tbuckley/cabot-search huggingface dataset:
PP49. ASSESSMENT OF APOPTOSIS INDUCED BY METFORMIN IN GBM IN VITRO
Authors: Mr Lawrence Eagles, Dr Farjana Begam Rowther, Prof Weiguang Wang, Prof John Darling, Prof Tracy Warr
Journal: Neuro-Oncology (2017)

The development of new treatments for glioblastoma multiforme (GBM) is time-consuming and expensive and hence, the repurposing of existing medication could expedite new treatment strategies. Metformin is currently the most common antidiabetic drug treatment for type 2 diabetes in the world. Recent studies have demonstrated anti-proliferative effects of metformin in vitro in a range of tumour types. Although the mechanisms by which metformin exerts its anti-tumour effects are not fully understood, in prostate, pancreatic and lung cancer metformin has been shown to induce apoptosis. Previously, the ID50 values of a panel of 13 patient-derived GBM short-term cultures and the U251MG cell line to metformin were determined. Response to metformin has been shown to be significantly linked to p53 status. Induction of apoptosis following treatment with an ID50 dose of metformin was determined in 5 GBM short-term cultures and U251MG (ID50 values range from 1.45 to 25.34mM) and NHA (ID50 75mM) using flow cytometry. This was carried out at 24, 48, 72 and 96 hours post-treatment with metformin in media containing 3mM or 6mM glucose. The activity of caspases 3 and 7 in these cultures was also assessed at 72 and 96 hours post-treatment with metformin. In all cultures, the response to metformin was evident towards the end of the time course, with changes in cell populations only becoming apparent after 72 hours of treatment. Reduction of glucose in treatment media caused a significant (p= 0.0113 to 0.0467) increase in response to metformin at 72 hours, leading to earlier cell death. Levels of early apoptosis varied throughout the time course but none of the GBM cultures tested showed any statistical significant changes in levels of early apoptosis after metformin treatment regardless of glucose concentration (p>0.05). Measurement of caspase 3/7 activity varied between cultures. Those with mutated or deleted p53 showed higher caspase activity compared to wild-type cultures and this activity increased under lower glucose concentrations. In contrast, the p53 wild-type cultures demonstrated a reduction in caspase levels at 3mM concentrations. This study has demonstrated that glucose availability is associated with the cytotoxic response of GBM cells to metformin treatment. Lack of early apoptosis detected across the time course indicates that other mechanisms are involved in the response to metformin such as autophagy.
To Prevent Rheumatoid Arthritis, Look Past the Joints to the Gums
Authors: Jennifer Abbasi
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
Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer
Authors: Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Riikka Huovinen, Arja Jukkola-Vuorinen, Minna Tanner, Riitta Kokko, Johan Ahlgren, Päivi Auvinen, Outi Lahdenperä, Sanna Kosonen, Kenneth Villman, Paul Nyandoto, Greger Nilsson, Paula Poikonen-Saksela, Vesa Kataja, Jouni Junnila, Petri Bono, Henrik Lindman
Journal: JAMA Oncology (2017)

Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC).To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2).This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015.Recurrence-free survival (RFS).Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively).Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis.clinicaltrials.gov Identifier: NCT00114816.
SWOG S0518: Phase III prospective randomized comparison of depot octreotide plus interferon alpha-2b versus depot octreotide plus bevacizumab (NSC #704865) in advanced, poor prognosis carcinoid patients (NCT00569127).
Authors: James C. Yao, Katherine Guthrie, Cesar Moran, Jonathan R. Strosberg, Matthew H. Kulke, Jennifer A. Chan, Noelle K. LoConte, Robert R. McWilliams, Edward M. Wolin, Bassam Ibrahim Mattar, Shannon McDonough, Helen X. Chen, Charles David Blanke, Howard S. Hochster
Journal: Journal of Clinical Oncology (2015)

4004 Background: Treatment options for advanced carcinoid tumors (NETs) are limited. Somatostatin analogues (SSA) prolong progression-free survival (PFS) among patients (pts) who are treatment naïve or have stable disease. Interferon (INF) added to SSA has also demonstrated antitumor activity. Bevacizumab (BEV), added to SSA, octreotide (OCT), was associated with tumor regression and encouraging antitumor activity in a phase II study. The current study compares BEV + OCT to INF α-2b + OCT. Method: Pts with metastatic or unresectable, well-differentiated, G1/2 NETs with progressive disease or other poor prognostic features were randomly assigned (1:1) to receive OCT LAR 20 mg q 21 days with either BEV 15 mg/kg every 21 days or INF α-2b 5 million units three times per week. PFS by central review was the primary endpoint. Results: 427 pts were enrolled, of whom 402 were eligible, between December 2007 and September 2012. Median PFS by central review was 16.6 (95% CI: 12.9 – 19.6) months in BEV arm and 15.4 (95% CI: 9.6 – 18.6) months in the INF arm (HR 0.93; 95% CI 0.73-1.18; P = 0.55). By investigator review, median PFS was 15.4 (95% CI: 12.6 – 17.2) months in BEV arm and 10.6 (95% CI: 8.5 – 14.4) months in the INF arm (HR 0.90; 95% CI: 0.72 - 1.12; P = 0.33). TTF was significantly longer with BEV compared to INF (HR 0.72; 95% CI 0.58 - 0.89; P = 0.003). Median TTF was 9.9 (95% CI: 7.3 – 11.1) months in the BEV arm and 5.6 (95% CI 4.3 – 6.4) months in the INF arm. Confirmed radiologic response rates were 12% (95% CI: 8% - 18%) in the BEV arm and 4% (95% CI: 2% - 8%) in the INF arm. Common AEs with BEV + OCT included HTN (32%), proteinuria (9%), and fatigue (7%); and with INF + OCT included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion: BEV + OCT was associated with longer TTF compared to IFN + OCT; radiologic responses also appeared to be more frequent among pts treated with BEV + OCT. However, no significant differences in PFS were observed, suggesting that BEV and IFN have similar antitumor activity in pts with advanced carcinoid. Support: NIH/NCI grants CA180888, CA180819, CA180799, CA180820, CA180821 and CA025224, and in part by Genentech. Clinical trial information: NCT00569127.
Interim-Positron Emission Tomography with [18F]Fluorodeoxyglucose (interim-PET) Evaluation In Mediastinal Lymphoma Including Hodgkin Lymphoma (HL) and Primary Mediastinal Large B-Cell Lymphoma (PMBL)
Authors: Caroline Algrin, Nathalie Bérenger, Sylvie Chevret, Laetitia Vercellino, Cédric de Bazelaire, Pauline Brice, David Sibon, Patricia Franchi, Josette Briere, Eric de Kerviler, Christian Gisselbrecht, Catherine Thieblemont
Journal: Blood (2010)
Chronic Kidney Disease and That Risk Factor In Patients Alive More Than 10 Years After Allogenic Hematopoietic Stem Cell Transplantation.
Authors: Tatsunori Shimoi, Minoru Ando, Takeshi Kobayashi, Kazuhiko Kakihana, Takuya Yamashita, Kazuteru Ohashi, Hideki Akiyama, Hisashi Sakamaki
Journal: Blood (2010)
HEE staff cuts threaten medical education and patient care, BMA and unions warn
Authors: Abi Rimmer
Journal: BMJ (2017)

Plans to cut staff at Health Education England could damage the care of patients and affect the number of doctors in training, trade unions have warned.

On 23 February HEE, which is responsible for medical education and training in England, wrote to all its 2614 staff announcing a scheme to allow them to take voluntary redundancy to save money.

In 2014 the Department of Health for England announced that it was cutting HEE’s budget, which ran to £4.9bn (€5.8bn; $6.1bn) in 2015-16,1 by 20% by 2020.2 The move was a result of a 20% cut to the department’s own budget and is on top of the …
Abstract IA19: Phase II human clinical trials in mice-modeling inter-patient response heterogeneity in PDXs
Authors: Hui Gao
Journal: Clinical Cancer Research (2016)

Abstract The current strategy of profiling candidate therapeutics using a limited set of cancer models during pre-clinical development rarely enables accurate predictions of clinical efficacy, or the identification of factors underlying heterogeneous patient responses that inform clinical patient selection strategies. Novartis established ~1000 patient-derived tumor xenograft models (PDXs), where mutation and copy number based genomic landscape analyses revealed a relatively broad conservation of driver mutations found in human cancers. Using this panel of PDXs, we performed population-based in vivo compound screens using a 1x1x1 experimental design (PDX clinical trial or PCT). We demonstrate both the reproducibility and translatability of this approach by identifying associations between genotype and drug response, and clinically established mechanisms of resistance. We therefore propose a new experimental paradigm that can potentially revolutionize preclinical evaluation of novel treatment modalities and improve our ability to predict clinical trial response. Citation Format: Hui Gao. Phase II human clinical trials in mice-modeling inter-patient response heterogeneity in PDXs. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA19.
Effectiveness and cost-effectiveness of a nurse-delivered intervention to improve adherence to treatment for HIV: a pragmatic, multicentre, open-label, randomised clinical trial
Authors: Marijn de Bruin, Edwin J M Oberjé, Wolfgang Viechtbauer, Hans-Erik Nobel, Mickaël Hiligsmann, Cees van Nieuwkoop, Jan Veenstra, Frank J Pijnappel, Frank P Kroon, Laura van Zonneveld, Paul H P Groeneveld, Marjolein van Broekhuizen, Silvia M A A Evers, Jan M Prins
Journal: The Lancet Infectious Diseases (2017)
Phase II Study of Timed Sequential Therapy (TST) with Topotecan, Cytosine Arabinoside (ARA-C), and Mitoxantrone (TAM) Induction Therapy Followed by Non-Cross-Resistant Consolidation Chemotherapy for Adults with Newly Diagnosed Acute Myelogenous Leukemia (AML).
Authors: Ivana Gojo, Lawrence Morris, Chuanfa Guo, Meyer Heyman, Michael Tidwell, Jackie Greer, Maureen Klein, Marianne Irani, Judith Karp
Journal: Blood (2004)
Gene Expression Profiling of Myeloma Cells at Diagnosis Can Predict Response to Therapy with Thalidomide and Dexamethasone Combination.
Authors: Shaji Kumar, Philip R. Greipp, Jessica Haug, Michael Kline, Wee Joo Chng, Emily Blood, Leif Bergsagel, John A. Lust, Morie A. Gertz, Rafael Fonseca, S. Vincent Rajkumar
Journal: Blood (2005)
Differences in Mentor-Mentee Sponsorship in Male vs Female Recipients of National Institutes of Health Grants
Authors: Elizabeth W. Patton, Kent A. Griffith, Rochelle D. Jones, Abigail Stewart, Peter A. Ubel, Reshma Jagsi
Journal: JAMA Internal Medicine (2017)

This study uses data from a survey of NIH Mentored Career Development grant awardees to determine if sponsorship critical for career advancement of young professionals differs among men and women.
Dietary Supplementation with Docosahexanoic Acid (DHA) Improves RBC Flexibility and Reduces Cold Hypersensitivity in Mice with Sickle Cell Disease.
Authors: Nancy J. Wandersee, Madelyn S. Hanson, Jamie L. Maciaszek, Michael C. Larson, Katie M. Giger, Suilan Zheng, Dawn M. Retherford, Barbara Mickelson, Cheryl L. Stucky, Philip S. Low, George Lykotrafitis, Neil Hogg, Cheryl A. Hillery
Journal: Blood (2012)
β-2-Glycoprotein Antibodies Activate the Alternative Pathway of Complement in Antiphospholipid Antibody Syndrome
Authors: Andrea C. Baines, Xuan Yuan, Eleni Gavriilaki, Alexander J. Ambinder, Alka Jain, Neal S. Fedarko, C. John Sperati, Alison R. Moliterno, Rakhi P. Naik, Michael Streiff, Wei Fu, Michelle Petri, Robert A. Brodsky
Journal: Blood (2016)
Growth Inhibition of Human Multiple Myeloma Cells by a CD40 Ligand (CD40L, CD154) Transgene - Oncolytic Virus Construct.
Authors: Margret S. Rodrigues, Erica M. Gomes, Reuben Hernandez, Jack Chang, Joe Kansopon, Joseph Newman, Marvin J. Stone, Alex W. Tong
Journal: Blood (2006)
Abstract A10: Correlating magnetic resonance and molecular imaging using three dimensional untreated virtual control
Authors: Joshua Jacobs, Andrea Hawkins-Darrud, Robert Harrison, Sandra Johnston, Paul Kinahan, Kristin Swanson
Journal: Cancer Research (2017)

Abstract With mean survival from glioblastoma multiforme (GBM) barely edging over 15 months, it become imperative to develop novel tools informing on both progression and treatment efficacy. As the aggressive growth of GBM outstrips available resources, regions of hypoxia develop. Hypoxia can be clinically assessed through [18F]-flouromisonidazole (FMISO) PET. However, PET imaging suffers from low resolution and reconstruction artifact. We present the comparative and predictive results of a multi-stage model utilizing the mathematical biology of cancer and the physics of PET imaging. Our mathematical model of GBM characterizes cancer cells into the interacting phenotypes of normoxic, hypoxic, and necrotic cells supported by vasculature. The pharmacokinetic activity of FMISO is induced in the simulated tissue then acquired and reconstructed by an analytic simulator of the PET process. This multi-stage process creates a patient-specific virtual PET images with characteristic of the clinical PET scan. Extending previous work, we model the full three-dimensional dynamics of tumor progression, pharmacokinetic activity, and FMISO PET for the tumor kinetics of six GBM patients. Virtual and clinical FMISO PET images are compared. Overall hypoxic burden and spatial distribution show strong correspondence between virtual and clinical FMISO PET images for all six patients. Simulated FMISO PET dynamics, with tumor kinetics derived from routine clinical MRI scans, provide a unique and evolving tool giving insight into the biological connections between magnetic resonance and molecular imaging. Citation Format: Joshua Jacobs, Andrea Hawkins-Darrud, Robert Harrison, Sandra Johnston, Paul Kinahan, Kristin Swanson. Correlating magnetic resonance and molecular imaging using three dimensional untreated virtual control. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A10.
Oxidative Stress: Ultrasound Detection of Regional Oxidative Stress in Deep Tissues Using Novel Enzyme Loaded Nanoparticles (Adv. Healthcare Mater. 5/2017)
Authors: Emilia S. Olson, Inanc Ortac, Christopher Malone, Sadik Esener, Robert Mattrey
Journal: Advanced Healthcare Materials (2017)

Inanc Ortac, Emilia S. Olson, Robert Mattrey, and co-workers introduce an intravenously injectable probe labeling sites of oxidative injury in vivo in article number 1601163. The probe they develop is a nanoparticle platform enzymatically catalyzing H2O2 to water and oxygen producing microbubbles detectable by a clinical ultrasound system. They demonstrate the functionality of 200 nm nanoparticles in vivo in rat ischemic renal injury (IRI) model.
Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer
Authors: Juan M. Cejalvo, Eduardo Martínez de Dueñas, Patricia Galván, Susana García-Recio, Octavio Burgués Gasión, Laia Paré, Silvia Antolín, Rosella Martinello, Isabel Blancas, Barbara Adamo, Ángel Guerrero-Zotano, Montserrat Muñoz, Paolo Nucíforo, María Vidal, Ramón M. Pérez, José I. Chacón López-Muniz, Rosalía Caballero, Vicente Peg, Eva Carrasco, Federico Rojo, Charles M. Perou, Javier Cortés, Vincenzo Adamo, Joan Albanell, Roger R. Gomis, Ana Lluch, Aleix Prat
Journal: Cancer Research (2017)

Abstract Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We identified 47 genes that were expressed differentially in metastatic versus primary disease. Metastatic tumors were enriched for proliferation-related and migration-related genes and diminished for luminal-related genes. Expression of proliferation-related genes were better at predicting overall survival in metastatic disease (OSmet) when analyzed in metastatic tissue rather than primary tissue. In contrast, a basal-like gene expression signature was better at predicting OSmet in primary disease compared with metastatic tissue. We observed correlations between time to tumor relapse and the magnitude of changes of proliferation, luminal B, or HER2-E signatures in metastatic versus primary disease. Although the intrinsic subtype was largely maintained during metastatic progression, luminal/HER2-negative tumors acquired a luminal B or HER2-E profile during metastatic progression, likely reflecting tumor evolution or acquisition of estrogen independence. Overall, our analysis revealed the value of stratifying gene expression by both cancer subtype and tissue type, providing clinicians more refined tools to evaluate prognosis and treatment. Cancer Res; 77(9); 2213–21. ©2017 AACR.
R-COMP 21 (Prednisone, Cyclophosphamide, Vincristine, Myocettm and Rituximab) for Frail and Elderly Patients with Aggressive B-Cell Non-Hodgkin Lymphoma: A Pilot Study.
Authors: Alessandro Isidori, Felicetto Ferrara, Francesco Alesiani, Sonia Ronconi, Massimo Catarini, Francesca D’Adamo, Barbara Guiducci, Daniele Bernardi, Giuseppe Visani
Journal: Blood (2007)
Multiparameter Microscopy Analysis of the Follicular Lymphoma Microenvironment and Normal Germinal Centers: In Vivo evidence That Follicular Helper T Cells Form Synapses with Neoplastic B Cells and Are Associated with Proliferation and Expression of Activation Induced Cytidine Deaminase
Authors: William M Townsend, Robert Marcus, Jon Salisbury, Deborah Yallop, Piers EM Patten, Andrea GS Buggins, Stephen Devereux
Journal: Blood (2014)
CKS1B, Mapping to an Amplicon on Chromosome 1q21 and over Expressed in Aggressive Disease, Regulates Multiple Myeloma Growth and Survival through p27Kip1-Dependent and Independent Mechanisms.
Authors: Fenghuang Zhan, Simona Colla, James B. Chen, James P. Stewart, Xiaosong Wu, Yongsheng Huang, Ichiro Hanamura, Bart Burington, Shmuel Yaccoby, Joshua Epstein, Bart Barlogie, John D. Shaughnessy
Journal: Blood (2006)
Concentrations of Metalloproteinased-9 (MMP-9), Metalloproteinases -1 and-2 Tissue Inhibitors (TIMP-1, TIMP-2), Tumor Necrosis Factor-α (TNF-α), Hepatocyte Growth Factor (HGF), Dickkopf Related Proten 1 (DKK-1) and Emmprin (CD147) Expression Are Increased in Patients with Myeloma Multiplex and MMP-9 Correlates with advanced Stage of Disease
Authors: Donata Urbaniak-Kujda, Katarzyna Kapelko-Slowik, Dariusz Wolowiec, Jaroslaw Dybko, Iwona Prajs, Jacek Jakubaszko, Lidia Karabon, Kazimierz Kuliczkowski
Journal: Blood (2011)