tbuckley/cabot-search huggingface dataset:
CELL SURFACE IMMUNOGLOBULIN
Authors: Ellen S. Vitetta, Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1974)

A new method for the detection of cell surface immunoglobulin labeled with isotopic precursors is described. The method consists of the aggregation of surface Ig on cells with specific antibody (heterologous) and the subsequent removal of antigen-antibody complexes by the combination of high speed centrifugation and immunoprecipitation of remaining soluble complexes using antibody to the heterologous Ig. Using this method, the kinetics of appearance of cell surface Ig and its turnover were studied in murine splenocytes. The results suggest that cell surface Ig is synthesized and transported in the same manner as secretory Ig rather than being synthesized on the plasma membrane. The turnover of intracellular and cell surface Ig in lymphocytes is slow. In contrast, intracellular Ig in plasma cells is rapidly secreted and usually without a cell surface phase. Cell surface Ig was shown to be radiolabeled with [3H]glucosamine, -galactose, and -fucose. The proportion of cell surface to intracellular (nonsurface) Ig labeled with these precursors suggests the same sequence of addition of sugars to Ig destined to be on the surface of lymphocytes as with Ig which will be secreted by plasma cells. Results with this new method also confirm earlier conclusions based on experiments using cell surface iodination: 8S IgM is the predominant Ig on the surface of murine splenocytes and the molecule appears to be attached by its µ-chains.
A Novel Agent SL-401 Triggers Anti-Myeloma Activity By Targeting Plasmacytoid Dendritic Cells: Implications for a Novel Immune-Associated Mechanism
Authors: Arghya Ray, Deepika Sharma DAS, Yan Song, Vincent Macri, Christopher L. Brooks, Eric K. Rowinsky, Paul G. Richardson, Dharminder Chauhan, Kenneth C Anderson
Journal: Blood (2015)
MicroRNA Signatures In B-Cell Lymphomas
Authors: Lorena Di Lisio, Margarita Sanchez-Beato, Gonzalo Gomez-Lopez, Maria E. E. Rodriguez, Santiago Montes-Moreno, Manuela Mollejo, Javier Menarguez, Miguel A. Martinez, Javier Alves, David G. Pisano, Miguel A. Piris, Nerea Martinez
Journal: Blood (2010)
High Rate of Initial Treatment Failure in Patients with Primary Mediastinal B-Cell Lymphoma Treated with R-CHOP
Authors: Jeremy S. Abramson, Matthew D Hellmann, Yang Feng, Jeffrey A. Barnes, Tak Takvorian, Christiana E. Toomey, Michael Sheppard, James S. Michaelson, Donna Neuberg, Ephraim P. Hochberg
Journal: Blood (2011)
CONCUSSIVE INJURIES IN AN AMATEUR EMERGING US COLLISION SPORT: RUGBY-7S
Authors: Victor Lopez, Richard Ma, Meryle Weinstein, Patria Hume, Robert Cantu, Laurel Myers, Christian Victoria, Nisha Nadkar, Allen Answorth
Journal: British Journal of Sports Medicine (2017)

Background Rugby-7s an emerging sport in the United States (US) encounters concussions, a growing public concern. Objective To report incidence of concussions in US Rugby-7s. We hypothesized that concussive injuries would occur with frequency in US Rugby-7s similar to international cohorts. Design Prospective descriptive epidemiology study. Setting The study encompassed U19 to elite players in USA Rugby tournaments (2010–2013). Participants A total of 13,644 US players (Men=9,768; Women=3,876; age: 13–49 years) were included over 28 tournaments of 2,688 matches (Men=1,886; Women=802) in 1,137 sides/teams (Men=814; Women=323). Assessment of Risk Factors Intrinsic and extrinsic risk factors in match injuries. Main measurement outcome Incidence (per 1000 player-hour (ph)) and mechanism, captured using Rugby Injury Survey &amp; Evaluation ( RISE ) Report methodology. Time-loss injuries=defined as players who did not return to play the day of their injury. Severity=defined as days absent before return to training/competition (including post tournament). Results Incidence of concussive injuries was 7.7/1000 ph. No difference was noted between women (8.1/1000 ph, n=21) or men (7.6/1000 ph, n=46; P =0.593). Most concussions had “no loss of consciousness” (86.6%; n=58). Higher levels of competition encountered greater incidence (18.3/1000 ph vs. 6.4/1000 ph; P=0.001). Concussions resulted in a mean 30.6 days absent from competition (range=0–135 days) for the 97% of players with follow-up data. Compliance with the 3-wk stand-down return-to-play recommendations was found at 60%. Players reported a repeat concussion at 43.2% (12 months). Players who had multiple concussions within a year, encountered more severity (42.8 mean days absent; CI=23.0–62.6; P=0.03). Conclusions The 7.7/1000 ph incidence of concussion among US amateur Rugby-7s is concerning given international incidences range from 2.0 to 8.3/1000 ph. The 40% of players non-compliant with the recommended 3-week stand-down regulation indicates that a formal mechanism to “clear” players for return to play is needed for Rugby-7s.
Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Versus Conventional Chemotherapy in Patients with Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS) Attaining Complete Remission (CR1) Post Induction Chemotherapy: a Retrospective Case Control Study.
Authors: Yvonne A Efebera, Hagop M. Kantarjian, Borje Andersson, Sherry Pierce, Leandro De Padua Silva, Farhad Ravandi, Sergio A. Giralt, Gautam Borthakur, Richard Champlin, Marcos De Lima
Journal: Blood (2008)
Abstract #2491: Repo-Man controls a protein phosphatase 1-dependent threshold for DNA damage checkpoint activation
Authors: Aimin Peng, William Schiemann, James Maller
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The DNA damage checkpoint is a critical surveillance mechanism employed by the cell to defend its genomic integrity. The cell activates checkpoints through kinase cascades and signal amplification loops, which are kept silent in unperturbed cells and respond to DNA damage in a dose-dependent manner. The DNA damage response is often deregulated in human cancer cells. Here we show that inhibition of PP1 and PP2A phosphatases synergistically turns on DNA damage signaling in the absence of actual DNA damage; moreover, inhibition of PP1 alone allows checkpoint activation with a subthreshold level of DNA damage. This aspect of PP1 function is mediated by a targeting subunit, Repo-Man (Recruits PP1 onto mitotic chromatin at anaphase). Repo-Man recruits PP1\#947; to chromatin to regulate ATM activation, and thereby sets the threshold for DNA damage checkpoint activation in both Xenopus egg extracts and human cells. Importantly, we show that expression of Repo-Man is upregulated in various human cancer tissues. Using the well-established MCF10A cell line model of breast cancer progression, we find that overexpression of Repo-Man during cancer progression is corelated with a blunted DNA damage response, and ectopic expression of Repo-Man renders early stage, precancerous cells less responsive to DNA damage. In summary, our results suggest upregulation of Repo-Man during cancer progression provides a means for the tumor cell to override cell cycle suppression mediated by the DNA damage response and accumulate genomic damage that contributes to cancer progression.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2491.
Novel insight into the role of microbiota in colorectal surgery
Authors: Radu Bachmann, Daniel Leonard, Nathalie Delzenne, Alex Kartheuser, Patrice D Cani
Journal: Gut (2017)

Recent literature undeniably supports the idea that the microbiota has a strong influence on the healing process of an intestinal anastomosis. Understanding the mechanisms by which the bacterial community of the gut influences intestinal healing could open the door for new preventive and therapeutic approaches. Among the different mechanisms, data have shown that the production of specific reactive oxygen species (ROS) and the activation of specific formyl peptide receptors (FPRs) regulate intestinal wound healing. Evidence suggests that specific gut microbes such as <i>Lactobacillus</i> spp and <i>Akkermansia muciniphila</i> help to regulate healing processes through both ROS-dependent and FPR-dependent mechanisms. In this review, we will discuss the current knowledge and future perspectives concerning the impact of microbiota on wound healing. We will further review available evidence on whether mechanical bowel preparation and the use of specific antibiotics are beneficial or harmful procedures, an ongoing matter of debate. These practices have a profound effect on the gut microbiota composition at the level of both the mucosal and the luminal compartments. Therefore, a key question remains unanswered: <i>should we continue to prepare the gut before surgical intervention?</i> Current knowledge and data do not clearly support the use of one technique or another to avoid complications such as anastomotic leak. There is an urgent need for appropriate interventions with a deep microbiota analysis to investigate both the surgical technical benefits of a proper anastomosis compared with the potential effect of the gut microbes (beneficial vs harmful) on the processes of wound healing and anastomotic leakage reduction.
Angiotensin II receptor polymorphism is associated with endothelial function on top of other cardiovascular risk factors : The intervention cardiology risk stratification (ICARIS) study
Authors: Shj Monnink, RA Tio, AJ van Boven, PP van Geel, Njgm Veeger, PJ de Kam, L Pont, WH van Gilst
Journal: Circulation (1999)
Anti-Myeloma Effects of the Janus Kinase 2 (JAK2) Inhibitor SAR503 Alone and in Combination Treatment
Authors: Haiming Chen, Mingjie Li, Jennifer Li, Kevin Delijani, Danielle Rauch, Kevin DeCorso, Andrew Prajogi, Cathy S Wang, Eric Sanchez, Benjamin Bonavida, James R. Berenson
Journal: Blood (2012)
Analysis of <i>ATP8B4</i> F436L Missense Variant in a Large Systemic Sclerosis Cohort
Authors: Elena López‐Isac, Lara Bossini‐Castillo, Ana B. Palma, Shervin Assassi, Maureen D. Mayes, Carmen P. Simeón, Norberto Ortego‐Centeno, Esther Vicente, Carlos Tolosa, Manuel Rubio‐Rivas, José A. Román‐Ivorra, Lorenzo Beretta, Gianluca Moroncini, Nicolas Hunzelmann, Jörg H. W. Distler, Gabriella Riemekasten, Jeska de Vries‐Bouwstra, Alexandre E. Voskuyl, Timothy R. D. J. Radstake, Ariane Herrick, Christopher P. Denton, Carmen Fonseca, Javier Martín
Journal: Arthritis & Rheumatology (2017)
ATPS-75TARGETING THE Mdm2-Akt SIGNALING NETWORK IN COMBINATION WITH TEMOZOLOMIDE IMPROVES EFFICACY IN ECTOPIC AND ORTHOTOPIC PATIENT-DERIVED GLIOBLASTOMA XENOGRAFT MODELS
Authors: Haiyan Wang, M. Reza Saadatzadeh, Barbara J. Bailey, Jixin Ding, Eva Tonsing-Carter, David R. Jones, Nimita Dave, Harlan E. Shannon, Aaron Cohen-Gadol, Karen E. Pollok
Journal: Neuro-Oncology (2015)

An elusive goal in the treatment of patients with glioblastoma multiforme (GBM) is the development of therapeutic strategies that prevent emergence of therapy-resistant tumor cells. Our laboratory has identified a novel combination therapy that targets the Akt-Mdm2 signaling network in the context of genotoxic temozolomide (TMZ) therapy. Inhibitors were specifically selected based on structural properties related to blood-brain barrier permeability, and pharmacokinetic profiles of plasma, normal brain, flank/ectopic brain tumors, and intracranial tumors. Isobolograms and combination indices indicated that Akt (GDC0068) and Mdm2 (RG7112) inhibitors either together or in combination with TMZ, resulted in synergistic inhibition of cell growth in both mtp53 and wt53 GBM primary patient cell lines (GBM10, GBM43, and MHBT32). When RG7112 and GDC0068 (at a ratio of 0.5:1) were combined with TMZ, strong synergism was evident at multiple dose-ratios. As downstream measures of blocking Akt and Mdm2, activation of the Forkhead box O-class 1/3a (FoxO) transcription factors and increased p53/p73 proteins were evident following TMZ + RG7112 + GDC0068. For in vivo studies, an intermittent dosing regimen of TMZ + RG7112 + GDC0068 was developed to avoid normal tissue toxicity. Mice with TMZ-resistant GBM43 ectopic tumors were treated 3 × weekly for 3 weeks. Combination of TMZ + RG7112 + GDC0068 significantly delayed tumor progression compared to other treatments (n = 8-9 per group, p < 0.05). TMZ + GDC0068 and TMZ + RG7112 + GDC0068 significantly reduced tumor volume relative to TMZ, and on the last day with surviving TMZ + GDC0068-treated mice (2500 mm3 endpoint), tumor volumes were significantly reduced in TMZ + RG7112 + GDC0068 compared to TMZ + GDC0068 (p < 0.05). In mice with GBM43 intracranial tumors, survival was significantly increased by GDC0068 + RG7112 (13 days), and further increased by TMZ + RG7112 + GDC0068 (24 days) compared to TMZ alone. These data suggest that blocking the Mdm2-Akt signaling network in the context of TMZ-mediated DNA damage holds therapeutic promise. Studies to identify mechanism and appropriate biomarkers of response are in progress.
Methylseleninic Acid (MSA) Decreases DNA Synthesis, Induces Cell Death, and Sensitizes Both Rituximab Sensitive and Rituximab-Resistant Non-Hodgkin’s Lymphoma Cell Lines to the Anti-Tumor Activity of Cisplatin and Gemcitabine.
Authors: Francisco J. Hernandez-Ilizaliturri, Minhas Ali, Joy Knight, Youcef M. Rustum, Myron S. Czuczman
Journal: Blood (2007)
Challenges in the hepatic histopathology in non-alcoholic fatty liver disease
Authors: Elizabeth M Brunt, David E Kleiner
Journal: Gut (2017)

Bedossa et al 1 present a cross-sectional clinicopathological correlation study of 798 consecutively prospectively obtained liver biopsies from patients who underwent bariatric surgery for severe obesity (body mass index >40 or >35 kg/m2 in whom at least one obesity-related comorbidity existed). Clinical phenotyping included body weight and composition by dual-emission X-ray absorptiometry (DXA), relative and total body fat mass, limb fat measurements and fasting venous samples for liver, glucose and insulin tests. Diabetes and metabolic syndrome were defined according to international criteria, and 84% of subjects also had abdominal subcutaneous fat needle aspiration biopsies. The latter were analysed for adipocyte size and volume by published methods.2

As expected, the majority of subjects were women (78%), and Caucasian (73.5%). A range of liver histology was found, including 141 (18%) with ‘no’ (grade 0) steatosis (0%–5%) and no other lesions, and 38 (5%) with grade 0 steatosis, but with either inflammation, ballooning or mild fibrosis. Thus, 77.5% of subjects in the study had some form of non-alcoholic fatty liver disease (NAFLD), and the authors detailed the findings according to the Fatty Liver Inhibition of Progression (FLIP) European Consortium scoring system3 ,4 further discussed below.

Several interesting findings resulted from this careful study. In spite of similar durations of obesity, younger individuals had less severe liver disease (most were categorised as ‘presumably normal’) compared with their older counterparts (whose biopsies showed the full spectrum of fatty liver including non-alcoholic steatohepatitis (NASH) and cirrhosis). The younger cohort was more often female (92% vs 73%), but less often Caucasian (40% vs 81%). …
The anatomical and physiological properties of the visual cortex argue against cognitive penetration
Authors: Moshe Gur
Journal: Behavioral and Brain Sciences (2016)

We are consciously aware of visual objects together with the minute details that characterize each object. Those details are perceived instantaneously and in parallel. V1 is the only visual area with spatial resolution and topographical exactitude matching perceptual abilities. For cognition to penetrate perception, it needs to affect V1 image representation. That is unlikely because of the detailed parallel V1 organization and the nature of top-down connections, which can influence only large parts of the visual field.
miR-135a-5p-mediated downregulation of protein tyrosine phosphatase receptor delta is a candidate driver of HCV-associated hepatocarcinogenesis
Authors: Nicolaas Van Renne, Armando Andres Roca Suarez, Francois H T Duong, Claire Gondeau, Diego Calabrese, Nelly Fontaine, Amina Ababsa, Simonetta Bandiera, Tom Croonenborghs, Nathalie Pochet, Vito De Blasi, Patrick Pessaux, Tullio Piardi, Daniele Sommacale, Atsushi Ono, Kazuaki Chayama, Masashi Fujita, Hidewaki Nakagawa, Yujin Hoshida, Mirjam B Zeisel, Markus H Heim, Thomas F Baumert, Joachim Lupberger
Journal: Gut (2017)

Background and aims HCV infection is a leading risk factor of hepatocellular carcinoma (HCC). However, even after viral clearance, HCC risk remains elevated. HCV perturbs host cell signalling to maintain infection, and derailed signalling circuitry is a key driver of carcinogenesis. Since protein phosphatases are regulators of signalling events, we aimed to identify phosphatases that respond to HCV infection with relevance for hepatocarcinogenesis. Methods We assessed mRNA and microRNA (miRNA) expression profiles in primary human hepatocytes, liver biopsies and resections of patients with HCC, and analysed microarray and RNA-seq data from paired liver biopsies of patients with HCC. We revealed changes in transcriptional networks through gene set enrichment analysis and correlated phosphatase expression levels to patient survival and tumour recurrence. Results We demonstrate that tumour suppressor protein tyrosine phosphatase receptor delta (PTPRD) is impaired by HCV infection in vivo and in HCC lesions of paired liver biopsies independent from tissue inflammation or fibrosis. In liver tissue adjacent to tumour, high PTPRD levels are associated with a dampened transcriptional activity of STAT3, an increase of patient survival from HCC and reduced tumour recurrence after surgical resection. We identified miR-135a-5p as a mechanistic regulator of hepatic PTPRD expression in patients with HCV. Conclusions We previously demonstrated that STAT3 is required for HCV infection. We conclude that HCV promotes a STAT3 transcriptional programme in the liver of patients by suppressing its regulator PTPRD via upregulation of miR-135a-5p. Our results show the existence of a perturbed PTPRD–STAT3 axis potentially driving malignant progression of HCV-associated liver disease.
Lysosomal Disruption Selectively Targets Leukemia Cells and Leukemia Stem Cells Through A Mechanism Related to Increased Reactive Oxygen Species Production
Authors: Mahadeo A. Sukhai, Rose Hurren, Angela Rutledge, Bozena Livak, Xiaoming Wang, Ayesh Seneviratne, Maria Christine Cusimano, Marinella Gebbia, Marko Skrtic, Hong Sun, Marcela Gronda, Paul A. Spagnuolo, Malene Urbanus, Kolja Eppert, Dilan Dissanayake, Xiaoming Li, Thomas Sun, Frederick Vizeacoumar, Alessandro Datti, Pamela Ohashi, Jeff L. Wrana, Ian M. Rogers, Mark D. Minden, Jean C.Y. Wang, John E. Dick, Seth J. Corey, Corey Nislow, Guri Giaever, Aaron D Schimmer
Journal: Blood (2011)
Outcome Comparisons between Two Cord Blood Banks on Different Continents Using Identical Procedures.
Authors: Allen Lin, Steven Yang, Brian Wang, Peggy Tseng, Tina Wu, Wendy Chan, Laura Gindy, Dick Brown, Richard Tonai, Jay Olmstead, Gerry Sotomayor, David Gjertson, Lawrence Petz, Tang-Her Jaing, Patrick Tan, Robert Chow
Journal: Blood (2006)
Acting is perceiving!
Authors: Rouwen Cañal-Bruland, John van der Kamp, Rob Gray
Journal: Behavioral and Brain Sciences (2016)

We challenge Firestone & Scholl's (F&S's) narrow conceptualization of what perception is and - most important - what it is for. Perception guides our (inter)actions with the environment, with attention ensuring that the actor is attuned to information relevant for action. We dispute F&S's misconceived (and counterfactual) view of perception as a module that functions independently from cognition, attention, and action.
Role of Defective High-Affinity Thiamine Transporter slc19a2 in Marrow from a Mouse Model of Thiamine-Responsive Anemia Syndrome: Evidence for Defective Deoxyribose and Heme Synthesis.
Authors: Inderneel Sahai, M. Claudia Montefusco, Judidth C. Fleming, Laszlo Boros, Elena Tartaglini, Gretchen Chick, Ellis J. Neufeld
Journal: Blood (2005)
Simplifying Complex Microarray Data To Derive Gene Expression Profiles Which Identify Childhood Acute Lymphoblastic Leukaemia Patients at Risk of Relapse.
Authors: Dachuan Guo, Alex Fong, Andy Lail, Maree O’Sullivan, Glenn Stone, Harri Kiiveri, Michael Henry, Dietrich Stephan, Luce Dalla-Pozza, Daniel R. Catchpoole
Journal: Blood (2005)
Abstract A29: The mechanism of differential effect of metformin on colorectal cancer stem cells: Metabolic alteration via glutamine metabolic pathway
Authors: Kyoung Jin Lee, Jae Hyun Kim, Ji-Hee Kwon, Yoo Jung Seo, Tae Il Kim
Journal: Cancer Research (2017)

Abstract Background/Aim: There have been reports about cancer stem cells (CSCs) suppressing effect of metformin in several cancers. However, the differential effect of metformin on CSCs and its mechanism has not been reported. We identified various effect of metformin in suppression of colorectal CSCs and its molecular mechanism in colorectal cancer (CRC) cell lines. Methods: Eight CRC cell lines including HT29 and SW620 cells were used. The CSC suppressing effects of metformin (10 mM), glutaminase inhibitor (compound 968, 10 μM), and combination of two drugs were measured by flow cytometry (CD133/44), and tumor sphere formation assay. AMPK and mTOR signaling were examined by Western blotting using anti-pAMPK and anti-pS6, and oxygen consumption rate was measured. The CSC inhibitory effects were also evaluated in xenografted nude mice of HT19 and SW620 cells, using immunohistochemical stain for CD133/CD44. Results: CSCs decreased after treatment of metformin in HT29, DLD-1, and LoVo, and HCT116 cells, but not in SW620, WiDr, Colo205, and Caco-2 cells. Treatment of metformin induced pAMPK activation and pS6 suppression in HT29 cells (metformin-sensitive cells), but not in SW620 cells (metformin-resistant cells). Oxygen consumption rate was higher in HT29 cells than in SW620 cells, and showed more prominent decrease after metformin treatment in HT29 cells. In addition, SW620 cells became sensitive to metformin in CSC-suppressing effect in glutamine-depleted media, but not in low glucose media. Considering the alternative energy source of glutamine, which escapes the effect of metformin on tumor cells, we found that combination of metformin and compound 968 induced CSC-suppressing effect in SW620 cells, and enhanced that effect in HT29 cells. Further, SW620 cells showed higher expression of glutaminase and glutamine transporter than HT29 cells. In xenograft model of HT29 and SW620 cells, combined treatment of metformin and 968 also showed the same results with in vitro experiments. Conclusion: The effect of metformin on CSCs of CRC cells is various depending on AMPK-mTOR pathway and glutamine metabolic pathway. Inhibition of glutamine pathway could enhance the CSC-suppressing effect of metformin, overcoming metformin-resistance. Citation Format: Kyoung Jin Lee, Jae Hyun Kim, Ji-Hee Kwon, Yoo Jung Seo, Tae Il Kim. The mechanism of differential effect of metformin on colorectal cancer stem cells: Metabolic alteration via glutamine metabolic pathway. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A29.