tbuckley/cabot-search huggingface dataset:
Histone deacetylase inhibitor depsipeptide (FR901228) represses nicotinamide n-methyltransferase (NNMT) and hepatocyte nuclear factor (HNF)-1β gene expression in human papillary thyroid cancer cells
Authors: Jerome M. Hershman, Jimin Xu
Journal: Cancer Research (2005)

4120  NNMT is a methytransferase catalyzing N-methylation of nicotinamide and other structural analogs. Its expression is enhanced in many papillary thyroid cancers and cell lines and activated by HNF-1β. The function of NNMT and HNF-1β in the papillary cancer cells that express them is unclear. It was reported recently that inhibition of HNF-1β expression caused apoptosis in ovarian clear cell cancer. Depsipeptide is a histone deacetylase inhibitor. It causes cell cycle arrest, differentiation and/or apoptosis of cancer cells. In this project, we studied the effects of depsipeptide on NNMT gene expression. Treating BHP 18-21 papillary thyroid cancer cells with depsipeptide reduced NNMT mRNA and protein levels and NNMT catalytic activity. The reduction was dose-dependent. In contrast, expression of the sodium iodide symporter, a gene for differentiated function, was enhanced in the treated cells. To study the mechanism of the depsipeptide-mediated NNMT gene repression, NNMT promoter activity in the presence of depsipeptide was determined by luciferase reporter gene assay. NNMT promoter activity was significantly reduced in the HNF-1β positive BHP 18-21 cells, but was not reduced in the HNF-1β negative BHP 14-9 papillary cancer cells. A mutant reporter construct with mutations in a HNF-1 binding site in the NNMT basal promoter region did not respond to depsipeptide in both HNF-1β positive and negative cells. Further study showed that depsipeptide reduced HNF-1β mRNA and protein levels as well as reducing binding to its target in the NNMT promoter region. The results of this study indicate that depsipeptide represses NNMT and HNF-1β gene expression. The repression of NNMT is at least partially through down-regulation of HNF-1β. Based on the fact that expression of many cancer related genes is down-regulated by depsipeptide, we propose that NNMT and HNF-1β may be involved in a cancer related function in some papillary thyroid cancers.
Abstract B48: Minimally invasive classification of pediatric solid tumors using reduced representation bisulfite sequencing of cell-free DNA
Authors: Ruben Van Paemel, Andries De Koker, Charlotte Vandeputte, Lieke Van Zogchel, Tim Lammens, Geneviève Laureys, Jo Vandesompele, Gudrun Schleiermacher, Matthieu Chicard, Nadine Van Roy, Ales Vicha, Godelieve A. M. Tytgat, Nico Callewaert, Bram De Wilde, Katleen De Preter
Journal: Clinical Cancer Research (2020)

Abstract In the clinical management of pediatric solid tumors, histologic examination of tumor tissue obtained by an invasive biopsy remains the gold standard to establish a conclusive pathologic diagnosis. However, correct diagnosis in pediatric oncology can be challenging in some tumor types, especially in renal tumors or central nervous system tumors. The DNA methylation pattern of a tumor is known to correlate with the histopathologic diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. It has previously been shown that this methylation pattern can be detected in the cell-free circulating DNA isolated from blood plasma of cancer patients. Here, we provide proof of concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. Using computational deconvolution of the DNA methylation profiles, we were able to obtain the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free circulating DNA. We could demonstrate that the majority of misclassifications were associated with bad sample quality, evidenced by an increase of the test accuracy to 94.3% when only including good-quality samples. Misclassifications were not associated with the extent of the disease. Furthermore, we were able to derive the copy number profile or tumor subtype from the same assay. Our findings show the potential of the approach to tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner. Given the fact that primary tumor material might be difficult to obtain, in particular in critically ill children or depending on the tumor location, and might be limited in terms of quantity or quality, our assay could become complementary to the classical tissue biopsy in these difficult cases. A preprint of the study manuscript is already available at bioRxiv: https://doi.org/10.1101/795047. Citation Format: Ruben Van Paemel, Andries De Koker, Charlotte Vandeputte, Lieke Van Zogchel, Tim Lammens, Geneviève Laureys, Jo Vandesompele, Gudrun Schleiermacher, Matthieu Chicard, Nadine Van Roy, Ales Vicha, Godelieve A. M. Tytgat, Nico Callewaert, Bram De Wilde, Katleen De Preter. Minimally invasive classification of pediatric solid tumors using reduced representation bisulfite sequencing of cell-free DNA [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B48.
FRI0613-HPR THE EFFECTS OF PILATES TRAINING ON RESPIRATORY MUSCLE STRENGHT IN PATIENTS WITH ANKYLOSING SPONDYLITIS
Authors: S. Baglan Yentur, D. C. Saraç, F. Sarİ, N. G. Tore, H. Satiş, M. A. Ozturk, D. Oskay
Journal: Annals of the Rheumatic Diseases (2020)

Background: Ankylosing Spondylitis (AS) is a chronic, inflammatory rheumatic disease that effects primarily axial spine. Reduction in flexibility and mobility is important factors that can cause muscle weakness, impairment quality of life, reduction of exercise tolerance and pulmonary capacity with the progression of AS. Objectives: The purpose of this study was to investigate the effects of pilates exercises on mobility, quality of life and respiratory muscle strength in patients with AS. Methods: Forty patients with AS were randomly divided into two groups as pilates group and control group. Pilates group was performed pilates exercises and control group performed conventional exercises at home for 8 weeks, 3 days a week. Main outcome measures were maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP). Secondary outcome measures were Forced Vital Capacity (FVC), Forced expiratory volume in one second/Forced Vital Capacity (FEV1/FVC), chest expansion, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI) and Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL), 6 minutes walk test (6MWT). All participants were assessed by a blind assessor before and after the study. Results: Thirty-six AS patients (n=19 in the pilates group, n= 17 in the control group) completed the study. In the pilates group, respiratory muscle strength, FEV1/FVC, chest expansion, BASDAI, BASMI, ASQoL and 6MWT showed significant improvements at 8 th week (p&lt;0.05), while inspiratory muscle strength, FEV1/FVC, chest expansion and 6MWT showed significant improvements in the control group at 8 th week compared to baseline (p&lt;0.05). Although the pilates group had better outcomes for all parameters compared to the control group, significant differences were only observed in MIP and MEP. Conclusion: Pilates method is an effective method for improving respiratory parameters, spinal mobility, disease activity and quality of life. Additionally, pilates training is found to be superior compared to conventional exercise training in improving respiratory muscle strength. References: [1] Sampaio-Barros PD, Cerqueira EMF, Rezende SM, Maeda L, Conde RA, Zanardi VA et al. Pulmonary involvement in ankylosing spondylitis. Clinical rheumatology. 2007;26(2):225-30. [2] Ozdem OY, Inanici F, Hascelik Z. Reduced vital capacity leads to exercise intolerance in patients with ankylosing spondylitis. European journal of physical and rehabilitation medicine. 2011;47(3):391-7. [3] Altan L, Korkmaz N, Dizdar M, Yurtkuran M. Effect of Pilates training on people with ankylosing spondylitis. Rheumatology international. 2012;32(7):2093-9. Disclosure of Interests: None declared
Screening for Unhealthy Drug Use
Authors: Alex H. Krist, Karina W. Davidson, Carol M. Mangione, Michael J. Barry, Michael Cabana, Aaron B. Caughey, Susan J. Curry, Katrina Donahue, Chyke A. Doubeni, John W. Epling, Martha Kubik, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2020)

An estimated 12% of adults 18 years or older and 8% of adolescents aged 12 to 17 years report unhealthy use of prescription or illegal drugs in the US.To update its 2008 recommendation, the USPSTF commissioned reviews of the evidence on screening by asking questions about drug use and interventions for unhealthy drug use in adults and adolescents.This recommendation statement applies to adults 18 years or older, including pregnant and postpartum persons, and adolescents aged 12 to 17 years in primary care settings. This statement does not apply to adolescents or adults who have a currently diagnosed drug use disorder or are currently undergoing or have been referred for drug use treatment. This statement applies to settings and populations for which services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred.In adults, the USPSTF concludes with moderate certainty that screening by asking questions about unhealthy drug use has moderate net benefit when services for accurate diagnosis of unhealthy drug use or drug use disorders, effective treatment, and appropriate care can be offered or referred. In adolescents, because of the lack of evidence, the USPSTF concludes that the benefits and harms of screening for unhealthy drug use are uncertain and that the balance of benefits and harms cannot be determined.The USPSTF recommends screening by asking questions about unhealthy drug use in adults 18 years or older. Screening should be implemented when services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred. (Screening refers to asking questions about unhealthy drug use, not testing biological specimens.) (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for unhealthy drug use in adolescents. (I statement).
Mof regulates glucose level via altering different α-cell subset mass and intra-islet glucagon-like peptide-1, glucagon secretion
Authors: Xinghong Guo, Danyang Li, Jia Song, Qibing Yang, Meng Wang, Yang Yang, Lingshu Wang, Xinguo Hou, Li Chen, Xiangzhi Li
Journal: Metabolism (2020)
Response to: ‘Telemedicine will not keep us apart in the COVID-19 pandemic’ by Perniola <i>et al</i>
Authors: Emanuele Bozzalla Cassione, Giovanni Zanframundo, Alessandro Biglia, Veronica Codullo, Carlomaurizio Montecucco, Lorenzo Cavagna
Journal: Annals of the Rheumatic Diseases (2020)

We thank Perniola et al for their interest in our paper and the circumstantial details on their outpatient activity.1 Our service is a referral rheumatology department with more than 100 outpatients evaluated every day. Since the first Italian subject has been diagnosed with COVID-19 and transferred to our Hospital on 21 February 2020, a prompt reorganisation of our department and of the entire hospital facilities has been carried out in order to create a COVID-19 hub hospital and deal with the emergency at best.2 Starting 24 February 2020, we have severely restricted the access to our outpatient clinic. Nevertheless, we have maintained the administration of intravenous therapies (biologics, antimetabolites and prostanoids) and the evaluation of patients requiring urgent interventions (eg, patients suffering from organ or life-threatening …
American Cancer Society guideline for diet and physical activity for cancer prevention
Authors: Cheryl L. Rock, Cynthia Thomson, Ted Gansler, Susan M. Gapstur, Marjorie L. McCullough, Alpa V. Patel, Kimberly S. Andrews, Elisa V. Bandera, Colleen K. Spees, Kimberly Robien, Sheri Hartman, Kristen Sullivan, Barbara L. Grant, Kathryn K. Hamilton, Lawrence H. Kushi, Bette J. Caan, Debra Kibbe, Jessica Donze Black, Tracy L. Wiedt, Catherine McMahon, Kirsten Sloan, Colleen Doyle
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.
OP0146 LONG TERM OUTCOME AND PROGNOSIS FACTORS OF ISOLATED AORTITIS
Authors: Y. Ferfar, S. Morinet, O. Espitia, C. Agard, M. Vautier, C. Comarmond, A. C. Desbois, F. Domont, M. Resche-Rigon, P. Cacoub, L. Biard, D. Saadoun
Journal: Annals of the Rheumatic Diseases (2020)

Background: Aortitis is a group of disorders characterized by the inflammation of the aorta. The most common causes of aortitis are the large-vessel vasculitis i.e. giant cell arteritis (GCA) and Takayasu arteritis (TA). However, aortitis may be isolated. Because of the wide variation in the course of aortitis, predicting outcome is challenging. The optimal management strategy of isolated aortitis (IA) is still unclear as IA is poorly defined, with data consisting of small retrospective and case control studies. Objectives: To assess the long-term outcome and prognosis factors for vascular complications in patients with isolated aortitis. Methods: Retrospective multicenter study of 353 patients with non-infectious aortitis including 136 giant cell arteritis (GCA), 96 Takayasu arteritis (TA) and 73 isolated aortitis (IA). Factors associated with event-free survival, vascular event-free survival and revascularization-free survival were assessed. Risk factors for vascular complications were identified in multivariate analysis. Results: After a median follow up of 52 months, vascular complications were observed in 32.3 %, revascularization in 30 % and death in 7.6%. The 5-year cumulative incidence of vascular complications was 58% (41; 71), 20% (13; 29), and 19 % (11; 28) in IA, GCA and TA, respectively. In multivariate analysis, IA [HR, 1.85 (1.19 to 2.88), p=0.017] and male gender [1.77 (1.26 to 2.49), p&lt;0.0001] were independently associated with vascular events. The 5-year surgery-free survival was 45% (31; 65), 71% (62; 81) and 76% (68; 86) in IA, TA and GCA, respectively. Conclusion: IA has a worse vascular prognosis than GCA and TA. Sixty percent of IA patients will experience a vascular complication within 5 years from diagnosis. Disclosure of Interests: None declared
Incidentally Detected 18F-PSMA Uptake in Glomus Jugulare
Authors: Anand Zade, Chintan Trivedi, Amol Ingule, Smriti Jha, Anup Agrwal
Journal: Clinical Nuclear Medicine (2020)

Abstract PSMA (prostate-specific membrane antigen) PET/CT scan is the imaging modality of choice for staging and restaging of carcinoma prostate. Although initially thought to be a tracer with high specificity for prostatic tissue, with its extensive clinical use, there has been a rise in published literature citing its uptake in nonprostatic conditions. We present a case where false-positive PSMA uptake was noted in glomus jugulare during staging workup for carcinoma prostate.
THU0391 THE INFLUENCE OF OBESITY ON TREATMENT RESPONSE TO BIOLOGIC AGENTS IN ANKYLOSING SPONDYLITIS
Authors: J. H. Kim, G. Y. Ahn, J. H. Jung, S. J. Choi, G. G. Song
Journal: Annals of the Rheumatic Diseases (2020)

Background: Obesity can be a factor that affects response to tumor necrosis factor inhibitors (TNFi). Few studies have investigated the impact of obesity on the response to TNFi in patients with ankylosing spondylitis (AS). Objectives: The aim of our study was to investigate the impact of different body mass index (BMI) categories on TNFi response in patients with AS. Methods: Patients with AS from the Korean College of Rheumatology Biologics (KOBIO) registry were included in the current study. Patients who started a first TNFi after recruitment, and had available BMI data as well as a baseline and follow-up visit at 1 year (±6 months) were included. Patients with a BMI &lt;18.5 were excluded. Patients were categorized according to BMI: normal (BMI 18.5 to &lt;25), overweight (BMI 25–30), and obese (BMI &gt;30). We evaluated the proportion of patients achieving the 40% improvement in ASAS criteria (ASAS40), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement status at 1 year. Results: A total of 1003 AS patients starting a first TNFi were considered in the current study (696 patients of normal weight, 267 patients with overweight, and 40 obese patients). After at 1 year follow-up visit, obese individuals were significantly higher ASDAS-CRP levels but were not significantly lower ASDAS major improvement in comparison to patients of normal weight. Conclusion: Obesity is associated with significantly higher ASDAS-CRP at follow-up visit in patients with AS. Disclosure of Interests: None declared
Kenneth Arthur Howlett
Authors: David C Howlett
Journal: BMJ (2020)

Kenneth Arthur Howlett (“Ken”) was the eldest son of a London dockyard worker. After evacuation to Wales during the blitz, he passed his 11+examination and attended Archbishop Tenison’s grammar school (as it was then) in Kennington, south London. From school Ken obtained a scholarship and was accepted for officer training at the Sandhurst military academy. From there he entered the Royal Artillery and rose to the rank of major in an anti-aircraft regiment.

After several years in …
International surgical guidance for COVID-19: Validation using an international Delphi process - Cross-sectional study
Authors: Beamish AJ, Brown C, Abdelrahman T, Ryan Harper E, Harries Rl, Egan RJ, Ansell J, Evans T, Hopkins L, James O, Lewis S, Lewis WG, Luton O, Mellor K, Robinson D, Thomas R, Williams A
Journal: International Journal of Surgery (2020)
Abstract IA11: The use of GEM tumor models to identify effective therapies against KRAS mutant tumors
Authors: Mariano Barbacid
Journal: Cancer Research (2020)

Abstract KRAS oncogenes are responsible for one fourth of all human tumors, including lung and pancreatic adenocarcinomas, two tumor types with some of the worse prognoses. Unfortunately, development of suitable therapies to treat these tumors has remained elusive for the last 35 years. Although KRAS remains an undruggable target (with the possible exception of the KRASG12C isoform), most of its downstream effectors are druggable kinases. Indeed, pharma and biotech companies have already developed dozens of selective inhibitors against these kinases. Yet none of them has been approved by the FDA, mostly due to unacceptable toxicities at antitumor effective doses. Hence, patients are still treated with old chemotherapy drugs. To address this important health issue, we have used a new generation of genetically engineered mouse (GEM) tumor models of KRas/Tp53 driven lung and pancreatic tumors to deconstruct oncogenic KRas signaling to identify those effectors whose systemic ablation/inactivation in tumor-bearing mice will result in therapeutic responses without inducing unacceptable toxicities. We have used this experimental strategy to interrogate the effect of ablating/inactivating each of the members of the MAPK cascade, including the Raf, Mek, and Erk kinases, as well as key effectors of the PI3K pathway, including PI3K p110alpha and mTOR. We have also evaluated additional downstream signaling elements such as the cell cycle Cdks. This systematic approach has revealed that most of the KRas signaling effectors are not suitable therapeutic targets due to either lack of therapeutic activity, such as Cdk2, Cdk6 A-Raf, or B-Raf, or to the induction of unacceptable toxicities such as the Mek1/2 and Erk1/2 kinases, PI3K p110alpha, mTOR, and Cdk1. Only Raf1 and Cdk4 turned out to be suitable therapeutic targets, based not only on their antitumor properties but also on the well-tolerated toxicities. Surprisingly, EGFR, an upstream effect of KRas, also has suitable therapeutic activity in pancreatic but not in lung tumors. We are now combining these targets to define more efficacious therapeutic strategies that could be eventually translated to the clinic. Moreover, we are using these experimental GEM tumor models to identify potential resistance mechanisms to these therapies. Citation Format: Mariano Barbacid. The use of GEM tumor models to identify effective therapies against KRAS mutant tumors [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA11.
Retraction: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621.
Authors: Mandeep R Mehra, Sapan S Desai, SreyRam Kuy, Timothy D Henry, Amit N Patel
Journal: New England Journal of Medicine (2020)

To the Editor: Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sour...
Targeting MDM2-dependent serine metabolism as a therapeutic strategy for liposarcoma
Authors: Madi Y. Cissé, Samuel Pyrdziak, Nelly Firmin, Laurie Gayte, Maud Heuillet, Floriant Bellvert, Maryse Fuentes, Hélène Delpech, Romain Riscal, Giuseppe Arena, Frédéric Chibon, Sophie Le Gellec, Aurélie Maran-Gonzalez, Marie-Christine Chateau, Charles Theillet, Sébastien Carrere, Jean-Charles Portais, Laurent Le Cam, Laetitia K. Linares
Journal: Science Translational Medicine (2020)

Chromatin-bound MDM2 regulates serine metabolism and nucleotide synthesis to sustain tumor growth in liposarcoma.