Abstract

This proposal addresses novel therapeutic approaches to treat osteosarcoma (OS), utilizing a mouse model and translating the findings to clinical trials. Specifically, the investigator proposes to use aerosolized delivery of liposomal 9-nitro-camptothecin and gene therapy (intranasal) using IL-12 delivered as an adenovirus vector or polyethyleneimine. These studies will be carried out in a nude mouse model with injection of a metastatic subline of SAOS. Studies of efficacy will include survival, tumor nodule number and size, and histological evaluation of vessel ingrowth and expression of IL-12. Clinical trials will consist of a phase I trial of aerosolized liposomal 9-nitro-camptothecin in which patients with relapsed OS will be enrolled. An additional aim of the proposal is to look at the role of Fas expression in the metastatic potential of LM6 cells and to determine if IL-12 affects Fas expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042992-18
Application #
6632876
Study Section
Special Emphasis Panel (ZRG1-ET-1 (01))
Program Officer
Wu, Roy S
Project Start
1986-08-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
18
Fiscal Year
2003
Total Cost
$339,750
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Biology
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Yang, Yuanzheng; Huang, Gangxiong; Zhou, Zhichao et al. (2018) miR-20a Regulates FAS Expression in Osteosarcoma Cells by Modulating FAS Promoter Activity and Can be Therapeutically Targeted to Inhibit Lung Metastases. Mol Cancer Ther 17:130-139
Guma, Sergei R; Lee, Dean A; Yu, Ling et al. (2014) Natural killer cell therapy and aerosol interleukin-2 for the treatment of osteosarcoma lung metastasis. Pediatr Blood Cancer 61:618-26
Rao-Bindal, Krithi; Rao, Chethan K; Yu, Ling et al. (2013) Expression of c-FLIP in pulmonary metastases in osteosarcoma patients and human xenografts. Pediatr Blood Cancer 60:575-9
Hollomon, Mario G; Gordon, Nancy; Santiago-O'Farrill, Janice M et al. (2013) Knockdown of autophagy-related protein 5, ATG5, decreases oxidative stress and has an opposing effect on camptothecin-induced cytotoxicity in osteosarcoma cells. BMC Cancer 13:500
Rao-Bindal, Krithi; Koshkina, Nadezhda V; Stewart, John et al. (2013) The histone deacetylase inhibitor, MS-275 (entinostat), downregulates c-FLIP, sensitizes osteosarcoma cells to FasL, and induces the regression of osteosarcoma lung metastases. Curr Cancer Drug Targets 13:411-22
Huang, Gangxiong; Yu, Ling; Cooper, Laurence Jn et al. (2012) Genetically modified T cells targeting interleukin-11 receptor ?-chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases. Cancer Res 72:271-81
Rao-Bindal, K; Zhou, Z; Kleinerman, E S (2012) MS-275 sensitizes osteosarcoma cells to Fas ligand-induced cell death by increasing the localization of Fas in membrane lipid rafts. Cell Death Dis 3:e369
Huang, Gangxiong; Nishimoto, Kazumasa; Zhou, Zhichao et al. (2012) miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res 72:908-16
Koshkina, Nadezhda V; Rao-Bindal, Krithi; Kleinerman, Eugenie S (2011) Effect of the histone deacetylase inhibitor SNDX-275 on Fas signaling in osteosarcoma cells and the feasibility of its topical application for the treatment of osteosarcoma lung metastases. Cancer 117:3457-67
Rodriguez Jr, Carlos O; Crabbs, Torrie A; Wilson, Dennis W et al. (2010) Aerosol gemcitabine: preclinical safety and in vivo antitumor activity in osteosarcoma-bearing dogs. J Aerosol Med Pulm Drug Deliv 23:197-206

Showing the most recent 10 out of 79 publications