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1.
International Journal of Radiation Oncology, Biology, Physics ; 114(3):e111-e112, 2022.
Article in English | CINAHL | ID: covidwho-2036093
2.
Espaces, Tourisme & Loisirs ; 355:73-78, 2020.
Article in French | CAB Abstracts | ID: covidwho-1998753

ABSTRACT

The COVID-19 crisis can be an opportunity to transform the current tourism model, characterized by strong inequalities of access, to imagine more sustainable, more resilient and more democratic tourism practices. This article projects into 2030 and describes what could be the sustainable, desirable and possible future of a tourism that has marked the programmed end of rapid carbon-intensive travel. This tourism reinvents the relationship to travel, places and people, and focuses on proximity and slowness.

4.
Annals of Oncology ; 31:S1015, 2020.
Article in English | EMBASE | ID: covidwho-806229

ABSTRACT

Background: SARS-CoV-2 infection is the cause of the respiratory illness COVID-19, which presents most frequently with respiratory symptoms. SARS-CoV-2 cell entry requires interactions with ACE2 and TMPRSS2 on the surface of the host cell. Cancer patients and, specifically, those with thoracic malignancies seem to experience poorer clinical outcomes. Methods: We utilized bulk and single-cell transcriptional data from a combination of normal and malignant tissues and cells from aerodigestive and respiratory tracts to explore mechanisms governing the expression of ACE2 and TMPRSS2. Additionally, we determined the effect of EMT induction, ZEB1 modulation, and SARS-CoV-2 infection on ACE2 expression. Results: Our bulk data suggests that aerodigestive and lung cancer models express a broad range of ACE2 and TMRPSS2, particularly in epithelial cells, and would serve as good models for studying SARS-CoV-2 infection. We assessed the relationship between ACE2 and epithelial differentiation in numerous datasets, and found consistent positive correlations with transcriptional and microRNA signifiers of epithelial differentiation. The miR-200 family – zinc finger E-box-binding homeobox 1 (ZEB1) pathway, which is an established regulator of EMT, also directly regulates ACE2 expression, likely via putative ZEB1 repressor sites located in the ACE2 promoter. Furthermore, SARS-CoV-2 infection reduces ACE2 expression and shifts cells to a more mesenchymal phenotype with loss of EPCAM and upregulation of ZEB1 and other EMT-associated genes. Conclusions: ACE2-positive cells are almost exclusively epithelial and unexpectedly rare, considering the devastating impact of this infection. Following viral entry, SARS-CoV-2 infection induces molecular changes within the cells that are reminiscent of EMT, including increased ZEB1. ZEB1, in turn, appears to directly repress the expression of ACE2. This SARS-CoV-2-induced ACE2 deficiency, compounded by the downregulation of genes, including claudins, which play a critical role in restricting epithelial and endothelial permeability, exposes respiratory cells to increased risk of edema and acute respiratory distress syndrome (ARDS). Legal entity responsible for the study: The authors. Funding: NIH/NCI R01-CA207295 (L.A.B.), NIH/NCI U01-CA213273 (L.A.B., J.V.H.), CCSG P30-CA01667 (L.A.B.), University of Texas SPORE in Lung Cancer P5-CA070907 (L.A.B., D.L.G., J.V.H., C.M.G.), the Department of Defense (LC170171;L.A.B.), Khalifa Bin Zayed Al Nahyan Foundation (C.M.G.), RP170067 (EMP), through generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shot Program and Andrew Sabin Family Fellowship, and The Rexanna Foundation for Fighting Lung Cancer. Disclosure: C. Gay: Research grant/Funding (self): Astra Zeneca. J.V. Heymach: Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Boehringer Ingelheim;Advisory/Consultancy: Exelixis;Advisory/Consultancy: Genentech;Advisory/Consultancy: GlaxoSmithKline;Advisory/Consultancy: Guardant Health;Advisory/Consultancy: Hengrui;Advisory/Consultancy: Spectrum. L.A. Byers: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (self): AbbVie;Advisory/Consultancy, Research grant/Funding (self): GenMab;Advisory/Consultancy: BergenBio;Advisory/Consultancy: Pharma Mar SA;Advisory/Consultancy, Research grant/Funding (self): Sierra Oncology;Advisory/Consultancy: Merck;Advisory/Consultancy: Bristol Myers Squibb;Advisory/Consultancy: Genentech;Advisory/Consultancy: Pfizer;Research grant/Funding (self): Tolero Pharmaceuticals. All other authors have declared no conflicts of interest.

5.
Annals of Oncology ; 31:S1015-S1016, 2020.
Article in English | EMBASE | ID: covidwho-805904

ABSTRACT

Background: Patients with thoracic cancers affected by the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appear to have poor clinical outcomes. AXL, a TAM (Tyro3, AXL, Mer) family receptor tyrosine kinase, is a known mediator of epithelial to mesenchymal transition (EMT) and therapeutic resistance in non-small cell lung cancer (NSCLC) and other cancers. Additionally, AXL plays a role in efficient Ebola and Zika viral entry and infection and AXL inhibition has demonstrated antiviral activities. Recently, bemcentinib, a highly selective and potent AXL inhibitor with antiviral activity, has been fast-tracked as the first potential treatment for assessment in the United Kingdom’s ACcelerating COVID-19 Research & Development (ACCORD) multicenter, randomized phase II trial. Methods: We analyzed mRNA expression of AXL and other TAM family members as well as angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, in treatment-naïve (n=1016) and previously treated (n=239) NSCLC tumors and in a panel of NSCLC cell lines (n=70). We also analyzed AXL mRNA levels in NSCLC cell lines (n=3) infected with SARS-CoV-2. Results: In treatment-naïve and previously-treated NSCLC tumors, AXL mRNA expression was higher in mesenchymal tumors, as expected, and inversely correlated with ACE2. Similarly, in NSCLC cell lines, high ACE2 expression was associated with low AXL mRNA and protein expression. Notably, expression of ACE2 was downregulated while that of AXL and ZEB1, an EMT transcription factor, were upregulated in NSCLC cells infected with SARS-CoV-2 as compared to mock infected cells, suggesting a shift to a more mesenchymal phenotype. Treatment with bemcentinib for 24h downregulated ZEB1 expression in mesenchymal cell lines, reversing EMT. Conclusions: These data, in the context of ACE2’s role in preventing acute respiratory distress syndrome, suggest a shift from ACE2-expressing epithelial cells to a more mesenchymal phenotype characterized by low ACE2 and high AXL expression, upon infection of NSCLC cells with SARS-CoV-2. In addition to bemcentinib’s antiviral activity, it can also reverse EMT, further supporting AXL and EMT as novel therapeutic targets for COVID-19 treatment. Legal entity responsible for the study: Lauren A. Byers. Funding: NIH/NCI CCSG P30-CA016672 (Bioinformatics Shared Resource), NIH/NCI T32 CA009666, ASCO Young Investigator Award (C.M.G.);University of Texas SPORE in Lung Cancer P5-CA070907 (L.A.B. C.M.G.), NIH/NCI R01-CA207295, NIH/NCI U01-CA213273, the Department of Defense (LC170171) (L.A.B.), The LUNGevity foundation (D.G., L.A.B.), through generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shot Program (J.V.H., J.W., L.A.B.);an Andrew Sabin Family Fellowship (L.A.B.), and The Rexanna Foundation for Fighting Lung Cancer (J.V.H., L.A.B.). Disclosure: C. Gay: Research grant/Funding (self): AstraZeneca. D. Gibbons: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy: GlaxoSmithKline;Advisory/Consultancy: Sanofi;Advisory/Consultancy, Research grant/Funding (self): Janssen;Research grant/Funding (self): Takeda;Research grant/Funding (self): Ribon Therapeutics;Research grant/Funding (self): Astellas. J.V. Heymach: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy: Boehringer Ingelheim;Advisory/Consultancy: Exelixis;Advisory/Consultancy: Genentech;Advisory/Consultancy, Research grant/Funding (self): GlaxoSmithKline;Advisory/Consultancy: Guardant Health;Advisory/Consultancy: Hengrui;Advisory/Consultancy: Lilly;Advisory/Consultancy: Novartis;Advisory/Consultancy, Research grant/Funding (self), Licensing/Royalties: Spectrum;Advisory/Consultancy: EMD Serono;Advisory/Consultancy: Synta;Research grant/Funding (self): Bayer. L.A. Byers: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;AbbVie;GenMab;Sierra Oncology;Advisory/Consultancy: BergenBio;Pharma Mar SA;Merck;Bristol Myers Squibb;G nentech;Pfizer;Research grant/Funding (self): Tolero Pharmaceuticals. All other authors have declared no conflicts of interest.

6.
Annals of Oncology ; 31:S1019, 2020.
Article in English | EMBASE | ID: covidwho-804330

ABSTRACT

Background: The novel coronavirus SARS-CoV-2 is the cause of the respiratory illness COVID-19—a global pandemic affecting over 4 million individuals worldwide. Viruses efficiently replicate by hijacking host cell machinery to obtain macromolecules and energy by similar mechanisms as cancer cells. Since viral infection is known to alter cellular nutrient requirements, this study explores the metabolites and metabolic pathways associated with SARS-CoV-2 infection. Methods: Bulk and single-cell seequencing data from cell lines and tumor samples were retrieved from publically available datasets. Transcriptional data were retrieved from publically available datasets of gefitinib- and erlotinib-resistant EGFR-mutant cell lines and Calu3 and A549 cells mock treated or infected with SARS-CoV-2. Single-cell RNAseq datasets of EGFR-mutant PC-9 mock and osimertinib treated were downloaded from GEO. 225 metabolites were profiled in CCLE cell lines using LC-MS. Results: To identify metabolic features of cells able to be infected by SARS-CoV-2 via the ACE2 receptor, metabolites associated with ACE2 expression were investigated. ACE2 expression positively correlates with glutamine in upper aerodigestive tract cell lines. Consistent with this, ACE2 expression was examined against a list of 253 metabolism-associated genes and GLUL, which encodes an enzyme (glutamine synthetase) responsible for conversion of glutamate to glutamine, was significantly positively correlated in NSCLC, HNSCC, and SCLC cell lines and confirmed in human tumor datasets. Additionally, GLS, which encodes the enzyme (glutaminase) that catalyzes the opposing reaction, is negatively correlated with ACE2 expression. Further, we analyzed RNA sequencing data from NSCLC cell lines infected with SARS-CoV-2 for 24 hours and revealed that upon infection there is a down regulation of GLUL signifying a metabolic-shift away from glutamine as the cells undergo EMT. Conclusions: We show that SARS-CoV-2 targeting of ACE-2 expressing, metabolically-primed epithelial cells is advantageous to exploit the abundance of glutamine to synthesize nucleotides for rapid replication and viral spread. Legal entity responsible for the study: Lauren A. Byers. Funding: NIH/NCI R01-CA207295 (L.A.B.), NIH/NCI U01-CA213273 (L.A.B., J.V.H.), CCSG P30-CA01667 (L.A.B.), University of Texas SPORE in Lung Cancer P5-CA070907 (L.A.B., D.L.G., J.V.H., C.M.G.), the Department of Defense (LC170171;L.A.B.), Khalifa Bin Zayed Al Nahyan Foundation(C.M.G.), The University of Texas MD Anderson Cancer Center-Oropharynx Cancer Program generously supported by Mr. and Mrs. Charles W. Stiefel (F.M.J.), through generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shot Program and Andrew Sabin Family Fellowship, and The Rexanna Foundation for Fighting Lung Cancer. Disclosure: C. Gay: Research grant/Funding (self): AstraZeneca. S. Heeke: Honoraria (self): Qiagen;Boehringer Ingelheim;Travel/Accommodation/Expenses: Roche. D. Gibbons: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Janssen;Advisory/Consultancy: GlaxoSmithKline;Sanofi;Research grant/Funding (self): Takeda;Ribon Therapeutics;Astellas. J.V. Heymach: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy: Boehringer Ingelheim;EMD Serono;Novartis;Lilly;Hengrui;Guardant Health;GSK;Genentech;Exelixis;Synta;Advisory/Consultancy, Research grant/Funding (self), Licensing/Royalties: Spectrum;Research grant/Funding (self): Bayer;GlaxoSmithKline. L.A. Byers: Advisory/Consultancy: Pfizer;Genentech;: Bristol Myers Squibb;Merck;Pharma Mar SA;BergenBio;Advisory/Consultancy, Research grant/Funding (self): Sierra Oncology;GenMab;AstraZeneca;AbbVie;Research grant/Funding (self): Tolero Pharmaceuticals. All other authors have declared no conflicts of interest.

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