tbuckley/cabot-search huggingface dataset:
AB0025 Evolution of Regulatory B Cells under Treatment by Biologics in Rheumatoid Arthritis
Authors: S. Salomon, C. Guignant, C. Brault, G. Flahaut, B. Gubler, Patrice Fardellone, Jean-Pierre Marolleau, V. Goeb
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> In clinical daily practice, the response to biologics is unpredictable in patients with rheumatoid arthritis (RA) and there is a crucial need for biomarkers of response. <h3>Objectives</h3> The main objective of our study is to describe the evolution of regulatory B cells (Bregs) in patients with RA treated with biologics and to investigate whether there is a correlation between the rate of Bregs and the clinical response. <h3>Methods</h3> This was a propective single-center pilot study, descriptive and not randomized. Patients were included with RA fulfilling the ACR/EULAR 2010 criteria, with an active disease according to the DAS28 score despite treatment, and in whom initiation or switch of a biologic except rituximab was required. Acontrol group of patients without any autoimmune disease or immune dysfunction was also assessed. B and T lymphocytes whole blood phenotyping, as well as an analysis of the production of IL-10 were performed by multicolor flow cytometry (FCM) in both patients and controls at baseline (M0) and in patients after 1 (M1), 3 (M3) and 6 (M6) months of treatment. CD24hiCD38hi CD24hiCD27+ subpopulations were selected for the phenotypic study of Bregs (24–38 and 24–27 Breg). The primary endpoint was the rate and absolute value of Bregs as a percentage and absolute value measured at each time of the study and compared with disease activity. <h3>Results</h3> Thirty patients and 15 controls were included in this study. Nowadays, phenotypic analysis was performed at baseline in all patients, but only in 15 patients at M1 and 13 patients at M3. The complete data will be available for the EULAR congress. There was an increase in circulating 24–38 Bregs between M1 and M3 (p=0.06) whatever the biologic prescribed. At baseline, the 24–38 Bregs were significantly lowered in patients compared to controls in percentage and absolute value (p=0.001 and p=0.013 respectively). The DAS28 remission and EULAR response at M3 were associated with a quantitative increase of 24–38 and 24–27 Breg at baseline compared to the values of the non-responders patients. Thus, a high initial rate of 24–27 and 24–38 Breg seemed associated with a good clinical response and an EULAR remission at 3 months. The rate of CD19 + B producing IL-10 obtained by PBMC culturing seemed lower in controls as compared to the patients. <h3>Conclusions</h3> We observed an increase of Bregs under treatment by biologics and a quantitative decrease in Bregs in patients with active RA compared to healthy subjects and patients with inactive disease. Thus, Bregs could be a marker of activity of the disease and their level may represent a potential predictor of the therapeutic response. Full data are required to confirmed these preliminary results. <h3>Disclosure of Interest</h3> None declared
TPLL-1 Protocol of the German CLL Study Group (GCLLSG) - A Prospective Phase II Trial of Fludarabine Phosphate, Mitoxantrone and Cyclophosphamide (FMC) Followed by Alemtuzumab Consolidation in T-PLL.
Authors: Georg Hopfinger, Raymonde Busch, Eichhorst Barbara, Cramer Paula, Kandler Gabriele, Fingerle-Rowson Gunther, Fink Anna-Maria, Stilgenbauer Stephan, Hallek Michael
Journal: Blood (2007)
Young Adult Patients with Post -HCT Relapse of AML May Benefit from Aggressive Salvage and 2nd Cellular Therapy
Authors: Syed Osman Ahmed, Amna Gamil, Muhamad Hitham Almahayni, Naeem A. Chaudhri, Fahad Alsharif, Said Y Mohamad, Hazza A Alzahrani, Walid Rasheed, Ghuzayel Aldawsari, Amr Hanbali, Marwan Shaheen, Feras Alfraih, Shad Ahmed, Khaled Ibrahim, Fahed Almhareb, Mahmoud Aljurf
Journal: Blood (2015)
Double Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation: French Society of Bone Marrow Graft Transplantation and Cellular Therapy Experience
Authors: Jacques-Olivier Bay, Aurelie Cabrespine-Faugeras, Reza Tabrizi, Pierre Bordigoni, Karin Bilger, Marc Renaud, Valerie Mialou, Marie Robin, Mathieu Kuentz, Patrice Chevallier, Nathalie Dhedin, Jean-Yves Cahn, Michel Attal, Didier Blaise, Mauricette Michallet
Journal: Blood (2008)
Retrospective study of predictors and consequences of nonadherence with lapatinib (LAP) in women with metastatic breast cancer (MBC) who were previously treated with trastuzumab.
Authors: Alex Kartashov, Thomas E. Delea, Puza P. Sharma
Journal: Journal of Clinical Oncology (2012)

e11067 Background: LAP, an oral small molecule dual tyrosine kinase inhibitor has been shown to improve time to progression in combination with capecitabine vs. capecitabine alone in women with HER2+ MBC previously treated with trastuzumab, an anthracycline, and taxanes. Data on adherence, persistence, predictors and consequences of non-adherence with LAP in typical clinical practice are scarce. Methods: This was retrospective observational study of predictors and consequences of non-adherence with LAP in women with MBC who were previously treated with trastuzumab using Thomson MedStat MarketScan® Commercial and Medicare claims databases covering 80 million lives. Measures of LAP adherence were calculated from information on pharmacy claims and included medication possession ratio (MPR) and time to first treatment interruption (gap during treatment of 30 days without supply). Predictors of non-adherence to LAP and the association between non-adherence and healthcare utilization and costs were examined using multiple regression analyses. Results: A total of 666 patients met all inclusion criteria. Median follow-up was 12 mos. Mean(SD) MPR was 87% (19%); 22% of patients had MPR&lt;80%. Twenty seven percent of patients had &gt;=1 treatment interruptions during follow-up. Concomitant therapy with a taxane was a predictor of non-adherence (Odds ratio MPR&lt;80%=10.3, 95%CI 3.3 to 31.9, p&lt;0.001). In generalized linear regression models, non-adherence with LAP (1-MPR[range: 0 to 1]) was associated with more physicians' office / hospital outpatient visits (Rate ratio = 1.26, 95%CI: 1.03-1.54, p=0.028). There was a statistically non-significant trend towards an association between adherence and total costs excluding the costs of LAP (Cost ratio = 1.23, 95%CI: 0.93-1.63, p=0.146). Conclusions: Most patients receiving LAP are adherent to therapy, although there is a small group with high non-adherence that may negatively impact healthcare resource utilization. Further research is needed to identify additional predictors of LAP non-adherence so that clinicians may develop strategies to enhance adherence and improve patient outcomes.
TTT-3002 Is a Novel FLT3 Tyrosine Kinase Inhibitor That Has the Potential to Overcome Some of the Limitations of Current FLT3 Inhibitors in Treatment of Acute Myeloid Leukemia
Authors: Hayley S Wall, Bao Nguyen, Li Li, Sarah M Greenblatt, Patrick Brown, Mark J. Levis, Donald Small
Journal: Blood (2012)
Idelalisib improves CD37 antibody BI 836826 cytotoxicity against chemo-resistant /relapse-initiating CLL cells: a rationale for combination treatment
Authors: S Betrian, L Ysebaert, K H Heider, J P Delord, J J Fournié, A Quillet-Mary
Journal: Blood Cancer Journal (2016)

Idelalisib improves CD37 antibody BI 836826 cytotoxicity against chemo-resistant /relapse-initiating CLL cells: a rationale for combination treatment
Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer
Authors: Agnieszka A. Rucki, Kelly Foley, Pingbo Zhang, Qian Xiao, Jennifer Kleponis, Annie A. Wu, Rajni Sharma, Guanglan Mo, Angen Liu, Jennifer Van Eyk, Elizabeth M. Jaffee, Lei Zheng
Journal: Cancer Research (2016)

Understanding how stromal signals regulate the development of pancreatic ductal adenocarcinoma (PDAC) may suggest novel therapeutic interventions in this disease. In this study, we assessed the metastatic role of stromal signals suggested to be important in the PDAC microenvironment. Src and IGF-1R phosphorylated the prometastatic molecule Annexin A2 (AnxA2) at Y23 and Y333 in response to stromal signals HGF and IGF-1, respectively, and IGF-1 expression was regulated by the Sonic Hedgehog (Shh) pathway. Both Shh and HGF were heterogeneously expressed in PDAC stroma, and only dual inhibition of these pathways could significantly suppress AnxA2 phosphorylation, PDAC growth, and metastasis. Taken together, our results illuminate tumor-stromal interactions, which drive metastasis, and provide a mechanism-based rationale for a stroma-directed therapy for PDAC. Cancer Res; 77(1); 41-52. ©2016 AACR.
A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export
Authors: Danyang Gong, Yong Hoon Kim, Yuchen Xiao, Yushen Du, Yafang Xie, Kevin K. Lee, Jun Feng, Nisar Farhat, Dawei Zhao, Sara Shu, Xinghong Dai, Sumit K. Chanda, Tariq M. Rana, Nevan J. Krogan, Ren Sun, Ting-Ting Wu
Journal: Cell Host & Microbe (2016)
FRI0075 Effects of Dmards on Citrullinated Peptide Autoantibody Levels in RA Patients- A Longitudinal Analysis
Authors: G. Schett, C. Wunderlich, C. Figueiredo, J.F. Cobra, A.J. Hueber, A. Kleyer, J. Rech
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Anti-citrullinated cyclic peptide 2 (CCP2) antibodiy levels are considered to be highly stable during disease-modifying anti-rheumatic drug (DMARD) therapy of rheumatoid arthritis (RA). However, no studies have actually analyzed sequential anti-CCP2 antibody levels during various DMARD therapies in a controll manner <h3>Objectives</h3> To study whether stable treatment with DMARDs affects anti-CCP2 antibody levels in patients with rheumatoid arthritis. <h3>Methods</h3> In this longitudinal observational study 100 RA patients were followed for anti-CCP2 IgG antibody (U/L) and total IgG level (mg/dL) every 6 months for a total period of 2.5 years. All patients received stable DMARD treatment during this period. Five groups comprising each 20 patients were analysed: (1) methotrexate (MTX) alone, (2) tumor necrosis factor inhibitors (TNFi), (3) tocilizumab (TCZ), (4) rituximab (RTX) and (5) abatacept (ABA). <h3>Results</h3> Baseline demographic and disease-specific characteristics were comparable between the 5 groups. Anti-CCP2 antibody levels did not show significant changes in patients treated with MTX (mean±SEM: -24.1±8.1%), TNFi (-14.0±11.1%) or TCZ (-24.3±11.3%) between baseline and the 2,5 years follow up. In contrast, anti-CCP2 antibody levels significantly decreased during treatment with RTX (-75.6±4.4%) and ABA (-82.5±3.7%). With respect to total IgG levels, no significant changes were observed with MTX (-24.1±8.1%), TNFi (-14.0±11.1%) or TCZ (-24.3±11.3%) over 2,5 years. In contrast, anti-CCP2 antibody levels significantly decreased during treatment with RTX (-75.6±4.4%) and ABA (-82.5±3.7%). Date for individual patients are summarized in Figure 1. <h3>Conclusions</h3> DMARDs targeting the adaptive immune response such as ABA and RTX significantly lowered anti-CCP2 IgG levels, while cytokine inhibitors and methotrexate had no significant effects on anti-CCP2 IgG levels. RTX is the only DMARD, which also lowers total IgG level. Lowering anti-CCP2 IgG levels is a step towards sero-conversion and immunological remission of disease. <h3>Disclosure of Interest</h3> None declared
Necroptosis of a Small Subset of Hematopoietic Progenitors Induces Autoimmune Bone Marrow Failure
Authors: Junping Xin, Ni Allen, Rafael Gutierrez, Haiyan Chen, Jing Li, Joseph Cannova, Grace Ng, Rachel Schmidt, Wei Wei, Peter Breslin, Paul C Kuo, Patrick J. Stiff, Jiwang Zhang
Journal: Blood (2015)
TBI Based Conditioning Regimen and Intra Osseous Application of PBSC to Overcome Graft Resistance In a Patient with Autoimmune Lymphoproliferative Syndrome (ALPS)
Authors: Daniel Stachel, Nora Naumann-Bartsch, Patrick Morhart, Markus Metzler, Thorsten Langer, Klaus Schwarz, Wolfgang Holter
Journal: Blood (2010)
Biochemical assays for selectivity profiling across the entire PI3 kinase family
Authors: Jeanne Dudek, Yi Gao, Laurie Reichling, Deborah Stafslien, Robert Horton, Steve Riddle, Kurt Vogel
Journal: Cancer Research (2008)

LB-39  The selectivity of small molecule kinase inhibitors impacts both efficacy and off-target toxicity and is therefore crucial for effective development of therapeutics. Although PI3 kinase/mTOR inhibitors are a major focus of drug discovery efforts in oncology, effective tools for assessing selectivity of these inhibitors have been lacking. We describe the development of assays for all types of PI3 Kinase family members, including Class I, II and III PI3 kinases, Type III PI4 kinases, and PIKKs (mTOR, DNA-PK). In addition to the development of a new universal kinase assay kit (Adapta™) to monitor activity, a series of optimized, ready-to-use lipid substrates were created for use as robust substrates for the lipid kinases. Data will be presented on a set of Class I PI3K inhibitors that were profiled across the family-wide panel of kinases.
Intensified Myeloablative Unrelated Cord Blood Transplantation for High-Risk or Advanced Hematological Malignancies: Experience at a Single-Institution in China
Authors: Zimin Sun, Huilan Liu, Baolin Tang, Xiaoyu Zhu, Wen Yao, Juan Tong, Kaidi Song, Liangquan Geng, Xingbing Wang, Kaiyang Ding, Changcheng Zheng, Weibo Zhu
Journal: Blood (2014)
Updated Results of Phase II Study of Cyclophosphamide(Cy), Bortezomib(Bz), Pegylated Doxorubicin(DOX), and Dexamethasone(dex), (CVDD), in Patients with Newly Diagnosed Myeloma:an Effective Induction Regimen for High Risk Disease
Authors: Melissa Alsina, Rachid Baz, Kenneth H. Shain, Leonel Ochoa, Taiga Nishihori, Daniel M Sullivan, Binglin Yue, Jongphil Kim, William Dalton
Journal: Blood (2012)
Germinal Center Phenotype Determined by Immunohistochemistry on Tissue Microarray Does Not Correlate with Outcome in Diffuse Large B-Cell Lymphoma Patients Treated with Immunochemotherapy in the Randomized Trial LNH98-5. A GELA Study.
Authors: Thierry Jo Molina, Philippe Gaulard, Jean-Philippe Jais, Gilles Andre Salles, Françoise Berger, Corinne Haioun, Herve Tilly, Jean-François Emile, Pierre Feugier, Karen Leroy, Josette Briere, Bertrand Coiffier
Journal: Blood (2007)
Unique Characteristics of Classical Hodgkin Lymphoma in Patients with Cutaneous T-Cell Lymphoma
Authors: Lauren E. Strelec, Erin Haley, Ellen J. Kim, Alain H. Rook, Nirav N. Shah, Anthony R. Mato, Daniel J. Landsburg, Sunita Dwivedy Nasta, Stephen J. Schuster, Jakub Svoboda
Journal: Blood (2015)
AB0922 FDG-PET/CT Is A Valuable Tool for Relapsing Polychondritis
Authors: R. Wakiya, H. Ozaki, H. Shimada, S. Nakashima, Y. Takeuchi, M. Izumikawa, T. Kameda, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Relapsing polychondritis (RP) is a comparatively rare inflammatory disorder t in which recurrent episodes of inflammation occur in the external ear, nose, and joints. Although the pathogenesis of RP is unclear, it is believed to involve autoimmune mechanism such as autoantibody to type II collagen. Clinically, diagnosis in early stages of RP is difficult because of few typical physical findings. Furthermore, airway involvement is the most important complication of RP, and is associated with significant morbidity and mortality. Therefore it is important to diagnosis and treat RP in early stages. On the other hand, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been an established in a field of oncology. Recently, FDG-PET/CT is used as diagnostic tool for inflammatory disorder such as infection or collagen vascular disease. <h3>Objectives</h3> We investigate the features and the usefulness of FDG-PET/CT in the diagnosis of RP. <h3>Methods</h3> We enrolled the five RP patients (M/F: 1/4) who fulfilled the RP criteria by Damiani and Levine, and treated in our facility between 2005 and 2015. All patients had undergone FDG-PET/CT before treatment. Inflammatory lesion was evaluated by using the maximum standardized uptake value (SUV max). Furthermore, we performed follow-up FDG-PET/CT due to evaluate the efficacy of treatment for RP. <h3>Results</h3> FDG-PET/CT findings revealed abnormal FDG accumulation in the cartilages for all five patients. The lesions of abnormal FDG accumulation were tracheal/bronchial in 3 cases, auricular cartilage in 2 cases. The mean SUV max in tracheal/bronchial was 4.84 and in auricular cartilage was 2.53. All RP patients received glucocorticoid (GC) treatment. 3 patients were performed methylprednisolone-pulse therapy. All RP patients had well responce to initial GC treatment. However three patients were refractory for GC treatment. In these patients, one treated with methotrexate combined with GC and another 2 cases cyclophosphamide. The follow-up FDG-PET/CT was undergone in 2 patients. These findings revealed that FDG accumulation was significantly decreased or disappeared. <h3>Conclusions</h3> In RP patients, FDG-PET/CT is useful for the early diagnosis. Additionally, we suggest that FDG-PET/CT is valuable for monitoring response to treatment. <h3>References</h3> Jinlin Wang et al. Ann Nucl. Med. (2014)28:276–284 Yamashita H et al. Rheumatology 2014 Aug;53(8):1482–90 <h3>Disclosure of Interest</h3> None declared
IL-6 Trans–Signaling Links Inflammation with Angiogenesis in the Peritoneal Membrane
Authors: Rusan Catar, Janusz Witowski, Nan Zhu, Christian Lücht, Alicia Derrac Soria, Javier Uceda Fernandez, Lei Chen, Simon A. Jones, Ceri A. Fielding, Andras Rudolf, Nicholas Topley, Duska Dragun, Achim Jörres
Journal: Journal of the American Society of Nephrology (2016)

Vascular endothelial growth factor (VEGF) is implicated in the peritoneal membrane remodeling that limits ultrafiltration in patients on peritoneal dialysis (PD). Although the exact mechanism of VEGF induction in PD is unclear, VEGF concentrations in drained dialysate correlate with IL-6 levels, suggesting a link between these cytokines. Human peritoneal mesothelial cells (HPMCs), the main source of IL-6 and VEGF in the peritoneum, do not bear the cognate IL-6 receptor and are thus unable to respond to classic IL-6 receptor signaling. Here, we investigated whether VEGF release by HPMCs is controlled by IL-6 in combination with its soluble receptor (IL-6 trans–signaling). Although treatment with either IL-6 or soluble IL-6 receptor (sIL-6R) alone had no effect on VEGF production, stimulation of HPMCs with IL-6 in combination with sIL-6R promoted VEGF expression and secretion through a transcriptional mechanism involving STAT3 and SP4. Conditioned medium from HPMCs cultured with IL-6 and sIL-6R promoted angiogenic endothelial tube formation, which could be blocked by silencing SP4. In vivo , induction of peritoneal inflammation in wild-type and IL-6–deficient mice showed IL-6 involvement in the control of Sp4 and Vegf expression and new vessel formation, confirming the role of IL-6 trans–signaling in these processes. Taken together, these findings identify a novel mechanism linking IL-6 trans–signaling and angiogenesis in the peritoneal membrane.
Comparison among Related Peripheral Blood Stem Cell Transplantation (R-PBSCT), Unrelated Bone Marrow Transplantation (U-BMT), and Unrelated Cord Blood Transplantation (U-CBT) with Reduced Intensity Regimens for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS).
Authors: Shigesaburo Miyakoshi, Koichiro Yuji, Eiji Kusumi, Daisuke Kato, Shinsuke Takagi, Naoyuki Uchida, Tomoko Matsumura, Kazuhiro Masuoka, Atsushi Wake, Shuichi Taniguchi
Journal: Blood (2005)
Risk for alcoholic liver cirrhosis after an initial hospital contact with alcohol problems: A nationwide prospective cohort study
Authors: Gro Askgaard, David A. Leon, Mette S. Kjær, Thomas Deleuran, Thomas A. Gerds, Janne S. Tolstrup
Journal: Hepatology (2016)

Alcoholic liver cirrhosis is usually preceded by many years of heavy drinking, in which cessation in drinking could prevent the disease. Alcohol problems are not consistently managed in hospital patients. We followed all Danish patients with an initial hospital contact with alcohol problems (intoxication, harmful use, or dependence) during 1998‐2002 for alcoholic liver cirrhosis development (n = 36,044). In this registry‐based cohort, we identified predictors of the absolute risk for alcoholic liver cirrhosis. Incidence rate ratios (IRRs) were estimated as the incidence rate of alcoholic liver cirrhosis in these patients relative to the general population. Age and alcohol diagnosis were significant predictors of alcoholic liver cirrhosis risk in men and women, whereas civil status, education, and type of hospital care were not. In men, the 15‐year absolute risk was 0.7% (95% confidence interval [CI], 0.4, 0.8) for 20‐29 years, 5.5% (95% CI, 4.9, 6.2) for 30‐39 years, 9.8% (95% CI, 9.0, 11) for 40‐49 years, 8.9% (95% CI, 8.1, 9.8) for 50‐59 years, 6.2% (95% CI, 5.1, 7.2) for 60‐69 years, and 2.5% (95% CI, 1.7, 3.3) for 70‐84 years. According to alcohol diagnosis in men, the 15‐year absolute risk was 2.6% (95% CI, 2.3, 2.9) for intoxication, 7.7% (95% CI, 6.4, 7.9) for harmful use, and 8.8% (95% CI, 8.2, 9.4) for dependence. The IRR for alcoholic liver cirrhosis in the cohort relative to the general population was 11 (95% CI, 10, 12) in men and 18 (95% CI, 15, 21) in women. Conclusion : Hospital patients with alcohol problems had a much greater risk for alcoholic liver cirrhosis compared to the general population. The risk was particularly increased for patients 40‐59 years and for patients diagnosed with harmful use or dependence. (H epatology 2017;65:929‐937).
The Distinct Clinical Features and Prognosis of the CD10+MUM1+ and CD10-Bcl6-MUM1- Diffuse Large B-Cell Lymphoma
Authors: Tingxun Lu, Yi Miao, Jia-Zhu Wu, Qi-Xing Gong, Jin-Hua Liang, Zhen Wang, Li Wang, Lei Fan, Yao-Yu Chen, Zhi-Hong Zhang, Wei Xu, Jian-Yong Li
Journal: Blood (2015)