tbuckley/cabot-search huggingface dataset:
Subgroup analysis of patients (pts) with Gorlin syndrome treated with vismodegib (VISMO) in the STEVIE study
Authors: N. Basset-Seguin, J. Hansson, R. Kunstfeld, J.J. Grob, B. Dreno, L. Mortier, P.A. Ascierto, N. Dimier, A. Fittipaldo, I. Xynos, A. Hauschild
Journal: Annals of Oncology (2016)
Is Antilymphocyte Globulin Useful in Conditioning Regimen of Unrelated Donor Hematopoïetic Stem Cell Transplantation?.
Authors: Helene Esperou, Marie Lorraine Appert, Ibrahim Yacoub Agha, Noel Milpied, Norbert Ifrah, Mathieu Kuentz, Zina Chir, Colette Raffoux
Journal: Blood (2005)
Tolerability, efficacy and acceptability of fentanyl pectin nasal spray for breakthrough cancer pain
Authors: A. Massimiliano, G. Bronte, F.P. Spataro, E. Bronte, V.B. Leonardi, A. Usset, A. Laudani, C. Arcuri, M.P. Cusimano, A. Russo
Journal: Annals of Oncology (2016)
Comprehensive molecular characterization of multifocal glioblastoma proves its monoclonal origin and reveals novel insights into clonal evolution and heterogeneity of glioblastomas
Authors: Khalil Abou-El-Ardat, Michael Seifert, Kerstin Becker, Sophie Eisenreich, Matthias Lehmann, Karl Hackmann, Andreas Rump, Gerrit Meijer, Beatriz Carvalho, Achim Temme, Gabriele Schackert, Evelin Schröck, Dietmar Krex, Barbara Klink
Journal: Neuro-Oncology (2016)

The evolution of primary glioblastoma (GBM) is poorly understood. Multifocal GBM (ie, multiple synchronous lesions in one patient) could elucidate GBM development.We present the first comprehensive study of 12 GBM foci from 6 patients using array-CGH, spectral karyotyping, gene expression arrays, and next-generation sequencing.Multifocal GBMs genetically resemble primary GBMs. Comparing foci from the same patient proved their monoclonal origin. All tumors harbored alterations in the 3 GBM core pathways: RTK/PI3K, p53, and RB regulatory pathways with aberrations of EGFR and CDKN2A/B in all (100%) patients. This unexpected high frequency reflects a distinct genetic signature of multifocal GBMs and might account for their highly malignant and invasive phenotype. Surprisingly, the types of mutations in these genes/pathways were different in tumor foci from the same patients. For example, we found distinct mutations/aberrations in PTEN, TP53, EGFR, and CDKN2A/B, which therefore must have occurred independently and late during tumor development. We also identified chromothripsis as a late event and in tumors with wild-type TP53. Only 2 events were found to be early in all patients: single copy loss of PTEN and TERT promoter point mutations.Multifocal GBMs develop through parallel genetic evolution. The high frequency of alterations in 3 main pathways suggests that these are essential steps in GBM evolution; however, their late occurrence indicates that they are not founder events but rather subclonal drivers. This might account for the marked genetic heterogeneity seen in primary GBM and therefore has important implications for GBM therapy.
Erratum to: Trans effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models
Authors: Maite Mendioroz, Catherine Do, Xiaoling Jiang, Chunhong Liu, Huferesh K. Darbary, Charles F. Lang, John Lin, Anna Thomas, Sayeda Abu-Amero, Philip Stanier, Alexis Temkin, Alexander Yale, Meng-Min Liu, Yang Li, Martha Salas, Kristi Kerkel, George Capone, Wayne Silverman, Y. Eugene Yu, Gudrun Moore, Jerzy Wegiel, Benjamin Tycko
Journal: Genome biology (2016)
Younger age as a prognostic indicator in breast cancer: Correlation between clinical-pathologic factors and miRNAs and long-term follow-up
Authors: M.T.M. Martinez, M. PeÑa-Chilet, S.S. Oltra, J.A. Perez-Fidalgo, E. Alonso, O. Burgues, I. Chirivella Gonzalez, B. Bermejo, A. Lluch-Hernandez, G. Ribas
Journal: Annals of Oncology (2016)
Urinary prostanoids in preschool wheeze
Authors: Jonathan Grigg, Abigail Whitehouse, Hitesh Pandya, Stephen Turner, Christopher J. Griffiths, Tom Vulliamy, Robert T. Walton, David B. Price, Marek Sanak, John W. Holloway, Lee Noimark, Maia Lesosky, Rossa Brugha, Lee Koh, Chinedu Nwokoro
Journal: European Respiratory Journal (2016)

Acute episodes of wheeze in children of preschool age are frequently triggered by viral upper respiratory tract infections and result in a significant burden to health services [1]. However, to date, the inflammatory mechanisms underlying preschool wheeze remain unclear. Mediators that have not been studied in preschool wheeze, but are implicated in the pathogenesis of wheeze in adults with asthma, include the pro-inflammatory prostanoid prostaglandin D2 (PGD2) [2] and the anti-inflammatory prostanoid PGE2 [3, 4]. In this study, we sought evidence for either increased PGD2 biosynthesis or reduced PGE2 biosynthesis, or a combination of both in children with preschool wheeze. To achieve this, we measured the major metabolites of PGD2 and PGE2 in the urine: 9α-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostan-1,20-dioic acid (tetranor-PGDM) and 9,15-dioxo-11α-hydroxy-13,14-dihydro-2,3,4,5-tetranor-prostan-1,20-dioic acid (tetranor-PGEM), respectively [5, 6]. Tetranor PGDM, a urinary metabolite of prostaglandin D2, is increased in children with preschool wheeze <http://ow.ly/Ynjy305ZY9L> The author contributions are as follows. J. Grigg was the chief investigator, planned and provided overall supervision of the study, wrote the manuscript and vouches for these data. A. Whitehouse performed data analysis and contributed to the final manuscript. M. Lesosky undertook the multiple regression analysis and contributed to the final manuscript. C. Nwokoro and R. Brugha supervised the study and contributed to the final manuscript. H. Pandya, S. Turner, R. Walton and D. Price contributed to study planning and to drafting the final manuscript. T. Vulliamy, J.W. Holloway and C.J. Griffiths contributed to study planning and contributed to the final manuscript. M. Sanak performed urinary prostanoid analysis and contributed to the final manuscript. L. Noimark obtained data from controls and contributed to the final manuscript. L. Koh supervised data from controls, collated data and contributed to the final manuscript.
P53 non-disruptive mutation is a negative predictive factor in EGFR M+ NSCLC treated with TKI
Authors: F. Griesinger, M. Netchaeva, A. Lüers, R. Prenzel, D. Scriba, K.C. Willborn, U. Stropiep, C. Hallas, M. Falk, M. Tiemann, N. Neemann, L.C. Heukamp, J. Roeper
Journal: Annals of Oncology (2016)
Myeloablative Versus Reduced Intensity Allogeneic Stem Cell Transplantation in Relapsed Hodgkin’s Lymphoma in Recent Years. a Retrospective Analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Sonja G Genadieva Stavrik, Ariane Boumendil, Kirsty Thomson, Javier Briones, Paolo Corradini, Andrea Bacigalupo, Gerard Socie, Guiseppe Bandini, Herve Finel, Andrea Velardi, Michael Potter, Bruno Benedetto, Luca Castagna, Charles Craddock, Nigel Russell, Peter Dreger, Sureda Anna
Journal: Blood (2014)
TAA/ecdCD40L VPP Vaccination Induces Robust Adaptive Immune Response Even in Individuals with Post Transplantation Lymphopenia
Authors: Tae Hae Han, Yucheng Tang, Yeon Hee Park, Jonathan Maynard, Pingchuan Li, Hakan Akbulut, Line Petersen, Albert B. Deisseroth
Journal: Blood (2008)
Targeted Nanoparticles for the Delivery of Antagomir17: New Approach for the Treatment of Chronic Lymphocytic Leukemia
Authors: Sara Capolla, Riccardo Bomben, Sonia Zorzet, Ruben Spretz, Tiziana D'Agaro, Gustavo Larsen, Gabriele Pozzato, Valter Gattei, Luis Nunez, Paolo Macor
Journal: Blood (2015)
IMST-03. A CRITICAL ROLE FOR DENDRITIC CELLS IN PRIMING A ROBUST ANTI-GLIOMA CD8 T CELL RESPONSE FOLLOWING PICORNAVIRUS VACCINATION
Authors: Courtney Malo, Danielle Renner
Journal: Neuro-Oncology (2016)

Vaccine strategies to treat central nervous system (CNS) cancers hold great promise. However, the mechanisms leading to generation of an immune response to CNS cancers are unclear. Specifically, the antigen presenting cell (APC) required to activate a CNS tumor antigen-specific T cell response is unknown. To address this question, we generated a novel cell-type specific deletion of the H-2Kb MHC I molecule in C57BL/6 mice. By deleting H-2Kb on proposed APCs, including dendritic cells (DCs), macrophages, and microglia, we can define which APCs are required to result in effective vaccination for the murine GL261-quad cassette glioma model, which expresses the chicken ovalbumin peptide SIINFEKL as a model antigen. We hypothesized that DCs are required for generation of a natural adaptive immune response to SIINFEKL, and that DC-specific deletion of H-2Kb would abrogate efficacy of a picornavirus vaccination encoding SIINFEKL. We assessed tumor burden and immune infiltration in GL261-quad cassette bearing mice that had a complete deletion of H-2Kb (CMV-cre Kb cKO), DC-specific deletion of H-2Kb (CD11c-cre Kb cKO), or littermate controls. We demonstrated that DC-specific deletion of H-2Kb increases the proportion of animals bearing gliomas, suggesting a role for DCs in induction of a natural anti-tumor immune response. Additionally, we determined that vaccination of CD11c-cre Kb cKO mice resulted in an intermediate level of efficacy as measured by immune infiltration and tumor size. Thus, DCs are critical for generation of a complete anti-glioma T cell response, but they are not the sole APC in the context of a CNS tumor. Importantly, because DCs are modulated by many standard-of-care therapies, understanding their role in anti-tumor responses in the CNS is critical for vaccine development. Furthermore, because DC-specific deletion of H-2Kb resulted in an intermediate phenotype, a critical future direction will address the role of other candidate APCs, including macrophages and microglia.
TITAN: A randomized, double-blind, placebo-controlled, phase 3 trial of apalutamide (ARN-509) plus androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC)
Authors: K.N. Chi, S. Chowdhury, P. Radziszewski, T. Lebret, M. Ozguroglu, C. Sternberg, R.B. Sims, M. Yu, V. Naini, M. Darif, A.S. Merseburger
Journal: Annals of Oncology (2016)
Racial Differences in Associations of Blood Pressure Components in Young Adulthood With Incident Cardiovascular Disease by Middle Age
Authors: Yuichiro Yano, Jared P. Reis, Yacob G. Tedla, David C. Goff, David R. Jacobs, Stephen Sidney, Hongyan Ning, Kiang Liu, Philip Greenland, Donald M. Lloyd-Jones
Journal: JAMA Cardiology (2017)

Data are sparse regarding which blood pressure (BP) components in young adulthood optimally determine cardiovascular disease (CVD) by middle age.To assess which BP components best determine incident CVD events in young adults and determine whether these associations vary by race and age at BP measurement.Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, this study assessed the longitudinal race-stratified associations between BP and cardiovascular outcomes. CARDIA is a community-based cohort that recruited black and white individuals (age range, 18-30 years) from March 26, 1985, through June 7, 1986. CARDIA followed up participants for up to 28 years, and 94% of the surviving cohort completed at least 1 telephone interview or examination from August 2009 through August 2014.Blood pressures measubred at baseline (Y0) and 15 years later (Y15).Composite CVD events, including coronary heart disease, stroke, heart failure, and other vascular diseases.A total of 4880 participants participated in the study (mean [SD] age, 24.9 [3.6] years at Y0 and 25.0 [3.6] years at Y15; 2223 male [45.6%] at Y0 and 1800 [44.2%] at Y15; 2657 female [54.4%] at Y0 and 2277 [55.8%] at Y0; 2473 black individuals [50.7%] at Y0 and 1994 [48.9%] at Y15; and 2407 white individuals [49.3%] at Y0 and 2083 [51.1%] at Y15). The mean SBP/DBP was 112/69 mm Hg in blacks and 109/68 mm Hg in whites at Y0 and 117/77 mm Hg in blacks and 110/72 mm Hg in whites at Y15. During a 25-year follow-up from Y0, 210 CVD events occurred (twice as many events in blacks [n = 140] compared with whites), of which 131 (87 in blacks) occurred after Y15. With adjustments for covariates, results from Cox proportional hazards models, including SBP and DBP, jointly suggested that, at Y0, SBP (hazard ratio [HR] per 1-SD increase, 1.32; 95% CI, 1.09-1.61) but not DBP (HR, 1.05; 95% CI, 0.88-1.26) was associated with CVD risk in blacks, whereas DBP (HR, 1.74; 95% CI, 1.21-2.50) but not SBP (HR, 0.82; 95% CI, 0.57-1.18) was associated with CVD risk in whites. At Y15, SBP was the strongest indicator of CVD in blacks (HR, 1.64; 95% CI, 1.25-2.16) and whites (HR, 1.67; 95% CI, 1.02-2.69).This study questions the classic view that DBP is more able to identify future CVD events than SBP in all individuals younger than 50 years. In young adulthood, SBP in black individuals and DBP in white individuals were the most robust indicators of future CVD. In middle-age, SBP in both races identified risk of incident CVD.
Use of co-expression of HGF and c-Met to predict peritoneal dissemination established by autocrine HGF/c-Met signaling in gastric cancer.
Authors: Y. Toiyama, K. Tanaka, H. Yasuda, S. Saigusa, H. Fujikawa, Y. Mohri, Y. Inoue, C. Miki, T. Tabata, M. Kusunoki
Journal: Journal of Clinical Oncology (2011)

40 Background: Epithelial mesencymal transition (EMT) promotes facilitates migration and invasion of epithelial tumour cells. EMT is induced by growth factors implicated in theses process such as hepatocyte growth factor (HGF). Our aim of this study is whether HGF/c-Met pathway is associated with metastasis of gastric cancer (GC), especially in peritoneal dissemination (PD). Methods: HGF and c-Met expression and EMT related molecules were evaluated using real-time PCR and immunohistochemistry in GC tissues. The role of HGF/c-Met pathway for EMT and anoikis was determined and c-Met TKI (SU11274) was tested for their ability to block HGF-induced biological effects in vitro and vivo. Results: In HGF(-)c-Met(+) GC cells,recombinant HGF promoted EMT phenotype characterized by morphology, impaired E-cadherin and induction of Vimentin. HGF promoted cell growth, invasiveness, migration ability and inhibition of anoikis. SU11274 blocked HGF-induced EMT and the biological effects in vitro. In contrast of HGF(+)c-Met(+) GC cells, HGF exposure was not affected biological outcome of EMT and anoikis but SU11274 blocked biological effect as same as in HGF(-)c-Met(+) GC cells. In vivo, HGF(+)c-Met(+) GC cell line only established PD and SU11274 intraperitoneally caused an inhibition of PD growth. Clinically, HGF expression was significantly positive correlated with c-Met expression in GC specimens. Increased HGF and c-Met demonstrated a significantly associated with poor prognosis and can predict PD, respectively. Furthermore, HGF was one of the independent factors for predicting PD. Immunohistochemical analysis showed HGF and c-Met were predominantly co-expressed in cancer cell of both primary GC and PD. Conclusions: We have demonstrated that HGF/c-Met pathway as an inducer of EMT and anoikis inhibition in GC cell. Co-expression of HGF and c-Met implicates its potential to promote PD in GC. Blocking the autocrine HGF/c-Met pathway may be clinically useful for the treatment of PD in GC. No significant financial relationships to disclose.
FDG PET/CT Findings of Primary Hepatic Leiomyosarcoma in an Immunocompetent Pediatric Patient
Authors: Peng Xie, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2017)

Primary hepatic leiomyosarcoma generally occurs only in adult patients or pediatric patients with immunodeficiency. We report here the FDG PET/CT findings of primary hepatic leiomyosarcoma in a 10-year-old immunocompetent girl.
P01.08 Targeting DNA repair mechanisms in glioblastoma: from basic mechanisms to pre-clinical aspects and personalized therapy
Authors: E. Van Dyck, H. Erasimus, M. Gobin, P. Nazarov, S. Fritah, L. Vallar, M. Timmer, R. Goldbrunner, S. Niclou
Journal: Neuro-Oncology (2016)

AbstractIntroduction:Despite surgical resection and genotoxic treatment with ionizing radiation (IR) and the DNA alkylating agent temozolomide (TMZ), glioblastoma remains one of the most lethal cancers, due in great part to the action of complex DNA repair mechanisms that drive resistance and tumour relapse. One such mechanism involves the DNA-repair protein O6-methylguanine-DNA methyltransferase (MGMT) which mediates the direct removal of O6-methylguanine, the most highly cytotoxic lesion induced by TMZ. Importantly, silencing of MGMT through promoter methylation, which is observed in about 40% of GBM patients, confers a small but significant survival benefit in patients treated with TMZ and IR compared to IR only. In addition to MGMT, several DNA repair pathways have been involved in the repair of TMZ-induced lesions. Understanding the molecular details of these mechanisms and identifying potential pharmacological targets have emerged as vital tasks to improve treatment. At the same time, deciphering the genetic and epigenetic alterations that shape the “DNA repair makeup” of GBM cells should help tailor therapy to individual patients.Approach and Results:We have undertaken complementary approaches to understand the molecular basis behind chemoresistance, tumour progression and relapse in GBM patients. Firstly, we have measured the mRNA expression levels of a selection of DNA repair and cell cycle factors in paired, primary and recurrent GBM biopsies from patients treated or not with TMZ. Classification of the deregulated genes led to the identification of a gene signature that segregated 3 groups of biopsies. Inspection of these groups suggests that one route to tumour progression is associated with profound alterations in cell cycle genes as well as genes encoding crucial DNA repair factors. We have further exploited our differential gene expression analysis to learn how cancer cells modulate the expression of specific pathways in response to glioblastomagenesis and genotoxic treatment, and propose novel therapeutic strategies based on the inhibition of DNA repair factors. Lastly, we have carried out a large-scale shRNA screen of DNA repair/chromatin factors to identify those gene silencings that sensitize GBM cells to TMZ, as well as synthetic lethal interactions with MGMT. We are currently validating the most promising candidates in vitro as well as in vivo, using orthotopic xenograft models of GBM.
Treatment of Childhood T Cell Lymphoblastic Lymphoma (TLL), Results of the SFOP LMT96.
Authors: Christophe Bergeron, David Perol, Helene Pacquement, Yves Perel, Carole Coze, Virginie Gandemer, Jean P. Vannier, Francois Mechinaud, Claudine Schmitt, Guy Leverger, Andre Baruchel, Catherine Patte
Journal: Blood (2005)
The Methylation-Sensitive Enhancer Derare Maintains Hematopoietic Stem Cells through Regulation of Hoxb Cluster
Authors: Pengxu Qian, Bony De Kumar, Youngwook Ahn, Christof Nolte, Ariel Paulson, Xi C He, Zhenrui Li, John M. Perry, Meng Zhao, Fang Tao, Robb Krumlauf, Linheng Li
Journal: Blood (2016)
MPTH-37. COMPUTATIONAL MODELING APPROACH IN DERIVING A MESENCHYMAL TRANSITION LANDSCAPE IN LOW GRADE AND HIGH GRADE GLIOMAS
Authors: Anita Tandle, Orieta Celiku, Joon-Yong Chung, Stephen Hewitt, Kevin Camphausen, Uma Shankavaram
Journal: Neuro-Oncology (2016)

One of the important question in glioma therapy is that the biological modeling of gliomas in vitro is inadequate due to the heterogeneous and aggressive nature of this disease. The existing experimental techniques are insufficient to study the molecular diversity and processes like epithelial to mesenchymal transition (MT) which are known to be responsible for resistance to various therapeutic agents in many cancers including glioblastomas. In the current study, we address this issue by integrating publically available database, computational modeling, pathway enrichment network analysis and data validation tools to come up with a prognostic index gene signature for glioblastomas. By analyzing 275 glioma samples consisting of low grade gliomas (grade II) and high grade glioblastoma (grade IV) from The Cancer Genome Atlas database, we report specific differences between the two, including molecular markers associated with increased survival, and potential therapeutic targets. We stratified our cohort based on a recently proposed 64-gene MT signature as high MT (overexpressing this signature) and low MT (with relatively low expression of the signature). Transcription factor and enrichment analysis of these cohorts identified 5 major pathways and 118 transcription factors regulating these cohorts. Using a penalized regression method, LASSO, we explored the Extracellular matrix organization, the most significant pathway, for prognostic relevance and prioritized a 20-gene signature including 5 transcription factors associated with survival outcome. The signature genes showed a prognostic index hazard ratio (HR = 3.2. 95% CI = 1.53-8.33) in glioblastomas. Validation in an independent data confirmed the results. We also found that the signature is strongly correlated with the putative stem cell marker CD44. Our results suggest that transition of low grade gliomas to glioblastoma is associated with a shift in the expression of the signature genes, raising the possibility of inhibiting this transition might prolong the survival in glioma patients.
Abstract 5715: Development Of A Temporary Lead For In Utero Pacing: A New Approach For Cardiac Interventions In Fetuses
Authors: Younes Boudjemline, Jonathan Rosenblatt, Damien Bonnet, Jean-Marie Jouannic
Journal: Circulation (2008)

Background: Cardiac fetal intervention has been applied to human. It is presently limited to the dilatation of obstructive valvular diseases and the creation or dilatation of atrial septal defect in fetuses with hypoplastic left heart syndrome and restrictive atrial septal defect. In this study, we propose a new application of fetal intervention represented by fetal pacing using a specially designed implantable pacing lead in the fetal lamb. Methods and results: In twelve pregnant ewes (110 –112 days’ gestation), a 17 Gauge needle was placed in contact with cardiac chambers under echo-guidance. Using the lumen of the needle, a 3Fr unipolar pacing lead was advanced and fixed on the cardiac wall using a built-in screw. Pacing was, then, attempted using an external pacing system. Assessment of pacing was confirmed using ultrasound modalities. Pacing lead insertion was successful and uncomplicated in all 15 attempts (atrial and/or ventricular wall respectively n=3 and12) excepted one. In the first fetus, the needle was advanced too far into the right ventricle leading to pericardial bleeding after the retrieval of the needle. The fetal heart rate was overdriven in all at 220/min using the lead. After assessment, pacing lead was unscrewed and retrieved without any complication. Pregnancy was electively interrupted in 6 animals. The other six fetuses were delivered vaginally after an uneventful pregnancy and autopsy at day 3 did not show any significant injury. Conclusion: Echo-guided fetal pacing is feasible using a specially designed lead. It enlarges present indications of human fetal cardiac interventions.