tbuckley/cabot-search huggingface dataset:
Interim Results of a First in Man Study with the Fc-Optimized FLT3 Antibody Flysyn for Treatment of Acute Myeloid Leukemia with Minimal Residual Disease
Authors: Sabine Kayser, Jonas S. Heitmann, Daniela Dörfel, Felicitas Thol, Michael Heuser, Melanie Märklin, Carsten Müller-Tidow, Martin Steiner, Ludger Grosse-Hovest, Gundram Jung, Richard F. Schlenk, Helmut R. Salih
Journal: Blood (2019)
Development of T-Cell Therapy Targeting Hematopoietic Minor Histocompatibility Antigen HA-1
Authors: Artem Pilunov, Dmitrii Romaniuk, Savely Sheetikov, Alexandra Khmelevskaya, Anton Shmelev, Nadia Bykova, Alina Shomuradova, Dmitry Olegovych Kiryukhin, Dmitry Dianov, Grigory Aleksandrovich Efimov, Valery G. Savchenko
Journal: Blood (2019)
Efficacy Analysis of Ruxolitinib in Treatment of 72 Patients with Myelofibrosis in a Chinese Institution
Authors: Yunfan Yang, Zhongqing Zou, Ting Liu, Yongqian Jia, Ting Niu, Huanling Zhu, Yu Wu, Yuping Gong, Hong Chang, Jie Ji, Jian Li, Ling Pan
Journal: Blood (2019)
Randomized, Open-Label, Multicenter, Phase 2 Study of Asciminib (ABL001) As an Add-on to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients with Chronic Myeloid Leukemia in Chronic Phase Who Have Not Achieved a Deep Molecular Response with Frontline Imatinib
Authors: Giuseppe Saglio, Timothy P. Hughes, Jan Geissler, Shruti Kapoor, Anne-Sophie Longin, Ayon Mukherjee, Jorge E. Cortes
Journal: Blood (2019)
B-Cell Maturation Antigen (BCMA) in Systemic Light-Chain Amyloidosis (AL): Association with Disease Activity and Its Modulation with Gamma-Secretase Inhibition
Authors: Amandeep Godara, Ping Zhou, Benjamin Rosenthal, Adin Kugelmass, Denis Toskic, Teresa Fogaren, Cindy Varga, Raymond L Comenzo
Journal: Blood (2019)
Abstract 4067: PD-L1 expression, CD8 cells and MHC-class-1 Beta-2-microglobulin expression in advanced non-small lung cancer
Authors: Lucie Hijmering-Kappelle, Jeroen Hiltermann, Birgitta Hiddinga, Anthonie van der Wekken, Nils 't Hart, Harry Groen, Wim Timens
Journal: Cancer Research (2019)

Abstract Introduction: PD-L1 expression has been approved as predictive biomarker for immune checkpoint inhibitors (ICI) in non-small cell lung carcinoma (NSCLC). In case of lack of PD-L1 expression in tumor biopsies, 8-10% of patients will respond to ICI. However, in case of &amp;gt; 50% PD-L1 tumor expression half of patients show no response. Tumor immune escape phenotypes are characterized by loss of MHC-class-I and a lower grade of CD8 T-cell infiltration, despite upregulation of PD-L1 expression. At least one of the four phenotypes of MHC-class-I and PD-L1 co-expression is considered responsible for non-responsiveness. We investigated the frequency of PD-L1, MHC-class-I β2-microglobulin (β-2M) co-expression and presence of CD8 cells in advanced NSCLC. Methods: Analysis was performed on formalin fixed, paraffin embedded (FFPE) transbronchial or transthoracic tumor biopsies of 27 patients with advanced NSCLC. Immunohistochemistry was performed using Ventana Benchmark Ultra immunostainer. PD-L1 was detected using Ventana PD-L1 (SP263) Assay (CE IVD), CD8 by Ventana CONFIRM anti-CD8 (SP57) antibody and MHC-class I β2-M by Agilent-Dako polyclonal rabbit anti-human beta-2-Microglobulin. PDL1 expression was scored as percentage positive tumor cells according to the manufacturers guideline, β2-M was scored as positive or negative in tumor cells and CD8 cells as low (+), intermediate (++) or high (+++) numbers in tumor or peritumoral stroma. Results: In 27 patients IHC staining was performed. PDL1 expression was scored as &amp;lt;1%, 1-49% and ≥50% in 17, 3, and 7 patients, respectively. PD-L1 positive (&amp;gt;1%) patients had positive β-2M in 10 of 10 cases. PD-L1 negative tumors showed presence of β-2M in 10 of 17 cases. Seven out of 27 cases (26%) were β-2M negative; all of them were PD-L negative cases. Low CD8 score was seen in 7 patients and 2 of these patients have a PD-L1 expression &amp;gt;1% and positive β-2M. Conclusion: In this ongoing study one quarter of advanced NSCLC patients had no tumor MHC-class-1 β-2M expression. In our cohort β-2M negative phenotype was associated with lack of PD-L1 tumor expression. Citation Format: Lucie Hijmering-Kappelle, Jeroen Hiltermann, Birgitta Hiddinga, Anthonie van der Wekken, Nils 't Hart, Harry Groen, Wim Timens. PD-L1 expression, CD8 cells and MHC-class-1 Beta-2-microglobulin expression in advanced non-small lung 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 4067.
IMMU-10. ESTABLISHING EFFECTIVE MODELS FOR IMMUNOTHERAPY IN GBM
Authors: Daniel Zamler, Er-Yen Yen, Takashi Shingu, Jiangong Ren, Cynthia Kassab, Jintan Liu, Amy Heimberger, Jian Hu, Giulio Draetta, Michael Curran
Journal: Neuro-Oncology (2019)

Abstract The introduction of immunotherapies has been paradigm shifting for cancers that were previously a death sentence. However, preclinical/clinical studies on glioblastoma (GBM) have generated mixed outcomes in patients, likely due to its great heterogeneity of immune microenvironment, particularly the myeloid cell populations. Primary patient studies have been limited by a difficulty in performing longitudinal studies, uncontrolled environmental conditions, and genetic variability. There is also, unfortunately, a paucity of mouse models that effectively re-capitulate the immune microenvironment of the human disease. To address these difficulties, we have established the Qk/p53/Pten (QPP) triple knockout mouse model established in our lab. The QPP model uses a cre-lox system to induce Qk deletion on a Pten−/−; p53−/− background which helps NSCs maintain their stemness outside the SVZ in Nes-CreERT2;QkiL/L PtenL/L p53L/L mice, which develops glioblastoma with survival of ~105 days. We have preliminarily assessed the QPP tumors as a faithful model to study the immune response to GBM and found them to recapitulate human GBM with respect to differential response to checkpoint blockade therapy and myeloid and T-cells histopathologically, particularly regarding upregulation of Arginase-1 (Arg1). Arg1 is the canonical marker for tumor-associated macrophages (TAMs), which is a major population of myeloid cells that greatly infiltrate in human GBM, sometimes making up more than ~30% of all GBM cells. Given TAMs’ prevalence in the tumor microenvironment and their upregulation of Arg1 in both human GBM and our QPP model, we are testing whether manipulation of Arg1 will impact TAM function and influence GBM growth. We are also evaluating arginine metabolism in TAMs effect on T cell function in GBM. Lastly, we have developed a genetically engineered mouse model to study the role of Arg1 knockout in a GBM context in-vivo. Our studies suggest that Arg1 plays an important role in GBM immune interaction.
PDTM-42. CROSS-PLATFORM PROFILING OF ctDNA USING ddPCR: STANDARDIZATION OF THE LIQUID BIOPSY FOR PEDIATRIC DIFFUSE MIDLINE GLIOMA
Authors: Daphne Li, Erin Bonner, Stefanie Stallard, Eshini Panditharatna, Tina Huang, Rishi Lulla, Carl Koschmann, Javad Nazarian, Amanda Saratsis
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Pediatric diffuse midline glioma (DMG) with histone H3 mutations (80%), are highly morbid tumors with poor response to therapy. We previously detected H3 mutations in circulating tumor DNA (ctDNA) from CSF derived from children with DMG and high grade glioma. Here, we describe a high-throughput, sensitive and specific approach for H3 mutation detection and quantification in plasma and CSF specimens, validated across multiple centers. METHODS DNA extracted from tissue-validated H3.3K27M specimens (4 tumor, 5 CSF, 4 plasma) and pediatric glioma cell lines (1 wild-type, 1 H3.3K27M) were used to standardize ddPCR workflows. ctDNA extracted from 500uL of CSF or plasma was pre-amplified using sequence-specific primers, then analyzed on RainDance and BioRad ddPCR systems using two sets of custom primers and fluorescent LNA probes (Assays A and B). H3 mutation allelic frequency (MAF) was determined across specimens, and validated through parallel analysis of additional matched H3.3K27M tumor tissue, CSF and plasma specimens (n=3). RESULTS ctDNA processing and detection was standardized across three institutions and two platforms with sensitive, specific and reproducible H3 mutation detection. H3K27M mutations were detected in as little as 0.3-2pg input DNA on both platforms, with comparable MAFs across instruments and assays. RainDance yielded greater overall positive droplet number detection (increased sensitivity). Differences in optimal sample input volume between platforms were circumvented by vacuum concentration or dilution to maintain equal input DNA. Assay A yielded superior specificity so was used for subsequent matched specimen analysis. Mutation detection in plasma, as in previous studies, remained challenging due to low [ctDNA], while CSF analysis yielded reliable results across assays and platforms. CONCLUSIONS We demonstrate the utility of liquid biopsy for identifying H3K27M mutations in plasma and CSF via ddPCR with low starting [DNA], representing a rapid, minimally invasive method for diagnosis and therapeutic monitoring of DMG.
Annals Story Slam - Icebergs
Authors: Samik Doshi
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 November 2019Annals Story Slam - IcebergsFREESamik Doshi, MD, MScSamik Doshi, MD, MScSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0030 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Icebergs "Icebergs," by Samik Doshi, MD, MSc (Duration 5:45)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 November 2019Volume 171, Issue 9Page: SS1 ePublished: 5 November 2019 Issue Published: 5 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Safe Work-Hour Standards for Parents of Children With Medical Complexity
Authors: Theodore E. Schall, Carolyn C. Foster, Chris Feudtner
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
Easix and Modified-Easix Are Early Predictors of Severe Cytokine Release Syndrome and Neurotoxicity in Patients Treated with Chimeric Antigen Receptor T Cells
Authors: Martina Pennisi, Miriam Sanchez-Escamilla, Jessica Flynn, Molly A. Maloy, Mari Lynne Silverberg, Yakup Batlevi, Roni Shouval, Connie Lee Batlevi, Renier J. Brentjens, Sean M. Devlin, Parastoo B. Dahi, Claudia Diamonte, Sergio A Giralt, Elizabeth Halton, Tania Jain, Elena Mead, Maria Lia Palomba, Bianca Santomasso, Craig S. Sauter, Michael Scordo, Gunjan L. Shah, Jae H. Park, Miguel-Angel Perales
Journal: Blood (2019)
The "Intractable" Vesico-vaginal Fistula
Authors: P. Keen
Journal: BMJ (1946)

Lipid staining, using oil red 0 and Sudan black B stain, was carried out on frozen sections of formalin-fixed tumour tissue from 142 cases of malignant lymphoma. Most cases of Burkitt9s tumour contained abundant coarse lipid droplets both within the cytoplasm of the lymphoid cells and within non-neoplastic histiocytes scattered throughout the tumour. Lymphocytic lymphomas contained little stainable fat. Histiocytic and stem-cell lymphomas were almost equally divided between those containing abundant lipid droplets and those devoid of lipid. It is suggested that the demonstration of abundant cytoplasmic lipid droplets may assist in the diagnosis of Burkitt9s tumour although this feature is not in itself diagnostic. The significance of the lipid droplets in the cells of Burkitt9s tumour is discussed in relation to the histogenesis of the tumour.
Tumor-infiltrating lymphocytes (TIL) contain a subset of suppressor CD8+ T cells which can inhibit primary sensitization of tumor-specific effector T cells
Authors: Li-Xin Wang, Suyu Shu, Gregory Plautz
Journal: Cancer Research (2008)

4634  We previously demonstrated that TIL are mixtures of distinct T cell subsets with effector or suppressor function. The two populations can be efficiently segregated by MACS based on differential expression of L-selectin (CD62L). Adoptive transfer of purified and in vitro stimulated CD62L-low effector cells mediated regression of established metastatic tumors, whereas co-transfer of the purified and activated CD62L-high subset abrogated efficacy. Here, we tested whether co-inoculation of naive hosts with tumor cells and suppressor TIL altered the rate of tumor growth or modified the primary sensitization of T cells in tumor-draining lymph nodes. TIL were enriched from a single cell digest of MCA 205 tumors through Percoll gradient and lymphocytes were fractionated into CD62L-high T cells, CD62L-low/CD8+, and CD62L-low/CD4+ subsets using MACS. T cell subsets were activated in vitro using two cycles of immobilized anti-CD3 mAb with IL-2 (4U/ml) plus IL-7 (10ng/ml) as mitogenic factors. The activated CD62L-high T cells, consisting of 95.3% CD8+ and 0% CD4+, accelerated the growth of MCA 205 tumors when they were co-inoculated subcutaneously compared with tumor cells alone. By contrast, co-inoculation of tumor with activated CD62L-low/CD8+ or CD62L-low/CD4+ TIL cells prevented tumor growth. Additional studies demonstrated dramatic differences in therapeutic efficacy between T cells derived from lymph nodes draining tumor alone (TDLN) and tumor mixed with suppressor CD8+ cells. Adoptive transfer of 2 x 107 un-fractionated TDLN cells eliminated 10-day pulmonary metastases whereas 4x107 un-fractionated cells derived from LNs draining tumor mixed with suppressor CD8+ cells had no therapeutic efficacy. More importantly, infusion of 5x106 CD62L-low effector T cells isolated from TDLN can completely mediate the regression of 10-day pulmonary metastases, but infusion of 5x106 CD62L-low T cells isolated from LNs draining tumor mixed with suppressor CD8+ cells had no effect. Interestingly, co-inoculation of suppressor TIL cells with tumor cells inhibited, but did not completely block, the sensitization of host T cells for IFN-γ production upon subsequent in vitro stimulation with tumor antigens. Theses results indicate that TIL with suppressor function develop during progressive tumor growth and such cells can block primary sensitization of tumor-reactive T cells as well as inhibit the function of effector T cells.
The Science and the Art
Authors: Reginald Fitz
Journal: New England Journal of Medicine (1951)

FIFTY years ago the first number of the Boston Medical and Surgical Journal for the new year contained an interesting editorial.In commenting on the truly impressive changes in medicine during the period from 1801 to 1900, the editorial mentioned that one of the greatest was due to the establishment of bacteriology as a science. For, now, it was possible not only to find the cause of diseases that were of bacterial origin but also, by virtue of this knowledge, to prevent their ravages. Certainly, the concept of preventive medicine was a forward stride.Next in importance in the mind . . .
Blinatumomab and Venetoclax for Minimal Residual Disease Relapse in Acute Lymphoblastic Leukemia
Authors: Gregorio Campos-Cabrera, Noe-Benjamin Vega-Tapia, Virgina Campos-Cabrera, Salvador Campos-Cabrera, Jose-Luis Campos-Villagomez, Esther Mendez-Garcia
Journal: Blood (2019)
A Novel and Potent EZH1/2 Dual Inhibitor HM97594 for the Treatment of Hematological Malignancies
Authors: Seung Hyun Jung, DongJin Hong, SeoHee Kim, Jiyoung Hwang, Jooyun Byun, Miyoung Lee, Kyounghwa Koo, Gunwoo Lee, TaeHun Song, SunYoung Lim, Yu-Yon Kim, Hyunjin Park, Yesol Bak, Myoungsil Ko, Sunyoung Jung, Yuri Han, YoungGil Ahn, YoungHoon Kim, KweeHyun Suh
Journal: Blood (2019)
A Phase II Trial of Topical Sodium Nitrite in Patients with Sickle Cell Disease and Leg Ulcers
Authors: Shuo You, Andrew Crouch, Ugochi Olivia Ogu, Clemencia Solorzano, Gracy Sebastian, Markenya Mirander, Giacomo Vinces, Gregory J Kato, Caterina P. Minniti
Journal: Blood (2019)
CSIG-18. NERVE/GLIAL ANTIGEN (NG)2 EXPRESSION IN GLIOBLASTOMA IS REGULATED BY miR-29b-3p
Authors: Beate Schmitt, Anne Boewe, Yuan Gu, Christoph Sippl, Steffi Urbschat, Joachim Oertel, Matthias Laschke, Michael Menger, Emmanuel Ampofo
Journal: Neuro-Oncology (2019)

Abstract Overexpression of NG2 in human glioblastoma cells is associated with an elevated drug resistance and thereby worsens clinical outcome. However, the regulatory mechanisms of NG2 expression are largely unknown. In this study, we identified miR-29b-3p as a posttranscriptional factor of NG2 expression. The basal mRNA levels of miR-29b-3p and NG2 were detected in the NG2-positive glioblastoma cell lines A1207 and U87 by qRT-PCR. The cells were transfected with miR-29b-3p-mimic or scrambled-miR (control) and the expression of NG2 was analyzed by qRT-PCR, flow cytometry and Western blot. Reporter gene analyses of the NG2 promotor region and 3’UTR were performed to study the effect of miR-29b-3p on NG2 expression. Finally, we analyzed the mRNA levels of NG2 and miR-29b-3p in samples from glioblastoma patients. We found that the two NG2-positive glioblastoma cell lines A1207 and U87 are positive for miR-29b-3p. Transfection with miR-29b-3p-mimic reduced NG2 mRNA levels in A1207 (29%±9.9; Mean±SD) and U87 (6%±2.8), resulting in a significantly decreased NG2 protein expression in A1207 (67%±6.4) and U87 (75%±4) when compared to controls. The analysis of the 3’UTR revealed that miR-29b-3p is a posttranscriptional regulator of NG2 expression. Moreover, miR-29b-3p affects the pretranscriptional NG2 expression by diminishing SP-1-dependent NG2 promotor activity. These results were confirmed by the analysis of glioblastoma patient-derived samples, demonstrating that a high NG2 expression is associated with low levels of miR-29b-3p. In conclusion, we identified miR-29b-3p as a crucial regulator of NG2 expression in glioblastoma. Hence, targeting NG2 expression by miR-29b-3p may provide a novel therapeutic strategy to overcome drug resistance in NG2-positive glioblastoma cells.
CMET-28. DECREASED FREQUENCY OF BRAIN METASTASES DUE TO THE USE OF PDL1-INHIBITORS IN RCC
Authors: Mark Damante, Kristin Huntoon, Dante Pezzutti, Thomas Olencki, J Bradley Elder
Journal: Neuro-Oncology (2019)

Abstract INTRO Programmed cell death protein 1 (PD1)-inhibitor, nivolumab, and cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-inhibitor, ipilimumab, have been shown to be efficacious in treatment of metastatic renal cell carcinoma (RCC). Clinical trials utilizing PD1- and CTLA4-inhibitors to treat RCC have demonstrated an increase in survival, however history of brain metastases (BM) has typically excluded patients from these trials. This study evaluated the benefit of these agents in terms of overall survival from RCC diagnosis (OSRCC), from BM diagnosis (OSBM) and frequency of BM occurrence in patients with metastatic RCC. METHODS A retrospective single-center review between 2011–2018 identified 1149 patients treated for RCC. The study group included patients who received immunotherapy and/or non-immunotherapeutic agents during the course of their disease. Data analyzed included demographic information, systemic treatments, OS and status of BM. Two-sided Fisher’s exact test was used to evaluate frequency of BM occurrence. OSRCC and OSBM were assessed using Kaplan-Meier curves and log-rank tests. RESULTS Of 1149 patients, 425 (35.6%) were treated with systemic therapies during their clinical course and divided into two treatment groups: those receiving immunotherapy (n=125) and those receiving non-immunotherapeutic agents (n=300). OSRCC was improved in the immunotherapy group (80.3months 95%CI 58.7–101.9 vs 45.0 95%CI 36.4–53.6, p=0.003), with 1-, 3- and 5-year survival of 93.6%, 74.2% and 62.6%. BM were diagnosed in 113 of 425 patients. Use of immunotherapy was associated with increased OSBM (21.7months vs 8.5, p=0.001). In patients receiving systemic treatment prior to a potential BM diagnosis, BM occurred at a frequency of 8.0% in the immunotherapy group compared to 17.7% for the control (n=100 and n=266 respectively, p=0.021). CONCLUSION Immunotherapy not only improves OSRCC and OSBM, but also decreases the incidence of BM in patients with metastatic RCC. Prospective clinical trials are needed to further evaluate the activity of immunotherapy in treatment of RCC BM.
Acute Inflammation Induces Lactate Release By Bone Marrow Neutrophils That Promotes Their Mobilization Via Endothelial GPR81 Signaling
Authors: Eman Khatib-Massalha, Suditi Bhattacharya, Hassan Massalha, Karin Golan, Orit Kollet, Anju Kumari, Francesca Avemaria, Tomer Itkin, Shiri Gur-Cohen, Abraham Avigdor, Shalev Itzkovitz, Stefan Offermanns, Amiram Ariel, Ronen Alon, Tsvee Lapidot
Journal: Blood (2019)
Long-Term Outcome of Children with Acute Leukemia (AL) Given Alphabeta T and B-Cell Depleted HLA-Haploidentical Hematopoietic Stem Cell Transplantation (TBdepl-haploHSCT)
Authors: Pietro Merli, Daria Pagliara, Mattia Algeri, Federica Galaverna, Giuseppina Li Pira, Valentina Bertaina, Mauro Montanari, Giovanna Leone, Stefania Gaspari, Michele Massa, Valentina Cirillo, Maria Giuseppina Cefalo, Simone Biagini, Marco Becilli, Elia Girolami, Roberto Carta, Annalisa Ruggeri, Franco Locatelli
Journal: Blood (2019)