tbuckley/cabot-search huggingface dataset:
Identification and characterization of highly potent and specific FLT3 kinase inhibitors effective against FLT3-driven leukemia in culture and in vivo
Authors: Todd A. Carter, Daniel K. Trieber, William H. Biggs, Miles A. Fabian, Anne-Marie Velasco, Philip T. Edeen, Julia T. Ford, Zdravko V. Milanov, Shamal A. Mehta, Robert M. Grotzfeld, Andiliy G. Lai, Pietro Ciceri, Mark Floyd, Darren E. Insko, Sanna Herrgard, Corey E. Atteridge, Lisa M. Wodicka, Hitesh K. Patel, Patrick P. Zarrinkar, David J. Lockhart
Journal: Cancer Research (2005)

5990   Mutations resulting in constitutive activation of the receptor tyrosine kinase FLT3 occur in 25-40% of patients with Acute Myeloid Leukemia (AML) and correlate with poor prognosis. Although several ATP-competitive inhibitors of FLT3 have progressed into the clinic, recent experience suggests that increases in compound potency and specificity may be necessary for the use of small molecule inhibitors of FLT-3 in AML treatment. To this end, we have identified and characterized a series of compounds that have high affinity for wild type and mutant forms of FLT3 observed in human AML (K d  range: 0.15 - 50 nM). This series of compounds also demonstrates remarkable specificity for the kinases FLT3, KIT and/or PDGFR (confirmed across a broad panel of up to 170 independent kinase assays). The AML-derived human cell line MV4;11 expresses a commonly observed Internal Tandem Duplication (ITD) mutation that results in constitutive activation of FLT3 and FLT3-driven proliferation. Exposure of MV4;11 cells to these compounds demonstrates dose-dependent inhibition of both proliferation and FLT3 receptor autophosphorylation (IC 50  range: 0.2 - 50 nM). The compounds are orally bioavailable and have favorable pharmacokinetic properties in mice. Preliminary xenograft studies in nude mice show that the compounds have potent anti-tumor effects in MV4;11 solid tumor and leukemia models.
Marijuana and hostility in a small-group setting
Authors: C Salzman, B A Van Der Kolk, R I Shader
Journal: American Journal of Psychiatry (1976)

The authors used several indices to assess the relationship between marijuana and hostility as both inner affect and verbal behavior in a small-group setting. Marijuana subjects reported a small but statistically significant decrease in hostile feelings after the introduction of a frustration stimulus. They also showed significantly less verbal hostility than placebo subjects both before and after introduction of a frustration stimulus. The authors note that research findings on marijuana and hostility are not consistent and suggest a multidetermined relationship based on dose, environment, nature of the frustration stimulus, and intraindividual factors.
Institute Probes Music's Therapeutic Potential
Authors: M J Friedrich
Journal: JAMA (2004)

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 413: Validation of methylation biomarkers that distinguish normal colon mucosa from cancer patients from normal colon mucosa of patients without cancer
Authors: Matteo Cesaroni
Journal: Cancer Research (2014)

Abstract We have attempted to validate differences in DNA methylation levels of 30 candidate genes reported to discriminate between normal colon mucosa of colon cancer patients and normal colon mucosa of individuals without cancer. We found that CpG sites in 16 of the 30 candidate genes show significant differences in mean methylation level in normal colon mucosa in an independent cohort of 24 cancer patients and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs set yielded an 18-gene signature, composed of 10 of the validated candidate genes plus 8 additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r=0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These 7 CpGs, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. Citation Format: Matteo Cesaroni. Validation of methylation biomarkers that distinguish normal colon mucosa from cancer patients from normal colon mucosa of patients without cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 413. doi:10.1158/1538-7445.AM2014-413
Foundations of Evidence-Based Medicine
Authors: S. Satya-Murti
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
Effect of heart rate and autonomic tone on the QT interval.
Authors: A Susmano
Journal: Circulation (1982)

Influence of Heart Rate and Inhibition of Autonomic Tone on the QT Interval" by Ahnve and Vallin.I Their study confirms observations previously made in man in our laboratory.'Ahnve and Vallin also questioned in their discussion that "both heart rate and adrenergic activity affect the duration of the QT interval, but it is not clear as to what extent these effects are interrelated or whether the heart rate effects are independent of autonomic tone.We demonstrated in intact unanesthesized man and in one patient after cardiac transplantation that intravenous infusion of isoproterenol did not modify the dura- tion of the QT interval independent of its effects on heart rate.3In the patient with the cardiac transplant, the QT interval was markedly short- ened at any given heart rate; however, we did not know whether that could be a normal finding in the denervated human heart.
Postprescription review improves in-hospital antibiotic use: A multicenter randomized controlled trial
Authors: P. Lesprit, A. de Pontfarcy, M. Esposito-Farese, H. Ferrand, J.L. Mainardi, M. Lafaurie, P. Parize, C. Rioux, F. Tubach, J.C. Lucet
Journal: Clinical Microbiology and Infection (2014)
Shc signaling in differentiating neural progenitor cells
Authors: Luciano Conti, Simonetta Sipione, Lorenzo Magrassi, Luca Bonfanti, Dorotea Rigamonti, Valentina Pettirossi, Marc Peschanski, Bassam Haddad, PierGiuseppe Pelicci, Gabriele Milanesi, Giuliana Pelicci, Elena Cattaneo
Journal: Nature Neuroscience (2001)
Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS
Authors: Takao Omura, Kumiko Omura, Andrea Tedeschi, Priscilla Riva, Michio W Painter, Leticia Rojas, Joshua Martin, Véronique Lisi, Eric A Huebner, Alban Latremoliere, Yuqin Yin, Lee B Barrett, Bhagat Singh, Stella Lee, Tom Crisman, Fuying Gao, Songlin Li, Kush Kapur, Daniel H Geschwind, Kenneth S Kosik, Giovanni Coppola, Zhigang He, S Thomas Carmichael, Larry I Benowitz, Michael Costigan, Clifford J Woolf
Journal: Neuron (2015)
Diagnostic Strategies for Common Medical Problems.
Authors: Robert J. Panzer, Edgar R. Black, Paul F. Griner
Journal: Annals of Internal Medicine (1991)

At last, the second edition of Diagnostic Strategies for Common Medical Problems has arrived to replace the well-used first edition, published in 1991.Evidence about the precision and accuracy of diagnostic tests is not always readily available, and this resource attempts to overcome the problem.Its aim is to help clinicians with both critical appraisal of diagnostic tests and quantitative decision making about diagnostic strategies.It provides information about the operating characteristics of diagnostic tests and procedures that are commonly used in clinical practice, particularly in internal medicine.Unfortunately, this book does not provide any information on whether the literature was systematically reviewed and critically appraised for each topic.References are provided in each chapter, but no mention is made of the methodological rigour of the referenced studies.The authors provide quantification of the results of the diagnostic studies and present them as sensitivities, specificities, and likelihood ratios, although no confidence intervals are included.An electronic version of Diagnostic Strategies will be published with the year 2000 issue of Best Evidence.No information, however, is provided on how often it will be updated.The editors suggest that users go to the literature to retrieve the most up-todate evidence, and indeed, they provide a chapter on searching and appraising evidence about diagnostic tests.
An internal teacher for neural computation
Authors: Dario Floreano
Journal: Behavioral and Brain Sciences (1997)

Contextual signals might supervise the discovery of coherently varying information between cortical modules computing different functions of their receptive field input. This hypothesis is explored in two sets of computational experiments, one studying the effects on learning of long-range unidirectional contextual signals mediated by intervening processors, and the other showing contextually supervised discovery of a high-order variable in a multilayer network.
MYOGLOBINURIA AFTER SPONTANEOUS AND INDUCED FEVER: REPORT OF A CASE
Authors: Perry Berg, Eugene P. Frenkel
Journal: Annals of Internal Medicine (1958)

ExcerptMyoglobinuria in man, known to be a consequence of trauma to striated muscle, has occurred also in a number of ill defined clinical circumstances. All of the latter have involved striated muscle, although without clear-cut injury. Sometimes severe muscular exercise alone has been the background; in other cases, true muscular disease, of unknown etiology, has been present. The last group consists of "Haff disease," a geographically localized, epidemic, acute affliction of muscle and idiopathic paroxysmal myoglobinuria, with or without interval muscle weakness and atrophy.The traumas to striated muscle that have resulted in myoglobinuria include crushing injuries,1arterial occlusion with...
Hypoxia-dependent proliferation and protease expression in oral carcinoma cell lines
Authors: Wolfgang Zacharias, Nalinie Wickramasinghe, Kasturi Banerjee, Nagaraj Nagathihalli, Nadarajah Vigneswaran
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1822 

Objective: Microenvironmental hypoxia has been implicated in the progression of cancer from neoplasia to invasive cancer. Determination of protein expression patterns of carcinoma cell lines under hypoxic and normoxic conditions may offer new therapeutic targets for treatment of cancer. The objective of the present study was to determine the cell proliferation rates and expression patterns of hypoxia-inducible factor1a (HIF1a), lysosomal proteases cathepsin B (CB), D (CD), and L (CL), and matrix metalloproteinases (MMPs) in primary tumor and metastatic cell lines under normoxic and hypoxic conditions. Methods: The oral cancer cell lines 1386Tu, 1386Ln, 686Tu and 686Ln derived, from the primary tumors (Tu) or lymph node metastases (Ln) of two different patients (1386 and 686, respectively), were used. Cells were exposed to normoxia or hypoxia (1% O2, 5% CO2 and 94% N2) for 24, 48, or 72 h, and cell proliferation rates were studied using the MTT assays. Protein expression of HIF-1a, CB, CD, CL, MMP2, and MMP9 were investigated with Western Blot analysis. Activities of cathepsins and cysteine proteinase inhibitors (CPI) were studied using fluorometric assays; MMP2 and MMP9 were also quantitated by ELISA. Results: Expression levels of HIF-1a, CB and CD under normoxia varied in cell lines, with the 1386Tu cells expressing low and 1386Ln cells expressing higher levels (CB, 3-fold; CD, 2-fold; HIF-1a, 10-fold relative to Tu). Under hypoxia, HIF-1a was upregulated in both cell lines in a time-dependent manner with optimum at 24 hours. Hypoxia for 24h had no apparent effects on the expression of these proteases in all the four cell lines. However, 48h exposure to hypoxia resulted in increased expression, secretion, and activity of CB and CD in all cell lines. Hypoxia reduces the expression of MMP2 in 1386Tu cells by 45% with no significant change in 1386Ln cells; whereas MMP9 is poorly expressed in those cells. CL was observed only at very low levels and appeared not to be responsive to hypoxia. The proliferation rates of all four cell lines under normoxic and hypoxic conditions were not significantly different up to 48 hours, and microscopic examination of cells after hypoxia revealed no apparent changes in their morphology. Conclusions: Exposure of a set of oral carcinoma cells to hypoxia for a period of 48 h results in: i) increased expression of HIF-1a; ii) no significant effect on cell proliferation; iii) reduced expression of MMP2 in a primary tumor cell line with no apparent change in its corresponding metastatic cell line; iv) changes in the secretion and activities of CB, and CD in all cell lines. These observations will help to rationalize the effects of intra-tumor microenvironmental conditions on the malignant phenotypes of oral carcinoma cells. Supported by grants from the NIH/NIDCR and the Philip Morris External Research Program (to W.Z).
Sphingosine Blocks Human Polymorphonuclear Leukocyte Phagocytosis Through Inhibition of Mitogen-Activated Protein Kinase Activation
Authors: Evelin M.B. Raeder, Pamela J. Mansfield, Vania Hinkovska-Galcheva, Lars Kjeldsen, James A. Shayman, Laurence A. Boxer
Journal: Blood (1999)
Protease-Activated Receptors in Hemostasis, Thrombosis and Beyond
Authors: Shaun Coughlin
Journal: Circulation (2012)

Protease-activated receptors (PARs) provide a mechanism by which thrombin and related proteases can regulate the behavior of platelets and other cells. Overall, the coagulation cascade and PARs together provide an elegant system that links mechanical information in the form of disruption of vascular integrity to appropriate cellular responses involved in hemostasis, inflammation, repair, and even pain perception. This talk will focus on lessons from ex vivo studies of human platelets, animal models and human clinical trials that speak to the roles of PARs in platelet activation, hemostasis and thrombosis and on work in progress that speaks to roles for this system in blood vessel formation and other processes in the vertebrate embryo.
Treatment of Anemia in Myelodysplastic Syndromes With Granulocyte Colony-Stimulating Factor Plus Erythropoietin: Results From a Randomized Phase II Study and Long-Term Follow-Up of 71 Patients
Authors: Eva Hellström-Lindberg, Tomas Ahlgren, Yves Beguin, Magnus Carlsson, Jan Carneskog, Inger Marie Dahl, Ingunn Dybedal, Gunnar Grimfors, Lena Kanter-Lewensohn, Olle Linder, Michaela Luthman, Eva Löfvenberg, Herman Nilsson-Ehle, Jan Samuelsson, Jon-Magnus Tangen, Ingemar Winqvist, Gunnar Öberg, Anders Österborg, Åke Öst
Journal: Blood (1998)
A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Francais des Myelodysplasies and European CMML Group
Authors: E Wattel, A Guerci, B Hecquet, T Economopoulos, A Copplestone, B Mahe, ME Couteaux, L Resegotti, V Voglova, C Foussard, B Pegourie, JL Michaux, E Deconinck, AM Stoppa, G Mufti, D Oscier, P Fenaux
Journal: Blood (1996)
The Ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis
Authors: Xiangming Xing, Shao-Chun Wang, Weiya Xia, Yiyu Zou, Ruping Shao, Ka Yin Kwong, Zhenming Yu, Su Zhang, Susan Miller, Leaf Huang, Mien-Chie Hung
Journal: Nature Medicine (2000)
Press: Fergie and parents' diet dilemmas
Authors: R. MacDonald
Journal: BMJ (2000)

Sarah Ferguson, the Duchess of York, was slated in the tabloid press last week for playing “diet games” with her two daughters. On 26 November the Sunday Mirror led with the story that “self-confessed binge eater Fergie has admitted making Beatrice, 12, and Eugenie, 10, diet conscious after a summer of too many sodas, cookies and pizza.” Statements of condemnation from “health experts” followed.

On Monday the story was rehashed in all the other tabloids, including the Daily Mail , which ran with the headline: “Fergie: how I teach the little princesses to calorie count.” More condemnation followed. It also featured on the BBC's television news that day, with nutritional experts giving their opinion and adding to the dilemma of what parents are supposed to tell their children about healthy eating.

Childhood obesity is rising (affecting 15% of children at the last estimate in September) but so is the prevalence …
Abstract 4557: Expression of p16 in colon cancer and cyclin D1 in gastric cancer predicts response to CDK4/6 inhibition <i>in vitro</i>
Authors: Zev A. Wainberg, Ann Yufa, Adrian Anghel, Amy M. Rogers, Tin Manivong, Shahriar Adhami, Habib Hamidi, Dylan Conklin, Richard S. Finn, Dennis J. Slamon
Journal: Cancer Research (2014)

Abstract Background: Cyclin-dependent kinases (CDKs) play a significant role in regulating cell cycle progression through association with cyclins. CDK4 and CDK6 interact with cyclin D1 to mediate hyperphosphorylation of retinoblastoma (Rb) during early G1 phase. Palbociclib is a highly selective inhibitor of CDK4 and CDK6 which functions by blocking pRb phosphorylation resulting in G1 arrest in sensitive cell lines. We evaluated the effect of palbociclib in gastric and colon cancer cell lines to explore potential biomarkers of response and to guide patient selection in colon and gastric cancer. Methods: Panels of 17 gastric and 27 colon cancer cell lines were exposed in vitro to palbociclib over various concentrations to generate dose response curves. Analysis of variance (ANOVA) was used to identify differentially expressed genes between sensitive and resistant cell lines. Genes identified by ANOVA and effects of palbociclib on pRB were analyzed via western blot. Results: Palbociclib was found to have potent anti-proliferative activity in the low nanomolar range (&amp;lt; 150 nM) for 14 of the 44 gastric and colon cancer cell lines tested. In gastric cancer, cyclin D1-amplified cells cells expressed greater sensitivity to the compound when compared to cyclin D1-negative cells. HER2 amplified cell lines were also statistically more sensitive than HER2 negative cells. Combination studies with palbociclib and trastuzumab demonstrated significant synergy in HER2 amplified gastric cancer models. Furthermore, cyclin E emerged as a biomarker for resistance to the compound in gastric cancers. Contrary to observations made in other cancers, expression levels of p16 (CDK4 inhibitor) and p21 (CDK2 inhibitor) in colon cancer indicated that p16 loss and p21 gain predict for resistance rather than sensitivity to CDK4 and CDK6 inhibition. Conclusions: Palbociclib demonstrates anti-proliferative activity in several gastric and colon cancer cell lines. Molecular markers found to predict for sensitivity to this agent enhance patient selection for future clinical studies of palbociclib. Citation Format: Zev A. Wainberg, Ann Yufa, Adrian Anghel, Amy M. Rogers, Tin Manivong, Shahriar Adhami, Habib Hamidi, Dylan Conklin, Richard S. Finn, Dennis J. Slamon. Expression of p16 in colon cancer and cyclin D1 in gastric cancer predicts response to CDK4/6 inhibition in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4557. doi:10.1158/1538-7445.AM2014-4557