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Inhibitory effect of adenosine dialdehyde on in situ murine neuroblastoma growth
B Bostrom1, H P Hogenkamp, B L Mirkin
1Department of Pediatrics, Variety Club Children's Hospital, University of Minnesota, Minneapolis 55455.
Abstract:
The effect of adenosine dialdehyde (AD) on in situ tumor growth and host survival was evaluated in the C1300 murine neuroblastoma tumor model prepared by implantation of murine neuroblastoma cells into A/J mice. AD was administered s.c. by one of the following treatment regimens: regimen A, single daily dose for 5 days; regimen B, minipump infusion for 7 days; regimen C, minipump infusion for 14 days; regimen D, minipump infusion for two 7-day periods interspersed by a 7-day drug free interval. AD doses of 1.5 to 2.5 mg/kg/day infused over a 7-day period (regimen B) significantly increased the mean life span of tumor bearing mice from 20.9 +/- 1.2 days (mean +/- 2 SEM) in diluent treated controls to 35.3 +/- 2.1 days in AD treated animals (mean increase +/- 2 SEM: 69 +/- 10%; P less than 0.0001). This treatment regimen also produced a 56 +/- 13% decrease in tumor diameter (P less than 0.0001). Administration of AD for two 7-day infusion periods, interspersed by a 7-day drug free interval (regimen D), increased mean life span 80% (controls, 21.3 +/- 4.4 days; AD treated 38.4 +/- 5.6 days; P less than 0.0005). Hematopoietic toxicity was not observed when doses between 2 and 3 mg/kg/day of AD were infused for 7 days (regimen B). These data suggest that steady state infusions of AD can significantly suppress murine neuroblastoma tumor growth with little systemic toxicity. In contrast, single daily injections of AD were ineffective and toxic to the tumor bearing host.
Insights
Adenosine dialdehyde (AD) significantly improved survival and reduced tumor size in mice with neuroblastoma when administered via continuous infusion. Daily injections of AD were ineffective and toxic, highlighting the importance of delivery method for this cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Neuroblastoma is a pediatric cancer with varying prognoses.
- Developing effective treatments with minimal toxicity is crucial.
- Adenosine dialdehyde (AD) is being investigated for its anti-cancer properties.
Purpose of the Study:
- To evaluate the efficacy of adenosine dialdehyde (AD) in treating C1300 murine neuroblastoma.
- To assess the impact of different administration regimens on tumor growth and host survival.
- To determine the toxicity profile of AD in a preclinical cancer model.
Main Methods:
- Murine neuroblastoma cells (C1300) were implanted into A/J mice.
- Adenosine dialdehyde (AD) was administered via subcutaneous injection or minipump infusion over 5, 7, or 14 days, or two 7-day cycles.
- Tumor growth, host survival, and systemic toxicity were monitored.
Main Results:
- Continuous 7-day infusion of AD (1.5-2.5 mg/kg/day) significantly increased mean lifespan by 69% and reduced tumor diameter by 56%.
- A repeated 7-day infusion regimen also increased mean lifespan by 80%.
- No hematopoietic toxicity was observed with 7-day infusions at doses of 2-3 mg/kg/day, whereas daily injections were toxic and ineffective.
Conclusions:
- Steady-state infusions of adenosine dialdehyde (AD) show significant potential in suppressing murine neuroblastoma growth.
- Continuous infusion is a superior delivery method compared to daily injections for AD efficacy and safety.
- AD demonstrates a favorable therapeutic window for neuroblastoma treatment in this preclinical model.