tbuckley/cabot-search huggingface dataset:
Abstract IA14: Imaging tumor metabolism with hyperpolarized 13C-labeled cell substrates
Authors: Kevin M. Brindle
Journal: Cancer Research (2017)

Abstract Molecular imaging can play an important role in predicting and detecting tumor responses to treatment and thus in guiding treatment in individual patients [1]. Nuclear spin hyperpolarization can increase sensitivity in the magnetic resonance experiment by &amp;gt;10,000x. This has allowed imaging of injected hyperpolarized 13C labelled cell substrates in vivo and, more importantly, their metabolic conversion into other metabolites. We have been using this metabolic imaging technique both to detect treatment response and to investigate the tumor microenvironment. A recent perspective on this field of research is given in [2]. Exchange of hyperpolarized 13C label between lactate and pyruvate and net flux of label between glucose and lactate have been shown to decrease post-treatment and hyperpolarized [1,4-13C]fumarate has been shown to detect subsequent cell necrosis. Tumor pH can be imaged using hyperpolarized H13CO3- and redox state can be determined by monitoring the oxidation and reduction of [1-13C]ascorbate and [1-13C]dehydroascorbate respectively. In this talk I will discuss more recent work in which we have used hyperpolarized [1-13C]pyruvate to investigate metabolism in PDX models of glioblastoma. These measurements have shown significant heterogeneity between tumors derived from different patients, which we believe is related to underlying oncogenic mutations. I will also show how hyperpolarized [1-13C]pyruvate can be used to follow the progression of pancreatic precursor lesions, in a genetically engineered mouse model of the disease, which potentially could be used clinically to guide earlier intervention [3]. Finally I will discuss how we have used hyperpolarized [U-2H, U-13C]glucose [4] to investigate flux in the pentose phosphate pathway (PPP) and the relationship between PPP flux and the rate of reduction of hyperpolarized [1-13C]dehydroascorbate. Metabolic imaging with hyperpolarized 13C-labelled cell substrates has recently translated to the clinic with a study in prostate cancer [5] and we have conducted our first clinical study in Cambridge using this technique earlier this year. 1. Brindle, K. Nature Rev Cancer 8, 94-107 (2008). 2. Brindle, K.M. J. Amer. Chem. Soc. 137, 6418-6427 (2015). 3. Serrao, E.M., et al. Gut 65, 465-475 (2016). 4. Rodrigues, T.B., et al. Nat Med 20, 93-97 (2014). 5. Nelson, S.J., et al. Science Translational Medicine 5, 198ra108 (2013). Citation Format: Kevin M. Brindle. Imaging tumor metabolism with hyperpolarized 13C-labeled cell substrates. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA14.
Hepatitis B virus X protein-mediated MDR1 activation: Potential role of C/EBP-beta activation
Authors: Chang Yup Han, Hyo-Kyung Han, Keon Wook Kang
Journal: Cancer Research (2007)

2289  Hepatitis B virus infections play an important role in the development of chronic liver diseases including hepatocellular carcinoma. The transition from chemotherapy-responsive cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multidrug resistance 1 (MDR1, p-glycoprotein). This study found that HBx increases the transcriptional activity and protein level of MDR1 in a rat hepatoma cell line, H4IIE. Moreover, the cells overexpressing HBx was more resistant to verapamil-uptake than the control H4IIE cells. Immunoblot analysis using subcellular fractions revealed that HBx caused the nuclear translocation of C/EBPβ. However, the pregenane X-receptor, p53 and Y-box binding protein-1 were not activated by HBx overexpression. Reporter gene analyses showed that HBx increased the activity of the luciferase reporter gene in the cells transfected with the luciferase reporter containing MDR1 gene promoter. Moreover, C/EBPβ overexpression also significantly increased the luciferase reporter gene activity. These results imply that HBx increases the MDR1 transporter activity through the transcriptional activation of the MDR1 gene with C/EBPβ activation being involved in this process.
CLL Cells Can Diversify, Switch, and Differentiate in Response to Autologous T Cell Stimuli Present in a Murine Adoptive Transfer Model
Authors: Piers E.M. Patten, Shih-Shih Chen, Davide Bagnara, Rita Simone, Sonia Marsilio, Xiao-Jie Yan, Jacqueline C. Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai, Thomas MacCarthy, Charles C. Chu, Nicholas Chiorazzi
Journal: Blood (2012)
Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care
Authors: David S. Channin
Journal: Annals of Internal Medicine (2017)

Letters7 March 2017Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient CareDavid S. Channin, MDDavid S. Channin, MDFrom Insightful Medical Informatics, Vestal, New York.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0625 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Detsky and Gropper's commentary (1) with great interest and would like to present a counterargument. There is, perhaps, consensus that—within the department—researchers, section chiefs, chairs, and others in administrative roles will participate in clinical practice. I also stipulate that some participation in professional societies, national committees, and other organizations is of recognized value but expected to be incorporated into the rubric of “other duties as assigned,” with limited allocation of additional resources or time. Certain higher positions within those organizations might come with the expectation of limited clinical practice during the term of office but ...Reference1. Detsky AS, Gropper MA. Why physician leaders of health care organizations should participate in direct patient care. Ann Intern Med. 2016;165:519-20. [PMID: 27399305]. doi:10.7326/M16-0820 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Insightful Medical Informatics, Vestal, New York.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L16-0625. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoWhy Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care Allan S. Detsky and Michael A. Gropper Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care Richard Rohr Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care Allan S. Detsky and Michael A. Gropper Metrics 7 March 2017Volume 166, Issue 5Page: 376KeywordsConflicts of interestDisclosureEmotionsGamesHealth careMotivationPatientsScars ePublished: 7 March 2017 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abnormal 18F-FDG and 82Rb PET Findings in Chagas Heart Disease
Authors: Medhi S. Salimy, Purvi J. Parwani, Kanae Mukai, Miguel Hernandez Pampaloni, Robert R. Flavell
Journal: Clinical Nuclear Medicine (2017)

Uptake of the radiopharmaceutical F-FDG visualized by PET imaging can reflect abnormal myocardial inflammation. When utilized in conjunction with other imaging modalities, such as echocardiography, PET F-FDG imaging can help distinguish between active cardiac sarcoidosis and other etiologies of nonischemic cardiomyopathy. We present a case of a 46-year-old man with nonischemic cardiomyopathy and ventricular tachycardia who underwent an echocardiogram suggestive of cardiac Chagas disease. A subsequent F-FDG PET demonstrated abnormal hypermetabolism. The diagnosis was confirmed by positive serologic examination results.
Distribution and Quantity of Sites of John Cunningham Virus Persistence in Immunologically Healthy Patients
Authors: Joseph R. Berger, Craig S. Miller, Robert J. Danaher, Kathryn Doyle, Kenneth J. Simon, Elizabeth Norton, Leonid Gorelik, Ellen Cahir-McFarland, Divya Singhal, Nawaz Hack, Joseph Ryan Owens, Peter T. Nelson, Janna H. Neltner
Journal: JAMA Neurology (2017)

<h3>Importance</h3> Although seroepidemiological studies indicate that greater than 50% of the population has been infected with John Cunningham virus (JCV), the sites of JCV persistence remain incompletely characterized. <h3>Objective</h3> To determine sites of JCV persistence in immunologically healthy individuals. <h3>Design, Setting, and Participants</h3> Tissue specimens from multiple sites including brain, renal, and nonrenal tissues were obtained at autopsy performed in the Department of Pathology at the University of Kentucky from 12 immunologically healthy patients between February 9, 2011, and November 27, 2012. Quantitative polymerase chain reaction was performed on the tissue specimens and urine. Serum JCV antibody status was determined by enzyme-linked immunosorbent assay. <h3>Main Outcomes and Measures</h3> The detection and quantification of JCV from the tissues by quantitative polymerase chain reaction illuminated sites of viral persistence. These results were correlated with JCV antibody levels. <h3>Results</h3> Autopsies were performed on 12 individuals, 10 men and 2 women, ranging in age from 25 to 75 years (mean, 55.3 years). Seven of 12 individuals were JCV antibody seropositive based on absorbance units. Serostatus was associated with amounts of JCV DNA in urine and its tissue distribution. John Cunningham virus DNA was found in 75% of genitourinary tissue samples from donors (18 of 24) with high JCV antibody levels, 13.3% of donors with low levels i(4 of 30), and 0% of seronegative persons (0 of 32). In nongenitourinary tissues, JCV DNA was detected in 45.1% of tissue samples of donors (32 of 71) with high JCV, 2.2% of donors with low JCV serostatus (2 of 93), and 0% of seronegative persons (0 of 43). Genitourinary tissues had higher copy numbers than other sites. John Cunningham virus DNA was detected in urine of seronegative individuals in a research-grade assay. <h3>Conclusions and Relevance</h3> Persistent (latent or actively replicating) JCV infection mostly predominates in genitourinary tissues but distributes in other tissues at low copy number. The distribution and copy numbers of the virus appear to correlate with urinary JCV shedding and serostatus.
Diagnosing idiopathic pulmonary fibrosis without a lung biopsy: honeycombing not required
Authors: Robert Homer, David J Lederer
Journal: Thorax (2017)

Nearly 50 years ago, idiopathic interstitial pneumonias (IIPs) were defined by Liebow and Carrington based on the histological pattern present in the lung.1 ,2 Today, we consider histological patterns in the context of clinical and radiological information in order to diagnose a specific IIP, a paradigm shift initially introduced by a Consensus Statement published by the American Thoracic Society and European Respiratory Society in 2002 and developed further in 2011.3 With regard to idiopathic pulmonary fibrosis (IPF), this approach requires the presence of a usual interstitial pneumonia pattern (UIP), either on high resolution CT (HRCT) or histology or both, and the absence of any clinical history or morphological pattern that suggests another aetiology or another disease. The most recent iteration also introduced two new and related features. The first was a formal recognition that even in cases in which a biopsy was obtained, radiology had a role in modifying the interpretation of the pathological findings. In some cases, this meant that a definitive pathological diagnosis of IPF, once considered the gold standard, could be overridden by a negative radiological impression. In other cases, a diagnosis of IPF could be made even in the absence of definitive pathological evidence. The second major change was to introduce a multidisciplinary consensus conference as the mechanism for implementing the integration of pathology, radiology and clinical findings, such as in those cases just described in which there was substantial disagreement between pathology and radiology or those in which both evaluations were inconclusive. In many cases, however, pathology is still the definitive study especially in cases in which the …
PPARγ Agonists Inhibit Adhesion Signal to Endothelial Cells in the Differentiation Induction of HL-60 Acute Promyelocytic Leukemia Cells
Authors: Jinny Park, JiWon Yoon, Hong-Nu Yu, Eun-Mi Noh, On-Yoo Hong, Jong-Suk Kim
Journal: Blood (2016)
Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials
Authors: Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Alden Moccia, Jana Markova, Julia Meissner, Andrea Kerkhoff, Wolf-Dieter Ludwig, Michael Fuchs, Peter Borchmann, Andreas Engert
Journal: Journal of Clinical Oncology (2017)

Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared with early relapses.
Low Rates of CNS Relapse in High Risk DLBCL Patients Treated with R-CODOX-M and R-IVAC: Results from a Phase 2 UK NCRI/Bloodwise Trial
Authors: Elizabeth H Phillips, Amy A Kirkwood, Anthony Lawrie, Simon Rule, Russell Patmore, Ruth Pettengell, Cathy H Burton, Kirit M Ardeshna, Silvia Montoto, Shankaranarayana Paneesha, Paul Smith, Katharina Wanek, Laura Clifton-Hadley, David C. Linch, Andrew McMillan
Journal: Blood (2016)
Biological therapies in nonsmall cell lung cancer
Authors: Jon Zugazagoitia, Sonia Molina-Pinelo, Fernando Lopez-Rios, Luis Paz-Ares
Journal: European Respiratory Journal (2017)

Biological therapies have improved survival outcomes of advanced-stage nonsmall cell lung cancer (NSCLC). Genotype-directed therapies have changed treatment paradigms of patients with EGFR -mutant and ALK/ROS1 -rearranged lung adenocarcinomas, and the list of druggable targets with demonstrated clinical actionability ( BRAF, MET, RET, NTRK1 and HER2 ) continues to expand. Furthermore, we have incrementally understood the mechanisms of cancer immune evasion and foresee ways to effectively circumvent them, particularly at the immune checkpoint level. Drugs targeting the tumour immune-evasive PD-1 pathway have demonstrated remarkable treatment benefits in this disease, with a non-negligible fraction of patients potentially receiving long-term survival benefits. Herein, we briefly discuss the role of various medical disciplines in the management of advanced-stage NSCLC and review the most relevant biological therapies for this disease, with particular emphasis in genotype-directed therapies and immune checkpoint inhibitors.
Reply to Hao Lun Luo, Yen Ta Chen, Yuan Tso Cheng, and Po Hui Chiang's Letter to the Editor re: Re: Thomas Seisen, Benoit Peyronnet, Jose Luis Dominguez-Escrig, et al. Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel. Eur Urol 2016;70:1052–68
Authors: Thomas Seisen, Marko Babjuk, Morgan Rouprêt
Journal: European Urology (2016)
Automated squeeze test (Gaenslen’s manoeuvre) to identify patients with arthralgia suspicious for progression to RA: improving time delay to rheumatology consultation
Authors: David Vega-Morales, Jorge A Esquivel-Valerio, Ana C Arana-Guajardo
Journal: Annals of the Rheumatic Diseases (2017)

Automated squeeze test (Gaenslen's manoeuvre) to identify patients with arthralgia suspicious for progression to RA: improving time delay to rheumatology consultationWe read with interest the article by van Steenbergen et al 1 and the response by Mankia et al. 2 In the former, a definition of suspicious arthralgia was proposed and in the latter a new approach to identifying individuals at risk of progression to rheumatoid arthritis (RA) was discussed.We agree with Mankia et al that general practitioners (GPs) are the first contact for those patients at risk.In other countries a delay in referring patients with RA has been seen, and we have similarly detected a delay of 28.2 (SD 46.9) months. 3Thus, we are interested in clinical signs that allow GPs to identify patients with arthralgia suspicious for progression to RA-particularly, use of the squeeze test (ST) (also known as Gaenslen's compression test). 4Previously, we found that the ST was useful in identifying RA progression in patients with undifferentiated arthritis in a year of follow-up. 5ecause of the importance of physical examination and also medical education, we devised a study protocol.In the first phase, we noted the variations in the ST results by certified rheumatologists, and found important differences. 6This supports the observations of van Steenbergen et al 7 about the importance of clinical expertise and its reliability for diagnosing patients with arthritis.In the second phase, having found differences in performance of the test, we constructed an automated device to evaluate the ST performance.We carried out a study in patients with established RA and in healthy individuals.The median squeeze force necessary to evoke pain in the RA group was 3.07 (IQR 2.4) kg and 2.78 (IQR 3.8) kg in the right and left hand, respectively; and in the healthy group these values were 4.2 (IQR 9.5) kg and 4.6 (9.7) kg. 8 Mankia et al, in their study, 2 sought to reduce the impact of clinical inexperience by using the anti-cyclic citrullinated peptide test for the detection of individuals at risk of RA.However, the cost-benefit of this test is controversial and several causes contribute to the dearth of such specialised studies-for example, inadequate clinical expertise of the first contact physician, inadequate number of rheumatologists in a given population, long waiting times for evaluation or even economic factors.The automated test could reduce this gap.The force of the ST which is applied to distinguish between a healthy individual, and a patient with active disease is already established.The strength of the squeeze needed to screen the patient with arthralgia which it is suspected will progress to RA is in the process of determination.The objective of all investigations is to develop an easy to use, cheap tool that can identify RA in patients at an early stage.
Silencing c-Myc Using Myc Inhibitor JQ1 and EZH2 Inhibitor DZNep Blocks Converging Survival Signals in Aggressive B-Cell Lymphomas
Authors: Xiaohong Zhao, Tint Lwin, Xinwei Zhang, Andy Huang, Jian Wang, Victor E. Marquez, Selina Chen-Kiang, James E Bradner, William S. Dalton, Eduardo M. Sotomayor, Jianguo Tao
Journal: Blood (2012)
The Value of Beta2 Microglobulin, Retinol Binding Protein, Endothelin-1, N Amino ß-d-Glucoaminodase and Cystatin C for the Evaluation Sickle Cell Nephropathy
Authors: Selma Unal, Caglar Kotan, Ali Delibas, Ali Ertug Arslankoylu
Journal: Blood (2010)
Dermatology Life Quality Index (DLQI) as a psoriasis referral triage tool
Authors: A. Atwan, V. Piguet, A.Y. Finlay, N.A. Francis, J.R. Ingram
Journal: British Journal of Dermatology (2017)

e d fo r p u blic a tio n.Cit a tio n fo r fin al p u blis h e d ve r sio n: Atw a n, Aus a m a , Pi g u e t, Vinc e n t, Fi nl ay, And r e w Y. , F r a n ci s, Ni c h ol a s A. a n d In g r a m , Joh n R. 2 0 1 7. D e r m a t olo gy life q u ality in d ex (DLQI) a s a p s o ri a sis r ef e r r al t ri a g e t ool.Britis h Jou r n al of D e r m a t olo gy 1 7 7 (4) , e 1 3 6-e 1 3 7. 1 0. 1 1 1 1/ bj d. 1 5 4 4 6 P u blis h e r s p a g e : h t t p:// dx.d oi.o r g/ 1 0. 1 1 1 1/ bj d. 1 5 4 4
Target-Directed Development of a Proposed Biosimilar Rituximab (GP2013): Comparability of Antibody-Dependent Cellular Cytotoxicity Activity and Pre-Clinical Pharmacokinetics and Pharmacodynamics with Originator Rituximab
Authors: Antonio da Silva, Ulrich Kronthaler, Ines Meyer, Anastassia Papandrikopoulou, Thomas Stangler, Jan Marinus Visser
Journal: Blood (2012)
Improving Shared Decision Making in Management of Dementia
Authors: Anita Slomski
Journal: JAMA (2017)

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