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, F�鶹��ýӳ��	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stanley H. Appel, MD, F�鶹��ýӳ�� (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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