tbuckley/cabot-search huggingface dataset:
Abstract 3819: A simple method for selectively isolating small size circulating cell-free DNA
Authors: Milka A. Rodriguez, Amanda Conroy, Wei wei Li
Journal: Cancer Research (2015)

Abstract Elevated levels of circulating cell-free DNA (ccfDNA) in plasma/serum have been associated with several pathological and clinical disorders such as cancer. It was demonstrated that ccfDNA of clinical importance exists predominantly as ∼170 bp fragments in mononucleosomal complexes and isolation of this DNA is challenging. Traditional methods for isolation of ccfDNA have been unreliable since they cannot selectively capture small size DNA from mononucleosomes. Here we describe a simple and reliable method which can be used for selectively isolating ccfDNA from plasma/serum. Different amounts of HeLa mononucleosomes (10-500 ng) were spiked into 0.5 ml of bovine plasma to mimic ccfDNA. First, nucleosomal complexes were captured using size-fractionation magnetic beads. The DNA in the captured nucleosomal complexes was then purified with DNA purification beads. As a control, 500 ng of polynucleosomes (DNA size 2270 bps) were simultaneously spiked with mononucleosomes into 0.5 ml of plasma and subjected to the isolation procedures described above. Fluorescent quantification showed 70-100% recovery of DNA from plasma with the highest recovery (100%) at lower concentrations of spiked mononucleosomes (10 ng). Bioanalyzer results further showed that only 170 bp peak size fragments were present for mononucleosomes alone or for both mono- and poly-nucleosomes spiked into plasma. No peak was observed for polynucleosomes spiked into plasma. These results demonstrate that this method is highly selective and specific for isolation of small size ccfDNA generated from mononucleosomes in plasma and would benefit early cancer detection that uses ccfDNA as biomarkers. Citation Format: Milka A. Rodriguez, Amanda Conroy, Wei wei Li. A simple method for selectively isolating small size circulating cell-free DNA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3819. doi:10.1158/1538-7445.AM2015-3819
Different expression of BRCA1 status and clinical variables in a sample of Italian women with early onset breast cancer (EOBC)
Authors: M. A. Bella, M. Michiara, A. Musolino, N. Naldi, P. Zanelli, B. Bortesi, M. Capelletti, N. Bandini, V. Franciosi
Journal: Journal of Clinical Oncology (2004)

9670 Background: to estimate the spectrum of genetic alteration, family history (FH) and clinical variables in a EOBC population, diagnosed before 41 yrs, consecutively seen at the Genetic Oncology Service of the Parma Hospital from 1999 to 2003, and to investigate the contribution of BRCA1/2 germline mutation to the phenotype of these tumors. Methods: we analyzed clinical and pathological characteristics of 60 EOBC pts. All women underwent full genetic counseling. Of these, 52 (86%) were tested for BRCA1 and BRCA2 mutation analysis while 8 (14%) pts refused it. Exon 11 was screened for BRCA1 mutations using Protein Truncation test (PTT); mutations detected by PTT were confirmed by Direct Sequencing (DS). All the other exons were analyzed by DS. BRCA2 gene was screened using Denaturing High Performance Liquid Chromatography (DHPLC) for all coding exons. Samples showing a heterozygous DHPLC elution profile were subsequently analyzed by DS. Results: 33 (55%) and 10 (16%) out of the 60 pts had breast and ovarian cancer FH, respectively. Median age of BC diagnosis was 34 yrs (range: 23–41); 7 pts (13%) had Bilateral Breast Cancer (BBC). Two pts had similar history of sarcoma at 11–12 years and EOBC at 31–32 years and one patient had EOBC + Ovarian cancer + Malignant Melanoma. Of the 19 pts with completed mutation analysis, 14 (74%) had wild-type BRCA1(WT) (including 3 pts with EOBC+other tumors), 3 (16%) had variants of unclear significance, 2 (10%) had deleterious mutations in BRCA1. Breast FH was similarly distributed in the 5 mutation carriers (MC) and in the 14 WT (60% vs 78%), while ovarian FH was more frequent in MC (60% vs 21%). One of 5 MC had BBC (age 28 and 42) and 1 had no FH. Stage II-III (80% vs 36%), grade 3 (75 % vs 33%), lack of estrogen (50% vs 20%) and progesterone receptor (67% vs 20%), and high proliferation rate (75% vs 43%) were more common in MC than in WT. BRCA2 analysis is still ongoing. Until now, a deleterious mutation in BRCA2 gene was detected in two pts. Conclusion: our data confirm that in EOBC adverse histopathologic features and ovarian FH are more predictive of being MC than good histopathologic features and breast FH. No significant financial relationships to disclose.
PO75A STANDARDISED ANATOMICAL AND FUNCTIONAL CLASSIFICATION OF CORTICAL AND SUBCORTICAL BRAIN FUNCTION FOR INTRAOPERATIVE MAPPING DURING AWAKE CRANIOTOMY
Authors: J. Ekanayake, G. Samandouras
Journal: Neuro-Oncology (2015)

INTRODUCTION: Extent of resection for intrinsic brain tumors has been established as an important determinant of survival Intraoperative stimulation brain mapping enables significantly higher rates of GTR. Additionally, there has been a 4-fold increase publications related to awake craniotomy in the past decade (45% increase in past 5 years). However there are limited publications worldwide (n <300), which report a range of practices for assessing cortical function. A standardised approach is lacking, which may be a contributor. We propose a unified approach for intraoperative cognitive assessment based on validated neurocognitive practice. This will provide the field with a state-of-the-art approach to awake craniotomy. METHOD: We propose a battery of tests, using 7 lobes of the brain (frontal, parietal, temporal, occipital, insular, central, cingulate). Further fractionation of cognitive function is considered, using major cortical surface markings, and subcortical tracts (i.e. uncinate fasiciulus, arcuate fasiculus, superior longitudinal fasciculus etc.). Criteria for use include ease of delivery, replicability, lack of routine neuropsychology involvement and a tablet-base. RESULTS: Based on institutional experience over 24 months, anatomical dissection, and peer-reviewed cognitive neuroscientific findings of functional specialisation and network connectivity, a whole brain map has been designed with functional subdivision, and corresponding tasks with measurable behavioural outputs. CONCLUSION: The proposed classification will need consensus among surgeons and the neuroscience community establish a validated system with non-significant inter-observer variability and optimal functional outcomes.
Long Term Outcomes for Patient with Diffuse Large B-Cell (DLBCL) or Hodgkin’s Lymphoma (HL) following Autologous Stem Cell Transplant (ASCT) Who Are Disease Free at Five Years Post Transplant.
Authors: Julie M. Vose, Fausto Loberiza, Philip Bierman, Robert Bociek, James Armitage
Journal: Blood (2008)
Planned First Efficacy and Safety Analysis of De-Intensified Induction with Fludarabine, Cyclophosphamide Plus Rituximab (FCR) Followed by Fludarabine Plus Rituximab (FR) and Remission Maintenance Therapy with Rituximab in Previously Untreated B-Chronic Lymphocytic Leukemia (B-CLL): The Chairos Study.
Authors: Alexander Egle, Lukas Weiss, Gudrun Russ, Ralf Thoedtmann, Lisa Pleyer, Guenther Gastl, Josef Thaler, Andreas Petzer, Inge Tinhofer, Richard Greil
Journal: Blood (2007)
Utilization and costs of non-evidence-based (non-EBM) antineoplastic agents in patients with metastatic colon cancer (mCC).
Authors: J. A. de Souza, B. N. Polite, S. Zhu, J. J. Dignam, N. J. Meropol, M. J. Ratain, L. N. Newcomer, G. C. Alexander
Journal: Journal of Clinical Oncology (2011)

6002 Background: New biologic and cytotoxic therapies have successfully improved mCC survival, yet have the potential to increase the use of non-EBM regimens. Insight into utilization patterns of non-EBM antineoplastic drugs is crucial as new reimbursement methods and evidence-based clinical pathways are being developed. Methods: Using UnitedHealthcare data, we retrospectively identified incident cases of mCC from 01/2007 to 06/2010. We excluded patients (pts) with multiple primary tumors and evaluated the use of 3 regimens not recommended by the NCCN Guidelines: 1) Bevacizumab (BEV) beyond progression on a BEV/chemotherapy regimen (addressed as “insufficient data to support” in the NCCN guidelines); 2) Single agent capecitabine (CAPE) as a salvage therapy after failure on a fluoropyridimidine-containing regimen (NCCN: “shown to be ineffective”); 3) Panitumumab (PAN) or cetuximab after progression on a prior epidermal growth factor receptor antibody (NCCN: “no data, nor is there a compelling rationale”). Sensitivity analyses of key assumptions for the mCC cohort selection and for treatment definitions were performed, as well as analyses examining non-EBM use based on pts’ age, line of treatment, co-morbidities and geographic area. Results: A total of 7642 colon cancer cases were identified, and 1041 (14%) developed mCC. Of those, 140 (13%) received at least one of the 3 non-EBM therapies; 884 pts received BEV, and 91 (10%) of those received it as non-EBM; CAPE was administered to 121 pts, 59 (49%) non-EBM; 38 pts received PAN and 6 (16%) received it non-EBM. The total cost to acquire the non-EBM drugs was estimated at $2,009,480 ($1,930/mCC case). Conclusions: In a large privately insured mCC cohort, a substantial number of pts received non-EBM therapies. This resulted in a high social cost for the pts (who may have experienced toxicities without proven benefits), and for payers. Further study is warranted to identify patient and physician factors associated with use of non-EBM regimens. Non-EBM cycles (n) Estimated drug costs from a CMS perspective ($) BEV 632 1,318,352 CAPE 218 621,463 PAN 19 69,665 2011 average sales price (70kg, 170cm, male): BEV $5.96/mg, CAPE $0.045/mg and PAN $8.73/mg.
566. Selective and Stable Transduction of Human CD4+ T Cells In Vivo Upon Systemic Administration of CD4-Targeted Lentiviral Vectors
Authors: Qi Zhou, Katharina M. Uhlig, Anke Muth, Janine Kimpel, Camille Lévy, Robert Münch, Janna Seifried, Alexandra Trkola, Dorothee von Laer, Winfried S. Wels, Udo Hartwig, Els Verhoeyen, Christian J. Buchholz
Journal: Molecular Therapy (2015)

Playing a central role in both innate and adaptive immunity, CD4+ T cells are the key target for genetic modifications in basic research and immunotherapy. Specific and stable delivery of therapeutic genes into these cells is therefore highly desirable. Here, we describe novel lentiviral vectors (CD4-LV) that have been rendered selective for human or simian CD4+ cells by surface engineering. This novel CD4-LV was highly specific and effective in genetic modification of human CD4+ T cells both in vitro and in vivo. When applied to peripheral blood mononuclear cells (PBMC), CD4-LV transduced CD4+ but not CD4− cells. Notably, also unstimulated T cells were stably genetically modified. Upon systemic or intrasplenic administration into mice reconstituted with human PBMC or hematopoietic stem cells, reporter gene expression was predominantly detected in lymphoid organs. Evaluation of GFP expression in organ-derived cells and blood by flow cytometry demonstrated exclusive gene transfer into CD4+ human lymphocytes. In bone marrow and spleen memory T cells were preferentially hit. Towards potential therapeutic applications, we show that CD4-LV can deliver genes protecting T cells from infection with HIV-1 or encoding chimeric antigen receptors thereby inducing tumor cell killing. This study demonstrates for the first time highly selective and stable gene delivery into human CD4+ T lymphocytes upon in vivo administration of lentiviral vectors, opening an avenue towards novel strategies in immunotherapy.
PTU-011 Predicting outcome in patients deferred for percutaneous endoscopic gastrostomy: is the Levine score or the Sheffield gastrostomy score more accurate?: Abstract PTU-011
Authors: H E Robson, J S Leeds, J Grant, M E McAlindon, D S Sanders
Journal: Gut (2010)

<h3>Introduction</h3> Percutaneous endoscopic gastrostomy (PEG) insertion is widely accepted as the best means of providing medium and long-term enteral nutrition. There are limited data on outcomes in patients referred for gastrostomy insertion that are either refused or do not survive until PEG insertion. Scoring systems such as the Levine score have been created to try and predict survival rates over 1 year for any patients admitted acutely. We have also created a score to specifically predict mortality after gastrostomy insertion. These two scores have not been directly compared. The aim of this study was to identify which scoring system is the most useful for predicting survival after PEG. <h3>Methods</h3> All patients referred for PEG insertion in our institute are reviewed by the PEG nurse specialist and prospectively included in a database. Demographic, biochemical and outcome data are also included. PEG referrals from March 2007 to March 2009 were analysed and both the Levine score and the Sheffield gastrostomy score calculated. Mortality rates were then compared. <h3>Results</h3> During the study period 78 patients (mean age 69.5 years) were assessed for gastrostomy insertion but were turned down. Overall 30-day and 1 year mortality in this group was 33.3% and 73.1%, respectively. 1-year mortality as predicted by Levine score or Sheffield score is shown in Abstract 011. <h3>Conclusion</h3> The Sheffield score is more accurate at predicting 1-year mortality in patients deferred for gastrostomy insertion. This may suggest that the Sheffield PEG score could be used in the pre-assessment of patients who are being referred for PEG as a means of estimating/predicting mortality for those involved in the decision making process. Larger comparative studies are required to validate this finding.
Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome
Authors: Benjamin A Fisher, Roland Jonsson, Troy Daniels, Michele Bombardieri, Rachel M Brown, Peter Morgan, Stefano Bombardieri, Wan-Fai Ng, Athanasios G Tzioufas, Claudio Vitali, Pepe Shirlaw, Erlin Haacke, Sebastian Costa, Hendrika Bootsma, Valerie Devauchelle-Pensec, Timothy R Radstake, Xavier Mariette, Andrea Richards, Rebecca Stack, Simon J Bowman, Francesca Barone
Journal: Annals of the Rheumatic Diseases (2016)

Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0-10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus.
High Dose Busulfan and Fludarabine with Anti-Thymocyte Globulin (ATG) Followed by Unmodified Marrow Grafts from HLA-Matched Siblings for the Treatment of High Risk Hemoglobinopathies (HGBpathies).
Authors: Farid Boulad, Nancy A. Kernan, Trudy N. Small, Joseph Chewning, Susan Prockop, Andromachi Scaradavou, Anna Keating, Richard J. O’Reilly
Journal: Blood (2005)
PTH-029 Ampullary Characteristics as A Novel Means of Predicting ERCP Complexity
Authors: KA Mcwhirter, J McLaughlin, A Makin
Journal: Gut (2016)

<h3>Introduction</h3> ERCP is a technically demanding procedure, with significant risk of complications. Cannulation success is widely regarded as a key performance indicator of high- quality ERCP practice (1). Multiple factors affecting the complexity of a complete ERCP procedure have been suggested as a way of adding relevance to success rates and complication incidence. We propose a novel concept where complexity stratification is used to predict outcome based on ampullary characteristics. <h3>Methods</h3> 200 ERCPs performed on a virgin ampulla were prospectively recorded. We classified ampulla as non-prominent, prominent or distorted by tumour. Cannulation method and number of ampullary contacts were recorded. Cannulation success and incidence of complications were the primary outcome measures. <h3>Results</h3> The most common indication was biliary duct stones (54%). Ampullae were classified as non-prominent in 107 cases, prominent in 78 and involving tumour in 15. Overall deep cannulation was successful in 189 cases (94%), with significant variation between ampullary groups. Non-prominent and prominent ampullae were more likely to be cannulated successfully, (95.3%, 94.9% respectively), than those involving tumour (80%) (p = 0.004). Fewest contacts prior to cannulation were made on the non-prominent ampullae and most on those involving tumour (p &lt; 0.001). Needleknife assisted cannulation was used most frequently on ampullae involving tumours and least often on non-prominent ampullae (p = 0.044). The presence of a peri-ampullary diverticulum or a covering mucosal fold, did not reduce cannulation success. 15 patients had complications (7.5%) - pancreatitis (10), perforation (3), infection (1) and bleeding (1). 12 complications occurred in the non-prominent group, with increased incidence of perforation, pancreatitis and bleeding (p = 0.04). Complications were more likely in younger patients (p = 0.03). Complication rate was not affected by patient gender, cannulation outcome, number of ampullary contacts or trainee involvement. Neither presence of diverticulae nor covering folds increased complication rate. <h3>Conclusion</h3> The assessment of ampullary characteristics may prove to be a novel means of predicting cannulation difficulty and anticipating risk of complication. Non-prominent ampullae appear to be easier to cannulate, with fewer ampullary contacts and less use of needleknife fistulotomy, but complication rates appear highest. Statistical significance is limited by the sample size and low incidence of cannulation failure and complications, so further study is required. These findings may have implication for case selection in ERCP training, and may add validity to key outcome quality indicators in practice. <h3>Reference</h3> 1 ASGE. Quality Indicators for ERCP. 2015. <h3>Disclosure of Interest</h3> None Declared
Myeloid Derived Suppressor Cells (MDSCs) Regulate Tumor Growth, Immune Response and Regulatory T Cell (Treg) Development in the Multiple Myeloma Bone Marrow Microenvironment
Authors: Gullu Topal Gorgun, Gregory Whitehill, Jennifer Lindsey Anderson, Teru Hideshima, Jacob P. Laubach, Noopur Raje, Nikhil C. Munshi, Paul G. Richardson, Kenneth C. Anderson
Journal: Blood (2012)
Osteonecrosis of jaw (ONJ) with and without bone exposure in patients receiving antiangiogenic agents (+/- bisphosphonates or denosumab)
Authors: V. Fusco, A. Fasciolo, R. Gaino, D. Tartara, I. De Martino, M. Alessio, L. Benzi, M. Rapetti, R. Cammarata, E. Caravaggio, M. Vincenti, P. Gugliemini
Journal: Annals of Oncology (2015)
503. Adeno-Associated Virus Vector (AAV) Microdystrophin Gene Therapy Prolongs Survival and Restores Muscle Function in the Canine Model of Duchenne Muscular Dystrophy (DMD)
Authors: Caroline Le Guiner, Laurent Servais, Marie Montus, Thibaut Larcher, Bodvael Fraysse, Sophie Moullec, Taeyoung Koo, Alberto Malerba, Christine Le Bec, Matthias Hebben, Carole Masurier, Federico Mingozzi, Oumeya Adjali, Pierre Carlier, Jean-Yves Hogrel, Bernard Gjata, Yan Cherel, Takis Athanasopoulos, Fulvio Mavilio, Thomas Voit, Philippe Moullier, George Dickson
Journal: Molecular Therapy (2016)

Duchenne Muscular Dystrophy (DMD) is a X-linked inherited muscle-wasting disease primarily affecting young boys with a prevalence of 1:5,000. The disease is caused by loss-of-function mutations in the gene encoding for the Dystrophin protein and is characterized by systemic, progressive, irreversible and severe loss of muscle function. Among vector systems that allow efficient in vivo gene transfer, recombinant Adeno-Associated Virus vectors (rAAV) hold great promise and allow very efficient transduction of skeletal and cardiac muscles. However, full-length dystrophin cDNA exceeds the packaging capacity for a single rAAV gene-delivery cassette. Therefore, truncated versions namely micro-dystrophins have been designed and optimized to contain few clinically important regions of the dystrophin protein. We have tested a rAAV2/8 vector encoding a sequence optimised canine micro-dystrophin transgene, driven by a muscle-synthetic Spc512 promoter (rAAV2/8-Spc512-µDys) in a total of 12 Golden Retriever Muscular Dystrophy (GRMD) dogs, the canine model of DMD. Isolated limb perfusion studies using a single administration of vector induced high levels of micro-dystrophin expression in the treated limb (up to 90% dystrophin positive fibres) with significant normalisation of histological, NMR imaging and spectroscopy parameters and muscle strength, without deleterious immune responses. Similarly, single-dose intravascular delivery of the same rAAV2/8-Spc512-µDys, in absence of immunosuppression, led to long-term transduction of distant muscle groups and extended lifespan (up to 2 years). Profound improvement of multiple clinical features was observed, including gait and respiratory parameters and no toxicity or deleterious humoral and/or cell-mediated immune responses were observed. This study demonstrates the safety and long term efficacy of rAAV2/8-Spc5.12-µDys gene therapy in a relevant large-animal models of DMD and paves the way towards human clinical gene therapy using systemic peripheral vein administration of vector, and applicable to all DMD patients regardless of their genotype.
Chronic Myeloid Leukemia Stem Cells Possess Unique Properties That Predict Intrinsic and Acquired Resistance to Imatinib Mesylate.
Authors: Xiaoyan Jiang, Yun Zhao, Clayton Smith, Maura Gasparetto, Kyi Min Saw, Ali Turhan, Allen Eaves, Connie Eaves
Journal: Blood (2006)