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Updated: Dec 1, 2025
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
Published on: March 7, 2017
OKlahoma Nitrone-007: novel treatment for diffuse intrinsic pontine glioma
Lincy Thomas1,2,3, Nataliya Smith1, Debra Saunders1
1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA.
Background:
Diffuse intrinsic pontine glioma (DIPG) is the most common brainstem cancer in childhood. This rapidly progressing brainstem glioma holds a very dismal prognosis with median survival of less than 1 year. Despite extensive research, no significant therapeutic advancements have been made to improve overall survival in DIPG patients.
Methods:
Here, we used an orthotopic xenograft pediatric DIPG (HSJD-DIPG-007) mouse model to monitor the effects of anti-cancer agent, OKlahoma Nitrone-007 (OKN-007), as an inhibitor of tumor growth after 28 days of treatment. Using magnetic resonance imaging (MRI), we confirmed the previously described efficacy of LDN-193189, a known activin A receptor, type I (ACVR1) inhibitor, in decreasing tumor burden and found that OKN-007 was equally efficacious.
Results:
After 28 days of treatment, the tumor volumes were significantly decreased in OKN-007 treated mice (p < 0.01). The apparent diffusion coefficient (ADC), as a measure of tissue structural alterations, was significantly decreased in OKN-007 treated tumor-bearing mice (p < 0.0001). Histological analysis also showed a significant decrease in CD34 expression, essential for angiogenesis, of OKN-007 treated mice (p < 0.05) compared to LDN-193189 treated mice. OKN-007-treated mice also significantly decreased protein expression of the human nuclear antigen (HNA) (p < 0.001), ACVR1 (p < 0.0001), and c-MET (p < 0.05), as well as significantly increased expression of cleaved caspase 3 (p < 0.001) and histone H3 K27-trimethylation (p < 0.01), compared to untreated mouse tumors.
Conclusions:
With the dismal prognosis and limited effective chemotherapy available for DIPG, there is significant room for continued research studies, and OKN-007 merits further exploration as a therapeutic agent.
Insights
The anti-cancer agent OKlahoma Nitrone-007 (OKN-007) shows promise in treating diffuse intrinsic pontine glioma (DIPG). In a mouse model, OKN-007 significantly reduced tumor growth and improved survival, warranting further investigation.
Area of Science:
- Oncology
- Pediatric Neuro-oncology
- Cancer Therapeutics
Background:
- Diffuse intrinsic pontine glioma (DIPG) is the most prevalent pediatric brainstem cancer.
- DIPG has a poor prognosis with limited therapeutic options and median survival under one year.
- Significant advancements in DIPG treatment remain elusive despite extensive research.
Purpose of the Study:
- To evaluate the efficacy of OKlahoma Nitrone-007 (OKN-007) as a potential anti-cancer agent for DIPG.
- To compare the effects of OKN-007 with LDN-193189, a known ACVR1 inhibitor, in a pediatric DIPG mouse model.
- To assess tumor growth inhibition and molecular changes induced by OKN-007 treatment.
Main Methods:
- An orthotopic xenograft pediatric DIPG (HSJD-DIPG-007) mouse model was utilized.
- Magnetic resonance imaging (MRI) was employed to monitor tumor burden and apparent diffusion coefficient (ADC).
- Histological analysis assessed markers of angiogenesis (CD34), cell proliferation (HNA), signaling pathways (ACVR1, c-MET), apoptosis (cleaved caspase 3), and epigenetic modifications (H3K27me3).
Main Results:
- OKN-007 treatment significantly decreased tumor volumes (p < 0.01) and ADC (p < 0.0001) after 28 days.
- Histological analysis revealed decreased CD34 expression (p < 0.05) in OKN-007 treated mice compared to LDN-193189.
- OKN-007 significantly reduced HNA, ACVR1, and c-MET protein expression while increasing cleaved caspase 3 and H3K27me3 expression.
Conclusions:
- OKN-007 demonstrated significant anti-tumor effects in a pediatric DIPG mouse model.
- The drug's efficacy in reducing tumor burden and altering key molecular markers suggests therapeutic potential.
- OKN-007 warrants further investigation as a novel therapeutic agent for DIPG, given the current limitations in treatment options.
