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stephen baylin

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https://www.readbyqxmd.com/read/28486105/chd4-has-oncogenic-functions-in-initiating-and-maintaining-epigenetic-suppression-of-multiple-tumor-suppressor-genes
#1
Limin Xia, Wenjie Huang, Marina Bellani, Michael M Seidman, Kaichun Wu, Daiming Fan, Yongzhan Nie, Yi Cai, Yang W Zhang, Li-Rong Yu, Huili Li, Cynthia A Zahnow, Wenbing Xie, Ray-Whay Chiu Yen, Feyruz V Rassool, Stephen B Baylin
An oncogenic role for CHD4, a NuRD component, is defined for initiating and supporting tumor suppressor gene (TSG) silencing in human colorectal cancer. CHD4 recruits repressive chromatin proteins to sites of DNA damage repair, including DNA methyltransferases where it imposes de novo DNA methylation. At TSGs, CHD4 retention helps maintain DNA hypermethylation-associated transcriptional silencing. CHD4 is recruited by the excision repair protein OGG1 for oxidative damage to interact with the damage-induced base 8-hydroxydeoxyguanosine (8-OHdG), while ZMYND8 recruits it to double-strand breaks...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28445481/hypomethylating-agents-synergize-with-irinotecan-to-improve-response-to-chemotherapy-in-colorectal-cancer-cells
#2
Anup Sharma, Rajita Vatapalli, Eihab Abdelfatah, K Wyatt McMahon, Zachary Kerner, Angela A Guzzetta, Jasvinder Singh, Cynthia Zahnow, Stephen B Baylin, Sashidhar Yerram, Yue Hu, Nilofer Azad, Nita Ahuja
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA) in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28407701/correction-a-new-immunohistochemistry-prognostic-score-ips-for-recurrence-and-survival-in-resected-pancreatic-neuroendocrine-tumors-pannet
#3
Antonio Viúdez, Filipe L F Carvalho, Zahra Maleki, Marianna Zahurak, Daniel Laheru, Alejandro Stark, Nilofer S Azad, Christopher L Wolfgang, Stephen Baylin, James G Herman, Ana De Jesus-Acosta
No abstract text is available yet for this article.
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388418/inhibiting-dna-methylation-causes-an-interferon-response-in-cancer-via-dsrna-including-endogenous-retroviruses
#4
Katherine B Chiappinelli, Pamela L Strissel, Alexis Desrichard, Huili Li, Christine Henke, Benjamin Akman, Alexander Hein, Neal S Rote, Leslie M Cope, Alexandra Snyder, Vladimir Makarov, Sadna Budhu, Dennis J Slamon, Jedd D Wolchok, Drew M Pardoll, Matthias W Beckmann, Cynthia A Zahnow, Taha Merghoub, Timothy A Chan, Stephen B Baylin, Reiner Strick
No abstract text is available yet for this article.
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28202634/dietary-patterns-are-associated-with-metabolic-outcomes-among-adult-samoans-in-a-cross-sectional-study
#5
Dongqing Wang, Nicola L Hawley, Avery A Thompson, Viali Lameko, Muagatutia Sefuiva Reupena, Stephen T McGarvey, Ana Baylin
Background: The Samoan population has been undergoing a nutrition transition toward more imported and processed foods and a more sedentary lifestyle.Objectives: We aimed to identify dietary patterns in Samoa and to evaluate their associations with metabolic outcomes.Methods: The sample of this cross-sectional study includes 2774 Samoan adults recruited in 2010 (1104 with metabolic syndrome compared with 1670 without). Principal component analysis on food items from a 104-item food-frequency questionnaire was used to identify dietary patterns...
April 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28186961/combination-epigenetic-therapy-in-metastatic-colorectal-cancer-mcrc-with-subcutaneous-5-azacitidine-and-entinostat-a-phase-2-consortium-stand-up-2-cancer-study
#6
Nilofer S Azad, Anthony El-Khoueiry, Jun Yin, Ann L Oberg, Patrick Flynn, Douglas Adkins, Anup Sharma, Daniel J Weisenberger, Thomas Brown, Prakriti Medvari, Peter A Jones, Hariharan Easwaran, Ihab Kamel, Nathan Bahary, George Kim, Joel Picus, Henry C Pitot, Charles Erlichman, Ross Donehower, Hui Shen, Peter W Laird, Richard Piekarz, Stephen Baylin, Nita Ahuja
PURPOSE: Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. EXPERIMENTAL DESIGN: We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 75 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10...
February 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107650/acetylation-enhances-tet2-function-in-protecting-against-abnormal-dna-methylation-during-oxidative-stress
#7
Yang W Zhang, Zhihong Wang, Wenbing Xie, Yi Cai, Limin Xia, Hariharan Easwaran, Jianjun Luo, Ray-Whay Chiu Yen, Yana Li, Stephen B Baylin
TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28031159/evolution-of-neoantigen-landscape-during-immune-checkpoint-blockade-in-non-small-cell-lung-cancer
#8
Valsamo Anagnostou, Kellie N Smith, Patrick M Forde, Noushin Niknafs, Rohit Bhattacharya, James White, Theresa Zhang, Vilmos Adleff, Jillian Phallen, Neha Wali, Carolyn Hruban, Violeta B Guthrie, Kristen Rodgers, Jarushka Naidoo, Hyunseok Kang, William Sharfman, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V Brock, Cynthia A Zahnow, Stephen B Baylin, Robert B Scharpf, Julie R Brahmer, Rachel Karchin, Drew M Pardoll, Victor E Velculescu
Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in patients with non-small cell lung cancer after initial response to immune checkpoint blockade with anti-PD-1 or anti-PD-1/anti-CTLA-4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones...
March 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27979916/combination-epigenetic-therapy-in-advanced-breast-cancer-with-5-azacitidine-and-entinostat-a-phase-ii-national-cancer-institute-stand-up-to-cancer-study
#9
Roisin M Connolly, Huili Li, Rachel C Jankowitz, Zhe Zhang, Michelle A Rudek, Stacie C Jeter, Shannon A Slater, Penny Powers, Antonio C Wolff, John H Fetting, Adam Brufsky, Richard Piekarz, Nita Ahuja, Peter W Laird, Hui Shen, Daniel J Weisenberger, Leslie Cope, James G Herman, George Somlo, Agustin A Garcia, Peter A Jones, Stephen B Baylin, Nancy E Davidson, Cynthia A Zahnow, Vered Stearns
Purpose: In breast cancer models, combination epigenetic therapy with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor led to reexpression of genes encoding important therapeutic targets, including the estrogen receptor (ER). We conducted a multicenter phase II study of 5-azacitidine and entinostat in women with advanced hormone-resistant or triple-negative breast cancer (TNBC).Experimental Design: Patients received 5-azacitidine 40 mg/m(2) (days 1-5, 8-10) and entinostat 7 mg (days 3, 10) on a 28-day cycle...
December 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27880934/tumors-with-unmethylated-mlh1-and-the-cpg-island-methylator-phenotype-are-associated-with-a-poor-prognosis-in-stage-ii-colorectal-cancer-patients
#10
Tao Fu, Yanliang Liu, Kai Li, Weiwei Wan, Emmanouil P Pappou, Christine A Iacobuzio-Donahue, Zachary Kerner, Stephen B Baylin, Christopher L Wolfgang, Nita Ahuja
We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27729459/early-detection-of-lung-cancer-using-dna-promoter-hypermethylation-in-plasma-and-sputum
#11
Alicia Hulbert, Ignacio Jusue-Torres, Alejandro Stark, Chen Chen, Kristen Rodgers, Beverly Lee, Candace Griffin, Andrew Yang, Peng Huang, John Wrangle, Steven A Belinsky, Tza-Huei Wang, Stephen C Yang, Stephen B Baylin, Malcolm V Brock, James G Herman
PURPOSE: CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer-specific gene panel to detect DNA methylation in sputum and plasma. EXPERIMENTAL DESIGN: This is a case-control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained preoperatively. Cases (n = 150) had pathologic confirmation of node-negative (stages I and IIA) non-small cell lung cancer...
October 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27728808/enhancing-the-cytotoxic-effects-of-parp-inhibitors-with-dna-demethylating-agents-a-potential-therapy-for-cancer
#12
Nidal E Muvarak, Khadiza Chowdhury, Limin Xia, Carine Robert, Eun Yong Choi, Yi Cai, Marina Bellani, Ying Zou, Zeba N Singh, Vu H Duong, Tyler Rutherford, Pratik Nagaria, Søren M Bentzen, Michael M Seidman, Maria R Baer, Rena G Lapidus, Stephen B Baylin, Feyruz V Rassool
Poly (ADP-ribose) polymerase inhibitors (PARPis) are clinically effective predominantly for BRCA-mutant tumors. We introduce a mechanism-based strategy to enhance PARPi efficacy based on DNA damage-related binding between DNA methyltransferases (DNMTs) and PARP1. In acute myeloid leukemia (AML) and breast cancer cells, DNMT inhibitors (DNMTis) alone covalently bind DNMTs into DNA and increase PARP1 tightly bound into chromatin. Low doses of DNMTis plus PARPis, versus each drug alone, increase PARPi efficacy, increasing amplitude and retention of PARP1 directly at laser-induced DNA damage sites...
October 10, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27660325/tankyrase-inhibition-promotes-a-stable-human-na%C3%A3-ve-pluripotent-state-with-improved-functionality
#13
Ludovic Zimmerlin, Tea Soon Park, Jeffrey S Huo, Karan Verma, Sarshan R Pather, C Conover Talbot, Jasmin Agarwal, Diana Steppan, Yang W Zhang, Michael Considine, Hong Guo, Xiufeng Zhong, Christian Gutierrez, Leslie Cope, M Valeria Canto-Soler, Alan D Friedman, Stephen B Baylin, Elias T Zambidis
The derivation and maintenance of human pluripotent stem cells (hPSCs) in stable naïve pluripotent states has a wide impact in human developmental biology. However, hPSCs are unstable in classical naïve mouse embryonic stem cell (ESC) WNT and MEK/ERK signal inhibition (2i) culture. We show that a broad repertoire of conventional hESC and transgene-independent human induced pluripotent stem cell (hiPSC) lines could be reverted to stable human preimplantation inner cell mass (ICM)-like naïve states with only WNT, MEK/ERK, and tankyrase inhibition (LIF-3i)...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27643594/methylation-of-mgmt-is-associated-with-poor-prognosis-in-patients-with-stage-iii-duodenal-adenocarcinoma
#14
Tao Fu, Anup Sharmab, Fei Xie, Yanliang Liu, Kai Li, Weiwei Wan, Stephen B Baylin, Christopher L Wolfgang, Nita Ahuja
BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) methylation status has not been extensively investigated in duodenal adenocarcinoma (DA). The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA. METHODS: Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI), and KRAS mutations...
2016: PloS One
https://www.readbyqxmd.com/read/27634286/genome-wide-positioning-of-bivalent-mononucleosomes
#15
Subhojit Sen, Kirsten F Block, Alice Pasini, Stephen B Baylin, Hariharan Easwaran
BACKGROUND: Bivalent chromatin refers to overlapping regions containing activating histone H3 Lys4 trimethylation (H3K4me3) and inactivating H3K27me3 marks. Existence of such bivalent marks on the same nucleosome has only recently been suggested. Previous genome-wide efforts to characterize bivalent chromatin have focused primarily on individual marks to define overlapping zones of bivalency rather than mapping positions of truly bivalent mononucleosomes. RESULTS: Here, we developed an efficacious sequential ChIP technique for examining global positioning of individual bivalent nucleosomes...
September 15, 2016: BMC Medical Genomics
https://www.readbyqxmd.com/read/27629931/targeting-the-cancer-epigenome-for-therapy
#16
REVIEW
Peter A Jones, Jean-Pierre J Issa, Stephen Baylin
Next-generation sequencing has revealed that more than 50% of human cancers harbour mutations in enzymes that are involved in chromatin organization. Tumour cells not only are activated by genetic and epigenetic alterations, but also routinely use epigenetic processes to ensure their escape from chemotherapy and host immune surveillance. Hence, a growing emphasis of recent drug discovery efforts has been on targeting the epigenome, including DNA methylation and histone modifications, with several new drugs being tested and some already approved by the US Food and Drug Administration (FDA)...
September 15, 2016: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/27573823/vitamin-c-increases-viral-mimicry-induced-by-5-aza-2-deoxycytidine
#17
Minmin Liu, Hitoshi Ohtani, Wanding Zhou, Andreas Due Ørskov, Jessica Charlet, Yang W Zhang, Hui Shen, Stephen B Baylin, Gangning Liang, Kirsten Grønbæk, Peter A Jones
Vitamin C deficiency is found in patients with cancer and might complicate various therapy paradigms. Here we show how this deficiency may influence the use of DNA methyltransferase inhibitors (DNMTis) for treatment of hematological neoplasias. In vitro, when vitamin C is added at physiological levels to low doses of the DNMTi 5-aza-2'-deoxycytidine (5-aza-CdR), there is a synergistic inhibition of cancer-cell proliferation and increased apoptosis. These effects are associated with enhanced immune signals including increased expression of bidirectionally transcribed endogenous retrovirus (ERV) transcripts, increased cytosolic dsRNA, and activation of an IFN-inducing cellular response...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27467919/unraveling-the-molecular-pathways-of-dna-methylation-inhibitors-human-endogenous-retroviruses-induce-the-innate-immune-response-in-tumors
#18
Reiner Strick, Pamela L Strissel, Stephen B Baylin, Katherine B Chiappinelli
Loss of DNA methylation can activate endogenous retroviral expression and dsRNA in cancer cells. This leads to induction of toll-like receptor signaling stimulating an antiviral interferon response. Recent findings provide a therapeutic rationale for combining DNA methylation inhibitors with blockage of immune checkpoint proteins to fight cancer.
May 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27197249/jacob-monod-the-lac-operon-and-the-pajama-experiment-gene-expression-circuitry-changing-the-face-of-cancer-research
#19
Stephen B Baylin
No abstract text is available yet for this article.
April 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27194046/epigenetic-determinants-of-cancer
#20
REVIEW
Stephen B Baylin, Peter A Jones
SUMMARYEpigenetic changes are present in all human cancers and are now known to cooperate with genetic alterations to drive the cancer phenotype. These changes involve DNA methylation, histone modifiers and readers, chromatin remodelers, microRNAs, and other components of chromatin. Cancer genetics and epigenetics are inextricably linked in generating the malignant phenotype; epigenetic changes can cause mutations in genes, and, conversely, mutations are frequently observed in genes that modify the epigenome...
2016: Cold Spring Harbor Perspectives in Biology
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