Exth-48. Oral Gallium Maltolate Impairs Tumor Growth and Extends Disease-specific Survival in a Xenograft Model of Recurrent Gbm
Year: 2018
Type: conference-abstract
Abstract: Recurrent glioblastoma (rGBM) is a distinctly different disease condition than de novo GBM, characterized by chemo- and radioresistance. Consequently, treatment options remain limited. Given our recently published promising results using the novel iron mimetic, gallium maltolate (GaM), in a rat xenograft of de novo GBM, we set out to investigate the effects of oral GaM in an in vivo model of rGBM. Irradiated adult human GBM cells were stereotactically implanted into the right striatum of 12 male athymic rats. Following confirmation of in vivo tumor growth by advanced MRI at 9.4T on day 14 post-implantation, animals received GaM (50 mg/kg/day, n=5) in an oral preparation for voluntary ingestion. Two animals received daily oral GaM continuously throughout the study period, while three underwent a 2-week on, 1-week off treatment cycle. Tumor growth was monitored weekly by MRI, and lesion volume and associated parameter maps were determined using enhancing tumor ROIs. Mean compliance with voluntary ingestion of GaM was 97% (49 mg/kg/day). Complete longitudinal MRI data was available for 5 GaM rats and 5 controls. The mean weekly tumor growth rates of enhancing lesions were 78% and 156% in GaM-treated and control animals, respectively (p=0.006). Median disease-specific survival was 28 days in controls and 49 days in GaM-treated animals, with 3/5 treated animals still alive (p=0.004). Preliminary histological findings in GaM-treated tumor tissue indicate treatment effect (swollen cells, degeneration and/or granulation of cytoplasm) and apoptotic cells throughout the lesions, compared to pseudopalisading necrosis and standard tumor cell size in control tissues. No adverse physiological effects due to treatment were noted. We presented compelling evidence that oral GaM significantly impairs tumor growth and extends disease-specific survival in a xenograft model of rGBM. We propose that GaM shows great promise as a new interventional strategy for GBM therapy.
Source: Neuro-Oncology
Authors: Mona Al-Gizawiy, Wujek Robert, Hisham Alhajala, Jonathan Cobb, Melissa Prah, Shama Mirza, Christopher Chitambar, Kathleen Schmainda
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2899608982