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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: The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events.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.This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa.

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

TUNEL staining on PC3 xenograft specimens.Xenograft tissues of mice (Group 1: untreated control and Group 4: BPA-mediated BNCT) were stained with TUNEL and the number of apoptotic cells was quantified. White arrows indicate TUNEL+ cells.
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pone.0136981.g005: TUNEL staining on PC3 xenograft specimens.Xenograft tissues of mice (Group 1: untreated control and Group 4: BPA-mediated BNCT) were stained with TUNEL and the number of apoptotic cells was quantified. White arrows indicate TUNEL+ cells.

Mentions: At 9 weeks post-treatment, tissue samples from untreated control mice (Group 1) and mice subjected to BPA-mediated BNCT (Group 4) were first examined histologically using standard hematoxylin and eosin (H&E) staining after formalin fixation. In both groups, vacuolated tumor cells with multiple nuclear fragmentations were observed, although the histological findings did not differ significantly between them (data not shown). Next, in order to assess how BPA-mediated BNCT affected PC3 xenograft growth, immunohistochemistry for the proliferation marker, Ki-67, and TUNEL staining were performed on PC3 xenograft specimens from Groups 1 and 4. Apoptosis was observed in both groups, without any obvious differences between them, and quantification of apoptotic cells also indicated no significant inter-group difference (Fig 5). However, double-positive staining for Ki-67 was observed significantly more frequently in Group 1 than in Group 4 (mean±SD 12.7±4.0 vs 6.9±1.5, respectively, p<0.05) (Fig 6). These IHC studies suggested that BPA-mediated BNCT slowed PCa progression without affecting apoptosis at 9 weeks post-treatment.


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)

TUNEL staining on PC3 xenograft specimens.Xenograft tissues of mice (Group 1: untreated control and Group 4: BPA-mediated BNCT) were stained with TUNEL and the number of apoptotic cells was quantified. White arrows indicate TUNEL+ cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0136981.g005: TUNEL staining on PC3 xenograft specimens.Xenograft tissues of mice (Group 1: untreated control and Group 4: BPA-mediated BNCT) were stained with TUNEL and the number of apoptotic cells was quantified. White arrows indicate TUNEL+ cells.
Mentions: At 9 weeks post-treatment, tissue samples from untreated control mice (Group 1) and mice subjected to BPA-mediated BNCT (Group 4) were first examined histologically using standard hematoxylin and eosin (H&E) staining after formalin fixation. In both groups, vacuolated tumor cells with multiple nuclear fragmentations were observed, although the histological findings did not differ significantly between them (data not shown). Next, in order to assess how BPA-mediated BNCT affected PC3 xenograft growth, immunohistochemistry for the proliferation marker, Ki-67, and TUNEL staining were performed on PC3 xenograft specimens from Groups 1 and 4. Apoptosis was observed in both groups, without any obvious differences between them, and quantification of apoptotic cells also indicated no significant inter-group difference (Fig 5). However, double-positive staining for Ki-67 was observed significantly more frequently in Group 1 than in Group 4 (mean±SD 12.7±4.0 vs 6.9±1.5, respectively, p<0.05) (Fig 6). These IHC studies suggested that BPA-mediated BNCT slowed PCa progression without affecting apoptosis at 9 weeks post-treatment.

Bottom Line: The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events.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.This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa.

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