Article

Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

Department of Environmental and Radiological Health Sciences, Colorado State University, Ft. Collins, CO 80523, USA.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 4.44). 03/2011; 711(1-2):150-7. DOI: 10.1016/j.mrfmmm.2011.02.012
Source: PubMed

ABSTRACT Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation.

0 Followers
 · 
108 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hsp90 inhibitors have become well-studied antitumor agents for their selective property against tumors versus normal cells. The combined treatment of Hsp90 inhibitor and conventional photon radiation also showed more effective tumor growth delay than radiation alone. However, little is known regarding the combined treatment of Hsp90 inhibitor and heavy-ion irradiation. In this study, SQ5 human lung tumor cells were used in vitro for clonogenic cell survival and in vivo for tumor growth delay measurement using a mouse xenograft model after 17-allylamino-17-demethoxygeldanamycin (17AAG) pretreatment and carbon ion irradiation. Repair of DNA double strand breaks (DSBs) was also assessed along with expressions of DSB repair-related proteins. Cell cycle analysis after the combined treatment was also performed. The combined treatment of 17AAG and carbon ions revealed a promising treatment option in both in vitro and in vivo studies. One likely cause of this effectiveness was shown to be the inhibition of homologous recombination repair by 17AAG. The more intensified G2 cell cycle delay was also associated with the combined treatment when compared with carbon ion treatment alone. Our findings indicate that the combination of Hsp90 inhibition and heavy-ion irradiation provides a new effective therapeutic alternative for treatment of solid tumors.
    Cancer Medicine 01/2015; DOI:10.1002/cam4.377
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hadron therapy is a novel technique of cancer radiation therapy which employs charged particles beams, (1)H and light ions in particular. Due to their physical and radiobiological properties, they allow one to obtain a more conformal treatment, sparing better the healthy tissues located in proximity of the tumor and allowing a higher control of the disease. Objective : As it is well known, these light particles can interact with nuclei in the tissue, and produce the different secondary particles such as neutron and photon. These particles can damage specially the critical organs behind of thyroid gland. In this research, we simulated neck geometry by MCNPX code and calculated the light particles dose at distance of 2.14 cm in thyroid gland, for different particles beam: (1)H, (2)H, (3)He, and (4)He. Thyroid treatment is important because the spine and vertebrae is situated right behind to the thyroid gland on the posterior side. The results show that (2)H has the most total flux for photon and neutron, 1.944E-3 and 1.7666E-2, respectively. Whereas (1)H and (3)He have best conditions, 8.88609E-4 and 1.35431E-3 for photon, 4.90506E-4 and 4.34057E-3 for neutron, respectively. The same calculation has obtained for energy depositions for these particles. In this research, we investigated that which of these light particles can deliver the maximum dose to the normal tissues and the minimum dose to the tumor. By comparing these results for the mentioned light particles, we find out (1)H and (3)He is the best therapy choices for thyroid glands whereas (2)H is the worst.
  • [Show abstract] [Hide abstract]
    ABSTRACT: In several researches, it has been demonstrated that charged particles can induce more complex DNA damages. These complex damages have higher ability to cause the cell death or cell carcinogenesis. For this reason, clarifying the DNA repair mechanism after charged particle irradiation plays an important role in the development of charged particle therapy and space exploration. Unfortunately, the detail spatiotemporal kinetic of DNA damage repair is still unclear. In this study, we used gamma-H2AX protein to investigate the spatiotemporal kinetics of DNA double strand breaks in alpha-particle irradiated HeLa cells. The result shows that the intensity of gamma-H2AX foci increased gradually, and reached to its maximum at 30 min after irradiation. A good linear relationship can be observed between foci intensity and radiation dose. After 30 min, the gamma-H2AX foci intensity was decreased with time passed, but remained a large portion (similar to 50%) at 48 h passed. The data show that the dissolution rate of gamma-H2AX foci agreed with two components DNA repairing model. These results suggest that charged particles can induce more complex DNA damages and causing the retardation of DNA repair.
    Applied Surface Science 08/2014; 310:62-65. DOI:10.1016/j.apsusc.2014.03.079 · 2.54 Impact Factor

Full-text (2 Sources)

Download
13 Downloads
Available from
Nov 13, 2014

Similar Publications