tbuckley/cabot-search huggingface dataset:
NIMG-75. RADIOMIC FEATURES LOCALIZED TO STEREOTACTIC BIOPSY LOCATIONS CAN CAPTURE EGFR PRESENCE IN GLIOBLASTOMA
Authors: Marwa Ismail, Ramon Correa, Kaustav Bera, Anas Saeed Bamashmos, Volodymyr Statsevych, Prateek Prasanna, Niha Beig, Anant Madabhushi, Manmeet Ahluwalia, Pallavi Tiwari
Journal: Neuro-Oncology (2019)

Abstract PURPOSE Epidermal growth factor receptor amplification (EGFRamp), occurs in &gt;60% of Glioblastoma (GBM) patients, and can predict response to alkylating chemotherapy. However, due to high genetic instability in GBM, a significant caveat to sampling EGFRamp during biopsy, is that reliable identification of its presence is dependent on the site of the biopsy, and may vary throughout the tumor. Previous studies have employed radiomics (computerized feature extraction) from the entire tumor to characterize EGFRamp presence. Our work is based on the rationale that radiomics measurements from stereotactic biopsy locations on Gd-T1w MRI, may allow to build accurate training models for predicting EGFRamp compared to using radiomic features from the entire tumor. METHODS MRI scans from 78 GBM subjects (33 EGFRamp, 45 non-amp) were obtained, of which 54 subjects were used for training while 24 were used for testing. Stereotactic biopsy locations were mapped by co-registering CT-images with MRIs (confirmed by two radiologists). For each biopsy region (1-cm diameter sphere), gradient entropy features and gender information were used to train a discriminant analysis classifier, on a voxel-wise manner. Our training model also included per-voxel spatial probabilities that were obtained by building atlases to quantify frequency of occurrence of EGFRamp and non-amp cases. All of these features were then used within the test set to predict EGFR status. RESULTS The model achieved a training accuracy of 81.4%, correctly classifying 17/23-amp, 27/31 non-amp cases. Accuracy on test set was 79.2% (7/10 amp, 12/14 non-amp cases correctly classified). Extracting features from the entire tumor achieved a training accuracy of 74% (17/23-amp, 23/31 non-amp cases correctly classified), and a testing accuracy of 70.8% (6/10 amp, 11/14 non-amp cases correctly classified). CONCLUSION Radiomic features, trained using features from only the stereotactic biopsy locations, may be more reliable in training models to predict EGFR mutation in GBM.
PDTM-33. EUROPEAN GENETIC ANCESTRY ASSOCIATED WITH RISK OF CHILDHOOD EPENDYMOMA
Authors: Chenan Zhang, Quinn Ostrom, Helen Hansen, Adam de Smith, Cassie Kline, Carol Kruchko, Zalman Vaksman, Sharon Diskin, Jill Barnholtz-Sloan, Vijay Ramaswamy, Michael Taylor, Melissa Bondy, Catherine Metayer, Joseph Wiemels, Kyle Walsh
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Ependymoma is a histologically-defined central nervous system tumor most commonly occurring in children. Incidence differs by race/ethnicity, with individuals of European ancestry at highest risk. No large-scale genomic analyses of ependymoma predisposition have been conducted to date. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk. METHODS In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among admixed Hispanic and African-American subjects and estimated European substructure among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local European ancestry. We also re-analyzed CBTRUS data to examine subtype-specific differences in ependymoma incidence across racial/ethnic groups. RESULTS Each 20% increase in European ancestry was associated with 1.31-fold greater odds of ependymoma among Hispanic and African-American subjects (95% CI: 1.08–1.59, Pmeta=6.7×10–3). Among non-Hispanic whites, European ancestral substructure was also significantly associated with ependymoma risk. Local admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and genotype association analysis in the region identified an association upstream of R-spondin 4 that survived Bonferroni correction (P=2.2x10-5) but was not validated in an independent set of posterior fossa type A (PF-EPN-A) patients. In complementary CBTRUS analyses, American Indian/Alaskan Natives were at reduced risk relative to non-Hispanic whites (RR=0.64, 95% CI:0.46–0.87), as were African-Americans (RR=0.67, 95% CI:0.60–0.74) and Asian/Pacific Islanders (RR=0.86, 95% CI:0.73–1.00). Although overall ependymoma rates were similar in U.S. Hispanics (RR=0.96, 95% CI:0.88–1.05), lower rates were observed for myxopapillary ependymoma and other spinal ependymoma. CONCLUSION Inter-ethnic differences in ependymoma risk vary by histopathologic and potentially molecular subgroup, and are recapitulated in the genomic ancestry of ependymoma patients.
Clinical Validation of the Myelofibrosis Transplant Scoring System in an Independent Series of Myelofibrosis Patients Undergoing Allogeneic Hematopoietic Transplantation
Authors: Juan-Gonzalo Correa, Rosalía de la Puerta, Ana Benzaquen, Jorge Mora, Ana A. Martín, Nieves Dorado, María Laura Fox, Adolfo Saez-Martin, Montserrat Rovira, Elvira Mora Castera, Rafael Hernani, Albert Esquirol, Ignacio Gómez-Centurión, Veronica Aguilar-Perea, Valentin Garcia Gutierrez, Santiago Osorio-Prendes, Fermin Sanchez-Guijo, Irene García-Cadenas, Jose Luis Pinana, Alberto Alvarez-Larrán, Rodrigo Martino, Carlos Solano, Francisco Cervantes, Juan Carlos Hernandez Boluda
Journal: Blood (2019)
Complementary Base Editing Approaches for the Treatment of Sickle Cell Disease and Beta Thalassemia
Authors: Ling Lin, Adrian P. Rybak, Conrad Rinaldi, Jonathan Yen, Yanfang Fu, Elsie Akrawi, Sarah Smith, Scott J. Haskett, Minerva E. Sanchez, Yeh-Chuin Poh, Michael S. Packer, Nicole M. Gaudelli, Manmohan Singh, Giuseppe Ciaramella, Dana N. Levasseur
Journal: Blood (2019)
Sensitization to Low Dose 5-Fluorouracil
Authors: Rudolf E. Falk, Mark Hardy, Leonard Makowka, Julita Teodorczyk-Injeyan, Judith A. Falk
Journal: Journal of Clinical Investigation (1982)

This report describes a novel method of immunochemotherapy; the active immunization to the drug 5-fluorouracil (5-FU) with enhanced antitumor activity resulting from its subsequent systemic administration. Two metastasizing carcinomas in the Fischer strain (F344) rat have been used: a chemically induced bladder carcinoma (FBCa) and a spontaneous mammary adenocarcinoma (MACa). Both tumors grow rapidly and result in 100% mortality within 10 wk of implantation. Neither tumor is sensitive to systemic 5-FU alone. Intradermal sensitization to 5-FU before FBCa tumor implantation, followed by 5-FU administered systemically, resulted in significant tumor regression and improvement in survival with eradication of all tumor and cure in 20% of animals. A similar antitumor effect was observed with the MACa. A comparable drug effect was observed when methotrexate sensitization was given before FBCa implantation followed by systemic MTX. Specificity to the sensitizing drug was demonstrated by the lack of effect of sensitization with either 5-FU or MTX unless followed by systemic therapy with the requisite sensitizing agent. Sensitization to 5-FU has also been assessed after FBCa implantation followed by resection of the local tumor. Resection was performed after distant tumor metastases had occurred, and was followed by systemic 5-FU therapy. Whereas tumor resection alone failed to cure any animal, sensitization to 5-FU increased cure rate fourfold over animals receiving systemic 5-FU alone. Antibody to 5-FU in the sera of sensitized animals has been suggested by an immunoenzymatic staining technique and its specificity confirmed in a radioimmunoassay. It is postulated that a combination of the systemic agent and the antibody elicited to it by sensitization produces the significant antitumor effect observed. The antitumor effect observed with this new approach to immunochemotherapy warrants further experimental and clinical study.
Recurrent Gene Mutations in Pediatric Patients with AML By Targeted Sequencing ―the Jccg Study, JPLSG AML-05―
Authors: Taeko Kaburagi, Genki Yamato, Norio Shiba, Kenichi Yoshida, Yusuke Hara, Yuichi Shiraishi, Kentaro Ohki, Manabu Sotomatsu, Hirokazu Arakawa, Hidemasa Matsuo, Akira Shimada, Tomohiko Taki, Nobutaka Kiyokawa, Daisuke Tomizawa, Keizo Horibe, Satoru Miyano, Takashi Taga, Souichi Adachi, Seishi Ogawa, Yasuhide Hayashi
Journal: Blood (2019)
PF-114: A 4th Generation Tyrosine Kinase-Inhibitor for Chronic Phase Chronic Myeloid Leukaemia Including BCRABL1T315I
Authors: Anna G. Turkina, Olga Vinogradova, Elza Lomaia, Evgeniya Shatokhina, Oleg A. Shukhov, Ekaterina Yu. Chelysheva, Dzhariyat Shikhbabaeva, Irina Nemchenko, Anna Petrova, Anastasiya Bykova, Andrey Zaritskey, Nadia Siordia, Vasily Shuvaev, Jorge E. Cortes, Robert Peter Gale, Michele Baccarani, Oliver Ottmann, Ilya Mikhailov, Fedor Novikov, Veronika Shulgina, Ghermes Chilov
Journal: Blood (2019)
Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with GATA2-Related Myelodysplastic Syndrome
Authors: Rachel Bortnick, Marcin Wlodarski, Valerie de Haas, Barbara De Moerloose, Michael Dworzak, Henrik Hasle, Riccardo Masetti, Jan Stary, Dominik Turkiewicz, Marek Ussowicz, Michael H. Albert, Peter Bader, Victoria Bordon, Alexander Claviez, Bernhard Kremens, Jörn Sven Kühl, Arjan C. Lankester, Ingo Müller, Herbert Pichler, Petr Sedlacek, Karl-Walter Sykora, Marco Zecca, Gudrun Göhring, Franco Locatelli, Peter Noellke, Charlotte M. Niemeyer, Brigitte Strahm
Journal: Blood (2019)
TMIC-23. A SEQUENTIAL IMAGING STRATEGY TO STUDY ONCOLYTIC VIRUS INFILTRATION, REPLICATION AND TUMOR MICROENVIRONMENTAL PERTURBATIONS, EX VIVO
Authors: Munisha Smalley, Saravanan Thyiagarajan, Misti Jain, Douglas Best, Suniti Saha, Komal Prasad, Emiliy Alonzo, Erin Hathaway, Kira Henderson, Antonio Chiocca, Sean Lawler, Aaron Goldman
Journal: Neuro-Oncology (2019)

Abstract The use of oncolytic viruses (OV) as therapeutic agents for glioblastoma multiforme (GBM) is an emerging clinical focus. OV have the potential to reinvigorate the immune contexture in the tumor microenvironment (TME). However, current pre-clinical models are insufficient to study the immune effects of OV. Here, we describe an imaging approach using a human ex-vivo platform to study the effects of OV on tumor-associated immune cells in GBM. Using the rQNestin34.5v.1 herpes simplex virus (rQNestin) we treated human GBM ex-vivo, incorporating autologous patient-derived peripheral-blood mononucleated cells and whole tissue fragments. We treated GBM (n=10) with rQNestin, capable of expressing GFP, and profiled GFP expression as a proxy for replication. We analyzed serial sections of H&amp;E, HSV-1, and multiplex immunohistochemistry (mIHC) to investigate the impact of rQNestin on the spatial context of the immune compartment. Cell Signaling Technology antibodies, CD3e (D7A6E™,ID:85061), CD68 (D4B9C,ID:76437), CD11c (D3V1E,49420), MHC-Class II ((HLA-DRB)LGII-612.14,NA) and Pan-keratin (C11,4545) were optimized for identifying intratumoral T-cells (CD3e+), macrophages (CD68) and dendritic cells (CD11c+MHCII+) in relation to the surrounding tissue architecture (pan cytokeratin). Using the serial-section imaging approach, we overlaid infiltration and replication of rQNestin. Additionally, strategic sectioning identified dynamic spatial alterations in the immune compartment, via visualization of the tumor-immune interface with indications of infiltration and replication. Quantitative pathology showed dynamic re-arrangement of immune cells - in spatial orientation, quantity and localization, relative to the tumor, under rQnestin pressure, ex-vivo. Here, we report that our ex-vivo human tumor model can be used to evaluate the effects of OV in the TME – not only viral replication but also the direct effect on the immune compartment. In particular, we can assess changes in immune subsets post-OV treatment in a 3-D manner, therefore providing greater insight into their spatial arrangement and distribution. These findings could develop our understanding of anti-tumor OV mechanisms.
Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data
Authors: Richard F. Spaide, Glenn J. Jaffe, David Sarraf, K. Bailey Freund, Srinivas R. Sadda, Giovanni Staurenghi, Nadia K. Waheed, Usha Chakravarthy, Philip J. Rosenfeld, Frank G. Holz, Eric H. Souied, Salomon Y. Cohen, Giuseppe Querques, Kyoko Ohno-Matsui, David Boyer, Alain Gaudric, Barbara Blodi, Caroline R. Baumal, Xiaoxin Li, Gabriel J. Coscas, Alexander Brucker, Lawrence Singerman, Phil Luthert, Steffen Schmitz-Valckenberg, Ursula Schmidt-Erfurth, Hans E. Grossniklaus, David J. Wilson, Robyn Guymer, Lawrence A. Yannuzzi, Emily Y. Chew, Karl Csaky, Jordi M. Monés, Daniel Pauleikhoff, Ramin Tadayoni, James Fujimoto
Journal: Ophthalmology (2019)

To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data.
GENE-29. INCREASED COPY NUMBER BURDEN (CNB) IS ASSOCIATED WITH GRADE IN IDH-MUTANT, 1p/19q-CODELETED OLIGODENDROGLIOMAS.
Authors: Desmond Brown, Seiji Yamada, Thomas Kollmeyer, Paul Decker, Matthew Kosel, Corinne Praska, Aditya Raghunathan, Caterina Giannini, Daniel Lachance, Jeanette Eckel-Passow, Robert Jenkins
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Oligodendrogliomas are classified as either WHO grade II or III depending on histologic features. Grade often influences treatment decisions. However, there is variability in patient outcome within tumors of similar grade. We hypothesized that copy number burden (CNB) and specific copy number variants (CNV) might be associated with oligodendroglioma grade and prognosis. METHODS Copy number array analyses were performed on 285 molecular oligodendrogliomas (IDH-mutant, 1p/19q-whole arm-codeleted) from the Mayo Clinic internal and consult neuropathology practice and 167 TCGA molecular oligodendrogliomas. CNB was defined as the total number of copy number alterations. The association of CNB and CNV with grade and overall survival (when available) was assessed. All Mayo and TCGA data were evaluated using the ChAS software suite (Thermo- Fisher) and blindly reviewed by a clinical cytogeneticist (RBJ). RESULTS The mean CNB was 5.0 and 10.4 in the Mayo WHO grade II and III oligodendrogliomas, respectively (p = 5.4 x 10–17). Among the TCGA WHO grade II and III oligodendrogliomas the mean CNB was 4.4 and 5.3, respectively (p = 0.034). Common CNVs (occurring in at least 5% of cases) were -4/4q-, +8/8q+, -9/9p-/cnLOH 9p, +11/11q+, -14/14q-, -15 and -18/18q-. Of these, -9/9p-/cnLOH 9p was significantly associated with higher grade in both the Mayo and TCGA cohorts (p = 8.3 x 10-10 and 0.018, respectively). In the TCGA cohort the presence of &gt;10 CNVs or +11/11q+ was associated with a poorer survival (p = 0.016 and 0.006, respectively). CONCLUSIONS CNB is significantly associated with WHO grade in IDH-mutant, 1p/19q co-deleted oligodendrogliomas. The presence of a significantly elevated CNB in some WHO grade II tumors may be suspicious for the presence of unappreciated grade III histologic features. Longer follow-up will be necessary to determine if CNB or single CNVs are associated with survival.
Cancer and the Community
Authors: R. W. Raven
Journal: BMJ (1953)

county rates were around 20% below.By way of contrast, breast cancer mortality in the 29 years showed no important differences between these areas, that in North Wales being 5% below average, and that in the West Midlands 5% above.Justification for Research into Environmental Factors Suggestions have been made that doctors in Wales tend to certify cancer of the stomach as the cause of death when- ever haematemesis or obscure gastric symptoms make it seem feasible, and often with insufficient justification.No evidence that such a practice is in fact more prevalent in Welsh than in English rural areas has been produced.The relative excess is smaller at ages over 65 than in mid-life; and no compensating deficiency can be found in the group of deaths attributed to those conditions likely to be' mistaken for gastric cancer, such as peptic ulcer, cancer of the liver, pancreas, and colon, other diseases of the stomach, and pernicious anaemia.Inquiries from a first sample of 100 certifiers of deaths said to be due to stomach cancer in North Wales show that there was necropsy, biopsy, opera- tion, or x-ray evidence for 50%, compared with 65% of 100 deaths so certified in rural districts of Cheshire and Lan- cashire, and about 60% in the large towns other than Liver- pool.If half the cases in which the diagnosis is unsup- ported by any of these tests are rejected, the North Wales rates would be reduced by a quarter and the Cheshire-Lancashire rates by a sixth, correcting the ratio between them to 1.8 at ages under 65 and 1.6 at ages over 65.These preliminary statistical tests justify the Cheshire and North Wales Branch of the British Empire Cancer Cam- paign in-their belief that there exists a real, phenomenon to be explained, and in their determination to investigate race and residence, work and workplace, soil, air, and water, food, drink, and every conceivable vehicle of carcinogenic substances, or co-carcinogenic irritants.With this line of approach the community of the research area seem to be very much in sympathy.It is something they can under- stand and welcome because it holds out some hope of pre- vention, which from the patients' standpoint would be so much better than cure by surgery or radiation, no matter how skilful or high-powered that may be.
Left Atrial Enlargement Could Be Detected on Extended Computed Tomography Angiography Within Initial Stroke Assessment—Reply
Authors: Jeff S. Healey, David J. Gladstone, Robert G. Hart
Journal: JAMA Neurology (2019)

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High Incidence of Hematopoietic Stem Cell Mosaicism in Fanconi Anemia.
Authors: Jakub Tolar, Margaret L. MacMillan, Sat Dev Batish, Cindy Eide, Yeva Flit, Stella M. Davies, Bruce R. Blazar, Arleen D. Auerbach, John E. Wagner
Journal: Blood (2006)
EXTH-29. GALECTIN-3 AS A POTENTIAL THERAPEUTIC TARGET IN RECURRENT ATYPICAL AND MALIGNANT MENINGIOMA
Authors: Arabinda Das, Jaime Martinez Santos, Indira Kanginakudru, Daniel G McDonald, Libby Kosnik Infinger, William Vandergrift III, Abhay Varma, Kenneth N Vanek, Scott Lindhorst, Sunil Patel, David Cachia
Journal: Neuro-Oncology (2019)

Abstract Atypical and malignant meningiomas are rare tumors that unlike WHO I meningiomas are characteristically more aggressive in nature and are associated with higher recurrence risks of recurrence. In fact despite aggressive treatment of malignant meningiomas, the average 5-year survival rates are in the range of 30% to 60%. Still the standard of care for atypical and malignant meningiomas (AM and MM) has yet to be established. Our laboratory data demonstrated that galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is highly expressed in AM and MM as compared to normal tissue. However, the biological functions of Gal-3 in meningioma cells are not fully understood. To address this, we used either small interfering RNA (siRNA) to knock down Gal-3 expression or Gal-3 inhibitor, TD139 to suppress Gal-3 expression in in vitro cell culture model. Silencing or inhibiting of Gal-3 expression significantly decreased the protein levels of urokinase-type plasminogen activator receptor (uPAR) as well as uPAR’s downstream signaling transduction pathway, including phosphorylation of AKT. In both cases, we found that silencing of Gal-3 or inhibiting Gal-3 expression decreased the proliferative activity, and migratory potential of AM and MM cells. Furthermore, we demonstrated that TD139 inhibits MM growth in an in vivo xenograft MM model. Taken together, our results suggest that Gal-3 modulates uPAR expression and that Gal-3 may be a potential therapeutic target for the treatment of atypical and malignant meningiomas.
Role of Autophagy in Resistance of FLT3-ITD AML Stem Cells to FLT3 TKI Treatment
Authors: Shaowei Qiu, Chengcheng Yan, Andrew J Paterson, Hui Li, Nick Anderson, Ajay Abraham, Jianbo He, Mansi Shah, Puneet Agarwal, Jing Yang, Min Xie, Rui Lu, Rob S. Welner, Ravi Bhatia
Journal: Blood (2019)
A Th1/IFNγ Gene Signature Is Prognostic in the Adjuvant Setting of Resectable High-Risk Melanoma but Not in Non–Small Cell Lung Cancer
Authors: Benjamin Dizier, Andrea Callegaro, Muriel Debois, Brigitte Dreno, Peter Hersey, Helen J. Gogas, John M. Kirkwood, Johan F. Vansteenkiste, Lecia V. Sequist, Djordje Atanackovic, Jelle Goeman, Hans van Houwelingen, Susana Salceda, Fawn Wang, Patrick Therasse, Channa Debruyne, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Fernando Ulloa-Montoya
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Immune components of the tumor microenvironment (TME) have been associated with disease outcome. We prospectively evaluated the association of an immune-related gene signature (GS) with clinical outcome in melanoma and non–small cell lung cancer (NSCLC) tumor samples from two phase III studies. Experimental Design: The GS was prospectively validated using an adaptive signature design to optimize it for the sample type and technology used in phase III studies. One-third of the samples were used as “training set”; the remaining two thirds, constituting the “test set,” were used for the prospective validation of the GS. Results: In the melanoma training set, the expression level of eight Th1/IFNγ-related genes in tumor-positive lymph node tissue predicted the duration of disease-free survival (DFS) and overall survival (OS) in the placebo arm. This GS was prospectively and independently validated as prognostic in the test set. Building a multivariate Cox model in the test set placebo patients from clinical covariates and the GS score, an increased number of melanoma-involved lymph nodes and the GS were associated with DFS and OS. This GS was not associated with DFS in NSCLC, although expression of the Th1/IFNγ-related genes was associated with the presence of lymphocytes in tumor samples in both indications. Conclusions: These findings provide evidence that expression of Th1/IFNγ genes in the TME, as measured by this GS, is associated with clinical outcome in melanoma. This suggests that, using this GS, patients with stage IIIB/C melanoma can be classified into different risk groups.
Unmanipulated Haploidentical Transplant Followed By Post-Transplant Cyclophosphamide and Selective Ex Vivo T-Cell Depleted Haploidentical Transplant Results in Comparable Outcome As Unrelated Cord Blood Transplant for Adults with Haematological Malignancies- a Multicenter Study in Singapore
Authors: Cheryl XQ Lim, Yeh Ching Linn, Yin Jie Koh, Michelle Poon, Aloysius YL Ho, William YK Hwang, Lip Kun Tan, Liang Piu Koh
Journal: Blood (2019)