Browsing by Subject "lung"

Now showing 1 - 5 of 5
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    Evaluation of initial setup errors of two immobilization devices for lung stereotactic body radiation therapy (SBRT)
    (Wiley, 2017-07) Ueda, Yoshihiro; Teshima, Teruki; Cárdenes, Higinia; Das, Indra J.; Radiation Oncology, School of Medicine
    The aim of this study was to investigate the accuracy and efficacy of two commonly used commercial immobilization systems for stereotactic body radiation therapy (SBRT) in lung cancer. This retrospective study assessed the efficacy and setup accuracy of two immobilization systems: the Elekta Body Frame (EBF) and the Civco Body Pro-Lok (CBP) in 80 patients evenly divided for each system. A cone beam CT (CBCT) was used before each treatment fraction for setup correction in both devices. Analyzed shifts were applied for setup correction and CBCT was repeated. If a large shift (>5 mm) occurred in any direction, an additional CBCT was employed for verification after localization. The efficacy of patient setup was analyzed for 105 sessions (48 with the EBF, 57 with the CBP). Result indicates that the CBCT was repeated at the 1st treatment session in 22.5% and 47.5% of the EBF and CBP cases, respectively. The systematic errors {left–right (LR), anterior–posterior (AP), cranio-caudal (CC), and 3D vector shift: (LR2 + AP2 + CC2)1/2 (mm)}, were {0.5 ± 3.7, 2.3 ± 2.5, 0.7 ± 3.5, 7.1 ± 3.1} mm and {0.4 ± 3.6, 0.7 ± 4.0, 0.0 ± 5.5, 9.2 ± 4.2} mm, and the random setup errors were {5.1, 3.0, 3.5, 3.9} mm and {4.6, 4.8, 5.4, 5.3} mm for the EBF and the CBP, respectively. The 3D vector shift was significantly larger for the CBP (P < 0.01). The setup time was slightly longer for the EBF (EBF: 15.1 min, CBP: 13.7 min), but the difference was not statistically significant. It is concluded that adequate accuracy in SBRT can be achieved with either system if image guidance is used. However, patient comfort could dictate the use of CBP system with slightly reduced accuracy.
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    Hypoxia-Inducible Factor-1α Regulates CD55 in Airway Epithelium
    (American Thoracic Society, 2016-12) Pandya, Pankita H.; Fisher, Amanda J.; Mickler, Elizabeth A.; Temm, Constance J.; Lipking, Kelsey P.; Gracon, Adam; Rothhaar, Katia; Sandusky, George E.; Murray, Mary; Pollok, Karen; Renbarger, Jamie; Blum, Janice S.; Lahm, Tim; Wilkes, David S.; Microbiology and Immunology, School of Medicine
    Airway epithelial CD55 down-regulation occurs in several hypoxia-associated pulmonary diseases, but the mechanism is unknown. Using in vivo and in vitro assays of pharmacologic inhibition and gene silencing, the current study investigated the role of hypoxia-inducible factor (HIF)-1α in regulating airway epithelial CD55 expression. Hypoxia down-regulated CD55 expression on small-airway epithelial cells in vitro, and in murine lungs in vivo; the latter was associated with local complement activation. Treatment with pharmacologic inhibition or silencing of HIF-1α during hypoxia-recovered CD55 expression in small-airway epithelial cells. HIF-1α overexpression or blockade, in vitro or in vivo, down-regulated CD55 expression. Collectively, these data show a key role for HIF-1α in regulating the expression of CD55 on airway epithelium.
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    Inhibition of MEK signaling prevents SARS-CoV2-induced lung damage and improves the survival of infected mice
    (Wiley, 2022-08-28) Xie, Jingwu; Klemsz, Michael J.; Kacena, Melissa A.; Sandusky, George; Zhang, Xiaoli; Kaplan, Mark H.; Pathology and Laboratory Medicine, School of Medicine
    Coronavirus disease 2019 (COVID-19) is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 500 million confirmed cases of COVID-19 have been recorded, with 6 million deaths. Thus, reducing the COVID-19-related medical burden is an unmet need. Despite a vaccine that is successful in preventing COVID-19-caused death, effective medication to relieve COVID-19-associated symptoms and alleviate disease progression is still in high demand. In particular, one in three COVID-19 patients have signs of long COVID syndrome and are termed long haulers. At present, there are no effective ways to treat long haulers. In this study, we determine the effectiveness of inhibiting mitogen-activated protein kinase (MEK) signaling in preventing SARS-CoV-2-induced lung damage in mice. We showed that phosphorylation of extracellular signal-regulated kinase (ERK), a marker for MEK activation, is high in SARS-CoV-2-infected lung tissues of mice and humans. We show that selumetinib, a specific inhibitor of the upstream MEK kinases, reduces cell proliferation, reduces lung damage following SARS-CoV-2 infection, and prolongs the survival of the infected mice. Selumetinib has been approved by the US Food and Drug Administration (FDA) to treat cancer. Further analysis indicates that amphiregulin (AREG), an essential upstream molecule, was upregulated following SARS-CoV-2 infection. Our data suggest that MEK signaling activation represents a target for therapeutic intervention strategies against SARS-CoV-2-induced lung damage and that selumetinib may be repurposed to treat COVID-19.
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    Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?
    (Liebert, 2020) Abouhashem, Ahmed S.; Singh, Kanhaiya; Azzazy, Hassan M. E.; Sen, Chandan K.; Surgery, School of Medicine
    Human lungs single cell RNA sequencing data from healthy donors (elderly and young; GEO accession number GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Co-localization of ACE2 and TMPRSS2 enables SARS-CoV 2 to enter the cells. Expression of these genes in the alveolar type II cells of elderly and young patients were comparable and therefore do not seem to be responsible for worse outcomes observed in COVID-19 affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. SOD3 was identified as the top-ranked gene that was most down-regulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included ATF4 and M2TA. ATF4, an ER stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway AnalysisTM, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this work propose the hypotheses that lung-specific delivery of SOD3/ATF4 related antioxidants may work in synergy with promising anti-viral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly.
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    Methods in Lung Microbiome Research
    (American Thoracic Society, 2019-10-29) Carney, Sharon M.; Clemente, Jose C.; Cox, Michael J.; Dickson, Robert P.; Huang, Yvonne J.; Kitsios, Georgios D.; Kloepfer, Kirsten M.; Leung, Janice M.; LeVan, Tricia D.; Molyneaux, Philip L.; Moore, Bethany B.; O’Dwyer, David N.; Segal, Leopoldo N.; Garantziotis, Stavros; Pediatrics, School of Medicine
    The lung microbiome is associated with host immune response and health outcomes in experimental models and patient cohorts. Lung microbiome research is increasing in volume and scope; however, there are no established guidelines for study design, conduct, and reporting of lung microbiome studies. Standardized approaches to yield reliable and reproducible data that can be synthesized across studies will ultimately improve the scientific rigor and impact of published work and greatly benefit microbiome research. In this review, we identify and address several key elements of microbiome research: conceptual modeling and hypothesis framing; study design; experimental methodology and pitfalls; data analysis; and reporting considerations. Finally, we explore possible future directions and research opportunities. Our goal is to aid investigators who are interested in this burgeoning research area and hopefully provide the foundation for formulating consensus approaches in lung microbiome research.