tbuckley/cabot-search huggingface dataset:
PP14. NETWORK ANALYSIS REVEALS INSIGHTS INTO H3F3A BIOLOGY IN PEDIATRIC GLIOBLASTOMA
Authors: Dr Anbarasu Lourdusamy, Prof Richard Grundy
Journal: Neuro-Oncology (2017)

BACKGROUND: H3 histone, family 3A (H3F3A) encodes H3.3 histone protein monomers, which plays a central role in chromatin structure and gene regulation. Recent studies have reported highly recurrent mutations affecting the N-terminal tail of H3.3 and causing amino acid substitution of lysine 27 to methionine (K27M) and of glycine 34 to arginine or valine (G34A or G34V) in pediatric glioblastoma (GBM), which in turns linked to two subgroups with distinct clinical and pathological features. However, effect of H3F3A mutations on other closely related genes is not yet fully explored. Thus, we performed a network analysis to gain insights into the biology of H3F3A in pediatric GBM. METHODS: We constructed H3F3A network by extracting gene products that directly interact with H3F3A from protein-protein interaction (PPI) databases. To examine the network wiring around H3F3A, we combined pediatric GBM gene expression data from three independent studies and computed the correlation between H3F3A and all interacting genes for each mutation status (K27M or G34) and H3F3A wild type (WT). We then identified network of differentially co-expressed gene pairs that either gained or lost correlation in mutation relative to the WT tumours. RESULTS: Through mining of PPI networks, 106 gene products were identified to interact with H3F3A. Many of these genes were known to be involved in chromatin modification (47 genes; FDR = 2.17E-38), DNA metabolic process (34 genes; FDR = 3.23E-16), DNA repair (22 genes; FDR = 8.18E-12), and histone methylation (13 genes; FDR = 2.75E-11). H3F3A network was largely perturbed by K27M mutation than G34 (44 interactions changed in K27M and 24 in G34 when compared with WT, FDR < 0.05). Of these interactions, only four were perturbed by both mutations: H3F3A - ASB9, H3F3A - CBX3, H3F3A - HIST2H2BE, and H3F3A - PDGFRA, suggesting distinct mechanisms by which H3F3A mutations might be inducing transcriptional programming in pediatric GBM. A relatively small number of H3F3A interactions were identified between IDH1 mutation and WT tumours from adult GBM (7 interactions from K27M and 1 from G34) and in pediatric medulloblastomas (2 interactions from K27M and 1 from G34), demonstrating the robustness and specificity of identified interactions in pediatric GBM. CONCLUSION: In conclusion, the network analysis represents a new approach for the prioritization of H3F3A interacting partners in pediatric GBM, providing new insights into network dependencies in pediatric GBM subgroups and potentially enabling the identification of new diagnostic and therapeutic targets.
Modulation of drug-linker design to enhance in vivo potency of homogeneous antibody-drug conjugates
Authors: Martin Pabst, William McDowell, Anaïs Manin, Andrew Kyle, Nicolas Camper, Elena De Juan, Vimal Parekh, Felicity Rudge, Hiteshri Makwana, Terrence Kantner, Hemal Parekh, Aurelie Michelet, XiaoBo Sheng, Gina Popa, Carolyn Tucker, Farzad Khayrzad, Derek Pollard, Katarzyna Kozakowska, Ricardo Resende, Alan Jenkins, Fabio Simoes, Dave Morris, Paul Williams, George Badescu, Matthew P Baker, Matthew Bird, Mark Frigerio, Antony Godwin
Journal: Journal of Controlled Release (2017)
Long-Term Hematologic Reconstitution and Clinical Evaluation of APBSCT with Cryopreservation of Stem Cells with 5- and 10-Percent DMSO at -80°C Mechanical Freezer.
Authors: A. Galmes, A. Gutierrez, A. Sampol, M. Morey, M. Canaro, J. Iglesias, N. Matamoros, M.A. Duran, A. Novo, L. Viñas, P. Galan, J. Balansat, J. Martinez, J. Besalduch
Journal: Blood (2005)
Questioning Feeding Tubes to Treat Dysphagia
Authors: Thomas E. Finucane
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs
Authors: Giulia Girelli Zubani, Marija Zivojnovic, Annie De Smet, Olivier Albagli-Curiel, François Huetz, Jean-Claude Weill, Claude-Agnès Reynaud, Sébastien Storck
Journal: The Journal of Experimental Medicine (2017)

During somatic hypermutation (SHM) of immunoglobulin genes, uracils introduced by activation-induced cytidine deaminase are processed by uracil-DNA glycosylase (UNG) and mismatch repair (MMR) pathways to generate mutations at G-C and A-T base pairs, respectively. Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis. Thus, how detection of U:G mismatches is translated into the single-strand nick required for error-prone synthesis is an open question. One model proposed that UNG could cooperate with MMR by excising a second uracil in the vicinity of the U:G mismatch, but it failed to explain the low impact of UNG inactivation on A-T mutagenesis. In this study, we show that uracils generated in the G1 phase in B cells can generate equal proportions of A-T and G-C mutations, which suggests that UNG and MMR can operate within the same time frame during SHM. Furthermore, we show that Ung−/−Pms2−/− mice display a 50% reduction in mutations at A-T base pairs and that most remaining mutations at A-T bases depend on two additional uracil glycosylases, thymine-DNA glycosylase and SMUG1. These results demonstrate that Pms2/Mlh1 and multiple uracil glycosylases act jointly, each one with a distinct strand bias, to enlarge the immunoglobulin gene mutation spectrum from G-C to A-T bases.
PP74. SERIAL IMAGING OF INCIDENTAL MENINGIOMAS: ARE WE DOING TOO MANY SCANS?
Authors: Dr Andrea Perera, Prof Philip Kane
Journal: Neuro-Oncology (2017)

INTRODUCTION: We have observed a rise in referrals of patients with incidental meningiomas. It is widely accepted that the majority of these cases can be managed conservatively by monitoring with serial scans. However, there is no clear consensus or widely accepted guidance on the frequency of scanning or the duration of follow up. We reviewed the management of conservatively treated meningiomas in our unit. METHOD: Patients presenting to the unit between 06/01/2009 and 12/08/2015 with a radiological diagnosis of meningioma were identified from neuro-oncology MDT records. Incidental meningiomas were defined as either being asymptomatic (i.e. scan performed for other reason) or meningiomas in patients whose symptomatology was discrete from their radiological appearances. The baseline characteristics for each patient, dates of each scan and scan outcome were recorded. RESULTS: 131 incidental meningiomas managed under a conservative, ‘watch and wait’ strategy were identified and a total of 448 surveillance scans were performed. The mean duration of follow up was 28.5 months (range 3.0–71.9 months). 11 patients showed radiological progression during their follow up period and two underwent surgical excision. The median time to progression was 24.8 months (range 3.7–67.2 months). No patient was shown to have progression after their fourth consecutive scan. There was no clear factor (i.e. location or size of tumour) to indicate risk of progression. CONCLUSION: It is likely that the majority of patients with incidental meningiomas are being over imaged during extended surveillance periods, taking up valuable radiological resources and clinic time. Our preliminary data suggests that 5 serial scans over a 5 year period are likely to provide safe and sufficient follow up for small asymptomatic meningiomas. Expansion and follow up of this cohort continues with a view to identifying factors which may predict tumour growth.
Implications of Concurrent Ibrutinib Therapy on CAR T-Cell Manufacturing and Phenotype and on Clinical Outcomes Following CD19-Targeted CAR T-Cell Administration in Adults with Relapsed/Refractory CLL
Authors: Mark Blaine Geyer, Jae H. Park, Isabelle Riviere, Brigitte Senechal, Xiuyan Wang, Terence J. Purdon, Michel W. Sadelain, Renier J. Brentjens
Journal: Blood (2016)
More than 1 TP53 abnormality is a dominant characteristic of pure erythroid leukemia
Authors: Guillermo Montalban-Bravo, Christopher B. Benton, Sa A. Wang, Farhad Ravandi, Tapan Kadia, Jorge Cortes, Naval Daver, Koichi Takahashi, Courtney DiNardo, Elias Jabbour, Gautam Borthakur, Marina Konopleva, Sherry Pierce, Carlos Bueso-Ramos, Keyur Patel, Steven Kornblau, Hagop Kantarjian, Ken H. Young, Guillermo Garcia-Manero, Michael Andreeff
Journal: Blood (2017)
Health-adjusted life expectancy in HIV-positive and HIV-negative men and women in British Columbia, Canada: a population-based observational cohort study
Authors: Robert S Hogg, Oghenowede Eyawo, Alexandra B Collins, Wendy Zhang, Shahab Jabbari, Mark W Hull, Viviane Dias Lima, Tareq Ahmed, Claire E Kendall, Keri N Althoff, Amy C Justice, Rolando Barrios, Jeannie Shoveller, Julio S G Montaner
Journal: The Lancet HIV (2017)
Effects of Extracellular NM23 Protein on In Vitro Survival of Acute Myeloid Leukemia Cells and Normal Peripheral Blood Mononuclear Cells.
Authors: Junko Okabe-Kado, Takashi Kasukabe, Hirofumi Kobayashi, Nobuo Maseki, Yoshio Honma, Yasuhiko Kaneko
Journal: Blood (2006)
Targeting the Wnt/β-Catenin Signaling Pathway and CD44-Mediated Adhesion As a Rational Approach to Overcome Lenalidomide Resistance in Multiple Myeloma
Authors: Chad C. Bjorklund, Sharon Lea Aukerman, Antonia Lopez-Girona, Mohamad Hussein, Rajesh Chopra, Isere Kuiatse, Deborah J. Kuhn, Caimiao Wei, Robert Z. Orlowski
Journal: Blood (2011)
Elafin Is a Biomarker of Graft Versus Host Disease of the Skin
Authors: Sophie Paczesny, John E. Levine, Jason Hogan, Jeffrey Crawford, Thomas Braun, Hong Wang, Vitor Faca, Qing Zhang, Sharon Pitteri, Alice Chin, Sung Choi, Carrie Kitko, Oleg I. Krijanovski, Pavan Reddy, Shin Mineishi, Joel Whitfield, Dawn Jones, Samir Hanash, James L.M. Ferrara
Journal: Blood (2008)
What women want: Sexual quality of life after the treatment of gynecologic cancer.
Authors: Elizabeth Louise Dickson, Jessica L. Hubbs, Rachel Isaksson Vogel, Colleen Lee Rivard, Deanna Gek Koon Teoh, Melissa Ann Geller
Journal: Journal of Clinical Oncology (2015)

e20617 Background: Previous studies of sexual function after treatment for gynecologic malignancies describe sexual problems, but few address how patients want to achieve resolution of these issues. Our objective was to evaluate the sexual function of women treated for gynecologic cancer, and to describe their desire for discussion and management of these issues. Methods: Patients undergoing treatment for a gynecologic cancer completed a modified Changes in Sexual Function Questionnaire (CSFQ) once during the study period of 13 months. Analysis of the CSFQ total score by treatment received was conducted using t-tests assuming unequal variances and analysis of variance (ANOVA) as appropriate. Results: The survey was provided to 277 women, and response rate was 30.7%. The mean age was 52.2 years. The majority were Caucasian (78.8%), partnered (73.2%), had either endometrial or ovarian cancer (30.6% and 44.7% respectively), and were undergoing post-treatment surveillance for their cancer (57.3%). The majority had received surgical (91.8%) and chemotherapy (63.5%) treatment, and only 23.8% received radiation therapy. 64.7% of patients’ reported much or great enjoyment in their sex life 1 year prior to cancer treatment. 43.5% of patients stated their sexual enjoyment significantly decreased since cancer treatment. Only 27% reported much or great enjoyment in their sex life at the time of the survey, 33.3% of patients rarely engaging in sexual activity. There was no statistical difference in mean total CSFQ score depending on type of treatment received. 55.7% of patients wanted to discuss issues related to sexual activity; however, 46.2% of patients felt there were more important issues to address than sexual health. While 37.5% did not want any treatment for their sexual health concerns, 32.9% patients wanted written education, rather than personal or group counseling. Conclusions: Many women with gynecologic malignancies report changes in their sexual function following treatment. However, nearly half the respondents feel that there are other issues more important to discuss than sexual health at their surveillance visits. Further investigation into the sexual health needs of women receiving cancer treatment is warranted.
Abstract P5-13-18: The feasibility of nurse intervention to improve and maintain the BMI of breast cancer survivors over 25 to appropriate levels
Authors: M Arakaki, K Tamaki, Y Kamada, K Uehara, H Gushikawa
Journal: Cancer Research (2017)

Abstract Background: Some studies have shown that women with breast cancer who have a BMI value gain of more than 2.0 kg/m2 after diagnosis have an elevated risk of dying of breast cancer, and likewise breast cancer patients who gained 5 or more kilogramshad a higher mortality rate than those who maintained their weight. Therefore it can be said that weight control is important for women with breast cancer. In addition to the survival benefit, preliminary research suggests that exercise intervention for weight control may also be effective for enhancing the QOL of cancer survivors. Purpose: We designed an exercise intervention study to assess the feasibility of the intervention in maintaining standard weight and also the effect of the excercise in breast cancer patients. Patients and methods: Breast cancer patients aged 20 to 75 years, stage I to IIIA, with no metastases, who had completed chemotherapy, with BMI values greater than 25 kg/m2 are eligible for participation. The intervention will be to have the patients do aerobic exercise 150 minutes per week, and assess the BMI and health-related QOL using the care note questionnaire, at baseline, 6 months, and 12 months later for each participant. We are also planning dietary interventions for the patients. We will calculate the actual calorie consumption of each patient and give dietary advice for optimal calorie intake. Patients will be required to record their exercise in a formatted note so we can check the exercise adherenece. Citation Format: Arakaki M, Tamaki K, Kamada Y, Uehara K, Gushikawa H. The feasibility of nurse intervention to improve and maintain the BMI of breast cancer survivors over 25 to appropriate levels [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-13-18.
A phase I study investigating the combination of orally bioavailable platinum and nanoparticle albumin-bound paclitaxel in advanced solid tumors
Authors: H. A. Deshpande, S. Gettinger, E. Rowen, M. M. Abu-Khalaf, J. Clarke, A. J. Burns, W. K. Kelly
Journal: Journal of Clinical Oncology (2009)

e13501 Background: The combination of a taxane and a platinum agent is considered a standard chemotherapy regimen for many solid tumors. Adverse effects often limit the administration of these drugs. Satraplatin (S) is an orally bioavailable platinum agent with a similar spectrum of activity to other platinum analogs, but less renal or neurological side effects. The nanoparticle albumin-bound paclitaxel (A) has shown greater efficacy and less toxicity than Cremophor-based paclitaxel as a single agent in the treatment of breast cancer. The primary aim of this study was to determine a safe dose for the combination of S +A and to investigate if there were pharmacokinetic (PK) interactions between S + A in patients (pts) with advanced malignancies. Methods: Cohorts of 3–6 pts were enrolled and treated. Escalating oral doses of S (40–60- 80mg) were administered on days 1–5 in combination with intravenous fixed dose of A (100 mg/m 2 ) on 1, 8, and 15 of a 28 day cycle. Prior to cycle 1 all patients received A day -14. Blood samples for PK studies were drawn with the day -14 and Day 1 treatments. Results: To date 15 pts (2 renal, 3 prostate, 2 bladder, 1 hypopharyngeal, 1 mesothelioma, 1 colorectal, 1 melanoma and 2 leiomyosarcomas) with a median age 51 (range 37 - 78 yrs) have been treated in 3 cohorts. Doses were escalated as follows; Cohort 1 (40 (S)/100(A), n = 4), Cohort 2 (60/100, n = 7), Cohort 3 (80/100, n = 3). 1 patient (testicular cancer) intended for cohort 1 was a screen failure. Two patients in cohort 3 had grade 3\/4 neutropenia (DLT). An additional 4 patients were treated in cohort 2 without DLT and this dose level was determined to be the MTD. Most common severe adverse events were Grade 3 anemia (5%), neutropenia (22%), fatigue (5%) and dehydration (5%). 3 patients had grade 4 neutropenia, 2 in cycle 1 of cohort 3 and 1 in cycle 2 of cohort 2. To date 6 patients had progressive disease, 4 had stable disease (3.8 months), 3 patients (2 with prostate cancer and 1 with hypopharyngeal cancer) had a partial response. Conclusions: The combination of A plus S was well tolerated and the recommended dose for phase 2 studies is paclitaxel 100 mg/m2 weekly for 3 weeks plus satraplatin 60 mg/m 2 daily for 5 days every 28 days. PK analyses will be presented. [Table: see text]
Addition of Intermediate-Dose Methotrexate Is Beneficial in Terms of Both Progression-Free Survival and Overall Survival for Patients with Diffuse Large B Cell Lymphoma Receiving Either R-CHOP or CHOP
Authors: Eldad J. Dann, Neta Goldschmidt, Vered Heffes, Tanya Mashiach, Moshe E. Gatt, Netanel A Horowitz
Journal: Blood (2016)
Treatment of Myeloid and Lymphoid Malignancies with Highly Purified Alloreactive CD56+CD3− NK-Cells and Haploidentical Stem Cell Transplantation: Promising Results of a Phase I Study.
Authors: Chiara Gentilini, Urte Hilbers, Goetz Hartung, Thoralf Lange, Constanze Kliem, Ute Hegenbart, Mathias Zeis, Volker Huppert, Bertram Glass, Marcus Uhrberg, Norbert Schmitz, Eckhard Thiel, Dietger W. Niederwieser, Lutz Uharek
Journal: Blood (2005)
US Supreme Court allows accused doctor to be forcibly medicated
Authors: Owen Dyer
Journal: BMJ (2017)

A doctor accused of the murder of another doctor will be administered antipsychotic drugs against his will in an effort to make him competent to stand trial, after the US Supreme Court declined to hear his appeal against a Connecticut Supreme Court ruling.

Lishan Wang, 49, is accused of shooting dead Yale University physician Vajinder Toor in April 2010, and is also charged with attempted murder for shooting at Toor’s pregnant wife.

Both physicians had worked at Kingsbrook Jewish Medical Center in New York City, where they had often argued. Wang, a Chinese citizen, was eventually dismissed from the facility, and later filed a federal complaint alleging discrimination by ethnic Indian doctors there. …
Cardiac Fibroblast–Specific Activating Transcription Factor 3 Protects Against Heart Failure by Suppressing MAP2K3-p38 Signaling
Authors: Yulin Li, Zhenya Li, Congcong Zhang, Ping Li, Yina Wu, Chunxiao Wang, Wayne Bond Lau, Xin-liang Ma, Jie Du
Journal: Circulation (2017)

Hypertensive ventricular remodeling is a common cause of heart failure. However, the molecular mechanisms regulating ventricular remodeling remain poorly understood.We used a discovery-driven/nonbiased approach to identify increased activating transcription factor 3 (ATF3) expression in hypertensive heart. We used loss/gain of function approaches to understand the role of ATF3 in heart failure. We also examined the mechanisms through transcriptome, chromatin immunoprecipitation sequencing analysis, and in vivo and in vitro experiments.ATF3 expression increased in murine hypertensive heart and human hypertrophic heart. Cardiac fibroblast cells are the primary cell type expressing high ATF3 levels in response to hypertensive stimuli. ATF3 knockout (ATF3KO) markedly exaggerated hypertensive ventricular remodeling, a state rescued by lentivirus-mediated/miRNA-aided cardiac fibroblast-selective ATF3 overexpression. Conversely, conditional cardiac fibroblast cell-specific ATF3 transgenic overexpression significantly ameliorated ventricular remodeling and heart failure. We identified Map2K3 as a novel ATF3 target. ATF3 binds with the Map2K3 promoter, recruiting HDAC1, resulting in Map2K3 gene-associated histone deacetylation, thereby inhibiting Map2K3 expression. Genetic Map2K3 knockdown rescued the profibrotic/hypertrophic phenotype in ATF3KO cells. Last, we demonstrated that p38 is the downstream molecule of Map2K3 mediating the profibrotic/hypertrophic effects in ATF3KO animals. Inhibition of p38 signaling reduced transforming growth factor-β signaling-related profibrotic and hypertrophic gene expression, and blocked exaggerated cardiac remodeling in ATF3KO cells.Our study provides the first evidence that ATF3 upregulation in cardiac fibroblasts in response to hypertensive stimuli protects the heart by suppressing Map2K3 expression and subsequent p38-transforming growth factor-β signaling. These results suggest that positive modulation of cardiac fibroblast ATF3 may represent a novel therapeutic approach against hypertensive cardiac remodeling.
Uneven Progress in Preventing and Treating HIV Infections Worldwide
Authors: M.J. Friedrich
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma
Authors: P.J. Bröckelmann, H. Müller, O. Casasnovas, M. Hutchings, B. von Tresckow, M. Jürgens, S.J. McCall, F. Morschhauser, M. Fuchs, P. Borchmann, C.H. Moskowitz, A. Engert
Journal: Annals of Oncology (2017)
Genetic Polymorphisms in the Promoter Region of the beta-2 Adrenergic Receptor Are Associated with the Early Response of Acute Lymphoblastic Leukemia to Chemotherapy.
Authors: Meyling H. Cheok, Cong Ding, Wenjian Yang, Somas Das, Dario Campana, Cheng Cheng, Edwin H. Cook, Ching-Hon Pui, Mary V. Relling, William E. Evans
Journal: Blood (2004)