tbuckley/cabot-search huggingface dataset:
Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies
Authors: Fabio Bozzi, Giacomo Manenti, Elena Conca, Silvia Stacchiotti, Antonella Messina, GianPaolo Dagrada, Alessandro Gronchi, Pietro Panizza, Marco A. Pierotti, Elena Tamborini, Silvana Pilotti
Journal: Neuro-Oncology (2013)

Chordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies. In this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor. All 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and posttreatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors. Overall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.
Plasma 25-hydroxyvitamin D, lung function and risk of chronic obstructive pulmonary disease
Authors: Shoaib Afzal, Peter Lange, Stig E Bojesen, Jacob J Freiberg, Børge G Nordestgaard
Journal: Thorax (2013)

<h3>Background</h3> 25-hydroxyvitamin D (25(OH)D) may be associated with lung function through modulation of pulmonary protease-antiprotease imbalance, airway inflammation, lung remodelling and oxidative stress. We examined the association of plasma 25(OH)D levels with lung function, lung function decline and risk of chronic obstructive pulmonary disease (COPD). <h3>Methods</h3> Plasma 25(OH)D was measured in 10 116 participants in the Copenhagen City Heart Study and in 8391 participants in the Copenhagen General Population Study. In the former study, up to three measurements of lung function spanning 20 years allowed analyses of lung function decline. <h3>Results</h3> In both cohorts, forced vital capacity in % of predicted was 7% lower and forced expiratory volume in 1 s in % of predicted was 7–10% lower for lowest versus highest decile of 25(OH)D (p<sub>trend</sub>≤1×10<sup>−28</sup>). In prospective analyses, participants in the lower versus higher 25(OH)D quintiles had a faster decline in forced expiratory volume in 1 s % predicted (p<sub>interaction</sub>=1×10<sup>−7</sup>) and forced vital capacity % predicted (p<sub>interaction</sub>=8×10<sup>−8</sup>). In cross-sectional analyses, multivariable adjusted ORs for COPD were 2.30 (95% CI 1.55 to 3.41) and 3.06 (1.97 to 4.76) for lowest versus highest quintile in the Copenhagen City Heart Study using Global Initiative for Chronic Obstructive Lung Disease (GOLD) and lower limit of normal criteria. The corresponding ORs were 1.82 (1.13 to 2.92) and 2.23 (1.35 to 3.69) in the Copenhagen General Population Study. In prospective analyses, corresponding multivariable adjusted HRs for developing COPD were 1.58 (1.05 to 2.40) and 2.00 (1.19 to 3.36). <h3>Conclusions</h3> We observed a novel association of lower plasma 25(OH)D levels with faster decline in lung function and with a higher risk of COPD in prospective analyses.
Pertussis toxin inhibits neutrophil recruitment to delay antibody-mediated clearance of Bordetella pertussis
Authors: G. S. Kirimanjeswara
Journal: Journal of Clinical Investigation (2005)

Whooping cough is considered a childhood disease, although there is growing evidence that children are infected by adult carriers. Additionally, increasing numbers of vaccinated adults are being diagnosed with Bordetella pertussis disease. Thus it is critical to understand how B. pertussis remains endemic even in highly vaccinated or immune populations. Here we used the mouse model to examine the nature of sterilizing immunity to B. pertussis. Antibodies were necessary to control infection but did not rapidly clear B. pertussis from the lungs. However, antibodies affected B. pertussis after a delay of at least a week by a mechanism that involved neutrophils and Fc receptors, suggesting that neutrophils phagocytose and clear antibody-opsonized bacteria via Fc receptors. B. pertussis blocked migration of neutrophils and inhibited their recruitment to the lungs during the first week of infection by a pertussis toxin-dependent (PTx-dependent) mechanism; a PTx mutant of B. pertussis induced rapid neutrophil recruitment and was rapidly cleared from the lungs by adoptively transferred antibodies. Depletion of neutrophils abrogated the defects of the PTx mutant. Together these results indicate that PTx inhibits neutrophil recruitment, which consequently allows B. pertussis to avoid rapid antibody-mediated clearance and therefore successfully infect immune hosts.
Dose-Dense Anthracycline-Based Chemotherapy for Node-Positive Breast Cancer
Authors: Georgiana K. Ellis, Robert B. Livingston, Julie R. Gralow, Stephanie J. Green, Tove Thompson
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor–negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m 2 . Cyclophosphamide 60 mg/m 2 was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m 2 /wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m 2 /wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with “standard” doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.
Selective IgA deficiency and spondyloarthropathy: a distinct disease?
Authors: G Herrero-Beaumont, J B Armas, J Elswood, R K Will, A Calin
Journal: Annals of the Rheumatic Diseases (1990)

A woman with selective IgA deficiency and severe ankylosing spondylitis (AS), complicated by intractable peripheral arthritis, is described. Three previous cases of selective IgA deficiency and AS have been reported, all of whom had severe AS. It is suggested that selective IgA deficiency is a poor prognostic factor in AS and therefore warrants further investigation to determine the clinical course of such patients.
Gene amplification and protein overexpression of HER-2/neu in human extrahepatic cholangiocarcinoma as detected by chromogenic in situ hybridization and immunohistochemistry: its prognostic implication in node-positive patients
Authors: H.J. Kim, T.W. Yoo, D.I. Park, J.H. Park, Y.K. Cho, C.I. Sohn, W.K. Jeon, B.I. Kim, M.K. Kim, S.W. Chae, J.H. Sohn
Journal: Annals of Oncology (2007)
Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity.
Authors: C E Alford, T E King, P A Campbell
Journal: The Journal of Experimental Medicine (1991)

It is not yet known what properties distinguish macrophages which can kill facultative intracellular bacteria, such as Listeria monocytogenes, from those which cannot. Listeria is an organism which requires iron for growth, yet macrophage listericidal mechanisms are also likely to be iron dependent. We show here that resident peritoneal macrophages and thioglycollate-elicited macrophages cannot kill listeria, but proteose peptone-elicited and FCS-elicited macrophages can. All these cell populations phagocytose listeria. Transferrin receptor expression is low on resident cells, intermediate on peptone- and FCS-elicited cells, and high on thioglycollate-elicited cells. Transferrin transports iron into cells via the transferrin receptor: thus, iron content of resident cells is low, of peptone- and FCS-elicited cells is intermediate, and of thioglycollate-elicited cells is high. Moreover, antibody to transferrin, which prevents it binding its receptor, inhibits listericidal macrophages from killing this bacterium. Finally, nonlistericidal cells with high transferrin receptor expression and high intracellular iron become listericidal if they are incubated with apotransferrin, an iron-free ligand which prevents iron uptake by cells. These data suggest that macrophages must have enough available intracellular iron to support listericidal mechanisms, but too much iron favors growth of the bacterium, which no longer can be killed by the macrophage.
Predictors of therapy resistant asthma: outcome of a systematic evaluation protocol
Authors: L G Heaney
Journal: Thorax (2003)

It has been suggested that asthmatic subjects with persisting symptoms despite adequate maintenance therapy should be systematically evaluated to identify factors contributing to poor control. The aims of this study were to examine the prevalence of these factors in a cohort of sequentially referred poorly controlled asthmatics, and to determine if any factor or combination of factors predicted true therapy resistant asthma (TRA). Patients were evaluated using a systematic evaluation protocol including induced sputum analysis, psychiatric assessment, ear, nose and throat examination, pulmonary function testing, high resolution CT scan of the thorax, and 24 hour dual probe ambulatory oesophageal pH monitoring; any identified provoking factor was treated. Asthma was managed according to BTS guidelines. Of 73 subjects who completed the assessment, 39 responded to intervention and 34 had TRA. Subjects with TRA had a greater period of instability, a higher dose of inhaled steroids at referral, more rescue steroid use, and a lower best percentage forced expiratory volume in 1 second (FEV(1)%). Oesophageal reflux, upper airway disease, and psychiatric morbidity were common (57%, 95%, 49%, respectively) but were not more prevalent in either group. Using multivariate logistic regression analysis, inhaled steroid dose >2000 micro g BDP, previous assessment by a respiratory specialist, and initial FEV(1)% of <70% at referral predicted a final diagnosis of TRA. In poorly controlled asthmatics there is a high prevalence of co-morbidity, identified by detailed systematic assessment, but no difference in prevalence between those who respond to intervention and those with TRA. Targeted treatment of identified co-morbidities has minimal impact on asthma related quality of life in those with therapy resistant disease.
A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma
Authors: Patrick B. Johnston, David J. Inwards, Joseph P. Colgan, Betsy R. Laplant, Brian F. Kabat, Thomas M. Habermann, Ivana N. Micallef, Luis F. Porrata, Stephen M. Ansell, Craig B. Reeder, Vivek Roy, Thomas E. Witzig
Journal: American Journal of Hematology (2010)

Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin lymphoma (HL). The goal of this trial was to learn the antitumor activity and toxicity of everolimus in patients with relapsed/refractory HL. Patients were eligible if they had measurable disease, a platelet count >75,000, and an absolute neutrophil count >1,000. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Response was assessed after two and six cycles and then every three cycles until progression. Patients could remain on drug until progression or toxicity. Nineteen patients were enrolled. Median age was 37 years (range, 27-68). Patients had received a median of six prior therapies (range, 3-14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24-71%) with eight patients achieving a PR and one patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. Patients received a median of seven cycles of therapy. Of the 19 patients, one remains on therapy at 36 months; the others went off study because of progressive disease (16), toxicity (1), and death from infection (1). Four patients experienced a Grade 3 or higher pulmonary toxicity. Everolimus has single-agent activity in relapsed/refractory HL and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant.
Safety, Pharmacokinetics, and Efficacy of AMG 706, an Oral Multikinase Inhibitor, in Patients With Advanced Solid Tumors
Authors: Lee S. Rosen, Razelle Kurzrock, Marilyn Mulay, Andy Van Vugt, Michelle Purdom, Chaan Ng, Jeffrey Silverman, Antonis Koutsoukos, Yu-Nien Sun, Michael B. Bass, Ren Y. Xu, Anthony Polverino, Jeffrey S. Wiezorek, David D. Chang, Robert Benjamin, Roy S. Herbst
Journal: Journal of Clinical Oncology (2007)

AMG 706 is an investigational, orally bioavailable inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and stem-cell factor receptor. This phase I, dose-finding study evaluated the safety, pharmacokinetics, and pharmacodynamics of AMG 706 in patients with refractory advanced solid tumors.AMG 706 was administered at escalating doses of 50 to 175 mg once daily or 25 mg bid for the first 21 days of a 28-day cycle. The 125-mg once-daily dose was also administered continuously. The maximum-tolerated dose (MTD), safety, pharmacokinetics, tumor response, and serum levels of proangiogenic markers were determined.Seventy-one patients received AMG 706. The MTD was 125 mg once daily administered continuously. The most frequent adverse events were fatigue (55%), diarrhea (51%), nausea (44%), and hypertension (42%). Plasma AMG 706 concentrations increased in a dose-proportional manner with no accumulation after multiple doses. Five patients (7%) had a partial response, 35 patients (49%) had stable disease (at least through day 50), and 31 patients (44%) had progressive disease. Changes in tumor size correlated significantly with an increase in placental growth factor (P = .003) and a decrease in soluble kinase domain receptor (P = .001).In this study of patients with advanced refractory solid tumors, AMG 706 was well tolerated and displayed favorable pharmacokinetics and evidence of antitumor activity. Additional studies of AMG 706 as monotherapy and in combination with various agents are ongoing.
The Prenatal Diagnosis of Genetic Disorders
Authors: C J Epstein, M S Golbus
Journal: Annual Review of Medicine (1978)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Preclinical Biomarkers in Alzheimer Disease
Authors: Susan M. Resnick
Journal: JAMA Neurology (2014)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Alteration of Cholesterol Metabolism in the Rat with Linoleic Acid
Authors: JOSEPH M. MERRILL
Journal: Circulation Research (1959)

When linoleic acid is added to the diet of the rat there is an average increase in incorporation of radiocarbon into liver cholesterol of 259 per cent. By contrast, the addition of coconut oil to the diet does not increase the incorporation of radiocarbon into liver cholesterol. The addition of linoleic acid to a stock diet is associated with an increased fecal excretion of Liberman-Burchard chromogens, 3-β-hydroxy sterols and bile acids.
Pathway-Based Identification of Biomarkers for Targeted Therapeutics: Personalized Oncology with PI3K Pathway Inhibitors
Authors: Jannik N. Andersen, Sriram Sathyanarayanan, Alessandra Di Bacco, An Chi, Theresa Zhang, Albert H. Chen, Brian Dolinski, Manfred Kraus, Brian Roberts, William Arthur, Rich A. Klinghoffer, Diana Gargano, Lixia Li, Igor Feldman, Bethany Lynch, John Rush, Ronald C. Hendrickson, Peter Blume-Jensen, Cloud P. Paweletz
Journal: Science Translational Medicine (2010)

Phosphorylation sites on proteins in the phosphatidylinositol 3-kinase pathway that are regulated by candidate drugs can serve as useful biomarkers to predict tumor sensitivity to AKT inhibitors.
STUDIES ON THE MECHANISM OF THE SHWARTZMAN PHENOMENON
Authors: Chandler A. Stetson
Journal: The Journal of Experimental Medicine (1955)

The cutaneous, ophthalmic, and systemic reactions of normal rabbits to Gram-negative bacterial endotoxins have been compared with the classical reactions of bacterial hypersensitivity, and in each case certain similarities have been found. It has also been shown that the Shwartzman phenomenon can be reproduced with tuberculin, in BCG-vaccinated rabbits, and with suspensions or extracts of heat-killed Group A streptococci in rabbits previously sensitized to these bacteria. These considerations suggest the hypothesis that the biologic activity of endotoxins may be based on the existence in "normal" animals of delayed or tuberculin-type hypersensitivity to these materials.
Clinical and Biological Significance of Vascular Endothelial Growth Factor in Endometrial Cancer
Authors: Aparna A. Kamat, William M. Merritt, Donna Coffey, Yvonne G. Lin, Pooja R. Patel, Russell Broaddus, Elizabeth Nugent, Liz Y. Han, Charles N. Landen, Whitney A. Spannuth, Chunhua Lu, Robert L. Coleman, David M. Gershenson, Anil K. Sood
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Vascular endothelial growth factor (VEGF) is critical for angiogenesis and tumor progression; however, its role in endometrial cancer is not fully known. Therefore, we examined the clinical and therapeutic significance of VEGF in endometrial carcinoma using patient samples and an endometrioid orthotopic mouse model. Experimental Design: Following Institutional Review Board approval, VEGF expression and microvessel density (MVD) counts were evaluated using immunohistochemistry in 111 invasive endometrioid endometrial cancers by two independent investigators. Results were correlated with clinicopathologic characteristics. For the animal model, Ishikawa or Hec-1A cancer cell lines were injected directly into the uterine horn. Therapy experiments with bevacizumab alone or in combination with docetaxel were done and samples were analyzed for markers of angiogenesis and proliferation. Results: Of 111 endometrial cancers, high expression of VEGF was seen in 56% of tumors. There was a strong correlation between VEGF expression and MVD (P &amp;lt; 0.001). On multivariate analysis, stage (P = 0.04), grade (P = 0.003), VEGF levels (P = 0.03), and MVD (P = 0.037) were independent predictors of shorter disease-specific survival. In the murine model, whereas docetaxel and bevacizumab alone resulted in 61% to 77% tumor growth inhibition over controls, combination therapy had the greatest efficacy (85-97% inhibition over controls; P &amp;lt; 0.01) in both models. In treated tumors, combination therapy significantly reduced MVD counts (50-70% reduction over controls; P &amp;lt; 0.01) and percent proliferation (39% reduction over controls; P &amp;lt; 0.001). Conclusions: Increased levels of VEGF and angiogenic markers are associated with poor outcome in endometrioid endometrial cancer patients. Using a novel orthotopic model of endometrioid endometrial cancer, we showed that combination of antivascular therapy with docetaxel is highly efficacious and should be considered for future clinical trials.
What Goes Up Must Come Down: The Emerging Spectrum of Inhibitory Receptors
Authors: Wayne M. Yokoyama
Journal: The Journal of Experimental Medicine (1997)

For much of the last few decades, investigators have concentrated on delineating the parameters that involve the direct activation of the immune system. In general, receptor engagement, by antigen, cytokine, or counterreceptor, initiates a cascade of distinct biochemical events in lymphocytes and
Constructivist and ecological approaches in tactual perception
Authors: Edouard Gentaz, Yvette Hatwell, Arlette Streri
Journal: Behavioral and Brain Sciences (2002)

Constructivist and ecological approaches are also observed in tactile perception studies. The question is whether identification and localization are dissociated in the tactile modality as well, and whether Norman's conception may be generalized to the field of touch. An analogue to blindsight was evidenced in passive touch, but no such dissociation was observed in active touch. A study is in progress in this domain.
Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
Authors: Axel Hauschild, Jean-Jacques Grob, Lev V Demidov, Thomas Jouary, Ralf Gutzmer, Michael Millward, Piotr Rutkowski, Christian U Blank, Wilson H Miller, Eckhart Kaempgen, Salvador Martín-Algarra, Boguslawa Karaszewska, Cornelia Mauch, Vanna Chiarion-Sileni, Anne-Marie Martin, Suzanne Swann, Patricia Haney, Beloo Mirakhur, Mary E Guckert, Vicki Goodman, Paul B Chapman
Journal: The Lancet (2012)
The meaning of hominid species – culture as process and product?
Authors: Kate Robson Brown
Journal: Behavioral and Brain Sciences (2000)

One implication of Laland, Odling-Smee &amp; Feldman's niche construction model concerns the significance of the role of behavioural or cultural traits in comparative analysis. In this commentary it is suggested that cladistic methods already recognise this importance, and that behavioural characters may play a key role in hominid speciation and the definition of species.