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- Gleissman, Helena, et al.
(author)
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Omega-3 fatty acid supplementation delays the progression of neuroblastoma in vivo
- 2011
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 128:7, s. 1703-1711
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Journal article (peer-reviewed)abstract
- Epidemiological and preclinical studies have revealed that omega-3 fatty acids have anticancer properties. We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA) induces apoptosis of neuroblastoma cells in vitro by mechanisms involving intracellular peroxidation of DHA by means of 15-lipoxygenase or autoxidation. In our study, the effects of DHA supplementation on neuroblastoma tumor growth in vivo were investigated using two complementary approaches. For the purpose of prevention, DHA as a dietary supplement was fed to athymic rats before the rats were xenografted with human neuroblastoma cells. For therapeutic purposes, athymic rats with established neuroblastoma xenografts were given DHA daily by gavage and tumor growth was monitored. DHA levels in plasma and tumor tissue were analyzed by gas liquid chromatography. DHA delayed neuroblastoma xenograft development and inhibited the growth of established neuroblastoma xenografts in athymic rats. A revised version of the Pediatric Preclinical Testing Program evaluation scheme used as a measurement of treatment response showed that untreated control animals developed progressive disease, whereas treatment with DHA resulted in stable disease or partial response, depending on the DHA concentration. In conclusion, prophylactic treatment with DHA delayed neuroblastoma development, suggesting that DHA could be a potential agent in the treatment of minimal residual disease and should be considered for prevention in selected cases. Treatment results on established aggressive neuroblastoma tumors suggest further studies aiming at a clinical application in children with high-risk neuroblastoma.
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| 2. |
- Rasmuson, Agnes, et al.
(author)
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Tumor Development, Growth Characteristics and Spectrum of Genetic Aberrations in the TH-MYCN Mouse Model of Neuroblastoma
- 2012
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12
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Journal article (peer-reviewed)abstract
- Background: The TH-MYCN transgenic neuroblastoma model, with targeted MYCN expression to the developing neural crest, has been used to study neuroblastoma development and evaluate novel targeted tumor therapies. Methods: We followed tumor development in 395 TH-MYCN (129X1/SvJ) mice (125 negative, 206 hemizygous and 64 homozygous mice) by abdominal palpations up to 40 weeks of age. DNA sequencing of MYCN in the original plasmid construct and mouse genomic DNA was done to verify the accuracy. Copy number analysis with Affymetrix(R) Mouse Diversity Genotyping Arrays was used to characterize acquired genetic aberrations. Results: DNA sequencing confirmed presence of human MYCN cDNA in genomic TH-MYCN DNA corresponding to the original plasmid construct. Tumor incidence and growth correlated significantly to transgene status with event-free survival for hemizygous mice at 50%, and 0% for homozygous mice. Hemizygous mice developed tumors at 5.6-19 weeks (median 9.1) and homozygous mice at 4.0-6.9 weeks (5.4). The mean treatment window, time from palpable tumor to sacrifice, for hemizygous and homozygous mice was 15 and 5.2 days, respectively. Hemizygous mice developing tumors as early as homozygous mice had a longer treatment window. Age at tumor development did not influence treatment window for hemizygous mice, whereas treatment window in homozygous mice decreased significantly with increasing age. Seven out of 10 analysed tumors had a flat DNA profile with neither segmental nor numerical chromosomal aberrations. Only three tumors from hemizygous mice showed acquired genetic features with one or more numerical aberrations. Of these, one event corresponded to gain on the mouse equivalent of human chromosome 17. Conclusion: Hemizygous and homozygous TH-MYCN mice have significantly different neuroblastoma incidence, tumor growth characteristics and treatment windows but overlap in age at tumor development making correct early genotyping essential to evaluate therapeutic interventions. Contrasting previous studies, our data show that TH-MYCN tumors have few genetic aberrations.
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