tbuckley/cabot-search huggingface dataset:
Fc-null anti-PD-1 monoclonal antibodies deliver optimal checkpoint blockade in diverse immune environments
Authors: Julia Moreno-Vicente, Jane E Willoughby, Martin C Taylor, Steven G Booth, Vikki L English, Emily L Williams, Christine A Penfold, C Ian Mockridge, Tatyana Inzhelevskaya, Jinny Kim, H T Claude Chan, Mark S Cragg, Juliet C Gray, Stephen A Beers
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Despite extensive clinical use, the mechanisms that lead to therapeutic resistance to anti-programmed cell-death (PD)-1 monoclonal antibodies (mAbs) remain elusive. Here, we sought to determine how interactions between the Fc region of anti-PD-1 mAbs and Fcγ receptors (FcγRs) affect therapeutic activity and how these are impacted by the immune environment. Methods Mouse and human anti-PD-1 mAbs with different Fc binding profiles were generated and characterized in vitro. The ability of these mAbs to elicit T-cell responses in vivo was first assessed in a vaccination setting using the model antigen ovalbumin. The antitumor activity of anti-PD-1 mAbs was investigated in the context of immune ‘hot’ MC38 versus ‘cold’ neuroblastoma tumor models, and flow cytometry performed to assess immune infiltration. Results Engagement of activating FcγRs by anti-PD-1 mAbs led to depletion of activated CD8 T cells in vitro and in vivo, abrogating therapeutic activity. Importantly, the extent of this Fc-mediated modulation was determined by the surrounding immune environment. Low FcγR-engaging mouse anti-PD-1 isotypes, which are frequently used as surrogates for human mAbs, were unable to expand ovalbumin-reactive CD8 T cells, in contrast to Fc-null mAbs. These results were recapitulated in mice expressing human FcγRs, in which clinically relevant hIgG4 anti-PD-1 led to reduced endogenous expansion of CD8 T cells compared with its engineered Fc-null counterpart. In the context of an immunologically ‘hot’ tumor however, both low-engaging and Fc-null mAbs induced long-term antitumor immunity in MC38-bearing mice. Finally, a similar anti-PD-1 isotype hierarchy was demonstrated in the less responsive ‘cold’ 9464D neuroblastoma model, where the most effective mAbs were able to delay tumor growth but could not induce long-term protection. Conclusions Our data collectively support a critical role for Fc:FcγR interactions in inhibiting immune responses to both mouse and human anti-PD-1 mAbs, and highlight the context-dependent effect that anti-PD-1 mAb isotypes can have on T-cell responses. We propose that engineering of Fc-null anti-PD-1 mAbs would prevent FcγR-mediated resistance in vivo and allow maximal T-cell stimulation independent of the immunological environment.
Respiratory tract infection and CAD: The influence of haemophilus influenzae on cardiovascular events in patient with CAD Ailaiti Maimaitiming, Stephan Blankenberg, Manfred Ossendorf, Christoph Bickel, Hans-Jurgen Rupprecht, Jurgen Meyer. Department of Medicine II, Johannes Gutenberg University Mainz, Mainz, Germany
Journal: Journal of the American College of Cardiology (2001)
Association of American Medical Colleges.
Authors: Bayard Holmes
Journal: JAMA (1899)

measured in its application to penology, morality, and the great unsolved problem of human responsibility.But the bestof men -wise and experienced as well-are sometimes carried by the rushing waves of enthusiasm beyond, or rather, outside, that safest area, where calm reasoning, reflection and judgment hold sway-that realm in which the consensus of opinion of the most competent is held to be the nearest approach to the criterion of truth.Viewed from the height of this least-assail¬ able standpoint, how shall we deal with the uncompromising, dogmatic assertion of Dr. Crothers, as previously quoted?If we refer to alcohol as an analeptic, or tonic, or both, and, as such, a generator, or at least a conservator of force, we are told it has no such power ; if we venture to offer it as a stimu¬
Research brief
Authors: Jane Bradbury
Journal: The Lancet Infectious Diseases (2012)

Long-lived memory lymphocytes generate short-lived terminal progeny and also replenish the long-lived memory pool upon reinfection. Chronic viral infections strain the renewal capacity of antiviral T-cell populations, however, which can lead to failure of long-term immunity. Researchers have now identified two distinct subsets of antiviral CD8 T cells in mice that are characterised by differential expression of the T-bet and Eomesodermin transcription factors and that cooperate to contain chronic viral infections.
Prognostic Factors for Outcome in Patients (pts) with Refractory and Relapsed Acute Lymphocytic Leukemia (ALL) Treated with Inotuzumab Ozogamicin (IO), a CD22 Monoclonal Antibody
Authors: Elias Jabbour, Susan O'Brien, Koji Sasaki, Xuelin Huang, Deborah A. Thomas, Michael E. Rytting, Guillermo Garcia-Manero, Jorge E. Cortes, Pierce Sherry, Tapan M. Kadia, Kantarjian Hagop
Journal: Blood (2014)
Use of Participation to Prevalence Ratio for Evaluating the Representation Status of Women in Oncology Clinical Trials
Authors: Siliang Chen, Jiarui Li, Meijun Shu
Journal: JAMA Oncology (2022)

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
Exploiting macropinocytosis for drug delivery into KRAS mutant cancer
Authors: Huiqin Liu, Feng Qian
Journal: Theranostics (2022)

KRAS mutations are one of the most common gene mutations linked to cancer, presenting in approximately 25% of all tumors, especially pancreatic, lung, and colorectal cancers. Mutant KRAS has long been considered an undruggable target, stalling progress in direct KRAS targeting for many years, while targeted drug delivery into KRAS mutant cells utilizing their transformed metabolic behavior might present an alternative opportunity. Macropinocytosis, a nonselective, fluid-phase, endocytic route, was found to be upregulated as a metabolic feature in KRAS-driven tumors and plays a critical role in nutrient acquisition from extracellular fluids. With the observation that a variety of drug delivery systems could be internalized by KRAS mutant cancer cells through macropinocytosis, exploiting macropinocytosis for intracellular delivery of therapeutics into KRAS mutant tumor cells is emerging as a new drug delivery expedition. In this article, we summarized cancer biology studies that examined KRAS mutation-induced macropinocytosis, reviewed recent studies exploiting macropinocytosis enhancement for KRAS mutant cancer cell-selective drug delivery, and discussed the potential opportunities, challenges and pitfalls of this strategy.
Correction: CD95L Cell Surface Cleavage Triggers a Prometastatic Signaling Pathway in Triple-Negative Breast Cancer
Authors: Marine Malleter, Sébastien Tauzin, Alban Bessede, Rémy Castellano, Armelle Goubard, Florence Godey, Jean Levêque, Pascal Jézéquel, Loic Campion, Mario Campone, Thomas Ducret, Gaëtan MacGrogan, Laure Debure, Yves Collette, Pierre Vacher, Patrick Legembre
Journal: Cancer Research (2020)

In the original version of [this article][1] ([1][2]), the Western blot image used in Fig. 5D to represent CD95 lysate was inadvertently duplicated from the image of c-yes lysate. The image has been replaced with the intended image for CD95 lysate. In addition, in Supplementary Fig. S5H MDA-MB-468
Six Haiku
Authors: Bhuvana Chandra
Journal: Annals of Internal Medicine (2008)

Ad Libitum2 September 2008Six HaikuBhuvana Chandra, MDBhuvana Chandra, MDFrom Northridge, CA 91327.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-5-200809020-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail jacaranda bloomscloak the pavement with purple—cane's tap is muffled.hummingbird feedersways in invisible breeze …her plate is untouched.barest scent of rainslips into hot waiting room;oh, how much longer?ice cream van's music!inside the elder care homesummer's lost children.rainbow paints clear skyno trace of battering storm …she hides her bruises.pomegranate splits.in the operating room,the first incision. Author, Article, and Disclosure InformationAffiliations: From Northridge, CA 91327.Current Author Address: Bhuvana Chandra, MD, PO Box 7694, Northridge, CA 91327. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 September 2008Volume 149, Issue 5Page: 367KeywordsChildrenStorms ePublished: 2 September 2008 Issue Published: 2 September 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Immune targets for therapeutic development in depression: towards precision medicine
Authors: Wayne C. Drevets, Gayle M. Wittenberg, Edward T. Bullmore, Husseini K. Manji
Journal: Nature Reviews Drug Discovery (2022)

Over the past two decades, compelling evidence has emerged indicating that immune mechanisms can contribute to the pathogenesis of major depressive disorder (MDD) and that drugs with primary immune targets can improve depressive symptoms. Patients with MDD are heterogeneous with respect to symptoms, treatment responses and biological correlates. Defining a narrower patient group based on biology could increase the treatment response rates in certain subgroups: a major advance in clinical psychiatry. For example, patients with MDD and elevated pro-inflammatory biomarkers are less likely to respond to conventional antidepressant drugs, but novel immune-based therapeutics could potentially address their unmet clinical needs. This article outlines a framework for developing drugs targeting a novel patient subtype within MDD and reviews the current state of neuroimmune drug development for mood disorders. We discuss evidence for a causal role of immune mechanisms in the pathogenesis of depression, together with targets under investigation in randomized controlled trials, biomarker evidence elucidating the link to neural mechanisms, biological and phenotypic patient selection strategies, and the unmet clinical need among patients with MDD.
Long-term safety and absorption assessment of a novel bioresorbable nitrided iron scaffold in porcine coronary artery
Authors: Jian-Feng Zheng, Zi-Wei Xi, Yang Li, Jia-Nan Li, Hong Qiu, Xiao-Ying Hu, Tong Luo, Chao Wu, Xin Wang, Lai-Feng Song, Li Li, Hai-Ping Qi, Gui Zhang, Li Qin, Wan-Qian Zhang, Xiao-Li Shi, Shu-Han Wang, De-Yuan Zhang, Bo Xu, Run-Lin Gao
Journal: Bioactive Materials (2022)

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 μm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.
N-terminal pro brain natriuretic peptide plasma level is dependent of age and gender: A survey of a large urban population aged older than fifty years Ilan Raymond, Bjoern A. Groenning, Frants Pedersen, Jeanett Dimsits, Matthias Baumann, J�rgen Trawinski, Per R. Hildebrandt. Department of Cardiology and Endocrinology, H:S Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark, Integrated Health Care Solutions, F. Hoffmann-La Roche Ltd, Basel, Switzerland
Journal: Journal of the American College of Cardiology (2001)
Comment on Schäfer et al. “Impact of COVID-19 on Public Mental Health and the Buffering Effect of a Sense of Coherence”: High Level of COVID-19-Related Posttraumatic Stress in COVID-19 Survivors with Low Sense of Coherence
Authors: Hannah Dinse, Leoni-Johanna Speichert, Adam Schweda, Oliver Witzke, Margarethe Konik, Markus Zettler, Hana Rohn, Mark Stettner, Venja Musche, Benjamin Weismüller, Klaas Herchert, Madeleine Fink, Sheila Moradian, Martin Teufel, Eva-Maria Skoda, Alexander Bäuerle
Journal: Psychotherapy and Psychosomatics (2022)
Other Books
Journal: JAMA (1966)

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
Clinical, histopathological and prognostic features of primary cutaneous acral <scp>CD8</scp> <sup>+</sup> T‐cell lymphoma and other dermal <scp>CD8</scp> <sup>+</sup> cutaneous lymphoproliferations: results of an <scp>EORTC</scp> Cutaneous Lymphoma Group workshop*
Authors: Werner Kempf, Tony Petrella, Rein Willemze, Patty Jansen, Emilio Berti, Marco Santucci, Eva Geissinger, Lorenzo Cerroni, Eve Maubec, Maxime Battistella, John Goodlad, Emmanuella Guenova, Katariina Lappalainen, Annamari Ranki, Paul Craig, Eduardo Calonje, Blanca Martin, Sean Whittaker, Ilske Oschlies, Ulrike Wehkamp, Jan P. Nicolay, Marion Wobser, Julia Scarisbruck, Nicola Pimpinelli, Rudi Stadler, Katrin Kerl French, Pietro Quaglino, Jinran Lin, Lianjun Chen, Michaela Beer, Patrick Emanuel, Stephane Dalle, Alistair Robson
Journal: British Journal of Dermatology (2022)

The differential diagnosis of atypical dermal nonepidermotropic CD8+ lymphocytic infiltrates includes a heterogeneous spectrum of lymphoproliferations with overlapping histological and phenotypic features, but divergent clinical manifestations and prognoses. As these neoplasms are rare, more data on their clinicopathological presentation and course are needed.To assess the clinical, histological and immunophenotypic features; outcomes of; and differences between dermal CD8+ lymphoproliferations.Retrospective analysis of a series of 46 patients and biopsies by the international EORTC Cutaneous Lymphoma Group.The dermal CD8+ lymphoproliferations (n = 46) could be assigned to one of three groups: (i) cutaneous acral CD8+ T-cell lymphoma (n = 31), characterized mostly by a solitary nodule arising at acral sites, a monotonous dermal infiltrate of small-to-medium-sized CD8+ lymphocytes with a characteristic dot-like pattern of CD68, a low proliferation rate and an excellent prognosis; (ii) primary cutaneous CD8+ peripheral T-cell lymphoma, unspecified/NOS (n = 11), presenting with one or multiple rapidly evolving tumours, mostly medium-sized pleomorphic CD8+ tumour cells with expression of several cytotoxic markers, and high proliferative activity; and (iii) cutaneous CD8+ lymphoproliferations (n = 4), associated with congenital immunodeficiency syndromes in two patients with persisting localized or disseminated violaceous to brownish plaques on the extremities, a histiocyte-rich infiltrate of mostly small CD8+ lymphocytes with subtle atypia and a protracted course; and papular CD8+ eruptions in two patients with acquired immunosuppression.A constellation of distinct clinical, histopathological and phenotypic features allows discrimination and assignment of dermal CD8+ infiltrates into distinct disease entities. Primary cutaneous acral CD8+ lymphoma, assigned a provisional category in current lymphoma classifications, is a distinct and reproducible entity. A correct diagnosis is essential to avoid unnecessarily aggressive treatment for indolent CD8+ lymphoproliferations and to identify cases with underlying immuno-deficiency or potential for dismal outcome.
Error in Number
Authors: Xiang-Dong Wu, Timothy Bhattacharyya, Marian Hannan, Douglas Kiel
Journal: JAMA Internal Medicine (2020)

In Reply In their Letter in response to our Original Investigation, 1 Fuller-Thompson and Munro provide an interesting insight that improvements in environmental factors, specifically the phase out of leaded gasoline, could have contributed to the reduction in hip fractures observed in the United States and Canada.The role of lead is biologically plausible and important for the future: lead paint continues to be a source of lead exposure in Massachusetts and the rest of the United States.Shao and colleagues bring up 2 areas of hip fracture research that require further study.Although the members of the Framingham cohorts were overwhelmingly suburban residents, hip fractures are known to occur at a higher incidence in urban areas for unknown reasons.The long-standing US trend toward urbanization thus would tend to increase fracture incidence.Fall prevention efforts were not tracked in the Framingham cohorts.
Transcardiac gradient of plasma matrix metalloprotainase correlates with vascular remodeling in coronary artery disease: Intravascular ultrasound study Hiromitsu Yamamoto, Shiro Uemura, Shinichi Fujimoto, Yoshio Tomoda, Toshio Hashimoto, Kazuhiro Dohi. Nara Medical University, Kashihara, Japan
Journal: Journal of the American College of Cardiology (2001)
The acute-phase response of interleukin(IL)-6 is genetically modulated. A prospective study in patients with multivessel coronary disease undergoing surgical revascularization Francesco Burzotta, Felicita Andreotti, Licia Iacoviello, Augusto Di Castelnuovo, Franco Glieca, Nicola Luciani, Roberto Zamparelli, Rocco Schiavello, Filippo Santarelli, Elisabetta Lapenna, GianFederico Possati, Attilio Maseri. Institute of Cardiology, Catholic University, Rome, Italy, Department of Vascular Biology and …
Journal: Journal of the American College of Cardiology (2001)
Does detection of microsatellite instability-high (MSI-H) by plasma-based testing predict tumor response to immunotherapy (IO) in patients with pancreatic cancer (PC)?
Authors: Sakti Chakrabarti, Leslie A. Bucheit, Jason S. Starr, Racquel Innis-Shelton, Ardaman Shergill, Regina Resta, Stephanie Ann Wagner, Pashtoon Murtaza Kasi
Journal: Journal of Clinical Oncology (2022)

607 Background: Immunotherapy (IO) is known to have robust anti-tumor activity in patients with MSI-H solid tumors. However, clinical trials investigating IO activity have used tissue-based testing to determine MSI-H status. Pancreatic tumor biopsy often does not provide sufficient tumor tissue for MSI testing. We investigated if the MSI-H status detected by plasma-based circulating tumor DNA (ctDNA) testing predicts robust response to IO in patients with PC. Methods: Genomic results from a well-validated plasma-based ctDNA assay (Guardant360[G360]) performed as part of routine clinical care between October 1, 2018 and September 7, 2021 in patients with PC were queried to identify patients with MSI-H tumors. Patient characteristics, tumor characteristics, treatment details, and outcomes were reported by ordering clinicians where available. The data cut-off date was September 1, 2021. Results: A total of 52 patients with PC who had MSI-H tumors on G360 were identified. Clinical outcomes data were available for 10/52 (19%) patients who were included for analysis. This patient cohort had a median age of 68 years (range: 56-82); 80% were male and 80% of patients had metastatic disease. 9/10 patients received IO: 3 in the first-line, 3 in the second-line, 3 in the third-line setting; most received pembrolizumab (8/9) while 1 received ipilimumab plus nivolumab. The median duration of IO was 8 months (range: 1-24). The overall response rate was 77% (7/9) and 6 of the 7 responders continue to show response at the time of data cut-off after a median follow-up of 21 months (range:11-33). The median progression-free survival and overall survival were not reached in the IO-treated cohort. Tissue-based MSI testing results were concordant with plasma-based G360 results in 5 of 6 patients (83%) who had tissue-based test results available. The patient with the discordant result was MSI-H by G360 but had intact mismatch repair protein expression by immunohistochemistry. This patient received neoadjuvant IO followed by surgery and the resected specimen confirmed pathological complete response. Conclusions: The detection of MSI-H status by plasma-based ctDNA testing is highly concordant to tissue-based testing and predicts robust and durable response to IO in patients with PC. The use of a well-validated plasma-based ctDNA analysis may expand the identification of MSI-H tumors in patients with PC and enable treatment with IO resulting in improved outcomes.
An introduction to diagnostic neurology; a course of instruction for students. Vol I-II.
Journal: JAMA (1963)

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