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The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

Takahara K, Inamoto T, Minami K, Yoshikawa Y, Takai T, Ibuki N, Hirano H, Nomi H, Kawabata S, Kiyama S, Miyatake S, Kuroiwa T, Suzuki M, Kirihata M, Azuma H - PLoS ONE (2015)

Bottom Line: 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.The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

The mean body weight of mice in four groups.Mean body weight of mice (Group 1: untreated control, Group 2: BPA, Group 3: neutron, Group 4: BPA-mediated BNCT) from 0 to 9 week were shown. Each point represents the mean body weight ± SEM.
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pone.0136981.g002: The mean body weight of mice in four groups.Mean body weight of mice (Group 1: untreated control, Group 2: BPA, Group 3: neutron, Group 4: BPA-mediated BNCT) from 0 to 9 week were shown. Each point represents the mean body weight ± SEM.

Mentions: In order to assess whether BPA-mediated BNCT influenced the growth and body weight of mice, the animals were monitored once a week from 0 week to 9 weeks. The day of injection of PC3 cells was taken as the starting point and defined as day 0. At week 2 after PC3 cell injection, when PC3 xenografts were palpable, the mice were divided into four groups: Group 1: untreated control, Group 2: BPA, Group 3: neutron, and Group 4: BPA-mediated BNCT. The mean body weights of the mice in the four groups are shown in Fig 2. No significant effect on animal body weight was observed during the treatment period. These results indicated that none of the treatments—BPA, neutron irradiation or BPA-mediated BNCT—produced severe side effects in this in vivo mouse xenograft model.


The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

Takahara K, Inamoto T, Minami K, Yoshikawa Y, Takai T, Ibuki N, Hirano H, Nomi H, Kawabata S, Kiyama S, Miyatake S, Kuroiwa T, Suzuki M, Kirihata M, Azuma H - PLoS ONE (2015)

The mean body weight of mice in four groups.Mean body weight of mice (Group 1: untreated control, Group 2: BPA, Group 3: neutron, Group 4: BPA-mediated BNCT) from 0 to 9 week were shown. Each point represents the mean body weight ± SEM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556531&req=5

pone.0136981.g002: The mean body weight of mice in four groups.Mean body weight of mice (Group 1: untreated control, Group 2: BPA, Group 3: neutron, Group 4: BPA-mediated BNCT) from 0 to 9 week were shown. Each point represents the mean body weight ± SEM.
Mentions: In order to assess whether BPA-mediated BNCT influenced the growth and body weight of mice, the animals were monitored once a week from 0 week to 9 weeks. The day of injection of PC3 cells was taken as the starting point and defined as day 0. At week 2 after PC3 cell injection, when PC3 xenografts were palpable, the mice were divided into four groups: Group 1: untreated control, Group 2: BPA, Group 3: neutron, and Group 4: BPA-mediated BNCT. The mean body weights of the mice in the four groups are shown in Fig 2. No significant effect on animal body weight was observed during the treatment period. These results indicated that none of the treatments—BPA, neutron irradiation or BPA-mediated BNCT—produced severe side effects in this in vivo mouse xenograft model.

Bottom Line: 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.The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.

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.

No MeSH data available.


Related in: MedlinePlus