tbuckley/cabot-search huggingface dataset:
Abstract 3014: Gene signatures identify quinolate phosphoribosyltransferase as a key mediator of acquired resistance to Panobinostat and Bortezomib in glioma, and NAD+ biosynthesis as a targetable pathway to reverse treatment resistance
Authors: Esther P. Jane, Daniel R. Premkumar, Sameer Agnihotri, Max Myers, Ansuman Chattopadhyay, D. Lansing Taylor, Mark Schurdak, Andrew Stern, Ian F. Pollack
Journal: Cancer Research (2019)

Abstract Resistance of tumor cells to the induction of apoptosis is an important reason for the failure of anticancer treatments in patients with gliomas. Several factors working in concert have been implicated as sources of this treatment resistance; therefore, innovative therapeutic approaches that conspire to attack key tumor vulnerabilities are needed. HDAC and proteasome inhibitors are two classes of agents that have shown some benefit in the clinic, but patients often rapidly manifest intrinsic or acquired resistance mechanisms that limits their individual efficacy. We demonstrate that the combination of the HDAC inhibitor panobinostat and the proteasome inhibitor bortezomib synergistically induces apoptosis of human glioma cell lines. However, acquired resistance is observed even with this initially effective combination. To examine the mechanism of this resistance, we performed RNA sequencing and pharmacological screening of resistant compared to sensitive cells. Based on these studies, we present evidence that quinolinic acid phosphoribosyltransferase (QPRT), an enzyme catalyzes a rate determining step in de novo NAD+ biosynthesis, provides a critical adaptive survival mechanism that allows cancer cells to evade an initially effective therapeutic combination. We identified 1004 genes that had a significant change between panobinostat and bortezomib- resistant cells versus inhibitor naïve control cells. Furthermore, pathway analysis revealed that the experimental regimen significantly altered metabolic pathways. By silencing QPRT (using siRNA) we demonstrated that we can overcome resistance, thus suggesting QPRT as a crucial crossroad for cancer cell survival and as a new anticancer target. We also showed that treatment of panobinostat and bortezomib resistant cells with FK866, niraparib, selisistat, epacadostat, gemcitabine, 5-fluoruracil, and methotrexate significantly increased cell death highlighting the importance of NAD+ and folate pathway inhibitors in resensitizing the resistant cells. Together, targeting QPRT or NAD+ consuming enzymes hold promise for eliminating recurrent disease in glioma. Citation Format: Esther P. Jane, Daniel R. Premkumar, Sameer Agnihotri, Max Myers, Ansuman Chattopadhyay, D. Lansing Taylor, Mark Schurdak, Andrew Stern, Ian F. Pollack. Gene signatures identify quinolate phosphoribosyltransferase as a key mediator of acquired resistance to Panobinostat and Bortezomib in glioma, and NAD+ biosynthesis as a targetable pathway to reverse treatment resistance [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 3014.
Lost authors.
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
Unpowered Scooter-Related Injuries—United States, 1998-2000
Journal: JAMA (2001)

Injuries associated with unpowered scooters have increased dramatically since May 2000. These scooters are a new version of the foot-propelled scooters first popular during the 1950s. Most scooters are made of lightweight aluminum with small, low-friction wheels similar to those on in-line skates. They weigh <10 pounds and fold for easy portability and storage. Up to 5 million scooters are expected to be sold in 2000, an increase from virtually zero last year (Consumer Product Safety Commission [CPSC], unpublished data, 2000). This report summarizes the results of a descriptive analysis of scooter-related injuries during the past 34 months and provides recommendations to reduce these injuries.
A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice
Authors: Megan N. Roberts, Marita A. Wallace, Alexey A. Tomilov, Zeyu Zhou, George R. Marcotte, Dianna Tran, Gabriella Perez, Elena Gutierrez-Casado, Shinichiro Koike, Trina A. Knotts, Denise M. Imai, Stephen M. Griffey, Kyoungmi Kim, Kevork Hagopian, Marissa Z. McMackin, Fawaz G. Haj, Keith Baar, Gino A. Cortopassi, Jon J. Ramsey, Jose Alberto Lopez-Dominguez
Journal: Cell Metabolism (2018)
Graduate Education In Public Health
Journal: JAMA (1969)

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
Abstract 2505: Sorafenib inhibits non-small cell lung cancer cell growth by targeting B-RAF in <i>KRAS</i> wild-type cells and C-RAF in <i>KRAS</i> mutant cells
Authors: Ken Takezawa, Isamu Okamoto, Kimio Yonesaka, Yuki Yamada, Erina Hatashita, Masahiro Fukuoka, Kazuhiko Nakagawa
Journal: Cancer Research (2010)

Abstract Sorafenib is a multikinase inhibitor whose targets include B-RAF and C-RAF, both of which function in the extracellular signal-regulated kinase (ERK) signaling pathway but which also have distinct downstream targets. The relative effects of sorafenib on B-RAF and C-RAF signaling in tumor cells remain unclear, however. We have now examined the effects of sorafenib as well as of B-RAF or C-RAF depletion by RNA interference on cell growth and ERK signaling in non-small cell lung cancer (NSCLC) cell lines with or without KRAS mutations. Sorafenib inhibited ERK phosphorylation in cells with wild-type KRAS but not in those with mutant KRAS. Despite this difference, sorafenib inhibited cell growth and induced G1 arrest in both cell types. Depletion of B-RAF, but not that of C-RAF, inhibited ERK phosphorylation as well as suppressed cell growth and induced G1 arrest in cells with wild-type KRAS. In contrast, depletion of C-RAF inhibited cell growth and induced G1 arrest, without affecting ERK phosphorylation, in cells with mutant KRAS; depletion of B-RAF did not induce G1 arrest in these cells. These data suggest that B-RAF-ERK signaling and C-RAF signaling play the dominant roles in regulation of cell growth in NSCLC cells with wild-type or mutant KRAS, respectively. The G1 arrest induced by either C-RAF depletion or sorafenib in cells with mutant KRAS was associated with down-regulation of cyclin E. Our results thus suggest that sorafenib inhibits NSCLC cell growth by targeting B-RAF in cells with wild-type KRAS and C-RAF in those with mutant KRAS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2505.
This Week in &lt;EMPH&gt;JAMA&lt;/EMPH&gt;
Journal: JAMA (2005)

Tien Y. Wong, MD, PhD; Wayne Rosamond, PhD; Patricia P. Chang, MD, MHS; David J. Couper, PhD; A. Richey Sharrett, MD, DrPH; Larry D. Hubbard, MAT; Aaron R. Folsom, MD; Ronald Klein, MD, MPH
Rare Cases in Midwifery
Authors: E. Copeman
Journal: BMJ (1862)

looked like motions"; but this had not been kept for in- spectioti.Oct. 21st.He was no better.He complained of being much weaker.He had been losing flesh the last few days, evidently.Pulse 120, without much power.The abdomen was swollen and tender.The urine was high coloured; not so much had been passed the last two days.The sickness was just the sarmie; large quan- tities of fluid, with stinking flatus, gurgled up into the moutb.Flatus was passed per anumt in the night; and this morning, whiile I was itl the house, he discharged, while passing uirine, about an ounce or a little inore of "semifluid, healthy, brownish fecal matter, normal ini smell and appearance, tinging lineni with the usuial stain".He complained very much of pain; said be could not wear it out many days more.The morphia injection was continued.Oct. 22nd.There was no change; he was perhaps not in suchi constant pain.Pulse 1220; face very anxiouis.The question of gastrotomy was carefully considered, and ultimately deferred for another day or two.Oct. 23rd.He had not a good night; sick as usual; face not so anxious.Puilse 120, feeble.At 9 A.M., he bad the sensationi (so he sai(l) of some rush of fiuid in the intestinie, and presently passed per aturn, six or eight ounces of yellowish facal matter.The abdomen was more easy.
Prognostic importance of pruritus in Hodgkin's disease
Authors: A. S. Feiner
Journal: JAMA (1978)

In 1971 participants in the Ann Arbor Conference on Hodgkin's disease thought that pruritus had no independent prognostic importance. We reviewed our series of patients with Hodgkin's disease and found six patients in whom severe itching was a major clinical problem. When compared with similarly treated patients without pruritus, these patients appeared to have more-aggressive disease. Severe itching, alone or with B symptoms, needs further study, since it may presage a poor prognosis. (<i>JAMA</i>240:2738-2740, 1978)
The Cover
Authors: M. Therese Southgate
Journal: JAMA (1991)

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
一种新的皮肤严重药物反应标志物——干扰素‐γ‐诱导蛋白 10
Journal: British Journal of Dermatology (2020)

史蒂文斯‐约翰逊综合征/中毒性表皮坏死松解症以及伴有嗜酸性粒细胞增多症和全身症状的药物反应（DRESS）都是严重的、可能危及生命的药物反应，这些反应在外观和与之相关的皮肤体征和症状的发展方式上各不相同。
Thyroid-stimulating autoantibodies in Graves disease preferentially recognize the free A subunit, not the thyrotropin holoreceptor
Authors: Gregorio D. Chazenbalk, Pavel Pichurin, Chun-Rong Chen, Francesco Latrofa, Alan P. Johnstone, Sandra M. McLachlan, Basil Rapoport
Journal: Journal of Clinical Investigation (2002)

Graves disease is directly caused by thyroid-stimulating autoantibodies (TSAb’s) that activate the thyrotropin receptor (TSHR). We observed upon flow cytometry using intact cells that a mouse mAb (3BD10) recognized the TSHR ectodomain with a glycosidylphosphatidylinositol (ECD-GPI) anchor approximately tenfold better than the same ectodomain on the wild-type TSHR, despite the far higher level of expression of the latter. The 3BD10 epitope contains the N-terminal cysteine cluster critical for TSAb action. Consequently, we hypothesized and confirmed that TSAb (but not thyrotropin-blocking autoantibodies [TBAb’s]) also poorly recognize the wild-type TSHR relative to the ECD-GPI. Despite poor recognition by TSAb of the holoreceptor, soluble TSHR A subunits (known to be shed from surface TSHR) fully neutralized autoantibody-binding activity. These data indicate that the epitope(s) for TSAb’s, but not for TBAb’s, are partially sterically hindered on the holoreceptor by the plasma membrane, the serpentine region of the TSHR, or by TSHR dimerization. However, the TSAb epitope on the soluble A subunit is freely accessible. This observation, as well as other evidence, supports the concept that A subunit shedding either initiates or amplifies the autoimmune response to the TSHR, thereby causing Graves disease in genetically susceptible individuals.
From the Centers for Disease Control and Prevention. Erythromycin-resistant Bordetella pertussis--Yuma County, Arizona, May-October 1994
Journal: JAMA (1995)

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
Abstract 14: A new orally available drug for the treatment of metastatic cancers
Authors: Kun Zhou, Jae Eun Cheong, Michaela Zaffagni, Yingjie Xu, Lijun Sun, Bruce Zetter
Journal: Cancer Research (2019)

Abstract Metastatic cancers account for the great majority of cancer deaths. We conducted a screen to indetify known drugs that selectively inhibit the viability of metastatic tumor cells. Results of the screen identified members of the FDA-approved benzimidazole methylcarbamate family (e.g. mebendazole (MBZ) and albendazole (ALB)) as potential therapies for metastatic disease. Earlier work also supports a role for this chemical family in the potential treatment of activity in multiple cancers, but progress has been stalled by their poor water solubility and poor bioavailability for systemic delivery to disseminated tumors. We therefore synthesized a novel compound (OBD9) containing the scaffold of MBZ coupled to an oxetane group to enhance aqueous solubility to 361 μM. OBD9 demonstrates significant cytotoxicity toward a variety of cancer cell types including colon, lung, and prostate cancers (IC50: 0.9-2 μM). In a mouse xenograft model of human A549 lung cancer cell line OBD9 dramatically inhibited the growth of established tumors at 30 or 90 μM without noticeable toxicity. In a mouse xenograft model using highly aggressive PCMLN3 prostate cancer cells, oral administration of OBD9 at 30 mg/kg also significantly repressed growth of established tumors with no visible toxicity. We have studied the working mechanisms behind OBD9 and found that the Wnt signaling pathway is suppressed by OBD9 treatment. Both qPCR and Western blot data suggest that the beta-catenin/TCF complex in the Wnt signaling pathway are inhibited by OBD9. Among the downstream targets of Wnt signaling pathway, the oncogene cMyc is also significantly decreased in different cancers including colon, lung and prostate cancer. Overall, our in vitro and in vivo data suggest that OBD9 potentially represents a novel therapeutic option for multiple cancers especially metastatic cancer through targeting Wnt signaling pathway and the downstream oncogene cMyc. Citation Format: Kun Zhou, Jae Eun Cheong, Michaela Zaffagni, Yingjie Xu, Lijun Sun, Bruce Zetter. A new orally available drug for the treatment of metastatic cancers [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 14.
Notes on the Opium Habit.
Authors: None C. E. W.
Journal: JAMA (1885)

The fundamental cause of the opium habit, aside from the accidents which may arouse it into potent energy, is in the moral nature of the individual. Dr. Maylert does not take quite as broad a view of the subject as that above suggested, but recognizing the psychical element in the cause eloquently insists on the use of moral measures in the case. In fact he recommends that therapeutic agents should be employed to meet the various symptoms that may arise, while the entire confidence of the patient and the gradual diminution of the dose are the prime requisites to success. He also considers that the patient should be kept under surveillance for a considerable length of time after the opium is stopped or until the normal degree of self control is reached. He is greatly opposed to the sudden entire stopping of the drug as subjecting the patient to dangerous
Propranolol
Authors: Morton A. Goldmann
Journal: JAMA (1975)

<h3>To the Editor.—</h3> As physicians and cardiologists, we are sensitive to the very important hemodynamic effects that are accomplished with propranolol hydrochloride. Unfortunately, the patient is not always fully aware of the extent to which propranolol may mask various physiologic stresses to the cardiovascular system. Moreover, as a result of accident or acute illness, he may be unable to communicate the fact that he is under the influence of this drug. I, therefore, strongly urge all patients to carry a card or some other form of identification that identifies him as a recipient of propranolol. I trust that readers ofThe Journalwill see fit to encourage their patients who are taking this drug to follow a similar program.
National Cancer Institute begins laetrile clinical trial
Journal: JAMA (1980)

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
Release of mast-cell-derived mediators after endobronchial adenosine challenge in asthma.
Authors: R Polosa, W H Ng, N Crimi, C Vancheri, S T Holgate, M K Church, A Mistretta
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Preformed and newly generated mediators released from airway mast cells may play a role in adenosine-induced bronchoconstriction. To investigate the possible role of mast-cell-derived mediator release in mediating bronchoconstriction induced by adenosine 5'-monophosphate (AMP), we have examined the fluid obtained by bronchoalveolar lavage for inflammatory mediators and markers of airway permeability immediately after instillation of AMP directly into an airway segment of 10 asthmatic subjects. Eight subjects completed the protocol. When compared with the saline-challenged segment, the response to endobronchial stimulation with AMP was characterized by a prompt reduction in airway caliber paralleled by a significant rise in PGD2, histamine, and tryptase levels in the lavage fluid. After AMP challenge, the median (range) concentration for PGD2 increased from 36 to 205 pg/ml (p = 0.006), for histamine from 184 to 433 pg/ml (p = 0.018), and for tryptase from 0.30 to 0.54 ng/ml (p = 0.013). In addition, a small but significant rise in albumin levels (from 27.8 to 36.1 micrograms/ml; p = 0.031) was detected after endobronchial challenge with AMP. These findings indicate that adenosine-induced responses may be initiated by the acute release of mast-cell-derived mediators, including PGD2, histamine, and tryptase.