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353 results on '"Askin, Frederic B."'

1. Pathology of Systemic Sclerosis

Author

Rooper, Lisa M., Askin, Frederic B., Allanore, Yannick, editor, Varga, John, editor, Denton, Christopher P., editor, Kuwana, Masataka, editor, Chung, Lorinda, editor, and Shah, Ami A., editor

Published
2024
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2. SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801

Author

Wahl, Angela, Gralinski, Lisa E., Johnson, Claire E., Yao, Wenbo, Kovarova, Martina, Dinnon, Kenneth H., III, Liu, Hongwei, Madden, Victoria J., Krystek, Halina M., De, Chandrav, White, Gregory R., Kolykhalov, Alexander A., Natchus, Michael G., Askin, Frederic B., Painter, George, Browne, Edward P., and Jones, Corbin D.

Subjects
Antiviral agents -- Testing, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

All coronaviruses known to have recently emerged as human pathogens probably originated in bats.sup.1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801--an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials--markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19. Human and bat coronaviruses replicate efficiently in immunodeficient mice implanted with human lung tissue, and treatment or prophylaxis using EIDD-2801 in this model suggests that this oral antiviral agent may be effective in preventing COVID-19., Author(s): Angela Wahl [sup.1] [sup.2] [sup.3] , Lisa E. Gralinski [sup.4] , Claire E. Johnson [sup.1] [sup.2] [sup.3] , Wenbo Yao [sup.1] [sup.2] [sup.3] , Martina Kovarova [sup.1] [sup.2] [sup.3] [...]

Published
2021
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5. Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis

Author

Kim, Sulgi, primary, Li, Lang, additional, Lin, Feng‐Chang, additional, Stack, Taylor, additional, Lamb, Meredith M., additional, Mohammad, Ibtisam, additional, Norris, Meghan, additional, Klatt‐Cromwell, Cristine, additional, Thorp, Brian D., additional, Ebert, Charles S., additional, Masters, Daniel, additional, Senior, Brent A., additional, Askin, Frederic B., additional, and Kimple, Adam J., additional

Published
2023
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6. Pathology of Systemic Sclerosis

Author

Rooper, Lisa M., Askin, Frederic B., Varga, John, editor, Denton, Christopher P., editor, Wigley, Fredrick M., editor, Allanore, Yannick, editor, and Kuwana, Masataka, editor

Published
2017
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7. Human T cells efficiently control RSV infection

Author

De, Chandrav, primary, Pickles, Raymond J., additional, Yao, Wenbo, additional, Liao, Baolin, additional, Boone, Allison E., additional, Choi, Mingyu, additional, Battaglia, Diana M., additional, Askin, Frederic B., additional, Whitmire, Jason K., additional, Silvestri, Guido, additional, Garcia, J. Victor, additional, and Wahl, Angela, additional

Published
2023
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8. Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease

Author

Kato, Takafumi, primary, Asakura, Takanori, additional, Edwards, Caitlin E., additional, Dang, Hong, additional, Mikami, Yu, additional, Okuda, Kenichi, additional, Chen, Gang, additional, Sun, Ling, additional, Gilmore, Rodney C., additional, Hawkins, Padraig, additional, De la Cruz, Gabriela, additional, Cooley, Michelle R., additional, Bailey, Alexis B., additional, Hewitt, Stephen M., additional, Chertow, Daniel S., additional, Borczuk, Alain C., additional, Salvatore, Steven, additional, Martinez, Fernando J., additional, Thorne, Leigh B., additional, Askin, Frederic B., additional, Ehre, Camille, additional, Randell, Scott H., additional, O’Neal, Wanda K., additional, Baric, Ralph S., additional, and Boucher, Richard C., additional

Published
2022
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9. Non‐small cell lung carcinomas with diffuse coexpression of TTF1 and p40: clinicopathological and genomic features of 14 rare biphenotypic tumours

Author

Savari, Omid, primary, Febres‐Aldana, Christopher, additional, Chang, Jason C., additional, Fanaroff, Rachel E., additional, Ventura, Katia, additional, Bodd, Francis, additional, Paik, Paul, additional, Vundavalli, Murty, additional, Saqi, Anjali, additional, Askin, Frederic B., additional, Travis, William D., additional, and Rekhtman, Natasha, additional

Published
2022
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13. Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease

Author

Martinez, Fernando J., Edwards, Caitlin E, Chertow, Daniel S., Hawkins, Padraig, Chen, Gang, NIH COVID-19 Autopsy Consortium, Boucher, Richard C, Ehre, Camille, Gilmore, Rodney C, Dang, Hong, Okuda, Kenichi, Borczuk, Alain C, Mikami, Yu, Randell, Scott H, De la Cruz, Gabriela, Thorne, Leigh B, Sun, Ling, Cooley, Michelle R, Kato, Takafumi, Salvatore, Steven, Bailey, Alexis B, O'Neal, Wanda K, Baric, Ralph S., Askin, Frederic B, Asakura, Takanori, and Hewitt, Stephen M

Abstract

Rationale: The incidence and sites of mucus accumulation, and molecular regulation of mucin gene expression, in COVID-19 lung disease have not been reported. Objectives: Characterize incidence of mucus accumulation and the mechanisms mediating mucin hypersecretion in COVID-19 lung disease. Methods: Airway mucus and mucins were evaluated in COVID-19 autopsy lungs by AB-PAS and immunohistochemical staining, RNA in situ hybridization, and spatial transcriptional profiling. SARS-CoV-2-infected human bronchial epithelial (HBE) cultures were utilized to investigate mechanisms of SARS-CoV-2-induced mucin expression and synthesis and test candidate countermeasures. Measurements and Main Results: MUC5B and variably MUC5AC RNA levels were increased throughout all airway regions of COVID-19 autopsy lungs, notably in the sub-acute/chronic disease phase following SARS-CoV-2 clearance. In the distal lung, MUC5B-dominated mucus plugging was observed in 90% of COVID-19 subjects in both morphologically identified bronchioles and microcysts, and MUC5B accumulated in damaged alveolar spaces. SARS-CoV-2-infected HBE cultures exhibited peak titers 3 days post inoculation, whereas induction of MUC5B/MUC5AC peaked 7-14 days post inoculation. SARS-CoV-2 infection of HBE cultures induced expression of EGFR ligands and inflammatory cytokines (e.g., IL-1α/β) associated with mucin gene regulation. Inhibiting EGFR/IL-1R pathways, or dexamethasone administration, reduced SARS-CoV-2-induced mucin expression. Conclusions: SARS-CoV-2 infection is associated with a high prevalence of distal airspace mucus accumulation and increased MUC5B expression in COVID-19 autopsy lungs. HBE culture studies identified roles for EGFR and IL-1R signaling in mucin gene regulation post SARS-CoV-2 infection. These data suggest that time-sensitive mucolytic agents, specific pathway inhibitors, or corticosteroid administration may be therapeutic for COVID-19 lung disease. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org.libproxy.lib.unc.edu/licenses/by-nc-nd/4.0/).

Published
2022
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15. Non-small cell lung carcinomas with diffuse coexpression of TTF1 and p40: clinicopathological and genomic features of 14 rare biphenotypic tumours.

Author

Savari, Omid, Febres-Aldana, Christopher, Chang, Jason C., Fanaroff, Rachel E., Ventura, Katia, Bodd, Francis, Paik, Paul, Vundavalli, Murty, Saqi, Anjali, Askin, Frederic B., Travis, William D., and Rekhtman, Natasha

Subjects
LUNGS, SQUAMOUS cell carcinoma, TUMORS, CARCINOMA, CLINICAL pathology
Abstract

Thyroid transcription factor 1 (TTF1) and p40 are widely-utilized diagnostic markers of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), respectively. Diffuse coexpression of TTF1 and p40 has been described in only rare case reports. In a multiinstitutional study, we collected the largest cohort of these unusual tumours to-date (n = 14), with the goal of elucidating their clinicopathological and genomic characteristics. Lung tumours with diffuse coexpression (labelling 50–100% tumour cells) of TTF1 clone 8G7G3/1 and p40 clone BC28 were identified. Detailed clinicopathological and immunohistochemical parameters were analyzed. Eight tumours were analyzed by next-generation sequencing (NGS) and the results were compared to those in > 9 K LUAD and > 1 K LUSC. All tumours with diffuse TTF1/p40 coexpression were poorly differentiated non-small cell lung carcinomas (NSCLC), 42% of which had basaloid features. Some tumours exhibited focal keratinization (14%), napsin A and/or mucicarmine labelling (46%) or both squamous and glandular features (7%). NGS revealed a uniquely high rate of FGFR1 amplifications (70%) compared to either LUAD (0.7%, P < 0.0001) or LUSC (11%, P = 0.001). LUAD-type targetable driver alterations were identified in 38% of cases (one EGFR, two KRAS G12C). The tumours were clinically aggressive, exhibiting metastatic disease in most patients. Lung carcinomas with diffuse TTF1/p40 coexpression represent poorly differentiated NSCLCs with frequent basaloid features, but some show evidence of focal squamous, glandular or dual differentiation with a distinctly high rate of FGFR1 amplifications. The presence of targetable LUAD-type alterations (EGFR, KRAS G12C) emphasizes the importance of molecular testing in these tumours. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis

Author

Zhen, Gehua, Wen, Chunyi, Jia, Xiaofeng, Li, Yu, Crane, Janet L., Mears, Simon C., Askin, Frederic B., Frassica, Frank J., Chang, Weizhong, Yao, Jie, Carrino, John A., Cosgarea, Andrew, Artemov, Dmitri, Chen, Qianming, Zhao, Zhihe, Zhou, Xuedong, Riley, Lee, Sponseller, Paul, Wan, Mei, Lu, William Weijia, and Cao, Xu

Subjects
Stem cells -- Models -- Physiological aspects -- Genetic aspects -- Research, Transforming growth factors -- Models -- Physiological aspects -- Genetic aspects -- Research, Osteoarthritis -- Genetic aspects -- Care and treatment -- Research, Biological sciences, Health
Abstract

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth [...]

Published
2013
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24. Biomimetic human small muscular pulmonary arteries

Author

Jin, Qianru, primary, Bhatta, Anil, additional, Pagaduan, Jayson V., additional, Chen, Xing, additional, West-Foyle, Hoku, additional, Liu, Jiayu, additional, Hou, Annie, additional, Berkowitz, Dan, additional, Kuo, Scot C., additional, Askin, Frederic B., additional, Nguyen, Thao D., additional, Gracias, David H., additional, and Romer, Lewis H., additional

Published
2020
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25. Diffuse Lung Disease in Young Children: Application of a Novel Classification Scheme

Author

Deutsch, Gail H., Young, Lisa R., Deterding, Robin R., Fan, Leland L., Dell, Sharon D., Bean, Judy A., Brody, Alan S., Nogee, Lawrence M., Trapnell, Bruce C., Langston, Claire, Albright, Eric A., Askin, Frederic B., Baker, Peter, Chou, Pauline M., Cool, Carlyne M., Coventry, Susan C., Cutz, Ernest, Davis, Mary M., Dishop, Megan K., Galambos, Csaba, Patterson, Kathleen, Travis, William D., Wert, Susan E., and White, Frances V.

Published
2007
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33. K-ras oncogene activation in lung adenocarcinomas from former smokers: evidence that K-ras mutations are an early and irreversible event in the development of adenocarcinoma of the lung

Author

Westra, William H., Slebos, Robbert J.C., Offerhaus, G. Johan A., Goodman, Steven N., Evers, Siegina G., Kensler, Thomas W., Askin, Frederic B., Rodenhuis, Sjoerd, and Hruban, Ralph H.

Subjects
Ras genes -- Physiological aspects, Smoking -- Health aspects, Lung cancer -- Development and progression, Adenocarcinoma -- Development and progression, Carcinogenicity testing, Health
Abstract

Background. Point mutations in codon 12 of the K-ras protooncogene occur more frequently in lung adenocarcinomas from smokers (30%) than they do in lung adenocarcinomas from nonsmokers (7%), suggesting that smoking is an important factor in the induction of these mutations. The lack of well defined 'early' premalignant or in situ glandular neoplasms of the lung, however, has not permitted direct evaluation of the chronology of ras activation in the development of lung adenocarcinomas. To circumvent the need to evaluate precursor lesions, we examined lung adenocarcinomas from former smokers for point mutations in K-ras. Methods. Mutations in codon 12 of K-ras were detected using polymerase chain reaction amplification and mutation-specific oligonucleotide probes. The types and frequencies of mutations found in adenocarcinomas obtained from 57 former smokers were compared to those found in 27 adenocarcinomas from patients who never smoked and to those found in 27 adenocarcinomas from patients who were current smokers. Results. The overall prevalence of K-ras point mutations in lung adenocarcinomas obtained from former smokers (32%) was not different from that seen in adenocarcinomas from patients who were current smokers (30%, P = 0.83), and was greater than that seen in adenocarcinomas from patients who never smoked (7%, P 0.015). This pattern was independent of the duration of abstinence from smoking. Furthermore, the predominant type of mutation found in tumors from former smokers was a guanine-to-thymine transversion, the specific type of mutation induced by benzo(a)pyrene, one of the chemical carcinogens found in tobacco smoke. Conclusions. These findings support previous findings that suggest that codon 12 of the K-ras oncogene may be a specific target of the mutagenic activity of tobacco smoke, and suggest that DNA alterations at this site can occur early and irreversibly during the development of adenocarcinomas of the lung.

Published
1993

34. Ewing sarcoma of bone in infants and toddlers: a clinicopathologic report from the Intergroup Ewing's study

Author

Maygarden, Susan J., Askin, Frederic B., Siegal, Gene P., Gilula, L.A., Schoppe, Janice, Foulkes, Mary, Kissane, John M., and Nesbit, Mark

Subjects
Ewing's sarcoma, Tumors in children, Chemotherapy -- Complications, Health
Abstract

Background. Nineteen patients with Ewing sarcoma of bone, each younger than 3 years of age at the time of initial presentation, are reported. These children represent an unusually young age group for documented Ewing sarcoma and represent 2.6% of all patients registered in the Intergroup Ewing's Sarcoma Study (IESS). Methods. The diagnosis was made on combined histologic, clinical, and radiographic grounds and was supported by immunohistochemistry in nine patients and electron microscopic study in eight patients. Immunohistochemical studies showed no staining against neuronspecific enolase, chromogranin, or S-100 in any patients, and in only one in nine patients were results of such studies focally positive against Leu-7. Results. The most marked clinical variation between this group of infants and the general IESS patient population was a striking predominance of female patients in the younger age group (P < 0.001). There was a trend toward more rib, pelvis, and proximal long bone tumors in the infants and toddlers. The overall survival rate of the infants was 56%, almost identical to the survival rates of the older children. All of the infants who died of disease did so within 4 years. Extended follow-up as long as 9.9 years has found no late deaths attributable to tumor. The most significant late complications of therapy included cardiotoxicity with cerebral embolization from the heart and a short lower limb secondary to radiation therapy. Conclusions. Ewing sarcoma must be considered in the differential diagnosis of small cell, round cell, and blue cell tumors in bone, even in infants and toddlers. Cancer 1993; 71:2109-18.

Published
1993

35. Clinical mutational profiling of 1006 lung cancers by next generation sequencing

Author

Illei, Peter B., primary, Belchis, Deborah, additional, Tseng, Li-Hui, additional, Nguyen, Doreen, additional, De Marchi, Federico, additional, Haley, Lisa, additional, Riel, Stacy, additional, Beierl, Katie, additional, Zheng, Gang, additional, Brahmer, Julie R., additional, Askin, Frederic B., additional, Gocke, Christopher D., additional, Eshleman, James R., additional, Forde, Patrick M., additional, and Lin, Ming-Tseh, additional

Published
2017
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36. Heterogeneity of resistance mutations detectable by next-generation sequencing in TKI-treated lung adenocarcinoma

Author

Belchis, Deborah A., primary, Tseng, Li-Hui, additional, Gniadek, Thomas, additional, Haley, Lisa, additional, Lokhandwala, Parvez, additional, Illei, Peter, additional, Gocke, Christopher D., additional, Forde, Patrick, additional, Brahmer, Julie, additional, Askin, Frederic B., additional, Eshleman, James R., additional, and Lin, Ming-Tseh, additional

Published
2016
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40. Prognosis of Minimally Invasive Carcinoma Arising in Mucinous Cystic Neoplasms of the Pancreas

Author

Lewis, Gloria H., primary, Wang, Huamin, additional, Bellizzi, Andrew M., additional, Klein, Alison P., additional, Askin, Frederic B., additional, Schwartz, Lauren Ende, additional, Schulick, Richard D., additional, Wolfgang, Christopher L., additional, Cameron, John L., additional, O’Reilly, Eileen M., additional, Yu, Kenneth H., additional, and Hruban, Ralph H., additional

Published
2013
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46. Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Children's Oncology Group

Author

Bhatia, Smita, primary, Krailo, Mark D., additional, Chen, Zhengjia, additional, Burden, Laura, additional, Askin, Frederic B., additional, Dickman, Paul S., additional, Grier, Holcombe E., additional, Link, Michael P., additional, Meyers, Paul A., additional, Perlman, Elizabeth J., additional, Rausen, Aaron R., additional, Robison, Leslie L., additional, Vietti, Teresa J., additional, and Miser, James S., additional

Published
2006
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47. Correction

Author

Song, Zhimin, primary, Marzilli, Lisa, additional, Greenlee, Brian M., additional, Chen, Edward S., additional, Silver, Richard F., additional, Askin, Frederic B., additional, Teirstein, Alvin S., additional, Zhang, Ying, additional, Cotter, Robert J., additional, and Moller, David R., additional

Published
2005
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