tbuckley/cabot-search huggingface dataset:
RDNA-09. RADIATION PRIMES SB28 GLIOBLASTOMA FOR RESPONSE TO TGFβ AND PD-L1 NEUTRALIZING ANTIBODIES
Authors: Luis Borrero Garcia, Oliver Reiners, Alba Gonzalez-Junca, Hideho Okada, Mary Helen Barcellos-Hoff
Journal: Neuro-Oncology (2019)

Abstract SB28 is a new luciferase expressing murine glioblastoma (GBM) cell line whose morphology, growth pattern, mutational burden immune infiltrate more closely resembles human GBM and is unresponsive to immunotherapy (OncoImmunology, 7:12, e1501137). Radiation therapy (RT) has the potential to improve response to combinations by multiple means: cell kill that may activate an immune response, effects on vascular system may improve drug access, induction of DNA damage that can be augmented by targeted or chemotherapy, and modulation of the tumor microenvironment. High transforming growth factor β (TGFβ) activity in most GBM, which increases with radiation, likely opposes effective therapy by endorsing an effective DNA damage response and being immunosuppressive. Here evaluated the response of SB28 to radiation in combination with PD-L1 checkpoint blockade or neutralizing TGFβ. Establishment of intracranial tumors was monitored by bioluminescence. We determined that SB28 endogenously activate TGFβ as evaluated by biomarkers. We used radiolabeled antibodies and PET-CT to demonstrate access to intracranial tumors, indicative of a compromised blood-brain barrier. TGFβ neutralizing antibody, 1D11, had little effect on tumor growth compared to mice receiving IgG control antibody (median survival control: 19 days vs 1D11: 20.5 days). A single dose of radiation of 10 Gy delivered to the tumor site increased median survival to 21 day, which was increased to 31 days in mice treated with 1D11. In a second experiment in which the radiation dose was 6 Gy, 1D11 provided no benefit. In contrast, median survival of mice treated with PD-L1 neutralizing antibodies 3 days after being irradiated with 6 Gy demonstrated increased median survival (Control: 18 day; anti-PD-L1 20.5; RT: 25 days; RT + anti- PD-L1: 28 days). Double treatment resulted in 1/7 long term survival and loss of bioluminescence indicative of tumor elimination. Thus, radiation can prime SB28 GBM for response to biological agents.
A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients
Authors: Catherine Meyer-Schwesinger, Nicola M. Tomas, Silke Dehde, Larissa Seifert, Irm Hermans-Borgmeyer, Thorsten Wiech, Friedrich Koch-Nolte, Tobias B. Huber, Gunther Zahner
Journal: Kidney International (2019)
Impact of malnutrition on surgical outcome of patients with ovarian cancer: Results of a prospective study
Authors: P. Skowronek, M. Kuhberg, F. Chen, J. Schwarz, W. Lichtenegger, J. Sehouli
Journal: Journal of Clinical Oncology (2009)

e16564 Background: The purpose of this study was to examine an influence of poor nutritional status on surgical outcome in patients with ovarian cancer. Methods: Data from 152 consecutive patients with histologically confirmed ovarian cancer were prospectively analyzed. Overall 79 suffered from primary and 73 from recurrent disease. All patients received a systematic nutritional assessment prior to cytoreductive surgery and postoperative all complications were analyzed in detail. The Nutritional Risk Score (NRS-2002) was used to identify patients at high nutritional risk (NRS≥3). Intraoperatively, a standardized documentation script (IMO) was applied including tumor localization, surgical interventions, and postoperative residual tumor mass. Results: 29 patients (19%) were classified as malnourished, including 19 (24%) with primary and 10 (14%) with recurrent disease. These patients showed a significantly poorer performance status preoperatively compared to patients with NRS&lt;3 (p &lt; 0.05), which was assessed according to the American Society of Anesthesiologists (ASA). Also an intra-operatively documented tumor spread was significantly more extended in group with NRS≥3 than among patients with NRS&lt;3 (p &lt; 0.05). In malnourished patients complete resection rate was significantly decreased (31% vs. 69%, p &lt; 0.001) and they required more often a colo- or ileostoma (17% vs. 6%, p = 0.041). Malnourished patients suffered more often from post-operative complications (62% vs. 37%, p &lt; 0.05), especially infectious like pneumonia or sepsis. All postoperative mortality events (3 cases) occurred in the malnourished group. Conclusions: Malnourished ovarian cancer patients have significantly more often post-operative complications. They suffer from more extended tumor spread and were less frequently postoperatively tumor-free. Based on our results further prospective trials of preoperative nutritional therapy to improve surgical outcome are warranted. No significant financial relationships to disclose.
IMMU-42. CD8+ T-CELLS MEDIATE IMMUNOEDITING, AND INFLUENCE GENOTYPE, TUMOR ONCOGENIC PATHWAYS AND MICROENVIRONMENT DURING PROGRESSION OF MURINE GLIOMAS
Authors: J Robert Kane, Junfei Zhao, Takashi Tsujiuchi, Brice Laffleur, Aayushi Mahajan, Ganesh Rao, Angeliki Mela, Crismita Dmello, Victor A Arrieta, Li Chen, Daniel Y Zhang, Catalina Lee-Chang, Ting Xiao, Gerson Rothschild, Uttiya Basu, Craig Horbinski, Maciej S Lesniak, Amy Heimberger, Raul Rabadan, Peter D Canoll, Adam Sonabend
Journal: Neuro-Oncology (2019)

Abstract Cancer immunoediting shapes tumor progression by the immunological selection of tumor cell variants that can evade immune recognition. Given the immune evasive cellular diversity of glioblastoma, we hypothesized that CD8+ T-cells mediate immunoediting in this tumor. We evaluated tumor progression in the absence of CD8+ T-cells by depleting this immune cell population in a transgenic murine glioma model. Tumors generated in the absence of CD8+ T-cells developed poorly in recipients with intact immunity, implying a more immunogenic profile. These tumors demonstrated increased chromosomal instability, gene fusions, MAPK signaling, and macrophage infiltration. These observations were stochastic, suggesting variability in the mode of tumor evolution in the absence of this immune effector. MAPK activation was correlated with macrophage recruitment in two transgenic murine models and the human disease. Our results indicate that CD8+ T-cells mediate a strong immunoediting selection in glioblastoma that protect against the hallmarks of cancer and drive immune evasion.
The expression and clinical significance of clusterin and ki67 in cervical cancer
Authors: E. Shrestha
Journal: Journal of Clinical Oncology (2009)

e16554 Background: To explore the expression pattern and clinical significance of the CLU and proliferation indices ki67 in cervical cancer. Methods: 59 cases treated at Cancer Center Sun Yat-sen University during 1989–2006 were enrolled in the study group. The relationship was analyzed for the expressions of CLU and Ki67 with clinical factors. Results: In this study positivity of CLU in cervical SCC, 10% (3/31) cases weak positive, adenocarcinoma 21% (4/19) weak positive in small cell carcinoma 11% (1/9) moderate positive. Control groups, CLU weak positive expression, 21% (3/14) CIN 2–3 and 14% (2/13) normal squamous epithelium.CLU expression found 100% (31/31) normal endocervical glands.The Ki67 in SCC 13% (4/31) cases weak positive and 5% (1/19) adenocarcinoma. All cases small cell carcinoma revealed negative. No significant difference of the CLU expression rate between normal cervical epithelium, CIN II-III and SCC (p = 0.561). No significant difference of CLU expression rate between normal endocervical gland and adenocarcinoma (p = 0.119) as well. In Ki67, there was no significant difference of Ki67 rates between CIN 2–3 and normal squamous epithelium (p = 0.585). No significant difference of Ki67 expression rates between adenocarcinoma and normal squamous epithelium (p = 0.341). The expression of CLU and Ki67 had no correlation with FIGO stage, SCC antigen level, grade of differentiation, deep stromal invasion, and lymph node metastasis. Finally, the expression of CLU and Ki67 was not related to the 5-years DFS rates, and CLU expression was not correlated with Ki67 expression (r s = 0.500, p = 0.391). Conclusions: CLU and Ki67 was in lower rates in cervical cancer, and was not associated with any clinicopathological features. It is suggested that CLU and Ki67 have no distinct role in carcinogenesis. The further larger studies are needed to verify the results of this study. No significant financial relationships to disclose.
PATH-22. MULTIPLEXED IMMUNOHISTOCHEMISTRY AND THE IMMUNE MICROENVIRONMENT OF PRIMARY CENTRAL NERVOUS SYSTEM TUMORS
Authors: Carli Bullis, Seunggu Han, Monika Davare
Journal: Neuro-Oncology (2019)

Abstract Studying the immune microenvironment of primary CNS tumors is critical for the development of novel immunotherapies. At this time, immunotherapy is likely underused and may have a promising future in their treatment. Current limitations in studying the TME of the CNS are the small amount of tissue often available and the laborious, time consuming process of testing for individual markers. Multiplexed immunohistochemistry (mIHC) is a process of evaluating multiple tumor biomarkers on a single piece of tissue. This process has been validated in some non-CNS tumors, including papillary thyroid carcinomas, mesothelioma, and breast and pancreatic tumors, but has not yet been validated in CNS tumors. Our aim in this study is to validate the use of mIHC to study the CNS TME for the development of future immunotherapies. Tissue samples from 5 astrocytomas, 4 neuroblastomas, and 4 medulloblastomas, as well as 2 tissue microarrays (TMAs) were analyzed. The mIHC process was performed as detailed in the paper by Coussens et al. Briefly, the tissues were put through a process of deparaffinization, counterstained with hematoxylin, and incubated with a series of antibodies. They were then scanned and registered into the computer, where color deconvolution and detailed cellular analysis was performed. Two antibody panels were used with the following markers: 1) myeloid panel: CD45, CD66b, CD68, CD163, CSF1, DCLAMP, DCSIGN, MHCII, PANCK, PDL1; 2) lymphoid panel: TBET, CD3, CD8, CD45, GATA3, NKP46, PANCK, PD1, PDL1, RORGT. Populations of macrophages, microglia, T-cells, natural killer cells, and tumor cells were all identified. Macrophages were CD45+CD66b-CD68+. Microglia were CD45+CD66-CD68+CSF1+. Granulocytes were CD45+CD66b+. T-cells were CD45+CD3+. Natural killer cells were CD45+CD3-NKP46+. Tumor cells were CD45-PDL1+. We conclude that mIHC is an efficient and novel way of studying CNS TME. This may have implications in the development of future immunotherapies.
Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering
Authors: Kai Kang, Jun-bo Chuai, Bao-dong Xie, Jian-zhong Li, Hui Qu, Hua Wu, Shao-hong Fang, Jin-jin Cui, Li-li Xiu, Jin-cheng Han, Tian-hui Cao, Xiao-ping Leng, Hai Tian, Ren-Ke Li, Shu-lin Jiang
Journal: Biomaterials (2019)
Effects of Exercise During Long-term Support With a Left Ventricular Assist Device
Authors: Brian E. Jaski, Joseph Kim, Richard S. Maly, Kelley R. Branch, Robert Adamson, Laurence K. Favrot, Sidney C. Smith, Walter P. Dembitsky
Journal: Circulation (1997)

Long-term implantation of a left ventricular assist device (LVAD) may be a future alternative treatment for end-stage heart failure. The objective of the present study was to determine the hemodynamic effects of supine bicycle exercise and functional capacity during upright treadmill exercise in 10 patients after LVAD implantation placed for refractory heart failure as a bridge to cardiac transplantation.With supine bicycle exercise, 46 +/- 25 days after device placement, heart and LVAD rates increased in parallel from 87 +/- 12 to 117 +/- 14 bpm and 82 +/- 18 to 107 +/- 21 bpm, respectively. Peak O2 consumption was 8.2 +/- 1.7 mL O2.kg-1.min-1. Fick Systemic blood flow rose from 5.0 +/- 1.2 to 7.8 +/- 2.5 L/min. Right atrial and pulmonary capillary wedge pressures increased from 6 +/- 4 and 5 +/- 3 mm Hg to 12 +/- 5 and 13 +/- 8 mm Hg, respectively. End-diastolic left ventricular dimension increased from 3.9 +/- 1.3 to 4.8 +/- 1.6 cm; however, right ventricular dimension decreased from 3.2 +/- 1.0 to 2.3 +/- 0.9 cm. With upright treadmill exercise, peak O2 consumption was 14.1 +/- 2.9 mL O2.kg-1.min-1.This study indicates that exercise during long-term LVAD support is safe and is not limited by right heart decompensation. It also justifies a larger study to examine how exercise after LVAD implantation compares with that after cardiac transplantation.
Clingen Coagulation Factor Deficiency Variant Curation Expert Panel: Meeting the Need for Recommendations to Curate Variants in the Coagulation Factor Genes
Authors: Shruthi Mohan, Kristy Lee, Manuel Carcao, Bhavya S Doshi, Kate Downes, Geoff Kemball-Cook, Frank Leebeek, Jamie McCreery, Connie H. Miller, Amanda B Payne, Valerie Trapp-Stamborski, Barbara A. Konkle, Keith Gomez
Journal: Blood (2019)
Genomic Landscape and Risk-Stratification for De Novo Acute Myeloid Leukemia with Normal Cytogenetics and No NPM1 or FLT3-itd Mutation
Authors: Ya-Lan Zhou, Li-Xin Wu, Robert Peter Gale, Zi-Long Wang, Jin-Lan Li, Hao Jiang, Qian Jiang, Bin Jiang, Shan-Bo Cao, Feng Lou, Ying Sun, Chengcheng Wang, Ting Li, Yan-Rong Liu, Yu Wang, Ying-Jun Chang, Lan-Ping Xu, Xiaohui Zhang, Kaiyan Liu, Guorui Ruan, Xiaojun Huang
Journal: Blood (2019)
Epigenetic reprogramming and chromatin accessibility in pediatric diffuse intrinsic pontine gliomas: a neural developmental disease
Authors: Flor M Mendez, Felipe J Núñez, Maria B Garcia-Fabiani, Santiago Haase, Stephen Carney, Jessica C Gauss, Oren J Becher, Pedro R Lowenstein, Maria G Castro
Journal: Neuro-Oncology (2019)

Diffuse intrinsic pontine glioma (DIPG) is a rare but deadly pediatric brainstem tumor. To date, there is no effective therapy for DIPG. Transcriptomic analyses have revealed DIPGs have a distinct profile from other pediatric high-grade gliomas occurring in the cerebral hemispheres. These unique genomic characteristics coupled with the younger median age group suggest that DIPG has a developmental origin. The most frequent mutation in DIPG is a lysine to methionine (K27M) mutation that occurs on H3F3A and HIST1H3B/C, genes encoding histone variants. The K27M mutation disrupts methylation by polycomb repressive complex 2 on histone H3 at lysine 27, leading to global hypomethylation. Histone 3 lysine 27 trimethylation is an important developmental regulator controlling gene expression. This review discusses the developmental and epigenetic mechanisms driving disease progression in DIPG, as well as the profound therapeutic implications of epigenetic programming.
Progression of Follicular Lymphoma within 24 Months of First Treatment (POD -24) As a Predictor of Overall Survival - a Single Center Retrospective Analysis
Authors: Guy Bitansky, Elena Vasilev, Maya Zlotnick, Elena Ribakovsky, Ohad Benjamini, Arnon Nagler, Abraham Avigdor, Meirav Kedmi
Journal: Blood (2019)
Dual Targeting of Mitochondrial Unfolded Protein Response and BCL2 in Acute Myeloid Leukemia
Authors: Ran Zhao, Sarah Zarabi, Takenobu Nii, Ondrej Halgas, Yulia Jitkova, Vivian Ruvolo, Lauren Heese, Yuki Nishida, Gautam M. Borthakur, Kensuke Kojima, Martin Stogniew, Wolfgang Oster, Emil Pai, Eric Davis, Hagop M. Kantarjian, Aaron D Schimmer, Michael Andreeff, Jo Ishizawa
Journal: Blood (2019)
Whole Body Diffusion Weighted MRI (WB DWI) for the Management of Multiple Myeloma: High Concordance between MRI Diffuse Pattern and BONE Marrow Plasma CELL Infiltration RATE
Authors: Silvia Mangiacavalli, Zacchino Michela, Virginia Valeria Ferretti, Claudio Salvatore Cartia, Giovanni Savietto, Pietro Benvenuti, Marzia Varettoni, Sara Rattotti, Brociner Marco, Gabriele Merati, Luca Arcaini
Journal: Blood (2019)
NIMG-05. THE T2-FLAIR MISMATCH SIGN IN IDH-MUTANT ASTROCYTOMAS - IS THERE AN ASSOCIATION WITH FET PET UPTAKE?
Authors: Norbert Galldiks, Jan-Michael Werner, Gabriele Stoffels, Martin Kocher, Caroline Tscherpel, Rajan Jain, Nadim Shah, Gereon Fink, Karl-Josef Langen, Philipp Lohmann
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The purpose of this study was (i) to assess the reproducibility of the previously described T2-FLAIR mismatch sign as a highly specific MR imaging marker in non-enhancing IDH-mutant, 1p/19q non-codeleted lower-grade gliomas (LGG) of the WHO grades II or III, and (ii) its association with the uptake of the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) in PET to further metabolically characterize that sign, which is currently poorly understood. METHODS Consecutive MRI and dynamic FET PET scans (n=134) from newly diagnosed and neuropathologically confirmed IDH-mutant LGG (n=65) and IDH-wildtype gliomas as control group (n=69) were evaluated by two independent raters to assess presence/absence of the T2-FLAIR mismatch sign as well as FET uptake. Interrater agreement was assessed using Cohen’s kappa (κ), as well as diagnostic performance (i.e., positive/negative predictive value; PPV, NPV) of the T2-FLAIR mismatch sign to identify IDH-mutant astrocytomas. RESULTS In the LGG group, 13 patients (20%) had a T2-FLAIR mismatch sign, which could be identified with a substantial interrater agreement (κ=0.75). In contrast, that sign was absent in IDH-wildtype gliomas. All 13 cases that were positive for the T2/FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (PPV=100%, NPV=57%). Interestingly, compared to IDH-mutant gliomas without the T2-FLAIR mismatch sign, the sign was significantly (P=0.027; 10 of 13 patients) associated with a negative FET PET scan (i.e., 5 tumors with indifferent FET uptake comparable to the background activity, or FET uptake below background activity (photopenic defect) in 5 tumors). CONCLUSIONS With a robust interrater agreement, our findings are in line with previously reported findings regarding the T2-FLAIR mismatch sign. Additionally, the T2-FLAIR mismatch sign seems to be significantly related with a lack of increased FET uptake in PET, which may help to further characterize patients with that sign. Notwithstanding, the clinical relevance of this imaging constellation warrants further investigation.
The Revolution in Anaesthesia
Authors: J. Halton
Journal: BMJ (1947)

lie was a capable sketcher tind pastel painter, and some of his portraits of-his father, mother, and friends are shown.Striking mo-dels illustrate the preparation of antisera in laboratories in France's Oriental possessions, and enlarged photographs and dis- play panels show phically the signifiCanCe 0 is diovenes of micro-organisms and irmuniiy factors.The Wellcome Museum exhibit includes crystals and diagrams showing the foundations of stereochemistry which Pasteur laid.Much of his oijginal apparatus in on view., together with some of his personal possessions.
Differential Metabolomics and Lipidomics of Hypoxic/Hypocapnic Long-Term Stored Red Cells Associate with Improved 24-Hour Recovery after Transfusion
Authors: Tatsuro Yoshida, Angelo D'Alessandro, Xiaoyun Fu, Travis Nemkov, Davide Stefanoni, Michael Dioguardi, Neeta Rugg, Shawnagay Nestheide, William Iselin, Andrew Dunham, James C. Zimring, Jose A Cancelas
Journal: Blood (2019)
Curriculum in Chronic Lymphocytic Leukemia Narrows the Educational Gaps of the Oncology Healthcare Team
Authors: Lauren Willis, Lisa Brauer, Emily S Van Laar, Patrick Kugel, Katie S Lucero, John N. Allan, Farrukh T. Awan, Danielle M. Brander, Jonathon B. Cohen, Jacqueline C Barrientos
Journal: Blood (2019)
Pediatric Acute Promyelocytic Leukemia in Brazil: Epidemiology, Molecular Features, and Importance of GST-Theta 1 in Chemotherapy Response and Outcome
Authors: Francianne G. Andrade, Suellen V. M. Feliciano, Ingrid Sardou-Cezar, Gisele D. Brisson, Filipe V. S. Bueno, Danielle T. Vianna, Eugênia Terra-Granado, Ilana Z. Renault, Marceli O. Santos, Elda P. Noronha, Joseph L. Wiemels, Maria S. Pombo-de-Oliveira
Journal: Blood (2019)
Renal Metastasis From Neuroblastoma Shown on MIBG Imaging
Authors: Zhe Wen, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2019)

Abstract A 6-year-old girl with high-risk neuroblastoma underwent a 123 I-MIBG scan to monitor the disease status. In addition to the known lesion in the right retroperitoneal region, there were additional foci of increased activity in the right upper quadrate of the abdomen, which were not typical bowel activity. SPECT/CT images located the activity in the cortex of the lower pole of the right kidney, which was partially calcified. Subsequent biopsy confirmed neuroblastoma metastasis to the right kidney, which is extremely rare.
Married Quarters in Hospital
Authors: W. R. Hain
Journal: BMJ (1963)

general surgery to one of the " special " subjects should be more flexible.Greater latitude should be given to medical education committees to increase registrar establishment as necessary in one or other specialty.The overall picture of establishment should be con- stantly under review.Better liaison should be established between general surgery, medicine, and the " special " subjects, so that there would be no difficulty in the registrar obtaining his basic training.4. The teachers of the " special " subjects should consider whether their teaching methods could not be improved to make the " special " subjects more attrac- tive, and whether rotating house officer appointments of two months' duration could not be instituted so that the graduate could gain knowledge of three of the special subjects during a six months' term of office.Such a post should prove of great value to the general practi- tioner.This latter suggestion could apply just as well in larger peripheral hospitals as in a teaching hospital.5. All posts should be regarded as instructional, and junior staff posts should not be considered as appoint- ments to relieve the consultant of routine and frustrating aspects of his work.-Iam, etc.,
A man with weak limbs
Authors: Shing Fung Lee, Pui Lam Yip, Frank Chi Sing Wong
Journal: BMJ (2019)

A 58 year old man presented with one week of progressive right sided weakness and headache. He drank approximately 7 units of alcohol a week and had stopped smoking cigarettes 20 years ago (10 pack year history). He had no recent head injuries and took no medications or recreational drugs. He had no fever, weight loss, or night sweats and was fully alert. He had no signs of meningism or papilloedema and was afebrile with normal observations. Power in his right upper and lower limbs was of Medical Research Council grade 4/51 and he had …
From the authors
Authors: C. E. Kuehni, G. Michel, M-P. F. Strippoli, M. Zwahlen, A. M. Brooke, J. Grigg, M. Silverman
Journal: European Respiratory Journal (2007)

We would like to thank S.S. Cunha and P.J. Newcombe for their discussion of our paper. Although we generally agree with most arguments raised by the two authors, we want to emphasise that their points did not accurately represent our carefully worded statements.

First, using different scenarios, we have shown how estimates of the prevalence of wheeze differ if understanding of the word “wheeze” by parents is taken into account 1. In our paper, table 4 shows that misunderstanding of “wheeze” does …
Blockade of CD47-Sirpα Interactions Improved Myeloid Effector Cell Mediated Lymphoma Cell Killing By the HLA-DR Antibody Apolizumab
Authors: Judith Petersen, Thies Rösner, Max Kölling, Katja Klausz, Christian Kellner, Andreas Humpe, George J Weiner, Denis Martin Schewe, Matthias Peipp, Thomas Valerius
Journal: Blood (2019)