Analysis of the antiangiogenic features of carbon nanoparticles (UDD and MW-RF) in terms of the growth of brain GBM tumors and their blood vessels was performed in ovo on the chicken embryo experimental model.
Tumor weight, volume, blood vessel area, and FGF-2 and VEGF expression levels were assessed. A decrease in tumor growth in terms of its weight and volume was observed in both treated groups (). In the UDD group, the weight was reduced by 73% and the volume by 61%, and in the MW-RF group, the weight decreased by 69% and the volume by 68% compared to the control group (P < 0.05).
Weight, volume, and area of blood vessels of glioblastoma tumors
A decrease in blood vessel area was detected in the UDD and MW-RF groups versus the control group (). In the control group, 58% area of vessels was detected on average, but 19% and 25% in the UDD and MW-RF groups was detected, respectively. Except for the decreased blood vessel density after UDD and MW-RF treatment, characteristic changes in the macroscopic images of the observed blood vessels were found (). In the control group, distinctive blood vessel branching was observed; however, in the UDD and MW-RF groups, only the fragments of blood vessels and hemorrhagic processes were seen.
Images of a glioblastoma multiforme tumor cultured on chorioallantoic membrane: (A) control group, (B) ultradispersed detonation diamond group, and (C) microwave-radiofrequency group.
In the histology of GBM between the control ( ), UDD (), and MW-RF ( ) groups, strong differences were noticed. Chicken chorioallantoic membrane surrounding the tumor in the control group was thick with strong vascularity, while in the UDD and MW-RF groups, it was thin without any blood vessels. In the central part of the tumor in all the groups, fewer blood vessels were found than in the lateral part in contact with the host.
In the control group, the diameter of blood vessels varied between 2–30 μm, with a wide, transparent, and well-defined lumen. In the UDD and MW-RF groups, the blood vessels had similar dimensions as the capillary vessels (2–7 μm), while the lumen was irregular, narrow, and chink-like shaped. Endothelial cells of blood vessels in the control group had a typical shape with a flattened nucleus. In the UDD and MW-RF groups, endothelial cells had tube-like shapes and their nuclei were round. In these groups, there were also a lower number of blood vessels compared with the control group, with erythrocytes being present between the parenchymal cells of the tumor and necrotic area.
shows the results of the transcription of messenger RNA encoding FGF-2 and VEGF. There was a 69% decrease in FGF-2 expression in the UDD group compared to the control group (P < 0.05). A decrease of 33% was observed in the MW-RF group, but this was not significant. The amount of VEGF gene transcripts was also reduced in the UDD (by 72%) and MW-RF (by 48%) groups compared to the control (P < 0.05).
Fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) gene expression profile in glioblastoma tumors following ultradispersed detonation diamond (UDD) and microwave-radiofrequency (MW-RF) treatment