tbuckley/cabot-search huggingface dataset:
Abstract 1422: Dietary 2-deoxy-D-glucose (2-DG) reduces TLR-4 induced acute inflammation and prevents chronic inflammation driven carcinogenesis
Authors: Sanjay Pandey, Saurabh Singh, Vandana Anang, Dhananjay K. Shah, Saurabh Seth, Anant N. Bhatt, Kailash Manda, Bal G. Roy, K Natarajan, Bilikere S. Dwarakanath
Journal: Cancer Research (2016)

Abstract Inflammation is a critical component and contributor of carcinogenesis. Toll like receptors (TLRs) are key regulators of innate immunity and inflammatory signaling. Besides various microbe-associated molecular patterns, TLRs can also bind to endogenously generated damage associated molecular patterns (DAMPS) ligands such as heat shock proteins, surfactant protein A18 and homobility group box-1(HMGB1). While HMGB1, a TLR-4 ligand is over-expressed in several human neoplasms, preclinical studies in mouse tumor models have strengthened the role of TLR-4-HMGB1 axis in promoting carcinogenesis. TLR-4 dependent inflammation and stimulation is accompanied with a switch from respiratory to glycolysis dominated metabolism, which is critical for the differentiation and maturation of myeloid cells thus affecting the outcome of an inflammatory disease. In the present studies we investigated the potential of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) as an energy restriction mimetic agent for countering the acute and chronic inflammation which can be employed as a cancer preventive strategy. Oral administration of 2-DG in drinking water (0.4% w/v) for 7 days reduced the diethyl nitrosamine (DEN) induced acute inflammation reflected by reduced the serum levels of TNF(∼4 fold) and IL-6(∼7 fold). when administered chronically, 2-DG reduced the incidence (∼50%) and the number of papillomas (∼84%) in DMBA-TPA skin carcinogenesis model, which correlated with the reduced levels of TNF. In an acute inflammation model established using LPS (a TLR-4 ligand), we observed that 2-DG reduced the systemic and macrophage specific inflammatory response in LPS injected mice. 2-DG (1mM) significantly reduced the levels of co-stimulatory surface markers (CD80 and CD86) and associated ROS and NOS effecter functions in mouse macrophagic cell line (RAW 264.7). These studies suggest that dietary administration of 2-DG can be used as a strategy for preventing acute inflammation and associated carcinogenesis. Citation Format: Sanjay Pandey, Saurabh Singh, Vandana Anang, Dhananjay K. Shah, Saurabh Seth, Anant N. Bhatt, Kailash Manda, Bal G. Roy, K Natarajan, Bilikere S. Dwarakanath. Dietary 2-deoxy-D-glucose (2-DG) reduces TLR-4 induced acute inflammation and prevents chronic inflammation driven carcinogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1422.
Clinical and Hematologic Impact of Fetal and Perinatal Variables on Mutant GATA1 Clone Size in Neonates with Down Syndrome
Authors: Neha Bhatnagar, Kelly Perkins, Sarah Filippi, Helen Richmond, Joanna Bonnici, Kate Alford, Georgina Hall, Gaëtan Juban, Simon McGowan, Anindita Roy, Natalina Elliott, Michael Stumpf, Alice Norton, Paresh Vyas, Irene Roberts
Journal: Blood (2014)
Abstract 3260: Differential effects of antiangiogenesis treatments on betel-nuts-related head and neck squamous cell carcinoma in Taiwan
Authors: Jo-Pai Chen, Jui-Ying Chang, Sung-Hsin Kuo, Ruey-Long Hong
Journal: Cancer Research (2016)

Abstract Background: The treatment of head and neck squamous cell carcinoma(HNSCC) in Taiwan is very challenging and might be related to betel-nuts use. Betel-nuts chewing might contribute to (1)strong inflammation, invasion, and angiogenesis; (2)easy recurrence or metastasis; (3) poor response to chemotherapy, radiation, and epidermal growth factor receptor(EGFR) inhibitors. Purpose: We try to prove different kinds of anti-angiogenesis treatments will lead to different response on betel-nuts related HNSCC in Taiwan. Methods: Different anti-angiogenesis treatments, such as axitinib(VEGFR2 inhibitor), nintedanib(VEGFR2/FGFR inhibitor), and regorafenib(VEGFR2/FGFR/ more other signals inhibitor) were first used to treat (1)HUVEC; (2)HNSCC cell lines(SCC4, SCC9, SCC15, SCC25, FaDu, SAS, KB, Cal27, and TW2.6, betel-nuts related) to evaluate (a) invasion capacity by wound healing; (b) drug sensitivity by MTT assay; (c)synergistic effect with chemotherapy, EGFR inhibitor, and polo-like kinase inhibitor. Western blotting was also used to test signal change by treatments. TW2.6 had already been proved to possess defective p53, p16 loss, and increased Bcl2. Results: In our previous study, TW2.6 was resistant to chemotherapy, radiation, EGFR inhibitors, and ani-angiogenesis treamtents, such as axitinib and sunitinib. Axitinib, pure VEGFR2 inhibitor, was found to suppress HUVEC more prominently than nintedanib or regorafenib did. Invasion capacity of all HNSCC cell lines were all blocked by the three drugs but regorafenib did mostly well. However, axitinib had no effect on TW2.6; but nintedanb and regorafenib had moderate response on TW2.6. Besides, nintedanib and regorafenib both would resensitize TW2.6 to respond to chemotherapy, EGFR inhibitor, and polo-like kinase inhibitor again. Western blotting showed mesenchaml differentiation markers(slug, Twist, snail, Axl, c-MET, Vimentin) decreased after nintedanib and regorafenib use, too. Conclusion: TW2.6 might reflect treatment refractoriness of betel-nuts related HNSCC in Taiwan. In addition to PI3K/mTOR dual inhibition and polo-like kinase inhibitor with radiation(our studies shown in AACR and ESMO2015), VEGFR2/FGFR dual blockage might be effective on TW2,6 and resensitize TW2.6 to EGFR inhibitor, polo-like kinase inhibitor, &amp; chemotherapy, maybe through the inhibition of mesenchymal transformation. VEGFR2/FGFR dual blockage will be one future combination backbone of betel-nuts related HNSCC. Citation Format: Jo-Pai Chen, Jui-Ying Chang, Sung-Hsin Kuo, Ruey-Long Hong. Differential effects of antiangiogenesis treatments on betel-nuts-related head and neck squamous cell carcinoma in Taiwan. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3260.
Deciphering the Wisent Demographic and Adaptive Histories from Individual Whole-Genome Sequences
Authors: Mathieu Gautier, Katayoun Moazami-Goudarzi, Hubert Levéziel, Hugues Parinello, Cécile Grohs, Stéphanie Rialle, Rafał Kowalczyk, Laurence Flori
Journal: Molecular Biology and Evolution (2016)

As the largest European herbivore, the wisent (Bison bonasus) is emblematic of the continent wildlife but has unclear origins. Here, we infer its demographic and adaptive histories from two individual whole-genome sequences via a detailed comparative analysis with bovine genomes. We estimate that the wisent and bovine species diverged from 1.7 × 106 to 850,000 years before present (YBP) through a speciation process involving an extended period of limited gene flow. Our data further support the occurrence of more recent secondary contacts, posterior to the Bos taurus and Bos indicus divergence (∼150,000 YBP), between the wisent and (European) taurine cattle lineages. Although the wisent and bovine population sizes experienced a similar sharp decline since the Last Glacial Maximum, we find that the wisent demography remained more fluctuating during the Pleistocene. This is in agreement with a scenario in which wisents responded to successive glaciations by habitat fragmentation rather than southward and eastward migration as for the bovine ancestors. We finally detect 423 genes under positive selection between the wisent and bovine lineages, which shed a new light on the genome response to different living conditions (temperature, available food resource, and pathogen exposure) and on the key gene functions altered by the domestication process.
Immunotherapy with Long-Lived Anti-CD38 × Anti-CD3 Bispecific Antibodies Stimulates Potent T Cell-Mediated Killing of Human Myeloma Cell Lines and CD38+ Cells in Monkeys: A Potential Therapy for Multiple Myeloma
Authors: Seung Y. Chu, Yvonne Miranda, Sheryl Phung, Hsing Chen, Rumana Rashid, Nancy A. Endo, Emily W. Chan, Erik Pong, Christine Bonzon, Umesh S. Muchhal, Irene W.L. Leung, Matthew J. Bernett, Gregory L. Moore, David E. Szymkowski, John R. Desjarlais
Journal: Blood (2014)
The Consult Guys - Are Those Ventricular Premature Contractions Really Benign?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2016)

Web Exclusives19 July 2016The Consult Guys - Are Those Ventricular Premature Contractions Really Benign?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W16-0007 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 July 2016Volume 165, Issue 2Page: CG1KeywordsDisclosureResearch grantsResearch reporting guidelines ePublished: 19 July 2016 Issue Published: 19 July 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Invariant NKT Cells Regulate Osteoclast Development and Function Under Homeostatic and during Conditions of Immune Activation
Authors: Ming Hu, J.H. Duncan Basssett, Lynette Danks, Emmanouil Spanoudakis, Ke Xu, Peter GT Howell, Alan Boyde, Nikki Horwood, Graham Williams, Irene AG Roberts, Anastasios Karadimitris
Journal: Blood (2008)
Developmental Control of Polycomb Subunit Composition Mediates a Switch to Non-Canonical Functions during Hematopoiesis
Authors: Jian Xu, Zhen Shao, Dan Li, Huafeng Xie, Woojin Kim, Jialiang Huang, Luca Pinello, Kimberly Glass, Guo-Cheng Yuan, Stuart H. Orkin
Journal: Blood (2014)
Accelerating the Uptake and Timing of Antiretroviral Therapy Initiation in Sub-Saharan Africa: An Operations Research Agenda
Authors: Sydney Rosen, Matthew P. Fox, Bruce A. Larson, Papa Salif Sow, Peter D. Ehrenkranz, Francois Venter, Yukari C. Manabe, Jonathan Kaplan
Journal: PLoS Medicine (2016)

Under 2015 World Health Organization guidelines calling for antiretroviral therapy (ART) for all HIV-infected persons (the "treat all" approach), millions of new patients will be eligible to initiate ART, but existing procedures for treatment initiation are cumbersome and slow, contributing to high loss to follow-up before antiretroviral medications are dispensed.Simpler, more efficient, accelerated algorithms for ART initiation are needed.
P1172 : Colectomy is associated with development of cholangiocarcinoma in patients with primary sclerosing cholangitis and inflammatory bowel disease
Authors: A. Gulamhusein, J.E. Eaton, J.H. Tabibian, E.J. Atkinson, G.J. Gores, K.N. Lazaridis
Journal: Journal of Hepatology (2015)
A Targeted Resequencing Study Allows the Detection of a Common Polymorphism At Mirna-223 Binding Site in 3′Untranslated Region Which Deregulates HSP90B1 Expression in Chronic Lymphocytic Leukemia
Authors: Ana E Rodríguez, Dalia Qwaider, Rocío Benito, Irena Misiewicz-Krzeminska, María Hernández-Sánchez, M Eugenia Sarasquete, Jesús F San Miguel, Jose Ángel Hernández-Rivas, Norma Gutierrez, Jesús M Hernández-Rivas
Journal: Blood (2012)
Case 41-1966
Authors: Edwin W. Salzman, Benjamin Castleman
Journal: New England Journal of Medicine (1966)

Presentation of CaseA thirty-seven-year-old man was admitted to the hospital because of diarrhea.Nineteen years previously he underwent partial gastrectomy because of a bleeding duodenal ulcer. Thereafter, he returned to the clinic at irregular intervals. Nine years before admission hypochromic anemia was found, and during the next five years he entered the hospital annually because of severe anemia that required blood transfusions. Periodic x-ray studies of the upper gastrointestinal tract showed no sign of a marginal ulcer. Repeated barium-enema examinations, the last of which was performed six years before entry, were negative except for slight prominence of a few . . .
Abstract 1859: Bioinformatic and experimental evaluation of regulatory variants in breast cancer susceptibility genes
Authors: Jan Sevcik, Leslie Burke, Gaetana Gambino, Brooke L. Brewster, Emma Tudini, Philip J. Whiley, Siranoush Manoukian, Thomas van Overeem Hansen, Marta Santamariña Pena, Ana Vega, Maria A. Caligo, Paolo Radice, Paolo Peterlongo, Etienne Rouleau, Amanda B. Spurdle, Melissa A. Brown
Journal: Cancer Research (2016)

Abstract Many germline DNA sequence variants in gene regulatory elements are associated with an increased risk of cancer. These include large genomic deletions of the promoter of the BRCA1 gene, through to single nucleotide variants in the promoter, UTRs and long-range enhancers of multiple other cancer related genes. Next generation sequence analysis of early onset and familial breast cancer cases is currently identifying an escalating number of variants in non-coding regions of the genome, however for most of these the significance in unknown. This project aims to determine the functional and clinical significance of breast cancer associated variants in regulatory regions of BRCA1 and BRCA2, as part of an international collaborative project arising from the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium. To date over two hundred variants mapping to promoter, UTR and deep intronic regions have been identified in early onset or familial breast cancer patients that have no identifiable coding or splicing changes in BRCA1 or BRCA2. Through a pipeline of bioinformatics analyses using ENCODE datasets, these variants have been prioritized for experimental evaluation. This has lead to the identification of several variants that significantly alter the regulation of BRCA1 or BRCA2 expression, through mechanisms including altered binding of transcription factors and microRNAs. These studies will lay the groundwork for comprehensive statistical analyses, in which bioinformatics and experimental data is combined with clinical and genetic data to establish multifactorial risk prediction models that can ultimately be used in a clinical setting. Citation Format: Jan Sevcik, Leslie Burke, Gaetana Gambino, Brooke L. Brewster, Emma Tudini, Philip J. Whiley, Siranoush Manoukian, ENIGMA Consortium, Thomas van Overeem Hansen, Marta Santamariña Pena, Ana Vega, Maria A. Caligo, Paolo Radice, Paolo Peterlongo, Etienne Rouleau, Amanda B. Spurdle, Melissa A. Brown. Bioinformatic and experimental evaluation of regulatory variants in breast cancer susceptibility genes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1859.
133P The mTOR kinase inhibitor AZD-2014 enhances the antitumor effects of XPO1 antagonist KPT-185 in mantle cell lymphoma
Authors: K. Sekihara, S. Yamamoto, M. Kikkawa, H. Taka, N. Kaga, H. Matsushita, H. Hayashi, M. Tanaka, T. Miida, M. Andreeff, M.Y. Konopleva, Y. Tabe
Journal: Annals of Oncology (2015)
Patterns of referral for peri-operative chemotherapy among patients with muscle-invasive bladder cancer (MIBC): A population-based study.
Authors: Christopher M. Booth, D. Robert Siemens, Yingwei Peng, William J. Mackillop
Journal: Journal of Clinical Oncology (2014)

e15507 Background: Reasons for low uptake of peri-operative chemotherapy for MIBC are not well described. Here we report referral patterns from urology to medical oncology (MO) in routine clinical practice and subsequent use of chemotherapy. Methods: Treatment and physician billing records were linked to the population-based Ontario Cancer Registry to describe referral patterns from urology to MO and subsequent use of neoadjuvant or adjuvant chemotherapy (NACT/ACT) among all patients with MIBC treated with cystectomy in Ontario 1994-2008. Referral and treatment patterns were described over 3 study periods: 1994-1999, 2000-2004, 2005-2009. Logistic regression was used to analyze factors associated with referral to MO and use of NACT/ACT. Results: Eighteen percent (520/2944) of the study population was seen by MO prior to cystectomy and 25% (128/520) of referred cases were treated with NACT. The proportion of cases seen by MO before cystectomy decreased across the study periods (20%, 18%, 16%, p=0.075) and varied substantially across geographic regions (range 5-40%, p<0.001). Use of NACT among those patients seen by MO did increase over time (23%, 14%, 35%, p<0.001). Among patients not treated with neoadjuvant chemotherapy or radiation, 39% (1085/2809) were seen by MO following cystectomy; 51% (548/1085) of referred patients were treated with ACT. In multivariate analysis, referral to MO and subsequent use of ACT was greatest among younger patients (p<0.001), with less co-morbidity (p=0.001) and from higher socioeconomic backgrounds (p=0.021). There was wide geographic variation in rates of referral to MO after cystectomy (range 26 to 59%, p<0.001); referral rates remained stable over time. Patients seen by MO in 2004-2008 were more likely to receive ACT (57%) compared to patients treated in earlier years (41% 1994-1998 and 46% 1999-2003, p<0.001). Conclusions: Lack of referral to MO appears to be an important barrier to use of NACT/ACT suggesting upstream decision-making by urologists is an important target in future knowledge translation. Low treatment rates among patients seen by MO suggest that therapy has also not been wholly embraced by MOs or patients.
Abstract 1668: Bouvardinis a radiation modulator with a novel mechanism of action
Authors: Tin tin SU.
Journal: Cancer Research (2016)

Abstract Protein synthesis is essential for growth, proliferation and survival of cells. Translation factors are overexpressed in many cancers and their experimental inhibition curbs cancer growth in preclinical models. Differential regulation of translation also occurs upon exposure to cancer-relevant stresses such as hypoxia and ionizing radiation (IR). The failure to regulate translation has been shown to interfere with recovery after genotoxic stress. These findings suggest that modulation of translation, alone or in conjunction with genotoxins, may be therapeutic in oncology. Yet, only two drugs that directly inhibit translation are FDA-approved for oncology use today. We described before the identification of protein synthesis inhibitor bouvardin in a screen for small molecule enhancers of IR in Drosophila melanogaster. Bouvardin was independently identified in a screen for selective inhibitors of engineered human breast cancer stem cells. Here we report the effect of bouvardin in preclinical models of head and neck cancer (HNC) and glioma, two cancer types for which IR is a key therapy choice. Our data show for the first time that bouvardin blocked translation elongation on human ribosomes and suggest that it did so by blocking the dissociation of elongation factor 2 from the ribosome. Bouvardin enhanced the induction of clonogenic death by IR in HNC and glioma cells, although by different mechanisms. Bouvardin enhanced the anti-tumor effect of IR in HNC tumor xenografts in mice. These data suggest that inhibition of translation elongation, particularly in combination with IR, may be a promising treatment option for cancer. Citation Format: Tin tin SU. Bouvardinis a radiation modulator with a novel mechanism of action. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1668.
MRI screening for breast cancer in women with high familial and genetic risk: First results of the Dutch MRI screening study (MRISC).
Authors: M. Kriege, C. T. M. Brekelmans, C. Boetes, E. J. T. Rutgers, J. C. Oosterwijk, R. A. Tollenaar, R. A. Manoliu, R. Holland, H. J. De Koning, J. G. M. Klijn
Journal: Journal of Clinical Oncology (2003)
Abstract 100: The Wearable Cardioverter Defibrillator Is Cost-Effective in Protecting High-Risk Patients After Acute Myocardial Infarction
Authors: Chingping Wan, Jo Ann Glad, Nicole Bianco, Steven Szymkiewicz
Journal: Circulation (2011)

Introduction Patients after an acute myocardial infarction (AMI) are at high risk of sudden cardiac death (SCD). According to guidelines, they do not qualify for an implantable cardioverter defibri...