tbuckley/cabot-search huggingface dataset:
Abstract 1254: Mitochondrial SOD2 regulates EMT and cancer stem cell-like cell populations
Authors: Kelly A. Whelan, Hideaki Kinugasa, Koji Tanaka, Satish Srinivasan, Manti Guha, Daret St. Clair, Andres Klein-Szanto, Narayan Avadhani, Alan Diehl, Anil Rustgi, Hiroshi Nakagawa
Journal: Cancer Research (2015)

Abstract Epithelial-mesenchymal transition (EMT) is involved in cancer cell invasion, metastasis and treatment failure. EMT may promote conversion of a subset of cancer cells defined by low expression of CD44 (CD44L) to those with high expression of CD44 (CD44H), the latter associated with increased malignant properties of cancer cells. Triggered by a variety of stimuli such as transforming growth factor (TGF)-β, hypoxia and chemoradiation, EMT may be activated in cancer cells via stress-induced reactive oxygen species (ROS) in the tumor microenvironment. Excessive ROS may cause cell death or senescence; however, cells undergoing EMT may require a physiological level of ROS. It remains elusive as to how cellular antioxidant capabilities may influence EMT. Mitochondrial superoxide dismutase 2 (SOD2) is frequently overexpressed in oral and esophageal cancers. Here, we investigated mechanisms of SOD2 transcriptional regulation in EMT as well as the functional role of this antioxidant in EMT. Using well-characterized genetically engineered oral and esophageal human epithelial cell lines coupled with RNA interference (RNAi) and flow cytometric approaches, we find that TGF-β stimulates EMT, resulting in conversion of CD44L to CD44H cells, the latter of which display SOD2 upregulation. SOD2 induction in transformed cells was concurrent with suppression of TGF-β-mediated induction of both ROS and senescence. SOD2 gene expression appeared to be transcriptionally regulated by NF-κB and ZEB2, but not ZEB1. Moreover, SOD2-mediated antioxidant activity may restrict conversion of CD44L cells to CD44H cells at the early stages of EMT. In aggregate, this study provides novel mechanistic insights into the dynamic expression of SOD2 during EMT and delineates a functional role for SOD2 in EMT, influencing distinct CD44L and CD44H subsets of cancer cells that have been implicated in oral and esophageal tumor biology. Note: This abstract was not presented at the meeting. Citation Format: Kelly A. Whelan, Hideaki Kinugasa, Koji Tanaka, Satish Srinivasan, Manti Guha, Daret St. Clair, Andres Klein-Szanto, Narayan Avadhani, Alan Diehl, Anil Rustgi, Hiroshi Nakagawa. Mitochondrial SOD2 regulates EMT and cancer stem cell-like cell populations. [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 1254. doi:10.1158/1538-7445.AM2015-1254
340. Development of a Nuclease Screen to Improve Cas9 Targeting Specificity
Authors: Jeffrey M. Spencer, Xiaoliu Zhang
Journal: Molecular Therapy (2015)

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) bacterial immunity targets invading nucleic acid sequences using an RNA guide (gRNA). The well-defined Cas9 from Streptococcus pyogenes' type II CRISPR system has been utilized as a gene editing tool in a vast assortment of organisms. However, an inherent lack of specificity limits the potential of the current system and presents challenges to interpreting experimental results. A plasmid cleavage based screening platform has been developed with the intent to increase the fidelity of the Cas9 system. Utilizing both positive and negative selection, the screen can be used to identify variants of Cas9 or its gRNA with improved specificity. Positive selection of variants with activity towards the appropriate target site proceeds through the removal of a plasmid containing an inducible suicide gene. Conversely, negative selection of variants with reduced activity on off-target substrates involves the retention of a plasmid with an antibiotic resistance gene. Preliminary results suggest that a gRNA with an insertion in the scaffold region of the RNA can decrease the level of off-target cleavage. These results suggest that the screening platform has the potential to identify novel protein or RNA variants with greater targeting specificity compared to the naturally occurring components. A Cas9 system with enhanced fidelity will expand the potential applications of the technology and accelerate its ability to interrogate biological systems.
Anaemia is associated with hearing loss in adults
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Iron deficiency anaemia (IDA) has been found to be associated with hearing loss in adults by a study published in JAMA Otolaryngology - Head and Neck Surgery .1

Using the electronic medical records of 305 339 adults aged between 21 and 90 years, researchers at Pennsylvania State University College of Medicine examined the association between IDA and sensorineural hearing loss (when there is damage …
670. A Novel Approach to Expand Antigen Recognition in Chimeric Antigen Receptors
Authors: Robert Moot, Sunil Raikar, Lauren Fleischer, Melissa Querrey, Christopher Doering, Trent Spencer
Journal: Molecular Therapy (2016)

Chimeric antigen receptor (CAR) technology, although very promising, is limited in its application by the availability of target antigens. We propose to expand the pool of potentially targetable cell-surface antigens using the variable lymphocyte receptor (VLR) of the sea lamprey as the antigen recognition region of the CAR. VLRs represent the functional region of the lamprey and hagfish adaptive immune system. They are single chained and variable length, crescent shaped proteins that are produced by assembly of leucine-rich repeat cassettes to form a gene encoding region capable of exceeding 1015 unique variations. Due to their difference in structure compared to Ig based antibodies, VLRs bind antigen in a geometrically dissimilar manner. This unique property of VLRs allows them the ability to bind antigen epitopes that may not typically be bound by scFvs, the result being a potentially expanded repertoire of tumor cell target antigens that may be used in CAR design and application. In our studies, VLRs have been successfully developed from immunized lampreys and target cell specific VLRs have been cloned for several different antigens including VLRs specific for cancer cell lines and purified proteins. This is accomplished using yeast surface display combined with flow sorting and results in monoclonal VLRs specific for the cell line with which the lampreys were immunized. The functionality of the VLR was initially demonstrated in Jurkat cells transduced with a previously generated VLR specific for the B-cell receptor of the mouse tumor line, BCL. CAR protein expression from whole cell lysates of transduced Jurkat cells showed expression of CAR protein. CAR cell surface expression was also confirmed in Jurkat cells using a construct co-expressing GFP preceding a P2A sequence with >90% cells GFP positive. Transduced CAR-Jurkat cells showed upwards of 85% activation in co-culture assays with target cells. In transduced but not co-cultured cells, activation was <5% and activation in naïve cells co-cultured with BCL cells was <2%. These results establish the ability of these cells to effectively produce and express VLR-CAR protein. The BCL VLR-CAR construct was also shown to be functional in several different types of cytotoxic effector cells including gamma delta T-cells and NK-92 cells, where target cell killing was increased significantly over non-transduced cells, indicating that target cell specific toxicity is mediated through the VLR-CAR. From these results, showing that VLRs function effectively as the antigen recognition region of the CAR construct we have concluded that VLRs can serve as a unique alternative for directing CAR activity toward specific effector cells.
Cytoreduction Plus Low-Dose Aspirin Versus Cytoreduction in Monotherapy As Primary Prophylaxis of Thrombosis in Patients with Essential Thrombocythemia.
Authors: Alberto Alvarez-Larrán, Arturo Pereira, Eduardo Arellano-Rodrigo, Juan Carlos Hernández-Boluda, Francisco Cervantes, Carlos Besses
Journal: Blood (2012)
Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease
Authors: M.K. Wilson, E. Pujade-Lauraine, D. Aoki, M.R. Mirza, D. Lorusso, A.M. Oza, A. du Bois, I. Vergote, A. Reuss, M. Bacon, M. Friedlander, D. Gallardo-Rincon, F. Joly, S.-J. Chang, A.M. Ferrero, R.J. Edmondson, P. Wimberger, J. Maenpaa, D. Gaffney, R. Zang, A. Okamoto, G. Stuart, K. Ochiai
Journal: Annals of Oncology (2016)
New Method for in Vivo Hematopoiesis Microenvironment Research: Tissue-Engineering-Bone Femur Repairing Model and Semi-Solid Decalcification
Authors: Shan Jiang, Qianli Jiang, Liqiong Zhu, Feili Chen, Lezhong Yuan, Peiran Zhao, Mo Yang, Jing Sun, Fanyi Meng
Journal: Blood (2012)
Abstract 3988: MicroRNA expression associated with response grade in gastric cancer patients’ tumors
Authors: Michelle Maccarini Barcelos Baldoni, Cláudia Malheiros Coutinho Camillo, Renato David Puga, Maria Dirlei Ferreira Begnami
Journal: Cancer Research (2015)

Abstract Background: Many chemotherapy schemes have been used in neoadjuvant treatment scenario to improve the overall and disease-free survival of gastric cancer (GC) patients treated with surgery alone. However, in some cases, the objective clinical response is not achieved, and this lack of response to neoadjuvant chemotherapy may delay curative surgery and increase surgical complications. Therefore, a major challenge for improving clinical outcomes is to understand the molecular mechanisms that may play essential roles in patients responses of GC treatments. The expression levels of several miRNAs have been found to be correlated with GC prognosis and could determine the clinical response for neoadjuvant chemotherapy. Therefore, our goal was to analyze the relation between miRNA profile and the pathological response grade of GC patients tumors treated with neoadjuvant chemotherapy or surgery alone. Methods: We selected 34 biopsy tumor samples of patients treated with neoadjuvant chemotherapy (collected before the treatment) and 23 tumor samples of patients submitted to surgery without adjuvant treatment. All patients treated with neoadjuvant chemotherapy received ECF, DCF or ECX prior the surgery, and subsequently they were submitted to a complete resection. The identification of differentially expressed miRNAs was done by TLDA Quantitative Real Time PCR. Results: After categorizing neoadjuvant chemotherapy patients according to percentage of viable tumor cells present in gastric resection and the surgical patients according to their 5 years of follow up status we could segregate those with and without response for both treatments. The comparison between response grade versus miRNAs showed 9 and 14 downregulated miRNAs in samples of patients without response for neoadjuvant chemotherapy and surgery alone, respectively. We also could observe 3 common downregulated miRNAs between patients without response in both groups. Conclusion: We identified some downregulated miRNAs involved in gastric cancer pathways and mechanisms of drug resistance that should manage to determine a predictable miRNA signature to perform a correct patient selection for GC treatments. Note: This abstract was not presented at the meeting. Citation Format: Michelle Maccarini Barcelos Baldoni, Cláudia Malheiros Coutinho Camillo, Renato David Puga, Maria Dirlei Ferreira Begnami. MicroRNA expression associated with response grade in gastric cancer patients’ tumors. [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 3988. doi:10.1158/1538-7445.AM2015-3988
Exploring Genetic Basis of GVHD by Whole-Genome Association Studies in a Large Series from the Japan Marrow Donation Program (JMDP).
Authors: Yasuhito Nannya, Makoto Onizuka, Koichi Kashiwase, Masashi Sanada, Yoshiki Akatsuka, Masahiro Satake, Shigeru Chiba, Mineo Kurokawa, Ken Yamamoto, Hiroo Saji, Etsuko Maruya, Hidetoshi Inoko, Yasuo Morishima, Yoshihisa Kodera, Seishi Ogawa
Journal: Blood (2007)
521. AAV Immunotherapy Induces Functional Antigen Specific Regulatory T-Cells to a Neuroantigen: A Potential Treatment for MS
Authors: Brad E. Hoffman
Journal: Molecular Therapy (2015)

Immunotherapy for autoimmune disease aims at restoring a state of tolerance to the self-antigens that propagate disease. Multiple sclerosis (MS) is an immune-mediated disease of the CNS in which leads to demyelination and damage of axons. It is believed that a failure of central and peripheral mechanisms to maintain self-tolerance to auto-aggressive myelin-specific T cells plays a central role in the pathogenesis. It has been demonstrated that antigen (Ag)-specific regulatory T cells (Tregs) have a significant role in modulating autoimmune CNS disease and when used therapeutically, can be highly effective at treating MS. Thus, using AAV liver gene therapy to restore normal Treg function and re-establish immune tolerance to myelin proteins in early onset MS represents a novel treatment strategy for stabilization of disease progression. The development of protocols that directly affect the expansion Ag-specific Treg numbers and/or enhances their function has become a significant focus in the research community. Unfortunately, successful therapeutic use of Tregs has been limited by the lack of safe and effective protocols for isolation and expansion that are suitable for translation. However, hepatic gene transfer with AAV vectors containing liver specific promoters has been shown to produce stable transgene expression and induce a robust antigen-specific immune tolerance to a variety of therapeutic proteins. In a murine model for MS, we have previously demonstrated that liver directed AAV gene therapy represents a novel approach to not only prevent experimental autoimmune encephalomyelitis (EAE) disease, but more importantly, can also abrogate disease progression. The work presented here provides evidence that liver directed AAV gene therapy using the neuroantigen MOG does indeed produce functional Ag-specific Tregs. In a series of experiments, B6FoxP3-GFP mice were injected with AAV8-MOG via the tail vein. After 8 weeks, splenocytes were harvested and analyzed using I-Ab MOG35-55 (MHC II) or control tetramers (provided by NIH Tetramer Core). The results revealed that mice receiving AAV8-MOG did indeed produce Ag-specific Tregs (Fig.1). Functionality was further determined using an in vitro Treg suppression assay. Briefly, CD4+CD25+ Tregs were magnetically sorted and co-cultured with fluorescently labeled MOG-specific TCR+CD4+ cells at varying concentrations and in the presence of MOG35-55 antigen. FACS analysis confirmed that the Mice receiving AAV8-MOG did indeed produce Ag-specific Tregs and that they were functionally suppressive (Fig.2). The work presented here shows that liver directed gene transfer using an AAV vector expressing a neuro-antigen is capable of inducing Ag-specific Tregs that are able to suppress Ag-specific effector CD4 cells. More importantly, this work continues to advance the therapeutic use of AAV for the treatment of auto-immune diseases such as MS. View Large Image Figure ViewerDownload (PPT)
Stereotactic body radiotherapy followed by surgery for unstable spinal metastases: Technical feasibility and safety study according to the IDEAL stages 1 and 2a.
Authors: A. Versteeg, J. van der Velden, H. Verkooijen, W. Eppinga, N. Kasperts, S. Gerlich, C. Oner, M. van Vulpen, J.-J. Verlaan
Journal: International Journal of Surgery (2016)
Phase 3b UPFRONT Study: Safety and Efficacy of Weekly Bortezomib Maintenance Therapy After Bortezomib-Based Induction Regimens In Elderly, Newly Diagnosed Multiple Myeloma Patients
Authors: Ruben Niesvizky, Ian W. Flinn, Robert M. Rifkin, Nashat Y Gabrail, Veena Charu, Billy Clowney, James Essell, Yousuf A Gaffar, Thomas A. Warr, Rachel Neuwirth, Deyanira Corzo, James A Reeves
Journal: Blood (2010)
Analysis of Impact of Comorbidities Constituting the HCT-CI Score on the Outcome of Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia
Authors: Fotios V. Michelis, Hans A. Messner, Naheed Alam, Vikas Gupta, Dennis Dong Hwan Kim, John Kuruvilla, Anna Lambie, Auro Viswabandya, Jeffrey H. Lipton
Journal: Blood (2015)
Abstract 2210: DNA methylation to identify non-coding gene regulatory regions in tumor samples
Authors: Benjamin P. Berman
Journal: Cancer Research (2015)

Abstract Altered control of transcriptional regulation via mutations to transcription factors and chromatin modifiers is a hallmark of cancer. Many popular methods for studying transcriptional regulation, such as ChIP-seq, DNase-I hypersensitivity, and Chromatin Conformation Capture, can be challenging to apply to clinical samples. DNA methylation has long been the chromatin biomarker of choice in disease studies because of its stability under clinical collection conditions. We have used DNA methylation profiles of thousands of tumors within the TCGA to reconstruct cancer-specific transcription factor regulatory networks, including non-coding transcription factor binding sites in enhancer regions. We use methyl-expression QTL (M-&amp;gt;E QTL) analysis to associate changes at individual binding sites with their gene targets, often hundreds of thousands of base pairs away. This new approach allows for the first time the identification of in vivo enhancer changes in thousands of individuals, and provides a technology platform to identify key regulatory events in cancer progression. Note: This abstract was not presented at the meeting. Citation Format: Benjamin P. Berman. DNA methylation to identify non-coding gene regulatory regions in tumor samples. [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 2210. doi:10.1158/1538-7445.AM2015-2210
Abstract 995: Regulation of radiation by autophagic modulator
Authors: Keun Ho Lee, Yoon Kyung Lee
Journal: Cancer Research (2015)

Abstract Introduction: On account of limited therapeutic options for advanced and recurrent cervical cancer, novel therapeutic modalities are being investigated based on translational research. Among the promising topics is autophagy. Autophagy can be refered to as a double edged sword in a way that it is known to play a role in both tumor cell suppression and survival. This study was carried out to determine the effect of autophagy in treatment of cervical cancer cells with radiation alone and with autophagy inducer or inhibitor. Methods: Human cervical cancer cells, Hela and Caski were used. Western blot was implemented to detect protein expression. Fluorescence microscopy and inverted microscopy guided inspection confimed autophagy. Hela and Caski cells were irradiated with r-rays (2 Gy / min) and again each time after treatment with autophagy inducer (Rapamycin) and inhibitor (3-MA). Expression of LC3 and cell deaths in two cell preparations were examined. Results: Notable increment of LC3 expression were detected after radiation in both cell lines by western blot and microscope analyses. Radiation of pre-Rapamycin treated cells showed further increased LC3 expression and pre-3-MA treated cells, less increased LC3 expression than radiation alone compared to non-treated, not radiated cells. Cell viability decreased to 75% in Hela cells and 79% in Caski cells after radiation. When treated with Rapamycin, cell viabilities were 59% and 65%, and with 3-MA, 65% and 70% in each cell lines. Discussion: Radiation induces autophagy in cervical cancer cell lines. Autophagy induced by radiation could be modified when treated with Rapamycin / 3-MA which leads to more cell deaths. Further investigations are needed to identify the specific pathways mediating post-IR induced autophagy in order to confirm the functional link between autophagy and radiation treatment. Inhibition of autophagy seems to promote more cells to undergo apoptosis, however, the relationship between autophagy and apoptosis with IR treatment in cervical cancer cells remain to be enlightened. Induction of autophagy may interfere with the mechanism of homeostasis that is originally preserved by autophagy itself, and leads to cell death possibly altogether with apoptosis. The pathway via which this process conducts also waits to be distinguished. Citation Format: Keun Ho Lee, Yoon Kyung Lee. Regulation of radiation by autophagic modulator. [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 995. doi:10.1158/1538-7445.AM2015-995
Improved Progression-Free Survival (PFS) of Alemtuzumab (Campath®, MabCampath®) Plus Fludarabine (Fludara®) Versus Fludarabine Alone as Second-Line Treatment of Patients with B-Cell Chronic Lymphocytic Leukemia: Preliminary Results From a Phase III Randomized Trial.
Authors: Andreas Engert, Liana Gercheva, Tadeusz Robak, Pilipenko Galina, Jingyang Wu, Cynthia A. Sirard, Thomas Elter
Journal: Blood (2009)
Inhibition of XIAP Enhances Specific Cytotoxic T Lymphocyte (CTL) Killing and CD20-Directed Antibody-Dependent Cellular Cytotoxicity of Chronic Lymphocytic Leukemia B Cells.
Authors: Arnon P. Kater, Roman Rieger, Kate Welsh, Adel Nefzi, Richard Houghten, John C. Reed, Clemencia Pinilla, Thomas J. Kipps
Journal: Blood (2004)
Mll-AF4 Induction during Ontogeny Reveals Early Changes in Myeloid and Lymphoid potential and Results in Hematopoietic Malignancies in Adult Mice
Authors: Neil A Barrett, Chrysa Kapeni, Camille Malouf, George Giotopoulos, Simon Fitch, Wendi A. Bacon, Brian Huntly, Katrin Ottersbach
Journal: Blood (2014)
Identification of a Prognostic Gene Expression Signature for AZA Response in MDS and CMML Patients
Authors: Ashwin Unnikrishnan, Dominik Beck, Arjun Verma, Laura A Richards, Julie A I Thoms, Ashu Kumari, Sally Galbraith, Austin Kulasekararaj, Magnus Tobiasson, Petter S Woll, Andrea Pellagatti, Elli Papaemmanuil, Susan R Wilson, Robert Lindeman, Peter J Campbell, Jacqueline Boultwood, Kevin Lynch, Sten Eirik W Jacobsen, Ghulam J. Mufti, Eva Hellstrom-Lindberg, Karen L MacKenzie, Jason WH Wong, John E Pimanda
Journal: Blood (2014)