tbuckley/cabot-search huggingface dataset:
Immuno-gene therapy of non-hodgkin lymphoma using adenovirus encoding CD40 ligand (CD154)
Authors: Robier Aguillon, Januario Castro, David Whitaker, Carlos Suarez, Charles Prussak, Thomas Kipps
Journal: Cancer Research (2007)

1888  Non-Hodgkin lymphoma (NHL) is a highly prevalent disease with approximately 30,000 cases diagnosed every year in the United States.  Despite advance in the treatment of NHL the majority of patients relapsed after chemotherapy treatment and frequently die of disease progression or treatment related complications. Therefore there is a need for novel and effective treatment strategies for the treatment of patients with NHL.  NHL cells are capable of evading the immune system and this creates a major challenge to achieve durable complete responses. NHL cells are characterized by deficient mechanisms of antigen presentation that impair effective anti-lymphoma immune recognition.  Because breaking tolerance to NHL cells constitutes a potential target for immunotherapy of this disease we have developed strategies to improve immune recognition of lymphoma cells using gene therapy mediated by adenovirus encoding CD40 ligand (CD154).  We have constructed replication defective adenovirus encoding murine CD154 â\#8364;“ Ad-ISF154 and a chimeric human/mouse CD154, Ad-ISF35, this construct also contains an in-frame deletion of the major MMP-cleavage site, allowing for sustained high-level expression on the plasma membrane.  Using the A20 mouse lymphoma model we generated subcutaneous (S.Q.) NHL tumors that were injected with either Ad-ISF154 or Ad-ISF35.  BALB/c mice were injected S.Q. with 3x105 A20 cells. 14 days later the NHL tumors were injected with: Saline (control Group 1), Ad-ISF154 (Group 2), Ad-ISF35 (Group 3) and Ad-GFP (Group 4 - control adenovirus). On day 28, 87% (7/8) of mice treated with Ad-ISF35 intratumoral injection had complete tumor regression. Also, the majority of mice treated with Ad-ISF154 had tumor regression, 75% (6/8). Conversely, only 12.5% (1/8) of mice treated with Ad-GFP had no evidence of tumor progression while all those treated with control saline had rapid disease progression. Interestingly all the mice that achieved tumor regression after treatment with Ad-ISF154 and Ad-ISF35 were protected against tumor re-challenge.  Analysis of humoral and cellular immune responses in the mice treated with Ad-ISF154 and Ad-ISF35 indicated strong immune reactivity against A20 derived proteins by western blot and T cell reactivity measured by IFN-g ELISPOT assays suggesting anti-lymphoma activity.  >Together our data suggest that intratumoral injection of A20 NHL lymphoma tumors with Adenovirus encoding CD154 is capable of breaking immune tolerance resulting in tumor regression and systemic T and B cell mediated immune responses against tumor cells.
Transdifferentiation of lymphoma into sarcoma associated with profound reprogramming of the epigenome
Authors: Qian Zhang, Elena J. Orlando, Hong Y. Wang, Agata M. Bogusz, Xiaobin Liu, Simon F. Lacey, Honore T. Strauser, Selene Nunez-Cruz, Reza Nejati, Paul Zhang, Sarah Brooks, Christopher Watt, J. Joseph Melenhorst, Carl H. June, Stephen J. Schuster, Mariusz A. Wasik
Journal: Blood (2020)
Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3
Authors: Shannon M. Reilly, Chao-Wei Hung, Maryam Ahmadian, Peng Zhao, Omer Keinan, Andrew V. Gomez, Julia H. DeLuca, Benyamin Dadpey, Donald Lu, Jessica Zaid, BreAnne Poirier, Xiaoling Peng, Ruth T. Yu, Michael Downes, Christopher Liddle, Ronald M. Evans, Anne N. Murphy, Alan R. Saltiel
Journal: Nature Metabolism (2020)
DRC faces new Ebola outbreak, covid-19, and measles all at once
Authors: Owen Dyer
Journal: BMJ (2020)

The Democratic Republic of Congo (DRC)—on the point of declaring victory in a 22 month Ebola epidemic that has claimed 2268 lives—has detected a new Ebola outbreak on the other side of the country, just as covid-19 begins to gain a foothold, and as the world’s deadliest measles epidemic enters its second year.

The long running Ebola outbreak centred on North Kivu province in the east will be officially over if no new cases appear by 25 June, two 22 day incubation periods after the last active case. But six new cases, including four deaths, have now been announced near Mbandaka in Equateur …
Diagnosis of asthma in children: findings from the Swiss Paediatric Airway Cohort
Authors: Carmen C.M. de Jong, Eva S.L. Pedersen, Rebeca Mozun, Dominik Müller-Suter, Anja Jochmann, Florian Singer, Carmen Casaulta, Nicolas Regamey, Alexander Moeller, Cristina Ardura-Garcia, Claudia E. Kuehni
Journal: European Respiratory Journal (2020)

Introduction Diagnosing asthma in children remains a challenge because respiratory symptoms are not specific and vary over time. Aim In a real-life observational study, we assessed the diagnostic accuracy of respiratory symptoms, objective tests and two paediatric diagnostic algorithms (proposed by the Global Initiative for Asthma (GINA) and the National Institute for Health and Care Excellence (NICE)) in the diagnosis of asthma in school-aged children. Methods We studied children aged 5–17 years who were referred consecutively to pulmonary outpatient clinics for evaluation of suspected asthma. Symptoms were assessed by parental questionnaire. The investigations included specific IgE measurement or skin prick tests, measurement of exhaled nitric oxide fraction ( F eNO ), spirometry, body plethysmography and bronchodilator reversibility (BDR). Asthma was diagnosed by paediatric pulmonologists based on all available data. We assessed diagnostic accuracy of symptoms, tests and diagnostic algorithms by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC). Results Among 514 participants, 357 (70%) were diagnosed with asthma. The combined sensitivity and specificity was highest for any wheeze (sensitivity=75%, specificity=65%), dyspnoea (sensitivity=56%, specificity=76%) and wheeze triggered by colds (sensitivity=58%, specificity=78%) or by exercise (sensitivity=55%, specificity=74%). Of the diagnostic tests, the AUC was highest for specific total airway resistance (sR tot ; AUC=0.73) and lowest for the residual volume (RV)/total lung capacity (TLC) ratio (AUC=0.56). The NICE algorithm had sensitivity=69% and specificity=67%, whereas the GINA algorithm had sensitivity=42% and specificity=90%. Conclusion This study confirms the limited usefulness of single tests and existing algorithms for the diagnosis of asthma. It highlights the need for new and more appropriate evidence-based guidance.
Talin-1 is the principal platelet Rap1 effector of integrin activation
Authors: Frederic Lagarrigue, David S. Paul, Alexandre R. Gingras, Andrew J. Valadez, Hao Sun, Jenny Lin, Monica N. Cuevas, Jailal N. Ablack, Miguel Alejandro Lopez-Ramirez, Wolfgang Bergmeier, Mark H. Ginsberg
Journal: Blood (2020)
Myeloid signature reveals immune contexture and predicts the prognosis of hepatocellular carcinoma
Authors: Chong Wu, Jie Lin, Yulan Weng, Dan-Ni Zeng, Jing Xu, Shufeng Luo, Li Xu, Mingyu Liu, Qiaomin Hua, Chao-Qun Liu, Jin-Qing Li, Jing Liao, Cheng Sun, Jian Zhou, Min-Shan Chen, Chao Liu, Zhenhong Guo, Shi-Mei Zhuang, Jin-Hua Huang, Limin Zheng
Journal: Journal of Clinical Investigation (2020)

BACKGROUNDDespite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC).METHODSUsing in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts.RESULTSThe MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8+ T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC.CONCLUSIONWe identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes.FUNDINGThis work was supported by the National Science and Technology Major Project of China, the National Natural Science Foundation of China, the Science and Information Technology of Guangzhou, the Fundamental Research Funds for the Central Universities, the Guangdong Basic and Applied Basic Research Foundation, and the China Postdoctoral Science Foundation.
A randomized, open-label, Phase III study of obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-Cell lymphoma: final analysis of GOYA
Authors: Laurie H. Sehn, Maurizio Martelli, Marek Trněný, Wenxin Liu, Christopher R. Bolen, Andrea Knapp, Deniz Sahin, Gila Sellam, Umberto Vitolo
Journal: Journal of Hematology & Oncology (2020)

Rituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the current standard therapy for diffuse large B cell lymphoma (DLBCL). Obinutuzumab (G), a glycoengineered, type II anti-CD20 monoclonal antibody, has shown activity and an acceptable safety profile when combined with CHOP (G-CHOP) in patients with advanced DLBCL. We present the final analysis results of the Phase III GOYA study (NCT01287741), which compared the efficacy and safety of G-CHOP versus R-CHOP in patients with previously untreated DLBCL.Patients aged ≥ 18 years with previously untreated advanced DLBCL were randomly assigned to receive eight 21-day cycles of R or G, plus six or eight cycles of CHOP. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival, other time-to-event endpoints, and safety; investigator-assessed PFS by cell of origin subgroup was an exploratory endpoint.A total of 1418 patients were randomized, with 1414 included in this final analysis (G-CHOP, N = 704; R-CHOP, N = 710). Five-year PFS rates were 63.8% and 62.6% for G-CHOP and R-CHOP, respectively (stratified hazard ratio 0.94, 95% CI 0.78-1.12; p = 0.48). The results of the secondary efficacy endpoints did not show a benefit of G-CHOP over R-CHOP. In the exploratory analysis, a trend towards benefit with G-CHOP over R-CHOP was apparent in the patients with germinal center B cell DLBCL. The safety profile of G-CHOP was as expected, and no new safety signals were observed. More grade 3-5 (75.1% vs 65.8%), serious (44.4% vs 38.4%), and fatal (6.1% vs 4.4%) adverse events (AEs) were observed in the G-CHOP arm compared with the R-CHOP arm, respectively, with the most common fatal AEs being infections. A higher incidence of late-onset neutropenia occurred in the G-CHOP arm (8.7%) versus the R-CHOP arm (4.9%).The final analysis, similar to the primary analysis, did not show a PFS benefit of G-CHOP over R-CHOP in previously untreated patients with DLBCL. The results of the secondary endpoints were consistent with the primary endpoint. Further exploratory analyses and investigation of biomarkers are ongoing.
Results of an Early Access Treatment Protocol of Daratumumab Monotherapy in Spanish Patients With Relapsed or Refractory Multiple Myeloma
Authors: Adrián Alegre, Javier de la Rubia, Anna Sureda Balari, Cristina Encinas Rodríguez, Alexia Suárez, María Jesús Blanchard, Joan Bargay Lleonart, Paula Rodríguez-Otero, Andrés Insunza, Luis Palomera, María Jesús Peñarrubia, Rafael Ríos-Tamayo, Luis Felipe Casado Montero, Marta Sonia González, Anna Potamianou, Catherine Couturier, Huiling Pei, Henar Hevia, Iordanis Milionis, Maren Gaudig, María-Victoria Mateos
Journal: HemaSphere (2020)

Supplemental Digital Content is available in the text
A direct-acting antiviral drug abrogates viremia in Zika virus–infected rhesus macaques
Authors: So-Yon Lim, Christa E. Osuna, Katharine Best, Ray Taylor, Elsa Chen, Gyeol Yoon, Jessica L. Kublin, Dane Schalk, Nancy Schultz-Darken, Saverio Capuano, David Safronetz, Ma Luo, Steve MacLennan, Amanda Mathis, Yarlagadda S. Babu, William P. Sheridan, Alan S. Perelson, James B. Whitney
Journal: Science Translational Medicine (2020)

Zika virus infection in humans has been associated with serious reproductive and neurological complications. At present, no protective antiviral drug treatment is available. Here, we describe the testing and evaluation of the antiviral drug, galidesivir, against Zika virus infection in rhesus macaques. We conducted four preclinical studies in rhesus macaques to assess the safety, antiviral efficacy, and dosing strategies for galidesivir (BCX4430) against Zika virus infection. We treated 70 rhesus macaques infected by various routes with the Puerto Rico or Thai Zika virus isolates. We evaluated galidesivir administered as early as 90 min and as late as 72 hours after subcutaneous Zika virus infection and as late as 5 days after intravaginal infection. We evaluated the efficacy of a range of galidesivir doses with endpoints including Zika virus RNA in plasma, saliva, urine, and cerebrospinal fluid. Galidesivir dosing in rhesus macaques was safe and offered postexposure protection against Zika virus infection. Galidesivir exhibited favorable pharmacokinetics with no observed teratogenic effects in rats or rabbits at any dose tested. The antiviral efficacy of galidesivir observed in the blood and central nervous system of infected animals warrants continued evaluation of this compound for the treatment of flaviviral infections.
Lymphocyte transformation test can be useful for the diagnosis of delayed adverse reactions to sulfonamides
Authors: Francisca Vílchez‐Sánchez, David Loli‐Ausejo, Amelia Rodriguez‐Mariblanca, Jaime Montserrat‐Villatoro, Elena Ramírez, Javier Domínguez‐Ortega, Miguel González‐Muñoz
Journal: Allergy (2020)

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Obesity and covid-19: the role of the food industry
Authors: Monique Tan, Feng J He, Graham A MacGregor
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Obesity and covid-19: the role of the food industry Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
長期宇宙飛行後に宇宙飛行士で観察される視神経乳頭浮腫,眼球の平坦化,脈絡膜ひだ,及び遠視への変化
Authors: H Mader Thomas, Gibson C. Robert, Tran Duc, Lipsky William, Choi Jung, F Pass Anastas, A Kramer Larry, G Lee Andrew, Fogarty Jennifer, J Tarver William, P Dervay Joseph, D Polk James, R Hamilton Douglas, Sargsyan Ashot, L Phillips John, Stern Claudia, Kuyumjian Raffi
Journal: Ophthalmology (2011)
AB0589 THE IMPORTANCE OF A SYSTEMIC SCLEROSIS CLINIC IN A TERTIARY REFERRAL CENTER – A PORTUGUESE EXPERIENCE
Authors: P. Martins, E. Dourado, J. E. Fonseca, I. Cordeiro, C. Resende
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic sclerosis (SSc) is a rare systemic rheumatic disease (SRD) characterized by small vessel inflammation and fibrosis of skin and internal organs. Pulmonary and cardiac involvement contribute to both morbidity and mortality associated with the disease. A multidisciplinary approach with strict monitoring is therefore key to attain clinical success. Objectives: To describe the organization and patient pathways of our SSc outpatient clinic. Methods: Observational study using data extracted from Reuma.pt/SSc (a subset of the Rheumatic Diseases Portuguese Register). Data extracted included demographic variables and clinical and immunological manifestations. The disease was classified according to the 2013 ACR/EULAR criteria. Our SSc clinic is managed by two dedicated Rheumatologists and up to two Rheumatology residents on a weekly basis, but it is a dynamic multidisciplinary clinic where various medical specialties collaborate closely. There are two associated subspecialty clinics (pulmonary hypertension and pulmonary fibrosis) where the Rheumatologists engage with pneumologists and cardiologists, allowing greater collaboration in the management of these patients. Patients’ data is systematically registered in Reuma.pt/SSc as a part of the routine activity of this clinic, contributing to real-world data on SSc. Results: A total of 220 patients were registered between July 2011 and June 2019. 196 (89.1%) were female, with a mean age of 58.9±14 years and a mean disease duration of 14.6±9 years. Ninety-seven patients (44.1%) had limited cutaneous SSc, 52 (23.6%) had diffuse cutaneous SSc, 35 (15.9%) had overlap SSc, 24 (10.9%) had preclinical SSc and 12 (5.4%) had SSc sine scleroderma. Raynaud phenomenon was present in 92% of the SSc patients and 40% had a history of digital ulcers. Gastrointestinal manifestations included esophageal dismotility in 39.5% of patients, gastric disease in 24.4% and intestinal involvement in 15.5%. Pulmonary involvement was found in 47.6% of SSc patients, heart disease in 43.6% and kidney involvement in only two patients. Antinuclear antibodies were positive in 92.2% of the patients, anti-centromere in 44.1%, anti-topoisomerase I antibodies in 39.1%, anti-U1RNP in 4.5% and only three patients had anti-PM-Scl and one had anti-RNA polymerase III. 31 patients were lost to follow-up and 32 died. 18 patients are currently being followed up in the pulmonary hypertension clinic and seven in the pulmonary fibrosis clinic. Conclusion: The implementation of a standardized approach with regular multidisciplinary work has proven very helpful in evaluating patients with SSc. The continuous registry of patients in Reuma.pt/SSc has been essential for patient care, research and healthcare planning. Disclosure of Interests: None declared
COVID-19 infection in a patient with FMF: does colchicine have a protective effect?
Authors: Senol Kobak
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the report by Monti et al on the 320 rheumatic patients treated with various disease-modifying anti-rheumatic drugs (DMARDs) in the era of COVID-19 infection.1 They suggest that patients with chronic arthritis receiving DMARDs may not have an increased risk of severe COVID-19. We agree that patients under DMARD treatment should be closely monitored since data are lacking. Also, we hypothesise that some DMARDs (especially colchicine) may protect rheumatic patients from COVID-19 or perhaps cause them to pass in a milder form of the disease. COVID-19 is not just a simple viral infection; it is an autoinflammatory/autoimmune process that develops as a result of immune system dysfunction, cytokine release syndrome and haemophagocytic lymphohistiocytosis.2 Herein we reported COVID-19 infection in a patient with familial Mediterranean fever (FMF) under treatment with colchicine.

A 36-year-old …
Abstract A26: Modeling the ovarian cancer immune response and tumor microenvironment
Authors: Duygu Ozmadenci, Jayanth S. Shankara Narayanan, Jacob R. Andrew, Allison M. Barrie, Shulin Jiang, Esra Bilir, Thomas Bertotto, Rebekah R. White, Vijay K. Kuchroo, Jonathan A. Pachter, Dwayne G. Stupack, David D. Schlaepfer
Journal: Cancer Research (2020)

Abstract High-grade serous ovarian cancer (HGSOC) is the leading cause of death from gynecologic malignancies. Many patients initially respond well to surgery followed by chemotherapy, yet ~80% of patients recur with disease that is frequently recalcitrant to chemotherapy. Across a number of chemoresistant cancers, immunotherapies have shown great promise. Correlative studies in patients with HGSOC support a role for immune system in patient outcome. Yet the HGSOC tumor microenvironment (TME) is highly immunosuppressive, which constitutes a major barrier to immunotherapy success. Understanding the molecular signals in HGSOC that promote resistance to chemo- or immunotherapies is required for identification of actionable targets within HGSOC; yet, there are limited models that recapitulate the TME in ovarian cancer. We have generated a new syngeneic C57Bl6 mouse model of ovarian cancer that exhibits genomic copy number gains in KRAS, MYC, and (PTK2) FAK genes (termed KMF) and aggressive malignant phenotypes commonly observed in HGSOC. The KMF TME, like HGSOC, is populated by immunosuppressive myeloid-derived suppressor cells (MDSC) and T-regulatory (Treg) cells but lacks CD8+ T cell infiltration. We find that tumor-associated FAK expression and kinase activity are essential for KMF tumor growth. Mechanistically, by knockout and cell reconstitution approaches, FAK promotes expression of a select group of proteins mediating chemo- and immune-resistance. Inhibiting FAK modulates checkpoint inhibitor protein expression, limits MDSC and Treg recruitment, and enhances CD4 and CD8 T cell infiltration. Pharmacologic FAK inhibition reduced CD112/CD155 expression on KMF cells and, together with anti-TIGIT immunotherapy, significantly increased mouse survival from 28 to 60+ days. The chemoresistant KMF model recapitulates key aspects of the aggressive HGSOC TME including the generation of an immunosuppressive milieu, and may be used as a preclinical model to identify new therapeutic targets for HGSOC. Citation Format: Duygu Ozmadenci, Jayanth S. Shankara Narayanan, Jacob R. Andrew, Allison M. Barrie, Shulin Jiang, Esra Bilir, Thomas Bertotto, Rebekah R. White, Vijay K. Kuchroo, Jonathan A. Pachter, Dwayne G. Stupack, David D. Schlaepfer. Modeling the ovarian cancer immune response and tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A26.