Fast Neutrons and High-LET Particles in Cancer Therapy

1998 ◽  
Keyword(s):  
Cancer Therapy ◽  
Fast Neutrons ◽  
High Let

Fast neutrons and Π-1 mesons in cancer therapy

1971 ◽  
Vol 18 (3) ◽  
pp. 36-45 ◽  
Author(s):  
Max L. M. Boone ◽  
Albert L. Wiley
Keyword(s):  
Cancer Therapy ◽  
Fast Neutrons

Induction and disappearance of G2 chromatid breaks in lymphocytes after low doses of low-LET γ -rays and high-LET fast neutrons

2002 ◽  
Vol 78 (4) ◽  
pp. 249-257 ◽  
Author(s):  
A. Vral ◽  
H. Thierens ◽  
A. Baeyens ◽  
L. De Ridder
Keyword(s):  
Fast Neutrons ◽  
Low Doses ◽  
High Let ◽  
Γ Rays

Induction of apoptosis by high linear energy transfer radiation: role of p53

2002 ◽  
Vol 80 (7) ◽  
pp. 644-649 ◽  
Author(s):  
D Coelho ◽  
B Fischer ◽  
V Holl ◽  
P Dufour ◽  
J M Denis ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Cell Line ◽  
Linear Energy Transfer ◽  
Lymphoblastoid Cell Line ◽  
Cellular Damage ◽  
Fast Neutrons ◽  
X Rays ◽  
Carbon Ions ◽  
High Let Radiation ◽  
High Let

The involvement of the tumor suppressor p53 gene in the sensitivity of many cell types towards low linear energy transfer (LET) radiation is now well established. However, little information is available on the relationship between p53 status of tumor cells and their ability to undergo apoptosis following exposure to high-LET radiation. Here we present the results of experiments carried out with the human lymphoblastoid cell line TK6 and its p53 knock-out counterpart NH32. Cells were irradiated at doses ranging from 0.25 to 8 Gy with fast neutrons (65 MeV), carbon ions (95 MeV/nucleon), and X rays (15 MV). For both cell lines, the occurrence of apoptosis, determined by the quantification of hypodiploid particles as well as the activation of several caspases, was compared with their sensitivity towards high-LET radiation. Results indicate that p53 is involved in the response of TK6 cells to fast neutrons and carbon ions, as measured by cell proliferation and occurrence of apoptosis. However, p53-deficient cells are still able to undergo apoptosis following irradiation. This suggests that heavy ions and fast neutrons induce cellular damage that is not under the control of p53. The involvement of executioner caspases in high-LET radiation induced apoptosis was also evaluated by use of specific inhibitors.Key words: fast neutrons, carbon ions, apoptosis, p53, lymphoblastoid cell line.

Cisplatin enhances the cytotoxicity of fast neutrons in a murine lymphoma cell line

2004 ◽  
Vol 82 (2) ◽  
pp. 140-145 ◽  
Author(s):  
B Fischer ◽  
S Benzina ◽  
V Ganansia-Leymarie ◽  
J M Denis ◽  
J P Bergerat ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Cell Lymphoma ◽  
Fast Neutrons ◽  
Lymphoma Cell Line ◽  
Carbon Ions ◽  
Time Intervals ◽  
Proliferation And Apoptosis ◽  
High Let ◽  
High Linear Energy Transfer

The utilization of high linear energy transfer (LET) radiations, such as fast neutrons or carbon ions (hadrontherapy), offers promising perspectives in radiotherapy. While it is well known that by combining radiotherapy and chemotherapy, important therapeutic advantages can be obtained to cure cancer, there have been, so far, very few investigations on the effects of treatments combining an irradiation with high-LET particles and cancer drugs. The present study was therefore undertaken to examine the effects of exposure to 65 MeV fast neutrons combined with cisplatin in a murine T cell lymphoma (RDM4) in vitro. The cells were irradiated at doses ranging from 2 to 8 Gy without or with addition of cisplatin shortly before the irradiation, at concentrations between 0.3 and 12.5 µM. These treatments were applied concomitantly. Proliferation and apoptosis were assessed at different time intervals thereafter. The combination of irradiation with cisplatin was found to be more cytotoxic than either treatment alone. Furthermore, the cytotoxicity induced by this cotreatment resulted not only from apoptosis but also from other forms of cell death.Key words: apoptosis, cancer cells, fast neutrons, cisplatin.

Radiobiological rationale and patient selection for high-LET radiation in cancer therapy

2004 ◽  
Vol 73 ◽  
pp. S1-S14 ◽  
Author(s):  
André Wambersie ◽  
Jolyon Hendry ◽  
John Gueulette ◽  
Reinhard Gahbauer ◽  
Richard Pötter ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Patient Selection ◽  
High Let Radiation ◽  
High Let ◽  
Selection For

Fast neutrons: Inexpensive and reliable tool to investigate high-LET particle radiobiology

2010 ◽  
Vol 45 (10) ◽  
pp. 1414-1416 ◽  
Author(s):  
J. Gueulette ◽  
J.P. Slabbert ◽  
P. Bischoff ◽  
J.M. Denis ◽  
A. Wambersie ◽  
...  
Keyword(s):  
Fast Neutrons ◽  
Reliable Tool ◽  
High Let

scholarly journals Differential effects of high versus low linear energy transfer (LET) radiation on type-I interferon (IFNβ) and TREX1 responses

2021 ◽  
Author(s):  
Devin Miles ◽  
Ning Cao ◽  
George Sandison ◽  
Robert D Stewart ◽  
Greg Moffitt ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Bragg Peak ◽  
Type I Interferon ◽  
Absorbed Dose ◽  
Fast Neutrons ◽  
Type I ◽  
X Rays ◽  
High Let ◽  
Unit Dose

Purpose: Cancer cells produce innate immune signals following radiation damage, with STING pathway signaling as a critical mediator. High linear energy transfer (LET) radiations create larger numbers of DNA double-strand breaks (DSBs) per unit dose than low-LET radiations and may therefore be more immunogenic. We studied the dose response characteristics of pro-immunogenic type-I interferon, interferon-beta (IFNβ), and its reported suppressor signal, three-prime repair exonuclease 1 (TREX1), in vitro with low-LET x-rays and high-LET fast neutrons. Methods: Merkel cell carcinoma cells (MCC) were irradiated by graded doses of x-rays (1-24 Gy) or fast neutrons (1-8 Gy). IFNβ was measured as a function of dose via ELISA assay, and exonuclease TREX1 expression via immunofluorescence microscopy. The Monte Carlo damage simulation (MCDS) was used to model fast neutron relative biological effectiveness for DSB induction (RBEDSB) and compared to laboratory measurements of the RBE for IFNβ production (RBEIFNβ) and TREX1 upregulation (RBETREX1). RBEIFNβ models were also applied to radiation transport simulations to quantify the potential secretion of IFNβ in representative clinical beams. Results: Peak IFNβ secretion occurred at 5.7 Gy for fast neutrons and at 14.0 Gy for x-rays, i.e., an effective RBEIFNβ of 2.5 ± 0.2. The amplitude (peak value) of secreted IFNβ signal did not significantly differ between x-rays and fast neutrons (P > 0.05). TREX1 signal increased linearly with absorbed dose, with a four-fold higher upregulation per unit dose for fast neutrons relative to x-rays (RBETREX1 of 4.0 ± 0.1). Monte Carlo modeling of IFNβ suggests Bragg peak-to-entrance ratios of IFNβ production of 40, 100, and 120 for proton, alpha, and carbon ion beams, respectively, a factor of 10-20-fold higher compared to their corresponding physical dose peak-to-entrance ratios. The spatial width of the Bragg peak for IFNβ production is also a factor of two smaller. Conclusion: High-LET fast neutrons initiate a larger IFNβ response per unit absorbed dose than low-LET x-rays (i.e., RBEIFNβ value of 2.5). The RBE value for IFNβ is quite similar to data reported in the literature for DSB induction and cellular, post-irradiation micronucleation formation for neutrons and x-rays. The increased IFNβ release after high-LET radiation may be a contributing factor in stimulating a systemic anti-tumor, adaptive immune response (abscopal effect). However, our results indicate that TREX1 anti-inflammatory signaling in vitro for MCC cells is larger per unit dose for fast neutrons than for x-rays (RBETREX1 of 4.0). Given these competing effects, additional studies are needed to clarify whether or not high-LET radiations are therapeutically advantageous over low-LET radiation for pro-inflammatory immune signaling in other cell lines in vitro and for in vivo cancer models.

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