tbuckley/cabot-search huggingface dataset:
PP-005 Endoscopic resection of giant polyps – insight at the extreme end of modern emr practice: Abstract PP-005
Authors: R J Mead, M Duku, G Longcroft-Wheaton, P Bhandari
Journal: Gut (2010)

<h3>Abstract</h3> Posttraumatic Stress Disorder continues to be a highly stigmatized disease for the veteran population and stigma continues to be identified as the main deterrent in treatment seeking. Little attention has been paid to how the process of obtaining service-connected disability status can amplify veterans’ perceptions of being stigmatized. The following ethnographic study identified how combat veterans experienced stigma in processing through Veterans Affairs care and the effects of linking a Posttraumatic Stress Disorder diagnosis with disability compensation to perceived stigmas. Stigma was identified in two inter-related areas: 1) the structural level in the Veterans Affairs disability claims process and 2) the individual level in interactions with Veterans Affairs service providers. Results based on veterans’ narratives suggest that the disability claims process, requiring multiple repetitions of personal trauma, coupled with perceptions of institutional stigmas of malingering, created <i>bureaugenic effects</i>: a worsening of symptoms caused by bureaucratic protocols intended to help veterans. This process influenced first time treatment users of the Veterans Affairs by deterring treatment-seeking behavior but was not found to affect veterans who had already initiated treatment. Despite the experience of stigma and commodification of their suffering through disability and diagnostic screening, veterans still sought disability compensation. Veterans viewed this compensation as acknowledgment of their loss and validation of their sacrifice.
Lenalidomide, Bortezomib, and Dexamethasone in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Encouraging Response Rates and Tolerability with Correlation of Outcome and Adverse Cytogenetics in a Phase II Study.
Authors: Paul Richardson, Sundar Jagannath, Andrzej Jakubowiak, Sagar Lonial, Noopur Raje, Melissa Alsina, Irene Ghobrial, Amitabha Mazumder, Nikhil C Munshi, David H Vesole, Kathleen Colson, Mary L McKenney, Laura Lunde, Sarah Kennedy, Kara Kosakowski, Constantine Mitsiades, Teru Hideshima, Robert D Knight, Dixie-Lee Esseltine, Kenneth C Anderson
Journal: Blood (2008)
Clonal Evolution in Relapsed or Refractory Diffuse Large B Cell Lymphoma
Authors: Thomas Melchardt, Clemens Hufnagl, Oliver Weigert, David M. Weinstock, Nadja Kopp, Lukas Weiss, Daniel Neureiter, Wolfgang Tränkenschuh, Hubert Hackl, Richard Greil, Alexander Egle
Journal: Blood (2014)
First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP14 for young adults with diffuse large B-cell lymphoma: Preliminary results of the GOELAMS 075 prospective multicenter randomized trial.
Authors: S. Le Gouill, N. J. Milpied, T. Lamy, V. Delwail, R. Gressin, D. Guyotat, G. L. Damaj, C. Foussard, G. Cartron, H. Maisonneuve, E. Deconinck, F. Dreyfus, E. Gyan, L. Sutton, N. Morineau, M. Alexis, F. Perry, M. Sauvezie
Journal: Journal of Clinical Oncology (2011)

8003 Background: We have shown that first-line HDT leads to an improved EFS and OS over CHOP in adults with aggressive NHL (NEJM 2004) and that adding R to the HDT was feasible and might improve the results (BBMT 2010). We present the preliminary analysis of a multicenter RCT comparing R-CHOP14 to R-HDT in adults with DLBCL (clinical trial.gov: NCT 00561379). Methods: Pts 18 to 60 y.o. CD20 + DLBCL AA stage 1-2 with bulk ≥ 7 cm or 3 -4 were rdz at dg (stratified on aaIPI) between R-CHOP14 (8 courses if response after the first 4) and R-HDT. This consisted of 2 courses of HD CHOP-like, 15 days apart, with R (375/mg/m2) on day 1 of each, then R on d 22, harvest of G-CSF mobilized PBSC on d 28, 29, R on d 36 followed by HD methotrexate with cytarabin. For pts who achieved a response after these 3 courses, BEAM started on d 66 to 80 followed by PBSCT. In each arm, the interm response was assessed by CT Scan and PET (Cheson criteria JCO 2007). Pts not achieving a PR or a neg PET had a salvage Tx and auto PBSCT. Results: 340 pts included 01/2005 to 06/2010, 286 pts evaluable at time of abstract, 143 in each arm. Characteristics of the pts in the 2 arms are super imposable. Overall 56% bulk, 72% >2 AA stage and 58% aa IPI>1. The Rdz tx was completed in 67% in the R-CHOP arm and 53% in the R-HDT arm. The interm evaluation showed the same rate of response with CT scan (CR + CRu: 65% and 62% following 4 x R-CHOP14 and first 3 courses of R-HDT). PET remained more often pos after the first 3 courses of R-HDT (41% vs 28%; p=0.03). Of the 98 pts with pos interm PET, 84 had a salvage of which 62 underwent auto PBSCT. On ITT the ORR (CR + Cru) was 82% and 76% in the R-CHOP and R-HDT arms respectively (p=0.8). With a med FU of 25 m, the 3y OS is 83%. No difference according to the tx arm in any of the aaIPI strata. The 3y PFS and DFS are 76% and 83%, no difference according to the tx arm. The 3 y OS and DFS for pts in R-CHOP arm and in R-HDT arm acc to interm PET are shown in the table. Conclusions: R-CHOP14 is as efficient, less toxic, and spares resources as compared to this R-HDT program. Salvage based on interm PET is not harmful and provides excellent results. PET neg PET pos R-CHOP 3y OS/DFS 88% / 80% 84% / 82% R-HDT 3y OS/DFS 80% /92% 86% / 89%
Abstract A25: Pancreatic cancer cells scavenge complex lipids from stroma in the hypoxic tumor microenvironment
Authors: Petrus R. de Jong, Alejandro D. Campos, Sean-Luc Shanahan, Adam Richardson, Garth Powis
Journal: Cancer Research (2016)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is non-resectable in 85% of cases and highly resistant to chemotherapy, resulting in a poor 5-year survival (5-7%). Understanding the metabolic vulnerabilities of PDAC in the harsh tumor microenvironment (TME) may lead to novel therapeutic approaches with improved clinical efficacy. The pancreatic TME is characterized by widespread desmoplasia represented by alpha-smooth muscle actin-positive fibroblasts, pancreatic stellate cells and extracellular matrix components, among others. Up to 90% of the pancreatic tumor mass consists of non-neoplastic cells, and high interstitial pressures and poor perfusion both result in severe hypoxia, leading to a more malignant PDAC phenotype. We hypothesized that these conditions lead to specific metabolic constrains in oncogene-driven, rapidly proliferating PDAC cells that experience high levels of stress, in contrast to the surrounding quiescent stromal cells. We used co-culturing of PDAC (MIAPaCa2) and stromal (NIH/3T3) cells in transwell systems as a robust and reproducible model of cell contact-independent interactions in the pancreatic TME. A commercial metabolic profiling platform (Metabolon) and 13C-based flux assays were used to study changes in metabolite levels in both cell types in normoxia or hypoxia (1% O2). We found that hypoxia induced similar metabolic changes in the PDAC and stromal cells, suggesting that hypoxia-regulated metabolic rewiring is independent of cell-type. Interestingly, the metabolic effects of co-culturing were predominantly observed in the stromal compartment, e.g. enhanced glycogenolysis, metabolite changes indicative of gluconeogenesis, and increased dipeptide levels, all reminiscent of a ‘starvation’ phenotype. In contrast, the tumor cells maintained a mixed anabolic and catabolic phenotype, as shown by elevated intracellular levels of essential amino acids and ribonucleotide triphosphates, representative of a ‘feeding’ phenotype. Importantly, a unique dependence on complex lipid species was observed in cancer cells with reciprocal changes in stromal cells. These data suggest that pancreatic cancer cells reprogram stromal cells to ‘feed off’ the metabolic capacity of non-neoplastic cells in the tumor microenvironment, thereby inducing the release of diffusable metabolites to satisfy their specific catabolic needs. Citation Format: Petrus R. de Jong, Alejandro D. Campos, Sean-Luc Shanahan, Adam Richardson, Garth Powis.{Authors}. Pancreatic cancer cells scavenge complex lipids from stroma in the hypoxic tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A25.
Anaplastic Large Cell Lymphoma (ALCL) in Children: Equal Efficacy but Greater Toxicity of Chemotherapy Including Methotrexate (MTX) 1g/m2 in 24 Hour Infusion with Intra-Thecal Injection (IT) Than Chemotherapy with MTX 3g/m2 in 3 Hours Infusion without IT: Results of the ALCL99-R1 Randomised Trial.
Authors: Laurence Brugières, Marie Cécile Le Deley, Angelo Rosolen, Denise Williams, Ke Horibe, Grazyna Wrobel, Anne Uyttebroeck, Auke Beishuizen, Georg Mann, Karin Mellgren, Alfred Reiter
Journal: Blood (2006)
446. Stable Correction of Alkylator Resistance in Fanconi Anemia Cells By a Mitotically Replicating Non-Integrating Lentiviral Vector
Authors: Santhosh Chakkaramakkil Verghese, Natalya A. Goloviznina, Peter Kurre
Journal: Molecular Therapy (2015)

Fanconi anemia (FA) is an inherited multisystem disorder leading to symptomatic hematopoietic defects by early school age in most patients. Observations of lymphoid mosaicism and spontaneous intragenic correction of stem cells leading to clonal hematopoiesis in a small number of patients indicate that phenotypically corrected cells enjoy a survival advantage over FA deficient cells. Accordingly, FA is a leading genetic disorder target for HSPC directed gene therapy. However, reports over the insertional complications of commonly used integrating vectors continue to raise concerns, while available non-integrating lentivectors (NILVs) are generally lost from dividing hematopoietic stem cells. We recently showed that the incorporation of human Scaffold/Matrix Attachment Region (S/MAR) sequences in NILVs results in the cellular retention of NILV episomes in actively dividing cell lines and HSPCs without selection. Southern analysis, Alu PCR and episome specific PCR all confirmed long-term episomal existence of this vector without genomic integration (NAR. 2014; PMID: 24474068). Here, we designed and tested an episome lentivector to phenotypically correct FA cells (aNILV GFP-FANCC). Results showed the vector expressing the human FANCC ORF fused with GFP could be readily packaged, with stable persistence of vector episomes and sustained GFP expression. Taking advantage of the selective expansion of phenotypically corrected cells, we transduced a FANCC -deficient human cell line pD331 by using aNILV-GFP-FANCC vector. Exaggerated sensitivity to DNA alkylating agents (e.g. Mitomycin C, MMC) is a hallmark of FA deficient cells and can be used as a selection agent. At week 2, we observed 15% retention of GFP expressing cells in MMC treated pD331-aNILV-FANCC population versus 3% retention in non-treated pD331-aNILV-FANCC cells. Long-term maintenance of cells up to 6 weeks under MMC selection resulted the enrichment of corrected cells up to 95% that is comparable to the enrichment observed by integrating LV expressing GFP-FANCC in pD331 cells under MMC selection. Molecular studies of aNILV episomes from long-term cultures by episome specific PCR revealed LTR episome persistence. Integration analysis by Alu-PCR from the bulk population with Southern analysis of clones is ongoing. We already reported that episomal S/MAR NILV transduced short-term murine hematopoietic stem and progenitor cells and are currently characterizing this vector in a murine model of Fanconi Anemia. In conclusion, epsiome maintenance under selective pressure and reversal of canonical alkylator sensitivity in FA cells make this novel aNILV-GFP-FANCC vector a consideration for expanded preclinical exploration.
Biopsy correlation of surface area vs. single‐axis measurements on computed tomography scan of lymph nodes in patients with erythrodermic mycosis fungoides and Sézary syndrome
Authors: R. Haththotuwa, L. Zilinskiene, J. Oliff, B. Vydianath, R. Amel‐Kashipaz, A. Stevens, F. Shah, S. Chaganti, J. Scarisbrick
Journal: British Journal of Dermatology (2016)

Sezary syndrome (SS) presents with erythroderma, leukaemic blood involvement and frequent lymphadenopathy whilst 15% of mycosis fungoides (MF) patients present with erythroderma1. Staging of patients with erythrodermic (e)MF/SS includes IIIA, IIIB, IVA or IVB dependant on blood, lymph node (LN) or visceral involvement2.

In MF/SS; an abnormal LN is either firm, irregular, clustered, or fixed on examination or ≥15mm on imaging. Excisional biopsy is indicated of the largest, most suspicious node 2 −4.

This article is protected by copyright. All rights reserved.
Training program of cancer professionals and regional contribution in Sanin area
Authors: Takeshi Isobe, Shynichi Tsujitani, Toshihiko Nakatani, Taisuke Inomata, Tamio Okimoto, Yukari Tsubata, Akihisa Sutani, Kenji Ohyama, Kazuhisa Takahashi, Okio Hino
Journal: Annals of Oncology (2015)
Review: For warfarin reversal, prothrombin complex concentrates reduce mortality compared with fresh frozen plasma
Authors: Alexander Gallus
Journal: Annals of Internal Medicine (2016)

Source Citation Chai-Adisaksopha C, Hillis C, Siegal DM, et al. Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal. A systematic review and meta-analysis. Thromb Haemost. 2016;116:879-90. 27488143
Abstract 2205: Identification of transcript abundance difference at lung cancer and COPD risk genes in normal bronchial epithelial cells
Authors: Jiyoun Yeo, Xiaolu Zhang, Erin Crawford, James Willey
Journal: Cancer Research (2015)

Abstract Background: Lung cancer and chronic obstructive pulmonary disease (COPD) and are leading causes of morbidity and mortality both in the United States and worldwide. Inhalation of cigarette smoke is the primary known and preventable cause but only 10-15% of heavy smokers develop these diseases. This suggests that cigarette smoke exposure interacts with inherited susceptibility factors to determine risk. There is urgent need to identify heritable susceptibility factors that explain the majority of lung cancer and COPD risk. In prior studies, we and/or others have observed large inter-individual variation in normal bronchial epithelial cell (NBEC) expression of antioxidant, DNA repair, and cell regeneration control genes and altered regulation in NBEC of subjects with lung cancer or COPD. We collected normal bronchial epithelial cell (NBEC) samples from over 500 subjects with or demographically at risk for lung cancer. In this pilot study, we assessed total expression of multiple putative risk genes in NBEC samples from 78 subjects. Methods: A targeted competitive multiplex next generation sequencing (NGS) method (Blomquist et al, PLOS one 2013) was used to quantify transcript abundance at 70 marker sites among 33 target genes in NBEC total RNA from 78 subjects (18 cancer cases and 60 non-cancer controls). Approximately half of the cancer group (N = 10) and non-cancer group (N = 30) had COPD (FEV1/FVC&amp;lt;0.7). Results: TP73 was expressed higher and XRCC1 and MUC5B lower in cancer. GSTP1, MUC5B, OGG1, and TP73 were expressed at significantly higher level in COPD vs control by t-test in non-cancer group. Conclusions: This study of 78 subjects provides evidence for transcript abundance difference in selected genes with high prior likelihood for contributing to lung cancer and COPD risk. Those genes will be the focus of additional studies in BEC samples from over 500 subjects with or at risk for lung cancer and/or COPD in effort to further optimize current tests for lung cancer and COPD risk. Note: This abstract was not presented at the meeting. Citation Format: Jiyoun Yeo, Xiaolu Zhang, Erin Crawford, James Willey. Identification of transcript abundance difference at lung cancer and COPD risk genes in normal bronchial epithelial 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 2205. doi:10.1158/1538-7445.AM2015-2205
621. Fusion Between Neutrophils (PMN) and Target Cells Mediate Cytotoxicity During Measles Virus (MV) Oncolysis – A Novel Mechanism
Authors: A. Dey, A. Castleton, B. Rosen, A. Fielding
Journal: Molecular Therapy (2015)

We have previously shown that PMNs play a role in MV-mediated oncolysis (Grote et al) and that oncolytic vaccine strain of MV (as opposed to wild type) stimulates release of numerous cytokines with potential anti-tumor effects (Zhang et al). Recent data from our laboratory indicated that normal healthy PMNs were capable of specific killing of 35-40% of infected Jurkat target cells. On the basis that MV-induced cell-cell fusion amplifies IFN-alpha (α)/beta (β) production in infected cells, we sought to determine whether fusion between infected target cells and normal human PMNs specifically mediates cytotoxicity. First, we showed that PMN-mediated MV killing completely disappeared in the presence of FIP (fusion inhibitory peptide). Next, we examined the role of cell-cell fusion on PMN degranulation, reactive oxygen species (ROS) production and IFN production. We carried out all experiments with and without FIP. Jurkat cells were infected with MVNSe or mock-infected and incubated with PMNs isolated from healthy donors at 8:1 E:T ratio. At 24 hours, the cells were collected. PMN degranulation was determined by increase in cell surface expression of CD66b, CD63 and CD35 and ROS generation was determined by flow cytometry. IFN α and β production in the supernatant was quantified by ELISA. During co-culture of infected target cells and PMNs, IFN α (3000-5000pg/ml) and β (70-90pg/ml) were produced. No IFN α and β was produced by infected or uninfected Jurkats without PMNs present, confirming PMNs as the source. This was highly significantly abrogated in the presence of FIP (α – 200-300pg/ml; β – 0-3pg/ml). PMN degranulation and ROS generation followed the same pattern with abrogation in the presence of FIP, although the differences were not statistically significant. We confirmed that the α or β IFN was not directly responsible for cytotoxicity, since addition of the same quantity of exogenous IFN directly to Jurkat cells did not lead to cell death. Hence, we sought downstream cytotoxic effectors and evaluated TRAIL, which we know from our previous work, can be released from pre-formed granules in response to MV-infection of PMNs. The conditions that generated high levels of IFN also produced significant levels of soluble TRAIL (800-1500pg/ml), which was also abrogated in the presence of FIP (190-650pg/ml). Our data suggests infected target cells stimulate PMNs to display a cytotoxic effector phenotype, directly killing infected target cells. High levels of type I IFNs, are generated which are not in themselves responsible for the cytotoxicity. None of this occurs without target cell-neutrophil fusion as it is abrogated by FIP and does not occur in infected target cells alone or infected PMNs alone. This is a novel mechanism of stimulation of innate immunity by an oncolytic virus.
Targeting mTOR and JAK2 in Xenograft Models of CRLF2-Overexpressing Acute Lymphoblastic Leukemia (ALL)
Authors: Shannon L Maude, Sarah K Tasian, Tiffaney Vincent, Junior W Hall, Racquel Collins-Underwood, Charles G Mullighan, Stephen P Hunger, Cheryl L Willman, Mignon L Loh, Stephan A Grupp, David T Teachey
Journal: Blood (2011)
Effectiveness of the European chromium(<scp>vi</scp>) directive for cement implementation on occupational allergic contact dermatitis occurrence: assessment in France and the U.K.
Authors: L Bensefa-Colas, S J Stocks, R McNamee, S Faye, F Pontin, R M Agius, G Lasfargues, M Telle-Lamberton, I Momas, Rnv P members
Journal: British Journal of Dermatology (2016)

Hexavalent chromium is the main sensitizer in wet cement and a common cause of occupational allergic contact dermatitis (OACD), especially among workers in the construction industry.1,2 The European Chromium VI directive3 transposed into national regulations in France and UK respectively on May and January 2005, prohibits selling or using of hydrated cement with more than 0.0002% of chromium. This was achieved through the addition of ferrous sulphate to the dry product, allowing to reduce chromium VI to chromium III which is less sensitizing.

This article is protected by copyright. All rights reserved.
Abstract 1150: mTORC2 enhances flux through the hexosamine biosynthetic pathway by regulation of GFAT1 expression
Authors: Estela Jacinto, Joseph Moloughney, Thomas Lynch, Chang-Chih Wu, Olufunmilola Ibironke, Aixa Navia, Po-Chien Chou, Sisi Zhang, Joshua Rabinowitz, Guy Werlen
Journal: Cancer Research (2015)

Abstract Metabolic and biosynthetic pathways drive cell growth and proliferation in response to nutrients and growth factors. Highly proliferating cells utilize glucose and glutamine to fuel biosynthetic processes. These two nutrients serve as substrates for the glutamine:fructose-6-phosphate amidotransferase (GFAT1), the rate-limiting enzyme in the hexosamine biosynthetic pathway (HBP), which ultimately produces UDP-GlcNAc that is necessary for protein glycosylation. Despite a role for the HBP in insulin resistance and lifespan extension, the mechanisms underlying GFAT1 regulation in vivo has remained elusive. We found mTOR complex 2 (mTORC2) controls flux through the HBP via regulation of GFAT1 expression levels in response to glucose. In the absence of mTORC2, GFAT1 expression is reduced and highly sensitive to glucose starvation. Furthermore, UDP-GlcNAc is highly diminished and glycosylation of specific transmembrane proteins such as CD147 is defective upon mTORC2 disruption. However, mTORC2 is also required for glycolysis and other biosynthetic pathways whose metabolites feed into the HBP. Thus, although exogenous UDP-GlcNAc can partially rescue glycosylation defects, it does not rescue the metabolic deficiencies in the absence of mTORC2. Like GFAT1, key enzymes of biosynthetic pathways have decreased expression in mTORC2-disrupted cells. Thus, by regulating levels of metabolic enzymes, mTORC2 coordinates flux through biosynthetic pathways in response to glucose availability. Our findings have implications for therapeutic targeting of mTORC2 in insulin resistance and cancer metabolism. Citation Format: Estela Jacinto, Joseph Moloughney, Thomas Lynch, Chang-Chih Wu, Olufunmilola Ibironke, Aixa Navia, Po-Chien Chou, Sisi Zhang, Joshua Rabinowitz, Guy Werlen. mTORC2 enhances flux through the hexosamine biosynthetic pathway by regulation of GFAT1 expression. [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 1150. doi:10.1158/1538-7445.AM2015-1150
Arkansas Autotransplant (AT) Experience with &amp;gt; 2500 Myeloma (MM) Patients: Follow-Up Extending to &amp;gt;15 Years.
Authors: Frits van Rhee, Guido Tricot, Elias Anaissie, Maureen Reiner, Maurizio Zangari, Michael Burns, Joshua Epstein, John Shaughnessy, Erik Rasmussen, John Crowley
Journal: Blood (2005)
An Adverse Prognostic Effect of Homozygous TET2 Mutational Status on the Relapse Risk of Acute Myeloid Leukemia Patients of Normal Karyotype
Authors: Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Il-Kwon Lee, Nan Young Kim, Mark D Minden, Chul Won Jung, Jun-Ho Jang, Hee-Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Namshin Kim, Kenichi Yoshida, Seishi Ogawa, Dennis Dong Hwan Kim
Journal: Blood (2014)
Development of a Highly Efficient Method for Isolating Very Small Embryonic-Like Stem Cells Identified in Adult Mouse Bone and Their Stem Cell Characteristics.
Authors: Ryuji Iwaki, Ryusuke Nakatsuka, Yoshikazu Matsuoka, Masaya Takahashi, Tatsuya Fujioka, Yutaka Sasaki, Hiroaki Asano, Yasushi Uemura, A-Hon Kwon, Yoshiaki Sonoda
Journal: Blood (2012)