Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts
| Autor: | David I. Quinn, Leanne Drummond, Michael V Frost, Ashley Tornio, Lauren Hylle, Sara Dafoe, Ashish M. Kamat, Holly Maulhardt, Gere S. diZerega |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Immune system Prostate Medicine docetaxel cancer bladder genitourinary oncology Bladder cancer prostate business.industry nanoparticle NanoDoce® medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens intratumoral 030104 developmental biology Systemic toxicity medicine.anatomical_structure Oncology Docetaxel 030220 oncology & carcinogenesis Cancer research Immunohistochemistry renal business Local injection Infiltration (medical) medicine.drug |
| Zdroj: | Cancers, Vol 11, Iss 4, p 577 (2019) Cancers Volume 11 Issue 4 |
| ISSN: | 2072-6694 |
| Popis: | Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce® NanOlogy LLC, Fort Worth, TX, USA) and its efficacy against genitourinary-oncologic xenografts in rats and mice, xenograft-site docetaxel concentrations and immune-cell infiltration were studied. IT-NanoDoce® IV-docetaxel and IT-vehicle were administered to clear cell renal carcinoma (786-O: rats), transitional cell bladder carcinoma (UM-UC-3: mice) and prostate carcinoma (PC-3: mice). Treatments were given every 7 days with 1, 2, or 3 doses administered. Animals were followed for tumor growth and clinical signs. At necropsy, 786-O and UM-UC-3 tumor-site tissues were evaluated by H& E and IHC and analyzed by LC-MS/MS for docetaxel concentration. Two and 3 cycles of IT-NanoDoce® significantly reduced UM-UC-3 tumor volume (p < 0.01) and eliminated most UM-UC-3 and 786-O tumors. In both models, NanoDoce® treatment was associated with (peri)tumor-infiltrating immune cells. Lymphoid structures were observed in IT-NanoDoce® treated UM-UC-3 animals adjacent to tumor sites. IT-vehicle and IV-docetaxel exhibited limited immune-cell infiltration. In both studies, high levels of docetaxel were detected in NanoDoce® treated animals up to 50 days post-treatment. In the PC-3 study, IT-NanoDoce® and IV-docetaxel resulted in similar tumor reduction. NanoDoce® significantly reduced tumor volume compared to IT-vehicle in all xenografts (p < 0.0001). We hypothesize that local, persistent, therapeutic levels of docetaxel from IT-NanoDoce® reduces tumor burden while increasing immune-cell infiltration. IT NanoDoce® treatment of prostate, renal and bladder cancer may result in enhanced tumoricidal effects. |
| Databáze: | OpenAIRE |
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