Tumor suppression effect of ultrasound-sensitive nanoparticles with focused ultrasound in a pancreas cancer xenograft model.

BACKGROUND: We investigated the tumor suppression effect of an ultrasound-sensitive doxorubicin-loaded liposome-based nanoparticle, IMP301, to enhance the synergistic effect with focused ultrasound (FUS) in an animal model of pancreatic cancer. METHODS: Thirty nude mice with xenografts of PANC-1 human pancreatic cancer cells were randomly and prospectively allocated to 6 different groups (5 per group) each for Study-1 (dose-response test) and Study-2 (synergistic effect test). Study-1 consisted of control, gemcitabine, Doxil with FUS, and three different doses of IMP301 (2, 4, 6 mg/kg) with FUS groups. Study-2 consisted of control, FUS only, gemcitabine, Doxil with FUS, and IMP301 (4 mg/kg) with or without FUS groups. Differences in tumor volume and growth rate were evaluated by one-way ANOVA and Student-Newman-Keuls test. RESULTS: In Study-1, 4 mg/kg or greater IMP301 with FUS groups showed lower tumor growth rates of 14 ± 4 mm3/day (mean ± standard deviation) or less, compared to the control, gemcitabine, and Doxil with FUS groups with rates exceeding 28 ± 5 (p < 0.050). The addition of FUS in Study-2 decreased the tumor growth rate in the IMP301-treated groups from 36 ± 17 to 9 ± 6, which was lower than the control, FUS only, gemcitabine, and Doxil with FUS groups (p < 0.050). CONCLUSIONS: IMP301 combined with FUS exhibited higher tumor growth suppression compared to the use of a conventional drug alone or the combination with FUS. The present study showed the potential of IMP301 to enhance the synergistic effect with FUS for the treatment of pancreatic cancer. RELEVANCE STATEMENT: This article aims to evaluate the synergistic effect of FUS and ultrasound-responsive liposomal drug in tumor growth suppression by using xenograft mouse model of pancreatic ductal adenocarcinoma. FUS-induced ultrasound-sensitive drug release may be a potential noninvasive repeatable treatment option for patients with locally advanced or unresectable pancreatic cancer. KEY POINTS: • Modification of conventional drugs combined with FUS would maximize tumor suppression. • IMP301 with FUS had higher tumor suppression effect compared to conventional chemotherapy. • This image-guided drug delivery would enhance therapeutic effects of systemic chemotherapy.

Personalized 3D kidney model produced by rapid prototyping method and its usefulness in clinical applications

ABSTRACT Background: Three-dimensional (3D) printing has been introduced as a novel technique to produce 3D objects. We tried to evaluate the clinical usefulness of 3D-printed renal model in performing partial nephrectomy (PN) and also in the education of medical students. Materials and Methods: We prospectively produced personalized renal models using 3D-printing methods from preoperative computed tomography (CT) images in a total of 10 patients. Two different groups (urologist and student group) appraised the clinical usefulness of 3D-renal models by answering questionnaires. Results: After application of 3D renal models, the urologist group gave highly positive responses in asking clinical usefulness of 3D-model among PN (understanding personal anatomy: 8.9 / 10, preoperative surgical planning: 8.2 / 10, intraoperative tumor localization: 8.4 / 10, plan for further utilization in future: 8.3 / 10, clinical usefulness in complete endophytic mass: 9.5 / 10). The student group located each renal tumor correctly in 47.3% when they solely interpreted the CT images. After the introduction of 3D-models, the rate of correct answers was significantly elevated to 70.0% (p < 0.001). The subjective difficulty level in localizing renal tumor was also significantly low (52% versus 27%, p < 0.001) when they utilized 3D-models. Conclusion: The personalized 3D renal model was revealed to significantly enhance the understanding of correct renal anatomy in patients with renal tumors in both urologist and student groups. These models can be useful for establishing the perioperative planning and also education program for medical students.