دورية أكاديمية
Therapy-induced modulation of tumor vasculature and oxygenation in a murine glioblastoma model quantified by deep learning-based feature extraction
العنوان: | Therapy-induced modulation of tumor vasculature and oxygenation in a murine glioblastoma model quantified by deep learning-based feature extraction |
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المؤلفون: | Nadine Bauer, Daniel Beckmann, Dirk Reinhardt, Nicole Frost, Stefanie Bobe, Raghu Erapaneedi, Benjamin Risse, Friedemann Kiefer |
المصدر: | Scientific Reports, Vol 14, Iss 1, Pp 1-16 (2024) |
بيانات النشر: | Nature Portfolio, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | Abstract Glioblastoma presents characteristically with an exuberant, poorly functional vasculature that causes malperfusion, hypoxia and necrosis. Despite limited clinical efficacy, anti-angiogenesis resulting in vascular normalization remains a promising therapeutic approach. Yet, fundamental questions concerning anti-angiogenic therapy remain unanswered, partly due to the scale and resolution gap between microscopy and clinical imaging and a lack of quantitative data readouts. To what extend does treatment lead to vessel regression or vessel normalization and does it ameliorate or aggravate hypoxia? Clearly, a better understanding of the underlying mechanisms would greatly benefit the development of desperately needed improved treatment regimens. Here, using orthotopic transplantation of Gli36 cells, a widely used murine glioma model, we present a mesoscopic approach based on light sheet fluorescence microscopic imaging of wholemount stained tumors. Deep learning-based segmentation followed by automated feature extraction allowed quantitative analyses of the entire tumor vasculature and oxygenation statuses. Unexpectedly in this model, the response to both cytotoxic and anti-angiogenic therapy was dominated by vessel normalization with little evidence for vessel regression. Equally surprising, only cytotoxic therapy resulted in a significant alleviation of hypoxia. Taken together, we provide and evaluate a quantitative workflow that addresses some of the most urgent mechanistic questions in anti-angiogenic therapy. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2045-2322 |
Relation: | https://doaj.org/toc/2045-2322 |
DOI: | 10.1038/s41598-024-52268-0 |
URL الوصول: | https://doaj.org/article/ce15251859294f709e77304c0ff34145 |
رقم الأكسشن: | edsdoj.15251859294f709e77304c0ff34145 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 20452322 |
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DOI: | 10.1038/s41598-024-52268-0 |