tbuckley/cabot-search huggingface dataset:
Abstract 3253: A novel small-molecule inhibitor of Stat3 induces antitumor cell effects in human glioma and breast cancer cells.
Authors: Peibin Yue, Sina Haftchenary, Patrick T. Gunning, James Turkson
Journal: Cancer Research (2013)

Abstract Constitutive activation of Stat3, a member of signal transducer and activator of transcription (Stat) family of proteins, occurs with a high frequency in human tumors and contributes to carcinogenesis and tumor progression. Compelling evidence shows aberrant activation of Stat3 constitutes a point of convergence in oncogenic tyrosine kinase signaling, functioning as a master regulator of events crucial for tumorigenesis and malignant progression. We present a series of novel small-molecules that abrogate constitutive activation of Stat3 in human tumors, including glioma and breast cancer. The small-molecule, SH5-07, inhibits in vitro Stat3 DNA-binding activity, with IC50 value of 3.9 μM. Further, treatment with SH5-07 induces dose-dependent inhibition of constitutively-active Stat3 in human glioma U251MG and U373MG and breast cancer MDA-MB-231 cells. Moreover, treatment with low micromolar SH5-07 of U251MG, U373MG, and MDA-MB-231 cells blocks constitutive Stat3 phosphorylation, DNA-binding, and transcriptional activities by as early as 30 minutes. Furthermore, the inhibition of aberrantly-active Stat3 by SH5-07 blocks the anchorage-dependent and independent growth, survival, migration, and invasion in vitro of human glioma and breast cancer cells. Data together indicates SH5-07 is a promising small-molecule Stat3 inhibitor and a suitable drug candidate for clinical development. Citation Format: Peibin Yue, Sina Haftchenary, Patrick T. Gunning, James Turkson. A novel small-molecule inhibitor of Stat3 induces antitumor cell effects in human glioma and breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3253. doi:10.1158/1538-7445.AM2013-3253
Intronic BCL-6 mutations are preferentially targeted to the translocated allele in t(3;14)(q27;q32) non-Hodgkin B-cell lymphoma
Authors: Fabrice Jardin, Christian Bastard, Nathalie Contentin, Françoise Parmentier, Jean-Michel Picquenot, Hervé Tilly, Freda K. Stevenson, Surinder S. Sahota
Journal: Blood (2003)
Rab4 facilitates cyclic adenosine monophosphate-stimulated bile acid uptake and Na+-taurocholate cotransporting polypeptide translocation
Authors: Christopher M. Schonhoff, Krishna Thankey, Cynthia R.L. Webster, Yoshiyuki Wakabayashi, Allan W. Wolkoff, Sawkat M. Anwer
Journal: Hepatology (2008)

Abstract Cyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium-taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was designed to determine the role of Rab4 in cAMP-induced TC uptake and Ntcp translocation. HuH-Ntcp cells transiently transfected with empty vector, guanosine triphosphate (GTP) locked dominant active Rab4 (Rab4(GTP)), or guanosine diphosphate (GDP) locked dominant inactive Rab4 (Rab4(GDP)) were used to study the role of Rab4. Neither Rab4(GTP) nor Rab4(GDP) affected either basal TC uptake or plasma membrane Ntcp level. However, cAMP-induced increases in TC uptake and Ntcp translocation were enhanced by Rab4(GTP) and inhibited by Rab4(GDP). In addition, cAMP increased GTP binding to endogenous Rab4 in a time-dependent, but phosphoinositide-3-kinase–independent manner. Conclusion: Taken together, these results suggest that cAMP-mediated phosphoinositide-3-kinase–independent activation of Rab4 facilitates Ntcp translocation in HuH-Ntcp cells. (Hepatology 2008.)
Heart Failure Performance Measures and Outcomes
Authors: Gregg C. Fonarow, Eric D. Peterson
Journal: JAMA (2009)

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
Candidate Genes Associated with Tumor Regression Mediated by Intratumoral Il-12 Electroporation Gene Therapy
Authors: Shulin Li, Xueqing Xia, Francesca M Mellieon, Jianguo Liu, Stacy Steele
Journal: Molecular Therapy (2004)

<h2>Abstract</h2> Interleukin-12 (IL-12) is one of the most effective cytokines for treating malignancy. Intratumoral delivery of the murine <i>Il-12</i> gene, using electroporation, has been found effective in inducing regression of established tumors in mice, and more effective than intramuscular injection of this gene by electroporation, but what is not known is the molecular mechanism by which IL-12 exerts an antitumor effect. To define these candidate genes, the gene expression profiles of tumors treated with and without intratumoral <i>Il-12</i> electroporation gene therapy were analyzed by cDNA array. <i>Mig</i> (<i>Cxcl9</i>), <i>Stat1</i>, and <i>IRF7</i> are the three genes that are the most altered at the level of expression after administration of <i>Il-12</i> via intratumoral electroporation, when subjected to further characterization by Northern blot, Western blot, and immunostaining. The results from Northern blot and immunostaining analyses indicate that intratumoral delivery of the murine <i>Il-12</i> gene via electroporation induces accumulation of IRF7 in the nuclei of tumor cells and upregulates <i>Mig</i> and <i>Stat1</i> expression by 15- and 5-fold, respectively, compared to intratumoral electroporation of control plasmid DNA. Intramuscular injection of the same <i>Il-12</i> gene using electroporation upregulates <i>Mig</i> and <i>Stat1</i> by only 6- and 2.9-fold, respectively, but does not induce any IRF7 accumulation in the nuclei. Further functional analyses of Mig indicate that expression in tumors can induce CD4<sup>+</sup> but not CD8<sup>+</sup> T cell infiltration. Further functional analysis of Stat1 indicates that a lack of <i>Stat1</i> expression inhibits the Il-12-mediated induction of <i>IP10,</i> a known antiangiogenic gene. These data suggest that these three genes may positively correlate with the antitumor efficacy of intratumoral <i>Il-12</i> electroporation gene therapy.
Myocardial Rupture and Hemopericardium Associated with Anticoagulant Therapy
Authors: Barzillia R. Waldron, Robert H. Fennell, Benjamin Castleman, Edward F. Bland
Journal: New England Journal of Medicine (1954)

A DISTURBING feature of the occasional case of fatal hemopericardium following anticoagulant therapy for myocardial infarction is the absence of an obvious explanation for the hemorrhage. Heretofore, a pericardium distended with blood in a patient with myocardial infarction has usually been the result of a ruptured myocardium. However, Hammarsten1 reported in 1949 a case with massive hemopericardium that followed Dicumarol treatment in which low levels of prothrombin activity (10 per cent or less) were obtained; 800 cc. of blood was found in the pericardium and yet no rupture of the heart or a vessel could be demonstrated. Nichol,2 Goldstein and . . .
Coronary Thrombolysis— It's Worth the Risk
Authors: Alan J. Tiefenbrunn, Philip A. Ludbrook
Journal: JAMA (1989)

ALTHOUGH the concept of coronary thrombolysis for the treatment of acute evolving myocardial infarction has been extant for over three decades,<sup>1</sup>it is only in the last few years that profound benefits have been consistently documented in large numbers of patients, reflected by improved left ventricular function,<sup>2-5</sup>decreased incidence and severity of congestive heart failure,<sup>5</sup>decreased incidence of late fatal arrhythmias,<sup>6</sup>and improved short-<sup>7-10</sup>and long-term<sup>11,12</sup>mortality. However, as with any medical or surgical treatment, pharmacologic activation of the fibrinolytic system entails a risk—in its case, the primary risk being that of bleeding. This risk is not a "side effect" but a direct consequence of the desired action when lytic agents are administered, ie, fibrin degradation and clot dissolution. Unfortunately, plasmin activation cannot be confined presently to pathological deposits of fibrin, and protective thrombi also will be disrupted. Nevertheless, spontaneous bleeding (gastrointestinal, genitourinary, retroperitoneal,
Letter: Reversible infertility in male coeliac patients.
Authors: G Foss
Journal: BMJ (1975)

Drug-precipitated Acute Attacks of Gout SIR,-Though there has been little discussion about drug precipitation of acute atitacks of gout, it is known that diureftics such as hydrochlorothiazide, ethacrynic acid, and frusemide indiuce hyperuricaemia and thus precipitate acute attacks.'Among the other drugs implicated are pyrazinamide, niacin, pempidine, alcohol, mecamylamine, and salicylates if the dose is less than 4 g per day.2It would be of interest, therefore, to add a little to ,this list, seeing that the incidence of gout in Asians is much higher than was formerly thought.2
Doctors will be asked to help identify people at risk of becoming terrorists
Authors: C. Dyer
Journal: BMJ (2011)

Doctors and other health professionals are to be asked to help identify people who are at risk of being drawn into violent extremism as a part of an updated strategy to combat terrorism unveiled by the home secretary, Theresa May.

The document outlining the revised “Prevent” strategy, which applies mainly to England, says that the Department of Health will need to ensure that the “crucial relationship of trust and confidence between patient and clinician” is balanced with the healthcare worker’s duty to protect the wider public safety.

But the BMA said it had …
THE ADVANTAGES OF NITROUS OXIDE INHALATION IN PSYCHIATRIC TREATMENT
Authors: H. LEHMANN, C. BOS
Journal: American Journal of Psychiatry (1947)

1. Previously described methods of inhalation anæsthesia and hypoxia in psychiatric conditions have been reviewed. 2. A technique of nitrous oxide administration beyond the state of intoxication and avoiding the Stage of deep hypoxemia has been described. 3. Physiological changes with this form of anæsthesia are slight and the method may be considered safe. 4. After the anæsthesia, a period of facilitation of mental processes is observed, which is followed by a period of relaxation and sedation. 5. During the phase of facilitation, the patient has a feeling of increased well-being and shows greater spontaneity, less resistance, and enhanced insight, often expressing previously repressed ideational content and affects. 6. The period of sedation lasts for several hours and is not associated with drowsiness or confusion. Sleep is usually improved the following night and other sedation is often unnecessary. 7. In states of acute manic excitement, repeated daily administration of nitrous oxide has controlled and terminated the attack in some cases. 8. Nitrous oxide hypoxia produces some of the features of the "shock treatments" as well as of narcoanalysis, but it is safe, convenient, and simple in administration and may be used in ambulatory patients without interruption of their ordinary activities. 9. The theories on the pharmacological action of nitrous oxide and the reason for its choice are discussed.
Assessing the Safety of Adjuvanted Vaccines
Authors: S. Sohail Ahmed, Stanley A. Plotkin, Steven Black, Robert L. Coffman
Journal: Science Translational Medicine (2011)

Despite the very low risk-to-benefit ratio of vaccines, fear of negative side effects has discouraged many people from getting vaccinated, resulting in reemergence of previously controlled diseases such as measles, pertussis, and diphtheria. Part of this fear stems from the lack of public awareness of the many preclinical and clinical safety evaluations that vaccines must undergo before they are available to the general public, as well as from misperceptions of what adjuvants are or why they are used in vaccines. The resultant "black box" leads to a preoccupation with rare side effects (such as autoimmune diseases) that are speculated, but not proven, to be linked to some vaccinations. The focus of this review article is to open this black box and provide a conceptual framework for how vaccine safety is traditionally assessed. We discuss the strengths and shortcomings of tools that can be and are used preclinically (in animal studies), translationally (in biomarker studies with human sera or cells), statistically (for disease epidemiology), and clinically (in the design of human trials) to help ascertain the risk of the infrequent and delayed adverse events that arise in relation to adjuvanted vaccine administration.
Not just the powerhouse of the cell: emerging roles for mitochondria in the heart
Authors: D. J. Hausenloy, M. Ruiz-Meana
Journal: Cardiovascular Research (2010)

This editorial refers to the following articles in this issue which are part of the Review Focus on Mitochondria in Cardiac Disease: Emerging Concepts and Novel Therapeutic Targets: T. Miura et al .3, pp. 7–15; D. Hausenloy et al .4, pp. 67–74; S.-B. Ong and D. Hausenloy6, pp. 16–29; M. Ruiz-Meana et al .7, pp. 30–39; S.L. Hanninen et al .8, pp. 75–82; M.G. Rosca and C.L. Hoppel10, pp. 40–50; C.-H. Chen et al .13, pp. 51–57; S.M. Davidson14, pp. 58–66. It also refers to the following articles in the next issue (Vol. 88, Issue 2): M. Gucek and E. Murphy2; S. Cadenas et al .5; H. Bugger and E.D. Abel9; D.A. Brown and B. O'Rourke11; V.B. Pillai et al .12 

Mitochondria make up 30% of the volume of a single cardiomyocyte, underlining the importance of their conventional role as the ATP-producing ‘powerhouse’ of the cell. However, it is clear that this complex organelle plays a variety of roles within the cardiomyocyte that extend beyond its established function as the cellular powerhouse. In this regard, the most significant discovery was its critical role as an arbitrator of cell death1 in addition to its function in cellular survival. This review focus highlights several novel and emerging roles for mitochondria in the heart that may provide an opportunity for the identification and development and of new therapeutic strategies for the treatment of cardiac disease.

Several of the reviews contained in this spotlight issue explore the role of mitochondria as targets for cardioprotection, i.e. protecting the heart against the detrimental effects of acute ischaemia–reperfusion injury (IRI). It is well established that mitochondrial dysfunction lies …
The Learning-Disabled or Hyperactive Child-Reply
Authors: Stephen Sulzbacher
Journal: JAMA (1976)

<h3>In Reply.—</h3> I appreciate Dr Ament's critique of my approach to the hyperactive or learning-disabled child. How to diagnose and treat this syndrome complex is indeed a controversial subject because we still don't know enough about the brain to fully understand these children and their handicaps. It remains for the reader to choose the treatment strategies with which he or she is most comfortable, in the absence of really definitive data. I agree with Dr Ament that these learning and behavior disorders do have a neurological basis, but the neurochemical models to explain the malfunctions are still speculative. Treatment with stimulant medication is symptomatic, even when dramatically effective. I'm somewhat embarrassed to admit that most of the 7-and 8-year-olds to whom I proudly pointed in the late 1960s as having been successfully treated with medication alone are now back to haunt me as socially maladaptive and painfully unhappy adolescents. By
Lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury
Authors: Jing Ji, Anthony E Kline, Andrew Amoscato, Alejandro K Samhan-Arias, Louis J Sparvero, Vladimir A Tyurin, Yulia Y Tyurina, Bruno Fink, Mioara D Manole, Ava M Puccio, David O Okonkwo, Jeffrey P Cheng, Henry Alexander, Robert S B Clark, Patrick M Kochanek, Peter Wipf, Valerian E Kagan, Hülya Bayır
Journal: Nature Neuroscience (2012)
Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30
Authors: Ezogelin Oflazoglu, Ivan J. Stone, Kristine A. Gordon, Iqbal S. Grewal, Nico van Rooijen, Che-Leung Law, Hans-Peter Gerber
Journal: Blood (2007)

Increased expression of CD30 is associated with a variety of hematologic malignancies, including Hodgkin disease (HD) and anaplastic large cell lymphoma (ALCL). The anti-CD30 monoclonal antibody SGN-30 induces direct antitumor activity by promoting growth arrest and DNA fragmentation of CD30+ tumor cells. In this study, we investigated the contributions of Fc-mediated effector cell functions to SGN-30 activity. We determined that antibody-dependent cellular phagocytosis, mediated by macrophages, to contribute significantly to antitumor activity in vitro. To delineate the identity of the host effector cells involved in mediating antitumor activity in vivo, we studied the effects of effector cell ablation in a disseminated model of HD (L540cy). Depletion of macrophages markedly reduced efficacy of SGN-30, demonstrating that macrophages contribute significantly to SGN-30 efficacy in this model. These findings may have implications for patient stratification or combination treatment strategies in clinical trials conducted with SGN-30 in HD and ALCL.
MITRAL STENOSIS AS REVEALED BY THE ROENTGENOGRAM AND THE ELECTROCARDIOGRAM
Authors: Louis Faugeres Bishop
Journal: JAMA (1923)

The roentgenogram of the heart, taken with the tube 6 feet behind the chest, shows the left border so straight that it is almost like a line drawn with a ruler. This straight sided heart is due, of course, to the relatively poor development of the ventricle and the large auricle. It is very typical of mitral stenosis. The electrocardiogram shows a right predominance. The primary activity of the ventricle is down in the first lead and up in the third. The wave representing the auricle is atypical in shape, consisting of two summits instead of one. This particular person had a loud presystolic murmur, but many times the murmur is obscure, and findings such as these make the diagnosis of mitral stenosis easy. Any one who has lived in the pretechnical days of cardiology can recall the acrimonious controversy that arose as to the existence or nonexistence of mitral
Treating Tobacco Addiction — Nicotine or No Nicotine?
Authors: Neal L. Benowitz
Journal: New England Journal of Medicine (1997)

Nicotine has been the mainstay of pharmacotherapy for tobacco addiction, but other medications, such as the antidepressant drugs bupropion and nortriptyline, are also effective. These antidepressant agents are effective in patients without current depression. Identifying the mechanism by which such drugs help someone quit may increase our understanding of nicotine addiction. The availability of medications that do not contain nicotine provides physicians and other health care workers with new choices and decisions on the optimal approach to smoking cessation in their practices.The results of the first large clinical trial of bupropion as an aid to smoking cessation appear in . . .
Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate
Authors: J.J. Goedert, C.S. Rabkin, A.R. Cohen, C.M. Kessler, S. Eichinger, S.V. Seremetis, L.M. Aledort, F.J. Yellin, P.S. Rosenberg
Journal: The Lancet (1994)
Independent associations of alanine aminotransferase (ALT) levels with cardiovascular risk factor clustering in Chinese adolescents
Authors: Alice P.S. Kong, Kai Chow Choi, Clive S. Cockram, Chung Shun Ho, Michael H.M. Chan, Risa Ozaki, Gary W.K. Wong, Gary T.C. Ko, Wing Yee So, Peter C.Y. Tong, Christopher W.K. Lam, Joseph T.F. Lau, Francis C.C. Chow, Juliana C.N. Chan
Journal: Journal of Hepatology (2008)
Accumulation of Technetium-99m MDP in Distended Ureter
Authors: I GARTY, M TANZMAN, S REINER
Journal: Clinical Nuclear Medicine (1985)

A 17-year-old boy with persistent complaint of left low back pain and normal x-ray survey of lumbar and sacral vertebrae was further investigated by Tc-99m MDP blood pool and bone scintigraphies. Both latter studies showed increased activity of the tracer in the right lower pelvis. While this finding was initially suspected for hyperemic osteoblastic activity in ischium, it was later proved to represent accumulation of the radiopharmaceutical in distended left ureter.
Flt3 ligand therapy for recipients of allogeneic bone marrow transplants expands host CD8α+ dendritic cells and reduces experimental acute graft-versus-host disease
Authors: Takanori Teshima, Pavan Reddy, Kathleen P. Lowler, Mark A. KuKuruga, Chen Liu, Kenneth R. Cooke, James L. M. Ferrara
Journal: Blood (2002)