tbuckley/cabot-search huggingface dataset:
Potential Impact of Treatment with Inotuzumab Ozogamicin on Chimeric Antigen Receptor T-Cell Therapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia
Authors: Valeria Ceolin, Erica Brivio, Susan R. Rheingold, Allison Barz Leahy, Britta Julia Vormoor, Maureen M. O'Brien, Jeremy Rubinstein, Krzysztof Kalwak, Barbara De Moerloose, Elad Jacoby, Peter Bader, José L. Fuster, Franco Locatelli, Peter Hoogerbrugge, Friso Calkoen, Christian M. Zwaan
Journal: Blood (2021)
Genetic Variants Associated With Susceptibility to<i>Helicobacter pylori</i>
Authors: Mark M. Wurfel, Thomas R. Hawn
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Growth Media Conditions Influence the Secretion Route and Release Levels of Engineered Extracellular Vesicles
Authors: Jeremy P. Bost, Osama Saher, Daniel Hagey, Doste R. Mamand, Xiuming Liang, Wenyi Zheng, Giulia Corso, Oskar Gustafsson, André Görgens, CI Edvard Smith, Rula Zain, Samir El Andaloussi, Dhanu Gupta
Journal: Advanced Healthcare Materials (2021)

Extracellular vesicles (EVs) are nanosized cell-derived vesicles produced by all cells, which provide a route of intercellular communication by transmitting biological cargo. While EVs offer promise as therapeutic agents, the molecular mechanisms of EV biogenesis are not yet fully elucidated, in part due to the concurrence of numerous interwoven pathways which give rise to heterogenous EV populations in vitro. The equilibrium between the EV-producing pathways is heavily influenced by factors in the extracellular environment, in such a way that can be taken advantage of to boost production of engineered EVs. In this study, a quantifiable EV-engineering approach is used to investigate how different cell media conditions alter EV production. The presence of serum, exogenous EVs, and other signaling factors in cell media alters EV production at the physical, molecular, and transcriptional levels. Further, it is demonstrated that the ceramide-dependent EV biogenesis route is the major pathway to production of engineered EVs during optimized EV-production. These findings suggest a novel understanding to the mechanisms underlying EV production in cell culture which can be applied to develop advanced EV production methods.
Immunicy-1: Targeting BCMA with Cyad-211 to Establish Proof of Concept of an shRNA-Based Allogeneic CAR T Cell Therapy Platform
Authors: Ahmad-Samer Al-Homsi, Sebastien Anguille, Dries Deeren, Taiga Nishihori, Nathalie Meuleman, Maher Abdul-Hay, Gareth J. Morgan, Jason Brayer, Nathalie Braun, Caroline Lonez, Marie-Sophie Dheur, Erik Alcantar-Orozco, David Gilham, Anne Flament, Frédéric F. Lehmann
Journal: Blood (2021)
Development of CD19 CAR Engineered Human Placental CD34 +-Derived Natural Killer Cells (CAR19-CYNK) As an Allogeneic Cancer Immunotherapy
Authors: Marina Gergues, Irene Raitman, Joseph Gleason, Valentina Rousseva, Shuyang He, William Van Der Touw, Qian Ye, Lin Kang, Yanliang Zhang, Chin-I Pai, Wenzhong Guo, Henry Ji, Robert Hariri, Xiaokui Zhang
Journal: Blood (2021)
Polycythemia Vera Patients Respond Better to Ropeginterferon Alfa-2b Than HU/BAT Irrespective of Pretreatment or Mutational Status; Results from 5 Years' Treatment in a Randomized, Controlled Setting in the PROUD-PV/Continuation-PV Trials
Authors: Heinz Gisslinger, Christoph Klade, Pencho Georgiev, Dorota Krochmalczyk, Liana Gercheva-Kyuchukova, Miklos Egyed, Petr Dulicek, Arpad Illes, Halyna Pylypenko, Lylia Sivcheva, Jiri Mayer, Vera Yablokova, Kurt Krejcy, Victoria Empson, Hans C. Hasselbalch, Robert Kralovics, Jean-Jacques Kiladjian
Journal: Blood (2021)
Outcome of Post Solid Organ Transplant Burkitt Lymphoma (PSOT-BL): A Report from the Pediatric PTLD Collaborative (PPC)
Authors: Zeinab Afify, Manuela Orjuela, Christine Moore Smith, Mansi Dalal, James B. Ford, Pallavi Pillai, Joanna Robles, Sonika Reddy, Sarah McCormack, Matt J. Ehrhardt, Tonya Ureda, Holly Edington, Tamara P. Miller, Jeremy Rubinstein, Lianna Marks, Clint C. Mason
Journal: Blood (2021)
Pharmacokinetics and Pharmacodynamics of Recombinant FIX Variants in the FIX Knockout Mouse Tail Clip Bleeding Model
Authors: Sabine Pestel, Hendrik Peil, Steffi Knoll Machado, Philipp Claar, Elmar Raquet, Padmapriya Ponnuswamy, Marcel Mischnik, Oliver Ghobrial, Eva Herzog
Journal: Blood (2021)
Total Metabolic Tumor Volume and Tumor Dissemination Are Independent Prognostic Factors in Advanced Hodgkin Lymphoma
Authors: Salim Kanoun, Alina Berriolo-Riedinger, Anne Ségolène Cottereau, Veronique Edeline, Ilan Tal, Pauline Brice, Reda Bouabdallah, Herve Ghesquieres, Aspasia Stamatoullas-Bastard, Jehan Dupuis, Marc André, Thomas Gastinne, Julien Lazarovici, Samuel Griolet, Cedric Rossi, Michel Meignan, Rene-Olivier Casasnovas
Journal: Blood (2021)
Unifying the Definition of High-Risk in Multiple Myeloma
Authors: Ariel Siegel, Eileen M Boyle, Patrick Blaney, Yubao Wang, Hussein Ghamlouch, Jinyoung Choi, Jessica Caro, Louis Williams, Beatrice Razzo, Arnaldo A. Arbini, Marc Braunstein, David Kaminetzky, Daniel Auclair, Charlotte Pawlyn, David Cairns, Graham Jackson, Brian Walker, Benedetto Bruno, Gareth J. Morgan, Faith E. Davies
Journal: Blood (2021)
Venetoclax with Azacitidine or Low Dose Cytarabine As an Alternative to Intensive Chemotherapy in Fit Adults during the COVID19 Pandemic: Real World Data from the UK National Health Service
Authors: Jad Othman, Mariam Amer, Ruebina Amofa, Laura Anderson, Michael J Austin, Alex Bashford, Edward Belsham, Jesca Boot, Victoria Louise Campbell, Thomas Coats, Angela Collins, Charles Crawley, Francesca Crolla, Joe W Cross, Chris Dalley, Raymond Dang, Mike Dennis, Saniya Dhawan, Johnathon Elliott, Sofia Galli, Paolo Gallipoli, Katherine Hodgson, Manish Jain, Pallavi Kalkur, Vana Katsomitrou, Anjum Khan, Asim Khwaja, Pramila Krishnamurthy, Annie Latif, John Laurie, Michael Lim, Eleana Loizou, Justin Loke, Deepak Mannari, Cara Manson, Scott R. Marshall, Behnaz Mobashwera, Vidhya Murthy, Odong Ochaya, Shahzad Orthi, Renuka Palanicawandar, Srinivas Pillai, Dominika Radzova, Adam Rye, Jamie Saunders, Matthew Smith, David Taussig, Tom Taylor, Richard Whitmill, Rui Zhao, Sylvie D Freeman, Charles Craddock, Richard Dillon
Journal: Blood (2021)
The Effect of COVID-19 Vaccine in Patients with Immune Thrombocytopenia
Authors: Chantal Visser, Maurice Swinkels, Erik D. van Werkhoven, F. Nanne Croles, Heike Noordzij, Matthijs Eefting, Suzanne M. Last-Koopmans, Cecile Idink, Peter E. Westerweel, Bart Santbergen, Pieter A. Jobse, Fazil Baboe, Recovac-IR Consortium, Mark-David Levin, Marieke J.H.A. Kruip, A.J. Gerard Jansen
Journal: Blood (2021)
Contextualizing Risk Among Patients With Heart Failure
Authors: Stephen J. Greene, Javed Butler, Gregg C. Fonarow
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Ventricular extrasystoles during thiazide treatment: substudy of MRC mild hypertension trial.
Authors: W Peart, ) Mrs, G Barnes, P Broughton, K Green, Gillian Greenberg, M Hudson, T Meade, G Rose, W Miall, P Whelton, P Brennan, E Raftery, B Subramanian
Journal: BMJ (1983)

One short term and one long term study of the relation between ventricular extrasystoles and thiazide treatment were carried out during the Medical Research Council's mild hypertension trial. In the short term study 110 patients were randomly assigned to one of three treatment groups, bendrofluazide with or without potassium supplements, or placebo. They were studied before starting treatment and nine to 10 weeks later while still taking their randomly assigned drugs. No significant increase in the number of ventricular extrasystoles was associated with short term thiazide treatment, although serum potassium concentrations changed as expected. In the long term study 214 patients who had completed an average of two years' treatment with randomly assigned bendrofluazide or a placebo were studied while continuing to take their trial tablets; the 214 included 20 people who had been randomised at entry to the bendrofluazide group and who had a subsequent history of hypokalaemia. These 20 patients were studied before and after being further randomised to two groups, one continuing treatment without change and one continuing with bendrofluazide and also taking potassium supplements. Counts of ventricular extrasystoles were significantly higher (p = 0.025) in those receiving long term thiazide treatment than in their controls; however, there was no significant association between the number of ventricular extrasystoles and serum potassium concentrations in this group, although the correlation between number of extrasystoles and serum urate concentrations was significant (p = 0.035). Pooled data for both studies showed a highly significant correlation between number of ventricular extrasystoles, and serum potassium concentrations (r = -0.185; p = 0.003), but the correlation with serum urate concentrations was of similar strength (r = 0.178; p = 0.004). These biochemical changes may be acting merely as markers of thiazide intake, and the explanation of the association between thiazide treatment and ventricular extrasystolic activity therefore remains uncertain.
The Effect of Daratumumab, Lenalidomide, Dexamethasone (DRd) on Peripheral Blood Stem Cell Mobilisation (PBSC)
Authors: Tishya Indran, Michael Swain, Jacqueline Widjaja, Flora Yuen, Hang Quach, Wojt Janowski, Anna Hutchinson, Craig Thomas Wallington-Beddoe, Jane Estell, Ian H Kerridge, Andrew Spencer
Journal: Blood (2021)
Identification of blood-based biomarkers for diagnosis and prognosis of Parkinson’s disease: A systematic review of proteomics studies
Authors: Shalini Sundramurthi Chelliah, Saatheeyavaane Bhuvanendran, Kasthuri Bai Magalingam, Muhamad Noor Alfarizal Kamarudin, Ammu Kutty Radhakrishnan
Journal: Ageing Research Reviews (2021)
Assessing the Role of Venetoclax in Combination with Hypomethylating Agents in Higher Risk Myelodysplastic Syndromes
Authors: Rami S. Komrokji, Najla Al Ali, Onyee Chan, Eric Padron, Kendra Sweet, Andrew T. Kuykendall, Jeffrey E. Lancet, David A. Sallman
Journal: Blood (2021)
Frailty Scale for Outcome Predictions in Hematopoietic Cell Transplanted Adults
Authors: Maria Queralt Salas, Eshetu G Atenafu, Eshrak Al-Shaibani, Ora Bascom, Leeann Wilson, Carol Chen, Ivan Pasic, Arjun Law, Wilson Lam, Dennis Dong Hwan Kim, Armin Gerbitz, Auro Viswabandya, Jeffrey H. Lipton, Fotios Michelis, Jonas Mattsson, Shabbir Alibhai, Rajat Kumar
Journal: Blood (2021)
Discovery of Prolyl-tRNA Synthetase As a Novel Target in Multiple Myeloma
Authors: Keiji Kurata, Anna-James Bott, Teru Hideshima, James Dunford, Filiz Senbabaoglu, Catrine Johansson, Adam Cribbs, Martin Philpott, Sarah Gooding, Leona Yamamoto, Mehmet K. Samur, Yu-Tzu Tai, Mark A Tye, N Connor Payne, Patrick Hagner, Karthik Ramasamy, Anjan Thakurta, Ralph Mazitschek, Udo Oppermann, Kenneth C. Anderson
Journal: Blood (2021)
TP53 and KRAS Variants at Initial Diagnosis Identify an Ultra-High Risk Group of Pediatric T-Lymphoblastic Leukemia (T-ALL)
Authors: Tamara Kempter, Joachim B. Kunz, Paulina Richter-Pechanska, Katarzyna Tomska, Tobias Rausch, Busra Erarslan-Uysal, Cornelia Eckert, Martin Zimmermann, Martin Stanulla, Martin Schrappe, Gunnar Cario, Gabriele Escherich, Renate Kirschner-Schwabe, Martina U. Muckenthaler, Jan O. Korbel, Andreas E. Kulozik
Journal: Blood (2021)
Phase II Trial of Eprenetapopt (APR-246) in Combination with Azacitidine (AZA) As Maintenance Therapy for TP53 Mutated AML or MDS Following Allogeneic Stem Cell Transplantation (SCT)
Authors: Asmita Mishra, Roni Tamari, Amy E. DeZern, Michael T. Byrne, Mahasweta Gooptu, Yi-Bin Chen, H. Joachim Deeg, Phillip Gallacher, Anders Wennborg, Denice Kaylor Hickman, Eyal C. Attar, Hugo F. Fernandez
Journal: Blood (2021)
The similarity of class II HLA genotypes defines patterns of autoreactivity in idiopathic bone marrow failure disorders
Authors: Simona Pagliuca, Carmelo Gurnari, Hassan Awada, Ashwin Kishtagari, Sunisa Kongkiatkamon, Laila Terkawi, Misam Zawit, Yihong Guan, Thomas LaFramboise, Babal K. Jha, Bhumika J. Patel, Betty K. Hamilton, Navneet S. Majhail, Sofie Lundgren, Satu Mustjoki, Yogen Saunthararajah, Valeria Visconte, Timothy A. Chan, Chao-Yie Yang, Tobias L. Lenz, Jaroslaw P. Maciejewski
Journal: Blood (2021)
Efficacy and Safety of Orelabrutinib in Relapsed/Refractory Waldenstrom's Macroglobulinemia Patients
Authors: Daobin Zhou, Jie Jin, Zheng-zheng Fu, Shuhua Yi, Wei Li Zhao, Zimin Sun, Wei Yang, Dengju Li, Guohui Cui, Jianda Hu, Ting Liu, Yongping Song, Bing Xu, Zunmin Zhu, Wei Xu, Mingzhi Zhang, Yamin Tian, Huaqiang Zhu, Bin Zhang, Renbin Zhao, Xiang-Yang Zhang
Journal: Blood (2021)
Use of Positron Emission Tomography in Patients with Classical Hodgkin Lymphoma Outside of Europe and North America: Results from the International, Multi-Center, Retrospective B-Holistic Study
Authors: Burhan Ferhanoglu, Marta Zerga, Mubarak Al-mansour, Tae Min Kim, Su-Peng Yeh, Yuqin Song, Amado J Karduss, Gayane Tumyan, Soon Thye Lim, Silvia Rivas-Vera, Yok Lam Kwong, Kwang-Wei Wu, Zhongwen Huang, Mark Hertzberg
Journal: Blood (2021)
Novel Machine Learning Algorithm Predicts Disease Progression in Polycythemia Vera (PV) with Readily-Available Baseline Characteristics
Authors: Andrew Srisuwananukorn, Beth Percha, Ghaith Abu-Zeinah, Joseph Scandura, Spencer Krichevsky, Elwood Taylor, Richard T. Silver, Santiago Thibaud, Lukas Ronner, Nikolai Podoltsev, Jason Gotlib, Mark L. Heaney, Andrew T. Kuykendall, Casey O'Connell, Jamile M. Shammo, Angela Fleischman, Ruben A. Mesa, Abdulraheem Yacoub, Ronald Hoffman, John Mascarenhas, Douglas Tremblay
Journal: Blood (2021)
Abstract PO-065: SIWA318H, an advanced glycation end product (AGE) targeting antibody, is efficacious in a humanized mouse xenograft model for pancreatic cancer
Authors: Ashley Jensen, Gabriela R. Rossi, Ruben Muñoz, Kimberly Brothers, Lewis Gruber, Misty Gruber, Haiyong Han
Journal: Cancer Research (2021)

Abstract SIWA318H is a novel monoclonal antibody that selectively targets a biomarker (an advanced glycation end product) found on the surface of cells exhibiting a combination of: (a) an abnormally high level of aerobic glycolysis, a process known to be associated with initiation and progression of cancer as well as metastasis; and (b) oxidative stress. Cells with this biomarker are often dysfunctional and associated with aging, cancer, and infectious diseases. In this study, we evaluated the antitumor activity of SIWA318H in a humanized xenograft model for pancreatic cancer. SIWA318H was found to react to pancreatic cancer cells (PSN1) and cancer associated fibroblasts (CAF08) using immunofluorescent staining. SIWA318H also showed strong reactivity with tumor xenografts derived from patients with pancreatic cancer as demonstrated by immunohistochemistry. Humanized CD34+ NSG mice were injected subcutaneously with PSN1 pancreatic cancer tumor cells. Ten days later, mice were randomized and enrolled in one of the following groups (n=16/group): 1) IgG1 isotype control (20mg/kg, BIWx1 followed by 10 mg/kg, BIWx2); 2) high dose SIWA318H (20mg/kg, BIWx1 followed by 10 mg/kg, BIWx2); and 3) low dose SIWA318H (10 mg/kg, BIWx1 followed by 5mg/kg, BIWx2). Tumors in mice treated with SIWA318H grew significantly slower than those in mice treated with isotype control antibody (p&amp;lt;0.001). After 3 weeks of treatment with the high dose or the low dose of SIWA318H, the tumor growth was suppressed by 68.8% and 61.5%, respectively, when compared to the isotype antibody control (ANOVA p&amp;lt;0.002). Moreover, a significant increase in complete remission (CR) rate was observed in mice receiving high (60%, p&amp;lt;0.05) or low dose (77.8%, p&amp;lt;0.02) of SIWA318H treatment compared with the control mice (6.7%). No significant antibody treatment related weight loss in mice was observed. These results provide compelling evidence that SIWA318H is a promising novel therapeutic for pancreatic cancer. Additional studies to better understand the mechanism of action of this novel immunotherapy agent are underway. Citation Format: Ashley Jensen, Gabriela R. Rossi, Ruben Muñoz, Kimberly Brothers, Lewis Gruber, Misty Gruber, Haiyong Han. SIWA318H, an advanced glycation end product (AGE) targeting antibody, is efficacious in a humanized mouse xenograft model for pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-065.
Outcome of Relapsed and Refractory Peripheral T-Cell Lymphoma (PTCL) with Intention for Curative Therapy Incorporating High Dose Chemotherapy and Hematopoietic Stem Cell Transplant (HDC/SCT)
Authors: Henry S. Ngu, Stephen Parkin, David W. Scott, Diego Villa, Alina S. Gerrie, Cynthia L. Toze, Maryse Power, Graham W Slack, Joseph M. Connors, Kevin Song, Laurie H. Sehn, Kerry J. Savage
Journal: Blood (2021)
A Phase 1b/2 Study of Navtemadlin (KRT-232), a Murine Double Minute 2 Inhibitor, Combined with a BCR-ABL Tyrosine Kinase Inhibitor in Patients with Relapsed/Refractory, <i>TP53</i>WT, Ph+ Chronic Myeloid Leukemia
Authors: Jorge E. Cortes, Omer Hassan Jamy, Guillermo Ortí, Felipe Prosper, Sebastian Grosicki, Anne Uyei, Wayne P. Rothbaum, Franck E. Nicolini
Journal: Blood (2021)
LncRNA Snhg6 regulates the differentiation of MDSCs by regulating the ubiquitination of EZH2
Authors: Wei Lu, Fenghua Cao, Lili Feng, Ge Song, Yi Chang, Ying Chu, Zhihong Chen, Bo Shen, Huaxi Xu, Shengjun Wang, Jie Ma
Journal: Journal of Hematology & Oncology (2021)

Abstract Myeloid-derived suppressor cells (MDSCs) are derived from bone marrow progenitor cells commonly, which is a heterogeneous cell group composed of immature granulocytes, dendritic cells, macrophages and early undifferentiated bone marrow precursor cells. Its differentiation and immunosuppressive function are regulated by complex network signals, but the specific regulation mechanisms are not yet fully understood. In this study, we found that in mouse of Lewis lung cancer xenograft, long non-coding RNA Snhg6 (lncRNA Snhg6) was highly expressed in tumor-derived MDSCs compared with spleen-derived MDSCs. LncRNA Snhg6 facilitated the differentiation of CD11b + Ly6G − Ly6C high monocytic MDSCs (Mo-MDSCs) rather than CD11b + Ly6G + Ly6C low polymorphonuclear MDSCs (PMN-MDSCs), but did not affect the immunosuppressive function of MDSCs. Notably, lncRNA Snhg6 could inhibit the expression of EZH2 by ubiquitination pathway at protein level rather than mRNA level during the differentiation of mouse bone marrow cells into MDSCs in vitro. EZH2 may be an important factor in the regulation of lncRNA Snhg6 to promote the differentiation of Mo-MDSCs. So what we found may provide new ideas and targets for anti-tumor immunotherapy targeting MDSCs.
Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial
Authors: Yoshiaki Nakamura, Wataru Okamoto, Takeshi Kato, Taito Esaki, Ken Kato, Yoshito Komatsu, Satoshi Yuki, Toshiki Masuishi, Tomohiro Nishina, Hiromichi Ebi, Kentaro Sawada, Hiroya Taniguchi, Nozomu Fuse, Shogo Nomura, Makoto Fukui, Seiko Matsuda, Yasutoshi Sakamoto, Hiroshi Uchigata, Kana Kitajima, Naomi Kuramoto, Takashi Asakawa, Steve Olsen, Justin I. Odegaard, Akihiro Sato, Satoshi Fujii, Atsushi Ohtsu, Takayuki Yoshino
Journal: Nature Medicine (2021)

Abstract The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 ( HER2 ) amplification prospectively confirmed by tumor tissue or ctDNA analysis ( UMIN000027887 ). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC. The study met the primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, as compared to an objective response rate of 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc exploratory analyses revealed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations adjusted for tumor fraction stratified patients according to efficacy with similar accuracy to tissue genotyping. Decreased ctDNA fraction 3 weeks after treatment initiation associated with therapeutic response. Pertuzumab plus trastuzumab showed similar efficacy in patients with mCRC with HER2 amplification in tissue or ctDNA, showing that ctDNA genotyping can identify patients who benefit from dual-HER2 blockade as well as monitor treatment response. These findings warrant further use of ctDNA genotyping in clinical trials for HER2- amplified mCRC, which might especially benefit patients in first-line treatment.
Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units
Authors: Themoula Charalampous, Adela Alcolea-Medina, Luke B. Snell, Tom G. S. Williams, Rahul Batra, Christopher Alder, Andrea Telatin, Luigi Camporota, Christopher I. S. Meadows, Duncan Wyncoll, Nicholas A. Barrett, Carolyn J. Hemsley, Lisa Bryan, William Newsholme, Sara E. Boyd, Anna Green, Ula Mahadeva, Amita Patel, Penelope R. Cliff, Andrew J. Page, Justin O’Grady, Jonathan D. Edgeworth
Journal: Genome Medicine (2021)

Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity.