tbuckley/cabot-search huggingface dataset:
TMOD-42. CRISPR/Cas9-EDITED HUMAN NEURAL STEM CELLS GIVE RISE TO BRAIN TUMORS RESEMBLING GLIOBLASTOMAS
Authors: Tomoyuki Koga, Jorge Benitez, Sebastian Markmiller, Matteo D’Antonio, Alison Parisian, Shahram Saberi, Kristen Turner, Matthias-Florian Hessenauer, Amy Haseley Thorne, Ciro Zanca, Paul Mischel, Kelly Frazer, Gene Yeo, Webster Cavenee, Frank Furnari
Journal: Neuro-Oncology (2017)

Glioblastoma is the most malignant tumor of the brain with a median overall survival of 12-15 months. One of the factors that make the treatment of this disease difficult is its inherent and typical heterogeneity promoted by different genetic drivers. Here we show that neural stem cells (NSCs) derived from human induced pluripotent stem cells (iPSCs), with different combinations of these genetic drivers introduced by CRISPR/Cas9-mediated editing display mutations-specific in vitro proliferation and drug resistance characteristics and give rise to distinct intracranial tumors when engrafted in immunocompromised mice. NSCs deficient in PTEN and NF1, a genotype associated with the mesenchymal phenotype, generate highly-invasive intracranial tumors with spindle-shaped cells. Sphere cultures of these tumor cells yield euploid cell lines. In contrast, NSCs deficient in TP53 and expressing a PDGFRA activating mutation (PDGFRAD8-9), a genotype associated with the proneural glioblastoma subtype, give rise to aggressive tumors with high cellularity and characteristics of glioblastomas, such as mitosis, necrosis, and vascular proliferation. Cells obtained from these tumors show aneuploidy and display extrachromosomal DNA (ecDNA), including double-minute-like structures, which commonly harbor amplified oncogenes as seen in many cancer types including glioblastomas. This model represents the first human pluripotent-cell-derived cancer model showing pathognomonic progression with ecDNA amplification. Additionally, RNA-seq analysis of both models confirms their mesenchymal and proneural glioblastoma gene expression signatures, respectively. Using these engineered human cell derived xenograft models (eHDX), we aim to advance our understanding of the effect of each genomic abnormality on the neoplastic process and to provide a platform for the development of subtype specific targeted therapies.
TMOD-32. SUPPRESSION OF MUTANT BRAF EXPRESSION RESULTS IN GLIOMA REGRESSION AND INCREASED SURVIVAL IN VIVO
Authors: Diana Yu, Clifford Shin, James Robinson, Danika Sommer, Adam Welker, Sheri Holmen
Journal: Neuro-Oncology (2017)

Activating mutations in BRAF have been identified in a significant number of human cancers including both pediatric and adult gliomas of varying grades. Specifically, the BRAFV600E mutation, which is the most common mutational variant, has been found in ~27% of pediatric anaplastic astrocytoma (WHO grade III), ~12% of pediatric glioblastomas (GBM, WHO grade IV), and ~5% of adult GBMs. Using the RCAS/TVA glioma mouse model system, we previously demonstrated that activated BRAF induces GBM formation in vivo when combined with Ink4a/Arf loss and Akt activation (Robinson et al, Oncogene, 2010). In this study, we used the modified inducible RCAN/TVA glioma mouse model, which allows for temporal regulation of BRAFV600E expression in vivo, to determine the dependence of these gliomas on continued MAPK signaling in the context of Pten and Ink4a/Arf loss. Viral delivery of BRAFV600E, Tet-off, and Cre into Nestin::TVA;Ptenlox/lox;Ink4a/Arflox/lox mice produced gliomas in 80% (20/25) of the animals. Of these tumors, 65% (13/20) resembled highly invasive GBM with a diffuse growth pattern, aberrant angiogenesis, and psuedopalisading necrosis. Histological characterization revealed pleomorphic tumors displaying a spectrum of cellular morphologies ranging from small round cells to spindle cells and giant cells. Administration of doxycycline (DOX) allowed for suppression of BRAFV600E expression, which resulted in tumor regression, as verified by MRI, and a significant increase in survival. Interestingly, more than half of the DOX treated animals experienced disease progression while on DOX. With recent reports of mixed clinical outcomes in patients treated with mutant BRAF inhibitors, this model may allow for the identification of resistance mechanisms and novel therapeutic strategies to improve the outcome for patients with BRAFV600E glioma.
STEM-10. SUPER-ENHANCER SCREEN IDENTIFIES LIPID METABOLISM AS A CANCER STEM CELL DEPENDENCY IN GLIOBLASTOMA
Authors: Ryan Gimple, Stephen Mack, Jeremy Rich
Journal: Neuro-Oncology (2017)

Super-enhancer screen identifies lipid metabolism as a cancer stem cell dependency in glioblastoma Ryan C. Gimple, Stephen C. Mack, Jeremy N. Rich Glioblastoma is the most prevalent and aggressive primary intrinsic brain tumor in adults and is among the most lethal of all human cancers with poor responses to all therapeutic modalities. Functionally defined glioma stem cells (GSCs) are proposed to contribute to this poor prognosis by mediating therapy resistance, self-renewal, and maintenance of cellular heterogeneity. To understand the cell-type-specific molecular processes that underlie GSC maintenance and tumorigenicity, we profiled super-enhancers through analysis of active enhancer histone modification data (H3K27ac) in matched GSC and differentiated glioma cell (DGC) samples. Super-enhancers, defined as clusters of typical enhancers, function as master epigenetic regulators that define cell state, orchestrate cell-type dependent transcriptional networks, and drive key oncogenes in a variety of cancers. This approach revealed lipid biosynthesis as a potential epigenetically regulated GSC dependency pathway. Knockdown of a key lipid metabolism gene in patient-derived GSCs resulted in decreased cell proliferation, diminished self-renewal, and induction of apoptosis in vitro, as well as impaired tumor formation in vivo. In a validation cohort, patient derived GSC tumor models containing the identified super-enhancer exhibited high expression of the lipid metabolism gene, suggesting that the expression of this gene is epigenetically driven. Next, we analyzed the upstream transcription factor control circuits that underlie a critical super-enhancer in this pathway. Expression of two neurodevelopmental transcription factors, OLIG2 and SOX2, were found to be significantly positively correlated with that of a lipid metabolism gene in clinical samples, suggesting that occupancy of these factors may drive the persistence of this super-enhancer. This discovery implicates aberrant lipid metabolism networks in glioma pathogenesis and suggests that targeting of fatty acid synthesis may provide a specific way to more effectively treat patients with glioblastoma.
Hydrolysis of Glutathione by the Cathepsins of Normal Rat Tissues and Rat Hepatoma 31
Authors: Maver, Mary E., Thompson, J. W.
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Hydrolysis of Glutathione by the Cathepsins of Normal Rat Tissues and Rat Hepatoma 31 Get access Mary E. Maver, Mary E. Maver senior biochemist Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Thompson J. W. Thompson pharmacologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 4, February 1943, Pages 383–387, https://doi.org/10.1093/jnci/3.4.383 Published: 01 February 1943
Tendênçias no risco de transmissão de infeccões virais (VIH, VHC, VHB) a través de transfusões de sangue na França (1992-2003) e impacto do teste de ácidos nucleicos (NAT)
Authors: J Pillonel, S Laperche
Journal: Eurosurveillance (2005)

A vigilância das tendencias do risco residual de transmissao de infeccoes virais por transfusao sanguinea e importante para avaliar a melhoria da seguranca do sangue e de seus componentes e para adaptar as politicas de reducao do risco. Estas tendencias foram estudadas na Franca por quatro periodos de tres anos (1992-1994, 1995-1997, 1998-2000 e 2001-2003). Foram comparadas as estimacoes para 2001-2003 com os resultados do NAT (nucleic acid testing, teste dos acidos nucleicos) para o VIH-1 e o virus da hepatite C (VHC) realizados em Junho de 2001 em todas as doacoes de sangue. Devido a melhoria do recrutamento e da seleccao dos dadores, aos progressos nas technicas de rastreio e as medidas de prevencao para o controle das infeccoes, os riscos residuais para o VIH e os virus da hepatite C e B (VHC, VHB) decrescerem de maneira significativa entre 1992 e 2003. Actualmente, o risco residual e muito baixo ; entre 2001 e 2003 era estimado em 1 por 3,15 milhoes de doacoes para o VIH, 1 por 10 milhoes para o VHC e 1 por cada 640 000 para o VHB. Nos 6,14 milhoes de doacoes de sangue analizadas por NAT entre Julho de 2001 e Dezembro de 2003, foram eliminadas duas doacoes positivas para o VIH e tres para o VHC, representando uma melhoria de 1 por 3,07 milhoes para o VIH e de 1 por 2,05 milhoes para o VHC. Estos resultados mostram o interesse limitado do NAT como tambem a sua baixa relacao custo-eficacia.
P1.01-005 Overall Survival (OS) After Disease Progression (PD) on Brigatinib in Patients With Crizotinib-Refractory ALK+ NSCLC in ALTA
Authors: C. Langer, H. Huang, W. Reichmann, S. Lustgarten, D. Kerstein, D.R. Camidge
Journal: Journal of Thoracic Oncology (2017)
PATH-55. THE POTENTIAL ROLE OF ERCC1 AS A BIOMARKER FOR PLATINUM BASED THERAPY IN PRIMARY AND METASTATIC BRAIN TUMORS
Authors: Lyndon Kim, Kevin Judy, Christopher Farrell, James Evans, David Andrews
Journal: Neuro-Oncology (2017)

Previous studies have demonstrated an association between excision repair cross-complementation group 1 (ERCC1), an endonuclease responsible for the repair of DNA damages, and tumor response in patients with non–small-cell lung cancer and other malignancies treated with platinum-based regimens, indicating that ERCC1 could be a reliable biomarker of tumor sensitivity to platinum-based agents. Platinum compounds have been used for the treatment of recurrent malignant gliomas but only with modest response. The role of ERCC1 as a potential biomarker for platinum-based therapy in recurrent primary and metastatic brain tumors is not known. We reviewed a total of 163 patients who had ERCC1 test based on molecular genetic profiling to determine if there is an association between negativeERCC1 and tumor response in primary and metastatic brain tumors. MRI was obtained every 2-3 mo. Total NegativeERCC1: 133/163 patients. 28/133 negativeERCC1 patients were treated with platinum compounds(13 GBM, 4 AA, 1 Gr2 Astrocytoma, 2 Anaplastic Oliogodendromas, 2 Oligodendromas, 1 squamous-cell, 1 breast, 1 endometrium, 1 esthesioneuroblastoma, 2 meningiomas). M:F 19:9 Age: 22-86 yo. Treatment period. 7/14-6/17. Total Responders: 13/28 patients(3/13 GBM, 1/4 AA, 1/1 Gr2 Astrocytoma, 2/2 Anaplastic Oligodendrogliomas 12 mo, >2 mo both on Tx, 1/2 Gr2 Oligodendrolgiomas. 24 mo d/c’d on SD, 1/1 squamous-cell, >6 mo, 1/1 breast, 0/1 endometrium, 1/1 esthesioneuroblastoma, >12 mo, 2/2 meningiomas >2 mo). High percentage(81%) of negativeERCC1 was found and, of those, a significant portion of patients with lower grade astrocytomas, oligodendrogliomas, esthesioneuroblastoma, meningiomas and metastatic tumors showed durable high response rates(82%) compared to AA and GBM patients(24%). Although not tested in randomized trial comparing ERCC1 negative and positive patients with platinum compounds, given high response rate, especially in nonmalignant gliomas/metastatic tumors, the results suggest that negativeERCC1 could be considered as a potential biomarker for platinum-based therapy in recurrent primary and metastatic brain tumors.
Is It Acceptable to Assess Prenatal Smoking Risk to Infants without Considering Socioeconomic Status?
Authors: Thida Ong, Michael S. Schechter
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

AL.In this case, it is particularly noteworthy that patients considered very severe according to the z-score are younger than severe patients, and their mean age is even lower than the mean of the entire cohort.This finding is surprising, given the lungfunction trajectories in COPD (5), as one would expect that lung function would deteriorate as patients age.Apart from these considerations, the analysis of the hazard ratio of death splines of our patients (Figure 2 of Reference 1) clearly shows that FEV 1 z-score values between 23 and 25 lose the exponential correlation with risk for mortality, which is a circumstance that does not occur for %Pred.Finally, we believe it necessary to emphasize that our results are not intended to question the relevance of z-score as an essential parameter for interpreting lung function, much less the Global Lung Function Initiative.This is especially true after the recent irreparable loss of Professor Philip H. Quanjer, one of its main proponents (6).In our opinion, the identification of this prognostic limitation of the z-score in elderly patients with COPD could suggest the need to recalibrate reference values in elderly subjects by incorporating more groups of this age (7).
NCMP-03. POSSIBLE OVERUSE OF ORDERABLE ANTIBODY PANELS FOR PARANEOPLASTIC ETIOLOGIES IN DIAGNOSTIC EVALUATION OF NEUROLOGIC PATIENTS
Authors: Ryan L Wilson, Aleksey Tadevosyan, Lara K Ronan
Journal: Neuro-Oncology (2017)

Encephalitis is a devastating neurological disorder resulting in high mortality and morbidity in seemingly healthy patients. Historically most cases of encephalitis have been attributed to infection. However, over the last decade encephalitis due to autoimmune etiology has come to the forefront with the aid of newly discovered antibodies that correlate with specific encephalitis syndromes. We became concerned of overreliance on antibody panels in determining etiology of illness in patients presenting with unusual neurologic conditions. In this retrospective clinical study we reviewed 73 patient cases for whom 92 autoimmune antibody panels were ordered from Mayo Clinic Laboratories in Rochester, Minnesota over September 1 - November 30, 2016. We found 11 cases of positive GAD65 antibodies (0.03-0.20 nmol/L, ref < 0.02 nmol/L), 2 cases of ganglionic acetylcholine receptor antibodies (gAchR-Ab), 1 case of positive NMDA receptor antibodies, and 1 case of both voltage gated potassium and calcium channel antibodies. Clinical syndrome of autoimmune epilepsy and encephalopathy was diagnosed in patient with positive NMDAR-Ab. Patients found to have the other positive antibodies did not have clinical syndromes previously reported to be associated with the specific antibody. One patient with Hashimoto’s encephalitis was found to have positive gAchR-Ab. Five other patients were diagnosed with nonspecific autoimmune encephalitis; 1 positive for gAchR-Ab, 1 for GAD65-Ab, 3 with negative studies. We found very low frequency of appropriate antibody panel ordering behavior fitting a specific clinical syndrome. High number of false positive and incidental results may misdirect patient care and therapeutic intervention. Our results emphasize that the presence of low titer antibodies without a specific clinical syndrome may not be of utility, and that the absence of antibodies where a certain clinical syndrome is suspected should not exclude the diagnosis. We plan to continue this study, and educate our physicians regarding this important matter.
Abstract 15044: Cardiac Explant-derived Cells From Aged Donors With Ischemic Cardiomyopathy Demonstrate Impaired Cell Survival and Therapeutic Regeneration
Authors: Ghazaleh Rafatian, Maryam Kamkar, Richard Seymour, Patrick G Burgon, Erik J Suuronen, Darryl R Davis
Journal: Circulation (2015)

Background: While cardiac stem cells are emerging as a promising therapy for ischemic cardiomyopathy (ICM), the influence of advanced donor age and ICM on the regenerative performance of these cells are unknown. Hypothesis: Advanced donor age and a history of ICM combine to limit the regenerative performance of explant-derived cells (EDCs) through altered cell functions which reflects fundamental changes in the molecular signature of aged ischemic EDCs. Methods and Results: EDCs were cultured from myocardial biopsies of young (8 weeks; n=40) and old (52 weeks; n=36) C57/BL6 mice 4 weeks after randomization to sham or experimental myocardial infraction (MI; ejection fraction 28±2%, p=0.24 effect of donor age). Although advanced donor age was associated with reduced telomere length, aging alone had negligible effects on EDCs. In contrast, EDCs sourced from aged ICM donors showed reduced cardiomyogenic differentiation (i.e., greater propensity to adopt an endothelial or smooth muscle lineage), cytokine production (reduced angiogenin, angiopoietin-1 and VEGF), pro-angiogenic capacity (1.2±0.03 fold less tubules formed; p=0.02), reactive oxygen species metabolism (1.8±0.3 fold greater reactive oxygen species, p=0.04; 1.9±0.1 fold less superoxide dismutase activity, p&lt;0.01; 2.4±0.3 fold less glutathione peroxidase activity, p&lt;0.01), and apoptosis resistance (1.5±0.1 fold greater; p=0.02) as compared to young ICM EDCs. With the exception of 1.6±0.1 fold greater production of IL-6 (p=0.04), ICM did not influence young EDCs. Transplantation of EDCs from aged ICM donors into aged recipients 1 week after MI provided lesser degrees of cell-mediated cardiac repair (3±1 vs. 8±1% change in LVEF from baseline to 21 days post CSC transplant after transplant of young ICM EDCs; p&lt;0.01). Finally, transcriptome comparison of ICM EDCs showed aging promoted the differential expression of 145 genes (≥2 fold change; false discovery rate ≤0.05) which modify many of the pathways responsible for effective cell cycle control and DNA damage/repair. Conclusions: EDCs from aged donors with a history of ICM demonstrate an attenuated capacity for cardiac repair that reflects differential expression of transcripts suggestive of impaired cell cycle control and repair.
P2.02-053 The Prognostic Value of 18 Circulating Markers of Inflammation, Endothelial Activation and Extracellular Matrix Remodeling in Non-small Cell Lung Cancer Patients
Authors: J. Berg, A.R. Halvorsen, M. Bengtson, K. Taskén, G. Mælandsmo, A. Yndestad, B. Halvorsen, O.T. Brustugun, P. Aukrust, T. Ueland, Å. Helland
Journal: Journal of Thoracic Oncology (2017)
P3.01-006 Prognostic Impact of Tumor Spread through Air Spaces in Limited Resection for pStage I Lung Cancer
Authors: Kyohei Masai, Aoi Sukeda, Akihiko Yoshida, Keisuke Asakura, Kazuo Nakagawa, Hiroyuki Sakurai, Shun-Ichi Watanabe, Hisao Asamura, Noriko Motoi
Journal: Journal of Thoracic Oncology (2017)
P1.03-040 Smokers Having Activating EGFR Mutant Non-Small Cell Lung Cancer Might Benefit from EGFR-TKI Treatment - Single Center Experience
Authors: O. Ercelep, T. Telli, O. Alan, R. Hasanov, E. Simsek, S. Halil, M. Ozturk, N. Babacan, S. Kaya, H. Kaya, F. Dane, P. Yumuk
Journal: Journal of Thoracic Oncology (2017)
P2.02-002 Digital Multiplexed Detection of Single Nucleotide Variants (SNV) in Non-Small Cell Lung Cancer Using NanoString Technology
Authors: B. Parris, G. Meredith, P.M. Ross, M. Krouse, A. Mashadi-Hossein, R. Bowman, I. Yang, K. Fong
Journal: Journal of Thoracic Oncology (2017)
Increasing Survival in Patients With Congenital Heart Disease—A Glass Half Full or Half Empty?
Authors: Sarah Cohen, Ariane Marelli
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Are anti-HER2 agents the best choice in metastatic breast cancer with an HER2 positive switch from primary tumour? A retrospective multi institution analysis of clinical-pathological characteristics and outcomes
Authors: I. Bertolini, L. Diodati, A. Fontana, C. De Angelis, L. Cantini, S. Cecconi, I. Montagnani, B. Salvadori, I. Ferrarini, P. Ferrari, A. Michelotti, E. Landucci, G. Fanelli, C. Scatena, A.G. Naccarato, R. Berardi, M. Pistelli, A. Falcone
Journal: Annals of Oncology (2017)
RTHP-28. PREDICTION OF RECURRENCE PATTERNS USING DIFFUSION DRIVEN GROWTH MODELING FOR GLIOBLASTOMA
Authors: Lukacova Slavka, Michael Lundemann, Per Munck af Rosenschold, Morten Bjørn Jensen, Jesper Kallehauge
Journal: Neuro-Oncology (2017)

Clinical target volume (CTV) for radiotherapy of glioblastoma is typically defined as an isotropic 2 cm expansion to the area of residual enhancement on T1 weighted MR imaging plus the surgical bed. Tumor growth models allow for incorporating the biological information about preferential spread along the white matter fibers in target definition. We assessed the value of growth driven CTV in the prediction of non-central recurrences. Five glioblastoma patients treated with radiotherapy (dose 60 Gy in 30 fractions) with recurrences extending outside the 95% isodose were selected out of 56 patients. The brain was segmented into white matter, grey matter and cerebrospinal fluid. Anatomic boundaries were delineated manually. A reaction-diffusion growth model was used assuming uniform proliferation throughout the brain and difference in white and grey matter diffusion of a factor 10 with no migration across the barriers. The volume of growth driven CTV (gCTV) corresponded the standard CTV. The volumetric comparison was performed using the shortest distance (SD) between all surface points in the recurrence volume and respective CTV and gCTV. Three of five recurrences were distant, seperated at minimum 3 cm from the resection cavity or the residual enhancement. The median CTV and recurrence volume was 236 cm3 (range: 175-240 cm3) and 89 cm3 (range: 0.9-112 cm3), respectively. The median SD in the recurrence volume decreased from 7.0 mm (range: 4.7-36.0 mm) for CTV to 5.5 mm (range: 2.9-28.1 mm) for gCTV indicating that gCTV was closer to the recurrence volume. Two out of three distant recurrences were not encompassed by the gCTV while no distant recurrences were within the CTV. The growth driven CTV appears promising in the prediction of marginal recurrences outside 95% isodose compared to standard CTV.
P3.01-076 QTWiST Analysis to Compare the Benefit of Gefitinib Versus Pemetrexed Platinum for Patients with EGFR Mutated NSCLC
Authors: V. Patil, V. Noronha, A. Joshi, A. Goel, V. Talreja, A. Kapoor, R. Kumar, A. Mahajan, A. Janu, K. Prabhash
Journal: Journal of Thoracic Oncology (2017)
JCES 01.28 NGS Sequencing Based Liquid / Tissue Biopsy Identified Coexistence of HER2 Amplification and Mutation in Advanced NSCLC Patients
Authors: R. Chen, J. Zhao, G. Lin, L. Liu, L. Chen, X. Hu, X. Ai, Z. Fan, C. Xu, W. Wang, W. Zhuang, M. Fang, Y. Zhu, G. Chen, Y. Guan, L. Yang, X. Xia, X. Yi
Journal: Journal of Thoracic Oncology (2017)
P1.17-005 Pure Red Cell Aplasia Associated with Thymoma: A Report of a Single-Center Experience
Authors: S. Moriyama, H. Haneda, K. Okuda, O. Kawano, T. Sakane, R. Oda, T. Watanabe, M. Yano, R. Nakanishi
Journal: Journal of Thoracic Oncology (2017)