tbuckley/cabot-search huggingface dataset:
Targeting glioma-initiating cells in GBM: ABTC-0904, a randomized phase 0/II study targeting the Sonic Hedgehog-signaling pathway.
Authors: Andrew E. Sloan, Charles John Nock, Xiaobu Ye, Amber Kerstetter, Jeff Supko, Kathleen Lamborn, Jeremy N. Rich, Robert Miller, Naoko Takebe, Michael Prados, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2014)

2026 Background: The prognosis for GBM, which appears to be driven by glioma initiating cells (GIC), remains poor. Our hypothesis was that interrupting sonic hedgehog signaling (SHh) would inhibit GIC activity and improve PFS (PFS6). Methods: A two armed, randomized phase 0/II study of Vismodegib, an inhibitor of SMO, was performed in 40 patients undergoing resection for recurrent GBM (rGBM). The trial hypothesis was to achieve 25% PFS6 rate compared to a null of 10 % with a 90% power and a 10% type I error rate (1-sided). Arm I received Vismodegib for 7 days pre-operatively; Arm II was not treated pre-operatively. All patients were treated with Vismodegib post-operatively. Primary objective was to assess PFS6, with secondary endpoints of median overall survival, response and toxicity. Secondary objectives included determination of: intra-tumoral PK and PD; inhibition of SHh signaling by RT-PCR and immunohistochemistry; and inhibition of GIC proliferation and self-renewal by neurosphere proliferation and limited dilution assay. Results: PK/PD data and tumor specimens were obtained from 39 of the 40 patients. Median drug levels in plasma and tissue were7638 and 3270 ng/ml respectively for patients in Arm I. SHh signaling intermediates (Gli-1, Gli-2, PTCH-1b) were 3.3 to 110-fold decreased in Arm I vs. Arm II (p<0.0002). Finally, proliferating CD133+ neurospheres were derived from 14 of the 39 cultures assessed and array CGH suggested GIC (vs. NSC) as the cells of origin. The proportion of tumor-derived CD133+neurospheres undergoing proliferation and self-renewal was decreased in Arm I vs. II (p <0.005 and p < 0.003 respectively). PFS6 and OS were 1.8m and 8.3m respectively; but there was no difference between the two arms. Conclusions: Vismodegib was well tolerated but not efficacious as a single agent in rGBM. However, this agent achieved therapeutic intra-tumoral concentration in rGBM and had biological activity on proliferation and self-renewal of GBM derived CD133+neurospheres. Combinatorial therapy targeting SHh pathway in GBM should be pursued. Clinical trial information: NCT00980343.Incidence of CD133+ neurospheres by arm. Arm # Evaluable specimens # (%) which made CD133+NS (p = 0.005 Fisher exact test) I 20 3 II 19 11
Adaptive reprogramming of NK cells in X-linked lymphoproliferative syndrome
Authors: Stephen Opat, Anna C. Hearps, Kevin Thia, Agnes Yuen, Ben Rogers, Mkunde Chachage, Gregory Moore, Jake Shortt, Georgina Ryland, Piers Blombery, Anthony P. Schwarer, Tahereh Noori, Joseph A. Trapani, Anthony Jaworowski, Ilia Voskoboinik
Journal: Blood (2017)
Five-Year Cost-effectiveness of the Multidisciplinary Risk Assessment and Management Programme–Diabetes Mellitus (RAMP-DM)
Authors: Fang Fang Jiao, Colman Siu Cheung Fung, Eric Yuk Fai Wan, Anca Ka Chun Chan, Sarah Morag McGhee, Ruby Lai Ping Kwok, Cindy Lo Kuen Lam
Journal: Diabetes Care (2017)

OBJECTIVE To estimate the cost-effectiveness of the multidisciplinary Risk Assessment and Management Programme–Diabetes Mellitus (RAMP-DM) in primary care patients with type 2 diabetes in comparison with usual primary care in a cohort with 5 years’ follow-up. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study among 17,140 propensity score–matched participants in RAMP-DM and those under usual primary care. The effectiveness measures were cumulative incidences of complications and all-cause mortality over 5 years. In a bottom-up approach, we estimated the program costs of RAMP-DM and health service utilization from the public health service provider’s perspective. The RAMP-DM program costs included the setup costs, ongoing intervention costs, and central administrative costs. We calculated the incremental cost-effectiveness ratio by dividing the incremental costs by the incremental effectiveness of the RAMP-DM group compared with those of the usual-care group. RESULTS There were significantly lower cumulative incidences of individual on any complications (15.34% vs. 28.65%, P &amp;lt; 0.001) and all-cause mortality (7.96% vs. 21.35%, P &amp;lt; 0.001) in the RAMP-DM group compared with the usual-care group. The mean program cost of RAMP-DM was 157 U.S. dollars (range 66–209) per participant over 5 years. The costs of health service utilization among participants in RAMP-DM group was 7,451 USD less than that of the usual-care group, resulting in a net savings of 7,294 USD per individual. CONCLUSIONS RAMP-DM added to usual primary care was a cost-saving intervention in managing diabetes in patients over 5 years. These findings support the integration of RAMP-DM as part of routine primary care for all patients with diabetes.
Abstract 18728: Loss of Homeodomain-Interacting Protein Kinase 2 in Cardiomyocytes Leads to Cardiac Dysfunction
Authors: Yuanjun Guo, Jennifer Sui, Qinkun Zhang, Joey Barnett, Thomas Force, Hind Lal
Journal: Circulation (2017)

Introduction: Heart failure is the leading cause of mortality worldwide. Despite progresses made in the treatment of most cardiovascular diseases, the prevalence and mortality of heart failure are ...
First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with Advanced Solid Tumors
Authors: Manuel Hidalgo, Maria Martinez-Garcia, Christophe Le Tourneau, Christophe Massard, Elena Garralda, Valentina Boni, Alvaro Taus, Joan Albanell, Marie-Paule Sablin, Marie Alt, Ratislav Bahleda, Andrea Varga, Christophe Boetsch, Izolda Franjkovic, Florian Heil, Angelika Lahr, Katharina Lechner, Anthony Morel, Tapan Nayak, Simona Rossomanno, Kevin Smart, Kay Stubenrauch, Oliver Krieter
Journal: Clinical Cancer Research (2017)

Purpose: Vanucizumab is an investigational antiangiogenic, first-in-class, bispecific mAb targeting VEGF-A and angiopoietin-2 (Ang-2). This first-in-human study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of vanucizumab in adults with advanced solid tumors refractory to standard therapies.Experimental Design: Patients received escalating biweekly (3-30 mg/kg) or weekly (10-30 mg/kg) intravenous doses guided by a Bayesian logistic regression model with overdose control.Results: Forty-two patients were treated. One dose-limiting toxicity, a fatal pulmonary hemorrhage from a large centrally located mediastinal mass judged possibly related to vanucizumab, occurred with the 19 mg/kg biweekly dose. Arterial hypertension (59.5%), asthenia (42.9%), and headache (31%) were the most common toxicities. Seventeen (41%) patients experienced treatment-related grade ≥3 toxicities. Toxicity was generally higher with weekly than biweekly dosing. A MTD of vanucizumab was not reached in either schedule. Pharmacokinetics were dose-linear with an elimination half-life of 6-9 days. All patients had reduced plasma levels of free VEGF-A and Ang-2; most had reductions in KTRANS (measured by dynamic contrast-enhanced MRI). Two patients (renal cell and colon cancer) treated with 30 mg/kg achieved confirmed partial responses. Ten patients were without disease progression for ≥6 months. A flat-fixed 2,000 mg biweekly dose (phamacokinetically equivalent to 30 mg/kg biweekly) was recommended for further investigation.Conclusions: Biweekly vanucizumab had an acceptable safety and tolerability profile consistent with single-agent use of selective inhibitors of the VEGF-A and Ang/Tie2 pathway. Vanucizumab modulated its angiogenic targets, impacted tumor vascularity, and demonstrated encouraging antitumor activity in this heterogeneous population. Clin Cancer Res; 24(7); 1536-45. ©2017 AACR.
La déclaration obligatoire des laboratoires en Allemagne : une enquête sur les comportements, les pratiques et les besoins
Authors: A P Zucs, J Benzler, G Krause
Journal: Eurosurveillance (2005)

En 2000, le nouveau texte de loi allemand sur le controle des maladies infectieuses a remplace la declaration agregee de cas par la declaration individuelle. Le processus a ete facilite par l’introduction simultanee du transfert electronique de donnees dans le systeme de sante publique. Les laboratoires declarants n’ont pas ete connectes electroniquement a ce reseau. Une enquete a ete menee en 2003, par le biais d’un questionnaire envoye par la poste a 537 laboratoires de microbiologie medicaux allemands, afin de connaitre leur habitudes de declaration, leur preference pour une declaration electronique et l’equipement correspondant en logiciels. Pres de 90% des repondants ont indique un delai de declaration qui ne depassait pas 24 heures, et 45% continuaient a remplir manuellement des formulaires papier pour les notifications. 74% des laboratoires se montraient favorables a l’introduction de la notification electronique. 33% d’entre eux n’utilisent pas de logiciel specifique a la microbiologie et les 67% restants ont cite 62 produits differents. Des projets pilotes avec des fabricants de logiciels selectionnes pourraient etre utiles pour la mise en place d’un format electronique standardise de declaration des maladies infectieuses en Allemagne.
Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups
Authors: Niccolo Bolli, Giulia Biancon, Matahi Moarii, Silvia Gimondi, Yilong Li, Chiara de Philippis, Francesco Maura, Vijitha Sathiaseelan, Yu-Tzu Tai, Laura Mudie, Sarah O’Meara, Keiran Raine, Jon W. Teague, Adam P. Butler, Cristiana Carniti, Moritz Gerstung, Tina Bagratuni, Efstathios Kastritis, Meletios Dimopoulos, Paolo Corradini, Kenneth C. Anderson, Philippe Moreau, Stephane Minvielle, Peter J. Campbell, Elli Papaemmanuil, Herve Avet-Loiseau, Nikhil C. Munshi
Journal: Leukemia (2018)

In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication.
Emerging Role of CRISPR/Cas9 Technology for MicroRNAs Editing in Cancer Research
Authors: Guillermo Aquino-Jarquin
Journal: Cancer Research (2017)

MicroRNAs (miRNA) are small, noncoding RNA molecules with a master role in the regulation of important tasks in different critical processes of cancer pathogenesis. Because there are different miRNAs implicated in all the stages of cancer, for example, functioning as oncogenes, this makes these small molecules suitable targets for cancer diagnosis and therapy. RNA-mediated interference has been one major approach for sequence-specific regulation of gene expression in eukaryotic organisms. Recently, the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system, first identified in bacteria and archaea as an adaptive immune response to invading genetic material, has been explored as a sequence-specific molecular tool for editing genomic sequences for basic research in life sciences and for therapeutic purposes. There is growing evidence that small noncoding RNAs, including miRNAs, can be targeted by the CRISPR/Cas9 system despite their lacking an open reading frame to evaluate functional loss. Thus, CRISPR/Cas9 technology represents a novel gene-editing strategy with compelling robustness, specificity, and stability for the modification of miRNA expression. Here, I summarize key features of current knowledge of genomic editing by CRISPR/Cas9 technology as a feasible strategy for globally interrogating miRNA gene function and miRNA-based therapeutic intervention. Alternative emerging strategies for nonviral delivery of CRISPR/Cas9 core components into human cells in a clinical context are also analyzed critically. Cancer Res; 77(24); 6812-7. ©2017 AACR.
TK216, a Novel, Small Molecule Inhibitor of the ETS-Family of Transcription Factors, Displays Anti-Tumor Activity in AML and DLBCL
Authors: Katayoun Jessen, Eric Moseley, Elaine Yee Lin Chung, Lauren Otuski, Chiara Tarantelli, Eugenio Gaudio, James Breitmeyer, James Freddo, Jeffrey Toretsky, Francesco Bertoni, Brian J Lannutti
Journal: Blood (2016)
Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin
Authors: Sharraya Aschemeyer, Bo Qiao, Deborah Stefanova, Erika V. Valore, Albert C. Sek, T. Alex Ruwe, Kyle R. Vieth, Grace Jung, Carla Casu, Stefano Rivella, Mika Jormakka, Bryan Mackenzie, Tomas Ganz, Elizabeta Nemeth
Journal: Blood (2017)
The Role of Gabapentin in Multimodal Postoperative Pain Management
Authors: Michael A. Ashburn, Lee A. Fleisher
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
2008 George L. Duff Memorial Lecture—Cardiovascular Disease: From Genetics to Systems Biology
Authors: Aldons J. Lusis
Journal: Circulation (2008)

Cardiovascular disease involves hundreds of genes, many environmental factors, and myriad interactions. Although studies of Mendelian traits and transgenic mice have been very informative, analyzing the individual components of a system is not sufficient. We would like to know how these components interact with each other and how these interactions differ in disease states. Toward this end, we have over the last several years attempted to develop an approach that integrates common DNA variations, global gene expression array analyses, and clinical phenotypes. The approach uses segregating populations of mice or randomized populations of human subjects that are typed for genetic markers as well as clinically relevant traits. In addition, we carry out global expression array analyses of tissues or cells from the subjects. This approach greatly facilities gene discovery, since one can examine correlations between transcript levels and clinical traits. It also permits the construction of gene coexpression networks that underlie cardiovascular disease.  We have applied the approach in different ways to examine clinically relevant traits. First, we used knowledge of loci controlling transcript levels to help identify genes for vascular calcification and high-density lipoprotein levels. Second, we used probabilistic modeling to predict several novel genes involved in metabolic syndrome. Third, we used primary endothelial and smooth muscle cell lines from human subjects to construct gene networks for inflammatory responses.
Ethnic Differences in the Prevalence and Risk Factors of Diabetic Retinopathy
Authors: Gavin S. Tan, Alfred Gan, Charumathi Sabanayagam, Yih Chung Tham, Kumari Neelam, Paul Mitchell, Jie Jin Wang, Ecosse L. Lamoureux, Ching-Yu Cheng, Tien Y. Wong
Journal: Ophthalmology (2017)
<i>KRAS</i> Testing, Tumor Location, and Survival in Patients With Stage IV Colorectal Cancer: SEER 2010–2013
Authors: Mary E. Charlton, Amanda R. Kahl, Alissa A. Greenbaum, Jordan J. Karlitz, Chi Lin, Charles F. Lynch, Vivien W. Chen
Journal: Journal of the National Comprehensive Cancer Network (2017)

Purpose: KRAS mutations and tumor location have been associated with response to targeted therapy among patients with stage IV colorectal cancer (CRC) in various trials. This study performed the first population-based examination of associations between KRAS mutations, tumor location, and survival, and assessed factors associated with documented KRAS testing. Methods: Patients with stage IV adenocarcinoma of the colon/rectum diagnosed from 2010 to 2013 were extracted from SEER data. Analyses of patient characteristics, KRAS testing, and tumor location were conducted using logistic regression. Cox proportional hazards models assessed relationships between KRAS mutations, tumor location, and risk of all-cause death. Results: Of 22,542 patients, 30% received KRAS testing, and 44% of these had mutations. Those tested tended to be younger, married, and metropolitan area residents, and have private insurance or Medicare. Rates of KRAS testing also varied by registry (range, 20%–46%). Patients with right-sided colon cancer (vs left-sided) tended to be older, female, and black; have mucinous, KRAS-mutant tumors; and have a greater risk of death (hazard ratio [HR], 1.27; 95% CI, 1.22–1.32). KRAS mutations were not associated with greater risk of death in the overall population; however, they were associated with greater risk of death among patients with left-sided colon cancer (HR, 1.19; 95% CI, 1.05–1.33). Conclusions: This large population-based study showed that among patients initially diagnosed with stage IV CRC, right-sided colon cancer was associated with greater risk of death compared with left-sided cancer, and KRAS mutations were only associated with risk of death in left-sided colon cancer. An unexpected finding was that among patients with stage IV disease, right-sided cancer was more commonly seen in black patients versus whites. Future studies should further explore these associations and determine the role of biology versus treatment differences. In addition, use of KRAS testing is increasing, but there is wide geographic variation wherein disparities related to insurance coverage and rurality may warrant further study.
Improved Survival After Implementation of a Large-Scale Regional Dedicated Aortic Network
Authors: Baptiste Duceau, Jean-Marc Alsac, Florence Bellenfant, Arnaud Mailloux, Vibol Chhor, Alix Lagrange, Salma El Batti, Bernard Cholley, Paul Achouh, Romain Pirracchio
Journal: Journal of the American College of Cardiology (2017)
Zoledronic Acid Dosing in Patients With Metastatic Breast Cancer—Reply
Authors: Gabriel N. Hortobagyi, Ming Zheng
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Abstract IA11: Interactions between the genome and immune microenvironment in head and neck cancer
Authors: Luc G. T. Morris
Journal: Clinical Cancer Research (2017)

Abstract Precision oncology is a term used to describe the attempt to match every cancer patient's tumor to the right drug or treatment, generally based on molecular or genomic features. At Memorial Sloan Kettering Cancer Center, the implementation of a targeted next-generation sequencing panel into routine clinical care for all patients with advanced tumors has allowed us to profile over 16,000 tumors in the past few years. The goal of such an approach has primarily been to match patients with recurrent and metastatic tumors to targeted therapies under the aegis of basket studies, and secondarily, to learn more about the unique biology of advanced cancers. This presentation will review the implementation of this precision oncology approach to patients with advanced head and neck cancer, particularly focused on squamous cell (HNSCC) and salivary carcinoma. The low number of targetable alterations in most head and neck tumor histologies has allowed for a modest degree of matching with targeted therapies. The program, however, has provided unprecedented insight into unique molecular features in recurrent/metastatic head and neck cancer. Some of the unique aspects discussed will be the genetic findings in aggressive HPV+ HNSCC and major subtypes of salivary cancer including adenoid cystic and salivary duct carcinoma. We are now entering an exciting era where we now understand that immunotherapy is highly active in HNSCC. This is largely the result of decades of basic immunologic investigation into identifying and targeting specific T cell checkpoint molecules. Phenomenal responses have been observed in patients with HNSCC, with overall response rates for heavily pretreated patients with metastatic disease in the 15-25% range. Unfortunately, many patients currently do not experience tumor responses. There is therefore a critical need to understanding patient and tumor features that may be predictive of response to immunotherapies such as immune checkpoint inhibitors. Immunogenomic approaches can provide insight into some of the aspects of tumor cells (such as mutation or neoantigen burden), or the tumor immune microenvironment (such as immune cell infiltration, measures of T cell activation, and expression of immunoregulatory molecules). Implementation of such approaches for HNSCC and salivary cancers in the context of a precision oncology approach to cancer care, can provide important insights to guide the next steps of clinical research. Multidimensional immunogenomic analyses can provide new insights into how the tumor genome and immune system interact with and shape one another. Citation Format: Luc G. T. Morris. Interactions between the genome and immune microenvironment in head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA11.