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Abstract/Summary
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<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Whole lung transpulmonary chemoembolization using a combination of doxorubicin (DXO) and degradable starch microspheres (DSM-TPCE) might be a promising treatment option in soft tissue sarcoma. To pave the way for clinical studies, this study aimed to evaluate the short-term effects of DSM-TPCE with DXO using an <jats:italic>ex vivo</jats:italic> isolated lung perfusion (ILP) model.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>Nine lung specimens retrieved from patients undergoing lobectomy underwent <jats:italic>ex vivo</jats:italic> ILP. In groups of three, lung specimens were either treated with sole DXO, sole DSM, or combined substances (DSM + DXO). During <jats:italic>ex vivo</jats:italic> ILP, histological samples were obtained from each lung every 15 min. Quantitative DXO analysis and histopathological grading of possible tissue damage using a five-point Likert scale was performed. Two-way repeated measures ANOVA tested for differences between treatment groups and changes over time.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>We created a preclinical <jats:italic>ex vivo</jats:italic> ILP model to simulate the effects of DSM-TPCE. In histopathological analysis, only two specimens, treated with only DXO, showed an increase in parenchymal damage over time. No significant effect of time (3.3%, <jats:italic>p</jats:italic> = 0.305) or group (23.3; <jats:italic>p</jats:italic> = 0.331) was identified. Within the lung tissue, the DXO concentration ranged from 205 to 1,244 ng/g. No significant effects could be detected regarding different treatment groups (4.9% of total variation, <jats:italic>p</jats:italic> = 0.103).</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>In an <jats:italic>ex vivo</jats:italic> ILP model using human lung lobes, the physiological effects of DSM-TPCE with DXO could be tested. Neither increased DXO concentrations in lung tissue nor histopathological changes indicating early lung toxicity were observed.</jats:p>
</jats:sec><jats:sec>
<jats:title>Relevance statement</jats:title>
<jats:p>An <jats:italic>ex vivo</jats:italic> ILP model using human lung specimens did not show any signs of early lung toxicity after transpulmonary chemoembolization with DXO. These results support further evaluation of DSM-TPCE in phase I/II trials.</jats:p>
</jats:sec><jats:sec>
<jats:title>Key Points</jats:title>
<jats:p><jats:list list-type='bullet'>
<jats:list-item>
<jats:p>Transpulmonary chemoembolization can be investigated in an <jats:italic>ex vivo</jats:italic> ILP model.</jats:p>
</jats:list-item>
<jats:list-item>
<jats:p>DSM did not increase DXO in normal lung tissue.</jats:p>
</jats:list-item>
<jats:list-item>
<jats:p>DSM did not increase parenchymal toxicity compared to the control groups.</jats:p>
</jats:list-item>
</jats:list></jats:p>
</jats:sec><jats:sec>
<jats:title>Graphical Abstract</jats:title>
</jats:sec>
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Hinweis
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DeepGreen-ID: b551f19408684cb3a0c3d93b271eebb0 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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