Topotecan alleviates ventilator-induced lung injury via NF-κB pathway inhibition

Wan, Bing; Xu, Weizong; Zhan, Ping; Jin, Jiajia; Xi, Guangmin; Chen, Meizi; Hu, Yangbo; Zhu, Suhua; Liu, Hongbing; Wang, Xiaoxia; Zhang, Xiuwei; Lv, Tangfeng; Song, Yong

doi:10.1016/j.cyto.2018.04.016

Cited by 13 publications

(7 citation statements)

References 35 publications

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“…Their studies were consistent with ours, topotecan has shown remarkable e cacy in the treatment of leukemia, retinoblastoma and neuroblastoma in clinical and trials study [47][48][49]. Interestingly, topotecan also was an commonly used chemotherapy drug for lung cancer which triggers DCs activation and cytokine production [50]. These ndings revealed that topotecan combined with immunotherapy can effectively target NCAPD2 to against cancer progression, but the speci c mechanism of action still needs to be further con rmed.…”

Section: Discussionsupporting

confidence: 78%

NCAPD2 Is a Favorable Predictor of Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Lung Cancer

Feng

Yang

Lin

et al. 2022

Preprint

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Background: Non-SMC condensin I complex subunit D2 (NCAPD2) belongs to the chromosomal structural maintenance family. While the different contribution of NCAPD2 to chromosome in mitosis have been thoroughly investigated, much less is known about the expression of NCAPD2 in pan-cancer. Thus, we used a bioinformatics dataset to conduct a pan-cancer analysis of NCAPD2 to determine its regulatory role in tumors. Methods: Multiple online databases were analyzed NCAPD2 gene expression, protein level, patient survival and functional enrichment in pan-cancer. Genetic alteration and tumor stemness of NCAPD2 were analyzed using cBioPortal and SangerBox. The GSCA and CellMiner were used to explore the relationship between NCAPD2 and drug sensitivity. The diagnostic value of prognosis was evaluated by ROC curve. Subsequently, the immuneinfiltration level and immune subtype of NCAPD2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were analyzed using TIMER1 and TISIDB. Results: NCAPD2 gene expression was significantly higher in most cancers and associated with clinical stage and poor prognosis. Genomic heterogeneity of NCAPD2 promoted the occurrence and development of tumors. GO enrichment analysis suggested NCAPD2 might be involved in DNA repair and immune response. NCAPD2 was involved in immune infiltration of LUAD and LUSC. ROC curves showed that NCAPD2 has important prognosis diagnostic value in LUAD and LUSC. Moreover, NCAPD2 was drug sensitive to topotecan, which may be an optimize immunotherapy. Conclusions: It was found that NCAPD2 was overexpressed in pan-cancers, which was associated with poor outcomes. Importantly, NCAPD2 could be a diagnosticmarker and an immune related biomarker for LUAD and LUSC.

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Section: Discussionsupporting

confidence: 78%

NCAPD2 Is a Favorable Predictor of Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Lung Cancer

Feng

Yang

Lin

et al. 2022

Preprint

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“…Myeloperoxidase activities in lung tissue were higher in rats ventilated with low tidal volumes which is in contrast to previous reports. 29,30 However, this result appears to be statistically fragile.…”

Section: Discussionmentioning

confidence: 88%

Volutrauma Increases Exhaled Pentanal in Rats: A Potential Breath Biomarker for Ventilator-Induced Lung Injury

Müller-Wirtz

Kiefer

Maurer

et al. 2021

Anesthesia &Amp; Analgesia

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BACKGROUND: Mechanical ventilation injures lungs, but there are currently no reliable methods for detecting early injury. We therefore evaluated whether exhaled pentanal, a lipid peroxidation product, might be a useful breath biomarker for stretch-induced lung injury in rats. METHODS: A total of 150 male Sprague-Dawley rats were investigated in 2 substudies. The first randomly assigned 75 rats to 7 hours of mechanical ventilation at tidal volumes of 6, 8, 12, 16, and 20 mL·kg−1. The second included 75 rats. A reference group was ventilated at a tidal volume of 6 mL·kg−1 for 10 hours 4 interventional groups were ventilated at a tidal volume of 6 mL·kg−1 for 1 hour, and then for 0.5, 1, 2, or 3 hours at a tidal volume of 16 mL.kg−1 before returning to a tidal volume of 6 mL·kg−1 for additional 6 hours. Exhaled pentanal was monitored by multicapillary column–ion mobility spectrometry. The first substudy included cytokine and leukocyte measurements in blood and bronchoalveolar fluid, histological assessment of the proportion of alveolar space, and measurements of myeloperoxidase activity in lung tissue. The second substudy included measurements of pentanal in arterial blood plasma, cytokine and leukocyte concentrations in bronchoalveolar fluid, and cleaved caspase 3 in lung tissue. RESULTS: Exhaled pentanal concentrations increased by only 0.5 ppb·h−1 (95% confidence interval [CI], 0.3–0.6) when rats were ventilated at 6 mL·kg−1. In contrast, exhaled pentanal concentrations increased substantially and roughly linearly at higher tidal volumes, up to 3.1 ppb·h−1 (95% CI, 2.3–3.8) at tidal volumes of 20 mL·kg−1. Exhaled pentanal increased at average rates between 1.0 ppb·h−1 (95% CI, 0.3–1.7) and 2.5 ppb·h−1 (95% CI, 1.4–3.6) after the onset of 16 mL·kg−1 tidal volumes and decreased rapidly by a median of 2 ppb (interquartile range [IQR], 0.9–3.2), corresponding to a 38% (IQR, 31–43) reduction when tidal volume returned to 6 mL·kg−1. Tidal volume, inspiratory pressure, and mechanical power were positively associated with pentanal exhalation. Exhaled and plasma pentanal were uncorrelated. Alveolar space decreased and inflammatory markers in bronchoalveolar lavage fluid increased in animals ventilated at high tidal volumes. Short, intermittent ventilation at high tidal volumes for up to 3 hours increased neither inflammatory markers in bronchoalveolar fluid nor the proportion of cleaved caspase 3 in lung tissue. CONCLUSIONS: Exhaled pentanal is a potential biomarker for early detection of ventilator-induced lung injury in rats.

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“…It is suggested that downregulation of NF-κB results in the attenuation of inflammatory cytokine signaling. In addition, several pre-clinical studies have demonstrated the beneficial effects of NF-κB-targeting inhibitors in the prevention and treatment of lung inflammation induced by toxic agents in preclinical models [49][50][51][52][53][54][55]. HCQ inhibits IL-6, TNF-α, IL-1β and NF-κB [44,[56][57][58], also it inhibits the activation of NF-κB in the lung of bleomycintreated rats [59].…”

Section: Discussionmentioning

confidence: 99%

Febuxostat as an alternative therapy in COVID-19: A double-blind randomized clinical trial

Davoodi

Abedi

Salehifar

et al. 2020

Preprint

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Aims: The aim of this double-blind randomized clinical trial was to determine the effects of FBX in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in patients with COVID-19-causing moderate symptomatic disease. Methods: We conducted a randomized, double blind clinical trial involving adult outpatients' patients with COVID-19 infection, which causes the moderate respiratory illness. Sixty patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were clinical and laboratory data including rate of fever, cough, berating rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT lesions were evaluated on admission and 14 days of treatments in both groups. Results: Fever, cough and tachypnea significantly mitigated in both groups after five days of treatments. The lymphocytes count significantly increased in both treatment groups and the CRP values were dropped in normal range (negative) in major of patients receiving FBX or HCQ treatment. It was not observed any significantly difference between FBX and HCQ in frequency of these symptoms. The mean percentages of CT abnormality scores were significantly reduced to 7.3% and 8% after 14 days of FBX and HCQ treatments, respectively. In adult outpatients with moderate symptomatic Covid-19, the effectiveness of FBX was same to HCQ in improvement of clinical manifestations, laboratory tests and CT lesions. Conclusion: These findings suggest FBX as an alternative treatment for Covid-19 infection in patients with contraindication or precaution to HCQ.

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Topotecan alleviates ventilator-induced lung injury via NF-κB pathway inhibition

Cited by 13 publications

References 35 publications

NCAPD2 Is a Favorable Predictor of Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Lung Cancer

NCAPD2 Is a Favorable Predictor of Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Lung Cancer

Volutrauma Increases Exhaled Pentanal in Rats: A Potential Breath Biomarker for Ventilator-Induced Lung Injury

Febuxostat as an alternative therapy in COVID-19: A double-blind randomized clinical trial

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