Academic Journal
Neoadjuvant vascular-targeted photodynamic therapy improves survival and reduces recurrence and progression in a mouse model of urothelial cancer
| العنوان: | Neoadjuvant vascular-targeted photodynamic therapy improves survival and reduces recurrence and progression in a mouse model of urothelial cancer |
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| المؤلفون: | Rosenzweig, Barak, Corradi, Renato B., Budhu, Sadna, Alvim, Ricardo, Recabal, Pedro, La Rosa, Stephen, Somma, Alex, Monette, Sebastien, Scherz, Avigdor, Kim, Kwanghee, Coleman, Jonathan A. |
| المساهمون: | The Wade Thompson Foundation, NIH |
| المصدر: | Scientific Reports ; volume 11, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2021 |
| الوصف: | Locally advanced urothelial cancer has high recurrence and progression rates following surgical treatment. This highlights the need to develop neoadjuvant strategies that are both effective and well-tolerated. We hypothesized that neoadjuvant sub-ablative vascular-targeted photodynamic therapy (sbVTP), through its immunotherapeutic mechanism, would improve survival and reduce recurrence and progression in a murine model of urothelial cancer. After urothelial tumor implantation and 17 days before surgical resection, mice received neoadjuvant sbVTP (WST11; Tookad Soluble, Steba Biotech, France). Local and systemic response and survival served as measures of therapeutic efficacy, while immunohistochemistry and flow cytometry elucidated the immunotherapeutic mechanism. Data analysis included two-sided Kaplan–Meier, Mann–Whitney, and Fischer exact tests. Tumor volume was significantly smaller in sbVTP-treated animals than in controls (135 mm 3 vs. 1222 mm 3 , P < 0.0001) on the day of surgery. Systemic progression was significantly lower in sbVTP-treated animals (l7% vs. 30%, P < 0.01). Both median progression-free survival and overall survival were significantly greater among animals that received sbVTP and surgery than among animals that received surgery alone ( P < 0.05). Neoadjuvant-treated animals also demonstrated significantly lower local recurrence. Neoadjuvant sbVTP was associated with increased early antigen-presenting cells, and subsequent improvements in long-term memory and increases in effector and active T-cells in the spleen, lungs, and blood. In summary, neoadjuvant sbVTP delayed local and systemic progression, prolonged progression-free and overall survival, and reduced local recurrence, thereby demonstrating therapeutic efficacy through an immune-mediated response. These findings strongly support its evaluation in clinical trials. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-021-84184-y |
| الاتاحة: | http://dx.doi.org/10.1038/s41598-021-84184-y https://www.nature.com/articles/s41598-021-84184-y.pdf https://www.nature.com/articles/s41598-021-84184-y |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.30C6ACBA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-021-84184-y |
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