tbuckley/cabot-search huggingface dataset:
Activity of XL184 (Cabozantinib), an Oral Tyrosine Kinase Inhibitor, in Patients With Medullary Thyroid Cancer
Authors: Razelle Kurzrock, Steven I. Sherman, Douglas W. Ball, Arlene A. Forastiere, Roger B. Cohen, Ranee Mehra, David G. Pfister, Ezra E.W. Cohen, Linda Janisch, Forlisa Nauling, David S. Hong, Chaan S. Ng, Lei Ye, Robert F. Gagel, John Frye, Thomas Müller, Mark J. Ratain, Ravi Salgia
Journal: Journal of Clinical Oncology (2011)

XL184 (cabozantinib) is a potent inhibitor of MET, vascular endothelial growth factor receptor 2 (VEGFR2), and RET, with robust antiangiogenic, antitumor, and anti-invasive effects in preclinical models. Early observations of clinical benefit in a phase I study of cabozantinib, which included patients with medullary thyroid cancer (MTC), led to expansion of an MTC-enriched cohort, which is the focus of this article.
Self-renewal of thymocytes in the absence of competitive precursor replenishment
Authors: Thomas Boehm
Journal: The Journal of Experimental Medicine (2012)

Soon after transplantation of wild-type thymi into immunodeficient mice lacking functional T cell receptors, productive T cell development in the donor thymus ceases. This observation underlies one of the central dogmas of T cell biology: because thymocytes are seemingly short-lived, intrathymic T cell development depends on continuous import of lymphoid progenitors from the bone marrow. New work reinterprets the outcome of this classical experiment as being the result of competition for intrathymic niches specifically supporting the DN3 stage of early T cell development. Surprisingly, when this niche space is uncontested by immigrating host progenitors, development of T cells in the thymus grafts continues. These new findings suggest that early thymocytes do indeed have substantial self-renewing potential.
Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel.
Authors: A A Wilde, D Escande, C A Schumacher, D Thuringer, M Mestre, J W Fiolet, M J Janse
Journal: Circulation Research (1990)

We investigated the contribution of opening of the ATP-sensitive K+ channel to extracellular accumulation of K+ during ischemia with the use of glibenclamide, a specific blocker of this K+ channel. To characterize the electrophysiological effects of glibenclamide during metabolic inhibition (by either application of dinitrophenol or hypoxia) we performed patch-clamp studies in isolated membrane patches of guinea pig myocytes and in intact guinea pig myocytes and studied action potential parameters in isolated superfused guinea pig papillary muscle. We studied the effect of glibenclamide on extracellular accumulation of K+ and H+ in isolated retrogradely perfused globally ischemic hearts of rat, guinea pig, and rabbit. Experimental evidence is presented that supports the conclusions that glibenclamide 1) effectively blocks open K+ATP channels, 2) reverses the dinitrophenol-induced increase of the outward current and prevents the hypoxia-induced shortening of the action potential, 3) decreases the rate of K+ accumulation during the first minutes of ischemia in stimulated hearts, an effect which was entirely absent in quiescent hearts, and 4) does not influence the rate and extent of ischemia-induced extracellular acidification.
Atherosclerotic plaque rupture – pathologic basis of plaque stability and instability
Authors: A van der Wal
Journal: Cardiovascular Research (1999)

Time for primary reveiw 27 days 

Atherosclerosis continues to be one of the main subjects in pathology research. The intriguing complexity of its pathogenesis as well as the importance of its clinical sequelae provide a rationale for this [1]. A large number of diseases with totally different clinical presentations are basically atherosclerosis related, and among these, myocardial infarction, stroke, abdominal aneurysms and lower limb ischemia determine to a large extent the morbidity and mortality in Western style populations. But, despite this broad spectrum of clinical disease, most of the acute manifestations of atherosclerosis share a common pathogenetic feature: rupture of an atherosclerotic plaque [2–4]. Plaque disruptions may vary greatly in extent from tiny fissures or erosions of the plaque surface to deep intimal tears which extend into the soft lipid core of lesions; in all these instances, at least some degree of thrombus formation occurs [5, 6]. The abdominal aorta is the arterial site most prominently involved in the process of plaque formation, and also of plaque complications. In this large diameter vessel the process of plaque disruption and thrombosis is not ended by luminal occlusion, and may lead to extensive surface ulcerations comprising large areas of the aortic wall, as can be observed in many autopsy cases at older age. Apart from the undisputable role of atherosclerosis in abdominal aneurysm formation [7], mural thrombosis leads to a surprisingly low rate of clinically significant complications in these patients, although cholesterol emboli can be regularly found in their kidneys and skin at autopsy. Still, it is presently unclear what impact the various biologically active mediators released from eroded aortic surfaces may have on the human body.

In contrast, in small diameter vessels such as coronary arteries, occlusive thrombosis is a frequent and often fatal complication of plaque … 

* Corresponding author. Tel.: +31-20-5665-633; fax: +31-20-914-738; e-mail a.c.vanderwal@amc.uva.nl
Plasma EBV DNA Clearance Rate as a Novel Prognostic Marker for Metastatic/Recurrent Nasopharyngeal Carcinoma
Authors: Wen-Yi Wang, Chih-Wen Twu, Hsin-Hong Chen, Jian-Sheng Jan, Rong-San Jiang, Jeffrey Y.C. Chao, Kai-Li Liang, Kuan-Wen Chen, Ching-Te Wu, Jin-Ching Lin
Journal: Clinical Cancer Research (2010)

To investigate the prognostic effect of the concentrations and clearance rates of plasma EBV DNA in metastatic/recurrent nasopharyngeal carcinoma (NPC).Thirty relapsed and four previously nontreated metastatic NPC patients were treated according to the consensus guidelines of the head and neck cancer team in our hospital (i.v. chemotherapy first, followed by local irradiation boost and oral maintenance chemotherapy where applicable). Multiple plasma samples were collected during the first month of chemotherapy. Circulating EBV DNA concentrations were measured by a real-time quantitative PCR. The half-life values (t(1/2)) of plasma EBV DNA clearance were calculated. The associations between clinical outcome and plasma EBV DNA assays were analyzed.Tumor response evaluated after 12 weeks of treatment showed 14 complete responses (41.2%), 12 partial responses (35.3%), 7 stable diseases (20.6%), and 1 progression disease (2.9%). The plasma EBV DNA concentrations have no significant effects on outcome prediction. The t(1/2) of plasma EBV DNA clearance ranged from 1.85 to 28.29 days (median, 3.99). Patients with a short t(1/2) of plasma EBV DNA clearance have significantly higher complete response rate and overall survival than those with long t(1/2). Multivariate analysis revealed a significant effect of the t(1/2) of plasma EBV DNA clearance on survival.The clearance rates of plasma EBV DNA during the first month of chemotherapy can predict tumor response and patient survival. Early change of chemotherapy regimen may be considered for patients with slow plasma EBV DNA clearance rate.
Kidney Side Population Reveals Multilineage Potential and Renal Functional Capacity but also Cellular Heterogeneity
Authors: Grant A. Challen, Ivan Bertoncello, James A. Deane, Sharon D. Ricardo, Melissa H. Little
Journal: Journal of the American Society of Nephrology (2006)

Side population (SP) cells in the adult kidney are proposed to represent a progenitor population. However, the size, origin, phenotype, and potential of the kidney SP has been controversial. In this study, the SP fraction of embryonic and adult kidneys represented 0.1 to 0.2% of the total viable cell population. The immunophenotype and the expression profile of kidney SP cells was distinct from that of bone marrow SP cells, suggesting that they are a resident nonhematopoietic cell population. Affymetrix expression profiling implicated a role for Notch signaling in kidney SP cells and was used to identify markers of kidney SP. Localization by in situ hybridization confirmed a primarily proximal tubule location, supporting the existence of a tubular "niche," but also revealed considerable heterogeneity, including the presence of renal macrophages. Adult kidney SP cells demonstrated multilineage differentiation in vitro, whereas microinjection into mouse metanephroi showed that SP cells had a 3.5- to 13-fold greater potential to contribute to developing kidney than non-SP main population cells. However, although reintroduction of SP cells into an Adriamycin-nephropathy model reduced albuminuria:creatinine ratios, this was without significant tubular integration, suggesting a humoral role for SP cells in renal repair. The heterogeneity of the renal SP highlights the need for further fractionation to distinguish the cellular subpopulations that are responsible for the observed multilineage capacity and transdifferentiative and humoral activities.
Functional Neuroimaging of Major Depressive Disorder: A Meta-Analysis and New Integration of Baseline Activation and Neural Response Data
Authors: J. Paul Hamilton, Amit Etkin, Daniella J. Furman, Maria G. Lemus, Rebecca F. Johnson, Ian H. Gotlib
Journal: American Journal of Psychiatry (2012)

Objective: Functional neuroimaging investigations of major depressive disorder can advance both the neural theory and treatment of this debilitating illness. Inconsistency of neuroimaging findings and the use of region-of-interest approaches have hindered the development of a comprehensive, empirically informed neural model of major depression. In this context, the authors sought to identify reliable anomalies in baseline neural activity and neural response to affective stimuli in major depressive disorder. Method: The authors applied voxel-wise, whole-brain meta-analysis to neuroimaging investigations comparing depressed to healthy comparison groups with respect to baseline neural activity or neural response to positively and/or negatively valenced stimuli. Results: Relative to healthy subjects, those with major depression had reliably higher baseline activity, bilaterally, in the pulvinar nucleus. The analysis of neural response studies using negative stimuli showed greater response in the amygdala, insula, and dorsal anterior cingulate cortex and lower response in the dorsal striatum and dorsolateral prefrontal cortex in individuals with major depressive disorder than in healthy subjects. Conclusions: The meta-analytic results support an elegant and neuroanatomically viable model of the salience of negative information in major depressive disorder. In this proposed model, high baseline pulvinar activity in depression first potentiates responding of the brain's salience network to negative information; next, and owing potentially to low striatal dopamine levels in depression, this viscerally charged information fails to propagate up the cortical-striatal-pallidal-thalamic circuit to the dorsolateral prefrontal cortex for contextual processing and reappraisal.
Effect of Lactobacillus acidophilus Dietary Supplements on 1,2-Dimethylhydrazine Dihydrochloride-Induced Intestinal Cancer in Rats23
Authors: Barry R. Goldin, Sherwood L. Gorbach
Journal: JNCI Journal of the National Cancer Institute (1980)

The epidemiologic patterns of large bowel cancer have implicated a diet high in beef as a risk factor. Another study has shown less colon cancer in Finns than in Danes. Among the possible explanations were the consumption of milk and fermented dairy products and the numbers of lactobacilli in the fecal flora, both of which were higher in the Finns. As a test of these hypotheses, 20 mg 1,2-dimethylhydrazine dihydrochloride/kg body weight was administered for 20 weeks to male inbred F344 rats. Rats consuming a beef diet simulating a “Western” diet had higher rates of colon cancer than did grain-fed rats (83% vs. 31%, respectively). Viable cultures of Lactobacillus acidophilus were fed to rats eating the meat diet; the rats were then challenged with 1,2-dimethylhydrazine dihydrochloride. The colon cancer incidence after a 20-week induction period was lower in the animals receiving the L. acidophilus (40% vs. 77% in controls), but no difference in incidence was discerned after a 36-week period. Thus dietary supplements of L. acidophilus seemed to increase the latency or induction time for experimental colon cancer.
Dose-dense therapy is of benefit in primary treatment of ovarian cancer? In favor
Authors: N. Katsumata
Journal: Annals of Oncology (2011)

Paclitaxel and carboplatin given every 3 weeks is the current standard treatment in first-line chemotherapy regimens for ovarian cancer. The concept of 'dose-dense therapy' is based on the hypothesis that a shortening interval of the doses of cytotoxic agents will be more effective for tumor-cell kill. Recently published phase III trials in breast cancer have shown that dose-dense weekly paclitaxel improves response and survival. The Japanese Gynecologic Oncology Group reported a phase III study comparing the conventional 3-weekly paclitaxel and carboplatin schedule versus dose-dense weekly paclitaxel and 3-weekly carboplatin for advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer. The progression-free survival, as the primary endpoint of this study, was significantly prolonged with the dose-dense treatment [28 versus 17.2 months; hazard ratio (HR): 0.71; 95% confidence interval (CI): 0.58–0.88; P= 0.0015], as was the overall survival at 3 years (72.1% versus 65.1%; HR 0.75; 95% CI: 0.57–0.98; P= 0.03). Dose-dense weekly paclitaxel plus carboplatin represents a new treatment option in women with advanced epithelial ovarian cancer.
Role of Ceramide Synthase in Oxidant Injury to Renal Tubular Epithelial Cells
Authors: NORISHI UEDA, SIMONE M. R. CAMARGO, XIAOMAN HONG, ALEXEI G. BASNAKIAN, PATRICK D. WALKER, SUDHIR V. SHAH
Journal: Journal of the American Society of Nephrology (2001)

Ceramide has been implicated to play an important role in the cell signaling pathway involved in apoptosis. Most studies that have used the apoptotic model of cellular injury have suggested that enhanced ceramide generation is the result of the breakdown of sphingomyelin by sphingomyelinases. However, the role of ceramide synthase in enhanced ceramide generation in response to oxidant stress has not been previously examined in any tissue. Hydrogen peroxide (H(2)O(2)) (1 mM) resulted in a rapid increase in ceramide generation (as measured by in vitro diacylglycerol kinase assay) in LLC-PK1 cells. The intracellular ceramide level was significantly increased at 5 min after exposure of cells to H(2)O(2) and thereafter continuously increased up to 60 min. H(2)O(2) also resulted in a rapid increase (within 5 min) in ceramide synthase activity (as measured by incorporation of [(14)C] from the labeled palmytoyl-CoA into dihydroceramide) in microsomes. In contrast, the exposure of cells to H(2)O(2) did not result in any significant change in sphingomyelin content or acid or neutral sphingomyelinase activity. An increase in ceramide production induced by H(2)O(2) preceded any evidence of DNA damage and cell death. The specific inhibitor of ceramide synthase, fumonisin B1 (50 microM), was able to suppress H(2)O(2)-induced ceramide generation and provided a marked protection against H(2)O(2)-induced DNA strand breaks, DNA fragmentation, and cell death. Taken together, these data provide the first evidence that H(2)O(2) is a regulator of ceramide synthase rather than sphingomyelinases and that ceramide synthase-dependent ceramide generation plays a key role in DNA damage and cell death in oxidant stress to renal tubular epithelial cells.
Lack of Adverse Clopidogrel–Atorvastatin Clinical Interaction From Secondary Analysis of a Randomized, Placebo-Controlled Clopidogrel Trial
Authors: Jacqueline Saw, Steven R. Steinhubl, Peter B. Berger, Dean J. Kereiakes, Victor L. Serebruany, Danielle Brennan, Eric J. Topol
Journal: Circulation (2003)

Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel's metabolism to active metabolite, thus attenuating its inhibition of platelet aggregation ex vivo. However, the clinical impact of this interaction has not been evaluated.Clopidogrel for the Reduction of Events During Observation (CREDO) was a double-blind, placebo-controlled, randomized trial comparing pretreatment (300 mg) and 1-year (75 mg/d) clopidogrel therapy (clopidogrel) with no pretreatment and 1-month clopidogrel therapy (75 mg/d) (control) after a planned percutaneous coronary intervention. All patients received aspirin. The 1-year primary end point was a composite of death, myocardial infarction, and stroke. We performed a post hoc analysis to evaluate the clinical efficacy of concomitant clopidogrel and statin administration, categorizing baseline statin use to those predominantly CYP3A4-metabolized (atorvastatin, lovastatin, simvastatin, and cerivastatin) (CYP3A4-MET) or others (pravastatin and fluvastatin) (non-CYP3A4-MET). Of the 2116 patients enrolled, 1001 received a CYP3A4-MET and 158 a non-CYP3A4-MET statin. For the overall study population, the primary end point was significantly reduced in the clopidogrel group (8.5% versus 11.5%, RRR 26.9%; P=0.025). This clopidogrel benefit was similar with statin use, irrespective of treatment with a CYP3A4-MET (7.6% clopidogrel, 11.8% control, RRR 36.4%, 95% CI 3.9 to 57.9; P=0.03) or non-CYP3A4-MET statin (5.4% clopidogrel, 13.6% control, RRR 60.6%, 95% CI -23.9 to 87.4; P=0.11). Patients given atorvastatin or pravastatin had similar 1-year event rates. Additionally, concomitant therapy with statins had no impact on major or minor bleeding rates.Although ex vivo testing has suggested a potential negative interaction when coadministering a CYP3A4-metabolized statin with clopidogrel, this was not clinically observed statistically in a post hoc analysis of a placebo-controlled study.
Immunomodulatory and antioxidant function of albumin stabilises the endothelium and improves survival in a rodent model of chronic liver failure
Authors: Rita Garcia-Martinez, Fausto Andreola, Gautam Mehta, Katie Poulton, Marc Oria, Maria Jover, Junpei Soeda, Jane Macnaughtan, Francesco De Chiara, Abeba Habtesion, Rajeshwar P. Mookerjee, Nathan Davies, Rajiv Jalan
Journal: Journal of Hepatology (2014)
Users' Guides to the Medical Literature
Authors: Finlay A. McAlister, Andreas Laupacis, George A. Wells, David L. Sackett, None for the Evidence-Based Medicine Working Group
Journal: JAMA (1999)

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
Association of a dominantly inherited hyperphosphorylated paraprotein target with sporadic and familial multiple myeloma and monoclonal gammopathy of undetermined significance: a case–control study
Authors: Sandra Grass, Klaus-Dieter Preuss, Manfred Ahlgrimm, Natalie Fadle, Evi Regitz, Claudia Pfoehler, Niels Murawski, Michael Pfreundschuh
Journal: The Lancet Oncology (2009)
Serum pepsinogen I concentrations in peptic ulcer patients in relation to ulcer location and stage.
Authors: Y Tanaka, K Mine, Y Nakai, N Mishima, T Nakagawa
Journal: Gut (1991)

To investigate the relation of the serum group I pepsinogen (PG I) concentration to the location of gastric ulcers and chronicity of peptic ulcers, ulcer patients (n = 322) were compared with endoscopically normal subjects (n = 174). The mean PG I concentration was significantly higher in male control subjects (n = 90) than in female control subjects (n = 84). In male patients with ulcers in the duodenum (n = 69), antrum (n = 34), or angulus portion (the lower third of the body; n = 83), the mean serum PG I concentration was significantly higher than in the control subjects but in patients with an ulcer in the upper body (n = 49) it was similar to control values. Men with active or healing ulcers (n = 149) showed a significantly higher serum PG I concentration than those with scarred lesions (n = 86) when the abnormality was located in either the upper body or in the angulus portion. For female patients (n = 87), the results were similar. These results suggest that serum PG I concentrations reflect the stages of activity of peptic ulcer.
Lung cancer diagnosis in the emergency department
Authors: Anne-Pascale Meert, Jean-Paul Sculier, Thierry Berghmans
Journal: European Respiratory Journal (2015)

Lung cancer is the leading cause of cancer death worldwide, both in men and women, with an estimated incidence of 1.3 million cases per year. Active, but also passive, smoking represents the main risk factor for developing lung cancer. Smoking also causes other major health complications that could lead the smoker, whether they have cancer or not, to the emergency department (acute exacerbations of chronic obstructive pulmonary disease, acute coronary events, etc. ). Regardless of smoking, cancer patients require emergency visits with high frequency, at equal rates for complications related to the cancer itself (neoplastic involvement of specific organs, cancer-related immunosuppression, etc. ) and its treatment (haematological events, stomatitis, chemotherapy-related vomiting, etc. ), and for cancer-unrelated problems. This setting was summarised in a systematic review including only six prospective series from the 18 selected, which generally were of limited size (median 143 patients) [1]. A few other works have confirmed that lung cancer patients are a major component of those people consulting at the emergency department [2–4]. In a Belgian cancer hospital, we previously noted that 8% of all consultations in this context were lung cancer patients [5]. It was also noted that up to 40% of the patients with lung cancer will present to the emergency department at least once during the course of their disease [5]. Emergency departments must be aware that lung cancer patients are a major component of their population <http://ow.ly/EanYK>