keyword
https://read.qxmd.com/read/38683993/incomplete-penetrant-hypertrophic-cardiomyopathy-myh7-g256e-mutation-causes-hypercontractility-and-elevated-mitochondrial-respiration
#1
JOURNAL ARTICLE
Soah Lee, Alison S Vander Roest, Cheavar A Blair, Kerry Kao, Samantha B Bremner, Matthew C Childers, Divya Pathak, Paul Heinrich, Daniel Lee, Orlando Chirikian, Saffie E Mohran, Brock Roberts, Jacqueline E Smith, James W Jahng, David T Paik, Joseph C Wu, Ruwanthi N Gunawardane, Kathleen M Ruppel, David L Mack, Beth L Pruitt, Michael Regnier, Sean M Wu, James A Spudich, Daniel Bernstein
Determining the pathogenicity of hypertrophic cardiomyopathy-associated mutations in the β-myosin heavy chain ( MYH7 ) can be challenging due to its variable penetrance and clinical severity. This study investigates the early pathogenic effects of the incomplete-penetrant MYH7 G256E mutation on myosin function that may trigger pathogenic adaptations and hypertrophy. We hypothesized that the G256E mutation would alter myosin biomechanical function, leading to changes in cellular functions. We developed a collaborative pipeline to characterize myosin function across protein, myofibril, cell, and tissue levels to determine the multiscale effects on structure-function of the contractile apparatus and its implications for gene regulation and metabolic state...
May 7, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38575731/efficacy-and-safety-of-tepotinib-in-asian-patients-with-advanced-nsclc-with-met-exon-14-skipping-enrolled-in-vision
#2
JOURNAL ARTICLE
Terufumi Kato, James Chih-Hsin Yang, Myung-Ju Ahn, Hiroshi Sakai, Masahiro Morise, Yuh-Min Chen, Ji-Youn Han, Jin-Ji Yang, Jun Zhao, Te-Chun Hsia, Karin Berghoff, Rolf Bruns, Helene Vioix, Simone Lang, Andreas Johne, Xiuning Le, Paul K Paik
BACKGROUND: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022). METHODS: Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily...
April 4, 2024: British Journal of Cancer
https://read.qxmd.com/read/38492157/modelling-the-effectiveness-of-tepotinib-in-comparison-to-standard-of-care-treatments-in-patients-with-advanced-non-small-cell-lung-cancer-nsclc-harbouring-metex14-skipping-in-the-uk
#3
JOURNAL ARTICLE
Rachael Batteson, Emma Hook, Hollie Wheat, Anthony J Hatswell, Helene Vioix, Thomas McLean, Stamatia Theodora Alexopoulos, Shobhit Baijal, Paul K Paik
BACKGROUND: Patients with non-small cell lung cancer harbouring mesenchymal-epithelial transition exon 14 (METex14) skipping typically demonstrate poorer prognosis than overall non-small cell lung cancer. Until recently, no targeted treatments were available for patients with non-small cell lung cancer harbouring METex14 skipping in the UK, with limited treatments available. OBJECTIVE: This study estimates the long-term survival and quality-adjusted life-year benefit of MET inhibitor tepotinib versus current standard of care from a UK perspective...
March 16, 2024: Targeted Oncology
https://read.qxmd.com/read/38402853/long-term-experience-with-tepotinib-in-japanese-patients-with-met-exon-14-skipping-nsclc-from-the-phase-ii-vision-study
#4
JOURNAL ARTICLE
Masahiro Morise, Terufumi Kato, Shingo Matsumoto, Takako Inoue, Tomohiro Sakamoto, Takaaki Tokito, Shinji Atagi, Toshiyuki Kozuki, Hiroaki Takeoka, Kenichi Chikamori, Naofumi Shinagawa, Hiroshi Tanaka, Eisuke Horii, Svenja Adrian, Rolf Bruns, Andreas Johne, Paul K Paik, Hiroshi Sakai
Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non-small-cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.1 criteria. The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety...
February 25, 2024: Cancer Science
https://read.qxmd.com/read/38154515/initial-chemotherapy-for-locally-advanced-and-metastatic-nut-carcinoma
#5
JOURNAL ARTICLE
Jia Luo, Michelle Sanchez, Elinton Lee, Hans Hertzler, Nhi Luong, Emanuele Mazzola, Bryanna Finstein, Rubii Tamen, Gifty Brisbane, Tom Nguyen, Paul K Paik, Jamie E Chaft, Michael L Cheng, Hassan Khalil, Sarina A Piha-Paul, Lynette M Sholl, Mizuki Nishino, Pasi A Jänne, Steven G DuBois, Glenn J Hanna, Geoffrey I Shapiro, Christopher A French
INTRODUCTION: NUT carcinoma (NC) is an underdiagnosed and aggressive poorly differentiated or squamous cell cancer. A subset of NC is sensitive to chemotherapy, but the optimal regimen is unknown. Experts have recommended platinum- and ifosfamide-based therapy based on case reports. METHODS: Patients with pathologically confirmed NC with known survival outcomes after chemotherapy and consented to participate in a worldwide registry were studied. Results were summarized using descriptive methods...
December 27, 2023: Journal of Thoracic Oncology
https://read.qxmd.com/read/38062905/diagnosis-testing-treatment-and-outcomes-among-patients-with-advanced-non-small-cell-lung-cancer-in-the-united-states
#6
JOURNAL ARTICLE
Mo Yang, Joanna P MacEwan, Sai Sriteja Boppudi, Monica R McClain, Richard M O'Hara, Paul K Paik
INTRODUCTION: Characteristics of patients in clinical trials may differ from those of real-world patients. Our objective was to describe biomarker testing and outcomes among patients with advanced non-small cell lung cancer (aNSCLC) in a real-world setting. METHODS: This retrospective cohort study included patients ≥18 years old, diagnosed with stage IIIB/C or IV NSCLC, and in the TEMPUS oncology dataset from January 1, 2012, to December 31, 2020. Patient characteristics associated with biomarker testing were evaluated in patients with positive biomarkers using univariate logistic regression models...
December 7, 2023: Cancer Medicine
https://read.qxmd.com/read/37993205/novel-imaging-approaches-to%C3%A2-cardiac%C3%A2-manifestations-of-systemic%C3%A2-inflammatory%C3%A2-diseases-jacc-scientific-statement
#7
REVIEW
Brittany N Weber, Julie J Paik, Ayaz Aghayev, Allan L Klein, Sophie I Mavrogeni, Paul B Yu, Monica Mukherjee
Derangements in the innate and adaptive immune responses observed in systemic inflammatory syndromes contributes to unique elevated atherosclerotic risk and incident cardiovascular disease. Novel multimodality imaging techniques may improve diagnostic precision for the screening and monitoring of disease activity. The integrated application of these technologies lead to earlier diagnosis and noninvasive monitoring of cardiac involvement in systemic inflammatory diseases that will aid in preclinical studies, enhance patient selection, and provide surrogate endpoints in clinical trials, thereby improving clinical outcomes...
November 28, 2023: Journal of the American College of Cardiology
https://read.qxmd.com/read/37944528/tepotinib-in-patients-with-non-small-cell-lung-cancer-with-high-level-met-amplification-detected-by-liquid-biopsy-vision-cohort-b
#8
JOURNAL ARTICLE
Xiuning Le, Luis G Paz-Ares, Jan Van Meerbeeck, Santiago Viteri, Carlos Cabrera Galvez, Egbert F Smit, Marina Garassino, Remi Veillon, David Vicente Baz, Jose Fuentes Pradera, María Sereno, Toshiyuki Kozuki, Young-Chul Kim, Seung Soo Yoo, Ji-Youn Han, Jin-Hyoung Kang, Choon-Hee Son, Yoon Ji Choi, Christopher Stroh, Dilafruz Juraeva, Helene Vioix, Rolf Bruns, Gordon Otto, Andreas Johne, Paul K Paik
High-level MET amplification (METamp) is a primary driver in ∼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14...
November 7, 2023: Cell reports medicine
https://read.qxmd.com/read/37929643/breast-adipose-tissue-derived-extracellular-vesicles-from-obese-women-alter-tumor-cell-metabolism
#9
JOURNAL ARTICLE
Shuchen Liu, Alberto Benito-Martin, Fanny A Pelissier Vatter, Sarah Z Hanif, Catherine Liu, Priya Bhardwaj, Praveen Sethupathy, Alaa R Farghli, Phoebe Piloco, Paul Paik, Malik Mushannen, Xue Dong, David M Otterburn, Leslie Cohen, Rohan Bareja, Jan Krumsiek, Leona Cohen-Gould, Samuel Calto, Jason A Spector, Olivier Elemento, David C Lyden, Kristy A Brown
Breast adipose tissue is an important contributor to the obesity-breast cancer link. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we find that long-term education of breast cancer cells with EVs obtained from breast adipose tissue of women who are overweight or obese (O-EVs) results in increased proliferation. RNA-seq analysis of O-EV-educated cells demonstrates increased expression of genes involved in oxidative phosphorylation, such as ATP synthase and NADH: ubiquinone oxidoreductase...
November 6, 2023: EMBO Reports
https://read.qxmd.com/read/37923812/large-bi-axial-tensile-strain-effect-in-epitaxial-bifeo-3-film-grown-on-single-crystal-prsco-3
#10
JOURNAL ARTICLE
In-Tae Bae, Zachary R Lingley, Brendan J Foran, Paul M Adams, Hanjong Paik
A BiFeO3 film is grown epitaxially on a PrScO3 single crystal substrate which imparts ~ 1.45% of biaxial tensile strain to BiFeO3 resulting from lattice misfit. The biaxial tensile strain effect on BiFeO3 is investigated in terms of crystal structure, Poisson ratio, and ferroelectric domain structure. Lattice resolution scanning transmission electron microscopy, precession electron diffraction, and X-ray diffraction results clearly show that in-plane interplanar distance of BiFeO3 is the same as that of PrScO3 with no sign of misfit dislocations, indicating that the biaxial tensile strain caused by lattice mismatch between BiFeO3 and PrScO3 are stored as elastic energy within BiFeO3 film...
November 3, 2023: Scientific Reports
https://read.qxmd.com/read/37838086/microsatellite-instability-and-mismatch-repair-deficiency-define-a-distinct-subset-of-lung-cancers-characterized-by-smoking-exposure-high-tumor-mutational-burden-and-recurrent-somatic-mlh1-inactivation
#11
JOURNAL ARTICLE
Soo-Ryum Yang, Erika Gedvilaite, Ryan Ptashkin, Jason Chang, John Ziegler, Douglas A Mata, Liliana B Villafania, Khedoudja Nafa, Jaclyn F Hechtman, Ryma Benayed, Ahmet Zehir, Jamal Benhamida, Maria E Arcila, Diana Mandelker, Charles M Rudin, Paul K Paik, Alexander Drilon, Adam J Schoenfeld, Marc Ladanyi
INTRODUCTION: Microsatellite instability (MSI) and mismatch repair (MMR) deficiency represent a distinct oncogenic process and predict response to immune checkpoint inhibitors (ICIs). The clinicopathologic features of MSI-high (MSI-H) and MMR deficiency (MMR-D) in lung cancers remain poorly characterized. METHODS: MSI status from 5171 patients with NSCLC and 315 patients with SCLC was analyzed from targeted next-generation sequencing data using two validated bioinformatic pipelines...
October 12, 2023: Journal of Thoracic Oncology
https://read.qxmd.com/read/37631780/high-sensitivity-seismometer-development-for-lunar-applications
#12
JOURNAL ARTICLE
Leandro A N de Paula, Ronald S Norton, Ho Jung Paik, Nicholas C Schmerr, Paul R Williamson, Talso C P Chui, Inseob Hahn
Lunar seismology is a critical area of research, providing insights into the Moon's internal structure, composition, and thermal history, as well as informing the design of safe and resilient habitats for future human settlements. This paper presents the development of a state-of-the-art, three-axis broadband seismometer with a low-frequency range of 0.001-1 Hz and a target sensitivity over one order of magnitude greater than previous Apollo-era instruments. The paper details the design, assembly, methodology, and test results...
August 18, 2023: Sensors
https://read.qxmd.com/read/37613795/tem-study-on-epitaxial-bifeo3-film-under-biaxial-tensile-strain
#13
JOURNAL ARTICLE
In-Tae Bae, Zachary Lingley, Brendan Foran, Paul Adams, Hanjong Paik
No abstract text is available yet for this article.
July 22, 2023: Microscopy and Microanalysis
https://read.qxmd.com/read/37333118/multi-scale-models-reveal-hypertrophic-cardiomyopathy-myh7-g256e-mutation-drives-hypercontractility-and-elevated-mitochondrial-respiration
#14
Soah Lee, Alison S Vander Roest, Cheavar A Blair, Kerry Kao, Samantha B Bremner, Matthew C Childers, Divya Pathak, Paul Heinrich, Daniel Lee, Orlando Chirikian, Saffie Mohran, Brock Roberts, Jacqueline E Smith, James W Jahng, David T Paik, Joseph C Wu, Ruwanthi N Gunawardane, James A Spudich, Kathleen Ruppel, David Mack, Beth L Pruitt, Michael Regnier, Sean M Wu, Daniel Bernstein
RATIONALE: Over 200 mutations in the sarcomeric protein β-myosin heavy chain (MYH7) have been linked to hypertrophic cardiomyopathy (HCM). However, different mutations in MYH7 lead to variable penetrance and clinical severity, and alter myosin function to varying degrees, making it difficult to determine genotype-phenotype relationships, especially when caused by rare gene variants such as the G256E mutation. OBJECTIVE: This study aims to determine the effects of low penetrant MYH7 G256E mutation on myosin function...
June 9, 2023: bioRxiv
https://read.qxmd.com/read/37279923/generation-of-lexa-enhancer-trap-lines-in-drosophila-by-an-international-scholastic-network
#15
JOURNAL ARTICLE
Ella S Kim, Arjun Rajan, Kathleen Chang, Sanath Govindarajan, Clara Gulick, Eva English, Bianca Rodriguez, Orion Bloomfield, Stella Nakada, Charlotte Beard, Sarah O'Connor, Sophia Mastroianni, Emma Downey, Matthew Feigenbaum, Caitlin Tolentino, Abigail Pace, Marina Khan, Soyoun Moon, Jordan DiPrima, Amber Syed, Flora Lin, Yasmina Abukhadra, Isabella Bacon, John Beckerle, Sophia Cho, Nana Esi Donkor, Lucy Garberg, Ava Harrington, Mai Hoang, Nosa Lawani, Ayush Noori, Euwie Park, Ella Parsons, Philip Oravitan, Matthew Chen, Cristian Molina, Caleb Richmond, Adith Reddi, Jason Huang, Cooper Shugrue, Rose Coviello, Selma Unver, Matthew Indelicarto, Emir Islamovic, Rosemary McIlroy, Alana Yang, Mahdi Hamad, Elizabeth Griffin, Zara Ahmed, Asha Alla, Patricia Fitzgerald, Audrey Choi, Tanya Das, Yuchen Cheng, Joshua Yu, Tabor Roderiques, Ethan Lee, Longchao Liu, Jaekeb Harper, Jason Wang, Chris Suhr, Max Tan, Jacqueline Luque, A Russell Tam, Emma Chen, Max Triff, Lyric Zimmermann, Eric Zhang, Jackie Wood, Kaitlin Clark, Nat Kpodonu, Antar Dey, Alexander Ecker, Maximilian Chuang, Ramón Kodi Suzuki López, Harry Sun, Zijing Wei, Henry Stone, Chia Yu Joy Chi, Aiden Silvestri, Petra Orloff, Neha Nedumaran, Aletheia Zou, Leyla Ünver, Oscair Page, Minseo Kim, Terence Yan Tao Chan, Akili Tulloch, Andrea Hernandez, Aruli Pillai, Caitlyn Chen, Neil Chowdhury, Lina Huang, Anish Mudide, Garrett Paik, Alexandra Wingate, Lily Quinn, Chris Conybere, Luca Laiza Baumgardt, Rollo Buckley, Zara Kolberg, Ruth Pattison, Ashlyn Ahmad Shazli, Pia Ganske, Luca Sfragara, Annina Strub, Barney Collier, Hari Tamana, Dylan Ravindran, James Howden, Madeleine Stewart, Sakura Shimizu, Julia Braniff, Melanie Fong, Lucy Gutman, Danny Irvine, Sahil Malholtra, Jillian Medina, John Park, Alicia Yin, Harrison Abromavage, Breanna Barrett, Jacqueline Chen, Rachelle Cho, Mac Dilatush, Gabriel Gaw, Caitlin Gu, Jupiter Huang, Houston Kilby, Ethan Markel, Katie McClure, William Phillips, Benjamin Polaski, Amelia Roselli, Soleil Saint-Cyr, Ellie Shin, Kylan Tatum, Tai Tumpunyawat, Lucia Wetherill, Sara Ptaszynska, Maddie Zeleznik, Alexander Pesendorfer, Anna Nolan, Jeffrey Tao, Divya Sammeta, Laney Nicholson, Giao Vu Dinh, Merrin Foltz, An Vo, Maggie Ross, Andrew Tokarski, Samika Hariharan, Elaine Wang, Martha Baziuk, Ashley Tay, Yuk Hung Maximus Wong, Jax Floyd, Aileen Cui, Kieran Pierre, Nikita Coppisetti, Matthew Kutam, Dhruv Khurjekar, Anthony Gadzi, Ben Gubbay, Sophia Pedretti, Sofiya Belovich, Tiffany Yeung, Mercy Fey, Layla Shaffer, Arthur Li, Giancarlo Beritela, Kyle Huyghue, Greg Foster, Garrett Durso-Finley, Quinn Thierfelder, Holly Kiernan, Andrew Lenkowsky, Tesia Thomas, Nicole Cheng, Olivia Chao, Pia L'Etoile-Goga, Alexa King, Paris McKinley, Nicole Read, David Milberg, Leila Lin, Melinda Wong, Io Gilman, Samantha Brown, Lila Chen, Jordyn Kosai, Mark Verbinsky, Alice Belshaw-Hood, Honon Lee, Cathy Zhou, Maya Lobo, Asia Tse, Kyle Tran, Kira Lewis, Pratmesh Sonawane, Jonathan Ngo, Sophia Zuzga, Lillian Chow, Vianne Huynh, Wenyi Yang, Samantha Lim, Brandon Stites, Shannon Chang, Raenalyn Cruz-Balleza, Michaela Pelta, Stella Kujawski, Christopher Yuan, Elio Standen-Bloom, Oliver Witt, Karina Anders, Audrey Duane, Nancy Huynh, Benjamin Lester, Samantha Fung-Lee, Melanie Fung, Mandy Situ, Paolo Canigiula, Matijs Dijkgraaf, Wilbert Romero, Samantha Karmela Baula, Kimberly Wong, Ivana Xu, Benjamin Martinez, Reena Nuygen, Lucy Norris, Noah Nijensohn, Naomi Altman, Elise Maajid, Olivia Burkhardt, Jullian Chanda, Catherine Doscher, Alex Gopal, Aaron Good, Jonah Good, Nate Herrera, Lucas Lanting, Sophia Liem, Anila Marks, Emma McLaughlin, Audrey Lee, Collin Mohr, Emma Patton, Naima Pyarali, Claire Oczon, Daniel Richards, Nathan Good, Spencer Goss, Adeeb Khan, Reagan Madonia, Vivian Mitchell, Natasha Sun, Tarik Vranka, Diogo Garcia, Frida Arroyo, Eric Morales, Steven Camey, Giovanni Cano, Angelica Bernabe, Jennifer Arroyo, Yadira Lopez, Emily Gonzalez, Bryan Zumba, Josue Garcia, Esmeralda Vargas, Allen Trinidad, Noel Candelaria, Vanessa Valdez, Faith Campuzano, Emily Pereznegron, Jenifer Medrano, Jonathan Gutierrez, Evelyn Gutierrez, Ericka Taboada Abrego, Dayanara Gutierrez, Cristian Ortiz, Angelica Barnes, Eleanor Arms, Leo Mitchell, Ciara Balanzá, Jake Bradford, Harrison Detroy, Devin Ferguson, Ethel Guillermo, Anusha Manapragada, Daniella Nanula, Brigitte Serna, Khushi Singh, Emily Sramaty, Brian Wells, Matthew Wiggins, Melissa Dowling, Geraldine Schmadeke, Samantha Cafferky, Stephanie Good, Margaret Reese, Miranda Fleig, Alex Gannett, Cory Cain, Melody Lee, Paul Oberto, Jennifer Rinehart, Elaine Pan, Sallie Anne Mathis, Jessica Joiner, Leslie Barr, Cory J Evans, Alberto Baena-Lopez, Andrea Beatty, Jeanette Collette, Robert Smullen, Jeanne Suttie, Townley Chisholm, Cheryl Rotondo, Gareth Lewis, Victoria Turner, Lloyd Stark, Elizabeth Fox, Anjana Amirapu, Sangbin Park, Nicole Lantz, Anne E Rankin, Seung K Kim, Lutz Kockel
Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons...
June 6, 2023: G3: Genes—Genomes—Genetics
https://read.qxmd.com/read/37270698/tepotinib-treatment-in-patients-with-met-exon-14-skipping-non-small-cell-lung-cancer-long-term-follow-up-of-the-vision-phase-2-nonrandomized-clinical-trial
#16
MULTICENTER STUDY
Julien Mazieres, Paul K Paik, Marina C Garassino, Xiuning Le, Hiroshi Sakai, Remi Veillon, Egbert F Smit, Alexis B Cortot, Jo Raskin, Santiago Viteri, Yi-Long Wu, James C H Yang, Myung-Ju Ahn, Rui Ma, Jun Zhao, Aurora O'Brate, Karin Berghoff, Rolf Bruns, Gordon Otto, Andreas Johne, Enriqueta Felip, Michael Thomas
IMPORTANCE: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches. OBJECTIVE: To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study. DESIGN, SETTING, AND PARTICIPANTS: The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021...
September 1, 2023: JAMA Oncology
https://read.qxmd.com/read/37027811/orthogonal-testing-unravels-a-novel-ros1-oncogenic-fusion-variant-ros1-gpm6a-a-practical-approach-to-molecular-testing-for-actionable-fusion-variants
#17
JOURNAL ARTICLE
Hiba G Narvel, So Yeon Kim, Aspan M Shokrekhuda, Perry R Cohen, K H Ramesh, Sheila R Solomon, Paul K Paik, Balazs Halmos
No abstract text is available yet for this article.
April 2023: JCO Precision Oncology
https://read.qxmd.com/read/36999526/plain-language-summary-of-the-development-of-tepotinib-a-treatment-for-a-subtype-of-non-small-cell-lung-cancer%C3%A2-called-met-exon-14-skipping
#18
REVIEW
John Hallick, Anne-Marie Baird, Gerald Falchook, Xiuning Le, David Hong, Santiago Viteri, Jo Raskin, Niels Reinmuth, Soetkin Vlassak, Mihaela Militaru, Paul K Paik
WHAT IS THIS SUMMARY ABOUT?: This plain language summary provides an overview of two of the main clinical studies that led to tepotinib's approval, the phase I first-in-human study and the phase II VISION study. WHAT IS TEPOTINIB?: Tepotinib is a targeted anti-cancer treatment taken orally (by mouth). It is available in many countries for people with advanced or metastatic non-small cell lung cancer (NSCLC), where the tumor contains a genetic mutation (alteration) called ' MET exon 14 skipping'...
March 31, 2023: Future Oncology
https://read.qxmd.com/read/36991019/histone-demethylase-kdm2a-is-a-selective-vulnerability-of-cancers-relying-on-alternative-telomere-maintenance
#19
JOURNAL ARTICLE
Fei Li, Yizhe Wang, Inah Hwang, Ja-Young Jang, Libo Xu, Zhong Deng, Eun Young Yu, Yiming Cai, Caizhi Wu, Zhenbo Han, Yu-Han Huang, Xiangao Huang, Ling Zhang, Jun Yao, Neal F Lue, Paul M Lieberman, Haoqiang Ying, Jihye Paik, Hongwu Zheng
Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance...
March 29, 2023: Nature Communications
https://read.qxmd.com/read/36917985/endoplasmic-reticulum-stress-in-the-intestinal-epithelium-initiates-purine-metabolite-synthesis-and-promotes-th17-cell-differentiation-in-the-gut
#20
JOURNAL ARTICLE
Jinzhi Duan, Juan D Matute, Lukas W Unger, Thomas Hanley, Alexandra Schnell, Xi Lin, Niklas Krupka, Paul Griebel, Conner Lambden, Brandon Sit, Joep Grootjans, Michal Pyzik, Felix Sommer, Sina Kaiser, Maren Falk-Paulsen, Helmut Grasberger, John Y Kao, Tobias Fuhrer, Hai Li, Donggi Paik, Yunjin Lee, Samuel Refetoff, Jonathan N Glickman, Adrienne W Paton, Lynn Bry, James C Paton, Uwe Sauer, Andrew J Macpherson, Philip Rosenstiel, Vijay K Kuchroo, Matthew K Waldor, Jun R Huh, Arthur Kaser, Richard S Blumberg
Intestinal IL-17-producing T helper (Th17) cells are dependent on adherent microbes in the gut for their development. However, how microbial adherence to intestinal epithelial cells (IECs) promotes Th17 cell differentiation remains enigmatic. Here, we found that Th17 cell-inducing gut bacteria generated an unfolded protein response (UPR) in IECs. Furthermore, subtilase cytotoxin expression or genetic removal of X-box binding protein 1 (Xbp1) in IECs caused a UPR and increased Th17 cells, even in antibiotic-treated or germ-free conditions...
May 9, 2023: Immunity
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