tbuckley/cabot-search huggingface dataset:
High EVI1 expression Is Associated with MLL rearrangements and Predicts Decreased Survival in Pediatric AML: A Report From the Children's Oncology Group.
Authors: Phoenix A. Ho, Todd Alonzo, Robert B. Gerbing, Jessica A. Pollard, Susana C. Raimondi, Betsy A. Hirsch, Todd Cooper, Alan S. Gamis, Soheil Meshinchi
Journal: Blood (2012)
Impact of Antithrombin Deficiency on Efficacies of DU-176b, a Novel Orally Active Direct Factor Xa Inhibitor, and Antithrombin Dependent Anticoagulants, Fondaparinux and Heparin.
Authors: Toshio Fukuda, Yuko Honda, Chikako Matsumoto, Nobutoshi Sugiyama, Tadashi Matsushita, Masamitsu Yanada, Yoshiyuki Morishima, Toshiro Shibano
Journal: Blood (2005)
FRI0417 Prevalence of Osteoporosis in An Ankylosing Spondylitis Cohort
Authors: G. Fitzgerald, D.J. Lundon, P. Gallagher, K. O'Rourke, C. Sheehy, C. Sullivan, C. Silke, F. Stafford, M. Haroon, R. Mullan, O. FitzGerald, F. O Shea
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The Ankylosing Spondylitis Registry of Ireland (ASRI) is a web-based database established in 2013, the objectives of which are to provide descriptive epidemiological data on the ankylosing spondylitis (AS) population in Ireland and to establish a registry for potential future studies of genetics, aetiology and therapeutics. The prevalence of osteoporosis is higher in AS patients than age- and sex-matched controls, with potential for vertebral fractures increased. However, the true prevalence is unknown. There is no data on the prevalence of osteoporosis in an Irish cohort. <h3>Objectives</h3> To determine the prevalence of low bone mineral density (BMD) in an Irish AS cohort. <h3>Methods</h3> A standardised detailed clinical assessment was performed on each patient. Disease activity was assessed by Bath AS Disease Activity Index (BASDAI), function by the Bath AS Functional Index (BASFI) and Health Assessment Questionnaire (HAQ) and quality of life by AS Quality of Life (ASQoL). Structured interviews provided patient-reported data. Presence or absence of dual-energy x-ray absorptiometry (DXA) testing and result was recorded. Bone mineral density (BMD) was categorised according to the World Health Organisation criteria into normal BMD, osteopenia or osteoporosis. Statistical analysis was performed using SPSS. <h3>Results</h3> As of October 2015, 416 patients are enrolled in ASRI: 78.1% males, mean age 47.95 (SD 12.4), mean disease duration 20.9 years (SD 12.2), average delay to diagnosis of 8.8 years (SD 8.3). Mean BASDAI is 3.8 (SD 2.5), BASFI 3.7 (SD 2.7), HAQ 0.53 (SD 0.51) and ASQoL 6.15 (SD 5.5). DXAs have been performed in 24.75% (n=103) of the cohort, of which 39.8% (n=41) have osteopenia and 10.7% (n=11) have osteoporosis. Low BMD is significantly correlated with men and advancing age. There is no association with disease activity or duration. Low BMD is more prevalent in patients treated with one or more biologics compared to those never treated. The self-reported prevalence of osteoporosis is 6.4% (n=27; 19 males). <h3>Conclusions</h3> There is an elevated prevalence of low BMD in this cohort, with no association with disease severity. The majority of affected patients were unaware, as demonstrated by the low self-reported prevalence. More research and education is needed. <h3>Disclosure of Interest</h3> None declared
AB1080-HPR The Organizational and Environmental Factors That Affect Patient Satisfaction in Day Care Units
Authors: M. Pavic Nikolic, B. Huzjan, S. Kosir Jost, K. Perdan Pirkmajer
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Patients with inflammatory rheumatic disease, who are treated with biologics, often need a lifelong therapy and frequent examinations. Some of them receive biologics intravenously (i.v.) in a day care unit.Their satisfaction is an important indicator of quality in health care and is influenced by many yet undetermined nonclinical factors. <h3>Objectives</h3> The aim of our study was to determine the circumstances that have important influence on satisfaction of patients in our day care unit. <h3>Methods</h3> Patients treated in the day care unit of the Department of Rheumatology, University Medical Centre Ljubljana, Slovenia were enrolled from November 2014 to the end of January 2015. 130 questionnaires focusing on environmental adequacy of day care units, privacy during the treatments, organization of day care units, satisfaction with health care and access to phone advice were distributed. Data were analyzed using independent samples t-test when appropriate. <h3>Results</h3> One hundred and nineteen patients treated in our day care unit were included. Their average age was 57 ± 12, 6 years old, 73, 9% of them were women. The most frequently represented rheumatic disease was rheumatoid arthritis (77, 3%), the average disease duration was 14, 7 years. Most patients (41%) were being treated with biological therapy for 3–5 years. Most patients in our day care unit organised their own transport to the hospital (73, 9%), 49, 6% of patients commuted from places which are more than 25 km away. According to our questionnaire suitability of treatment rooms, have only marginal, t statistically unimportant, impact on patient satisfaction (p=0,050). The organization of work in daily hospital, the way of providing information about health condition, future treatment options, privacy during the treatment and possibility of obtaining information by phone all had important influence ob patient satisfaction (all p&lt;0.005). Overcrowded rooms, high environmental temperatures in the summer, long waiting times for the treatment and the absence of the rheumatologist during the treatment in day-care unit all negatively affected patient satisfaction. <h3>Conclusions</h3> Our study shows important connections between the level of patient satisfaction and environmental as well as organizational aspects of day care unit treatment. This data provide new opportunities for our day care unit environmental improvements and organizational changes. <h3>Disclosure of Interest</h3> None declared
PWE-090 Are Cancers of The Colon Biologically Different Compared to Rectal Cancer?
Authors: A Patel, F Peters, J Shah, R Ranat, N Williams, R Arasaradnam
Journal: Gut (2016)

<h3>Introduction</h3> Emerging evidence suggests that tumour biology of rectal cancers differs from colonic cancer. This study aimed to determine which clinic-pathological factors affect lymph node yield (LNY) and survival in colonic (CC) compared to rectal cancer (RC). <h3>Methods</h3> Patients [a1] with stage I-III disease undergoing curative surgery, between 2006 and 2012, were included. Multivariate linear/logistic regression and Kaplan Meier survival analysis with SPSS version 21 were performed. <h3>Results</h3> 726 patients (M:F-398: 328, median age-70 years(63–78 yrs) were included (median follow up-58 months-(37–78 months)); 205 patients had RC. Male gender and younger age were associated with RC. A higher LNY was detected with RC compared to CC (median LNY:20 (14–27.5) versus 18 (12–25), p = 0.013). No differences in locoregional recurrence or distant metastases were found (CC 40/521 versus RC 13/205, p = 0.635 and CC 98/521 versus RC 36/205, p = 0.750 respectively). Overall survival (OS) was better in CC compared to RC (mean OS 114 months versus 90 months, p = 0.004); no difference in disease free survival (DFS) was observed. An inadequate LNY (&lt;12 LN) was associated with poor OS in CC compared to RC patients (mean OS-80 months versus 91.5 months, p = 0.027, respectively). On multivariate analysis, T3 stage (p = 0.003), N1 stage (p = 0.016), tumour size (p = 0.018) and mucinous histology (p = 0.018) were associated with an inadequate LNY in CC only and not RC. <h3>Conclusion</h3> An inadequate LNY is related to aspects of the primary tumour and is a marker of poor prognosis for CC patients only. No survival differences are observed for RC patients with an inadequate LNY compared to those with &gt;12 lymph nodes questioning the prognostic significance of number of lymph nodes retrieval in RC. <h3>Disclosure of Interest</h3> None Declared
Sucessful Management of Pregnancy and Remission-Induction of a Patient with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) by Means of Imatinib Mesilate and HyperCVAD.
Authors: Toshiya Suzuki, Yu Abe, Yuki Mori, Yasunori Nakagawa, Keiko Saito, Yoko Matsumoto, Akito Miyauchi, Mitsuhiro Sugimoto, Kenshi Suzuki
Journal: Blood (2007)
Looking beyond the cancer cell for effective drug combinations
Authors: Jonathan R. Dry, Mi Yang, Julio Saez-Rodriguez
Journal: Genome Medicine (2016)

Combinations of therapies are being actively pursued to expand therapeutic options and deal with cancer's pervasive resistance to treatment. Research efforts to discover effective combination treatments have focused on drugs targeting intracellular processes of the cancer cells and in particular on small molecules that target aberrant kinases. Accordingly, most of the computational methods used to study, predict, and develop drug combinations concentrate on these modes of action and signaling processes within the cancer cell. This focus on the cancer cell overlooks significant opportunities to tackle other components of tumor biology that may offer greater potential for improving patient survival. Many alternative strategies have been developed to combat cancer; for example, targeting different cancer cellular processes such as epigenetic control; modulating stromal cells that interact with the tumor; strengthening physical barriers that confine tumor growth; boosting the immune system to attack tumor cells; and even regulating the microbiome to support antitumor responses. We suggest that to fully exploit these treatment modalities using effective drug combinations it is necessary to develop multiscale computational approaches that take into account the full complexity underlying the biology of a tumor, its microenvironment, and a patient's response to the drugs. In this Opinion article, we discuss preliminary work in this area and the needs-in terms of both computational and data requirements-that will truly empower such combinations.
FRI0096 Predictive Value of The Multi-Biomarker Disease Activity (MBDA) Score for Flare and Sustained Remission in The Honor Study
Authors: S. Hirata, S. Tang, C.C. Hwang, I. Miyagawa, S. Kubo, K. Nakano, S. Nakayamada, K. Saito, N.A. Defranoux, Y. Tanaka
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To determine the predictive value of the multi-biomarker disease activity (MBDA) (Vectra® DA) score for flare and sustained clinical remission after discontinuation of adalimumab (ADA) in patients with rheumatoid arthritis (RA) from the HONOR study [1,2]. <h3>Methods</h3> This retrospective sub-analysis was conducted on 42 RA patients from the HONOR study. Patients receiving ADA and methotrexate (MTX) who maintained DAS28-ESR remission (&lt;2.6) for ≥24 weeks and who subsequently agreed to discontinue ADA were enrolled. Clinical disease activity, functional status, and joint damage were recorded at ADA discontinuation (baseline), and after 24 and 52 weeks. MBDA scores (remission, ≤25; low, 26–29; moderate, 30–44; high, &gt;44) were determined from serum samples collected at baseline. The ability to predict flare (DAS28-ESR ≥3.2) or sustained clinical remission (SC-REM) (absence of flare with DAS28-ESR &lt;2.6 at all visits) by MBDA score and patient characteristics were determined. <h3>Results</h3> At ADA discontinuation, all patients had DAS28-ESR &lt;2.6 with 81% female, 69% RF+, 81% ACPA+ and 30-month mean disease duration. The median MBDA score was 24.5 [quartile; 14.3, 30.8] with 22 (52.4%) patients in remission, and 6 (14.3%) low, 9 (21.4%) moderate and 5 (11.9%) high MBDA score. At 52 weeks, flare and SC-REM were observed in 12/42 (28.6%) and 19/42 (45.2%) patients, respectively. Rate of flare and percentage of SC-REM by MBDA category (remission/low/moderate/high) were 13.6%/50.0%/33.3% and 60.0% (p=0.033) and 63.6%/33.3%/33.3% and 0% (p=0.0066), respectively (P-value by two-sided Cochran-Armitage trend test). Univariate regression analyses identified MBDA score, DAS28-ESR and disease duration as predictors of flare at 52 weeks (p≤0.05). <h3>Conclusions</h3> These findings suggest that the MBDA score could predict flare and SC-REM in RA patients in stable clinical remission, undergoing ADA withdrawal while maintaining MTX treatment. <h3>References</h3> Hirata S, et al, Arthritis Res Ther. 2013;15:R135 Tanaka Y, et al, Ann Rheum Dis. 2015;74:389–395 <h3>Disclosure of Interest</h3> S. Hirata Speakers bureau: AbbVie, Eisai, Bristol Meyers Squibb, S. Tang Employee of: Crescendo Bioscience Inc., C. Hwang Employee of: Crescendo Bioscience Inc., I. Miyagawa: None declared, S. Kubo: None declared, K. Nakano: None declared, S. Nakayamada: None declared, K. Saito: None declared, N. Defranoux Employee of: Crescendo Bioscience Inc., Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Chugai, MSD, Astellas, Novartis, Speakers bureau: Abbvie, Chugai, Astellas, Takeda, Santen, Mitsubishi-Tanabe, Pfizer, Janssen, Eisai, Daiichi-Sankyo, UCB, GlaxoSmithKline, Bristol-Myers
Nucleated Cell (NC) Dose of Autologous (Auto) Marrow Graft Is Not Predictive of Engraftment after Auto-Bone Marrow Transplant (auto-BMT) Following Failed Peripheral Blood Stem Cell (PBSC) Mobilization.
Authors: Stephen A. Strickland, Heidi Chen, Carole Hunt, Wichai Chinratanalab, Brian Engelhardt, Stacey A. Goodman, John P. Greer, Adetola A. Kassim, David Morgan, Katherine L. Ruffner, Friedrich Schuening, Madan Jagasia
Journal: Blood (2006)
OC-048 The Use of Volatile Organic Compounds Emitted from Stool as a Biomarker for Colonic Neoplasia
Authors: A Bond, R Greenwood, S Lewis, B Corfe, S Sarkar, P Rooney, C Probert
Journal: Gut (2016)

<h3>Introduction</h3> Colorectal cancer (CRC) remains a leading cause of mortality worldwide. The incidence has increased by 6% in the last decade and it is the third most common malignancy in the UK, accounting for approximately 15,000 deaths annually. The UK Bowel Cancer Screening Programme has demonstrated that detection of CRC at an earlier stage and identification of advanced pre-malignant adenomas can reduce cancer-associated mortality. We analysed the volatile organic compounds (VOCs) emitted from stool to assess their utility as a biomarker for colonic neoplasia. <h3>Methods</h3> Stool was collected from symptomatic patients referred for colonoscopy and those within the BCSP. SPME headspace extraction followed by GC-MS was performed, in order to identify VOCs. The outcome of colonoscopy was classified as no-neoplasia, adenomatous polyp(s) and cancer. Data analysis was performed in R, Stata and Metaboanalyst, utilising Student's t test, Fisher's exact test, ANOVA, false discovery rate correction, PLS-DA, factor analysis and ROC analysis. Logistic regression modelling with 10 fold cross validation was used to test potential biomarkers. <h3>Results</h3> 137 patients were included, with a mean age of 64 yrs (range 22–85), 54% were males. 60 patients had no neoplasia, 56 adenomatous polyp/s and 21 had CRC. 162 VOCs were identified across all samples, mean number in no-neoplasia 58.1 and 55.2 in neoplastic group, p = 0.51. VOC analysis was able to differentiate those with higher risk neoplastic disease with the greatest confidence. When comparing those with cancer to no neoplasia PLS-DA demonstrated separation, compound A was significantly more abundant in the CRC samples (p =&lt; 0.0001, q = 0.004), AUROC curve 0.76. When combined with compound B the AUROC curve was 0.82. Biomarker modelling, combining compounds A and B, used logistic regression and 10 fold cross validation: the AUROC for the initial cross validation set was 0.85, when applied to the hold-out set the AUROC was 0.82, sensitivity 87.9% (95% CI 0.87–0.99) and specificity 84.6% (95% CI 0.65–1.0). Further logisitic regression analysis of VOC presence identified a three VOC panel (compounds A, X and Y) AUROC =0.86: a person 6 times more likely to have cancer for each of the VOCs present in their stool (p =&lt; 0.0001). Factor analysis supported these findings. *VOCs referred to as Compound A, B, X and Y due to potential future IP. <h3>Conclusion</h3> VOC analysis has a superior diagnostic ability for the identification of colorectal adenocarcinoma, when compared to other faecal based biomarker, including those currently employed in UK population based screening. <h3>Disclosure of Interest</h3> None Declared
MTOR (Mammalian Target of Rapamycin) Inhibition with RAD001 Induces Cell Cycle Arrest in Diffuse Large B Cell Lymphoma (DLBCL) Cells and Sensitizes DLBCL Cells to Rituximab Therapy.
Authors: Kathrin Wanner, Susanne Hipp, Christian Peschel, Thomas Decker
Journal: Blood (2004)
Checkpoint Proteins in Pediatric Brain and Extracranial Solid Tumors: Opportunities for Immunotherapy
Authors: Eric K. Ring, James M. Markert, G. Yancey Gillespie, Gregory K. Friedman
Journal: Clinical Cancer Research (2016)

Pediatric brain and extracranial solid tumors are a diverse group of malignancies that represent almost half of all pediatric cancers. Standard therapy includes various combinations of surgery, cytotoxic chemotherapy, and radiation, which can be very harmful to a developing child, and survivors carry a substantial burden of long-term morbidities. Although these therapies have improved survival rates for children with solid tumors, outcomes still remain extremely poor for subsets of patients. Recently, immunosuppressive checkpoint molecules that negatively regulate immune cell function have been described. When found on malignant cells or in the tumor microenvironment, they contribute to immune evasion and tumor escape. Agents designed to inhibit these proteins have demonstrated significant efficacy in human adult solid tumor studies. However, there is limited research focusing on immune checkpoint molecules and inhibitors in pediatric solid tumors. In this review, we examine the current knowledge on immune checkpoint proteins with an emphasis on cytotoxic T lymphocyte antigen-4 (CTLA-4); programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1); OX-2 membrane glycoprotein (CD200); and indoleamine 2,3-dioxygenase (IDO). We review T-cell signaling, the mechanisms of action of these checkpoint molecules, pediatric preclinical studies on checkpoint proteins and checkpoint blockade, pediatric checkpoint inhibitor clinical trials conducted to date, and future immunotherapy opportunities for childhood cancers. Clin Cancer Res; 23(2); 342-50. ©2016 AACR.
Robust and Sensitive Detection of Insertions, Deletions and Point Mutations In CEBPA, a GC-Rich Content Gene, Using 454 Next-Generation Deep-Sequencing (NGS).
Authors: Vera Grossmann, Susanne Schnittger, Sonja Schindela, Hans-Ulrich Klein, Christiane Eder, Martin Dugas, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach, Alexander Kohlmann
Journal: Blood (2010)
Secretable Human Megakaryocyte Factor V Endocytosed from Plasma in Complex with Multimerin: The Origin of Human Megakaryocyte Factor V.
Authors: Youko Suehiro, Dragoslava K. Veljkovic, Nola Fuller, Yasuaki Motomura, Jean Masse, Elizabeth Cramer, Catherine P.M. Hayward
Journal: Blood (2004)
Self-Administered, Subcutaneous (SQ) Alemtuzumab To Eliminate Residual Disease in Patients (pts) with CLL.
Authors: William G. Wierda, Thomas J. Kipps, Michael J. Keating, Jennifer R. Brown, John G. Gribben, M.L. Browning, L. Rassenti, A. Greaves, Donna Neuberg, Susan M. O’Brien
Journal: Blood (2006)
Leuprolide Acetate (GnRH Agonist) to Enhance Immune Function Post-Autologous Hematopoietic Stem Cell Transplantation (HSCT)
Authors: Richard Champlin, Eva C. Guinan, Lee M. Nadler, Patricia McAdams, Lisa Brennan, Christine Barbon, Ping Jiang, Kristof Chwalisz, Cynthia Mattia-Goldberg, Karim Sajwani, Richard Boyd, Peter F. Thall, Robertson Parkman
Journal: Blood (2010)
The role of interleukin-33 in chronic rhinosinusitis
Authors: Dong-Kyu Kim, Hong Ryul Jin, Kyoung Mi Eun, Ji-Hun Mo, Seong H Cho, Sohee Oh, David Cho, Dae Woo Kim
Journal: Thorax (2016)

<h3>Rationale</h3> Interleukin (IL)-33, a new member of the IL-1 family, is constitutively expressed in epithelial tissues and lymphoid organs and plays an important role in the pathogenesis of allergic disease. However, the role of IL-33 in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. <h3>Objective</h3> To investigate the role of IL-33 in the pathophysiology of CRSwNP. <h3>Methods</h3> We investigated IL-33 expression and its cellular origins in the nasal polyps (NPs) of human subjects by immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and multiplex cytokine assays. Correlations between IL-33 expression and other inflammatory markers were also explored. To investigate the role of IL-33 in CRSwNP, anti-IL-33 antibody was used in a murine model of CRS. <h3>Results</h3> Uncinate process tissues from control (19), CRSsNP (61), CRSwNP (69) and NP tissues (71) were used in this study. Increased expression of IL-33 mRNA and protein in patients with CRSwNP compared with controls was observed. The concentration of IL-33 protein in CRSwNP was positively correlated with the number of neutrophils and the expression of several Th1 and Th17 inflammatory markers, including interferon (IFN)-γ, IL-1β, tumour necrosis factor (TNF)-α, IL-17A, IL-22, and various markers for neutrophil recruitment. However, protein levels of IL-5 and quantity of eosinophils were inversely correlated with levels of IL-33. The expression of tissue inhibitor of metalloproteinase (TIMP)-1 was negatively correlated with IL-33 protein levels, while the expression of matrix metalloproteinase (MMP)-2 and MMP-9 was positively correlated with IL-33 protein levels. In animal studies, IL-33 expression was upregulated in the CRSwNP group compared with controls. Anti-IL-33 treatment reduced the thickness of oedematous mucosa, subepithelial collagen deposition, and infiltration of neutrophils, but infiltration of eosinophils was not reduced. This treatment also inhibited the expression of neutrophilic inflammatory cytokines, but not IL-4. In addition, the expression of intracellular adhesion molecule 1, vascular adhesion molecule 1 and CXCL-2 in the nasal mucosa was suppressed in mice treated with anti-IL-33 antibody. <h3>Conclusions</h3> Our data suggest a role for IL-33 in the pathogenesis of CRSwNP via neutrophil recruitment. Therefore, anti-IL-33 may provide a new treatment strategy to target infiltrating neutrophils in CRSwNP.