Repair of potentially lethal damage by total and quiescent cells in solid tumors following a neutron capture reaction

Masunaga, Shin‐ichiro; Ono, Koji; Suzuki, Minoru; Sakurai, Yoshinori; Takagaki, Masao; Kobayashi, Tooru; Kinashi, Yuko; Akaboshi, Mitsuhiko

doi:10.1007/s004320050323

Cited by 7 publications

(1 citation statement)

References 15 publications

(24 reference statements)

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“…In contrast, thermal neutron irradiation without the 10 B-carrier induced the smallest recovery capacity in both cell populations. The use of a 10 B-carrier, especially BPA, resulted in an increase in the recovery capacity in both cell populations, and made the recovery patterns of the two cell populations look like those induced by γ-ray irradiation [ 37 ]. In both the total and Q tumor cells, the HFs increased suddenly immediately after neutron irradiation.…”

Section: Directly-demonstrated Characteristics Of Q Tumor Cell Populamentioning

confidence: 99%

An attempt to improve the therapeutic effect of boron neutron capture therapy using commonly employed 10B-carriers based on analytical studies on the correlation among quiescent tumor cell characteristics, tumor heterogeneity and cancer stemness

Masunaga

Yukitoshi

Tano

et al. 2020

Journal of Radiation Research

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Based on our previously published reports concerning the response of quiescent (Q) tumor cell populations to boron neutron capture therapy (BNCT), the heterogeneous microdistribution of 10B in tumors, which is influenced by the tumor microenvironment and the characteristics of the 10B delivery carriers, has been shown to limit the therapeutic effect of BNCT on local tumors. It was also clarified that the characteristics of 10B-carriers for BNCT and the type of combined treatment in BNCT can also affect the potential for distant lung metastases from treated local tumors. We reviewed the findings concerning the response of Q tumor cell populations to BNCT, mainly focusing on reports we have published so far, and we identified the mode of BNCT that currently offers the best therapeutic gain from the viewpoint of both controlling local tumor and suppressing the potential for distant lung metastasis. In addition, based on the finding that oxygenated Q tumor cells showed a large capacity to recover from DNA damage after cancer therapy, the interrelationship among the characteristics in Q tumor cell populations, tumor heterogeneity and cancer stemness was also discussed.

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Section: Directly-demonstrated Characteristics Of Q Tumor Cell Populamentioning

confidence: 99%

An attempt to improve the therapeutic effect of boron neutron capture therapy using commonly employed 10B-carriers based on analytical studies on the correlation among quiescent tumor cell characteristics, tumor heterogeneity and cancer stemness

Masunaga

Yukitoshi

Tano

et al. 2020

Journal of Radiation Research

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Computational assessment of improved cell-kill by gadolinium-supplemented boron neutron capture therapy

Culbertson

Jevremović

2003

Phys. Med. Biol.

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Potential improvement in neutron capture therapy (NCT) by utilizing both 157Gd and 10B is assessed considering two parameters calculated in transport models in MCNP4B, the dose to quiescent cells and the therapeutic ratio. Improved sterilization of quiescent or more generally non-uptaking cells is demonstrated with the addition of 157Gd to conventional 10B loading. The improved dose delivery to non-uptaking cells from concurrent administration of 157Gd and 10B is weighed against a second index, degradation in the therapeutic ratio resulting from the longer interaction lengths of the 157Gd capture products. Optimal concentrations of 157Gd are determined considering varying assumptions for boron uptake levels and selectivity. By analysing the dosimetry results of varying 157Gd concentrations applied concurrently with BPA-delivered boron in NCT, this work seeks to determine a balance between the high tumour-specific dose provided by BPA and the high dose to quiescent cells provided by potential gadolinium agents. Depending upon the assumptions for drug specificity, tumour size and fraction of quiescent cells, NCT with low levels of 157Gd (125 microg g(-1)) supplementing 10B loadings was shown to be superior to treatments applying 10B alone.

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Evaluation of the genotoxic effects of the boron neutron capture reaction in human melanoma cells using the cytokinesis block micronucleus assay

Oliveira¹

2001

Mutagenesis

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The present work reports on the genotoxicity of the boron neutron capture (BNC) reaction in human metastatic melanoma cells (A2058) assessed by the cytokinesis block micronucleus assay (CBMN) using p-borono-L-phenylalanine (BPA) as the boron delivery agent. Different concentrations of BPA (0.48, 1.2 and 2.4 mM) and different fluences of thermal neutrons were studied. Substantial genotoxic potential of alpha and lithium particles generated inside or near the malignant cell by the BNC reaction was observed in a dose-response manner as measured by the frequency of micronucleated binucleated melanoma cells and by the number of micronuclei (MN) per binucleated cell. The distribution of the number of MN per micronucleated binucleated cell was also studied. The BNC reaction clearly modifies this distribution, increasing the frequency of micronucleated cells with 2 and, especially, > or =3 MN and conversely decreasing the frequency of micronucleated cells with 1 MN. A decrease in cell proliferation was also observed which correlated with MN formation. A discrete genotoxic and anti-proliferative contribution from both thermal neutron irradiation and BPA was observed and should be considered secondary. Additionally, V79 Chinese hamster cells (chromosomal aberrations assay) and human lymphocytes (CBMN assay) incubated with different concentrations of BPA alone did not show any evidence of genotoxicity. The presented results reinforce the usefulness of the CBMN assay as an alternative method for assessment of the deleterious effects induced by high LET radiation produced by the BNC reaction in human melanoma cells.

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Repair of potentially lethal damage by total and quiescent cells in solid tumors following a neutron capture reaction

Abstract: Differences in sensitivity and repair patterns following the neutron capture reaction were thought to depend on differences in the distribution of the (10)B-labeled compound between the proliferating and Q cell populations.

Cited by 7 publications

References 15 publications

An attempt to improve the therapeutic effect of boron neutron capture therapy using commonly employed 10B-carriers based on analytical studies on the correlation among quiescent tumor cell characteristics, tumor heterogeneity and cancer stemness

An attempt to improve the therapeutic effect of boron neutron capture therapy using commonly employed 10B-carriers based on analytical studies on the correlation among quiescent tumor cell characteristics, tumor heterogeneity and cancer stemness

Computational assessment of improved cell-kill by gadolinium-supplemented boron neutron capture therapy

Evaluation of the genotoxic effects of the boron neutron capture reaction in human melanoma cells using the cytokinesis block micronucleus assay

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