tbuckley/cabot-search huggingface dataset:
Abstract A19: The role of metaplastic tuft cell chemosensory signaling in pancreatic cancer
Authors: Megan T. Hoffman, Stephanie The, Daniel J. Salas-Escabillas, Kathleen E. DelGiorno, Filip Bednar, Robert F. Margolskee, Arvind Rao, Howard C. Crawford
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the US with a 9% 5-year survival rate. PDA is characterized by a robust stromal reaction, a large portion of which is composed of infiltrating immune cells and supported by fibroblasts. This fibroinflammatory response promotes both the initiation and progression of PDA. Key to this progression is the crosstalk between the tumor epithelium and immune compartment. Metaplastic tuft cells (MTCs) are a subset of the neoplastic epithelium derived by the transdifferentiation of acinar cells. Tuft cells have been characterized to have a “sense-and-respond” role in luminal surfaces throughout the body, using the taste chemosensory system to promote an inflammatory response in infected and damaged tissues. Among the pancreatic epithelium, MTCs uniquely express components of the gustation sensory system including taste receptors, TRPM5 and αGustducin, as well as an array of inflammatory cytokines, suggesting they are capable of promoting an immune response to extracellular challenges. To explore this hypothesis, we ablated αGustducin, a key protein in the chemosensory cascade, in a model of pancreatitis-associated tumorigenesis. We found that neoplasia in the GNAT3-/-; KrasG12D; PTF1aCreERT mice initiates and progresses more rapidly, a difference associated with alteration in immune cell subtypes. To further quantitate changes in the immune response, we performed mass cytometry (CyTOF), as a way to explore changes in cell number and type, and single-cell sequencing, to more deeply probe the unique gene signatures of cells within the tumor stroma. These large-scale analyses suggest substantial changes in the number of T-cell and myeloid cell populations, as well as alterations of fibroblasts and myeloid cell polarity. We conclude that MTCs use chemosensory signaling to promote the formation of a tumor-suppressive microenvironment. Citation Format: Megan T. Hoffman, Stephanie The, Daniel J. Salas-Escabillas, Kathleen E. DelGiorno, Filip Bednar, Robert F. Margolskee, Arvind Rao, Howard C. Crawford. The role of metaplastic tuft cell chemosensory signaling in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A19.
Determination of anti-pancreatic islet cell antibodies for the prevention of type 1 diabetes mellitus as an immune-related adverse event secondary to treatment with immune checkpoint inhibitors
Authors: A. Olivares Hernández, R.A. Escala Cornejo, L. Figuero Pérez, M.R. Vidal Tocino, E. Escalera Martín, J. Claros Ampuero, A. Amores Martin, C.A. Rodríguez Sánchez, R. Gonzalez Sarmiento, J.P. Miramontes González, J.J. Cruz-Hernández
Journal: Annals of Oncology (2019)
Development of LAG-3 nanobodies as potent cancer imaging tracers
Authors: Q. Lecocq, R.M. Awad, K. Zeven, Y. De Vlaeminck, W. de Mey, P. Debie, J. Puttemans, C. Goyvaerts, G. Raes, M. Keyaerts, N. Devoogdt, K. Breckpot
Journal: Annals of Oncology (2019)
First-in-Man Phase I Trial of the Selective MET Inhibitor Tepotinib in Patients with Advanced Solid Tumors
Authors: Gerald S. Falchook, Razelle Kurzrock, Hesham M. Amin, Wenyuan Xiong, Siqing Fu, Sarina A. Piha-Paul, Filip Janku, Ghazaleh Eskandari, Daniel V. Catenacci, Manfred Klevesath, Rolf Bruns, Uz Stammberger, Andreas Johne, Friedhelm Bladt, Manja Friese-Hamim, Pascal Girard, Samer El Bawab, David S. Hong
Journal: Clinical Cancer Research (2019)

Tepotinib is an oral, potent, highly selective MET inhibitor. This first-in-man phase I trial investigated the MTD of tepotinib to determine the recommended phase II dose (RP2D).Patients received tepotinib orally according to one of three dose escalation regimens (R) on a 21-day cycle: R1, 30-400 mg once daily for 14 days; R2, 30-315 mg once daily 3 times/week; or R3, 300-1,400 mg once daily. After two cycles, treatment could continue in patients with stable disease until disease progression or unacceptable toxicity. The primary endpoint was incidence of dose-limiting toxicity (DLT) and treatment-emergent adverse events (TEAE). Secondary endpoints included safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effects.One hundred and forty-nine patients received tepotinib (R1: n = 42; R2: n = 45; R3: n = 62). Although six patients reported DLTs [one patient in R1 (115 mg), three patients in R2 (60, 100, 130 mg), two patients in R3 (1,000, 1,400 mg)], the MTD was not reached at the highest tested dose of 1,400 mg daily. The RP2D of tepotinib was established as 500 mg once daily, supported by translational modeling data as sufficient to achieve ≥95% MET inhibition in ≥90% of patients. Treatment-related TEAEs were mostly grade 1 or 2 fatigue, peripheral edema, decreased appetite, nausea, vomiting, and lipase increase. The best overall response in R3 was partial response in two patients, both with MET overexpression.Tepotinib was well tolerated with clinical activity in MET-dysregulated tumors. The RP2D of tepotinib was established as 500 mg once daily. MET abnormalities can drive tumorigenesis. This first-in-man trial demonstrated that the potent, highly selective MET inhibitor tepotinib can reduce or stabilize tumor burden and is well tolerated at doses up to 1,400 mg once daily. An RP2D of 500 mg once daily, as determined from translational modeling and simulation integrating human population pharmacokinetic and pharmacodynamic data in tumor biopsies, is being used in ongoing clinical trials.
Abstract C57: Organoid profiling identifies common responders to chemotherapy in pancreatic cancer
Authors: Herve Tiriac, Pascal Belleau, Dannielle Engle, Dennis Plenker, Astrid Deschenes, Tim Somerville, Fieke Froeling, Richard Moffitt, Jennifer Knox, Alexander Krasnitz, Steven Gallinger, David Tuveson
Journal: Cancer Research (2019)

Abstract Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we find that PDO therapeutic profiles paralleled patient outcomes and that PDOs enable longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection. Citation Format: Herve Tiriac, Pascal Belleau, Dannielle Engle, Dennis Plenker, Astrid Deschenes, Tim Somerville, Fieke Froeling, Richard Moffitt, Jennifer Knox, Alexander Krasnitz, Steven Gallinger, David Tuveson. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C57.
Effectiveness of brentuximab vedotin before and after allogeneic stem‐cell transplantation in the management of transformed mycosis fungoides
Authors: R. André, C. Ram‐Wolff, M. Battistella, R. Peffault de Latour, A. Petit, J.D. Bouaziz, P. Brice, M. Bagot, A. Masson
Journal: British Journal of Dermatology (2019)
Coca-Cola marketing to children is “serious public health concern,” researchers warn
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Two major campaigns from Coca-Cola were targeted at teenagers and mothers and used social media influencers and celebrities—including Olympic athletes—to make products seem healthier, researchers have warned.

US Right to Know, a non-profit investigative group that campaigns for transparency in the food industry, issued the warning after it obtained documents from the University of Colorado relating to two of Coca-Cola’s public relations (PR) campaigns: the 2013-14 Movement is Happiness campaign and the 2016 Rio de Janeiro Olympic Games campaign.

The group said that, although the company was publicly pledging to reduce children’s exposure to advertisements for products high in fat, sugar, or salt, behind closed doors it was actively targeting young age groups.

US Right to Know called for government policy to “effectively restrict the exposure of children to the marketing of unhealthy foods” and said that …
Loss of ADAMTS19 causes progressive non-syndromic heart valve disease
Authors: Florian Wünnemann, Asaf Ta-Shma, Christoph Preuss, Severine Leclerc, Patrick Piet van Vliet, Andrea Oneglia, Maryse Thibeault, Emily Nordquist, Joy Lincoln, Franka Scharfenberg, Christoph Becker-Pauly, Philipp Hofmann, Kirstin Hoff, Enrique Audain, Hans-Heiner Kramer, Wojciech Makalowski, Amiram Nir, Sebastian S. Gerety, Matthew Hurles, Johanna Comes, Anne Fournier, Hanna Osinska, Jeffrey Robins, Michel Pucéat, Harry C. Dietz, Andrew S. McCallion, Gregor Andelfinger, Bart L. Loeys, Lut Van Laer, Per Eriksson, Salah A. Mohamed, Luc Mertens, Anders Franco-Cereceda, Seema Mital, Orly Elpeleg, Marc-Phillip Hitz, Gregor Andelfinger
Journal: Nature Genetics (2019)
Inhibition of MDSC Trafficking with SX-682, a CXCR1/2 Inhibitor, Enhances NK-Cell Immunotherapy in Head and Neck Cancer Models
Authors: Sarah Greene, Yvette Robbins, Wojciech K. Mydlarz, Angel P. Huynh, Nicole C. Schmitt, Jay Friedman, Lucas A. Horn, Claudia Palena, Jeffrey Schlom, Dean Y. Maeda, John A. Zebala, Paul E. Clavijo, Clint Allen
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Natural killer (NK)-cell–based immunotherapy may overcome obstacles to effective T-cell–based immunotherapy such as the presence of genomic alterations in IFN response genes and antigen presentation machinery. All immunotherapy approaches may be abrogated by the presence of an immunosuppressive tumor microenvironment present in many solid tumor types, including head and neck squamous cell carcinoma (HNSCC). Here, we studied the role of myeloid-derived suppressor cells (MDSC) in suppressing NK-cell function in HNSCC. Experimental Design: The ability of peripheral and tumor-infiltrating MDSC from mice bearing murine oral cancer 2 (MOC2) non-T-cell–inflamed tumors and from patients with HNSCC to suppress NK-cell function was studied with real-time impedance and ELISpot assays. The therapeutic efficacy of SX-682, a small-molecule inhibitor of CXCR1 and CXCR2, was assessed in combination with adoptively transferred NK cells. Results: Mice bearing MOC2 tumors pathologically accumulate peripheral CXCR2+ neutrophilic-MDSC (PMN-MDSC) that traffic into tumors and suppress NK-cell function through TGFβ and production of H2O2. Inhibition of MDSC trafficking with orally bioavailable SX-682 significantly abrogated tumor MDSC accumulation and enhanced the tumor infiltration, activation, and therapeutic efficacy of adoptively transferred murine NK cells. Patients with HNSCC harbor significant levels of circulating and tumor-infiltrating CXCR1/2+ CD15+ PMN-MDSC and CD14+ monocytic-MDSC. Tumor MDSC exhibited greater immunosuppression than those in circulation. HNSCC tumor MDSC immunosuppression was mediated by multiple, independent, cell-specific mechanisms including TGFβ and nitric oxide. Conclusions: The clinical study of CXCR1/2 inhibitors in combination with adoptively transferred NK cells is warranted.
Hepatitis C Virus Antibody Testing Among 13- to 21-Year-Olds in a Large Sample of US Federally Qualified Health Centers
Authors: Rachel L. Epstein, Jianing Wang, Liesl Hagan, Kenneth H. Mayer, Jon Puro, Benjamin P. Linas, Sabrina A. Assoumou
Journal: JAMA (2019)

to $538 among 11 608 038 individuals in 2017 (Table 1), but declined as a share of total spending from 8.97% to 8.04% (difference, -0.93% [95% CI, -0.95% to -0.91%]; P < .001)(Table 2).Mean total spending increased from $5701 to $6688.Children had the highest primary care spending as a share of their total health care spending, with 20.33% in 2013 and 19.54% in 2017 (P < .001),and individuals aged 55 to 64 years had the lowest, with 7.25% in 2013 and 6.33% in 2017 (P < .001).Under the narrow definition, the primary care spending share declined from 4.60% to 4.35% (difference, -0.25% [95% CI, -0.27% to -0.23%]; P < .001).This decline was accounted for by children, for whom the share decreased from 13.68% to 12.51% (P < .001).The primary care spending share under this definition did not change substantially for any other age group.The share of individuals utilizing a PCC increased from 78.35% in 2013 to 79.65% in 2017 (difference, 1.30% [95% CI, 1.27%-1.34%];P < .001)and varied across age groups (Table 2).Discussion | From 2013 to 2017, the share of total spending attributed to primary care declined among individuals covered by employer-sponsored insurance despite an increase in PCC utilization and spending on primary care because total spending grew more quickly.Primary care may be both a substitute for and complement to non-primary care services. 3 As a substitute, primary care may decrease spending for specialty and inpatient care, where services are more expensive. 4 As a complement, it may increase utilization of more expensive care because patients are referred to a broader network of clinicians. 5A better understanding of the relationship between primary care and specialty utilization and spending is needed.The estimates of primary care spending share are higher than estimates among Medicare fee-for-service beneficiaries, 1 and fall between other estimates of individuals covered by employer-sponsored insurance using a convenience sample of insurers 2 and Medical Expenditure Panel data. 6 Factors affecting primary care spending, such as patient and PCC demographics and insurance plan benefit design, were not studied.The data may not be representative of the entire employer-sponsored insurance population.
Single-step endoscopic ultrasound-guided gastroenterostomy and ERCP in patient with Roux-en-Y hepaticojejunostomy after right lobe hepatectomy
Authors: Borathchakra Oung, Julien Faller, Isabelle Lienhart-Chambon, Jérôme Rivory, Jean-Christophe Saurin, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2019)

Since endoscopic ultrasound-guided gastroenterostomy (EUS-GE) with a lumen-apposing metal stent was introduced first in an animal model in 2012 [1], and then in humans in 2015 [2], this technique has become more and more promising; it is now used in many expert centers around the world [3] to treat gastric outlet obstruction and to perform endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy.
Towards selective tuberculosis screening of people in prison in a low-incidence country
Authors: Gerard de Vries, Sylvia Commandeur, Connie Erkens, Walid Haddad, Niesje Jansen, Peter Kouw, Margreet Kamphorst-Roemer
Journal: European Respiratory Journal (2019)

<b>Screening all prisoners in low-incidence countries is not effective. Screening data can help to direct screening activities. Continuity of tuberculosis treatment and care is a major concern in prisoners after their release from prison.</b>http://bit.ly/2rzn5l8
Impaired control of the contact system in hereditary angioedema with normal C1‐inhibitor
Authors: Maria Bova, Chiara Suffritti, Valeria Bafunno, Stefania Loffredo, Giorgia Cordisco, Stefano Del Giacco, Tiziana Maria Angela De Pasquale, Davide Firinu, Maurizio Margaglione, Vincenzo Montinaro, Angelica Petraroli, Anna Radice, Luisa Brussino, Andrea Zanichelli, Alessandra Zoli, Marco Cicardi
Journal: Allergy (2019)

Abstract Background Hereditary angioedema (HAE) comprises HAE with C1‐inhibitor deficiency (C1‐INH‐HAE) and HAE with normal C1‐INH activity (nl‐C1‐INH‐HAE), due to mutations in factor XII (FXII‐HAE), plasminogen (PLG‐HAE), angiopoietin 1 (ANGPT1‐HAE), kininogen 1 genes (KNG1‐HAE), or angioedema of unknown origin (U‐HAE). The Italian network for C1‐INH‐HAE (ITACA) created a registry including different forms of angioedema without wheals. Objective We analyzed clinical and laboratory features of a cohort of Italian subjects with nl‐C1‐INH‐HAE followed by ITACA to identify specific biomarkers. Methods A total of 105 nl‐C1‐INH‐HAE patients were studied. Plasma concentrations of cleaved high‐molecular‐weight kininogen (cHK), vascular endothelial growth factors (VEGFs), angiopoietins (Angs), and secreted phospholipase A 2 enzymes (sPLA 2 ) were evaluated. Results We identified 43 FXII‐HAE patients, 58 U‐HAE, and 4 ANGPT1‐HAE. We assessed a prevalence of 1:1.4 × 10 6 for FXII‐HAE and 1:1.0 × 10 6 for U‐HAE. cHK levels in U‐HAE patients were similar to controls in plasma collected using protease inhibitors cocktail (PIC), but they significantly increased in the absence of PIC. In FXII‐HAE patients, cHK levels, in the absence of PIC, were significantly higher than in controls. We found a significant increase of VEGF‐A, VEGF‐C, and Ang1 levels in U‐HAE patients compared to controls. In FXII‐HAE, only VEGF‐C levels were increased. Ang2 concentrations and sPLA 2 activity were not modified. The levels of these mediators in ANGPT1‐HAE patients were not altered. Conclusions Our results suggest that pathogenesis of FXII‐, ANGPT1‐, and U‐HAE moves through an unbalanced control of kallikrein activity, with bradykinin as most likely mediator. VEGFs and Ang1 participate in the pathophysiology of U‐HAE increasing the basal vascular permeability.
Periodontics in the <scp>USA</scp>: An introduction
Authors: Mark I. Ryder
Journal: Periodontology 2000 (2019)

Abstract The United States continues to be an incubator for new concepts and approaches to the diagnosis, treatment, and prevention of periodontal diseases. This volume of Periodontology 2000 presents some of these newer areas of research and paradigms that have emerged in the United States from both long‐established and new investigators. These areas include: (1) more comprehensive approaches to assessing the total periodontal microbiome, including bacteria, viruses, and fungi, and their interactions with both the local and systemic inflammatory and immune responses, as well as with other oral and systemic conditions and diseases; (2) new developments for a more comprehensive characterization of the patient genome, transcriptome, and proteome profiles and the role of these profiles in periodontal disease pathogenesis; (3) new developments in nonsurgical approaches to periodontal diseases, including broad‐based lines of attack using natural antimicrobials and host‐modulation therapies and more focused approaches that target specific interactions in the host response; and (4) new big data analysis, machine learning, and imaging approaches, both for understanding the pathogenesis of periodontal diseases and for developing improved risk‐assessment tools and better treatment outcomes.
Widespread Blood Shortages Threaten Global Public Health
Authors: Bridget Kuehn
Journal: JAMA (2019)

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
Ready for another big year!
Authors: Peter D. Siersema
Journal: Endoscopy (2019)

At the threshold of 2020, some of us may well have New Year’s resolutions, intending to change something in our habits or work, but one thing that probably remains unchanged is our dedication to endoscopy. And in 2020 Endoscopy will continue to publish stimulating high quality endoscopic research, reports of interesting new techniques and novel devices, and new or updated guidelines from the European Society of Gastrointestinal Endoscopy. Alongside these endeavors, you will also see some new features that will make our journal even more readable, and improvements in workflow to facilitate your submissions.
OCT-Based Management of Nilotinib-Associated CAD in a Patient With Chronic Myeloid Leukemia
Authors: Hiroyuki Kiriyama, Junichi Ishida, Hiroshi Kadowaki, Takeshi Iwasa, Arihiro Kiyosue, Satoshi Kodera, Jiro Ando, Hiroshi Akazawa, Issei Komuro
Journal: JACC CardioOncology (2019)
Clinical Benefit of Circulating Tumor DNA Analysis in Early-Stage Breast Cancer
Authors: Garvit Chitkara, Rohini Hawaldar, Rajendra A. Badwe
Journal: JAMA Oncology (2019)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal