tbuckley/cabot-search huggingface dataset:
ATIM-36. EVOLUTION OF CLONAL ARCHITECTURE AND NEOANTIGEN LANDSCAPE IN AN ULTRAMUTATED GLIOBLASTOMA TREATED WITH IMMUNOTHERAPY: A CASE REPORT OF A PATIENT WITH A GERMLINE POLE DEFICIENCY
Authors: Tanner Johanns, Chris Miller, Ian Dorward, Arie Perry, Cole Ferguson, Robert Schmidt, Sonika Dahiya, George Ansstas, Christina Tsien, Elaine Mardis, Gavin Dunn
Journal: Neuro-Oncology (2016)

We present the case of a patient found to have a germline POLE deficiency after presenting with a glioblastoma of the left frontal lobe. Following gross total resection and concurrent chemoradiation, the patient developed a metastasis in the cervical spine that was excised. Given the high mutational burden of the tumor based on a 315 gene panel assay, immunotherapy with the anti-PD-1 antibody, Pembrolizumab, was initiated. Subsequently, an additional metastatic lesion appeared in the thoracic spine. Immunohistochemistry revealed a brisk CD4 and CD8 T cell infiltrate with only necrotic tissue present. This was in stark contrast to the paucity of immune infiltrate seen in the primary and first spinal metastasis specimens. To fully characterize the genomic evolution of these metachronous tumors, whole DNA and RNA sequencing was performed and revealed an ultramutated phenotype with >15,000 somatic mutations similar to previously described POLE deficient tumors. Furthermore, neoantigen load was assessed using class I HLA binding prediction algorithms and demonstrated a high number of putative neoantigens (>2,000 in the founder clone) consistent with the observed clinical and radiographic response to immunotherapy. Unfortunately, despite an initial partial response to PD-1 blockade therapy, the patient eventually developed multiple intracranial metastases that were devoid of immune infiltrate suggestive of immunological escape. To our knowledge, this is the first reported case of a glioblastoma arising from a germline POLE mutation, and the first characterization the clonal architecture and neoantigen landscape of an ultramutated tumor before and after standard cytotoxic chemotherapy with radiation as well as following immunotherapy. Moreover, this is the first study describing the use of checkpoint blockade as treatment of glioblastomas with a hypermutated phenotype in adults. Thus, this case report provides proof-of-concept support to pursuing larger clinical trials evaluating the use of immune-based therapies to treat similar tumors in the future.
Tasa de pancreatitis post-CPRE cuando tras canular con guía el páncreas no puede insertarse una prótesis plástica
Authors: J García-Cano, L Valiente-González, Y Jiménez-Martínez, T Martínez-Pérez, R Martínez-Fernández, M Viñuelas-Chicano, J Gómez-Ruiz Carmen, J Morillas-Ariño, I Pérez-García José, Á Pérez-Sola
Journal: Endoscopy (2015)

Antecedentes y Objetivo: La administración de indometacina o diclofenaco parece prevenir la pancreatitis aguda post-CPRE. Cuando en los intentos de canulación del colédoco con guía, ésta entra en el páncreas, no está claramente definido si, junto a los AINES, es preciso colocar una prótesis pancreática plástica para aumentar la tasa de protección de pancreatitis aguda. Nuestro objetivo fue estudiar la incidencia de pancreatitis aguda en las CPRE en que, tras el paso de la guía al Wirsung, no pudo insertarse una prótesis pancreática.
An Open-Label, Unit Dose-Finding Study Evaluating the Safety and Platelet Response of a Novel Thrombopoietic Protein (AMG531) in Thrombocytopenic Adult Patients (Pts) with Immune Thrombocytopenic Purpura (ITP).
Authors: Adrian Newland, Marie T. Caulier, Martin R. Schipperus, Maria Kappers-Klunne, Bruno R. Varet, Karen Watkins, Chien-Feng Chen, Janet L. Nichol
Journal: Blood (2004)
Healthcare regulation will change, government says
Authors: Clare Dyer
Journal: BMJ (2017)

Major changes to the way doctors and other healthcare professionals are regulated are to be proposed by the UK government within months.

The plans could see doctors and nurses policed by a single regulator or even the creation of a super-regulator to replace the nine that currently cover doctors, dentists, nurses, pharmacists, and other healthcare professionals.

Ministers believe that the current regulatory regime—with separate rules and procedures for the different professions, which have been altered piecemeal over the years—is bureaucratic, outdated, and insufficiently focused on protecting the …
Exquisite Sensitivity of Plasma Cell Malignancies to a Novel Nucleoside Analog Is Mediated By Overexpressed Adenosine Kinase
Authors: Utthara Nayar, Jouliana Sadek, Jonathan B Reichel, David Bunn, Denise Hernandez-Hopkins, Peter Barelli, Michelle Sahai, Jennifer Totonchy, Sei Shizuko, Robert Shoemaker, David Warren, Olivier Elemento, Kenneth Kaye, Ethel Cesarman
Journal: Blood (2015)
Consistent Efficacy and Safety of 12 SQ House Dust Mite Sublingual Immunotherapy Tablet Among Subgroups with Allergic Rhinoconjunctivitis
Authors: Jose A. Bardelas, David I. Bernstein, Harold S. Nelson, Joerg R. Kleine-Tebbe, Gordon L. Sussman, Dorthe Seitzberg, Dorte Rehm, Amarjot Kaur, Ziliang Li, Susan Lu, Hendrik Nolte
Journal: Journal of Allergy and Clinical Immunology (2017)
Failure of CD34+ Mobilization in AML Patients Is Associated to an Abnormally High Chemosensitivity of Non Leukemic CFU-GM.
Authors: Giuseppe Milone, Benedetto Farsaci, Giuseppe Avola, Salvatore Mercurio, Aurora Strano, Maria Grazia Camuglia, Valeria Pinto, Antonella Privitera, Salvatore Leotta, Massimo Poidomani, Stefania Coppoletta, Elisa Mauro, Pamela Murgano, Katia Battiato, Andrea Spataro, Anna Triolo, Rosario Giustolisi
Journal: Blood (2007)
Mutational profiles in paired primary tumours and metastases in colorectal cancer patients: an NGS study of the Hellenic Cooperative Oncology Group
Authors: G. Pentheroudakis, V. Kotoula, V. Kourvelos, E. Charalambous, V. Karavasilis, E. Giannoulatou, G. Tsoulfas, E. Pazarli, G. Glantzounis, P. Papakostas, E. Samantas, D. Pectasides, G. Fountzilas
Journal: Annals of Oncology (2016)
Feasibility of two schedules of weekly paclitaxel as (neo)adjuvant treatment for patients (PTS) with HER2-negative breast cancer (BC) in the Brazilian community setting.
Authors: Iuri Amorim Santana, Julia Andrade De Oliveira, Alan Alves Amaral, Laura Testa, Luciana Garcia Landeiro, Romulo Leopoldo de Paula Costa, Marcelo Hajime, Marcela Simonis Martins Ferrari, Vanessa Petry, Daniela J. B. Heinemann Cohn, Paulo M. Hoff, Max S. Mano
Journal: Journal of Clinical Oncology (2012)

122 Background: Paclitaxel is one of the most active drugs in BC and the weekly administration has been shown more effective and better. GEICAM9906 was a phase III trial that demonstrated the effectiveness and safety of a pragmatic dose-dense schedule of 100mg/m 2 of paclitaxel given over 8 consecutive weeks (w), without G-CSF support. This schedule has been adopted at our institution in 2009 for HER2 negative disease and herein we present the first off-trial experience and also compare its safety profile with that of a historical cohort of pts treated with the conventional 80mg/m 2 x12w schedule. Methods: The study consists of a retrospective review of medical files from pts with locally advanced BC treated with (neo)adjuvant paclitaxel-based therapy with one of two schedules: (1) 80 mg/m² x 12w or (2) 100 mg/m² x 8w. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events 4.0 (CTCAE). Results: We reviewed files from 326 women with a median age of 52 (±10.9). Seventy and 256 pts received schedule (1) and (2), respectively. No significant difference was observed in the incidence of G3/4 toxicity: pneumonitis (2.8% vs 0.3% p=0.097), neuropathy (2.8% vs 0.7% p=0.303); hand-foot syndrome (1.4% vs 0.3% p=0.538); anaemia (0 vs 0.6% p=0.624); neutropenia (5.7% vs 6.2% p=0.408) with only one case of febrile neutropenia in schedule (2) arm; without cases of grade 3/4 thrombocytopenia, nausea, mucositis or anaphylaxis in both groups. Also, no significant difference was seen when comparing all grades toxicty. The dose intensity of paclitaxel was higher in schedule (2) with 97.72 mg/m² per week vs 77.07 mg/m² per week (p&lt;0.0001). Conclusions: Weekly paclitaxel given according to GEICAM9906 is a pragmatic and well tolerated schedule when used in the Brazilian community setting, with a safety profile comparable to the conventional 80mg/m 2 x12w schedule. In addition to being convenient to pts, it may also be cost-effective because of a lower number of clinic visits and infusions.
Phase III randomized, placebo-controlled clinical trial evaluating the use of adjuvant endocrine therapy with or without one year of everolimus in patients with high-risk, hormone receptor- (HR) positive and HER2-neu-negative breast cancer: SWOG/NSABP S1207.
Authors: Mariana Chavez-Mac Gregor, William E. Barlow, Ana M. Gonzalez-Angulo, Priya Rastogi, Eleftherios P Mamounas, Patricia A. Ganz, Anne Schott, Soonmyung Paik, Danika Lew, Hanna Bandos, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2013)

TPS657 Background: Abnormalities of the PI3kinase/AKT/mTOR signaling pathway are common in breast cancer. This pathway has been associated with endocrine resistance. Everolimus, an mTOR-inhibitor, has been shown to increase the biological activity endocrine therapies. S1207 proposes to evaluate the role of everolimus in combination with endocrine therapy in the adjuvant setting. Methods: S1207 is randomized phase III double-blinded, placebo-controlled clinical trial. The primary objective is to assess whether the addition of one year of everolimus to standard adjuvant endocrine therapy improves DFS. Secondary objectives include OS, DRFS, safety, adherence, and quality of life. Submission of tissue specimens/blood samples is required. Patients will be randomly assigned to receive standard adjuvant endocrine therapy in combination with one year of everolimus (10 mg PO daily) or in combination with one year of matched placebo. Eligibility Criteria: Patients with histologically confirmed invasive breast cancer HR-positive and HER2-negative with a) node-negative disease with tumors &gt;2cm and a recurrence score (RS) &gt;25; b) 1-3 positive lymph nodes RS &gt;25; c) &gt;4 positive lymph nodes are eligible after they have completed adjuvant chemotherapy; d) Patients with &gt;4 positive lymph nodes after neoadjuvant chemotherapy are also eligible. Patients must have completed surgery, chemotherapy, and radiation therapy (if indicated) before registration. Statistical methods/ target accrual: Parallel randomization design with equal allocation to the two treatment groups with stratification by 4 risk groups. All analyses are intent-to-treat. The study plans to randomize 3,500 patients over a 3.5-year accrual period. All patients will be followed for 10 years to assess survival and late adverse events. The first interim analysis would be after 39% of the expected events (n=295) have been observed or approximately 3.5 years after initiation of the study. Support: NCI U10-CA-37377, -12027, -69651; Breast Cancer Research Foundation; Novartis. Clinical trial information: NCT01674140.
Protective and Harmful Immunity to RSV Infection
Authors: Peter J.M. Openshaw, Chris Chiu, Fiona J. Culley, Cecilia Johansson
Journal: Annual Review of Immunology (2017)

Respiratory syncytial virus (RSV) is an exceptional mucosal pathogen. It specializes in infection of the ciliated respiratory epithelium, causing disease of variable severity with little or no direct systemic effects. It infects virtually all children by the age of three years and then repeatedly infects throughout life; this it does despite relatively slight variations in antigenicity, apparently by inducing selective immunological amnesia. Inappropriate or dysregulated responses to RSV can be pathogenic, causing disease-enhancing inflammation that contributes to short- and long-term effects. In addition, RSV's importance as a largely unrecognized pathogen of debilitated older people is increasingly evident. Vaccines that induce nonpathogenic protective immunity may soon be available, and it is possible that different vaccines will be optimal for infants; older children; young to middle-age adults (including pregnant women); and elderly persons. At the dawn of RSV vaccination, it is timely to review what is known (and unknown) about immune responses to this fascinating virus.
Distinct Mechanisms of Idiopathic and Thienopyridine-Assocaited Thrombotic Thrombocytopenia Purpura: Final Results from the Surveillance, Epidemiology, and Risk Factors for Thrombotic Thrombocytopenic Purpura (SERF-TTP) Study.
Authors: Charles L. Bennett, Anaadriana Zakarija, Hau C. Kwaan, Dilip Pandey, Paul Yarnold, John F Cursio, Robert Soltysik, Thanh Ha Luu, Elizabeth Richey, Ivy Weiss, June McKoy, Dennis W Raisch, Thomas Raife, Patricia Carey, Ravindra Sarode, Joseph Kiss, Constance Danielson, Bruce C. McLeod, Thomas L. Ortel, Jeffery Winters, William Clark, Nicholas Bandarenko, Gail Rock
Journal: Blood (2008)
Lactobacilli inhibits proliferation and induce cytotoxicity in bladder cancer cell-lines
Authors: Cai Shirong, Ratha Mahendran, Boon Huat Bay, Yuan Kun Lee
Journal: Clinical Cancer Research (2007)

B29  Background: Lactobacilli are part of the human commensal microflora and are commonly consumed in fermented milk products and dietary supplements. They are found to enhance the host’s immune response and exhibit anti-tumor properties. Several lactobacilli strains were reported to be cytotoxic to tumor cells in in vitro studies. It was postulated to be due to a secreted molecule or a component of the bacteria, for example their peptidoglycan.  Aim: To study how Lactobacillus species inhibit the proliferation of bladder cancer cells and induce cytotoxicity in vitro and study the properties of the inhibitory and cytotoxic molecule(s) responsible.  Material and methods: L. casei strain Shirota, L. rhamnosus strain GG, L. acidophilus or L. bulgaricus (5 x 107 cfu/ml) were added to complete RPMI 1640 (5% penicillin G and 10% FBS) and cultured for 24 hours then filtered to remove all bacteria to produce Lactobacilli treated supernatant (supernatant L). The growth of MGH, HUCT (human bladder carcinoma), MB49 (mouse bladder carcinoma) cells (5 x 104/ml) and splenocytes (2 x 106/ml) were determined by MTS after 2 and 24 hours of exposure to supernatant L. Cell viability was confirmed with a MultiTox-Fluor Multiplex Cytotoxicity Assay. Supernatant L was subjected to autoclaving or filtered through a 30 kDa membranes and its effects on the bladder cancer cells were monitored after 2 hours of incubation. MGH cells were stained with Hoechst 33258 after 24, 48 and 72 hours of incubation with supernatant L and viewed with confocal microscope. Statistical analyses were carried out by using the one-way Anova by SPSS. A significant difference was taken to exist when p value was
DDIS-01. TARGETING CYTOCHROME C OXIDASE WITH SMALL MOLECULE INHIBITORS: A NOVEL STRATEGY FOR CHEMORESISTANT GLIOBLASTOMA
Authors: Claudia Oliva, Corinne E. Griguer
Journal: Neuro-Oncology (2016)

The enzyme cytochrome c oxidase (CcO), or complex IV (EC 1.9.3.1), is a large transmembrane protein complex that serves as the last enzyme in the respiratory electron transport chain of eukaryotic mitochondria, receiving electrons from cytochrome c and transferring them to oxygen to produce two molecules of water. In the process, protons translocate across the mitochondrial membrane, establishing a transmembrane difference of proton electrochemical potential that drives the synthesis of ATP by ATP synthase. CcO promotes the switch from glycolytic to oxidative phosphorylation (OXPHOS) metabolism and has been associated with increased self-renewal characteristics in gliomas. Increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure, and patients with primary glioblastoma multiforme and high tumor CcO activity have worse clinical outcomes compared with those with low tumor CcO activity. Therefore, CcO is an attractive target for cancer therapy. Here, we conducted a high-throughput screen of over 130,000 small molecules to identify novel inhibitors of CcO. From this screen, we identified several CcO inhibitors which inhibit proliferation of glioma cells but did not display toxicity against non-cancer cells. One lead compound (ADDA 5) was chosen for more detailed study and inhibited proliferation of chemoresistant gliomas in vitro and in a xenograft model in vivo and GBM stem cells in self-renewal assays. These results suggest these novel CcO inhibitors are lead compounds that can be further optimized for GBM therapy.
T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED
Authors: Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Iaonnis Pandis, Ana Sousa, Julie Corfield, Ratko Djukanovic, Rene Lutter, Peter J. Sterk, Charles Auffray, Yike Guo, Ian M. Adcock, Kian Fan Chung
Journal: European Respiratory Journal (2017)

Asthma is characterised by heterogeneous clinical phenotypes. Our objective was to determine molecular phenotypes of asthma by analysing sputum cell transcriptomics from 104 moderate-to-severe asthmatic subjects and 16 nonasthmatic subjects. After filtering on the differentially expressed genes between eosinophil- and noneosinophil-associated sputum inflammation, we used unbiased hierarchical clustering on 508 differentially expressed genes and gene set variation analysis of specific gene sets. We defined three transcriptome-associated clusters (TACs): TAC1 (characterised by immune receptors IL33R , CCR3 and TSLPR ), TAC2 (characterised by interferon-, tumour necrosis factor-α- and inflammasome-associated genes) and TAC3 (characterised by genes of metabolic pathways, ubiquitination and mitochondrial function). TAC1 showed the highest enrichment of gene signatures for interleukin-13/T-helper cell type 2 (Th2) and innate lymphoid cell type 2. TAC1 had the highest sputum eosinophilia and exhaled nitric oxide fraction, and was restricted to severe asthma with oral corticosteroid dependency, frequent exacerbations and severe airflow obstruction. TAC2 showed the highest sputum neutrophilia, serum C-reactive protein levels and prevalence of eczema. TAC3 had normal to moderately high sputum eosinophils and better preserved forced expiratory volume in 1 s. Gene–protein coexpression networks from TAC1 and TAC2 extended this molecular classification. We defined one Th2-high eosinophilic phenotype TAC1, and two non-Th2 phenotypes TAC2 and TAC3, characterised by inflammasome-associated and metabolic/mitochondrial pathways, respectively.
Molecular analysis in serial biopsies in sinonasal mucosal melanoma
Authors: G. Anguera Palacios, M.Á Molina-Vila, J.R. Gras-Cabrerizo, X. León, C. Mayo, J. Codony Servat, A. Pérez-Rosado, S. Rodríguez, M. González-Cao, N. Karachaliou, A. Barnadas, R. Rosell, M. Majem
Journal: Annals of Oncology (2016)
New Role of the Regulatory Gene SOX2 in Hematopoiesis.
Authors: Elena Levantini, Francesca Bertolotti, Francesco Cerisoli, Anna L. Ferri, Elisa Brescia, Daniele Galvagno, Daniel G. Tenen, Sergio Ottolenghi, Silvia K. Nicolis, Maria C. Magli
Journal: Blood (2004)
CD20-Negative Phenotypic Change In B-Cell Lymphoma Cells After Using Rituximab: Possibility of a Particular Clinicopathologic Phenomenon Post-Rituximab Extranodal CD20-Negative Lymphoma
Authors: Akihiro Tomita, Takashi Tokunaga, Chisako Iriyama, Kazuyuki Shimada, Junji Hiraga, Takumi Sugimoto, Hitoshi Kiyoi, Shigeo Nakamura, Tomohiro Kinoshita, Tomoki Naoe
Journal: Blood (2010)
Updated Recommendations for Athletes with Heart Disease
Authors: Rachel Lampert, Douglas P. Zipes
Journal: Annual Review of Medicine (2018)

Professional society recommendations to decrease sudden cardiac death in athletes, including eligibility requirements with disqualification for athletes with diagnosed disease as well as preparticipation screening and emergency preparedness, were updated in 2015. The update includes new sections on aortic disease, channelopathies, and sickle cell trait, as well as a change in format from the previous binary yes/no format to the more nuanced and contemporary “class and level of evidence” format. Eighty-four of the 246 recommendations now carry Class II designation—“reasonable,” or “may be considered.” New language in the document emphasizes counseling as part of the decision process. New data on athletes with implantable cardioverter-defibrillators, and on those with long QT syndrome, have led to a change from blanket restriction of competitive sports participation to a Class IIB “may be considered” recommendation.
Donor Hematopoietic Stem Cells Did No Major Contribution to Hair Follicle Repair Either in Short or in Long Term Allogeneic Hematopoietic Stem Cell Transplants Recipients.
Authors: Alicia Rovo, Sandrine Meyer-Monard, Dominik Heim, Caroline Arber, Jakob R. Passweg, Alois Gratwohl, Andre Tichelli
Journal: Blood (2004)
Generation of Antigen-Specific Cytotoxic T Lymphocytes with Peripheral B Cells Activated By α-Galactosylceramide
Authors: Sun Ok Yun, Hee Young Ju, Che Ry Hong, Ji Won Lee, Hyery Kim, Kyung Duk Park, Hee Young Shin, Chang–Yuil Kang, Seung Shin Yu, Sunyoung Kim, Hyoung Jin Kang
Journal: Blood (2014)
Signal Transducer and Activator of Transcription (STAT)-3-Dependent Regulation of Non-Coding RNA Genes in Chronic Lymphocytic Leukemia (CLL).
Authors: Uri Rozovski, George Calin, Setoyama Tetsirp, Lucilla D'Abundo, David Harris, Ping Li, Zhiming Liu, Srdana Grgurevic, Alessandra Ferrajoli, Stefan Faderl, Jan A. Burger, Susan M. O'Brien, William G. Wierda, Michael J. Keating, Zeev Estrov
Journal: Blood (2012)
Midlife Approaches to Prevention of Ill Health in Later Life
Authors: Louise Lafortune, Steven Martin, Sarah Kelly
Journal: JAMA Internal Medicine (2017)

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RESPIRATORY ALLERGY DUE TO MILLET IN BIRD-KEEPERS: TWO CASES REPORT
Authors: Elena Mederos Luis, Alicia Enriquez Matas, Ismael García Moguel, Lys Herraez Herrera, Natividad De las Cuevas Moreno, Consuelo Rodríguez Fernández
Journal: Journal of Allergy and Clinical Immunology (2017)
Clinically Significant Improvements in Asthma Patient-Reported Outcomes: Results from the Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) Study
Authors: Erika G. Gonzalez-Reyes, Allan T. Luskin, William Busse, Thomas B. Casale, Bradley E. Chipps, Evgeniya Antonova, Susan L. Limb, Benjamin L. Trzaskoma, Noelle M. Griffin, Robert S. Zeiger
Journal: Journal of Allergy and Clinical Immunology (2017)