Jasmine Zeki1, Jordan S Taylor1, Burcin Yavuz2, Jeannine Coburn3, Naohiko Ikegaki4, David L Kaplan2, Bill Chiu5. 1. Department of Surgery, Stanford University, Stanford, CA. 2. Department of Biomedical Engineering, Tufts University, Medford, MA. 3. Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL. 4. Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL. 5. Department of Surgery, Stanford University, Stanford, CA. Electronic address: bhsc@stanford.edu.
Abstract
BACKGROUND: Advanced-stage neuroblastoma patients require multiagent chemotherapy. Intratumoral implantation of vincristine-loaded silk gel uses local diffusion to decrease orthotopic neuroblastoma tumor growth in mice. We hypothesize that injecting vincristine-loaded silk gel into 8 locations within the tumor, instead of only centrally, decreases the diffusion distance and improves tumor growth suppression. METHODS: Human neuroblastoma cells, KELLY, were injected into mouse adrenal glands to create orthotopic tumors. After the tumors reached 100 mm3 by ultrasound, silk gels loaded with 50 µg vincristine were injected centrally or in 8 areas throughout the tumor. Drug-release profile was measured in vitro. Endpoints were tumor size >1,000 mm3 and histologic examination. RESULTS: Vincristine-loaded silk gels suppressed tumor growth up to an inflection point (458.7 ± 234.4 mm3 for central, 514.3 ± 165.8 mm3 for 8-point injection) before tumor growth accelerated >200 mm3 over 3 days. The time to inflection point was 6.6 days for central, 13.3 days for 8-point injection (P < .05). Using the sphere volume equation to approximate tumor volume, splitting the volume into 1/8 decreased the diffusion radius by 1/2. Histologic examination confirmed tumor necrosis adjacent to vincristine-loaded silk gel. CONCLUSION: Injecting vincristine-loaded sustained release silk gel at 8 separate locations halved the diffusion distance and doubled the time for the tumor to reach the growth inflexion point.
BACKGROUND: Advanced-stage neuroblastomapatients require multiagent chemotherapy. Intratumoral implantation of vincristine-loaded silk gel uses local diffusion to decrease orthotopic neuroblastoma tumor growth in mice. We hypothesize that injecting vincristine-loaded silk gel into 8 locations within the tumor, instead of only centrally, decreases the diffusion distance and improves tumor growth suppression. METHODS:Humanneuroblastoma cells, KELLY, were injected into mouse adrenal glands to create orthotopic tumors. After the tumors reached 100 mm3 by ultrasound, silk gels loaded with 50 µg vincristine were injected centrally or in 8 areas throughout the tumor. Drug-release profile was measured in vitro. Endpoints were tumor size >1,000 mm3 and histologic examination. RESULTS:Vincristine-loaded silk gels suppressed tumor growth up to an inflection point (458.7 ± 234.4 mm3 for central, 514.3 ± 165.8 mm3 for 8-point injection) before tumor growth accelerated >200 mm3 over 3 days. The time to inflection point was 6.6 days for central, 13.3 days for 8-point injection (P < .05). Using the sphere volume equation to approximate tumor volume, splitting the volume into 1/8 decreased the diffusion radius by 1/2. Histologic examination confirmed tumor necrosis adjacent to vincristine-loaded silk gel. CONCLUSION: Injecting vincristine-loaded sustained release silk gel at 8 separate locations halved the diffusion distance and doubled the time for the tumor to reach the growth inflexion point.
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