tbuckley/cabot-search huggingface dataset:
Abstract 2260: Targeting PP2A with LB100 enhances efficacy of CAIX CAR-T cells against GBM
Authors: Jing Cui, Qi Zhang, Qi Song, Herui Wang, Pauline Dmitriev, Mitchell Sun, Jared S. Rosenblum, Kaiyong Yang, John Kovach, Mark R. Gilbert, Zhengping Zhuang
Journal: Cancer Research (2019)

Abstract The need for novel therapies for glioblastoma multiforme (GBM) is well established. Chimeric antigen receptor (CAR)-engineered T cells represent a promising cancer treatment modality for treating GBM. However, CAR-T therapy has limitations, such as low penetration into solid tumors and short duration of CAR-T survival. Protein phosphatase 2A (PP2A) inhibition has been implicated in enhancing T cell anti-tumor activity. LB-100 is a novel, first-in-class, small molecule inhibitor of PP2A recently shown in a Phase I trial to be well-tolerated at doses resulting in stabilization of progressive solid tumors. We set out to overcome limitations of CAR-T therapy by activating the mTOR signaling pathway through inhibition of PP2A by LB-100. GBM highly expresses CAIX due to increased hypoxia signaling. Thus, antitumor CAIX-specific CAR T cells were developed and tested against GBM in vitro and in vivo. CAR-T cells displayed GBM cells cytotoxicity and increased IFN-γ, TNF-α, and IL-2 production. Intra-tumor injection of the CAR-T cells into an intracranial GBM xenograft mouse model efficiently suppressed the tumor growth. We found that PP2A inhibition by LB-100 further enhanced CAIX CAR-T activity and significantly prolonged mouse survival. Herein we demonstrate that CAIX represents a viable target for CAR-T cells and inhibition of PP2A enhances CAR-T efficacy against GBM. Targeting PP2A via inhibition with LB-100 may be a promising therapeutic strategy to improve CAR-T efficacy in other solid tumors. Citation Format: Jing Cui, Qi Zhang, Qi Song, Herui Wang, Pauline Dmitriev, Mitchell Sun, Jared S. Rosenblum, Kaiyong Yang, John Kovach, Mark R. Gilbert, Zhengping Zhuang. Targeting PP2A with LB100 enhances efficacy of CAIX CAR-T cells against GBM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2260.
BOOK REVIEWS
Journal: Circulation (1952)

If the physician is willing to accept the premise that the patient with hypertension, like one with diabetes, should receive a careful indoctrination concerning the nature and treatment of his disorder, then this little book can be recommended with but few reservations.It is carefully edited with respect to clarity and definition of medical terms, and presents its subject in a positive and optimistic fashion.The discussions of therapy reflect Dr. Page's own extensive experience and research.
Erratum: CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis
Authors: Danay Cibrian, María Laura Saiz, Hortensia de la Fuente, Raquel Sánchez-Díaz, Olga Moreno-Gonzalo, Inmaculada Jorge, Alessia Ferrarini, Jesús Vázquez, Carmen Punzón, Manuel Fresno, Miguel Vicente-Manzanares, Esteban Daudén, Pedro M Fernández-Salguero, Pilar Martín, Francisco Sánchez-Madrid
Journal: Nature Immunology (2016)
Textbook of Gastroenterology
Authors: Frank Iber
Journal: JAMA (1991)

Gastroenterology is a rapidly changing field with new drugs, immunological techniques, and technology dramatically altering its fabric. Sleisenger and Fordtran presented us in 1973 with<i>Gastrointestinal Disease</i>(currently in its fourth edition), which broke away from traditional clinical gastroenterology and introduced extensive pathophysiology into GI teaching. Their fine text represented a quantum jump from the then existing texts and thinking. This has been further improved with each edition, retaining what was strong and enhancing the clinical sections, as well as incorporating new information. Now, after 18 years, a new major leap in GI texts has been accomplished by Yamada and his coeditors, making theirs clearly the best, and I hope to convince you of this. There are four major subdivisions: "Basic Mechanisms," "Clinical Approach to Common GI Problems," "Specific Diseases," and "Diagnostic and Therapeutic Modalities." All logic and decision making are related to the pertinent basic science. The genius of
Perceptual Neural Organization: Some Approaches Based On Network Models And Information Theory
Authors: R Linsker
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Bioassay of Genotoxic Effects of Environmental Particles in a Feeding Ciliate
Authors: Joan Smith-Sonneborn, Ronald A. Palizzi, Elizabeth A. McCann, Gerald L. Fisher
Journal: Environmental Health Perspectives (1983)

The ciliated protozoan, Paramecium, can be used to quantitate cytotoxic and genotoxic effects of ingested complex environmental particles. Cytotoxicity is quantitated by the increased proportion of treated versus control cells which do not retain their capacity for normal cell replication. Genotoxic effects are assessed by the increased fraction of nonviable offspring from treated versus control parent cells after the self-fertilization process of autogamy. Since these cells ingest nonnutrient respirable-sized particles, biological activity of intracellular extraction of dusts and fly ash can be compared before and after extraction with polar and nonpolar solvents. Previous studies indicated that coal fly ash was mutagenic in these eukaryotic cells. Mutagenicity of coal fly ash was not detectable after extraction with a concentration of HCl known to remove nonmatrix trace elements. These results suggested that this ciliate bioassay might be a detector of mineral mutagens. Fine particles of the carcinogenic nickel compounds, alpha-nickel subsulfide, and beta-nickel sulfide were compared for their biological activity in this bioassay. Both nickel compounds were ingested by the ciliates and induced heritable damage in the progeny of the treated parent cells.
Medical Legislation
Authors: James C. D. Pigeon
Journal: JAMA (1906)

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
Aspergillus Endophthalmitis in Intravenous-Drug Users—Kentucky
Journal: JAMA (1990)

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
Lay People Can Play Key Role in Reversing Drug Overdoses
Journal: JAMA (2015)

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
Process Measures and Short-term Mortality for Acute Myocardial Infarction—Reply
Authors: Elizabeth H. Bradley, Harlan M. Krumholz
Journal: JAMA (2006)

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
12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance
Authors: Stefan Uderhardt, Martin Herrmann, Olga Oskolkova, Susanne Aschermann, Wolfgang Bicker, Kerstin Sarter, Benjamin Frey, Tobias Rothe, Reinhard Voll, Falk Nimmerjahn, Valery N Bochkov, Georg Schett, Gerhard Krönke
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> During inflammation and tissue damage, pathogens and dying cells are ingested by different phagocytes such as macrophages and dendritic cells. Both the nature and the activation state of the respective phagocyte determine the resulting immune response, which ranges from specific immunity to tolerance. A regulated uptake of apoptotic cells (AC) imposes a special task on the innate immune system to prevent autoimmunity. Mechanisms regulating the sorting of apoptotic material into different phagocyte compartments, therefore, provide an important "tolerance-checkpoint" during the clearance of AC. In this study, the authors investigated the potential role of enzymatic lipid oxidation by 12/15-lipoxygenase (12/15-LO) in the uptake and sorting of AC. <h3>Materials and methods</h3> The authors both studied the clearance of AC and resulting immunological consequences in WT and 12/15-LO−/− animals in vitro and in vivo, respectively. <h3>Results</h3> During peritonitis, uptake of AC was confined to a population of 12/15-LO-expressing, alternatively-activated resident macrophages (resMΦ). ResMΦ utilised 12/15-LO-derived oxidation-products of phosphatidylethanolamine to selectively block the MFG-E8-dependent uptake of AC into freshly recruited inflammatory Ly6Chigh monocytes (infMΦ). In the absence of 12/15-LO, this uptake pattern was deranged and infMΦ started to engulf apoptotic cells. Moreover, this disturbed clearance in 12/15-LO−/− animals resulted in a markedly increased OT-II T cell-proliferation in vitro and in vivo, respectively, when challenged with ovalbumin-transgenic AC. In consistence, the authors observed a break in self-tolerance in aged 12/15-LO-deficient mice including spontaneous production of autoantibodies and occurrence of glomerulonephritis, which both exacerbated after apoptotic challenge in the pristane-induced model of experimental murine lupus. <h3>Conclusion</h3> Our data point towards a so far unrecognised role for lipid oxidation during the maintenance of self-tolerance and identify a mechanism, which orchestrates the cell- and context-specific uptake of antigens by different subsets of phagocytes, imposing a new paradigm in our understanding of the clearance of apoptotic cells.
The impact of weight change during treatment with targeted therapy in patients with metastatic renal cell carcinoma (mRCC).
Authors: Laurence Albiges, Rana R. McKay, Xun Lin, Guillermo de Velasco, Ronit Simantov, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2016)

557 Background: A growing body of evidence suggests a relationship between baseline body mass index and outcomes in patients (pts) with mRCC. However, the role of weight loss (WL) during treatment in pts with mRCC is poorly characterized. The aim of this study was to investigate the impact of weight change in mRCC pts treated with targeted agents. Methods: We conducted an analysis of mRCC pts treated on phase II-III clinical trials sponsored by Pfizer from 2003-2013. Weight change was defined as WL (≥ 5% weight reduction from baseline), stable weight (SW) or weight gain (WG, ≥2 % weight increase). We assessed the impact of weight change on overall survival (OS) (primary endpoint), progression-free survival (PFS) and overall response rate (ORR) at week (wk) 12. Statistical analyses were performed using Cox regression and Kaplan-Meier method. Multivariate analysis was adjusted for known prognostic factors for mRCC, including IMDC criteria. Results: Among 3,311 pts, 1,916 (58 %) had SW, 936 (28 %) had WL and 459 (14%) had WG at wk 12. Overall, pts with WL demonstrated both reduced OS and PFS compared to SW (median OS: 18.68 vs. 26.94 vs. 23.03 months in WL, SW and WG respectively; median PFS: 7.17 vs. 10.12 vs. 9.93 months in WL, SW and WG), and were consistent when considering 2 other time points (table). WL at wk 12 was associated with worse ORR (23.4 vs. 32.1 vs. 35.9% in WL, SW, WG; adjusted odd ratio 0.715, 95% CI 0.590-0.867, p=0.03). Discontinuation rate due to adverse events was similar between groups. Conclusions: We demonstrated that WL during therapy for mRCC is strongly associated with worse clinical outcomes. This observation remains valid for WL at 6, 12 and 24 weeks. Weight change may be an early prognostic factor and guide physician in clinical management. Measures to avoid WL during therapy may lead to better outcomes from targeted therapy. [Table: see text]
Meet the First Authors
Authors: Ly Tu, Humbert Marc, Nee Suet
Journal: Circulation Research (2019)

His study focused on the role of growth factors and their signaling in the acquisition and maintenance of the pro-proliferative and apoptosis-resistant phenotype of the dysfunctional endothelium in pulmonary arterial hypertension (PAH).In particular, he has highlighted the importance of the endothelial FGF-2 and p130cas signaling in PAH.Dr Tu is an expert in molecular and cellular biology, and he is now working on the cross-talk between pulmonary endothelial cells and arterial smooth muscle cells, as well as the endothelium/pericyte interactions.Recently, Ly Tu has obtained a permanent position at University Paris-Sud/ University Paris-Saclay, and his long-term goal is to become a leader in technological innovation to foster basic and applied research on PAH.Outside the laboratory, Ly enjoys playing badminton, traveling the world for new culinary experiences, and sharing good times with his family and friends (over a good glass of wine).In his spare time, he enjoys watching superhero movies that allow him to escape, such as The Alchemist.His favorite motto is, "Laughing is, and will always be, the best form of therapy.
Registration of Foreign Physicians
Authors: James A. Honeij
Journal: JAMA (1910)

Dorseys, and hosts of others now dead but great in the annals of medical discovery and service, like the laborious Diniglison and others, like l'ait!Heck (¡odilard.who should be honored.Why is there not a memorial medical university.not an annex to a literary institution, but an independent exclusively medical university to Ephraim McDowell, to Nicholas Senn, lo Valentine Mott and others like them, now gone to the glory of the skies, but not ye! properly glorified by us here below in suitable structures of stone'.'[f we look for the living to memorialize there are the .Mayo Brothers of Minnesota.There are Sajous.Shoemaker, and La Place of Philadelphia; to say nothing of Murphy, Kinhiy.Corgas, I'Mexner, Ochsner.Hillings, and many others among us yet in other cities and men abroad who have carved deathless naines on fame's memory tablets, and Osier, now not with us, but who worked like a trojan for Johns Hopkins.At one time St. Louis, through its independent medical Schools named after dead medical worthies, did more than any other city to keep the fame of its medical worthies alive by naming its medical colleges after them.Why mil bave a renaissance of great, men of medicine in memorial educational monuments to the work they did for the world's welfare, not in St. Louis and Chicago alone but m oilier cities and sections of the country?Two St. Louis public schools hein-the honored names of ''ope and llodgen.Why not.name medical schools after them, also; and Waiters, Linton.and others of that good "id school-.'I saw .lohnT. llodgen in the ampil heater of t he St. Louis Medical College more than thirty years ago, when he was teaching physiology there, repeat the demonstrations °f Floureus on the cerebelli of pigeons and the school was 'hen independent of Washington University, a two-year School with one previous year of home study with a preecp- '01' its minimum requirement, I saw practical toxicology demonstrated in such a way at the same school that I could never testify Ilia!-hydrocyanic ill'id could take all day to kill a man as was testified to as a *act in the recent Hyde trial at Kansas City.
IATROGENIC NONKETOTIC HYPERGLYCEMIC COMA
Journal: JAMA (1968)

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
Syphilis
Journal: BMJ (2019)

l4159) the second summary point of the "What you need to know" box wrongly stated: "Have a low index of suspicion for syphilis in any sexually active patient with genital lesions or rashes."It should have recommended a "high index of suspicion" (or a "low threshold" for diagnosis).In other words, syphilis should always be ruled out in such cases, with a consideration for empirical treatment at the initial point of care.The summary point has now been corrected.
High-Dose Oral Vitamin D Supplementation and Risk of Falls in Older Women—Reply
Authors: Bess Dawson-Hughes
Journal: JAMA (2010)

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
Increased outdoor recreation, diminished ozone layer pose ultraviolet radiation threat to eye
Authors: C. M. Olson
Journal: JAMA (1989)

THE LONG-TERM effects of ultraviolet (UV) light on the eye are of increasing concern as many people live longer and spend more of that time in outdoor recreation and as the diminishing ozone layer filters less UV light. Ultraviolet radiation is strongest at high altitude, low latitude, and open or reflective environments (sand, snow, or water). For people who lack an eye lens (aphakics), UV light is transmitted directly onto the retina. Ultraviolet light is that part of the spectrum with wavelengths from 100 to 400 nm. The visible spectrum begins at 400 nm. The UV range is subdivided into UV-A (from 320 to 400 nm), UV-B (from 290 to 320 nm), and UV-C (from 100 to 290 nm). Cumulative exposure to the 300- to 400-nm range of UV light is one factor causing cataracts. Ophthalmologists say cataracts cause visual deficits for more than 3.5 million people in the United