rosas, Sara Lopez-Magallon, Isabel Esteban Rodriguez, Ana Dopazo, Federico Rojo, Cristobal Belda, Rafael Alvarez, Jaime Valentin, Javier Benitez, Rosario Perona, Javier De Castro, Inmaculada Ibanez de Caceres
One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance. Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines...
2017: Theranostics
https://www.readbyqxmd.com/read/28975405/aberrant-serpine1-dna-methylation-is-involved-in-carboplatin-induced-epithelial-mesenchymal-transition-in-epithelial-ovarian-cancer
#6
Jie-Xue Pan, Fan Qu, Fang-Fang Wang, Jian Xu, Liang-Shan Mu, Long-Yun Ye, Jun-Jian Li
AIM: Resistance to platinum-based therapeutic agents is the major contributor to epithelial ovarian cancer (EOC) mortality. There is an urgent need to better understand the underlying mechanisms. Here we investigated the role of serpins in EOC chemoresistance and related mechanisms, and found that SERPINE1 played an important role in chemoresistance in A2780cp cells. MATERIALS AND METHODS: A2780cp and A2780s cells were used in our study. Microarray screening was used to identify the gene expression change under carboplatin treatment...
October 3, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28641578/methylome-analysis-of-extreme-chemoresponsive-patients-identifies-novel-markers-of-platinum-sensitivity-in-high-grade-serous-ovarian-cancer
#7
Tushar Tomar, Nicolette G Alkema, Leroy Schreuder, Gert Jan Meersma, Tim de Meyer, Wim van Criekinge, Harry G Klip, Heidi Fiegl, Els van Nieuwenhuysen, Ignace Vergote, Martin Widschwendter, Ed Schuuring, Ate G J van der Zee, Steven de Jong, G Bea A Wisman
BACKGROUND: Despite an early response to platinum-based chemotherapy in advanced stage high-grade serous ovarian cancer (HGSOC), the majority of patients will relapse with drug-resistant disease. Aberrant epigenetic alterations like DNA methylation are common in HGSOC. Differences in DNA methylation are associated with chemoresponse in these patients. The objective of this study was to identify and validate novel epigenetic markers of chemoresponse using genome-wide analysis of DNA methylation in extreme chemoresponsive HGSOC patients...
June 23, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28473707/dna-methylation-and-transcriptome-changes-associated-with-cisplatin-resistance-in-ovarian-cancer
#8
Riikka J Lund, Kaisa Huhtinen, Jussi Salmi, Juha Rantala, Elizabeth V Nguyen, Robert Moulder, David R Goodlett, Riitta Lahesmaa, Olli Carpén
High-grade serous ovarian cancer is the most common ovarian cancer type. Although the combination of surgery and platinum-taxane chemotherapy provide an effective treatment, drug resistance frequently occurs leading to poor outcome. In order to clarify the molecular mechanisms of drug resistance, the DNA methylation and transcriptomic changes, associated with the development of drug resistance in high-grade serous ovarian cancer, were examined from patient derived malignant ascites cells. In parallel with large-scale transcriptome changes, cisplatin resistance was associated with loss of hypermethylation at several CpG sites primarily localized in the intergenic regions of the genome...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150354/tet1-promotes-cisplatin-resistance-via-demethylating-the-vimentin-promoter-in-ovarian-cancer
#9
Xi Han, Yuanyuan Zhou, Yuanyi You, Jiaojiao Lu, Lijie Wang, Huilian Hou, Jing Li, Wei Chen, Le Zhao, Xu Li
The development of chemo-resistance impairs the outcome of the first line platinum-based chemotherapies for ovarian cancer. Deregulation of DNA methylation/demethylation provides a critical mechanism for the occurrence of chemo-resistance. The ten-eleven translocation (TET) family of dioxygenases including TET1/2/3 plays an important part in DNA demethylation, but their roles in cisplatin resistance have not been elucidated. Using cisplatin-sensitive and cisplatin-resistant ovarian cancer cell models, we found that TET1 was significantly upregulated in cisplatin-resistant CP70 cells compared with that in cisplatin-sensitive A2780 cells...
April 2017: Cell Biology International
https://www.readbyqxmd.com/read/27906967/platinum-ii-iodido-complexes-of-7-azaindoles-with-significant-antiproliferative-effects-an-old-story-revisited-with-unexpected-outcomes
#10
Pavel Štarha, Ján Vančo, Zdeněk Trávníček, Jan Hošek, Jarmila Klusáková, Zdeněk Dvořák
A series of platinum(II) diiodido complexes containing 7-azaindole derivatives, having the general formula cis-[PtI2(naza)2] (1-8), has been prepared and thoroughly characterized, including X-ray structure analysis of cis-[PtI2(2Me4Claza)2]∙DMF (8∙DMF; 2Me4Claza = 2-methyl-4-chloro-7-azaindole). Complexes showed high in vitro cytotoxicity against nine human cancer cell lines (IC50 ranging from 0.4 to 12.8 μM), including the cisplatin-resistant ovarian cancer cell line (A2780R; IC50 = 1.0-3.5 μM). The results of in vivo testing, using the L1210 lymphocytic leukaemia model, at the equimolar doses of Pt with cisplatin (2 mg/kg) confirmed the activity of complex 8 comparable to cisplatin...
2016: PloS One
https://www.readbyqxmd.com/read/27793894/the-effects-of-histone-deacetylase-inhibitor-and-calpain-inhibitor-combination-therapies-on-ovarian-cancer-cells
#11
Karolina Lapinska, Genevieve Housman, Shannon Byler, Sarah Heerboth, Amber Willbanks, Anuja Oza, Sibaji Sarkar
BACKGROUND: Ovarian cancer is difficult to treat due to absence of selective drugs and tendency of platinum drugs to promote resistance. Combination therapy using epigenetic drugs is predicted to be a beneficial alternative. MATERIALS AND METHODS: This study investigated the effects of combination therapies using two structurally different histone deacetylase (HDAC) inhibitors (HDACi), sodium butyrate and suberanilohydroxamic acid (SAHA), with the calpain inhibitor calpeptin on two characteristically different ovarian cancer cell lines, CAOV-3 and SKOV-3...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27765068/genome-wide-methylation-profiling-of-ovarian-cancer-patient-derived-xenografts-treated-with-the-demethylating-agent-decitabine-identifies-novel-epigenetically-regulated-genes-and-pathways
#12
Tushar Tomar, Steven de Jong, Nicolette G Alkema, Rieks L Hoekman, Gert Jan Meersma, Harry G Klip, Ate Gj van der Zee, G Bea A Wisman
BACKGROUND: In high-grade serous ovarian cancer (HGSOC), intrinsic and/or acquired resistance against platinum-containing chemotherapy is a major obstacle for successful treatment. A low frequency of somatic mutations but frequent epigenetic alterations, including DNA methylation in HGSOC tumors, presents the cancer epigenome as a relevant target for innovative therapy. Patient-derived xenografts (PDXs) supposedly are good preclinical models for identifying novel drug targets. However, the representativeness of global methylation status of HGSOC PDXs compared to their original tumors has not been evaluated so far...
October 20, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27374141/transmembrane-protein-88-tmem88-promoter-hypomethylation-is-associated-with-platinum-resistance-in-ovarian-cancer
#13
Maria de Leon, Horacio Cardenas, Edyta Vieth, Robert Emerson, Matthew Segar, Yunlong Liu, Kenneth Nephew, Daniela Matei
OBJECTIVES: Epigenetic alterations have been implicated in the development of platinum resistance in ovarian cancer (OC). In this study, we aimed to identify DNA methylation changes in platinum resistant tumors and their functional implications. METHODS: To identify DNA methylation alterations we used the Illumina 450k DNA methylation array and profiled platinum sensitive and resistant OC xenografts. Validation analyses employed RT-PCR and immunohistochemistry (IHC)...
September 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27087632/evaluation-of-rucaparib-and-companion-diagnostics-in-the-parp-inhibitor-landscape-for-recurrent-ovarian-cancer-therapy
#14
REVIEW
Zachary B Jenner, Anil K Sood, Robert L Coleman
Rucaparib camsylate (CO-338; 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt) is a PARP1, 2 and 3 inhibitor. Phase I studies identified a recommended Phase II dose of 600 mg orally twice daily. ARIEL2 Part 1 established a tumor genomic profiling test for homologous recombination loss of heterozygosity quantification using a next-generation sequencing companion diagnostic (CDx). Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy...
June 2016: Future Oncology
https://www.readbyqxmd.com/read/27051056/proteasome-inhibitor-mg132-enhances-sensitivity-to-cisplatin-on-ovarian-carcinoma-cells-in-vitro-and-in-vivo
#15
Na Guo, Zhilan Peng, Jiawen Zhang
BACKGROUND: Platinum-based combination chemotherapy after surgery is considered a standard treatment; therefore, any recent drug development should be new, effective, and low toxic, and should have a synergistic effect with platinum. This study aimed to observe the growth of SKOV3 cells after treatment with cisplatin by combining with carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) and to investigate the effect of the relationship between MG132 and cisplatin combination. MATERIALS AND METHODS: Cell growth was detected by methyl thiazolyl tetrazolium assay after treatment with MG132 at 0...
June 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/26763252/epigenetic-regulation-of-the-homeobox-gene-msx1-associates-with-platinum-resistant-disease-in-high-grade-serous-epithelial-ovarian-cancer
#16
Nair A Bonito, Jane Borley, Charlotte S Wilhelm-Benartzi, Sadaf Ghaem-Maghami, Robert Brown
PURPOSE: Although high-grade serous ovarian cancer (HGSOC) is frequently chemoresponsive, a proportion of patients do not respond to platinum-based chemotherapy at presentation or have progression-free survival (PFS) of less than 6 months. Validated predictive biomarkers of lack of response would enable alternative treatment stratification for these patients and identify novel mechanisms of intrinsic resistance. Our aim was to identify DNA methylation biomarkers of poor response to chemotherapy and demonstrate involvement of the associated gene in platinum drug cell sensitivity...
June 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26625211/epigenetic-inactivation-of-the-putative-dna-rna-helicase-slfn11-in-human-cancer-confers-resistance-to-platinum-drugs
#17
Vanesa Nogales, William C Reinhold, Sudhir Varma, Anna Martinez-Cardus, Catia Moutinho, Sebastian Moran, Holger Heyn, Ana Sebio, Agusti Barnadas, Yves Pommier, Manel Esteller
Platinum-derived drugs such as cisplatin and carboplatin are among the most commonly used cancer chemotherapy drugs, but very few specific molecular and cellular markers predicting differential sensitivity to these agents in a given tumor type have been clearly identified. Epigenetic gene silencing is increasingly being recognized as a factor conferring distinct tumoral drug sensitivity, so we have used a comprehensive DNA methylation microarray platform to interrogate the widely characterized NCI60 panel of human cancer cell lines with respect to CpG methylation status and cisplatin/carboplatin sensitivity...
January 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26351843/contributions-of-the-epidermal-growth-factor-receptor-to-acquisition-of-platinum-resistance-in-ovarian-cancer-cells
#18
Michaela L Granados, Laurie G Hudson, Sabrina L Samudio-Ruiz
Acquisition of platinum resistance following first line platinum/taxane therapy is commonly observed in ovarian cancer patients and prevents clinical effectiveness. There are few options to prevent platinum resistance; however, demethylating agents have been shown to resensitize patients to platinum therapy thereby demonstrating that DNA methylation is a critical contributor to the development of platinum resistance. We previously reported the Epidermal Growth Factor Receptor (EGFR) is a novel regulator of DNA methyltransferase (DNMT) activity and DNA methylation...
2015: PloS One
https://www.readbyqxmd.com/read/26122843/identification-of-prognostic-groups-in-high-grade-serous-ovarian-cancer-treated-with-platinum-taxane-chemotherapy
#19
Ping Chen, Kaisa Huhtinen, Katja Kaipio, Piia Mikkonen, Viljami Aittomäki, Rony Lindell, Johanna Hynninen, Annika Auranen, Seija Grénman, Rainer Lehtonen, Olli Carpén, Sampsa Hautaniemi
Disseminated high-grade serous ovarian cancer (HGS-OvCa) is an aggressive disease treated with platinum and taxane combination therapy. While initial response can be favorable, the disease typically relapses and becomes resistant to treatment. As genomic alterations in HGS-OvCa are heterogeneous, identification of clinically meaningful molecular markers for outcome prediction is challenging. We developed a novel computational approach (PSFinder) that fuses transcriptomics and clinical data to identify HGS-OvCa prognostic subgroups for targeted treatment...
August 1, 2015: Cancer Research
https://www.readbyqxmd.com/read/26017449/whole-genome-characterization-of-chemoresistant-ovarian-cancer
#20
Ann-Marie Patch, Elizabeth L Christie, Dariush Etemadmoghadam, Dale W Garsed, Joshy George, Sian Fereday, Katia Nones, Prue Cowin, Kathryn Alsop, Peter J Bailey, Karin S Kassahn, Felicity Newell, Michael C J Quinn, Stephen Kazakoff, Kelly Quek, Charlotte Wilhelm-Benartzi, Ed Curry, Huei San Leong, Anne Hamilton, Linda Mileshkin, George Au-Yeung, Catherine Kennedy, Jillian Hung, Yoke-Eng Chiew, Paul Harnett, Michael Friedlander, Michael Quinn, Jan Pyman, Stephen Cordner, Patricia O'Brien, Jodie Leditschke, Greg Young, Kate Strachan, Paul Waring, Walid Azar, Chris Mitchell, Nadia Traficante, Joy Hendley, Heather Thorne, Mark Shackleton, David K Miller, Gisela Mir Arnau, Richard W Tothill, Timothy P Holloway, Timothy Semple, Ivon Harliwong, Craig Nourse, Ehsan Nourbakhsh, Suzanne Manning, Senel Idrisoglu, Timothy J C Bruxner, Angelika N Christ, Barsha Poudel, Oliver Holmes, Matthew Anderson, Conrad Leonard, Andrew Lonie, Nathan Hall, Scott Wood, Darrin F Taylor, Qinying Xu, J Lynn Fink, Nick Waddell, Ronny Drapkin, Euan Stronach, Hani Gabra, Robert Brown, Andrea Jewell, Shivashankar H Nagaraj, Emma Markham, Peter J Wilson, Jason Ellul, Orla McNally, Maria A Doyle, Ravikiran Vedururu, Collin Stewart, Ernst Lengyel, John V Pearson, Nicola Waddell, Anna deFazio, Sean M Grimmond, David D L Bowtell
Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance...
May 28, 2015: Nature
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