tbuckley/cabot-search huggingface dataset:
Abstract 5083: BSCHL-2046, a lead chalcone derivative from a newly synthesized library, is a potent neddylation inhibitor against the growth of prostate cancer cell lines
Authors: Matthew A. Tippin, Dong Jun Fu, Liankun Song, Victor Pham, Xaolin Zi
Journal: Cancer Research (2019)

Abstract Members of the chalcone family of molecules and their derivatives have been shown to inhibit various forms of cancer cells. In particular, Flavokawain A has been shown to inhibit prostate cancer cell lines. In order to capitalize on the bioactive nature of chalcone derivatives, we created a library of chalcone derivatives based on the scaffold of Flavokawain A but with an additional anti-cancer moiety. Here we have demonstrated that BSCHL-2046, the most potent member of the library, inhibits cell growth of prostate cancer cell lines including LNCaP, C4-2B, DU145, 22Rv1, and PC3 with IC50’s ranging from 0.44µM-7.5µM. BSCHL-2046 inhibited Ubc12 neddylation in an in vitro assay at an IC50 of 1.5µM and demonstrated complete inhibition at a concentration of 6µM. BSCHL-2046 also reduced Nedd-8 conjugations to both Cullin-1 and Ubc12 in vivo in DU145 cells. The inhibition of neddylation by BSCHL-2046 resulted in an increased expression of p27 and CDT-1. Using molecular modeling, BSCHL-2046 was predicted to bind directly to the Cullin-RING E3 ligase complex. The Cellular Thermal Shift Assay (CETSA, an in vivo assay) demonstrated that BSCHL-2046 significantly decreased heat-induced protein degradation of E3 subunits, supporting BSCHL-2046 directly binding to the complex. Furthermore, BSCHL-2046 at a concentration of 500nM and 1.25µM displayed a 75% to complete inhibition of colony formation of C4-2B cells in soft agar. Taken together, these results demonstrate BSCHL-2046 and its structural analogs are potent neddylation inhibitors that deserve further investigation for the prevention and treatment of prostate cancer. Note: This abstract was not presented at the meeting. Citation Format: Matthew A. Tippin, Dong Jun Fu, Liankun Song, Victor Pham, Xaolin Zi. BSCHL-2046, a lead chalcone derivative from a newly synthesized library, is a potent neddylation inhibitor against the growth of prostate cancer cell lines [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 5083.
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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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Regorafenib (REG) as a single agent for first-line treatment of frail and/or unfit for polychemotherapy (PChT) patients (pts) with metastatic colorectal cancer (mCRC): A phase II study of the Spanish Cooperative Group for Digestive Tumor Therapy (TTD).
Authors: Alfredo Carrato, Manuel Benavides, Bartolomeu Massuti Sureda, Federico Longo, Pilar Garcia Alfonso, Esther Falco, Margarita Reboredo, M.Auxiliadora Gomez-España, Javier Gallego, Jose M Vieitez, Laura Llayos@Iconcologia.Net, Antonia Salud, Vicente Alonso, Emma Dotor, Silvia Gil, Ana Yuste, Vanesa Pachon, Aitana Calvo, Enrique Grande, Enrique Aranda
Journal: Journal of Clinical Oncology (2016)

3527 Background: A 15-20% of pts diagnosed of mCRC do not qualify to receive PChT as first-line therapy, due to age and/or comorbidities, and their optimal treatment strategy has not been defined. REG is an oral multikinase inhibitor indicated for pretreated mCRC. We aimed to assess the efficacy and safety of REG as a single agent in first-line setting of this frail and/or unfit patient population. Methods: Phase II, single-arm study in frail and/or unfit to receive PChT, mCRC pts. Inclusion criteria: pts ≥ 18 years, ECOG PS ≤ 2, adequate organ function, at least one of the following: dependence in activities of daily living, presence of 3 or more comorbidities or geriatric syndromes. Primary endpoint was progression-free survival (PFS) rate at 6 months. Pts received REG 160 mg PO, 3 weeks on/1 week off, in a 4-week cycle. Results: Forty-seven pts were included. Median age was 80 years (range 63-89), 36% had ECOG 2, 55% were dependent, 38% had geriatric syndromes and 57% ≥ 3 comorbidities; 63.8% had ≥ 2-affected organs and 34% did not undergo primary tumor surgery. Treatment: 192 cycles were administered (median 2, range 1-16). Median dose intensity was 75% due to dose reductions (DR) or delays. Average daily dose: 90.4 mg/day. Response rate 6.4%, disease control rate 51.1%. Median PFS 5 months. Six-month PFS rate: 43.6%. Median overall survival, 16.7 months. Eleven (23.4%) pts discontinued treatment due to toxicity. Three pts (6.4%) had grade 4 toxicity: hypertension, hyperuricemia and lipase increase, and two pts grade 5 toxicity: one sudden death and one rectorrhagia. Most frequent grade 3-4 toxicities: hypertension (37.5%), fatigue (35.0%), hypophosphatemia (15.0%) and increased AST (7.5%). Grade 2-3 skin toxicity, 19.1% of pts. Conclusions: In this group of mCRC pts, REG at a standard starting dose showed a modest antitumor activity and led to a considerable rate of adverse events with frequent DR and/or delays. In the absence of reliable biomarkers, first-line full-dose REG in frail and/or unfit mCRC pts did not achieve the prespecified efficacy threshold (55% PFS rate at 6 months). Clinical trial information: NCT01875380.
Impact of <i>UGT1A1</i> genotype on overall survival in Japanese advanced colorectal cancer patients treated by irinotecan-based regimens.
Authors: Wataru Ichikawa, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Hideaki Miyauchi, Sotaro Sadahiro, Katsunori Shinozaki, Kanehisa Fukumoto, Toshio Otsuji, Takeshi Kambara, Satoshi Morita, Yuichi Ando, Miyuki Arai, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata
Journal: Journal of Clinical Oncology (2016)

3571 Background: The association between UGT1A1 genotypesand clinical outcomes of irinotecan (IRI)-based regimens have been controversial. We conducted an open-label, multicenter, prospective observational study to evaluate the association between UGT1A1 genotypes and safety/efficacy of IRI-based regimens in Japanese patients (pts) with advanced colorectal cancer (aCRC) (NCT 01039506). We reported previously that the progression-free survival (PFS), the primary endpoint, in the UGT1A1 hetero group were non-inferior to those in the wild group, although the homo group had worse PFS as compared with the wild group (ASCO 2015, Abst No. 3525 and ECC 2015, Abst No. 2100). We present the updated overall survival (OS), the secondary endpoint, in terms of UGT1A1 genotypes. Methods: This study included 1,376 pts who had histologically confirmed aCRC and received IRI-based regimens. UGT1A1 genotypes were categorized into three groups: wild (*1/*1), hetero (*1/*6, *1/*28), and homo (*6/*6, *6/*28, *28/*28). The non-inferiority of hetero or homo to wild in OS was investigated under the non-inferiority margin of hazard ratio (HR) of 1.25, using propensity score weighting to adjust for baseline characteristics. The association of OS with the degree of IRI dose reduction was also examined. Results: The efficacy analysis was performed using 1,345 pts (data cut-off date of October 10, 2015). The median follow-up time was 15.0 months (m) (IQR 6.9–27.7). The median OS according to UGT1A1 genotypes were 21.3 (95% CI, 18.6–22.6) m in wild, 18.8 m (16.6–21.4) in hetero, 15.4 m (12.4–18.6) in homo. The HRs of hetero to wild was 0.991 (0.858–1.144; non-inferiority p = 0.0016) and that of homo to wild was 1.279 (1.026–1.595, non-inferiority p = 0.8365). The HRs to wild were 1.119 (0.845–1.483, p = 0.4324) and 1.438 (1.056–1.958, p = 0.0421) in the homo group treated with the initial dose 80% or more and with the initial dose less than 80% of IRI, respectively. In patients treated with the initial dose less than 80% of IRI, the HR of homo to wild was 1.419 (0.996–2.023, p = 0.0529). Conclusions: OS in the UGT1A1 hetero group was non-inferior to the wild group. However, the homo group had worse OS as compared with the wild group.
Influence of bezafibrate on hepatic cholesterol metabolism in gallstone patients: Reduced activity of cholesterol 7?-hydroxylase*1
Authors: D STAHLBERG
Journal: Hepatology (1995)

Bezafibrate is a hypolipidemic fibric acid derivative known to induce cholesterol supersaturation of bile. To characterize its effects on hepatic cholesterol metabolism, 31 normolipidemic, normal-weight patients with gallstones undergoing cholecystectomy were studied. Eleven patients (5 men) were randomized to treatment with bezafibrate, 200 mg three times daily for 4 weeks before operation; the remaining 20 patients (5 men) served as nontreatment controls. At operation, a liver biopsy specimen was obtained under standardized conditions and several important parameters of cholesterol metabolism were assayed. Bezafibrate treatment lowered total plasma cholesterol and triglycerides 30% and 37%, respectively. The hepatic cholesterol 7a-hydroxylase activity was reduced by ≈60% in the bezafibrate treated patients compared with the controls, whereas the acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity was similar in the two groups. The total 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity was increased twofold in the treated patients, whereas the active enzyme remained about the same as in the controls. The low-density lipoprotein (LDL) receptor binding activity was unaffected by the treatment. Bezafibrate treatment significantly reduces cholesterol 7a-hydroxylase activity, and it is suggested that this may play an important role for the development of supersaturated bile during such therapy.
Leading Cases
Authors: Angela R. Holder
Journal: JAMA (1975)

EVERY week, there are many court decisions that have an impact on the practice of medicine. These decisions are currently summarized in<i>The Citation</i>, a newsletter published twice a month by the Office of the General Counsel, American Medical Association. Some of these decisions are of such special importance that they deserve the wider publicity that can be obtained through the pages ofThe Journal. Trial court decisions, which are of little precedent value and are subject to reversal, are omitted. Selected decisions are usually restricted to those of the highest state or federal court. It should be remembered, however, that a decision by a court in one state is not necessarily binding elsewhere. <h3>Failure to Consult Specialist</h3> A 77-year-old woman slipped and fell in her home. She called her family physician, a general practitioner, who had her admitted to the local hospital. He was advised by the radiologist that
Thoracic Trauma
Authors: Alan T. Marty
Journal: JAMA (1981)

What is the human body? To a biomechanic it is either a "heterogeneous viscoelastic mass" or a "great nonlinear damping system." This text uses both models to promote a basic understanding of thoracic injury by first concentrating on the body's mechanical response to today's various environmental forces. It then blossoms with fresh and various insights into the clinical management of all types of chest trauma. Habitués will be awakened by some sharp and astonishing glimpses into such frontiers as independent lung ventilation for unilateral lung injury or high-frequency jet ventilation for bronchopleural fistulae. Generalist readers will find<i>Thoracic Trauma</i>well stocked with the approved verities, extensive citations, and coherent exposition. Among the topics most exhaustively described, vascular and esophageal injuries achieve the highest marks. Depth of perspective is exemplified by a unique chapter on the late results in war wounds of the chest. This section provides evidential ballast for the
Deaths
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 Journals 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 2024 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
Essai randomisé prospectif multicentrique évaluant l’administration agressive de Ringer Lactate en prévention de la pancréatite post-CPRE
Journal: Endoscopy (2018)

Cette étude visait à déterminer le type dʼhydratation intraveineuse optimale en prévention de la pancréatite aigüe post cholangio-pancréatographie-rétrograde endoscopique (CPRE). Au cours de cet essai randomisé prospectif multicentrique, des patients à risque moyen à élevé après CPRE ont reçu au hasard trois protocoles: hydratation intraveineuse agressive (3 ml/kg/h pendant la CPRE, un bolus de 20 ml/kg et 3 ml/kg/h pendant les 8 heures suivant la CPRE) avec soit du Ringer Lactate (LRS), soit du sérum physiologique salé (NSS), ou hydratation intraveineuse standard par LRS (1,5 ml/kg/h pendant et durant les 8 heures post CPRE). Le critère de jugement principal était la pancréatite post-CPRE (PEP). 395 patients ont été inclus et 385 patients ont reçu tout le protocole. Il n’existait aucune différence significative en termes de caractéristiques démographiques entre les 3 groupes. En intention de traiter (ITT), il ressortait une importante différence sur le critère de jugement principal (PEP) entre le groupe hydratation agressive LRS (3,0 %, [Intervalle de confiance(IC) 95 % = 0,1 % – 5,9 %]), le groupe hydratation agressive NSS (6,7 %, [IC 95 % = 2,5 % – 10,9 %]) et le groupe hydratation standard LRS.
<i>Diseases of the Spinal Cord.</i> By Byrom Bramwell, M. D., F. R. C. P. (Edin.), Lecturer on the Principles and Practice of Medicine, and on Medical Diagnosis, in the Extra-Academical School of Medicine, Edinburgh; Pathologist to the Edinburgh Royal Infirmary; Additional Examiner in Clinical Medicine in the University of Edinburgh, etc., etc., with 183 illustrations. Second edition. Edinburgh: Young J. Pentland, 1884
Journal: American Journal of Psychiatry (1885)
Official List of Legally Qualified Physicians, State of Illinois.
Journal: JAMA (1902)

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
Instantaneous and Sudden Deaths
Authors: Meyer Friedman
Journal: JAMA (1973)

A study of 59 persons dying of coronary artery disease revealed that persons dying instantaneously differed from persons dying suddenly of coronary artery disease in that (1) they rarely experienced acute symptoms or exhibited acute signs before death; (2) more than one half died during or immediately after physical exertion; (3) their deaths appeared to result from a primary arrhythmia; and (4) their hearts rarely showed an acute lesion of any kind and frequently exhibited two old occluded coronary arteries or one old occluded, left anterior descending artery. These latter differences should permit angiographic detection of many persons prone to instantaneous death.
Abstract 18672: Association Between Sleep Disordered Breathing and Electrocardiographic Markers of Atrial Abnormalities: The MESA Study
Authors: Younghoon Kwon, Jeffrey R Misialek, Daniel Duprez, Alvaro Alonso, David R Jacobs, Jr, Susan R Heckbert, Susan Redline, Elsayed Z Soliman
Journal: Circulation (2015)

Introduction: Abnormal P wave terminal force in V1 (PTFV1), an electrocardiographic marker of left atrial abnormalities, has been linked to increased risk of atrial fibrillation (AF). Examining the association between sleep disordered breathing (SDB) and PTFV1 might shed light on the potential mechanisms by which SDB increases risk of AF. Methods: A total of 1546 participants (mean age 67.2 (± 8.8) years, 53.4 % women and 63.3 % non-Whites) from the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 5 Sleep ancillary were included in this analysis. PTFV1 was measured from resting standard digital ECG tracings that were automatically processed centrally. Linear and logistic regression analyses were used to examine the cross-sectional associations between measures of SDB (apnea hypopnea index [AHI], obstructive AHI [OAHI] and % time spent with oxygen saturation &lt;90% [% SpO2 90]) and PTFV1. Results: There was a trend of higher PFTV1 values across quartiles of AHI, OAHI and % SpO2 90 (p for trend &lt;0.01 for each). In multivariable linear regression models, the upper quartile of AHI and OAHI measures were associated with higher values of PTFV1 compared with the lower quartile (Table). A 1-SD increase of AHI and OAHI were associated with increased levels of PTFV1 (Table). When PTFV1 was considered as a binary variable (using the cut point of 4000 μV.ms to define abnormality) in logistic regression analysis, AHI and OAHI were also associated with abnormal PTFV1. Conclusion: Severity of SDB, as measured by AHI is associated with subclinical left atrial disease, as measured by PTFV1. This could partially explain the reported association between SDB and AF.
Violence and epilepsy
Authors: J. A. Lewis
Journal: JAMA (1975)

THROUGHOUT history, epilepsy has been the victim of bad press. In ancient Greece, it was sometimes called the Herculean disease because Hercules was thought to have murdered his family in a fit of uncontrollable rage. Two thousand years later, Michael Crichton wrote in<i>The Terminal Man</i>, "Epileptics are predisposed to violent, aggressive behavior during their attacks." In later editions of his novel, Crichton softened his stance with a postscript, but many physicians and laymen still retain a belief that epileptics are dangerous, potentially violent people. In fact, the threads linking violence and epilepsy are tenuous and tangled. Epilepsy is one of the most common of neurological complaints. Epidemiological studies have placed prevalence at 0.5%, and there is good reason to suspect that this is an underestimation. In a recent publication of the National Institute for Neurological Diseases and Stroke, the figure 2% is cited. Since epilepsy appears early, lasts long,
ANCIENT PROBLEMS OF PHARMACY AND THEIR WARNING
Journal: JAMA (2003)

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
INNOCUOUS INSOMNIA?
Journal: JAMA (1900)

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