tbuckley/cabot-search huggingface dataset:
Low expression of T-cell transcription factor BCL11b predicts inferior survival in adult standard risk T-cell acute lymphoblastic leukemia patients
Authors: Isabelle Bartram, Nicola Gökbuget, Cornelia Schlee, Sandra Heesch, Lars Fransecky, Stefan Schwartz, Reingard Stuhlmann, Kerstin Schäfer-Eckhart, Michael Starck, Albrecht Reichle, Dieter Hoelzer, Claudia D Baldus, Martin Neumann
Journal: Journal of Hematology & Oncology (2014)

Risk stratification, detection of minimal residual disease (MRD), and implementation of novel therapeutic agents have improved outcome in acute lymphoblastic leukemia (ALL), but survival of adult patients with T-cell acute lymphoblastic leukemia (T-ALL) remains unsatisfactory. Thus, novel molecular insights and therapeutic approaches are urgently needed.We studied the impact of B-cell CLL/lymphoma 11b (BCL11b), a key regulator in normal T-cell development, in T-ALL patients enrolled into the German Multicenter Acute Lymphoblastic Leukemia Study Group trials (GMALL; n = 169). The mutational status (exon 4) of BCL11b was analyzed by Sanger sequencing and mRNA expression levels were determined by quantitative real-time PCR. In addition gene expression profiles generated on the Human Genome U133 Plus 2.0 Array (affymetrix) were used to investigate BCL11b low and high expressing T-ALL patients.We demonstrate that BCL11b is aberrantly expressed in T-ALL and gene expression profiles reveal an association of low BCL11b expression with up-regulation of immature markers. T-ALL patients characterized by low BCL11b expression exhibit an adverse prognosis [5-year overall survival (OS): low 35% (n = 40) vs. high 53% (n = 129), P = 0.02]. Within the standard risk group of thymic T-ALL (n = 102), low BCL11b expression identified patients with an unexpected poor outcome compared to those with high expression (5-year OS: 20%, n = 18 versus 62%, n = 84, P < 0.01). In addition, sequencing of exon 4 revealed a high mutation rate (14%) of BCL11b.In summary, our data of a large adult T-ALL patient cohort show that low BCL11b expression was associated with poor prognosis; particularly in the standard risk group of thymic T-ALL. These findings can be utilized for improved risk prediction in a significant proportion of adult T-ALL patients, which carry a high risk of standard therapy failure despite a favorable immunophenotype.
T regulatory cell suppression of colitis: the role of TGF- 
Authors: R Duchmann
Journal: Gut (2006)

Transforming growth factor β (TGF-β) and interleukin 2 may be involved in IBD peripheral regulatory T cell pathophysiology, raising the possibility of therapeutic application of TGF-β induced regulatory T cells in IBD patients

CD4+CD25+ regulatory T cells (Treg) expressing the lineage marker Foxp3 control immune responses to self- and foreign antigens and are an intensely studied member of the heterogenous group of regulatory T cells. Although initially described as a population of suppressor T cells required to avoid organ specific autoimmunity, it has subsequently become clear that Treg control immune responses in a much broader sense, including transplantation tolerance and immune responses to pathogens and tumours.1–3 Relevant to inflammatory bowel diseases (IBD), Treg prevent4 and treat established5 colitis in animal models of IBD and are numerically deficient in patients with active IBD.6 This underlines the fact that the immune dys-equilibrium characteristic of chronic inflammatory diseases involves concomitant disturbances in inflammatory and suppressive immune mechanisms and opens up novel approaches for IBD therapy by strengthening Treg mediated suppression.

Currently, efforts in laboratories worldwide are addressing the central questions of Treg immunology, resolution of which will help us see more clearly the role of Treg in disease pathogenesis and therapy. Some of these central questions are: where do Treg come from; how are they generated, expanded, and maintained; how and where do they function; why do they fail to control immune responses in disease; and how can their therapeutic potential be used most efficiently and safely. As current data indicate that Treg from IBD patients are functionally normal6–8 but numerically deficient during active disease,6 it will be interesting to understand the underlying mechanisms and, based on that knowledge, devise the most promising strategy to enlarge their …
Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines
Authors: Niels Halama, Monika Braun, Christoph Kahlert, Anna Spille, Christian Quack, Nuh Rahbari, Moritz Koch, Jürgen Weitz, Matthias Kloor, Inka Zoernig, Peter Schirmacher, Karsten Brand, Niels Grabe, Christine S. Falk
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Tumor infiltrating T lymphocytes in colorectal cancer (CRC) have prognostic impact, but the role of natural killer (NK) cells in CRC tissue is unclear. The contribution of intratumoral cytokines and chemokines in shaping the composition of the inflammatory lymphocytic infiltrate is also unclear. Experimental Design: In this study, localization and densities of NK and T cells within primary CRC, CRC liver metastases, adenomas, and normal tissues were analyzed on whole tissue sections from 112 patients. In a subset of these patients, the most important 50 cytokines and chemokines were quantified in paired serum, primary CRC and adjacent mucosa samples and in CRC liver metastases and correlated with NK and T-cell infiltration, respectively. Results: The various compartments displayed characteristic differences like significantly higher chemokine concentrations in CRC tissue. Most importantly, despite high local chemokine levels, NK cells were generally scarce within CRC tumor tissues, independent of human leukocyte antigen (HLA) class I expression. Adjacent normal mucosa contained normal levels of NK cells. In contrast, corresponding T-cell numbers varied substantially and were positively correlated with higher chemokine levels. Conclusions: Our findings indicate a distinct regulation of NK cells versus T cells in the CRC tumor microenvironment. NK-cell migration into CRC tumor tissue is obviously impaired early during tumor development by mechanisms that do not affect T-cell infiltration. Clin Cancer Res; 17(4); 678–89. ©2011 AACR.
Effect of Matrix Metalloproteinase Inhibitor Batimastat on Breast Cancer Regrowth and Metastasis in Athymic Mice
Authors: G. W. Sledge, M. Qulali, R. Goulet, E. A. Bone, R. Fife
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Effect of Matrix Metalloproteinase Inhibitor Batimastat on Breast Cancer Regrowth and Metastasis in Athymic Mice Get access George W. Sledge, Jr., George W. Sledge, Jr. * Department of Medicine, Indiana University School of Medicine, and the Richard L. Roudebush VA Medical CenterIndianapolis, Oxford, U.K. *Correspondence to : George W. Sledge, Jr., M.D., Indiana University Hospital, Rm. 1730, 550 N. University Blvd., Indianapolis, IN 46202. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mona Qulali, Mona Qulali Department of MedicineOxford, U.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Goulet, Robert Goulet Department of Surgery, Indiana University School of MedicineOxford, U.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar Elisabeth A. Bone, Elisabeth A. Bone British Biotech Pharmaceuticals, Ltd.Oxford, U.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar Rose Fife Rose Fife Department of MedicineOxford, U.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 20, 18 October 1995, Pages 1546–1551, https://doi.org/10.1093/jnci/87.20.1546 Published: 18 October 1995 Article history Received: 27 April 1995 Revision received: 25 July 1995 Accepted: 07 August 1995 Published: 18 October 1995
THE USE OF CARDIAC CATHETERISATION IN PRE-OPERATIVE WORK-UP FOR LIVER TRANSPLANTATION
Authors: C E M McClure, S Ahmed, P W Johnston, W J Cash, N I McDougall
Journal: Gut (2013)

<h3>Introduction</h3> Significant cardiac disease may exclude patients from orthotopic liver transplantation (OLT) or may require intervention to make OLT feasible. Non-invasive methods of cardiac assessment (ECHO and cardiopulmonary exercise stress test (CPEX)) are used to help minimise the need for cardiac catheterisation (CC). <h3>Aims/Background</h3> To audit the use of CC in OLT assessments at a regional liver unit in Northern Ireland. <h3>Method</h3> All patients who underwent formal OLT assessment in RVH from January 2008 to June 2012 were included. Information was obtained from the RVH Liver Unit database and cross referenced with radiology and patient centre records. Patient records for all those who had CC were reviewed to determine outcomes. <h3>Results</h3> 188 patients underwent full OLT assessment, of whom 43 (23%) required CC. The indications for CC were: 22 had multiple CVS risk factors, 11 had abnormal ECHO, 3 abnormal MPI, 1 abnormal CPEX and 6 other. Overall, 31 (72%) of 43 CC patients had no significant cardiac disease detected. 12 (28%) patients had significant cardiac disease, of whom, 7 were not listed and 5 had intervention (3 PCI with stenting, 2 PFO closures (1 not listed)). 27 (62.8%) patients who underwent CC were listed for OLT. One patient suffered a fatal variceal haemorrhage immediately post CC (without PCI). <h3>Conclusion</h3> The most common reasons for requiring CC during OLT workup were multiple CVS risk factors and abnormal ECHO. CPEX rarely detected significant disease. Mortality post CC was 2%, however, interpretation of this result is limited by the small sample size.
Essential Role of Phosphatidylinositol 3-Kinase-Dependent CCAAT/Enhancer Binding Protein Activation in the Induction of Glutathione S-Transferase by Oltipraz
Authors: Keon Wook Kang, Il Je Cho, Chang Ho Lee, Sang Geon Kim
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Cancer chemopreventive agents transcriptionally induce genes whose protein products can protect cells from chemical-induced carcinogenesis. Oltipraz, a dithiolthione, exerts chemopreventive responses through glutathione S-transferase (GST) induction. We investigated the role of the CCAAT/enhancer binding protein (C/EBP) in the induction of the GSTA2 gene (alpha class) by oltipraz and identified the enhancer element(s) responsible for GSTA2 gene expression. Methods: H4IIE rat hepatocyte-derived cells were treated with oltipraz, and GSTA2 expression was determined by northern and immunoblot analyses. The activation of C/EBPβ and α forms and NF-E2-related factor 2 (Nrf2) was assessed by immunochemical assays. C/EBPβ-DNA binding activity was determined by subcellular fractionation and electrophoretic mobility shift assays. The role of the C/EBP binding site in the induction of the GSTA2 gene was assessed by luciferase reporter-gene activity. The role of phosphatidylinositol 3-kinase (PI3-kinase) and mitogen-activated protein (MAP) kinase signaling pathways in C/EBP-mediated GSTA2 induction was studied by using chemical inhibitors, overexpression vectors, and dominant-negative mutants. All statistical tests were two-sided. Results: Oltipraz induced GSTA2 mRNA and protein expression. In oltipraz-treated cells, C/EBPβ translocated to the nucleus and bound to the consensus sequence of C/EBP (TTGCGCAA). Oltipraz treatment increased luciferase reporter-gene activity in H4IIE cells transfected with the C/EBP-containing regulatory region of the GSTA2 gene. Deletion of the C/EBP binding site or overexpression of a dominant-negative mutant form of C/EBP (AC/EBP) abolished the reporter gene activity. PI3-kinase, but not MAP kinases, was required for C/EBPβ-dependent induction of GSTA2 by oltipraz. Conclusions: Oltipraz-induced GSTA2 gene expression is dependent upon PI3-kinase-mediated nuclear translocation and binding of C/EBPβ to the C/EBP response element in the GSTA2 gene promoter.
Phase II Study of an Outpatient Palliative Care Intervention in Patients With Metastatic Cancer
Authors: Matthew Follwell, Debika Burman, Lisa W. Le, Kristina Wakimoto, Dori Seccareccia, John Bryson, Gary Rodin, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2008)

Although there is increasing advocacy for timely symptom control in patients with cancer, few studies have assessed outpatient palliative care clinics. This study assessed prospectively the efficacy of an Oncology Palliative Care Clinic (OPCC) in improving patient symptom distress and satisfaction.Eligible patients were new referrals to an OPCC, had metastatic cancer, were at least 18 years old, and were well enough and able to speak and read English sufficiently to provide informed consent and complete questionnaires. Patients received a consultation by a palliative care team. The primary end points of symptom control and patient satisfaction were assessed using the Edmonton Symptom Assessment Scale (ESAS) and patient-adapted Family Satisfaction with Advanced Cancer Care (FAMCARE) scale at baseline, 1 week, and 1 month. Initial and follow-up scores were compared using paired t tests.Of 150 patients enrolled, 123 completed 1-week assessments, and 88 completed 4-week assessments. At baseline, the mean ESAS Distress Score (EDS) was 39.5. The mean improvement in EDS was 8.8 points (P < .0001) at 1 week and 7.0 points (P < .0001) at 1 month. Statistically significant improvements were observed for pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, dyspnea, insomnia, and constipation at 1 week (all P < or = .005) and 1 month (all P < or = .05). The mean improvement in FAMCARE score was 6.1 points (P < .0001) at 1 week and 5.0 points (P < .0001) at 1 month.This phase II study demonstrates efficacy of an OPCC for improvement of symptom control and patient satisfaction with care. Randomized controlled trials are indicated to further evaluate the effectiveness of specialized outpatient palliative care.
Low-Dose Chenodiol to Prevent Gallstone Recurrence After Dissolution Therapy
Authors: JAY W. MARKS
Journal: Annals of Internal Medicine (1984)

Chenodiol is a safe and effective agent for the medical dissolution of gallstones in selected patients; however, after dissolution and cessation of treatment, gallstones recur. This study was done to determine the recurrence rate after successful medical treatment and cessation of chenodiol therapy; compare the efficacy and safety of low-dose chenodiol, as compared to placebo, for prophylaxis against recurrence; and identify factors predictive of recurrence. In a randomized, double-blind fashion, 53 patients with gallstone dissolution received either chenodiol, 375 mg/d, or placebo, for at least 2 years. Standardized oral cholecystograms were done at 6 months, 1 year, and then yearly thereafter. Routine laboratory testing was done every 6 months. The cumulative rate of recurrence (life-table) was 27% in patients followed for up to 3.5 years. Chenodiol, 375 mg/d, was ineffective in preventing the recurrence of gallstones. No demographic, clinical, roentgenographic, or biochemical characteristics were predictive of recurrence.
Postoperative nomogram for survival of patients with retroperitoneal sarcoma treated with curative intent
Authors: D.A. Anaya, G. Lahat, X. Wang, L. Xiao, P.W. Pisters, J.N. Cormier, K.K. Hunt, B.W. Feig, D.C. Lev, R.E. Pollock
Journal: Annals of Oncology (2009)
Specific Recruitment of γδ Regulatory T Cells in Human Breast Cancer
Authors: Jian Ye, Chunling Ma, Fang Wang, Eddy C. Hsueh, Karoly Toth, Yi Huang, Wei Mo, Shuai Liu, Bing Han, Mark A. Varvares, Daniel F. Hoft, Guangyong Peng
Journal: Cancer Research (2013)

Abstract Understanding the role of different subtypes of tumor-infiltrating lymphocytes (TIL) in the immunosuppressive tumor microenvironment is essential for improving cancer treatment. Enriched γδ1 T-cell populations in TILs suppress T-cell responses and dendritic cell maturation in breast cancer, where their presence is correlated negatively with clinical outcomes. However, mechanism(s) that explain the increase in this class of regulatory T cells (γδ Treg) in patients with breast cancer have yet to be elucidated. In this study, we show that IP-10 secreted by breast cancer cells attracted γδ Tregs. Using neutralizing antibodies against chemokines secreted by breast cancer cells, we found that IP-10 was the only functional chemokine that causes γδ Tregs to migrate toward breast cancer cells. In a humanized NOD-scid IL-2Rγnull (NSG) mouse model, human breast cancer cells attracted γδ Tregs as revealed by a live cell imaging system. IP-10 neutralization in vivo inhibited migration and trafficking of γδ Tregs into breast tumor sites, enhancing tumor immunity mediated by tumor-specific T cells. Together, our studies show how γδ Tregs accumulate in breast tumors, providing a rationale for their immunologic targeting to relieve immunosuppression in the tumor microenvironment. Cancer Res; 73(20); 6137–48. ©2013 AACR.
Targeting inflammation by modulating the Jun/AP-1 pathway
Authors: H. B. Schonthaler, J. Guinea-Viniegra, E. F. Wagner
Journal: Annals of the Rheumatic Diseases (2011)

Inflammation is a physiological response of the body to tissue injury, pathogen invasion and irritants. In the course of inflammation, immune cells of the innate and/or adaptive immune system are activated and recruited to the site of inflammation. Attraction and activation of immune cells is regulated by a variety of different cytokines and chemokines, which are predominantly regulated by transcription factors such as AP-1, NF-κB, NFATs and STATs. The evidence that Jun/AP-1 proteins control inflammation in the skin is summarised in this article. Genetic mouse models have demonstrated that a loss of Jun/AP-1 expression in epidermal cells controls cytokine expression through transcriptional and post-transcriptional pathways. The absence of JunB in epithelial K5-expressing tissues leads to a multiorgan disease, which is characterised by increased levels of granulocyte colony-stimulating factor and interleukin 6. Deletion of both JunB and c-Jun, in a constitutive or inducible manner, leads to perinatal death of newborn pups and to a psoriasis-like disease in adults, in which tumour necrosis factor α and the TIMP-3/TACE pathway have central roles. The loss or reduction of Jun expression in the epidermis relieves a block on cytokine expression. As a consequence, the increased levels of cytokines in mice lead to diseases reminiscent of psoriasis and systemic lupus erythematosus in human patients. New targets identified in mouse models, together with investigations on human samples, will provide important new avenues for therapeutic interventions in psoriasis and other inflammatory skin diseases.
The Four Distal Tyrosines Are Required for LAT-dependent Signaling in FcεRI-mediated Mast Cell Activation
Authors: Shin-ichiroh Saitoh, Sandra Odom, Gregorio Gomez, Connie L. Sommers, Howard A. Young, Juan Rivera, Lawrence E. Samelson
Journal: The Journal of Experimental Medicine (2003)

The linker for activation of T cells (LAT) is an adaptor protein critical for FcεRI-mediated mast cell activation. LAT is a substrate of the tyrosine kinases activated after TCR and FcεRI engagement. After phosphorylation of the cytosolic domain of LAT, multiple signaling molecules such as phospholipase C–γ1, Grb2, and Gads associate with phosphorylated LAT via their SH2 domains. The essential role of the four distal tyrosines in TCR-mediated signaling and T cell development has been demonstrated by experiments using LAT-deficient cell lines and genetically modified mice. To investigate the role of these four tyrosines of LAT in FcεRI-mediated mast cell activation, bone marrow–derived mast cells from LAT-deficient mice were infected with retroviral vectors designed to express wild-type or mutant LAT. Examination of bone marrow–derived mast cells expressing various tyrosine to phenylalanine mutants in LAT demonstrates a differential requirement for these different binding sites. In these studies, assays of biochemical pathways, degranulation, and cytokine and chemokine release were performed. Finally, the role of these tyrosines was also evaluated in vivo using genetically modified animals. Deletion of all four distal tyrosines, and in particular, loss of the primary phospholipase C–γ-binding tyrosine had a significant effect on antigen-induced histamine release.
Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia–reperfusion injury in rat heart
Authors: Riccarda Granata, Letizia Trovato, Maria Pia Gallo, Silvia Destefanis, Fabio Settanni, Francesca Scarlatti, Alessia Brero, Roberta Ramella, Marco Volante, Jorgen Isgaard, Renzo Levi, Mauro Papotti, Giuseppe Alloatti, Ezio Ghigo
Journal: Cardiovascular Research (2009)

AimsThe hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms.
GROWTH OF PSYCHIATRISTS DURING AND AFTER RESIDENCY TRAINING: AN OBJECTIVE EVALUATION
Authors: HERBERT C. MODLIN, WILLIAM BENJAMIN, S. BURRITT LACY, BERNARD H. HALL, JOSEPH SATTEN
Journal: American Journal of Psychiatry (1959)

For the past 7 years the Educational Research Committee of the psychiatric training center in Topeka, Kansas, has attempted to evaluate objectively (a) the impact of psychiatric training on residents and (b) the post-residency development of psychiatrists. Our initial project was confined to a study of the development of psychiatric knowledge, factual, theoretical and clinical, in our test subjects. The first year's efforts were reported in 1955(2). This paper describes our 1956-57 project in which we devised 100-item multiple choice questions and administered them to 7 test groups: beginning residents in their first week of training; residents at the end of their first, second and third years; junior hospital staff psychiatrists; senior staff psychiatrists (Board certified); our Board certified alumni in private practice. The examination investigated knowledge only in basic subjects such as psychodynamics, psychotherapy and ward management, but not subspecialties such as psychosomatic medicine, research methodology and forensic psychiatry. There is a discernible pattern of growth in psychiatric residents, year by year. The first year of training is the period for absorbing the psychiatric body of knowledge. Second and third year residents, and junior staff psychiatrists, perform slightly better than first year residents in most categories; on the whole, however, a remarkable lag in acquisition of basic psychiatric knowledge is evidenced by residents' scores, the one exception being the steady yearly improvement in knowledge of psychodynamics. Although advanced residents seem not to acquire much additional knowledge, the examination reveals a process of integration and facility in using it clinically which first year residents lack. A second significant development in useable knowledge coincides with the period of concentrated preparation for passing the examinations of the American Board of Psychiatry and Neurology. The Board certified psychiatrists exceed our other test groups in factual, theoretical and clinical knowledge. Post-residency psychoanalytic training produces a measurably greater proficiency in theory.
Differential gene expression in peripheral blood T cells from patients with psoriasis, lichen planus, and atopic dermatitis
Authors: Xinhua Li, Junqin Li, Yuanwen Yang, Ruixia Hou, Ruifeng Liu, Xincheng Zhao, Xin Yan, Guohua Yin, Peng An, Yong Wang, Kaiming Zhang
Journal: Journal of the American Academy of Dermatology (2013)