tbuckley/cabot-search huggingface dataset:
Abstract 3606: Blockade of the PPARα metabolic checkpoint with TPST-1120 suppresses tumor growth and stimulates anti-tumor immunity
Authors: Chan C. Whiting, Nick Stock, Davorka Messmer, Traci Olafson, Derek Metzger, Amanda Enstrom, Jennifer McDevitt, David Spaner, Peppi Prasit, Dipak Panigrahy, Ginna Laport
Journal: Cancer Research (2019)

Abstract Tumors evolve to modulate metabolism to promote their own survival and to suppress tumor-specific immunity. Hypoxic conditions in the tumor microenvironment (TME) induce fatty acid oxidation (FAO), and diverse malignancies are reliant on this metabolic pathway. Additionally, suppressive immune cell populations including M2 macrophages, myeloid-derived suppressor cells and regulatory T cells preferentially utilize FAO. Peroxisome proliferator-activated receptor alpha (PPARα) is the principal transcription factor that regulates the expression of FAO genes, and this metabolic checkpoint is critical for tumor proliferation. TPST1120 is a first-in-class selective competitive antagonist of the human PPARα. To test the hypothesis that blocking FAO with TPST-1120 confers anti-tumor efficacy, we assessed TPST-1120 in multiple syngeneic and xenograft mouse models. Blockade of PPARα with TPST-1120 mediated potent anti-tumor immune responses and significant tumor regression in syngeneic models of breast, lung, colon, pancreatic and melanoma in addition to xenograft models of CLL, AML, pancreatic and melanoma cancers as a monotherapy or in combination with chemotherapy. In pancreatic and breast cancer models, TPST-1120 augmented regression of tumor growth in combination with chemotherapy. In combination with anti-PD1, TPST-1120 treatment resulted in significant reduction of tumor growth in ovarian orthotopic (ID8) and colon (MC38) models; cured mice were completely protected against autologous tumor challenge, strongly suggesting immunological T cell memory against the primary tumor. Studies in genetic knock-out mice indicated that macrophages and antigen cross-presenting dendritic cells are required for TPST-1120 activity, mediated through thrombospondin-1(TSP-1) and stimulator of interferon genes (STING). Consistent with prior reports, inhibition of PPARα with TPST-1120 skewed macrophages in vivo toward an M1 effector phenotype. These results provide the rationale for evaluating TPST-1120 in patients with advanced malignancies. A Phase 1/1b open-label, dose-escalation and dose-expansion study of TPST-1120 as a single agent or in combination with systemic anti-cancer therapies is planned in early 2019. Citation Format: Chan C. Whiting, Nick Stock, Davorka Messmer, Traci Olafson, Derek Metzger, Amanda Enstrom, Jennifer McDevitt, David Spaner, Peppi Prasit, Dipak Panigrahy, Ginna Laport. Blockade of the PPARα metabolic checkpoint with TPST-1120 suppresses tumor growth and stimulates anti-tumor immunity [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 3606.
Repository Therapy
Authors: Walter H. Patt
Journal: JAMA (1964)

<h3>To the Editor:—</h3> I am in my third year of using so-called repository therapy and have seen a few cysts, all of which have been cleared by simple aspiration or associated corticosteroid injection into the "abscess" or cyst cavity. I would say, since the lesion in case 1 dragged over a period of two years, that the patient might not have reported back to the physician for a long time or might have neglected her follow-up care. Under different circumstances, the lesion may well have cleared in a few weeks. In case 2, I see no association between the injection and the clinical diagnosis two years later. From the limited and simple presentation, one can hardly have such varied comments. Cases like these are not an everyday occurrence, and I wonder if these patients had any further allergic difficulties.
INSULIN AND ACUTE INFECTIONS
Journal: JAMA (1933)

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
Data Errors in Table
Authors: Altaf Saadi
Journal: JAMA (2018)

Kiros Berhane, PhD; Chih-Chieh Chang, PhD; Rob McConnell, MD; W. James Gauderman, PhD; Edward Avol, MS; Ed Rapapport, MPH; Robert Urman, PhD; Fred Lurmann, MS; Frank Gilliland, MD, PhD
Special Communication
Journal: JAMA (1961)

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
The Cover
Authors: Lucy L. Bowditch
Journal: JAMA (1987)

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
EXTH-59. mtTERT PROMOTER AS A TARGET FOR TREATMENT OF GLIOBLASTOMA
Authors: Harshil Dhruv, Hyun-Jin Kang, Sen Peng, Vijay Gokhale, Laurence Hurley, Michael Berens
Journal: Neuro-Oncology (2016)

Approximately 86% of GBM tumors exhibit mutation at -124 or -146 bases upstream of the ATG start site in the transcription activating promoter region of Human telomerase reverse transcriptase (hTERT). Mutation in the promoter region of hTERT impairs repression, leading to overexpression of hTERT; inappropriate hTERT is associated with oncogenesis, tumor maintenance, and resistance to apoptosis. We surveyed long-term glioma cell lines and glioma PDX models for mt-hTERT; mRNA and protein expression of hTERT were assessed by qPCR and western blot. The -124 and -146 mutations are located in the major 5-12 G-quadruplex and result in misfolding of the silencer element and consequent over-expression of hTERT. From small molecule library screening, we identified a small drug-like pharmacological chaperone (pharmacoperone) molecule, TG-4260, which binds to the 26 mer base-pair heteroduplex loop, which is the nucleation site for cooperative folding of the major 5-12 G-quadruplex. The chaperone effect of TG-4260 corrects DNA hTERT G-quadruplex misfolding resulting from the somatic mutations and restores the silencer function of the G-quadruplex thereby reducing hTERT activity. TG-4260 directly decreases the transcription activity of the WT and the −124, −124/125, −138/139, and −146 mutants to a similar extent and suppresses the downstream gene BCL2, which activates caspase-3 and produces cell-cycle arrest, leading to cell death. Finally, TG-4260 significantly inhibits telomerase and shortens telomere length after five days of treatment and induces a senescence-like phenotype. This is the first example of the use of a pharmacoperone molecule to correct the misfolding of a DNA G-quadruplex element resulting from mutations in an early folding intermediate. Finally, we screened GBM cell models against a novel small molecule inhibitor that interferes with mutated hTERT promoter for its ability to suppress hTERT expression and induce senescence like phenotype in GBM cells.
Spontaneous Atherosclerosis and Experimental Thromboatherosclerosis
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
MEXICO
Journal: JAMA (1942)

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
New approaches for deep vein thrombosis occurring after surgery
Authors: J. Hirsh
Journal: JAMA (1984)

Fatal pulmonary embolism has been reported to occur in up to 200,000 patients each year in the United States.<sup>1,2</sup>Although many of these deaths occur in patients with terminal disease, many of these deaths also occur in patients who would otherwise have survived to live a normal life. The rate of fatal pulmonary embolism has been estimated to be approximately 3% after total hip replacement,<sup>1,2</sup>between 0.1% and 0.8% in patients undergoing elective general surgical operations,<sup>1,2</sup>and between 4% and 7% in patients with hip fractures.<sup>1,2</sup>Fatal pulmonary embolism is also an important complication in patients who are convalescing from congestive cardiac failure or respiratory conditions. Two approaches can be used to prevent clinically significant venous thromboembolism. These are primary prophylaxis and early detection and treatment of subclinical venous thrombosis. Primary prophylaxis is more effective and less expensive and is the method of choice in most
Starting a Conversation about the Future of Internal Medicine
Authors: The Editors
Journal: Annals of Internal Medicine (2004)

Editorials20 April 2004Starting a Conversation about the Future of Internal MedicineThe EditorsThe EditorsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-8-200404200-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Health care in the United States is like a rudderless vessel drifting close to the shoals of uncontrollable cost, inconsistent quality, and patient demand. Internal medicine is a passenger on this vessel, but it must also cope with dissatisfaction within its ranks, mostly from general internists, and reduced attractiveness to medical students who are choosing a career path. The problems that have brought general internists to this point are immensely complicated and important. They are our problems, and their solutions require our best effort.Asserting a role in solving these vast problems, Annals has published articles intended to help internists ...References1. Sox HC. Improving patient care [Editorial]. Ann Intern Med. 2003;138:996. [PMID: 12809457] LinkGoogle Scholar2. Showstack JA, Sox HC. The future of primary care. Ann Intern Med. 2003;138:S242-72. LinkGoogle Scholar3. Larson EB. Health care system chaos should spur innovation: summary of a report of the Society of General Internal Medicine Task Force on the Domain of General Internal Medicine. Ann Intern Med. 2004;140:639-43. LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Corresponding Author: Customer Service, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGeneralism as Intention Richard J. Baron Working Together—That's Innovation! Howard K. Rabinowitz Making It Possible for General Internal Medicine To Survive Robert B. Copeland Reforming Payment for Primary Care: Making It Happen Gail R. Wilensky Customizing Residency Education Holly J. Humphrey Health Care System Chaos Should Spur Innovation: Summary of a Report of the Society of General Internal Medicine Task Force on the Domain of General Internal Medicine Eric B. Larson and The Domain of General Internal Medicine: A Perspective from Trainees Eric B. Larson and Metrics Cited byA new emphasis on health care safety, quality, and cost containment: How will this affect dietetics practice?The Domain of General Internal Medicine: A Perspective from TraineesEric B. Larson, MD, MPH, for the SGIM Task Force on the Domain of General Internal Medicine 20 April 2004Volume 140, Issue 8Page: 659KeywordsCreativityForecastingHealth careMedicarePatientsResidencySub-specialty care ePublished: 20 April 2004 Issue Published: 20 April 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Presacral Ependymoma: Case Report and Review of Literature
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
Psychosomatic Appendicitis?
Authors: F. R. Brown
Journal: BMJ (1955)

<h3>ABSTRACT</h3> Cell-penetrating peptides (CPPs) are promising tools for transfection of various substances, including nucleic acids, into cells. The aim of current work was to search for novel safe and effective approaches for enhancing transfection efficiency of nanoparticles formed of CPP and splice-correcting oligonucleotide (SCO) without increasing the concentration of peptide. We analyzed an effect of inclusion of calcium and magnesium ions into nanoparticles on CPP-mediated transfection in cell culture. We also studied the mechanism of such transfection as well as its efficiency, applicability in case of different cell lines, nucleic acid types and peptides, and possible limitations. We discovered a strong positive effect of these ions on transfection efficiency of SCO, that translated to enhanced synthesis of functional reporter protein. We observed significant changes in intracellular distribution and trafficking of nanoparticles formed with addition of the ions, without increasing cytotoxicity. We propose a novel strategy of preparing CPP-oligonucleotide nanoparticles with enhanced efficiency and, thus, higher therapeutic potential. Our discovery may be translated to primary cell cultures and, possibly, <i>in vivo</i> studies, in the aim to increase CPP-mediated transfection efficiency and likelihood of using CPPs in clinics.
HLA-B27-Associated Cardiac Disease
Authors: Lennart Bergfeldt
Journal: Annals of Internal Medicine (1998)

Letters1 May 1998HLA-B27-Associated Cardiac DiseaseLennart Bergfeldt, MD, PhDLennart Bergfeldt, MD, PhDKarolinska Hospital; S-171 76 Stockholm, SwedenSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-9-199805010-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:I appreciate Dr. Arnason's letter and his suggestion that transesophageal echocardiography may be more sensitive than transthoracic echocardiography for evaluating cardiac manifestations related to the HLA-B27-associated disease process. The increased sensitivity is analogous to what has been proven for bacterial endocarditis. In the hands of Dr. Arnason and his colleagues, the transesophageal echocardiography-derived observations regarding the subaortic structures also seemed to be specific for patients with ankylosing spondylitis [1]. If these results can be confirmed and extended, they may also expand the proportion of HLA-B27-positive patients with disease manifestations related to this genetic trait beyond the present figure ...References1. Arnason JA, Patel AK, Rahko PS, Sundstrom WR. Transthoracic and transesophageal echocardiographic evaluation of the aortic root and subvalvular structures in ankylosing spondylitis. J Rheumatol. 1996; 23:120-3. Google Scholar Author, Article, and Disclosure InformationAuthors: Lennart Bergfeldt, MD, PhDAffiliations: Karolinska Hospital; S-171 76 Stockholm, Sweden PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1998Volume 128, Issue 9Page: 781KeywordsAnkylosing spondylitisAortic valveEchocardiographyEndocarditisGenetic diseasesHeart diseasesLongitudinal studies ePublished: 15 August 2000 Issue Published: 1 May 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Lymphangiomatosis with splenic involvement
Authors: S. Avigad
Journal: JAMA (1976)

Severe splenomegaly and anemia developed in a 5-year-old girl with diffuse lymphangiomatosis of the upper part of the body. Radioisotope scanning and celiac angiography demonstrated lymphangiomatosis of the spleen, a rare but diagnosable condition. Intractable infection in areas of ulcerated skin led to her death from overwhelming sepsis. (<i>JAMA</i>236:2315-2317, 1976)
Nova et Vetera
Journal: BMJ (1902)

PROFESSOR CORFIELD has drawn our attention to what is probably the first account of a necropsy made on the body of a victim of the Great Plague of London.The report is con- tained in a curious little work which Dr. Corficld, with a generosity somewhat uncommon in collectors of rare books, kindly placed at our disposal.The title page will serve as a summary of the contents of the book: the poifon being therewitlh excluded, and the Arcbeus of the Stomack redeemed from captivity.At the fame time there lay a Servant of Mr. Picks, a youth about 75 yeares of age, labouring under moft horrid fymptomes, raving as it were extimulated by fome Fury; wihich Tragical Interlude was quickly terminated by a mortal cataftrophe.Upon tlhis, I took occafion to requeft by then recovering Patient hiis Mafler, to grant me liberty to open this defunct body; for my ow;a inftruction, and the fatisfaction of all inquifitive perfons, to whiclh, having given him fome perfwafive reafons to that purpofe, he firait condefcended, yet nlot without fome jealoufie and kind fear leaft I fhould do myfelf injusy; upon his conceffton L being much exlhilarated in my fpirits, having obtained that defire which was ofteni denyed me by thofe who pretended feveral flight excufes, I girt up my felf witlh all expedition, getting in readinefs wlhat inftruments were fitting, witlh a porringer containing Sulplhur to bturn under the Corps, wilich was at that tinme placed in the open air in a yard there adjacent, which for feveral refpects was very convenient; and for my better accommodation, a Servant by the permiffion of the forefaid MafteT was ready to afford me his fervice, in opening the Coffin nailed up, and :adminiftering fome other tlhings neceffary for my defign.The hiead of the Coffin being taken off, and the linnen cleated away, I could not but admire, to behold a fkin fo befet with fpots black and blew, more remarkable for multitude and magnitude than any that I have yet feen; fosne of which beinig opened, conteined a con- gealed matter, in one more fhallow, and in another more deep.Here I conceived