|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Basic and Translational Investigations |
1 Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA 94103
2 Division of Hematology-Oncology, University of California, San Francisco, San Francisco, CA 94103
3 Hermes Biosciences, Inc., South San Francisco, CA 94080
4 Division of Hematology-Oncology, University of California, San Francisco, San Francisco, CA 94103 and Hermes Biosciences, Inc., South San Francisco, CA 94080
* To whom correspondence should be addressed. E-mail: Krystof.Bankiewicz{at}ucsf.edu.
 |
Abstract |
|---|
Despite multimodal treatment options, the response and survival rates for patients with malignant gliomas remain dismal. Clinical trials with convection-enhanced delivery (CED) have recently opened a new window in neuro-oncology to the direct delivery of chemotherapeutics to the CNS, circumventing the blood-brain barrier and reducing systemic side effects. Our previous CED studies with liposomal chemotherapeutics have shown promising antitumor activity in rodent brain tumor models. In this study, we evaluated a combination of nanoliposomal topotecan (nLs-TPT) and pegylated liposomal doxorubicin (PLD) to enhance efficacy in our brain tumor models, and to establish a CED treatment capable of improving survival from malignant brain tumors. Both liposomal drugs decreased key enzymes involved in tumor cell replication in vitro. Synergistic effects of nLs-TPT and PLD on U87MG cell death were found. The combination displayed excellent efficacy in a CED-based survival study 10 days after tumor cell implantation. Animals in the control group and those in single-agent groups had a median survival of less than 30 days, whereas the combination group experienced a median survival of more than 90 days. We conclude that CED of two liposomal chemotherapeutics (nLs-TPT and PLD) may be an effective treatment option for malignant gliomas.
Key Words: brain tumor, CED, convection-enhanced delivery, glioma, liposome, topotecan
This article has been cited by other articles:
|
|
 |
|
  M. T. Krauze, C. O. Noble, T. Kawaguchi, D. Drummond, D. B. Kirpotin, Y. Yamashita, E. Kullberg, J. Forsayeth, J. W. Park, and K. S. Bankiewicz Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts Neuro-oncol, October 1, 2007; 9(4): 393 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
