Applicability of Combination with Tirapazamine in Boron Neutron Capture Therapy

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

doi:10.1111/j.1349-7006.1998.tb03282.x

Cited by 3 publications

(1 citation statement)

References 14 publications

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“…Previous studies [5] suggest that the uptake of synthetic neutral amino acids by CHO-K1 cells is increased by co-loading with L-type amino acid esters. In some previous reports on in vitro experiments using BPA [1,[6][7][8][9][10], cell-lines including 9L, C6, SCCVII, V79, and T98 were used for neutron irradiation experiments not associated with amino acid transport control.…”

Section: Introductionmentioning

confidence: 99%

Intracellular boron accumulation in CHO-K1 cells using amino acid transport control

Sato

Yamamoto

Shikano

et al. 2014

Applied Radiation and Isotopes

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BPA used in BNCT has a similar structure to some essential amino acids and is transported into tumor cells by amino acid transport systems. Previous study groups have tried various techniques of loading BPA to increase intracellular boron concentration. CHO-K1 cells demonstrate system L (LAT1) activity and are suitable for specifying the transport system of a neutral amino acid. In this study, we examined the intracellular accumulation of boron in CHO-K1 cells by amino acid transport control, which involves co-loading with L-type amino acid esters. Intracellular boron accumulation in CHO-K1 cells showed the greatest increased upon co-loading 1.0mM BPA, with 1.0mM l-Tyr-O-Et and incubating for 60min. This increase is caused by activation of a system L amino acid exchanger between BPA and l-Tyr. The amino acid esters are metabolized to amino acids by intracellular hydrolytic enzymes that increase the concentrations of intracellular amino acids and stimulate exchange transportation. We expect that this amino acid transport control will be useful for enhancing intracellular boron accumulation.

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Section: Introductionmentioning

confidence: 99%

Intracellular boron accumulation in CHO-K1 cells using amino acid transport control

Sato

Yamamoto

Shikano

et al. 2014

Applied Radiation and Isotopes

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

Masunaga

Ono

Suzuki

et al. 1999

Journal of Cancer Research and Clinical Oncology

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Significance of the Response of Quiescent Cell Populations within Solid Tumors in Cancer Therapy

Masunaga

Ono

2002

JRR

130

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In analyzing the response of quiescent (Q) cells in solid tumors, we have developed a combined method with a micronucleus (MN) assay and the identification of proliferating (P) cells by 5-bromo-2'-deoxyuridine (BrdU) and an anti-BrdU monoclonal antibody. Using this method, the responses of Q tumor cells as well as total tumor (P + Q) cells within murine solid tumors to various DNA-damaging treatments were evaluated. Based on this evaluation, combining with tirapazamine, a well-known bioreductive agent, and/or heat treatment at mild temperatures was thought to be a promising modality for cancer therapy in terms of conventional anticancer treatment-resistant Q cell control. Recently, our method for detecting the Q-cell response using P cell labeling with BrdU and the MN frequency assay was also shown to be applicable to an apoptosis detection assay. Meanwhile, our method for detecting the intratumor Q-cell response was also applicable toward high linear energy transfer radiation, including reactor neutrons. Thus, using our method, a new neutron capture compound that has the potential to be distributed in neutron capture therapy-resistant intratumor Q cell populations is now under development.

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Applicability of Combination with Tirapazamine in Boron Neutron Capture Therapy

Cited by 3 publications

References 14 publications

Intracellular boron accumulation in CHO-K1 cells using amino acid transport control

Intracellular boron accumulation in CHO-K1 cells using amino acid transport control

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

Significance of the Response of Quiescent Cell Populations within Solid Tumors in Cancer Therapy

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