Abstract Details

Title Effects of Lazaroid U-74389G Liposomes in a Glioblastoma Mouse Model

Topic Neuro-oncology

Presentation(s) P02 - (-)

Poster/Presentation
Number 159

Objective

Background BACKGROUND: LAZ is a 21-aminosteroid that has radioprotective effects against radiation-induced lipid peroxidation. Also antiproliferative effects have been reported against glioblastoma cell lines.

Design/Methods DESIGN/METHODS: LAZ PEGylated liposomes (Lipo G) were developed at the University of Houston. Glioblastoma cell line U87-expressing firefly luciferase reporter gene (100,000 cells in 2 [mu]L) was injected intracranially in each SCID mouse. There were 4 treatment groups (n=8-9, each): brain model (M) without treatment (control), radiation 2Gy weekly (M+R), Lipo G at 5 mg/kg dose intraperitoneally twice per week (M+L) and radiation with Lipo G (M+R+L). Treatment lasted three weeks. Tumor size was monitored using bioluminescence imaging (BLI), in each mouse. Mice were sacrificed after 3 weeks. Brain was harvested. Lipid peroxidation of brain tissues was quantified by measuring malondialdehyde (MDA) as a surrogate biomarker. Survival was evaluated using Kaplan Meier analysis at P= 0.05.

Results RESULTS: BLI intensity was 4002.03±1737.67, 2034±737.72, 1387.36±684.53 and 2498.89±2521.32 % for M, M+R, M+L and M+R+L, respectively. Tumor size of the M+L group was reduced by 65% compared to control . There was no significant difference in tumor size of radiated groups compared to control group. MDA brain concentration in M+L and M+R+L groups was significantly less than in M+R group (8.27±0.78 and 10.37±3.30 [micro]M/gm vs. 23.09± 3.79 [micro]M/gm). The survival mean was 22.67, 25.33, 25.22 and 27.13 days for M, M+R, M+R+L and M+L groups, respectively. Mean survival of LAZ treated groups (M+L and M+R+L) was significantly longer than that of the control group.

Conclusions CONCLUSIONS: LAZ liposomal formulations reduced tumor growth by 65%. LAZ also protected brain tissue from radiation-induced lipid peroxidation by reducing MDA concentration by 50%. These provocative data warrant further investigation of LAZ as a radiation protectant and chemotherapeutic agent.

Authors/Disclosures
PRESENTER	No disclosure on file
Pamela Z. New, MD, FAAN	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stanley H. Appel, MD, FAAN (Methodist Neurological Institute)	Dr. Appel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Appel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eledon. The institution of Dr. Appel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Implicit. The institution of Dr. Appel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Coya Therapeutics. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Muscular Disease Association. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ALS Therapy Development Institute. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ALS Finding a Cure. Dr. Appel has stock in Stock holdings in retirement acct at Fidelity. The institution of Dr. Appel has received research support from Coya Therapeutics.

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