tbuckley/cabot-search huggingface dataset:
NIMG-26. PERIODIC TRANSDUCER ARRAY SHIFTING PRESERVES BOTH TTFIELDS INTENSITY IN THE GROSS TUMOR VOLUME (GTV) AND PROMOTES SCALP HEALTH DURING THE COURSE OF GLIOBLASTOMA THERAPY
Authors: Aafia Chaudhry, Ariel Naveh, Hadas Sara Hershkovich, Dario Garcia-Carracedo, Uri Weinberg, Ze’ev Bomzon, Yoram Palti
Journal: Neuro-Oncology (2016)

TTFields are delivered locally to the brain in glioblastoma patients through the continuous application of insulated ceramic transducer arrays placed on the scalp. Skin irritation under the arrays is the most common adverse event associated with treatment and can generally be prevented with periodic array shifting back and forth (in a prescribed direction) at each array change. Maintaining scalp health is critical given the continuous mode of delivery and minimum duration of compliant treatment required to observe antitumor effects. Given the non-focal nature of TTFields delivery, this study examines the impact of periodic array shifting on the EF intensity delivered to the GTV and proximal peritumoral brain zone (PBZ), sites commonly associated with contiguous glioblastoma recurrence. Standard TTFields treatment planning using the NovoTAL System was performed for 5 distinct tumors. EF simulations (realistic head model, ellipsoid tumor, 2 orthogonal array pairs (L-R & A-P), 200kHz, quasi-static solver) were performed using 1)NovoTAL planned array layout, 2) arrays shifted approximately one disc space (20mm) in the prescribed direction mimicking conventional treatment. Median EF intensity was determined in the GTV, and proximal PBZ for each array configuration. Array layout planning is influenced by cranial morphometry and tumor location. Shifting transducer arrays one disc space preserves median EF intensity delivered to the GTV and PBZ compared with the median intensity achieved with planned layout (all differences NS). Tumor specific properties influence the field intensity distribution in the GTV and PBZ. Periodic shifting of transducer arrays one disc space maintains EF intensity delivered to the tumor volume during conventional therapy. Shifting should be carefully performed per the appropriate direction/distance, in order to maintain the field intensity in regions at high risk for local recurrence, while balancing the local irritant effects of array application to the skin and promoting scalp health.
Gabrinox: A phase I-II of nab-paclitaxel plus gemcitabine followed by folfirinox in metastatic pancreatic adenocarcinoma
Authors: E. Assenat, Cdela Fouchardiere, C. Mollevi, E. Samalin, F. Portales, F. Desseigne, C. Carenco, M. Dupuy, E. Lopez-Martinez, C. Fiess, T. Mazard, M. Ychou
Journal: Annals of Oncology (2016)
Serum Biomarkers Predict Outcomes in Advanced Hodgkin Lymphoma Independent of International Prognostic Score (IPS) and Treatment: Correlative Analysis from a Large North American Cooperative Group Trial
Authors: Jennifer A. Kanakry, Fangxin Hong, Otoniel Martinez-Maza, Sandra J Horning, Leo I. Gordon, Randy D Gascoyne, Lan L Gellert, M. Victor Lemas, Bruce Cheson, Ranjana H Advani, Brad Pohlman, Vaishalee P. Kenkre, Jane N. Winter, Patrick J. Stiff, Joseph Tuscano, Jonathan Friedberg, Lydia Dreosti, Richard I. Fisher, Pierre Laneuville, Brad S Kahl, Richard F. Ambinder
Journal: Blood (2016)
Identification of baseline parameters associated with the inter-individual variability in cytidine deaminase serum activity, a key enzyme in the metabolism of pyrimidine analogue
Authors: R. Cohen, L.-H. Preta, A. Bessone, C. Narjoz, I. Nicolis, D. Desaulle, E. Curis, A. Cessot, O. Huillard, A. Thomas-Schoemann, M. Vidal, F. Goldwasser, J. Alexandre, B. Blanchet
Journal: Annals of Oncology (2016)
A randomised phase IIb study of mavrilimumab, a novel GM–CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis
Authors: Gerd R Burmester, Iain B McInnes, Joel Kremer, Pedro Miranda, Mariusz Korkosz, Jiri Vencovsky, Andrea Rubbert-Roth, Eduardo Mysler, Matthew A Sleeman, Alex Godwood, Dominic Sinibaldi, Xiang Guo, Wendy I White, Bing Wang, Chi-Yuan Wu, Patricia C Ryan, David Close, Michael E Weinblatt
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte–macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA. Methods In a phase IIb study ( NCT01706926 ), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)−C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28−CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24). Results 326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012–June 2013). Mavrilimumab treatment significantly reduced DAS28−CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: −1.90 (0.14), 100 mg: −1.64 (0.13), 30 mg: −1.37 (0.14), placebo: −0.68 (0.14); p&lt;0.001; all dosages compared with placebo). Significantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (p&lt;0.001)). Adverse events were reported in 43 (54.4%), 36 (42.4%), 41 (50.6%) and 38 (46.9%) patients in the mavrilimumab 150, 100, 30 mg eow and placebo groups, respectively. No treatment-related safety signals were identified. Conclusions Mavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential. Trial registration number NCT01706926 ; results.
CSIG-05. PUTTING THE BRAKES ON BRACHYURY: IDENTIFYING AND TARGETING A CONSERVED TRANSCRIPTIONAL NETWORK THAT DRIVES PRIMARY AND METASTATIC TUMOR INITIATION AND PROPAGATION
Authors: Sagar Shah, Justin David, Nathaniel Tippens, Ahmed Mohyeldin, Juan Carlos Martinez, Sara Ganaha, Andre Levchenko, Claudia Palena, Alfred Quinones-Hinojosa
Journal: Neuro-Oncology (2016)

Accumulating evidence suggests malignant neoplasms contain a distinct subset of cells that hijack stem cell transcriptional programs to attain tumor initiating and propagating abilities. As such, transcriptional programs coordinating early embryogenesis have recently emerged as oncogenic drivers and potential therapeutic targets. Brachyury, a core T-box transcription factor, plays a vital role during development. Incidentally, Brachyury is overexpressed in several cancers including primary and metastatic brain tumors where it promotes growth, confers resistance to chemo- and radiotherapy, drives metastatic potential, and subsequently confers poor patient prognosis. However, the molecular underpinnings of this aggressive transcriptional network are not fully understood. Patient-derived chordoma, glioblastoma, metastases to the brain, lung cancer tissues (n>20) and primary and commercial cells were subject to western blotting, qRT-PCR, bioinformatics analyses, in vitro and in vivo experiments (n=10) using genetic inhibitors. Our studies demonstrate that Brachyury drives cell cycle progression, stemness, and EMT through direct transcriptional activation of the proto-oncogene YAP, an effector of the Hippo pathway and master regulator of organ development, in chordoma (p<0.05). In addition, Brachyury regulates protein stability of YAP in more prevalent and lethal tumors such as glioblastoma (GBM), metastases to the brain, and epithelial-based cancers (p<0.05). Furthermore, we found the Brachyury-YAP signaling forms a negative feedback loop that ensures genetic stability of this aggressive network (p<0.05). Targeting this network, genetically and using a proprietary nanoparticle-based genetic inhibitor, attenuates aggressive cancer growth and progression in vitro and in vivo (p<0.05). Our work provides new molecular insights into the conserved biology of relatively slow progressing, rare tumors such as chordoma, and lethal cancers such as the highly aggressive GBM and metastases to the brain, and more the prevalent lung cancer. Moreover, our novel nanotechnology-based Brachyury-YAP targeting system offers hope for the management and treatment of a wide range of malignant neoplasms.
Safety and Efficacy of Bendamustine and Idarubicin in Combination Therapy for Patients Age ≥50 with Untreated Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome – Results From a Phase I/II Adaptive Design Study.
Authors: Mazyar Shadman, Jack M. Lionberger, Raya Mawad, Ravinder K Sandhu, Carol Dean, Kathleen Shannon-Dorcy, Kyle Wathen, Bart L Scott, Roland B. Walter, Pamela S. Becker, Frederick R. Appelbaum, Elihu H. Estey, John M. Pagel
Journal: Blood (2012)
Sensitive Monitoring of Minimal Residual Disease Status in CEBPA-Mutated Acute Myeloid Leukemia Using Amplicon Deep-Sequencing
Authors: Alexander Kohlmann, Vera Grossmann, Annette Fasan, Elisa Stopp, Tamara Alpermann, Sonja Schindela, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach, Susanne Schnittger
Journal: Blood (2011)
GENT-14. GENOME WIDE METHYLOMIC AND TRANSCRIPTOMIC ANALYSES IDENTIFY EPIGENETIC SIGNATURES UNIQUELY DYSREGULATED IN GBM SUBTYPES
Authors: Rajendra Pangeni, Angel Alvarez, Tianzhi Huang, Wei Zhang, Zhou Zhang, Namratha Sastry, Songijan Lu, John Kessler, Cameron Brenann, Erik Sulman, Xinghua Lu, Ichiro Nakano, Bo Hu, Shi-Yuan Cheng
Journal: Neuro-Oncology (2016)

Aberrant DNA methylation is implicated in GBM pathobiology contributing to tumorigenicity and clinical features. Gene expression profiling classified GBM into four clinically relevant subtypes; Proneural (PN), Mesenchymal (MES), Neural (N) and Classical (CL), of which PN, MES and CL are common to glioma stem cells (GSCs). We hypothesize that the unique patterns of aberrant DNA methylation regulate subtype-associated GBM phenotypes. To test this hypothesis, we investigated whether unique novel DNA methylation signatures are distinctly associated with each of the GBM subtypes. We carried out genomewide 450K methylation array on a panel of 23 patient-derived GSCs and identified uniquely hypermethylated or hypomethylated gene probes to generate subtype-specific methylation signatures. These candidate genes also correlate to their expression based on our expression array and RNA sequencing data. Next, we performed independent analyses of 450K methylation datasets from the TCGA in corresponding GBM subtypes. Our data showed that, in each subtype, there are unique as well as common novel epigenetic signatures between GBM and GSCs. Our analyses revealed well-established PN-associated genes such as OLIG2, PDGFRA, and NOTCH and MES-associated genes including VIM, BCL2A1, and CASP8 with distinct subtype specific methylation patterns. We then validated methylation and expression of the candidate genes using bisulphite sequencing and qRT-PCR, respectively. We further determined that global demethylation induced their expression, suggesting that these genes are dysregulated due to DNA methylation. Additionally, radiation treated PN GSCs exhibited MES-associated phenotype that showed dysregulation of several genes such as VRK2 and MEGF10 and alterations in DNA methylation patterns. This suggests the roles of DNA methylation in regulating glioma subtype, radiation resistance and proneural-mesenchymal transition in GBM. We plan to elucidate the regulatory role of these candidates in GBM tumorigenicity using in vitro and in vivo assays. Our results provide new epigenetic insights in GBM subtype-specific malignancy, prognosis and therapeutic response.
Characteristics of patients (pts) with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) who had progression-free survival (PFS) &gt;4 months (m): Subgroup analysis of the phase 3 CORRECT trial
Authors: A. Grothey, A. Falcone, Y. Humblet, O. Bouche, L. Mineur, A. Adenis, J. Tabernero, T. Yoshino, H.-J. Lenz, R.M. Goldberg, L. Huang, A. Wagner, E. Van Cutsem
Journal: Annals of Oncology (2016)
Gemcitabine, Ifosfamide, Oxaliplatin and Rituximab (R-GIFOX), a New Effective Cytoreductive/Mobilizing Salvage Regimen for Relapsed and Refractory Aggressive Non-Hodgkin’s Lymphoma: Results of a Pilot Study.
Authors: Gaetano Corazzelli, Filippo Russo, Gaetana Capobianco, Gianpaolo Marcacci, Paola Della Cioppa, Antonio Pinto
Journal: Blood (2005)
Cytogenetic Evolution (CE) In Patients (pts) with Low and Intermediate Risk Myelodysplastic Syndromes (MDS) Is Associated with Poor Prognosis
Authors: Liunan Li, Elias Jabbour, Gautam Borthakur, Stefan Faderl, Tapan Kadia, Farhad Ravandi, Sherry A. Pierce, William G. Wierda, Lynne V. Abruzzo, Hagop Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2010)
Prognostic significance of GRP78/BiP expression in advanced thymic cancer
Authors: Yosuke Miura, Kyoichi Kaira, Reiko Sakurai, Hisao Imai, Koichi Minato, Yoshio Tomizawa, Noriaki Sunaga, Toshitaka Maeno, Takeshi Hisada, Masanobu Yamada
Journal: Annals of Oncology (2016)
Stage III colon cancer prognosis prediction by gene expression profiling
Authors: A. Barrier, P. Boelle, D. Brault, S. Houry, F. Lacaine, A. Flahault, S. Dudoit, A. Lemoine
Journal: Journal of Clinical Oncology (2007)

10590 Background and Aims: Postoperative chemotherapy has become part of the standard treatment for stage III colon cancer patients. Since approximately half of patients are cured by surgery alone, adjuvant chemotherapy should not be used in all patients. This study aimed to assess the possibility to use microarray-based gene expression profiles to predict the prognosis of stage III colon cancer patients. Material and Methods: Forty-two patients operated on for a stage III colon cancer were included in this study. Twenty-one patients have received an adjuvant chemotherapy, while the other 21 have received no treatment. Twenty patients have developed a liver metastasis, while the other 22 have remained disease-free for at least 5 years. Tumor mRNA samples were profiled using the Affymetrix HGU133A GeneChip. Two analyses were performed: one with the 42 patients, the other with the 21 patients who did not receive any adjuvant chemotherapy. For each analysis, patients were repeatedly and randomly divided into 10,000 training (TS) and validation sets (VS) of 10 different sizes. For each TS/VS split, a 30-gene prognosis predictor (PP), identified on the TS, was used to predict the prognosis of VS patients. Performances of a 15-gene PP and a 34-gene PP, proposed by another research team, were also assessed on the same TS and VS. Results: First analysis (42 patients). The 10,000 30-gene PP yielded the following average prognosis prediction performance measures: 73.8% accuracy, 74.6% sensitivity, and 73.0% specificity. Improvements in prognosis prediction were observed with increasing TS size. A total of 4,446 genes were included in the 10,000 PP. The 15-gene PP yielded a 69.7% accuracy; the 34-gene PP yielded a 71.2% accuracy. Second analysis (21 patients). The 10,000 30-gene PP yielded the following average prognosis prediction performance measures: 77.7% accuracy, 75.8% sensitivity, and 79.9% specificity. Improvements in prognosis prediction were observed with increasing TS size. A total of 5,478 genes were included in the 10,000 PP. The 15-gene PP yielded a 78.5% accuracy; the 34-gene PP yielded a 81.9% accuracy. Conclusion: Microarray gene expression profiling is able to predict the prognosis of stage III colon cancer patients and, thus, might be used for an appropriate use of adjuvant chemotherapy. No significant financial relationships to disclose.
The Location of Genomic Breakpoints in AML1/RUNX1 and ETO in De Novo znd Therapy-Related Leukemia Patients sith T(8;21) Are Similar znd Colocalize with Topoisomerase II Cleavage Sites.
Authors: Yanming Zhang, Neelmini Emmanuel, Nimanthi Jayathilaka, Heidi Gerr, Michele Nassin, Pamela Strissel, Reiner Strick, Nicole Dastugue, Bertil Johansson, Claudia Schoch, Susanne Schnittger, Brigitte Schlegelberger, Janet D. Rowley
Journal: Blood (2004)
(R)-a-Lipoic acid for the treatment of peripheral neuropathy in breast cancer patients (BCP) receiving adjuvant (A) or neoadjuvant (N) paclitaxel (P)
Authors: L. Ginocchi, G. Allegrini, S. Lucchesi, G. Arrighi, L. Marcucci, M. Filidei, C. Finale, L. Coltelli
Journal: Annals of Oncology (2016)
ERBB2 alterations a new prognostic biomarker in stage III colon cancer from a FOLFOX based adjuvant trial (PETACC8)
Authors: P. Laurent-Puig, R. Balogoun, A. Cayre, K. Le Malicot, J. Tabernero, E. Mini, G. Folprecht, J.-L. van Laethem, J. Thaler, L. Nørgård Petersen, E. Sanchez, J. Bridgewater, S. Ellis, C. Locher, C. Lagorce, J.-F. Ramé, C. Lepage, F. Penault-Llorca, J. Taieb
Journal: Annals of Oncology (2016)
Airway dynamics in COPD patients by within-breath impedance tracking: effects of continuous positive airway pressure
Authors: András Lorx, Dorottya Czövek, Zoltán Gingl, Gergely Makan, Bence Radics, Dóra Bartusek, Szabolcs Szigeti, János Gál, György Losonczy, Peter D. Sly, Zoltán Hantos
Journal: European Respiratory Journal (2017)

Tracking of the within-breath changes of respiratory mechanics using the forced oscillation technique may provide outcomes that characterise the dynamic behaviour of the airways during normal breathing. We measured respiratory resistance ( R rs ) and reactance ( X rs ) at 8 Hz in 55 chronic obstructive pulmonary disease (COPD) patients and 20 healthy controls, and evaluated R rs and X rs as functions of gas flow ( V ′) and volume ( V ) during normal breathing cycles. In 12 COPD patients, additional measurements were made at continuous positive airway pressure (CPAP) levels of 4, 8, 14 and 20 hPa. The R rs and X rs versus V ′ and V relationships displayed a variety of loop patterns, allowing characterisation of physiological and pathological processes. The main outcomes emerging from the within-breath analysis were the X rs versus V loop area (AXV) quantifying expiratory flow limitation, and the tidal change in X rs during inspiration (Δ X I ) reflecting alteration in lung inhomogeneity in COPD. With increasing CPAP, AXV and Δ X I approached the normal ranges, although with a large variability between individuals, whereas mean R rs remained unchanged. Within-breath tracking of R rs and X rs allows an improved assessment of expiratory flow limitation and functional inhomogeneity in COPD; thereby it may help identify the physiological phenotypes of COPD and determine the optimal level of respiratory support.
Determinants of Exercise Capacity in the Hypertensive Elderly. A Study Based on the Assessment of Cardiac Reserve by Dipyridamole Radionuclide Angiography.
Authors: Hiromi Seo, Taishiro Chikamori, Toshikazu Yabe, Naoki Akagi, Toshio Ozawa, Yoshinori L. Doi
Journal: Circulation (1995)

To evaluate the determinants of exercise capacity in the hypertensive elderly with an assessment of cardiac reserve by dipyridamole radionuclide angiography, 31 elderly subjects (aged 62 to 78 years, 15 hypertensive and 16 normotensive) underwent symptom-limited maximum treadmill exercise with measurement of maximal oxygen consumption along with radionuclide angiography in list mode at rest and after dipyridamole infusion. In the normotensive elderly, maximal oxygen consumption correlated with relative filling volume during the rapid filling period at rest (r = 0.58; p < 0.05), and correlated inversely with the percent change in the peak ejection rate with dipyridamole (r = -0.63; p < 0.01). In contrast, maximal oxygen consumption correlated with atrial contribution at rest (r = 0.69; p < 0.005), and correlated inversely with the percent change in atrial contribution with dipyridamole (r = -0.87; p < 0.0001) in the hypertensive elderly. These results indicate that the mechanisms for maintaining exercise capacity are different in elderly subjects with or without hypertension.
A signalling cascade of IL-33 to IL-13 regulates metaplasia in the mouse stomach
Authors: Christine P Petersen, Anne R Meyer, Carlo De Salvo, Eunyoung Choi, Cameron Schlegel, Alec Petersen, Amy C Engevik, Nripesh Prasad, Shawn E Levy, R Stokes Peebles, Theresa T Pizarro, James R Goldenring
Journal: Gut (2017)

Objective Alternatively activated macrophages (M2) are associated with the progression of spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. However, the precise mechanism(s) and critical mediators that induce SPEM are unknown. Design To determine candidate genes important in these processes, macrophages from the stomach corpus of mice with SPEM (DMP-777-treated) or advanced SPEM (L635-treated) were isolated and RNA sequenced. Effects on metaplasia development after acute parietal cell loss induced by L635 were evaluated in interleukin (IL)-33, IL-33 receptor (ST2) and IL-13 knockout (KO) mice. Results Profiling of metaplasia-associated macrophages in the stomach identified an M2a-polarised macrophage population. Expression of IL-33 was significantly upregulated in macrophages associated with advanced SPEM. L635 induced metaplasia in the stomachs of wild-type mice, but not in the stomachs of IL-33 and ST2 KO mice. While IL-5 and IL-9 were not required for metaplasia induction, IL-13 KO mice did not develop metaplasia in response to L635. Administration of IL-13 to ST2 KO mice re-established the induction of metaplasia following acute parietal cell loss. Conclusions Metaplasia induction and macrophage polarisation after parietal cell loss is coordinated through a cytokine signalling network of IL-33 and IL-13, linking a combined response to injury by both intrinsic mucosal mechanisms and infiltrating M2 macrophages.
TMOD-39. A NOVEL EX VIVO TUMOR SLICE CULTURE SYSTEM AS A TOOL FOR BASIC AND CLINICAL RESEARCH
Authors: Archana Gopalan, Stephanie Wood, Keiko Yamamoto, James Keck, Susie Airhart, Lindsay Shopland, Jens Rueter, Kyuson Yun
Journal: Neuro-Oncology (2016)

Many cytotoxic and targeted therapies show promising activity in cultured cells but most fail to show equivalent efficacy in patients, indicating that the predictive power of cell culture models is limited. While patient derived xenograft (PDX) models are more faithful models of human cancer, they are very expensive and time consuming to generate and maintain, rendering them impractical models for most studies. To bridge the gap between in vitro cell culture and in vivo animal models, we developed a tumor slice culture system from PDX models and patient tumors. While other studies have described the use of tumor tissue slices cultures, our technology has multiple significant advantages. First, we developed a robust method to monitor real-time, longitudinal therapy response from each tumor slice over a 2-3-week period. This is in contrast to previous studies, which averaged sample responses at a single end point, usually 2-4 days in culture. Second, we adapted our technology to perform a medium-throughput drug screen. Our initial proof-of-principle study was performed with 119 FDA-approved oncology drugs on a colorectal PDX. We identified seven drugs that reproducibly suppressed tumor slice viability by >50% and we validated in vivo efficacy of one of the drugs. Third, we tested the robustness of our system by culturing multiple types of human cancer, including GBMs and medulloblastomas, indicating that our culture condition can be used to study brain tumors. In addition, we validated that our system can be used to culture fresh surgical discards from patient tumors for 12 days with intact histology and good viability. We propose that our tumor slice system is a powerful tool to understand the role of intra-tumoral heterogeneity, tumor microenvironment, therapy resistance, and the stem cell niche, and can be exploited to screen drug libraries to identify new drugs for brain cancer patients.