Magnetically-actuated drug delivery device (MADDD) for minimally invasive treatment of prostate cancer: An in vivo animal pilot study
Autor: | Mu Chiao, Alan I. So, Sebastian Frees, Zheng Tan, Claudia Chavez-Munoz, John K. Jackson, Werner J. Struss, Ali Shademani, Igor Moskalev, Ninadh M. D'Costa, Peter A. Raven, Payam Zachkani |
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Rok vydání: | 2017 |
Předmět: |
Male
Oncology medicine.medical_specialty Urology medicine.medical_treatment Mice Nude Antineoplastic Agents Docetaxel 02 engineering and technology Metastasis Mice 03 medical and health sciences Prostate cancer Drug Delivery Systems 0302 clinical medicine Prostate In vivo Internal medicine medicine Animals Minimally Invasive Surgical Procedures Prostatectomy business.industry Prostatic Neoplasms Prostate-Specific Antigen 021001 nanoscience & nanotechnology medicine.disease Tumor Burden Surgery Treatment Outcome medicine.anatomical_structure 030220 oncology & carcinogenesis Cohort Magnets Immunohistochemistry Taxoids Drug Monitoring 0210 nano-technology business medicine.drug |
Zdroj: | The Prostate. 77:1356-1365 |
ISSN: | 0270-4137 |
DOI: | 10.1002/pros.23395 |
Popis: | Background The vast majority of prostate cancer presents clinically localized to the prostate without evidence of metastasis. Currently, there are several modalities available to treat this particular disease. Despite radical prostatectomy demonstrating a modest prostate cancer specific mortality benefit in the PIVOT trial, several novel modalities have emerged to treat localized prostate cancer in patients that are either not eligible for surgery or that prefer an alternative approach. Methods Athymic nude mice were subcutaneously inoculated with prostate cancer cells. The mice were divided into four cohorts, one cohort untreated, two cohorts received docetaxel (10 mg/kg) either subcutaneously (SC) or intravenously (IV) and the fourth cohort was treated using the magnetically-actuated docetaxel delivery device (MADDD), dispensing 1.5 μg of docetaxel per 30 min treatment session. Treatment in all three therapeutic arms (SC, IV, and MADDD) was administered once weekly for 6 weeks. Treatment efficacy was measured once a week according to tumor volume using ultrasound. In addition, calipers were used to assess tumor volume. Results Animals implanted with the device demonstrated no signs of distress or discomfort, neither local nor systemic symptoms of inflammation and infection. Using an independent sample t-test, the tumor growth rate of the treated tumors was significant when compared to the control. Post hoc Tukey HSD test results showed that the mean tumor growth rate of our device cohort was significantly lower than SC and control cohorts. Moreover, IV cohort showed slight reduction in mean tumor growth rates than the ones from the device cohort, however, there was no statistical significance in tumor growth rate between these two cohorts. Furthermore, immunohistochemistry demonstrated an increased cellular apoptosis in the MADDD treated tumors and a decreased proliferation when compared to the other cohorts. In addition, IV cohort showed increased treatment side effects (weight loss) when compared to the device cohort. Finally, MADDD showed minimal expression of CD45 comparable to the control cohort, suggesting no signs of chronic inflammation. Conclusions In conclusion, this study showed for the first time that MADDD, clearly suppressed tumor growth in local prostate cancer tumors. This could potentially be a novel clinical treatment approach for localized prostate cancer. |
Databáze: | OpenAIRE |
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