The anti-proliferative effect of boron neutron capture therapy in a prostate cancer xenograft model

Kiyoshi Takahara, Teruo Inamoto, Koichiro Minami, Yuki Yoshikawa, Tomoaki Takai, Naokazu Ibuki, Hajime Hirano, Hayahito Nomi, Shinji Kawabata, Satoshi Kiyama, Shin Ichi Miyatake, Toshihiko Kuroiwa, Minoru Suzuki, Mitsunori Kirihata, Haruhito Azuma

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods: Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results: The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions: This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

Original languageEnglish
Article numbere0136981
JournalPloS one
Volume10
Issue number9
DOIs
Publication statusPublished - 01-09-2015

Fingerprint

Boron Neutron Capture Therapy
Boron
prostatic neoplasms
boron
Heterografts
Prostatic Neoplasms
Neutrons
therapeutics
Tumors
Cells
neoplasms
Therapeutics
Growth
neutrons
Bearings (structural)
In Situ Nick-End Labeling
Head and Neck Neoplasms
Radiotherapy
Gait
radiotherapy

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Takahara, K., Inamoto, T., Minami, K., Yoshikawa, Y., Takai, T., Ibuki, N., ... Azuma, H. (2015). The anti-proliferative effect of boron neutron capture therapy in a prostate cancer xenograft model. PloS one, 10(9), [e0136981]. https://doi.org/10.1371/journal.pone.0136981
Takahara, Kiyoshi ; Inamoto, Teruo ; Minami, Koichiro ; Yoshikawa, Yuki ; Takai, Tomoaki ; Ibuki, Naokazu ; Hirano, Hajime ; Nomi, Hayahito ; Kawabata, Shinji ; Kiyama, Satoshi ; Miyatake, Shin Ichi ; Kuroiwa, Toshihiko ; Suzuki, Minoru ; Kirihata, Mitsunori ; Azuma, Haruhito. / The anti-proliferative effect of boron neutron capture therapy in a prostate cancer xenograft model. In: PloS one. 2015 ; Vol. 10, No. 9.
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abstract = "Purpose: Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods: Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results: The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions: This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.",
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Takahara, K, Inamoto, T, Minami, K, Yoshikawa, Y, Takai, T, Ibuki, N, Hirano, H, Nomi, H, Kawabata, S, Kiyama, S, Miyatake, SI, Kuroiwa, T, Suzuki, M, Kirihata, M & Azuma, H 2015, 'The anti-proliferative effect of boron neutron capture therapy in a prostate cancer xenograft model', PloS one, vol. 10, no. 9, e0136981. https://doi.org/10.1371/journal.pone.0136981

The anti-proliferative effect of boron neutron capture therapy in a prostate cancer xenograft model. / Takahara, Kiyoshi; Inamoto, Teruo; Minami, Koichiro; Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito.

In: PloS one, Vol. 10, No. 9, e0136981, 01.09.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The anti-proliferative effect of boron neutron capture therapy in a prostate cancer xenograft model

AU - Takahara, Kiyoshi

AU - Inamoto, Teruo

AU - Minami, Koichiro

AU - Yoshikawa, Yuki

AU - Takai, Tomoaki

AU - Ibuki, Naokazu

AU - Hirano, Hajime

AU - Nomi, Hayahito

AU - Kawabata, Shinji

AU - Kiyama, Satoshi

AU - Miyatake, Shin Ichi

AU - Kuroiwa, Toshihiko

AU - Suzuki, Minoru

AU - Kirihata, Mitsunori

AU - Azuma, Haruhito

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Purpose: Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods: Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results: The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions: This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

AB - Purpose: Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods: Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results: The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions: This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

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