Alama A.,Lung Cancer Unit |
Bruzzo C.,Lung Cancer Unit |
Cavalieri Z.,Lung Cancer Unit |
Forlani A.,Laboratory of Tumor Genetics and Epigenetics |
And 3 more authors.
PLoS ONE | Year: 2011
Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs) and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated. We determined the activity of α-neurotoxins from Naja atra (short-chain neurotoxin, α-cobrotoxin) and Naja kaouthia (long-chain neurotoxin, α-cobratoxin) in vitro by cytotoxicity measurements in 5 lung cancer cell lines, by colony formation assay with α7nAChRs expressing and non-expressing cell lines and in vivo by assessing tumor growth in an orthotopic Non-Obese Diabetic/Severe Combined Immunodeficient (NOD/SCID) mouse model system utilizing different treatment schedules and dosages. No statistically significant reduction in tumor growth was observed in the treatment arms in comparison to the control for both toxins. Paradoxically α-cobrotoxin from Naja atra showed the tendency to enhance tumor growth although, even in this case, the statistical significance was not reached. In conclusion our results show that, in contrast with other reports, the nAChR inhibitors α-cobratoxin from N. kaouthia and α-cobrotoxin from N. atra neither suppressed tumor growth nor prolonged the survival of the treated animals. © 2011 Alama et al.
Vinci A.D.,Laboratory of Tumor Genetics and Epigenetics |
Casciano I.,Laboratory of Tumor Genetics and Epigenetics |
Marasco E.,S. Orsola Malpighi University Hospital |
Banelli B.,Laboratory of Tumor Genetics and Epigenetics |
And 13 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2012
Purpose The purpose of this study was to determine whether specific HOXA epigenetic signatures could differentiate glioma with distinct biological, pathological, and clinical characteristics. Methods Weevaluated HOXA3, 7, 9, and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing. Results We demonstrated the direct statistical correlation between the level ofmethylation of allHOXA genes examined andWHOgrading.Moreover, in glioblastoma patients, higher level of HOXA9 and HOXA10 methylation significantly correlated with increased survival probability (HOXA9-HR: 0.36, P = 0.007;HOXA10-HR: 0.46, P = 0.045; combined HOXA9 and 10-HR 0.28, P = 0.004). Conclusions This study identifies HOXA3, 7, 9, and 10 as methylation targets mainly in high-grade glioma and hypermethylation of the HOXA9 and 10 as prognostic factor in glioblastoma patients. Our data indicate that these epigenetic changes may be biomarkers of clinically different subgroups of glioma patients that could eventually benefit from personalized therapeutic strategies. © 2011 Springer-Verlag.