tbuckley/cabot-search huggingface dataset:
A Novel Mechanism of Action of Rivaroxaban: Inhibition of Monocyte and Macrophage Procoagulant Activity and Consequence On Inflammatory Process.
Authors: Marc Laurent, Remi Varin, Ulrich Joimel, Hong Li, He Lu, Emmanuel Blot, Shahsultan Mirshahi, Lionel Cazin, Jean Chidiac, Jean-Pierre Marie, Jeannette Soria, Claudine Soria
Journal: Blood (2009)
Abstract 173: SOX4 interacts with EZH2 and HDAC3 to suppress microRNA-31 in invasive esophageal cancer cells
Authors: Rainelli B. Koumangoye, Thomas Andl, Kenneth J. Taubenslag, Steven T. Zilberman, Chase Taylor, Claudia D. Andl
Journal: Cancer Research (2015)

Abstract Tumor metastasis is responsible for 90% of cancer-related deaths. A strong link between microRNA dysregulation and human cancers has recently been established. However, the molecular mechanisms through which microRNAs regulate metastasis and cancer progression remain unclear. We analyzed the reciprocal expression regulation of miR-31 and SOX4 in esophageal squamous and adenocarcinoma cell lines by qRT-PCR and Western Blotting using overexpression and shRNA knock-down approaches. Here we report that SOX4 promotes esophageal tumor cell proliferation and invasion by silencing miR-31 via activation and stabilization of a co-repressor complex with EZH2 and HDAC3. We demonstrate that miR-31 is significantly decreased in invasive esophageal cancer cells compared to non-invasive cell lines, while upregulation of miR-31 inhibits growth, migration and invasion of esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) cell lines. miR-31, in turn, targets SOX4 for degradation by directly binding to its 3′-UTR. Additionally, miR-31 regulates EZH2 and HDAC3 indirectly. SOX4, EZH2 and HDAC3 levels inversely correlate with miR-31 expression in ESCC cell lines. Ectopic expression of miR-31 in ESCC and EAC cell lines leads to down regulation of SOX4, EZH2 and HDAC3. Conversely, pharmacologic and genetic inhibition of SOX4 and EZH2 restore miR-31 expression. We show that SOX4, EZH2 and HDAC3 form a co-repressor complex that binds to the miR-31 promoter, repressing miR-31 through an epigenetic mark by H3K27me3 and by histone acetylation. Clinically, when compared to normal adjacent tissues, esophageal tumor samples show upregulation of SOX4, EZH2, and HDAC3, and EZH2 expression is significantly increased in metastatic ESCC tissues. Thus, we identified a novel molecular mechanism by which the SOX4, EZH2 and miR-31 circuit promotes tumor progression and potential therapeutic targets for invasive esophageal carcinomas. Citation Format: Rainelli B. Koumangoye, Thomas Andl, Kenneth J. Taubenslag, Steven T. Zilberman, Chase Taylor, Claudia D. Andl. SOX4 interacts with EZH2 and HDAC3 to suppress microRNA-31 in invasive esophageal cancer cells. [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 173. doi:10.1158/1538-7445.AM2015-173
GWAS Indicates the Presence of Rare Immunogenetic Polymorphisms as Possible Predisposition Factors in Aplastic Anemia.
Authors: Bartlomiej P Przychodzen, Monika Jasek, Sandra P Smieszek, Ron Paquette, Rainer Richter, Manuel Afable, Jaroslaw P. Maciejewski
Journal: Blood (2009)
Treatment of Patients with Multiple Myeloma Complicated by Renal Failure with Bortezomib - Based Regimens.
Authors: Maria Roussou, Efstathios Kastritis, Athanasios Anagnostopoulos, Erasmia Psimenou, Irini Grapsa, Charis Matsouka, Despina Barmparousi, Evangelos Terpos, Meletios Athanasios Dimopoulos
Journal: Blood (2007)
Oral Proteasome Inhibitor Marizomib and IMiD® Imunomodulatory Drug Pomalidomide Trigger Synergistic Anti-Myeloma Activity and Enhanced Proteasome Inhibition in Vitro and In Vivo
Authors: Deepika Sharma Das, Arghya Ray, Yan Song, Paul Richardson, Mohit Trikha, Dharminder Chauhan, Kenneth C Anderson
Journal: Blood (2015)
"PREDICTING WORSENING ASTHMA CONTROL FOLLOWING THE COMMON COLD". M.J. WALTER, M. CASTRO, S.J. KUNSELMAN, V.M. CHINCHILLI, M. RENO, T.P. RAMKUMAR, P.C. AVILA, H.A. BOUSHEY, B.T. AMEREDES, E.R. BLEECKER, W.J. CALHOUN, R.M. CHERNIACK, T.J. CRAIG, L.C. DENLINGER, E. ISRAEL, J.V. FAHY, N.N. JARJOUR, M. KRAFT, S.C. LAZARUS, R.F. LEMANSKE JR, R.J. MARTIN S.P. PETERS, J.W. RAMSDELL, C.A. SORKNESS, E.R. SUTHERLAND, S.J. SZEFLER, S.I. WASSERMAN, M.E. WECHSLER AND THE NATHIONAL HEART, LUNG AND BLOOD …
Authors: M Walter, M Castro, S Kunselman, V Chinchilli, M Reno, T Ramkumar, P Avila, H Boushey, B Ameredes, E Bleecker, W Calhoun, R Cherniack, T Craig, L Denlinger, E Israel, J Fahy, N Jarjour, M Kraft, S Lazarus, R Lemanske, R Martin, S Peters, J Ramsdell, C Sorkness, E Sutherland, S Szefler, S Wasserman
Journal: European Respiratory Journal (2009)
Phase II study of sunitinib malate in refractory germ cell tumors.
Authors: M. Reckova, M. Mego, Z. Sycova-Mila, J. Obertova, D. Svetlovska, J. Mardiak
Journal: Journal of Clinical Oncology (2011)

e15017 Background: Patients (pts) with platinum-refractory germ cell tumors (GCT) have very poor prognosis. Induction of angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) overexpression was most often seen in teratoma components of GCT. We hypothesized that inhibition of angiogenesis by multikinase oral inhibitor sunitinib could improve prognosis of these pts. The aim of the study was to investigate efficacy and toxicity of sunitinib in refractory GCT. Methods: Sunitinib was administered at a dose of 50mg daily for 4 weeks followed by 2 weeks off therapy. The response was evaluated every 12 weeks in a one-stage phase II trial. The primary end-point was 12-month post-treatment-initiation continuous progression-free survival (PFS) with type I and type II errors of <10%. For such study design 28 patients were planned for inclusion. Results: Ten patients were included in the trial from July 2008 till December 2010. Median age was 32 years (range: 19-55). With the exception of one patient, all were platinum-refractory. Patients were pretreated with median of 3 cisplatin-containing therapies (range: 3-6). The treatment was generally well tolerated. Toxicity grade 3 was the worst experienced toxicity (trombocytopenia in 2 pts, anemia in 1 pt and nausea and vomiting in 1 pt). Median follow-up has been 13 weeks (range: 5 - 47 weeks) and median follow-up of pts still alive has been 26 weeks (range: 5 - 47 weeks). A12-week PFS was 20%. Median PFS and overall survival was 10.8 and 13.1 weeks, respectively. One patient with teratocarcinoma achieved partial remission (PR) in lung, retroperitoneal lymph nodes, and decrease in AFP after two treatment-cycles but progressed after 4 cycles. Another patient with teratoma in primary tumor, but with high level of b-HCG at relapse, achieved PR in lung and lymph nodes after two treatment cycles, however with rapid elevation of b-HCG. Conclusions: Consistently with previous reports, we conclude that monotherapy with sunitinib has limited efficacy in heavily pretreated, unselected, refractory GCTs. Based on our observations we suggest that there might be some efficacy of sunitinib in GCTs with teratoma components that is in concordance with reported overexpression of VEGF in teratoma.
Pilot Study of Lenalidomide-Rituximab Combination in Relapsed/Refractory Diffuse Large B Cell Lymphoma
Authors: Vadim Ivanov, Diane Coso, Thérèse Aurran, Jean Marc Schiano, Anne-Marie Stoppa, Jerome Rey, Florence Broussais, Didier Blaise, Reda Bouabdallah
Journal: Blood (2012)
A Phase Ib Dose-Finding Study of Oral Panobinostat In Combination with Cytarabine (ara-C) and Mitoxantrone as Salvage Therapy for Refractory or Relapsed Acute Myeloid Leukemia (AML)
Authors: Jürgen Krauter, Richard F. Schlenk, Markus Schaich, Didier Bouscary, Hervé Dombret, Ivo J. Winiger, Margaret Squier, Bourras-Rezki Bengoudifa, Oliver G. Ottmann
Journal: Blood (2010)
Increased Aldehyde Dehydrogenase Activity Indentifies a Subset of Human Leukemic Blasts with Stem Cell Characteristics and Correlates with Poor Prognosis.
Authors: Dan Ran, Mario Schubert, Larissa Pietsch, Isabel Taubert, Christian Wallenwein, Katrin Miesala, Kerstin Woerner, Patrick Wuchter, Volker Eckstein, Tom Bruckner, Anthony Ho
Journal: Blood (2008)
P1175 : Ability of a simple radiologic score, assessed by three-dimensional Magnetic Resonance Cholangiography (MRC), to predict clinical outcome of patients with Primary Sclerosing Cholangitis (PSC)
Authors: S. Lemoinne, L. Arrivé, A. Donald Kemgang Fankem, C. Housset, C. Corpechot, O. Chazouillères
Journal: Journal of Hepatology (2015)
Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non–Small Cell Lung Cancer
Authors: Elena Tassi, Giulia Grazia, Claudia Vegetti, Ilaria Bersani, Giulia Bertolini, Alessandra Molla, Paola Baldassari, Francesca Andriani, Luca Roz, Gabriella Sozzi, Ugo Pastorino, Roberta Mortarini, Andrea Anichini
Journal: Cancer Research (2016)

Abstract Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1+ T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR+) T cells with an effector memory (TEM) profile are enriched in such lesions. Tumor-infiltrating lymphocytes coexpressed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3, and TIGIT, but also displayed a recently activated, nonexhausted phenotype. We also identified a subset of CD8+PD-1+FOXP3+ T lymphocytes at the earliest phase of functional differentiation after priming, termed “early effector cells” (EEC), which also exhibited an activated nonexhausted phenotype, but was less differentiated and associated with coexpression of multiple inhibitory receptors. In response to autologous tumor, EECs upregulated CD107a, produced IL2 and IFNγ, and were competent for differentiation. The identification of EECs marked by inhibitory receptor expression at tumor sites will enable investigations of early stages of adaptive antitumor immunity, as well as support the rationale for administering immunotherapy in early-stage non–small cell lung cancer. Cancer Res; 77(4); 851–61. ©2016 AACR.
Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy
Authors: Andrea Di Marco, Ignasi Anguera, Matthias Schmitt, Igor Klem, Tomas G. Neilan, James A. White, Marek Sramko, Pier Giorgio Masci, Andrea Barison, Peter Mckenna, Ify Mordi, Kristina H. Haugaa, Francisco Leyva, Jorge Rodriguez Capitán, Hiroshi Satoh, Takeru Nabeta, Paolo Domenico Dallaglio, Niall G. Campbell, Xavier Sabaté, Ángel Cequier
Journal: JACC Heart Failure (2016)
214. Specific Targeting of IL-13 Receptor alpha 2 Expressing Breast Cancer Cells by Paramyxovirus-Pseudotyped Lentiviral Vectors Displaying IL-13
Authors: Anna R. Kwilas, Wu Ou, Michael P. Marino, Takele Argaw, Akiko Suzuki, Bharat Joshi, Syed R. Husain, Raj K. Puri, Jakob Reiser
Journal: Molecular Therapy (2016)

The ability to selectively target specific cell types is highly desirable for the in vivo application of viral vectors for the treatment of multiple diseases including cancer. Lentiviral vectors (LV) have the advantage of being easily pseudotyped allowing their tropism to be altered. LV can also be engineered to deliver therapeutic or cytotoxic genes directly to cancer cells. IL-13 receptor alpha 2 (IL-13Rα2) is overexpressed in many different tumor types, including glioma, sarcoma, kidney, breast and ovarian cancer, making it an attractive target for tumor therapy. We have previously shown that firefly luciferase-expressing LV pseudotyped with a truncated fusion (F) protein derived from measles virus (MV) and a tail-truncated, receptor-blind MV hemagglutinin (H) protein bearing IL-13 at the C-terminus were capable of transducing IL-13Rα2-positive U251 glioma cells when administered intratumorally. In addition, we have shown the ability of LV to be pseudotyped using the F and H proteins from the Tupaia paramyxovirus (TPMV). TPMV does not infect human cells, potentially making it a safer choice for pseudotyping LV for in vivo delivery. Similar to the MV H protein, the TPMV H protein can also display IL-13 and bind specifically to IL-13Rα2-positive tumor cells. We plan to confirm and extend these findings by examining the targeting of LV-MV-IL-13 and LV-TPMV-IL-13 in metastatic orthotopic models of breast cancer by intratumoral and intravenous administration. In addition, LV expressing HSV1 thymidine kinase (TK) were constructed and are being evaluated for antitumor efficacy.
411. Predicting Tumor Response to Oncolytic Virotherapy Using Dual Isotope SPECT/CT Imaging with NIS Reporter Gene and Duramycin
Authors: Kah-Whye Peng, Lianwen Zhang, Lukkana Suksanpaisan, Stephen J. Russell, Ming Zhao
Journal: Molecular Therapy (2016)

Oncolytic virotherapy is a promising modality for cancer therapy and diverse viruses from various families have been genetically engineered to be tumor selective anticancer agents. To obtain an early readout on tumor susceptibility to the oncolytic virus, and potential toxicity from off target viral infection, we have engineered our oncolytic viruses to encode the thyroidal sodium iodide symporter gene (NIS) to enable noninvasive longitudinal imaging of the pharmacokinetics and sites of virus spread. The high resolution images obtained from the new generation of small animal SPECT/CT or PET/CT machines enable us to visualize increasing numbers of infectious foci daily within the subcutaneous tumors and to establish a mathematical model to develop strategies that will improve the outcome of virotherapy. In this study, we used the oncolytic Vesicular Stomatitis Virus (VSV) encoding NIS to evaluate the kinetics of intratumoral viral spread, and the subsequent aftermath of tumor cell death by apoptosis. Through I-125 SPECT/CT and NIS imaging, we showed rapid VSV spread within the susceptible MPC-11 murine plasmacytoma tumors, and the infectious foci grew larger and increased in numbers over 5 days. Since SPECT imaging enables concurrent dual isotope imaging, we also gave the same animal Tc-99m duramycin that detects apoptotic cells. In this MPC-11 model, we found rapid onset of apoptosis within the tumor. The infectious foci of viral infection (NIS imaging) and cell death (duramycin imaging) were coincident, overlapping at the acute phase of infection. In contrast, the CT-26 tumor was significantly less responsive to VSV-mIFN-NIS therapy, and there was minimal positive NIS signals or apoptosis. We are keen to further evaluate the potential of using dual isotope SPECT imaging using NIS reporter gene and the duramycin apoptosis tracer, with the goal of using this twin set of imaging methods to give us an early prediction of tumor response to oncolytic virotherapy.
562. Modification of TCR Specificity by TALEN and CRISPR
Authors: Friederike Knipping, Karl Petri, Eliana Ruggiero, Mark J. Osborn, Jakub Tolar, Christof von Kalle, Manfred Schmidt, Richard Gabriel
Journal: Molecular Therapy (2015)

Adoptive T-cell transfer of T-cells with transgenic high avidity T-cell receptors (TCR) holds a lot of promise as therapeutic approach, however comprising certain challenges. Endogenous and transferred TCR-chains compete for surface expression and may pair inappropriately, potentially leading to autoimmunity. Designer nucleases like transcription activator-like effector nucleases (TALEN) and RNA-guided nucleases of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated (Cas) system introduce specific DNA double strand breaks (DSB) at their target sites. This ability can be exploited for targeted genome editing. DSB repair through non-homologous end joining (NHEJ) can result in permanent gene knockout. Alternatively, if a homology-containing donor template is provided, transgenes can be inserted into the specific target locus by homology directed repair (HDR). In order to disrupt endogenous TCR expression, we assembled seven TALEN monomers and two guide RNAs targeting the constant regions of the TCR α-chain (TRAC) and the TCR β-chain (TRBC1 and TRBC2), respectively. Here we show the specific DSB induction by TALEN and CRISPR-Cas nucleases at their target sites, examined in K562 and T-cells using Cel1-assay and deep sequencing. Compared to nucleofection of TALEN-expressing plasmids, electroporation of mRNA considerably improved TCR knockout efficiency in primary T-cells. Using TRAC-TALEN and TRBC-TALEN mRNA, surface CD3 expression was successfully eliminated in about 75% and 60% of T-cells, respectively. The nuclease specificity was examined by identifying integrase-deficient lentiviral vector (IDLV)-marked DSB using LAM-PCR and deep sequencing. Although clustered IDLV integration sites were detected at the TALEN and CRISPR target sites, we did not detect any off-target activity, indicating high specificity. Additionally, K562 cells were nucleofected with TALEN-expressing plasmids and a donor template containing a GFP expression cassette flanked by 800bp homologous sequences to the TRAC locus. Thereby we were able to verify targeted gene addition through HDR of TALEN-mediated DSB in about 10% of treated cells. TALEN and CRISPR that show high efficiency and specificity to their target sequence will be used for generating T-cells with high avidity TCR.
Abstract 19719: Super Flexible Heart Replica With Vacuum Casting Technique Reproduces Real Structure and Texture of the Heart Fascinating Simulation Surgery in Complicted Congenital Heart Disease
Authors: Isao Shiraishi, Ken-ichi Kurosaki, Suzu Kanzaki, Katsunori Hatanaka, Hajime Ichikawa
Journal: Circulation (2015)

Introduction: Precise understanding of 3D anatomy is crucial for successful surgical operation in complicated congenital heart disease (CHD). We have developed a new technology that reproduces accurate and extremely flexible polyurethane biomodels of complicated CHD suitable for simulation surgery and medical education. Hypothesis: A novel 3D printing technique employing with stereolithography followed by vacuum casting is suitable for simulation surgery in complicated CHD. Methods: Thirty five replicas of CHD were produced with this technique; diagnosis included tetralogy of Fallot, pulmonary atresia with ventricular septal defect, double outlet right ventricle, persistent truncus arteriosus, hypoplastic left heart syndrome, interrupted aortic arch, congenitally corrected transposition of the great arteries, and so on. Three-dimensional volumetric datasets of MSCT angiography of CHD were converted into standard triangulated language files to make plastic stereolithographic biomodels representing outer and inner surface of the heart. Then, another outer mold was made with urethane using the outer surface biomodels as a cast. Then, rubbery polyurethane was injected between the outer and inner molds under the vacuum condition. After solidification, the molds were carefully removed and the final biomodels were obtained. Results: Wide variety of accurate and flexible biomodels of complicated CHDs from neonates to adults were reproduced. This technology allowed surgeons to precisely understand the internal chambers of the heart and allowed them to perform simulation surgery by way of cutting and suturing like a real heart tissue. Conclusions: These super flexible and accurate polyurethane biomodels were instructive for surgeons to understand the complex structures and hemodynamics of the disease and also helpful for planning the individual surgical operation of complicated CHD.
Epigenetic Profiling of Primary CLL Reveals Novel DNA Methylation-Based Clusters and Novel Mechanisms of Leukemogenesis
Authors: Fong Fong, Haim Y Bar, Kerby Shedden, Kamlai saiya-Cork, Peter Ouillette, Fabien Campagne, Ari Melnick, Sami Malek, Rita Shaknovich
Journal: Blood (2012)
Impact Of Vitamin D Level Pre and Post Allogeneic Hematopoietic Stem Cell Transplant
Authors: Kristen Beebe, Jane Olsen, Yu-hui Chang, Mary Burkhart, Lori DeCook, Susan Gerber, Kimberley Settineri, Jane Palmer, Joanne Schlesinger, Roberta Adams, Veena Fauble, Nandita Khera, Jared Klein, Jose Leis, Pierre Noel, Meagan Higgins, Craig Reeder, James L Slack, Lisa Sproat
Journal: Blood (2013)
Correlation of DNA Copy Number, Gene Expression, Protein Expression and Clinical Outcome in a Group of Patients with Diffuse Large B Cell Lymphoma (DLBCL) Treated with CHOP Plus Rituximab (CHOP-R).
Authors: N.A. Johnson, T. Relander, P. Farinha, T. Nayar, D.E. Horsman, Joseph M. Connors, Laurie Sehn, Randy D. Gascoyne
Journal: Blood (2006)
Abstract LB-094: Regorafenib and sildenafil interact to kill tumor cells
Authors: Mehrad Tavallai, Laurence Booth, Jane L. Roberts, Andrew Poklepovic, Paul Dent
Journal: Cancer Research (2015)

Abstract The present studies were to determine whether the multi-kinase inhibitor sorafenib or its derivative regorafenib interacted with phosphodiesterase 5 (PDE5) inhibitors such as sildenafil (Viagra) to kill tumor cells. PDE5 and PDGFR (alpha and beta) were over-expressed in liver tumors compared to normal liver tissue. In multiple cell types in vitro sorafenib/regorafenib and PDE5 inhibitors interacted in a greater than additive fashion to cause tumor cell death. Knock down of PDE5 or of PDGFR (alpha and beta) recapitulated the effects of the individual drugs. The drug combination increased ROS/RNS levels that were causal in cell killing. RNS stimulated the activation of the death receptor CD95 as well as the formation of autophagosomes and autolysosomes. Inhibition of CD95 / FADD / caspase 8 signaling suppressed drug combination toxicity. Knock down of ULK-1, Beclin1 or ATG5 suppressed drug combination lethality. The drug combination inactivated ERK, AKT, p70 S6K and mTOR and activated JNK. The drug combination also reduced mTOR protein expression. Activation of ERK or AKT was modestly protective whereas re-expression of an activated mTOR protein or inhibition of JNK signaling almost abolished drug combination toxicity. Sildenafil and sorafenib / regorafenib interacted in vivo to suppress xenograft tumor growth using liver and colon cancer cells. PDE5 inhibitors and sorafenib / regorafenib are FDA approved agents, and our data is now being translated into the clinic for further determination as to whether this drug combination is a useful anti-tumor therapy for solid tumor patients. Citation Format: Mehrad Tavallai, Laurence Booth, Jane L. Roberts, Andrew Poklepovic, Paul Dent. Regorafenib and sildenafil interact to kill tumor cells. [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 LB-094. doi:10.1158/1538-7445.AM2015-LB-094