tbuckley/cabot-search huggingface dataset:
Abstract 5452: Cancer-associated metabolite 2-hydroxyglutarate accumulates in AML with IDH1/2 mutations
Authors: Valeria R. Fantin, Stefan Gross, Rob A. Cairns, Mark D. Minden, Edward M. Driggers, Hyun Gyung Jang, Masato Sasaki, Shengfang Jin, David P. Schenkein, Shinsan M. Su, Lenny Dang, Tak W. Mak
Journal: Cancer Research (2010)

Abstract Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), are present in most gliomas and secondary glioblastomas, but are rare in other neoplasms. IDH1/2 mutations are heterozygous, and affect a single arginine residue. Recently, IDH1 mutations were identified in 8% of acute myelogenous leukemia (AML) patients. Our previous study revealed that IDH1 mutations cause a gain of function, resulting in the production and accumulation of 2-hydroxyglutarate (2-HG). Genotyping of 145 AML biopsies identified 11 IDH1 R132 mutant samples. Liquid chromatography-mass spectrometry metabolite screening revealed increased 2-HG levels in IDH1 R132 mutant cells and sera, and uncovered two IDH2 R172K mutations. IDH1/2 mutations were associated with normal karyotypes. Recombinant IDH1 R132C and IDH2 R172K proteins catalyze the novel NADPH -dependent reduction of alpha-ketoglutarate (a-KG) to 2-HG. The IDH1 R132C mutation commonly found in AML reduces the affinity for isocitrate, and increases the affinity for NADPH and a-KG. This prevents the oxidative decarboxylation of isocitrate to a-KG, and facilitates the conversion of a-KG to 2-HG. IDH1/2 mutations confer an enzymatic gain of function that dramatically increases 2-HG in AML. This provides an explanation for the heterozygous acquisition of these mutations during tumorigenesis. 2-HG is a tractable metabolic biomarker of mutant IDH1/2 enzyme activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5452.
INFLUENCE OF RENAL SYMPATHETIC DENERVATION ON CARDIAC EXTRACELLULAR MATRIX TURNOVER AND CARDIAC FIBROSIS
Authors: Oliver Doerr, Christoph Liebetrau, Helge Mollmann, Luise Gaede, Christian Troidl, Kareen Morczeck, Jens Wiebe, Jedrzej Hoffmann, Sandra Voss, Timm Bauer, Christian Hamm, Holger Nef
Journal: Journal of the American College of Cardiology (2015)
An Inactivated Enterovirus 71 Vaccine in Healthy Children
Authors: Rongcheng Li, Longding Liu, Zhaojun Mo, Xuanyi Wang, Jielai Xia, Zhenglun Liang, Ying Zhang, Yanping Li, Qunying Mao, Jingjing Wang, Li Jiang, Chenghong Dong, Yanchun Che, Teng Huang, Zhiwei Jiang, Zhongping Xie, Lichun Wang, Yun Liao, Yan Liang, Yi Nong, Jiansheng Liu, Hongling Zhao, Ruixiong Na, Lei Guo, Jing Pu, Erxia Yang, Le Sun, Pingfang Cui, Haijing Shi, Junzhi Wang, Qihan Li
Journal: New England Journal of Medicine (2014)

Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed.We conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71.A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per-protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the participants who received vaccine vs. 35.2% of those who received placebo), were significantly more common in the week after vaccination among children who received the vaccine than among those who received placebo.The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease. (Funded by the National Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.).
Andrew Gilbert Graham
Authors: M. A. Graham
Journal: BMJ (2014)

Almost two-thirds of patients with giant cell arteritis (GCA) develop ocular symptoms and up to 30% suffer permanent visual loss. We review the three most common mechanisms for visual loss in GCA, describing the relevant ophthalmic arterial anatomy and emphasising how ophthalmoscopy holds the key to a rapid diagnosis. The short posterior ciliary arteries supply the optic nerve head, while the central retinal artery and its branches supply the inner retina. GCA has a predilection to affect branches of posterior ciliary arteries. The most common mechanism of visual loss in GCA is anterior arteritic optic neuropathy due to vasculitic involvement of short posterior ciliary arteries. The second most common cause of visual loss in GCA is central retinal artery occlusion. When a patient aged over 50 years has both anterior ischaemic optic neuropathy and a central retinal artery occlusion, the diagnosis is GCA until proven otherwise, and they should start treatment without delay. The least common culprit is posterior ischaemic optic neuropathy, resulting from vasculitic involvement of the ophthalmic artery and its pial branches. Here, the ophthalmoscopy is normal acutely, but MR imaging of the orbits usually shows restricted diffusion in the optic nerve.
Abstract 5612: The PI3K/Akt inhibitor LY294002 reverses BCRP/ABCG2-mediated drug resistance without BCRP translocation
Authors: Yasuo Imai, Hidetsugu Yamagishi, Yoshihiko Ueda
Journal: Cancer Research (2012)

Abstract Cellular responses toward cytotoxic drugs are influenced by cross-talk between oncogenic signals and resistance mechanisms. Inhibition of the PI3K/Akt pathway is effective in sensitizing cancer cells of various organs, although the mechanisms have largely remained to be elucidated. Breast cancer resistance protein (BCRP)/ABCG2, a drug efflux pump, confers resistance to multiple anticancer agents such as SN-38 and topotecan. Previous studies reported that inhibition of the PI3K/Akt pathway, by gene knockout or PI3K inhibitors, modulated BCRP-mediated drug transport via BCRP translocation in hematopoietic stem cells, renal polarized cells, and glioma stem-like cells of mammals. In this paper, we tested reversing effects of PI3K inhibitors, LY294002 and wortmannin, on BCRP-mediated anticancer drug resistance of human cancer MCF-7 and A431 cells. LY294002 definitely reversed BCRP-mediated SN-38 and topotecan resistances but wortmannin did not. LY294002 treatment affected neither total nor cell surface BCRP levels by western blotting and flow cytometry but blocked BCRP-mediated topotecan efflux in a dose-dependent manner. Immunohistochemical analyses also demonstrated unchanged cellular BCRP distribution. BCRP overexpression in MCF-7 and A431 cells did not confer LY294002 resistance, suggesting that LY294002 would not be a transported substrate of BCRP. LY294002 is a derivative of quercetin, a member of flavonoid. Taken together, these results suggest that LY294002 inhibits BCRP-mediated drug transport not by BCRP translocation through the PI3K/Akt signal but putatively as a competitive inhibitor in a major subset of cancer cells. Due to its dual effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5612. doi:1538-7445.AM2012-5612
Tracking development assistance for HIV/AIDS by type of investment, 1990–2015
Authors: Joseph L Dieleman, Lavanya Singh, Maxwell Birger, Matthew Schneider, Abigail Chapin
Journal: The Lancet Global Health (2016)

Background Millennium Development Goal (MDG) 6 focused on halting the spread of HIV/AIDS. Since this goal was established, more development assistance for health has been devoted to combat HIV/AIDS in low-income and middle-income countries than any other cause of illness. In this study, we aim to track development assistance for the prevention and treatment of HIV/AIDS at a granular level, assessing the priorities over time for each major donor.
Abstract 3310: microRNAs regulate the transition between EMT and MET breast cancer stem cell states
Authors: Suling Liu, Li Shang, Shoumin Bai, Rachel Martin-Trevino, Sean McDermott, Christophe Ginestier, Ingrid Ibarra, Trenton Baker, Fayaz Malik, Jia Ke, Shivani H. Patel, Tahra Luther, Hasan Korkaya, Kevin J. Zhang, Shawn G. Clouthier, Gregory J. Hannon, Max S. Wicha
Journal: Cancer Research (2012)

Abstract Recent studies have suggested similarities between cancer stem cells and the epithelial mesenchymal transition (EMT) state. In contrast, other studies suggest that these “states” are mutually exclusive. Our studies suggest that these divergent views may be explained by the existence of multiple stem cell states, which are regulated by microRNAs. Utilizing primary breast tissue and established cell lines, we demonstrate that both normal and malignant breast stem cells exist in distinct, inter-convertible states. The EMT-like state is characterized by expression of vimentin and N-cadherin, slug, snail and twist transcription factors. EMT-like CSCs have a mesenchymal morphology, are largely quiescent, invasive and characterized by expression of the CSC markers CD44+CD24− and are EpCAM−CD49f+. In contrast, the MET (mesenchymal epithelial transition) state of CSCs is characterized by an epithelial morphology and expression of E-cadherin and EpCAM. MET-like CSCs undergo self-renewal and express the CSC marker Aldehyde dehydrogenase (ALDH) and are EpCAM+CD49F+. A subpopulation of cells expressing both CD44+CD24− and ALDH may represent cells in transition between these states. This transition is regulated by signals in the microenvironment which in turn modulate microRNA networks. Expression induction of mir100 in MCF10A cells and several cancer cell lines resulted in a decrease of ALDH-positive CSC population with a concomitant increase in the CD24−CD44+ population accompanied by induction of EMT. We demonstrated mir100 effects are mediated by targeting BMPR2, SMARCA5 and SMARCD1, all of which may contribute to induction of EMT. Moreover, we show that mir100 overexpression induces cellular quiescence as shown by Ki67 and Brdu staining. Induction of mir100 expression immediately upon orthotopic implantation or after the tumors are established significantly reduced the subsequent tumor growth in NOD/SCID mice. In contrast of overexpression of mir100 stimulates cell invasion in vitro matrigel assay. The existence of multiple cancer stem cell states has important implications for understanding stem cell plasticity as well as tumor growth and metastasis. In addition, the existence of these states has implications for the development of CSC-targeting therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3310. doi:1538-7445.AM2012-3310
Influence of the Genotype on the Clinical Course of the Long-QT Syndrome
Authors: Wojciech Zareba, Arthur J. Moss, Peter J. Schwartz, G. Michael Vincent, Jennifer L. Robinson, Silvia G. Priori, Jesaia Benhorin, Emanuela H. Locati, Jeffrey A. Towbin, Mark T. Keating, Michael H. Lehmann, W. Jackson Hall, Mark L. Andrews, Carlo Napolitano, Katherine Timothy, Li Zhang, Aharon Medina, Jean W. MacCluer
Journal: New England Journal of Medicine (1998)

The congenital long-QT syndrome, caused by mutations in cardiac potassium-channel genes (KVLQT1 at the LQT1 locus and HERG at the LQT2 locus) and the sodium-channel gene (SCN5A at the LQT3 locus), has distinct repolarization patterns on electrocardiography, but it is not known whether the genotype influences the clinical course of the disease.
PWE-045 Training in Advanced Polypectomy: Results from a National Uk Survey
Authors: J Anderson, P O’Toole, J Geraghty, R Valori, S Sarkar
Journal: Gut (2013)

<h3>Introduction</h3> Despite considerable developments in polypectomy techniques, the training of the skills necessary for removal of complex polyps remains a challenge. Little is known about the level of formal training in polypectomy among colonoscopists currently practising in the UK. <h3>Methods</h3> As part of a national survey of advanced polypectomy, targeted at BSG members and Bowel Cancer Screening Programme (BCSP) colonoscopists, individuals were asked about the training they had received in polypectomy and their perceived training needs. <h3>Results Respondents</h3> 268 fully trained colonoscopists with a median lifetime experience of 3000 procedures. 64% were BCSP colonoscopists. All but 4 had been involved in a hands-on colonoscopy-related training course and almost half had acted as course faculty. <h3>Competence</h3> 86% reported competence in endoscopic mucosal resection (EMR) of sessile polyps &gt; 2cm and half of responders had been doing EMR for &gt; 5years. 30% felt comfortable removing lesions up to 3cm with good access, 35% would tackle larger lesions (by EMR) or smaller lesions with difficult access. 30% considered themselves able to remove very large flat or polypoid lesions that were also suitable for surgery. <h3>Formal Training</h3> In relation to EMR, 58% regarded themselves as predominantly self-taught. 24% had been on an attachment at a recognised training centre and 36% had attended a hands-on advanced colonoscopy or polypectomy course. 20% reported that their only formal education in EMR was at a demonstration workshop or study day. <h3>Training Needs</h3> When asked what limited their advanced polypectomy practise, 18% identified lack of formal training in EMR, 18% lack of opportunity to gain experience and 7.5% lack of guidelines in the management of large polyps. Surprisingly, even colonoscopists claiming to operate at the most expert level admitted that they might decide against tackling a potentially resectable polyp because of lack of confidence in assessing surface morphology (7%). 2.5% indicated uncertainty about the correct techniques to use and 2.5% lacked confidence in managing immediate complications. Lack of formal training in endoscopic submucosal dissection was mentioned as a constraint to practise by 40% of responders. Overall 58% indicated they would welcome a national training scheme for complex polypectomy. <h3>Conclusion</h3> Less than half of this self-selected group of experienced colonoscopists felt they had been formally trained in advanced polypectomy. Lack of confidence appears to limit practise. Some of this stems from uncertainties that could be addressed through guidelines and formal courses in advanced polypectomy. There is support for a national training programme in this area. <h3>Disclosure of Interest</h3> J. Anderson: None Declared, P. O’Toole: None Declared, J. Geraghty Grant/Research Support from: COOK MEDICAL, R. Valori: None Declared, S. Sarkar: None Declared
AB1095 Identifying Under-Recognised, Clinically Significant Co-Morbidities and Assessing Disease Activity in RA Patients
Authors: R. Waller, L. Williamson, D. Collins, E. Price
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Many patients with RA have under-treated disease and failure to recognise co-morbidities in RA puts our patients at risk of significant increased morbidity and mortality. Complementing the clinical assessment with patient reported outcome measures using a patient completed pre-assessment tool allows a more in-depth assessment. <h3>Methods</h3> Pre-clinic, patient reported questionnaires (PRQs) were sent to all patients on our electronic database with a diagnosis of RA. Questions covered gastrointestinal (GI) symptoms, cardiovascular (CVS) symptoms and risk factors, foot symptoms (score out of 10) and anxiety and depression (Hospital Anxiety and Depression Scores (HADS)). All patients were then reviewed clinically, a full history and examination were undertaken and HAQ, DAS and QRISK2 scores were calculated for each patient. <h3>Results</h3> 597 questionnaires were sent, 301 (50%) completed and 129 patients were reviewed in clinic. <h3>Disease Activity</h3> Mean DAS score 3.04; Mean HAQ score 1.25 <h3>Mood</h3> HADS scores: Anxiety score &gt;11 in 41/129 (32%); mean 8. Depression score &gt;11 in 46/129 (36%) mean 9. <h3>Cardiovascular risk</h3> 54/129 (42%) had a QRISK2 greater than 20%. 60% agreement in score comparing information from postal questionnaire with clinic. Only 5% of patients assessed as low risk by PRQ were given a high risk score in clinic 19 patients had hypertension and 32 had raised cholesterol at clinic review, which was not picked up by PSQ. <h3>Foot symptoms</h3> 89% of patients reported foot symptoms in the week prior to postal questionnaire. Mean score 4/10. Mean score at clinic review 4/10 - correlation co-efficient 0.63. 65/129 (46%) required intervention by a podiatrist. <h3>GI symptoms</h3> 75% of patients reported GI symptoms on at least a monthly basis, with 17% reporting daily symptoms by PSQ. No extra symptoms of concern were elicited at clinic review in any patient <h3>Conclusions</h3> Pre clinic screening by questionnaire is an efficient, effective and feasible way of identifying co-morbidities and directing treatment. Co-existing conditions can have an important bearing upon treatment success, therefore global health review is important when assessing RA patients for annual review <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3664
Abstract 4740: Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment ofactivated T lymphocytes
Authors: Asis Palazon, Alvaro Teijeira, Iván Martínez-Forero, Sandra Hervás-Stubbs, Carmen Roncal, Juan Dubrot, Aizea Morales-Kastresana, Ana Rouzaut, Maria Jure-Kunkel, Ignacio Melero
Journal: Cancer Research (2011)

Abstract Agonist monoclonal antibodies to the immune co-stimulatory molecule CD137, also known as 4-1BB, are presently in clinical trials for cancer treatment based on their co-stimulatory effects on primed T cells and perhaps other cells of the immune system. Here we provide evidence that CD137 is selectively expressed on the surface of tumor endothelial cells. Hypoxia upregulated CD137 on murine endothelial cells. Treatment of tumor-bearing immunocompromised Rag-/- mice with agonist CD137 mAb did not elicit any measurable anti-angiogenic effects. In contrast, agonist mAb stimulated tumor endothelial cells, increasing cell surface expression of the adhesion molecules ICAM-1, VCAM-1 and E-selectin. When adoptively transferred into mice, activated T lymphocytes derived from CD137-deficient animals entered more avidly into tumor tissue after treatment with agonist mAb. This effect could be neutralized with anti-ICAM-1 and anti-VCAM-1 blocking antibodies. Thus, stimulation of CD137 not only enhanced T cell activation but also augmented their trafficking into malignant tissue, through direct actions on the blood vessels that irrigate the tumor. Our findings identify an additional mechanism of action that can explain the immunotherapeutic effects of agonist CD137 antibodies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4740. doi:10.1158/1538-7445.AM2011-4740
Abstract LB-469: An Epstein-Barr virus-encoded microRNA miR-BART5 upregulates human cellular microRNA miR-146a and downregulates IRAK1/NFκB in stomach cancer cells
Authors: Dong Ha Kim, jin Kyung Rho, Jun Hee Woo, Byung Lan Lee, Chul Woo Kim, Woo Ho Kim, Mee Soo Chang
Journal: Cancer Research (2012)

Abstract Epstein-Barr virus (EBV) contributes to the development of the specific subsets of stomach cancer, nasopharyngeal cancer and malignant lymphoma etc. MicroRNAs (miRNAs) have been implicated in the regulation of various pathobiological processes in cancer. Recently, EBV-encoded viral miRNAs have been disclosed, whereas the functions of which remain largely unknown. A notable example of this is the human miRNA, which is targeted by viral miRNA. In this study, we investigated EBV-encoded viral miRNA miR-BART5/human cellular target interaction. The EBV miR-BART5 in EBV-infected stomach cancer cell line SNU719 was highly expressed comparing with that in EBV-infected lymphoma cell lines, Raji and Jijoye. In addition, EBV-infected stomach cancer cell revealed high level of human cellular miR-146a comparing with EBV-negative stomach cancer cells SNU601 and SNU216. Either miR-BART5 inhibitor product (anti-miR-BART5) or miR-BART5 precursor product (pre-miR-BART5) was transfected into EBV-infected stomach cancer cell, or EBV-negative stomach cancer cell, respectively. As a result, the expression of human cellular miR-146a was decreased in EBV-infected stomach cancer cell transfected with anti-miR-BART5 comparing with that in its original cell, while miR-146a was increased in EBV-negative stomach cancer cell transfected with pre-miR-BART5. As a predicted target of miR-146a, based on predicted base pairing using miRBase online program, we focused on interleukin-1 receptor-associated kinase 1 (IRAK1). Once EBV-negative stomach cancer cell was transfected with pre-miR-BART5, IRAK1 protein level was reduced by 50%, and nuclear factor-kappaB (NF-κB) (p65) was decreased. To check miR-BART5 influences on cellular biologic properties, when pre-miR-BARF5 was transfected into EBV-negative stomach cancer cell, invasion capacity of cancer cell was suppressed with a statistical significance. In conclusion, miR-BART5 could inhibit invasion of stomach cancer cell, which is in part due to the upregulation of miR-146a and downregulation of IRAK-1/ NF-κB signal pathway, offering clinicopathologic entity with a better prognosis to EBV-infected stomach cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-469. doi:1538-7445.AM2012-LB-469