Intratumoral delivery of bortezomib: impact on survival in an intracranial glioma tumor model
| Autor: | Nagore I Marin’ Ramos, Florence M. Hofman, Thomas C. Chen, Hee-Yeon Cho, Kyle Hurth, Ryan Price, Rachel Rosenstein-Sisson, Axel H. Schönthal, Weijun Wang |
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| Rok vydání: | 2018 |
| Předmět: |
Mice
Nude Antineoplastic Agents Injections Intralesional Pharmacology Bortezomib Mice 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine In vivo Cell Line Tumor Glioma medicine Animals Humans U87 neoplasms Brain Neoplasms business.industry General Medicine medicine.disease Xenograft Model Antitumor Assays In vitro Tumor progression 030220 oncology & carcinogenesis Drug delivery Proteasome inhibitor Cancer research Glioblastoma business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Neurosurgery. 128:695-700 |
| ISSN: | 1933-0693 0022-3085 |
| DOI: | 10.3171/2016.11.jns161212 |
| Popis: | OBJECTIVEGlioblastoma (GBM) is the most prevalent and the most aggressive of primary brain tumors. There is currently no effective treatment for this tumor. The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. The authors' goal was to demonstrate that bortezomib can be effective in the orthotopic GBM murine model if the appropriate method of drug delivery is used. In this study the Alzet mini-osmotic pump was used to bring the drug directly to the tumor in the brain, circumventing the blood-brain barrier; thus making bortezomib an effective treatment for GBM.METHODSThe 2 human glioma cell lines, U87 and U251, were labeled with luciferase and used in the subcutaneous and intracranial in vivo tumor models. Glioma cells were implanted subcutaneously into the right flank, or intracranially into the frontal cortex of athymic nude mice. Mice bearing intracranial glioma tumors were implanted with an Alzet mini-osmotic pump containing different doses of bortezomib. The Alzet pumps were introduced directly into the tumor bed in the brain. Survival was documented for mice with intracranial tumors.RESULTSGlioma cells were sensitive to bortezomib at nanomolar quantities in vitro. In the subcutaneous in vivo xenograft tumor model, bortezomib given intravenously was effective in reducing tumor progression. However, in the intracranial glioma model, bortezomib given systemically did not affect survival. By sharp contrast, animals treated with bortezomib intracranially at the tumor site exhibited significantly increased survival.CONCLUSIONSBypassing the blood-brain barrier by using the osmotic pump resulted in an increase in the efficacy of bortezomib for the treatment of intracranial tumors. Thus, the intratumoral administration of bortezomib into the cranial cavity is an effective approach for glioma therapy. |
| Databáze: | OpenAIRE |
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