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https://www.readbyqxmd.com/read/29610121/response-to-erbb3-directed-targeted-therapy-in-nrg1-rearranged-cancers
#1
Alexander Drilon, Romel Somwar, Biju P Mangatt, Henrik Edgren, Patrice Desmeules, Anja Ruusulehto, Roger S Smith, Lukas Delasos, Morana Vojnic, Andrew J Plodkowski, Joshua Sabari, Kenneth Ng, Joseph Montecalvo, Jason Chang, Huichun Tai, William W Lockwood, Victor Martinez, Gregory J Riely, Charles M Rudin, Mark G Kris, Maria E Arcila, Christopher Matheny, Ryma Benayed, Natasha Rekhtman, Marc Ladanyi, Gopinath Ganji
NRG1 rearrangements are oncogenic drivers that are enriched in invasive mucinous adenocarcinomas (IMAs) of the lung. The oncoprotein binds ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic paradigm of ERBB3/ERBB2 inhibition. As proof of concept, a durable response was achieved with anti-ERBB3 monoclonal antibody therapy (GSK2849330) in an exceptional responder with an NRG1-rearranged IMA on a phase 1 trial (NCT01966445). In contrast, response was not achieved with anti-ERBB2 therapy (afatinib) in four NRG1-rearranged IMA patients (including the index patient post-GSK2849330)...
April 2, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29578911/adrenal-metastasectomy-in-the-presence-and-absence-of-extraadrenal-metastatic-disease
#2
Ashley E Russo, Brian R Untch, Mark G Kris, Joanne F Chou, Marinela Capanu, Daniel G Coit, Jamie E Chaft, Michael I D'Angelica, Murray F Brennan, Vivian E Strong
OBJECTIVE: To determine if there are differences in overall survival (OS) or event-free survival (EFS) in patients with and without concomitant extra-adrenal metastases undergoing adrenal metastasectomy. BACKGROUND: There is growing interest in the use of local therapies in patients with oligometastatic disease. Previously published series have indicated that long-term survival is possible with resection. Adrenalectomy has been used to treat adrenal metastases in select patients...
March 23, 2018: Annals of Surgery
https://www.readbyqxmd.com/read/29530932/concurrent-alterations-in-egfr-mutant-lung-cancers-associated-with-resistance-to-egfr-kinase-inhibitors-and-characterization-of-mtor-as-a-mediator-of-resistance
#3
Helena Yu, Ken Suzawa, Emmet J Jordan, Ahmet Zehir, Andy Ni, Hyunjae Ryan Kim, Mark G Kris, Matthew D Hellmann, Bob T Li, Romel Somwar, David B Solit, Michael F Berger, Maria E Arcila, Gregory J Riely, Marc Ladanyi
PURPOSE: To identify molecular factors that determine duration of response to EGFR tyrosine kinase inhibitors and to identify novel mechanisms of drug resistance, we molecularly profiled EGFR mutant tumors prior to treatment and after progression on EGFR TKI using targeted next-generation sequencing.      Experimental Design: Targeted next-generation sequencing was performed on 374 consecutive patients with metastatic EGFR mutant lung cancer. Clinical data were collected and correlated with somatic mutation data...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29494529/mycokey-round-table-discussions-of-future-directions-in-research-on-chemical-detection-methods-genetics-and-biodiversity-of-mycotoxins
#4
John F Leslie, Veronica Lattanzio, Kris Audenaert, Paola Battilani, Jeffrey Cary, Sofia N Chulze, Sarah De Saeger, Annamaria Gerardino, Petr Karlovsky, Yu-Cai Liao, Chris M Maragos, Giuseppe Meca, Angel Medina, Antonio Moretti, Gary Munkvold, Giuseppina Mulè, Patrick Njobeh, Ivan Pecorelli, Giancarlo Perrone, Amedeo Pietri, Juan M Palazzini, Robert H Proctor, Endang S Rahayu, Maria L Ramírez, Robert Samson, Jörg Stroka, Michael Sulyok, Mark Sumarah, Cees Waalwijk, Qi Zhang, Hao Zhang, Antonio F Logrieco
MycoKey, an EU-funded Horizon 2020 project, includes a series of "Roundtable Discussions" to gather information on trending research areas in the field of mycotoxicology. This paper includes summaries of the Roundtable Discussions on Chemical Detection and Monitoring of mycotoxins and on the role of genetics and biodiversity in mycotoxin production. Discussions were managed by using the nominal group discussion technique, which generates numerous ideas and provides a ranking for those identified as the most important...
March 1, 2018: Toxins
https://www.readbyqxmd.com/read/29462142/rnf8-and-scml2-cooperate-to-regulate-ubiquitination-and-h3k27-acetylation-for-escape-gene-activation-on-the-sex-chromosomes
#5
Shannel R Adams, So Maezawa, Kris G Alavattam, Hironori Abe, Akihiko Sakashita, Megan Shroder, Tyler J Broering, Julie Sroga Rios, Michael A Thomas, Xinhua Lin, Carolyn M Price, Artem Barski, Paul R Andreassen, Satoshi H Namekawa
The sex chromosomes are enriched with germline genes that are activated during the late stages of spermatogenesis. Due to meiotic sex chromosome inactivation (MSCI), these sex chromosome-linked genes must escape silencing for activation in spermatids, thereby ensuring their functions for male reproduction. RNF8, a DNA damage response protein, and SCML2, a germline-specific Polycomb protein, are two major, known regulators of this process. Here, we show that RNF8 and SCML2 cooperate to regulate ubiquitination during meiosis, an early step to establish active histone modifications for subsequent gene activation...
February 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29394301/issues-identified-by-postdischarge-contact-after-pediatric-hospitalization-a-multisite-study
#6
Kris P Rehm, Mark S Brittan, John R Stephens, Pradeep Mummidi, Michael J Steiner, James C Gay, Soleh Al Ayubi, Nitin Gujral, Vandna Mittal, Kelly Dunn, Vincent Chiang, Matt Hall, Kevin Blaine, Margaret O'Neill, Sarah McBride, Jayne Rogers, Jay G Berry
BACKGROUND: Many hospitals are considering contacting hospitalized patients soon after discharge to help with issues that arise. OBJECTIVE: To (1) describe the prevalence of contactidentified postdischarge issues (PDI) and (2) assess characteristics of children with the highest likelihood of having a PDI. DESIGN, SETTING, PATIENTS: A retrospective analysis of hospital-initiated follow-up contact for 12,986 children discharged from January 2012 to July 2015 from 4 US children's hospitals...
February 2, 2018: Journal of Hospital Medicine: An Official Publication of the Society of Hospital Medicine
https://www.readbyqxmd.com/read/29389750/18f-florbetapir-positron-emission-tomography-determined-cerebral-%C3%AE-amyloid-deposition-and-neurocognitive-performance-after-cardiac-surgery
#7
Rebecca Y Klinger, Olga G James, Salvador Borges-Neto, Tiffany Bisanar, Yi-Ju Li, Wenjing Qi, Miles Berger, Niccolò Terrando, Mark F Newman, P Murali Doraiswamy, Joseph P Mathew
BACKGROUND: Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively. METHODS: Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9)...
April 2018: Anesthesiology
https://www.readbyqxmd.com/read/29337640/molecular-determinants-of-response-to-anti-programmed-cell-death-pd-1-and-anti-programmed-death-ligand-1-pd-l1-blockade-in-patients-with-non-small-cell-lung-cancer-profiled-with-targeted-next-generation-sequencing
#8
Hira Rizvi, Francisco Sanchez-Vega, Konnor La, Walid Chatila, Philip Jonsson, Darragh Halpenny, Andrew Plodkowski, Niamh Long, Jennifer L Sauter, Natasha Rekhtman, Travis Hollmann, Kurt A Schalper, Justin F Gainor, Ronglai Shen, Ai Ni, Kathryn C Arbour, Taha Merghoub, Jedd Wolchok, Alexandra Snyder, Jamie E Chaft, Mark G Kris, Charles M Rudin, Nicholas D Socci, Michael F Berger, Barry S Taylor, Ahmet Zehir, David B Solit, Maria E Arcila, Marc Ladanyi, Gregory J Riely, Nikolaus Schultz, Matthew D Hellmann
Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240)...
March 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29217530/the-impact-of-smoking-and-tp53-mutations-in-lung-adenocarcinoma-patients-with-targetable-mutations-the-lung-cancer-mutation-consortium-lcmc2
#9
Dara L Aisner, Lynette M Sholl, Lynne D Berry, Michael R Rossi, Heidi Chen, Junya Fujimoto, Andre L Moreira, Suresh S Ramalingam, Liza C Villaruz, Gregory A Otterson, Eric Haura, Katerina Politi, Bonnie Glisson, Jeremy Cetnar, Edward B Garon, Joan Schiller, Saiama N Waqar, Lecia V Sequist, Julie Brahmer, Yu Shyr, Kelly Kugler, Ignacio I Wistuba, Bruce E Johnson, John D Minna, Mark G Kris, Paul A Bunn, David J Kwiatkowski
Purpose: Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. Experimental Design: Sixteen U.S. institutions enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and IHC...
March 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29146616/therapeutic-potential-of-afatinib-for-cancers-with-erbb2-her2-transmembrane-domain-mutations-g660d-and-v659e
#10
Hiromasa Yamamoto, Shinichi Toyooka, Takashi Ninomiya, Shigemi Matsumoto, Masashi Kanai, Shuta Tomida, Katsuyuki Kiura, Manabu Muto, Ken Suzawa, Patrice Desmeules, Mark G Kris, Bob T Li, Marc Ladanyi
We previously reported on a family with hereditary lung cancer, in which a germline mutation in the transmembrane domain (G660D) of avian erythroblastic leukemia viral oncogene homolog 2 (erb-b2 receptor tyrosine kinase 2) ( ERBB2 ; human epidermal growth factor receptor 2 [HER2]) seemed to be responsible for the cancer predisposition. Although few data are available on treatment, anti-ERBB2 therapeutic agents may be effective for ERBB2 -mutant cancers. The familial lung cancer patient in one of the authors' institutes developed bone metastasis with enlarging lung tumors and was treated with the ERBB2 inhibitor afatinib...
February 2018: Oncologist
https://www.readbyqxmd.com/read/29106880/utility-of-screening-questionnaire-and-polysomnography-to-predict-postoperative-outcomes-in-children
#11
Hiromi Kako, Jennifer Tripi, Hina Walia, Dmitry Tumin, Mark Splaingard, Kris R Jatana, Joseph D Tobias, Vidya T Raman
INTRODUCTION: The prevalence of pediatric obstructive sleep apnea (OSA) has increased concurrently with the increasing prevalence of obesity. We have previously validated a short questionnaire predicting the occurrence of OSA on polysomnography (PSG). This follow-up study assessed the utility of the questionnaire in predicting postoperative outcomes. METHODS: Children undergoing surgery and completing a sleep study were prospectively screened for OSA using a short questionnaire...
November 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/29089357/effects-of-co-occurring-genomic-alterations-on-outcomes-in-patients-with-kras-mutant-non-small-cell-lung-cancer
#12
Kathryn C Arbour, Emmett Jordan, Hyunjae Ryan Kim, Jordan Dienstag, Helena A Yu, Francisco Sanchez-Vega, Piro Lito, Michael Berger, David B Solit, Matthew Hellmann, Mark G Kris, Charles M Rudin, Ai Ni, Maria Arcila, Marc Ladanyi, Gregory J Riely
Purpose: KRAS mutations occur in approximately 25% of patients with non-small cell lung cancer (NSCLC). Despite the uniform presence of KRAS mutations, patients with KRAS -mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS -mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. Experimental Design: We identified patients with advanced KRAS -mutant NSCLC and evaluated the most common co-occurring genomic alterations...
January 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29028759/which-domains-of-the-odi-best-predict-change-in-physical-function-in-patients-after-surgery-for-degenerative-lumbar-spondylolisthesis
#13
Hamadi A Murphy, Eugene Warnick, Richard McGintee, Kristen Nicholson, Douglas A Hollern, Christie Stawicki, Daniel Tarazona, Gregory D Schroeder, Barrett I Woods, Mark F Kurd, Jeffrey A Rihn, Greg D Anderson, Christopher K Kepler, Alan S Hilibrand, Alexander R Vaccaro, Kris E Radcliff
STUDY DESIGN: Retrospective Review OBJECTIVE.: The purpose of this study is to determine the differential improvement of the various individual items of the ODI and to determine their relationship to other measures of HRQOL. SUMMARY OF BACKGROUND DATA: The oswestry disability index (ODI) is an easily scored, common, ten-item questionnaire about symptoms relevant to lumbar spine pathology. It is not clear if all of the items can be reliably applied to spine surgery...
October 12, 2017: Spine
https://www.readbyqxmd.com/read/28940498/twice-weekly-pulse-and-daily-continuous-dose-erlotinib-as-initial-treatment-for-patients-with-epidermal-growth-factor-receptor-mutant-lung-cancers-and-brain-metastases
#14
Kathryn C Arbour, Mark G Kris, Gregory J Riely, Ai Ni, Kathryn Beal, Mariza Daras, Sara A Hayes, Robert J Young, Christopher R Rodriguez, Linda Ahn, William Pao, Helena A Yu
BACKGROUND: In a phase 1 study of pulse/continuous-dose erlotinib, no patient had disease progression in the central nervous system (CNS). This expansion cohort of the phase 1 study tested the same regimen in a cohort of individuals with epidermal growth factor receptor (EGFR)-mutant lung cancers with untreated brain metastases. METHODS: Patients had not received EGFR tyrosine kinase inhibitors or radiation for brain metastases. All received 1200 mg of erlotinib on days 1 and 2 and 50 mg on days 3 to 7 weekly...
January 1, 2018: Cancer
https://www.readbyqxmd.com/read/28837374/antiemetics-american-society-of-clinical-oncology-clinical-practice-guideline-update-summary
#15
Paul J Hesketh, Kari Bohlke, Mark G Kris
No abstract text is available yet for this article.
December 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28759346/antiemetics-american-society-of-clinical-oncology-clinical-practice-guideline-update
#16
REVIEW
Paul J Hesketh, Mark G Kris, Ethan Basch, Kari Bohlke, Sally Y Barbour, Rebecca Anne Clark-Snow, Michael A Danso, Kristopher Dennis, L Lee Dupuis, Stacie B Dusetzina, Cathy Eng, Petra C Feyer, Karin Jordan, Kimberly Noonan, Dee Sparacio, Mark R Somerfield, Gary H Lyman
Purpose To update the ASCO guideline for antiemetics in oncology. Methods ASCO convened an Expert Panel and conducted a systematic review of the medical literature for the period of November 2009 to June 2016. Results Forty-one publications were included in this systematic review. A phase III randomized controlled trial demonstrated that adding olanzapine to antiemetic prophylaxis reduces the likelihood of nausea among adult patients who are treated with high emetic risk antineoplastic agents. Randomized controlled trials also support an expanded role for neurokinin 1 receptor antagonists in patients who are treated with chemotherapy...
October 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28743157/her2-mutations-in-lung-adenocarcinomas-a-report-from-the-lung-cancer-mutation-consortium
#17
Rathi N Pillai, Madhusmita Behera, Lynne D Berry, Mike R Rossi, Mark G Kris, Bruce E Johnson, Paul A Bunn, Suresh S Ramalingam, Fadlo R Khuri
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). METHODS: Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers...
November 1, 2017: Cancer
https://www.readbyqxmd.com/read/28714472/targeting-the-differential-addiction-to-anti-apoptotic-bcl-2-family-for-cancer-therapy
#18
Akane Inoue-Yamauchi, Paul S Jeng, Kwanghee Kim, Hui-Chen Chen, Song Han, Yogesh Tengarai Ganesan, Kota Ishizawa, Sylvia Jebiwott, Yiyu Dong, Maria C Pietanza, Matthew D Hellmann, Mark G Kris, James J Hsieh, Emily H Cheng
BCL-2 family proteins are central regulators of mitochondrial apoptosis and validated anti-cancer targets. Using small cell lung cancer (SCLC) as a model, we demonstrated the presence of differential addiction of cancer cells to anti-apoptotic BCL-2, BCL-XL or MCL-1, which correlated with the respective protein expression ratio. ABT-263 (navitoclax), a BCL-2/BCL-XL inhibitor, prevented BCL-XL from sequestering activator BH3-only molecules (BH3s) and BAX but not BAK. Consequently, ABT-263 failed to kill BCL-XL -addicted cells with low activator BH3s and BCL-XL overabundance conferred resistance to ABT-263...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28625636/prognostic-impact-of-ttf-1-expression-in-patients-with-stage-iv-lung-adenocarcinomas
#19
Juliana B Schilsky, Ai Ni, Linda Ahn, Sutirtha Datta, William D Travis, Mark G Kris, Jamie E Chaft, Natasha Rekhtman, Matthew D Hellmann
OBJECTIVES: Thyroid transcription factor 1 (TTF-1) is routinely tested in the diagnostic evaluation of suspected lung cancers, is commonly expressed by lung adenocarcinomas, and may modulate lung cancer biology. We examined the role of TTF-1 as a predictive and prognostic marker in patients with advanced lung adenocarcinomas. MATERIALS AND METHODS: We analyzed clinical, pathologic, and molecular features, treatments received, and overall survival obtained from the medical records of 479 consecutive patients at a single site with stage IV lung adenocarcinomas and evaluable TTF-1 expression...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28620111/dietary-fats-and-cardiovascular-disease-a-presidential-advisory-from-the-american-heart-association
#20
REVIEW
Frank M Sacks, Alice H Lichtenstein, Jason H Y Wu, Lawrence J Appel, Mark A Creager, Penny M Kris-Etherton, Michael Miller, Eric B Rimm, Lawrence L Rudel, Jennifer G Robinson, Neil J Stone, Linda V Van Horn
Cardiovascular disease (CVD) is the leading global cause of death, accounting for 17.3 million deaths per year. Preventive treatment that reduces CVD by even a small percentage can substantially reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them. This American Heart Association presidential advisory on dietary fats and CVD reviews and discusses the scientific evidence, including the most recent studies, on the effects of dietary saturated fat intake and its replacement by other types of fats and carbohydrates on CVD...
July 18, 2017: Circulation
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