keyword
https://read.qxmd.com/read/34680341/clinical-significance-of-plasma-cd9-positive-exosomes-in-hiv-seronegative-and-seropositive-lung-cancer-patients
#21
JOURNAL ARTICLE
Foteinos-Ioannis Dimitrakopoulos, Anastasia E Kottorou, Kristen Rodgers, John Timothy Sherwood, Georgia-Angeliki Koliou, Beverly Lee, Andrew Yang, Julie Renee Brahmer, Stephen B Baylin, Stephen C Yang, Hajime Orita, Alicia Hulbert, Malcolm V Brock
Recently, the role of exosomes in the progression of both cancer and HIV (human immunodeficiency virus) has been described. This study investigates the clinical significance of CD9-positive plasma exosomes in lung cancer patients, healthy individuals, and HIV-positive patients with or without lung cancer. Using a verified with transmission electron microscopy double-sandwich ELISA technique, plasma-derived exosomes were isolated and quantified from 210 lung cancer patients (including 44 metastatic patients with progressive disease after chemotherapy), 49 healthy controls, 20 patients with pulmonary granulomas, 19 HIV+ patients with lung cancer, 31 HIV+ patients without cancer, and 3 HIV+ patients with pulmonary granulomas...
October 16, 2021: Cancers
https://read.qxmd.com/read/34624208/role-of-mir-2392-in-driving-sars-cov-2-infection
#22
JOURNAL ARTICLE
J Tyson McDonald, Francisco J Enguita, Deanne Taylor, Robert J Griffin, Waldemar Priebe, Mark R Emmett, Mohammad M Sajadi, Anthony D Harris, Jean Clement, Joseph M Dybas, Nukhet Aykin-Burns, Joseph W Guarnieri, Larry N Singh, Peter Grabham, Stephen B Baylin, Aliza Yousey, Andrea N Pearson, Peter M Corry, Amanda Saravia-Butler, Thomas R Aunins, Sadhana Sharma, Prashant Nagpal, Cem Meydan, Jonathan Foox, Christopher Mozsary, Bianca Cerqueira, Viktorija Zaksas, Urminder Singh, Eve Syrkin Wurtele, Sylvain V Costes, Gustavo Gastão Davanzo, Diego Galeano, Alberto Paccanaro, Suzanne L Meinig, Robert S Hagan, Natalie M Bowman, Matthew C Wolfgang, Selin Altinok, Nicolae Sapoval, Todd J Treangen, Pedro M Moraes-Vieira, Charles Vanderburg, Douglas C Wallace, Jonathan C Schisler, Christopher E Mason, Anushree Chatterjee, Robert Meller, Afshin Beheshti
MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection...
October 19, 2021: Cell Reports
https://read.qxmd.com/read/34433584/epigenetic-therapies-in-ovarian-cancer-alter-repetitive-element-expression-in-a-tp53-dependent-manner
#23
JOURNAL ARTICLE
James I McDonald, Noor Diab, Elisa Arthofer, Melissa Hadley, Tomas Kanholm, Uzma Rentia, Stephanie Gomez, Angela Yu, Erin E Grundy, Olivia Cox, Michael J Topper, Xiaoyun Xing, Pamela L Strissel, Reiner Strick, Ting Wang, Stephen B Baylin, Katherine B Chiappinelli
Epithelial ovarian carcinomas (OC) are particularly deadly due to intratumoral heterogeneity, resistance to standard-of-care therapies, and poor response to alternative treatments such as immunotherapy. Targeting the OC epigenome with DNA methyltransferase inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi) increases immune signaling and recruits CD8+ T cells and NK cells to fight OC in murine models. This increased immune activity is caused by increased transcription of repetitive elements (RE) that form double-stranded RNA (dsRNA) and trigger an interferon response...
August 25, 2021: Cancer Research
https://read.qxmd.com/read/34433020/evaluating-the-impact-of-age-on-immune-checkpoint-therapy-biomarkers
#24
JOURNAL ARTICLE
Rossin Erbe, Zheyu Wang, Sharon Wu, Joanne Xiu, Neeha Zaidi, Jennifer La, David Tuck, Nathanael Fillmore, Nicolas A Giraldo, Michael Topper, Stephen Baylin, Marc Lippman, Claudine Isaacs, Reva Basho, Ilya Serebriiskii, Heinz-Josef Lenz, Igor Astsaturov, John Marshall, Josephine Taverna, Jerry Lee, Elizabeth M Jaffee, Evanthia T Roussos Torres, Ashani Weeraratna, Hariharan Easwaran, Elana J Fertig
Both tumors and aging alter the immune landscape of tissues. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care. We leverage large-scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased interferon gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy...
August 24, 2021: Cell Reports
https://read.qxmd.com/read/34230929/betacoronavirus-specific-alternate-splicing
#25
Guy Karlebach, Bruce Aronow, Stephen B Baylin, Daniel Butler, Jonathan Foox, Shawn Levy, Cem Meydan, Christopher Mozsary, Amanda M Saravia-Butler, Deanne M Taylor, Eve Wurtele, Christopher E Mason, Afshin Beheshti, Peter N Robinson
Viruses can subvert a number of cellular processes in order to block innate antiviral responses, and many viruses interact with cellular splicing machinery. SARS-CoV-2 infection was shown to suppress global mRNA splicing, and at least 10 SARS-CoV-2 proteins bind specifically to one or more human RNAs. Here, we investigate 17 published experimental and clinical datasets related to SARS-CoV-2 infection as well as datasets from the betacoronaviruses SARS-CoV and MERS as well as Streptococcus pneumonia, HCV, Zika virus, Dengue virus, influenza H3N2, and RSV...
July 2, 2021: bioRxiv
https://read.qxmd.com/read/33948587/the-great-deceiver-mir-2392-s-hidden-role-in-driving-sars-cov-2-infection
#26
J Tyson McDonald, Francisco Javier Enguita, Deanne Taylor, Robert J Griffin, Waldemar Priebe, Mark R Emmett, Mohammad M Sajadi, Anthony D Harris, Jean Clement, Joseph M Dybas, Nukhet Aykin-Burns, Joseph W Guarnieri, Larry N Singh, Peter Grabham, Stephen B Baylin, Aliza Yousey, Andrea N Pearson, Peter M Corry, Amanda Saravia-Butler, Thomas R Aunins, Sadhana Sharma, Prashant Nagpal, Cem Meydan, Jonathan Foox, Christopher Mozsary, Bianca Cerqueira, Viktorija Zaksas, Urminder Singh, Eve Syrkin Wurtele, Sylvain V Costes, Gustavo Gastão Davanzo, Diego Galeano, Alberto Paccanaro, Suzanne L Meinig, Robert S Hagan, Natalie M Bowman, Matthew C Wolfgang, Selin Altinok, Nicolae Sapoval, Todd J Treangen, Pedro M Moraes-Vieira, Charles Vanderburg, Douglas C Wallace, Jonathan Schisler, Christopher E Mason, Anushree Chatterjee, Robert Meller, Afshin Beheshti
MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection...
August 18, 2021: bioRxiv
https://read.qxmd.com/read/33632774/bacterial-driven-inflammation-and-mutant-braf-expression-combine-to-promote-murine-colon-tumorigenesis-that-is-sensitive-to-immune-checkpoint-therapy
#27
JOURNAL ARTICLE
Christina E DeStefano Shields, James R White, Liam Chung, Alyssa Wenzel, Jessica L Hicks, Ada J Tam, June L Chan, Christine M Dejea, Hongni Fan, John Michel, Ashley R Maiuri, Shruthi Sriramkumar, Ram Podicheti, Douglas B Rusch, Hao Wang, Angelo M De Marzo, Sepideh Besharati, Robert A Anders, Stephen B Baylin, Heather M O'Hagan, Franck Housseau, Cynthia L Sears
Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+ ) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas...
July 2021: Cancer Discovery
https://read.qxmd.com/read/33471554/interview-with-stephen-b-baylin
#28
Stephen B Baylin
No abstract text is available yet for this article.
January 2021: Epigenomics
https://read.qxmd.com/read/33301506/correction-inhibiting-dna-methylation-activates-cancer-testis-antigens-and-expression-of-the-antigen-processing-and-presentation-machinery-in-colon-and-ovarian-cancer-cells
#29
Cornelia Siebenkäs, Katherine B Chiappinelli, Angela A Guzzetta, Anup Sharma, Jana Jeschke, Rajita Vatapalli, Stephen B Baylin, Nita Ahuja
[This corrects the article DOI: 10.1371/journal.pone.0179501.].
2020: PloS One
https://read.qxmd.com/read/33253231/correction-hypomethylating-agents-synergize-with-irinotecan-to-improve-response-to-chemotherapy-in-colorectal-cancer-cells
#30
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
[This corrects the article DOI: 10.1371/journal.pone.0176139.].
2020: PloS One
https://read.qxmd.com/read/32984843/multimodal-genomic-features-predict-outcome-of-immune-checkpoint-blockade-in-non-small-cell-lung-cancer
#31
JOURNAL ARTICLE
Valsamo Anagnostou, Noushin Niknafs, Kristen Marrone, Daniel C Bruhm, James R White, Jarushka Naidoo, Karlijn Hummelink, Kim Monkhorst, Ferry Lalezari, Mara Lanis, Samuel Rosner, Joshua E Reuss, Kellie N Smith, Vilmos Adleff, Kristen Rodgers, Zineb Belcaid, Lamia Rhymee, Benjamin Levy, Josephine Feliciano, Christine L Hann, David S Ettinger, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Alexander S Baras, Edward Gabrielson, Malcolm V Brock, Rachel Karchin, Drew M Pardoll, Stephen B Baylin, Julie R Brahmer, Robert B Scharpf, Patrick M Forde, Victor E Velculescu
Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumors are likely to have inaccurate TMB estimates. We developed a new method to estimate a corrected TMB (cTMB) that was adjusted for tumor purity and more accurately predicted outcome to immune checkpoint blockade (ICB)...
January 2020: Nature Cancer
https://read.qxmd.com/read/32840624/genome-wide-association-meta-analysis-of-individuals-of-european-ancestry-identifies-suggestive-loci-for-sodium-intake-potassium-intake-and-their-ratio-measured-from-24-hour-or-half-day-urine-samples
#32
JOURNAL ARTICLE
Minjung Kho, Jennifer A Smith, Niek Verweij, Lulu Shang, Kathleen A Ryan, Wei Zhao, Erin B Ware, Ron T Gansevoort, Marguerite R Irvin, Jung Eun Lee, Stephen T Turner, Joohon Sung, Pim van der Harst, Donna K Arnett, Ana Baylin, Sung Kyun Park, Young Ah Seo, Kristen M Kelly, Yen Pei C Chang, Xiang Zhou, John C Lieske, Sharon L R Kardia
BACKGROUND: Excess sodium intake and insufficient potassium intake are risk factors for hypertension, but there is limited knowledge regarding genetic factors that influence intake. Twenty-hour or half-day urine samples provide robust estimates of sodium and potassium intake, outperforming other measures such as spot urine samples and dietary self-reporting. OBJECTIVE: The aim of this study was to investigate genomic regions associated with sodium intake, potassium intake, and sodium-to-potassium ratio measured from 24-h or half-day urine samples...
August 25, 2020: Journal of Nutrition
https://read.qxmd.com/read/32651270/pharmacologic-induction-of-innate-immune-signaling-directly-drives-homologous-recombination-deficiency
#33
JOURNAL ARTICLE
Lena J McLaughlin, Lora Stojanovic, Aksinija A Kogan, Julia L Rutherford, Eun Yong Choi, Ray-Whay Chiu Yen, Limin Xia, Ying Zou, Rena G Lapidus, Stephen B Baylin, Michael J Topper, Feyruz V Rassool
Poly(ADP ribose) polymerase inhibitors (PARPi) have efficacy in triple negative breast (TNBC) and ovarian cancers (OCs) harboring BRCA mutations, generating homologous recombination deficiencies (HRDs). DNA methyltransferase inhibitors (DNMTi) increase PARP trapping and reprogram the DNA damage response to generate HRD, sensitizing BRCA-proficient cancers to PARPi. We now define the mechanisms through which HRD is induced in BRCA-proficient TNBC and OC. DNMTi in combination with PARPi up-regulate broad innate immune and inflammasome-like signaling events, driven in part by stimulator of interferon genes (STING), to unexpectedly directly generate HRD...
July 10, 2020: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/32302562/epigenetic-therapy-for-epithelioid-sarcoma
#34
JOURNAL ARTICLE
Scott B Rothbart, Stephen B Baylin
Tazemetostat is the first epigenetic therapy to gain FDA approval in a solid tumor. This lysine methyltransferase inhibitor targets EZH2, the enzymatic subunit of the PRC2 transcriptional silencing complex. Tumors with mutations in subunits of the SWI/SNF chromatin remodeling complex, inclusive of most epithelioid sarcomas, are sensitive to EZH2 inhibition.
April 16, 2020: Cell
https://read.qxmd.com/read/32103175/epigenetic-therapy-inhibits-metastases-by-disrupting-premetastatic-niches
#35
JOURNAL ARTICLE
Zhihao Lu, Jianling Zou, Shuang Li, Michael J Topper, Yong Tao, Hao Zhang, Xi Jiao, Wenbing Xie, Xiangqian Kong, Michelle Vaz, Huili Li, Yi Cai, Limin Xia, Peng Huang, Kristen Rodgers, Beverly Lee, Joanne B Riemer, Chi-Ping Day, Ray-Whay Chiu Yen, Ying Cui, Yujiao Wang, Yanni Wang, Weiqiang Zhang, Hariharan Easwaran, Alicia Hulbert, KiBem Kim, Rosalyn A Juergens, Stephen C Yang, Richard J Battafarano, Errol L Bush, Stephen R Broderick, Stephen M Cattaneo, Julie R Brahmer, Charles M Rudin, John Wrangle, Yuping Mei, Young J Kim, Bin Zhang, Ken Kang-Hsin Wang, Patrick M Forde, Joseph B Margolick, Barry D Nelkin, Cynthia A Zahnow, Drew M Pardoll, Franck Housseau, Stephen B Baylin, Lin Shen, Malcolm V Brock
Cancer recurrence after surgery remains an unresolved clinical problem1-3 . Myeloid cells derived from bone marrow contribute to the formation of the premetastatic microenvironment, which is required for disseminating tumour cells to engraft distant sites4-6 . There are currently no effective interventions that prevent the formation of the premetastatic microenvironment6,7 . Here we show that, after surgical removal of primary lung, breast and oesophageal cancers, low-dose adjuvant epigenetic therapy disrupts the premetastatic microenvironment and inhibits both the formation and growth of lung metastases through its selective effect on myeloid-derived suppressor cells (MDSCs)...
March 2020: Nature
https://read.qxmd.com/read/31591209/dna-methyltransferase-inhibitors-induce-a-brcaness-phenotype-that-sensitizes-nsclc-to-parp-inhibitor-and-ionizing-radiation
#36
JOURNAL ARTICLE
Rachel Abbotts, Michael J Topper, Christopher Biondi, Daniel Fontaine, Reena Goswami, Lora Stojanovic, Eun Yong Choi, Lena McLaughlin, Aksinija A Kogan, Limin Xia, Rena Lapidus, Javed Mahmood, Stephen B Baylin, Feyruz V Rassool
A minority of cancers have breast cancer gene (BRCA) mutations that confer sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis), but the role for PARPis in BRCA-proficient cancers is not well established. This suggests the need for novel combination therapies to expand the use of these drugs. Recent reports that low doses of DNA methyltransferase inhibitors (DNMTis) plus PARPis enhance PARPi efficacy in BRCA-proficient AML subtypes, breast, and ovarian cancer open up the possibility that this strategy may apply to other sporadic cancers...
November 5, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31548600/the-emerging-role-of-epigenetic-therapeutics-in-immuno-oncology
#37
REVIEW
Michael J Topper, Michelle Vaz, Kristen A Marrone, Julie R Brahmer, Stephen B Baylin
The past decade has seen the emergence of immunotherapy as a prime approach to cancer treatment, revolutionizing the management of many types of cancer. Despite the promise of immunotherapy, most patients do not have a response or become resistant to treatment. Thus, identifying combinations that potentiate current immunotherapeutic approaches will be crucial. The combination of immune-checkpoint inhibition with epigenetic therapy is one such strategy that is being tested in clinical trials, encompassing a variety of cancer types...
February 2020: Nature Reviews. Clinical Oncology
https://read.qxmd.com/read/30956060/defining-uhrf1-domains-that-support-maintenance-of-human-colon-cancer-dna-methylation-and-oncogenic-properties
#38
JOURNAL ARTICLE
Xiangqian Kong, Jie Chen, Wenbing Xie, Stephen M Brown, Yi Cai, Kaichun Wu, Daiming Fan, Yongzhan Nie, Srinivasan Yegnasubramanian, Rochelle L Tiedemann, Yong Tao, Ray-Whay Chiu Yen, Michael J Topper, Cynthia A Zahnow, Hariharan Easwaran, Scott B Rothbart, Limin Xia, Stephen B Baylin
UHRF1 facilitates the establishment and maintenance of DNA methylation patterns in mammalian cells. The establishment domains are defined, including E3 ligase function, but the maintenance domains are poorly characterized. Here, we demonstrate that UHRF1 histone- and hemimethylated DNA binding functions, but not E3 ligase activity, maintain cancer-specific DNA methylation in human colorectal cancer (CRC) cells. Disrupting either chromatin reader activity reverses DNA hypermethylation, reactivates epigenetically silenced tumor suppressor genes (TSGs), and reduces CRC oncogenic properties...
April 15, 2019: Cancer Cell
https://read.qxmd.com/read/30800716/dna-methylation-in-senescence-aging-and-cancer
#39
JOURNAL ARTICLE
Wenbing Xie, Stephen B Baylin, Hariharan Easwaran
No abstract text is available yet for this article.
January 2019: Oncoscience
https://read.qxmd.com/read/30753828/aging-like-spontaneous-epigenetic-silencing-facilitates-wnt-activation-stemness-and-braf-v600e-induced-tumorigenesis
#40
JOURNAL ARTICLE
Yong Tao, Byunghak Kang, Daniel A Petkovich, Yuba R Bhandari, Julie In, Genevieve Stein-O'Brien, Xiangqian Kong, Wenbing Xie, Nicholas Zachos, Shinji Maegawa, Himani Vaidya, Stephen Brown, Ray-Whay Chiu Yen, Xiaojian Shao, Jai Thakor, Zhihao Lu, Yi Cai, Yuezheng Zhang, Izaskun Mallona, Miguel Angel Peinado, Cynthia A Zahnow, Nita Ahuja, Elana Fertig, Jean-Pierre Issa, Stephen B Baylin, Hariharan Easwaran
We addressed the precursor role of aging-like spontaneous promoter DNA hypermethylation in initiating tumorigenesis. Using mouse colon-derived organoids, we show that promoter hypermethylation spontaneously arises in cells mimicking the human aging-like phenotype. The silenced genes activate the Wnt pathway, causing a stem-like state and differentiation defects. These changes render aged organoids profoundly more sensitive than young ones to transformation by BrafV600E , producing the typical human proximal BRAFV600E -driven colon adenocarcinomas characterized by extensive, abnormal gene-promoter CpG-island methylation, or the methylator phenotype (CIMP)...
February 11, 2019: Cancer Cell
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