tbuckley/cabot-search huggingface dataset:
Abstract 1682: Development and activity of a novel antibody-drug conjugate for the treatment of P-cadherin expressing cancers
Authors: Daniel Menezes, Tinya J. Abrams, Christopher Karim, Yan Tang, Chi Ying, Kathy Miller, Christie Fanton, Majid Ghoddusi, Zhen Wang, Montesa Patawaran, Nancy Pryer, Emma Lees, Jason Damiano
Journal: Cancer Research (2015)

Abstract The cell surface glycoprotein P-cadherin is an attractive target for an antibody-drug conjugate (ADC) therapy as it is known to be highly expressed in a number of malignancies, including those arising in the epithelium of the breast, lung, bladder, esophagus, stomach, endometrium and colon, among others. In breast cancer, P-cadherin is frequently overexpressed in high grade invasive tumors and is a reliable marker of the basal-like breast cancer molecular subtype, a disease with no effective therapeutic treatment options. Based on the expression profile of P-cadherin in human cancer, a highly selective and potent ADC was developed to target cancer types overexpressing this glycoprotein. This ADC consists of a fully human anti-P-cadherin-specific antibody conjugated to the potent maytansine-derived microtubule-disruptor, DM1, via an SMCC non-cleavable thioether linkage (technology licensed from ImmunoGen, Inc.). In vitro, the ADC was demonstrated to selectively bind P-cadherin expressing cell lines, to rapidly internalize and traffic to lysosomes, and to release a sufficient amount of activated payload to potently induce a cytotoxic response in cell viability assays. Profiling of activity in a cell line panel indicated that this ADC can effectively target and kill P-cadherin-positive cancer cells representing breast, head and neck, and bladder carcinomas. In vivo, the ADC was highly efficacious in numerous relevant xenograft models of P-cadherin expressing cancers, including breast, head and neck, bladder and lung. From this promising cellular and in vivo activity, this ADC may be an effective treatment for patients with P-cadherin positive cancers of high unmet medical need. Citation Format: Daniel Menezes, Tinya J. Abrams, Christopher Karim, Yan Tang, Chi Ying, Kathy Miller, Christie Fanton, Majid Ghoddusi, Zhen Wang, Montesa Patawaran, Nancy Pryer, Emma Lees, Jason Damiano. Development and activity of a novel antibody-drug conjugate for the treatment of P-cadherin expressing cancers. [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 1682. doi:10.1158/1538-7445.AM2015-1682
Long-Term Clinical Outcome of Patients with Acquired Aplastic Anemia In Brazil Using Cyclosporine-A (CSA) and Prednisone (PRED): 20 Years Follow-up From a Single Institution
Authors: Larissa A Medeiros, Samir K Nabhan, Marco Antonio Bitencourt, Michel M. Oliveira, Vaneuza A M Funke, Vivian K B Franco, Daniela C. Setubal, Caroline B S Sola, Elenaide C Nunes, Carmem Bonfim, José Zanis Neto, Ricardo Pasquini
Journal: Blood (2010)
Analysis of Philadelphia Negative Clones Detected during Treatment with Tyrosine Kinase Inhibitors: A Study on 63 CML Cases.
Authors: Claudia Haferlach, Susanne Schnittger, Alice Fabarius, Armin Leitner, Wolfgang Kern, Ulrike Bacher, Rüdiger Hehlmann, Andreas Hochhaus, Torsten Haferlach
Journal: Blood (2007)
Population Screening for Thalassemia In West Bengal with a Goal to Make Zero Thalassmia Growth
Authors: Jayasri Basak, Deboshree Majumdar, Soma Mukhopadhyay, Swati Dasgupta, Priyabrata Das, Nabamita Pal, Subhasish Dey, Ashis Mukhopadhyay
Journal: Blood (2010)
Treatment of patients with metastatic colorectal cancer over 75 years: Rimini's monoinstitutional experience
Authors: L. Stocchi, E. Tamburini, A. Affatato, M. Fantini, V. Arcangeli, A. Polselli, M. Nicolini, B. Venturini, G. Drudi, E. Barzotti, D. Tassinari
Journal: Annals of Oncology (2015)
Do the SLC25A38 or ALAS2 Genes Play a Role In the Phenotypic Expression of Ringed Sideroblasts In Acquired Myelodysplastic Syndrome?
Authors: Conrad V Fernandez, Stephen Couban, Robert Liwski, Makota P Matsuoka, Barbara Morash, Jason N Berman, Wenda Greer, Andrew C Orr, Duane L Guernsey
Journal: Blood (2010)
Disease Modeling and Drug Discovery Using Induced Pluripotent Stem Cells From CINCA Syndrome Patients
Authors: Takayuki Tanaka, Akira Ohta, Masakatsu Yanagimachi, Ryuta Nishikomori, Toshio Heike, Tatsutoshi Nakahata, Shinya Yamanaka, Megumu Saito
Journal: Blood (2012)
Circulating Levels of the Wnt Inhibitors Dickkopf-1 and Sclerostin In Different Phases of Multiple Myeloma: Alterations Post-Therapy with Lenalidomide and Dexamethasone with or without Bortezomib
Authors: Evangelos Terpos, Dimitrios Christoulas, Maria Gkotzamanidou, Cornelia Bratengeier, Maria Gavriatopoulou, Magdalini Migkou, Athanasios Papatheodorou, Efstathios Kastritis, Wolfgang Woloszczuk, Meletios A. Dimopoulos
Journal: Blood (2010)
Abstract 3388: Analytical validation and clinical verification of phosphoprotein biomarker modulation using a novel preservation system-based flow cytometry assay in multiple myeloma clinical trials
Authors: Anil Pahuja, Shyam Sarikonda, Benjamin Lee, Armin Graber, Shabnam Tangri, Naveen Dakappagari
Journal: Cancer Research (2015)

Abstract Propelled by the advent of novel oncogenic pathway-targeting drugs and increasing regulatory expectations to fulfil proof of mechanism endpoints in clinical trials, there is a critical need to reliably evaluate target inhibition by investigational drugs in biologically relevant compartments. However, the ability to monitor modulation of labile oncogenic pathway biomarkers in global hematomalignancy clinical trials is complicated by varying technical expertise at clinical sites, when specimen stability considerations do not permit analysis at a central specialty laboratory. To address this critical gap, we developed a novel preservation system, designated NovaPerm3 (NP3), that enables stabilization of phosphoprotein based biomarker specimens in a single step, requires less than 20 minutes, and can be implemented in routine clinical trial settings. Stabilized specimens can be frozen and analyzed even after 90 days in a specialized laboratory. Using the NP3 preservation system, we systematically developed and validated a flow cytometry assay that not only enables reliable identification of neoplastic plasma cells but also allows for quantitation of phosphoprotein biomarkers in the tumor cells of interest present in both the peripheral blood (PB) and bone marrow (BM). We will describe a) modulation of phosphorylation levels of the S6 ribosomal protein (pS6RP) by a novel anticancer agent in multiple myeloma patients b) qualitative concordance between NP3-flow cytometry and western blot results from multiple drug treated leukemia cell lines c) sensitive detection of neoplastic plasma cells up to 1% of the total white cells and d) specimen (pS6RP) stabilization over a 90 day period. In conclusion, our novel preservation method and clinical trial laboratory validated flow assay enables reliable quantification of signaling biomarkers in hematomalignancy trials with ease in a specialized central laboratory while reducing the procedural burden for collecting biomarker specimens in global clinical trials. Citation Format: Anil Pahuja, Shyam Sarikonda, Benjamin Lee, Armin Graber, Shabnam Tangri, Naveen Dakappagari. Analytical validation and clinical verification of phosphoprotein biomarker modulation using a novel preservation system-based flow cytometry assay in multiple myeloma clinical trials. [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 3388. doi:10.1158/1538-7445.AM2015-3388
PWE-007 A single-centre 8-month experience of propofol sedation for endoscopic procedures
Authors: N E Burch, R Robinson
Journal: Gut (2010)

<h3>Introduction</h3> Propofol is being increasingly used for sedation in endoscopic procedures in the US and across Europe, but experience within UK centres remains limited. Over the last few years there has been an anaesthetist covered dedicated propofol sedation endoscopy list at the Leicester General Hospital. The aim was to evaluate the propofol sedation service with respect to current practice and complication rates, with a view to expanding the service and developing appropriate guidelines for more effective use. <h3>Methods</h3> Review of all endoscopic procedures using propofol for sedation over 8-months at the Leicester General Hospital. Data were collected for all relevant procedures from August 2008 to March 2009. Indication for propofol use was examined, type of procedure, dose of propofol, and significant complications evaluated. <h3>Result</h3> 48 procedures were done using propofol sedation during Aug 2008–March 2009: 54% OGD; 33% Colonoscopy; 8% PEG; 4% FOS. The patients9 age ranged from 21–78 years (mean 52), with 52% female and 48% male. Of these procedures 45% had no clear indication for the use of propofol, 35% had previously failed the procedure under “standard sedation”, 13% required therapeutic procedures, 8% had other relevant indications for propofol sedation as opposed to standard endoscopic sedation. Dose was documented in 31% of cases, with dose ranging from 120–600 mg propofol (mean 324 mg). 2/48 (4%) had respiratory compromise requiring airway support with bag and mask ventilation for a few minutes. There were 15 pending requests at the time of evaluation: 60% COL; 13% OGD+COL; 13% banding/dilatation; 7% OGD; 7% PEG. Patients9 age range was 25–65 years (mean 49), 67% female and 33% male. In 60% requests there was no reason identified for rationale behind use of propofol, 27% had previously failed procedure under standard sedation, 7% were therapeutic, and 7% were for surveillance purposes. <h3>Conclusion</h3> There is increasing demand for the use of propofol for sedation in endoscopic procedures within UHL NHS Trust. In our centre there has been effective use of anaesthetist led propofol endoscopy lists with minimal complications and a good level of patient satisfaction. With increasing patient popularity and a greater drive for surveillance and screening procedures in patients, perhaps a formal anaesthetist supported propofol endoscopy service should be established in all endoscopy units. Until more information is available on the safety of use of propofol for diagnostic and therapeutic endoscopy, clear guidelines need to be in place in centres developing a propofol endoscopy service to ensure safe and appropriate use.
Abstract 4307: In vitro drug sensitivity and genetic profile analysis from primary culture obtained from brain cancer
Authors: Franciele C. Kipper, Louise C. Mendonça, Rafael Becker, Gláucia Confortin, Pítia F. Ledur, André Marc, Eliseu Paglioli-Neto, Fabiana Viola, Fernanda B. Morrone, Guido Lenz
Journal: Cancer Research (2015)

Abstract The Cancer Genome Atlas effort subtyped gliomas in four molecular groups based on gene expression, mutation and deletion and retrospectively linked these subtypes to chemotherapy response. But up to now there is no protocol to use this or other methods to predict chemotherapy response in the clinic for gliomas. Patients are normally treated with ratiotherapy and temozolomide (TMZ) in a protocol of 5 days of treatment and 23 days of recovery. The goal of this study is to analyze gene expression and drug sensitivity in a relevant time frame to prospectively contribute to therapeutic decisions. For this, we prepared 19 cell cultures from 19 biopsies of brain tumors and treated them with a range of chemotherapy agents (TMZ, carmustine, lomustine, cisplatin, etoposide, paclitaxel, irinotecan, procarbazin, mebendazol, vincristin and vinblastin) at plasmatic concentration. Cells were counted for at least 12 days after treatment or tested for viability after 7 or 14 days and more that 60% reduction was considered a positive response. From eleven cell cultures tested with viability assay, only one responded to temozolomide (the first line chemotherapy for this tumor) after a single administration. The strongest effect was obtained using anti-microtubule agents. Cell counting after 12 days of treatment confirmed the resistance to TMZ and the sensitivity to antimicrotubule drugs, particularly paclitaxel. Combination of procarbazin, lomustine and vincristine (PCV), previously used to treat glioblastoma patients, killed very effectively cells of only 1 patient. The cell cultures from three of five patients display EGFR over-expression and four of five presented p53 and p21 expression. At this time, we are not able to correlate gene expression, subtyping and drug sensitivity. From these data we conclude that brain tumors can be routinely grown and tested for drug sensitivity in a time frame that more closely mimics the treatment of patients. Ethical protocol number UFRGS: 420.856; PUCRS: 429.849 Financial support: FAPERGS, CNPq e CAPES. Citation Format: Franciele C. Kipper, Louise C. Mendonça, Rafael Becker, Gláucia Confortin, Pítia F. Ledur, André Marc, Eliseu Paglioli-Neto, Fabiana Viola, Fernanda B. Morrone, Guido Lenz. In vitro drug sensitivity and genetic profile analysis from primary culture obtained from brain cancer. [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 4307. doi:10.1158/1538-7445.AM2015-4307
Abstract 1522: Survival of skin cancer tumor initiating cells requires the Ezh2 polycomb group protein
Authors: Gautam Adhikary, Dan Grun, Candace Kerr, Sivaprakasam Balasubramanian, Ellen Rorke, Wen Xu, Richard Eckert
Journal: Cancer Research (2015)

Abstract Epidermal squamous cell carcinoma is among the most common cancers in humans. These tumors are comprised of phenotypically diverse of cells that display varying potential for proliferation and differentiation. Polycomb group (PcG) proteins, including Ezh2, are important candidate stem cell maintanence proteins. Our previous study showed that Ezh2-enriched epidermal cancer stem cells (ECS cells) represent a minority of cells in tumors, yet drive aggressive tumor formation. In the present study, we show that Ezh2 is required for ECS cell survival, migration, invation and tumor formatiom and this is associated with increased histone H3 trimethylationon lysine 27, a mark of Ezh2 action. We also show that Ezh2 knockdown or treatment with Ezh2-selective inhibitors, GSK126 or EP-6438, reduce Ezh2 level and activity, leading to reduced spheroid formation, migration, invasion and tumor formation. Use of these inhibitors was associated with reduced ECS cell vaibility and induction of apoptosis. These studies indicate that epidermal squamous cell carcinoma cells contain a subpopulation of cancer stem cells-like tumor initiating cells that are enriched in Ezh2 expression and that Ezh2 is required for optimal survival of these cells and tumor formation. These studies suggest that treatment with Ezh2 inhibitors may be a strategy for reducing epidermal cancer stem cell survival and supressing tumor formation. Citation Format: Gautam Adhikary, Dan Grun, Candace Kerr, Sivaprakasam Balasubramanian, Ellen Rorke, Wen Xu, Richard Eckert. Survival of skin cancer tumor initiating cells requires the Ezh2 polycomb group protein. [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 1522. doi:10.1158/1538-7445.AM2015-1522
656. Effects of STAT3 Inhibition on the Innate Immune Response to OV Therapy
Authors: Alexander Weiss, George Koutras, Chelsea Bolyard, Balveen Kaur
Journal: Molecular Therapy (2016)

Objective. Our lab has established that an alteration in STAT3 signaling affects the replicative ability of oncolytic virus (OV) (Okemoto 2013). However, STAT3 inhibitors are currently in clinical trials for treating several cancers, including glioblastoma (NCT01904123). One STAT3 inhibitor, WP1066, has been shown to modulate the immune response to tumors (Hussein 2007). The innate immune response to OV is known to limit its therapeutic efficacy (Meisen 2015, Han 2015) This study examines the effects of STAT3 inhibition on the innate immune response to OV therapy. Methods. In vitro, we examined the effect of STAT3 inhibition on immune cell response to OV-infected glioma. We evaluated changes in migration of immune cells towards OV-infected tumor cells, using a modified Boyden chamber. Macrophages or microglia +/- STAT3 inhibitor pretreatment were seeded on the upper chamber, and tumor cells +/- OV infection were plated on the lower chamber, acting as a migration stimulus. Migration was quantified after 6 hours. To evaluate the effect of STAT3 inhibition on the direct immune cell response to OV-infected GBM cells, we utilized a co-culture. Herein, we infected tumor cells with OV, and then overlaid them with immune cells +/- drug pretreatment. Virus replication was visualized through fluorescent imaging, and quantified via plaque assay. We utilized murine models of glioblastoma (GBM) to evaluate the effect of combining STAT3 inhibitors with OV therapy. Female nude mice were implanted intracranially or subcutaneously with human GBM cells, and then treated with PBS, pharmacologic STAT3 inhibitor, luciferase-expressing OV, or combination. Using bioluminescent in vivo live imaging, we monitored viral replication by measuring luciferase activity. We also monitored mice for survival. Results. Pharmacologic inhibition of STAT3 signaling in macrophage and microglial cell lines (RAW264.7 and BV2) reduced their migration towards OV-infected glioma cells. Furthermore, pre-treating immune cells with STAT3 inhibitor reduced their reactivity to OV-infected glioma cells, permitting increased replication. In vivo, combination therapy with STAT3 inhibitor and OV resulted in a significant increase in viral replication. Survival studies are ongoing. Conclusions. We hypothesize STAT3 inhibitors may alter the immune response to oncolytic virus, permitting increased viral replication and prolonged survival in vivo. Further research into this area may prove useful in developing new treatments to be used in combination with OV for treatment of GBM.
Khorana Score and Histotype Predict the Incidence of Early Venous Thromboembolism (VTE) in Non Hodgkin Lymphoma (NHL). a Pooled Data Analysis of Twelve Clinical Trials of Fondazione Italiana Linfomi (FIL)
Authors: Roberto Mario Santi, Manuela Ceccarelli, Gioacchino Catania, Chiara Monagheddu, Andrea Evangelista, Elisa Bernocco, Federico Monaco, Massimo Federico, Umberto Vitolo, Sergio Cortelazzo, Maria Giuseppina Cabras, Michele Spina, Luca Baldini, Carola Boccomini, Annalisa Chiappella, Alessia Bari, Stefano Luminari, Marco Calabrese, Alessandro Levis, Laura Contino, Giovannino Ciccone, Marco Ladetto
Journal: Blood (2015)
Phase I/II Dose-Escalation Study of Tositumomab and Iodine I 131 Tositumomab for Relapsed/Refractory Classical or Lymphocyte-Predominant Hodgkin’s Lymphoma: Feasibility and Initial Safety
Authors: Heather A. Jacene, Yvette L. Kasamon, Richard F. Ambinder, Wayne Kasecamp, Donna Serena, Richard L. Wahl
Journal: Blood (2008)
Abstract B28: Co-occupancy of AML1-ETO and N-CoR defines a dominant phenotypic signature in leukemic cells.
Authors: Daniel J. Trombly, Troy W. Whitfield, Srivatsan Padmanabhan, Jonathan A. Gordon, Jane B. Lian, Andre J. van Wijnen, Sayyed K. Zaidi, Janet L. Stein, Gary S. Stein
Journal: Clinical Cancer Research (2015)

Abstract The t(8;21) chromosomal translocation produces AML1-ETO, an oncogenic fusion protein that compromises the function of AML1, a transcription factor critical for the myeloid cell differentiation. The differentiation arrest and self-renewal phenotypes of cells expressing AML1-ETO have been chiefly studied at the single gene level. In order to understand how the genome-wide occupancy of AML1-ETO and associated co-regulators contributes to the leukemic properties of Kasumi-1 cells, a model system for human t(8;21) leukemia, chromatin immunoprecipitation-sequencing (ChIP-seq) experiments were employed. Genome-wide DNA binding profiles for AML1 and AML1-ETO in Kasumi-1 cells showed that both proteins were enriched at introns and distal upstream regulatory regions, the latter implying that distal elements are likely important for target gene regulation. Importantly, A substantial fraction of AML1/AML1-ETO-p300 co-localization occurs near transcriptional start sites (TSSs) in promoter regions associated with transcriptionally active loci, as indicated by an observed enrichment of the H3K4me3 histone modification. A significant discovery of the current study is the co-localization of AML1/AML1-ETO with N-CoR on regions that are primarily distal to TSSs. Analyses of both gene expression data and gene ontology suggest that the AML1/AML1-ETO co-localization with N-CoR, more so than with p300, is associated with the leukemic phenotype of Kasumi-1 cells. De novo motif discovery reveals that PU.1 motifs are over-represented in regions co-occupied by AML1-ETO and N-CoR compared to other AML1-ETO bound regions. Our findings establish a novel and predominant AML leukemia signature characterized by occupancy of the AML1-ETO/N-CoR complex at genomic regions enriched in motifs for myeloid differentiation factors. We propose that this property is critical for maintenance of the leukemic phenotype. Citation Format: Daniel J. Trombly, Troy W. Whitfield, Srivatsan Padmanabhan, Jonathan A. Gordon, Jane B. Lian, Andre J. van Wijnen, Sayyed K. Zaidi, Janet L. Stein, Gary S. Stein. Co-occupancy of AML1-ETO and N-CoR defines a dominant phenotypic signature in leukemic cells. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr B28.