tbuckley/cabot-search huggingface dataset:
Abstract 2399: LAG-3/PD-L1 mAb2 can overcome PD-L1-mediated compensatory upregulation of LAG-3 induced by single-agent checkpoint blockade
Authors: Mustapha Faroudi, Matthew Kraman, Natalie Fosh, Claire Reader, Daniel Gliddon, Claire Seal, Christa Lucas, Alexander Koers, Mateusz Wydro, Michelle Morrow, Neil Brewis
Journal: Cancer Research (2019)

Abstract FS118, currently tested in Phase I clinical trial in patients with advanced malignancies (NCT03440437), is a first-in-class bispecific antagonistic antibody (known as mAb2) targeting LAG-3 (Lymphocyte-Activation Gene 3) and PD-L1 (Programmed Death-Ligand 1), two immune checkpoint molecules that promote tumour escape from immune surveillance. Resistance to anti-PD-1 treatment is associated with upregulation of other checkpoint inhibitor receptors such as LAG-3. Dual targeting in immune checkpoint blockade (ICB) using bispecific monoclonal antibodies could potentially overcome this resistance, further increase the clinical benefit of ICB therapy and prevent relapse or resistance after immunotherapy. In a syngeneic model we used a surrogate mAb2 of FS118 (blocking both mPD-L1 and mLAG-3 binding to their receptors) to determine the effect of dual checkpoint blockade on tumour growth and to elucidate the modulation of the underlying immune mechanisms following treatment with the mAb2. Dual blockade of LAG-3 and PD-L1 with the surrogate mAb2 in the MC38 tumour-bearing mice model resulted in an increased anti-tumour activity comparable to a combination of the single agents targeting LAG-3 and PD-L1. Moreover, the mAb2 and single agent combination resulted in distinct modulations of LAG-3 and PD-L1 cell surface expression within the spleen and tumour microenvironment (TME). While both the mAb2 and combination therapy significantly reduced the number of free PD-L1 binding sites on CD4+ and CD8+ T cells in spleen and TME, total LAG-3 cell surface expression increased following treatment with the combination, whereas it reduced with mAb2 treatment. In addition, analysis of serum samples collected at various timepoints confirmed evidence of drug target engagement with increasing levels of both soluble LAG-3 (sLAG-3) and soluble PD-L1 (sPD-L1) in the mAb2 treated animals. Modulation of sPD-L1 levels in the serum of treated animals was also observed in cynomolgus monkeys treated with FS118. These data provide a strong rationale for investigating both cell surface and soluble LAG-3 and PD-L1 levels as potential pharmacodynamic biomarkers in further clinical development. Citation Format: Mustapha Faroudi, Matthew Kraman, Natalie Fosh, Claire Reader, Daniel Gliddon, Claire Seal, Christa Lucas, Alexander Koers, Mateusz Wydro, Michelle Morrow, Neil Brewis. LAG-3/PD-L1 mAb2 can overcome PD-L1-mediated compensatory upregulation of LAG-3 induced by single-agent checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2399.
Abstract 19703: Prognostic Impacts of Antithrombotic Therapies in Patients With Atrial Fibrillation -Report From the CHART-2 Study-
Authors: Takashi Shiroto, Yasuhiko Sakata, Kotaro Nochioka, Ruri Abe, Takuya Oikawa, Shintaro Kasahara, Masayuki Sato, Hajime Aoyanagi, Masanobu Miura, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa
Journal: Circulation (2017)

Background: Atrial fibrillation (AF) is one of the major comorbidities in patients with heart failure (HF). Antithrombotic agents, especially anticoagulants (ACs), are widely used for AF patients t...
Abstract 19616: Down-Regulation of miR-23/27/24 Clusters by TGF-β1 Signalling Induces Phenotypic Switching of Vascular Smooth Muscle Cells in vitro and in Response to Vascular Injury in vivo
Authors: Claudio Iaconetti, Alberto Polimeni, Sabato Sorrentino, Jolanda Sabatino, Clarice Gareri, Francesco Passafaro, Maria Colangelo, Caterina Covello, Filomena Caria, Alessandra Carvelli, Antonio Curcio, Salvatore De Rosa, Ciro Indolfi
Journal: Circulation (2012)

Background: The differentiated state of SMCs plays a key role in the pathogenesis of several major human diseases, including atherosclerosis and restenosis after vascular injury. Several miRNAs hav...
Outcome of Acute Myeloid Leukemia (AML) Induction Therapy Based on D14 Marrow Biopsy According to European Leukemia Net (ELN) Risk Classification
Authors: David Ray, Jamie L. Koprivnikar, James K. McCloskey, Genique Stanislaus, Christina Howlett, Amy Davidow, Samantha Depadova, Stuart L. Goldberg, Stefan Faderl
Journal: Blood (2016)
Abstract 62: HIC1 inhibits cells metastasis via epithelial-mesenchymal transition in esophageal squamous cell carcinoma
Authors: Beibei Sha, Ping Chen, Xingge Liu, Xuanyu Hu, Miaomiao Li, Pei Li
Journal: Cancer Research (2019)

Abstract Invasion and metastasis are the main causes of death in patients with esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) has been reported to be closely related with tumor metastasis. Although HIC1 (hypermethylated in cancer 1) gene has been observed to be epigenetically modified in many cancers, its intrinsic role and mechanism in ESCC metastasis, especially in EMT, remains unclear. Our previous study showed that hypermethylation of the HIC1 promoter markedly elevated in metastatic ESCC tissues compared with primary and adjacent normal tissues and it was associated with poor patients’ survival. In the present study, we used immunohistochemistry (IHC) to detect the expression of HIC1 in ESCC tissues and adjacent normal tissues, and the results showed that HIC1 was down-expressed in ESCC tissues and overexpressed in adjacent normal tissues. Results from trans-well-migration and wound healing experiments showed that overexpression of HIC1 in ESCC cells (KYSE 30) can reduce cell migration and metastasis behavior. Moreover, Western blot showed that overexpression of HIC1 could down-regulate EphA2 expression, simultaneously induced the markers of EMT target changed, in which E-cadherin was observed up-regulated, Snail and Vimentin were down-regulated. In summary, our results suggests that HIC1 may regulate EphA2-SirT1-P53 signaling pathway to mitigate ESCC aggressiveness. Note: This abstract was not presented at the meeting. Citation Format: Beibei Sha, Ping Chen, Xingge Liu, Xuanyu Hu, Miaomiao Li, Pei Li. HIC1 inhibits cells metastasis via epithelial-mesenchymal transition in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 62.
Role of stereotactic body radiation therapy in the management of oligometastatic pancreatic cancer: single institution experience
Authors: M. Scorsetti, T. Comito, C. Franzese, D. Franceschini, F. De Rose, S. Tomatis, A. D’alessio, M. Prete, S. Bozzarelli, L. Rimassa, N. Personeni, A. Santoro
Journal: Annals of Oncology (2019)
Use of Genetic Variants Related to Antihypertensive Drugs to Inform on Efficacy and Side Effects
Authors: Dipender Gill, Marios K. Georgakis, Fotios Koskeridis, Lan Jiang, Qiping Feng, Wei-Qi Wei, Evropi Theodoratou, Paul Elliott, Joshua C. Denny, Rainer Malik, Evangelos Evangelou, Abbas Dehghan, Martin Dichgans, Ioanna Tzoulaki
Journal: Circulation (2019)

Drug effects can be investigated through natural variation in the genes for their protein targets. The present study aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are among the most commonly used medications worldwide.
Deletion of <scp>Mucosa‐Associated Lymphoid Tissue Lymphoma Translocation Protein</scp> 1 in Mouse T Cells Protects Against Development of Autoimmune Arthritis but Leads to Spontaneous Osteoporosis
Authors: Elisabeth Gilis, Djoere Gaublomme, Jens Staal, Koen Venken, Maarten Dhaenens, Stijn Lambrecht, Julie Coudenys, Tine Decruy, Nadia Schryvers, Yasmine Driege, Emilie Dumas, Annelies Demeyer, Amélie De Muynck, Jolanda van Hengel, Luc Van Hoorebeke, Dieter Deforce, Rudi Beyaert, Dirk Elewaut
Journal: Arthritis & Rheumatology (2019)

Objective Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 ( MALT ‐1) plays a crucial role in innate and adaptive immune signaling by modulating the threshold for activation of immune cells, including Treg cells. Therefore, MALT ‐1 is regarded to be an interesting therapeutic target in several immune‐mediated diseases. The goal of this study was to examine the role of MALT ‐1 in experimental animal models of rheumatoid arthritis ( RA ). Methods MALT ‐1 activation was assessed by measuring cleavage of the deubiquitinase CYLD in lymphocytes from mice with collagen‐induced arthritis ( CIA ). Furthermore, the impact of MALT ‐1 deficiency on arthritis was evaluated in Malt1 KO mice with CIA or with collagen antibody–induced arthritis ( CAIA ). T cell–specific MALT ‐1 deficiency was measured in mice with deletion of T cell–specific MALT‐1 ( Malt1 Tcell KO ), and the time‐dependent effects of MALT ‐1 deficiency were assessed in mice with deletion of tamoxifen‐inducible T cell–specific MALT‐1 ( Malt1 iTcell KO ). Bone density was determined in MALT ‐1–deficient mice using micro–computed tomography and femur‐bending tests. Reconstitution of Treg cells was performed using adoptive transfer experiments. Results MALT ‐1 activation was observed in the lymphocytes of mice with CIA . T cell–specific MALT ‐1 deletion in the induction phase of arthritis (incidence of arthritis, 25% in control mice versus 0% in Malt1 iTcell KO mice; P &lt; 0.05), but not in the effector phase of arthritis, completely protected mice against the development of CIA . Consistent with this finding, MALT ‐1 deficiency had no impact on CAIA , an effector phase model of RA . Finally, mice with MALT ‐1 deficiency showed a spontaneous decrease in bone density (mean ± SEM trabecular thickness, 46.3 ± 0.7 μm in control mice versus 40 ± 1.1 μm in Malt1 KO mice; P &lt; 0.001), which was linked to the loss of Treg cells in these mice. Conclusion Overall, these data in murine models of RA highlight MALT ‐1 as a master regulator of T cell activation, which is relevant to the pathogenesis of autoimmune arthritis. Furthermore, these findings show that MALT ‐1 deficiency can lead to spontaneous osteoporosis, which is associated with impaired Treg cell numbers.
Are we assuming too much with our statistical assumptions? Lessons learned from the ALTTO trial
Authors: E.M. Holmes, I. Bradbury, L.S. Williams, L. Korde, E. de Azambuja, D. Fumagalli, A. Moreno-Aspitia, J. Baselga, M. Piccart-Gebhart, A.C. Dueck, R.D. Gelber
Journal: Annals of Oncology (2019)
Abstract 1468: Synergistic cancer immunotherapy combination of MVA-CD40L with tumor targeting antibodies or checkpoint blockade to achieve strong antitumor immune responses against large, established tumors
Authors: Jose Medina-Echeverz, Maria Hinterberger, Raphael Giessel, Barbara Bathke, Ronny Kassub, Giovanna Fiore, Paul Chaplin, Hubertus Hochrein, Henning Lauterbach
Journal: Cancer Research (2019)

Abstract Virus-based vaccines and appropriate costimulation potently enhance antigen-specific T cell immunity against cancer. In the present study, we exploit both innate and adaptive immune responses triggered by recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L against large, established tumors in different combinatory settings. Therapeutic treatment with rMVA-CD40L resulted in the control or eradication of solid tumors in several unrelated tumor models. The expansion of non-exhausted, tumor-specific cytotoxic CD8+ T cells was essential for the therapeutic activity and was partially dependent on CD8α+ cross-presenting dendritic cells. Combination of rMVA-CD40L with PD-1 checkpoint blockade further enhanced the therapeutic activity of MVA virotherapy in colorectal carcinoma. In addition, rMVA-CD40L combined with antibodies targeting Tumor-Associated Antigens (TAA) resulted in increased therapeutic antitumor efficacy against two unrelated tumor models. We describe a translationally relevant therapeutic synergy between viral vaccination and CD40L costimulation. We show strengthened antitumor immune responses when both rMVA-CD40L-induced innate and adaptive immune mechanisms are exploited by combining immunotherapeutic regimes, such as checkpoint blockade and TAA targeting antibodies. This novel immunotherapeutic approach could translate into clinical cancer therapies where ADCC competent TAA targeting antibodies PD-1 checkpoint blockade are employed. Citation Format: Jose Medina-Echeverz, Maria Hinterberger, Raphael Giessel, Barbara Bathke, Ronny Kassub, Giovanna Fiore, Paul Chaplin, Hubertus Hochrein, Henning Lauterbach. Synergistic cancer immunotherapy combination of MVA-CD40L with tumor targeting antibodies or checkpoint blockade to achieve strong antitumor immune responses against large, established tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1468.
Caution About Displaying State-Level Differences in the Prevalence of Autism Spectrum Disorder—Reply
Authors: Guifeng Xu, Lane Strathearn, Wei Bao
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract P93: Heart Rate Variability Analysis using Wavelet Transform to Predict Hemorrhage Severity
Authors: Soo-Yeon Ji, Kevin Ward, Kathy Ryan, Kayvan Najarian
Journal: Circulation (2008)

Introduction: The Pulse Initiative on resuscitation identified the need to develop biosensing for detection of critical limitations of blood flow. The ability to rapidly detect the severity of hemorrhage based on heart rate has been limited. Use of heart rate variability (HRV) is problematic. We used a number of new defined ECG features based on discrete wavelet transformation (DWT) that may be used to estimate blood loss severity. The features are defined based on the energy of detail coefficients of Daubecies DWT. Methods: The performance of DWT was tested using ECG data from a human model of hemorrhage using lower body negative pressure (LBNP). LBNP consisted of a 5-minute rest period (0 mm Hg) followed by 5 minutes of chamber decompression of the lower body to −15, −30, −45, and −60 mm Hg and additional increments of −10 mm Hg every 5 minutes until the onset of cardiovascular collapse. These levels were divided into 3 classes (mild: −15 to −30 mmHg; moderate: −45 to −60 mmHg; severe: over −60 mmHg). These levels correspond to estimated blood losses of 400 –550 cc, 500 –1000 cc and greater than 1000 cc respectively. The ECG DWT features of subjects were used for classification of each ECG recording during volume loss levels. Before classification in order to eliminate redundancy among the features, principal component analysis is applied to the feature set. Machine learning algorithms (SVM, AdaBoost, C4.5) were then applied to analyze the processed features and predict the severity of blood loss. Results: A 219 sample set was used to classify groups by using machine learning algorithms with 10-fold cross validation. C4.5 outperformed other algorithms with a prediction accuracy of 74.4%. The average precision and recall (sensitivity) for the three classes were 77.4% and 76.1%, respectively. In particular, 30 out of 39 cases in the severe class were correctly classified by C4.5. These results required sampling rates of only 125 Hz. Conclusion: This is the first reported use of an ECG analysis method to classify volume loss. The DWT method described may have the ability to rapidly determine the degree of volume loss from hemorrhage providing for more rapid triage and decision making. This may be particularly helpful for remote monitoring of war fighters or for mass casualty care.
Abstract 46: 3D reconstruction and quantitative analysis of histology for prostate cancer
Authors: Pekka Ruusuvuori, Kimmo Kartasalo, Mira Valkonen, Masi Valkonen, Tapio Visakorpi, Matti Nykter, Leena Latonen
Journal: Cancer Research (2019)

Abstract The integration of serial sectioning of tissue, digital whole slide imaging (WSI) and computational reconstruction algorithms enable the examination of histological samples in 3D at subcellular resolution. This allows visualizing and analyzing the imaged sample in its true three-dimensional context, offering a more comprehensive view on its spatial and morphological characteristics than that obtained via typical 2D examination. The advantages of reconstructing 3D models computationally using WSI over direct 3D imaging include the combination of high resolution, large sample sizes and compatibility with existing biochemical techniques such as in situ hybridization, immunohistochemistry and established histological staining and interpretation protocols. For this purpose, we developed a software pipeline to perform routine 3D reconstruction tasks for large image sizes and datasets in a fully automatic manner. The steps in our 3D reconstruction process are image acquisition, alignment of images to a shared coordinate space, and visualization of the reconstructed 3D data. We optimized algorithm selection and computationally intensive hyperparameter tuning using a quantitative benchmarking framework and Bayesian optimization. Further, we applied our existing pipeline for feature based analysis of tissue and extended it into 3D, allowing quantification and visualization of hundreds of features characterizing the tissue. We currently apply this system to characterize prostate cancer tumors. Prostate cancer is a heterogenous, often multifocal disease. In order to understand why and how certain tumor foci develop to a life-threatening disease over others, the tissue growth patterns and evolution of tumors with different genetic backgrounds need to be studied. We use mouse models of prostate cancer to study early tumor development connected to common genetic cancer alterations. By computing hundreds of features from the histology, and studying these in the spatial context, we gain important information of tumor characteristics as well as intra- and intertumor heterogeneity. In the future, we will further scale up the protocol to perform 3D reconstruction for serially sectioned human prostates in the near future. Citation Format: Pekka Ruusuvuori, Kimmo Kartasalo, Mira Valkonen, Masi Valkonen, Tapio Visakorpi, Matti Nykter, Leena Latonen. 3D reconstruction and quantitative analysis of histology for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 46.
Abstract 19374: Utility of Activities of Daily Living to Predict Early Mortality in Patients With Critical Limb Ischemia
Authors: Kimihiro Osada, Atsushi Tosaka, Youiti Sugimura, Toshitake Tamamura, Taisuke Mizumura, Masako Maeda, Yuriko Sato, Ryuma Ishihara, Akira Miyabe, Nozomi Fuse
Journal: Circulation (2017)

Background: Endovascular treatment (EVT) is essential for limb salvage in patients with critical limb ischemia (CLI). On the other hands, previous research reported the presence of CLI was strongly...
CONSORT 2010 statement: extension to randomised crossover trials
Authors: Kerry Dwan, Tianjing Li, Douglas G Altman, Diana Elbourne
Journal: BMJ (2019)

Evidence shows the quality of reporting of randomised controlled trials is not optimal. The lack of transparent reporting impedes readers from judging the reliability and validity of trial findings, prevents researchers from extracting information for systematic reviews, and results in research waste. The Consolidated Standards of Reporting Trials (CONSORT) statement was developed to improve the reporting of randomised controlled trials. The primary focus of the statement was on parallel group trials with two treatment groups. Crossover trials are a particular type of trial for chronic conditions in which participants are randomised to a sequence of interventions. They are a useful and efficient design because participants act as their own control. However, the reporting of crossover trials has been variable and incomplete, which hinders their use in clinical decision making and by future researchers. We present the CONSORT extension to randomised crossover trials, which aims to facilitate better reporting of crossover trials. The CONSORT 2010 checklist is revised for crossover designs, and introduces a modified flowchart and baseline table to enhance transparency. Examples of good reporting and evidence based rationale for CONSORT crossover checklist items are provided.
Psychologic Distress Is Associated with Cancer-Specific Mortality among Patients with Cervical Cancer
Authors: Donghao Lu, Bengt Andrae, Unnur Valdimarsdóttir, Karin Sundström, Katja Fall, Pär Sparén, Fang Fang
Journal: Cancer Research (2019)

Abstract Emerging evidence suggests a role of psychologic factors in the progression of different cancer types. However, it is unclear whether psychologic distress around the time of diagnosis of invasive cervical cancer places patients at a higher risk of cancer-specific mortality, independently of tumor characteristics and treatment modalities. We conducted a nationwide cohort study, including 4,245 patients with newly diagnosed cervical cancer during 2002–2011 in Sweden. Psychologic distress was indicated by a clinical diagnosis of depression, anxiety, or stress reaction and adjustment disorders, or the experience of a stressful life event, including death or severe illness of a family member, divorce, or between jobs, from one year before cancer diagnosis and onwards. We calculated the HRs of cancer-specific mortality among the patients exposed to psychologic distress, compared with unexposed patients, controlling for socioeconomic characteristics and other known prognostic indicators such as tumor and treatment characteristics. We found that patients exposed to psychologic distress had an increased risk of cancer-specific mortality (HR 1.33; 95% CI, 1.14–1.54). The association was primarily driven by distress experienced within one year before or after diagnosis (HR 1.30; 95% CI, 1.11–1.52), but not thereafter (HR 1.12; 95% CI, 0.84–1.49). In summary, our study shows that psychiatric disorders and stressful life events around cancer diagnosis are associated with increased cancer-specific mortality among patients with cervical cancer, independent of tumor characteristics and treatment modality. Significance: These findings support the integration of psychologic screening and intervention in the clinical management of patients with cervical cancer, particularly around the time of cancer diagnosis.