The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model
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,...
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| Veröffentlicht in: | PloS one 2015-09, Vol.10 (9), p.e0136981-e0136981 |
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| creator | 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 |
| description | 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.
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.
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 |
| doi_str_mv | 10.1371/journal.pone.0136981 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0136981</identifier><identifier>PMID: 26325195</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>21st century ; Abnormalities ; Analysis ; Androgens ; Animals ; Antiproliferatives ; Apoptosis ; Apoptosis - radiation effects ; Blood-brain barrier ; Body weight ; Boron ; Boron Compounds - pharmacology ; Boron Neutron Capture Therapy - methods ; Brain ; Brain cancer ; Brain research ; Brain tumors ; Cancer ; Cancer therapies ; Care and treatment ; Cell Line, Tumor ; Cell Proliferation - radiation effects ; Disease Models, Animal ; Dose-Response Relationship, Radiation ; Drugs ; Gait ; Head ; Head & neck cancer ; Head and neck cancer ; Health aspects ; Humans ; In vivo methods and tests ; Laboratory animals ; Male ; Medicine ; Melanoma ; Methods ; Mice ; Mice, Nude ; Neurosurgery ; Neutrons ; Neutrons - therapeutic use ; Nuclear capture ; Oncology ; Phenylalanine - analogs & derivatives ; Phenylalanine - pharmacology ; Physiological aspects ; Prostate cancer ; Prostatic Neoplasms - radiotherapy ; Radiation ; Radiation therapy ; Radiotherapy ; Skin cancer ; Studies ; Therapeutic applications ; Tomography ; Tumors ; Urology ; Xenograft Model Antitumor Assays - methods ; Xenografts</subject><ispartof>PloS one, 2015-09, Vol.10 (9), p.e0136981-e0136981</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Takahara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Takahara et al 2015 Takahara et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c802t-7f3a734cd7c8e78c0685bc24a98aa853535eb1a88c6c23a15bea8ab62de1c4fd3</citedby><cites>FETCH-LOGICAL-c802t-7f3a734cd7c8e78c0685bc24a98aa853535eb1a88c6c23a15bea8ab62de1c4fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556531/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556531/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26325195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takahara, Kiyoshi</creatorcontrib><creatorcontrib>Inamoto, Teruo</creatorcontrib><creatorcontrib>Minami, Koichiro</creatorcontrib><creatorcontrib>Yoshikawa, Yuki</creatorcontrib><creatorcontrib>Takai, Tomoaki</creatorcontrib><creatorcontrib>Ibuki, Naokazu</creatorcontrib><creatorcontrib>Hirano, Hajime</creatorcontrib><creatorcontrib>Nomi, Hayahito</creatorcontrib><creatorcontrib>Kawabata, Shinji</creatorcontrib><creatorcontrib>Kiyama, Satoshi</creatorcontrib><creatorcontrib>Miyatake, Shin-Ichi</creatorcontrib><creatorcontrib>Kuroiwa, Toshihiko</creatorcontrib><creatorcontrib>Suzuki, Minoru</creatorcontrib><creatorcontrib>Kirihata, Mitsunori</creatorcontrib><creatorcontrib>Azuma, Haruhito</creatorcontrib><title>The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.
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.</description><subject>21st century</subject><subject>Abnormalities</subject><subject>Analysis</subject><subject>Androgens</subject><subject>Animals</subject><subject>Antiproliferatives</subject><subject>Apoptosis</subject><subject>Apoptosis - radiation effects</subject><subject>Blood-brain barrier</subject><subject>Body weight</subject><subject>Boron</subject><subject>Boron Compounds - pharmacology</subject><subject>Boron Neutron Capture Therapy - methods</subject><subject>Brain</subject><subject>Brain cancer</subject><subject>Brain research</subject><subject>Brain tumors</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - radiation effects</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Drugs</subject><subject>Gait</subject><subject>Head</subject><subject>Head & neck cancer</subject><subject>Head and neck cancer</subject><subject>Health aspects</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Medicine</subject><subject>Melanoma</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neurosurgery</subject><subject>Neutrons</subject><subject>Neutrons - therapeutic use</subject><subject>Nuclear capture</subject><subject>Oncology</subject><subject>Phenylalanine - analogs & derivatives</subject><subject>Phenylalanine - pharmacology</subject><subject>Physiological aspects</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - radiotherapy</subject><subject>Radiation</subject><subject>Radiation therapy</subject><subject>Radiotherapy</subject><subject>Skin cancer</subject><subject>Studies</subject><subject>Therapeutic applications</subject><subject>Tomography</subject><subject>Tumors</subject><subject>Urology</subject><subject>Xenograft Model Antitumor Assays - methods</subject><subject>Xenografts</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBEQkJw0eKPxHFuJpVqQKXBEAzEnXXinLSu0rjYzsT-Pc6aTS3aBfKFLft532Mfn5MkzymZUl7Qd2vbuw7a6dZ2OCWUi1LSB8kxLTmbCEb4w731UfLE-zUhOZdCPE6OmOAsp2V-nOjLFaazLpjJV2db06CDYK4wPWsa1CG1TfreOtulX7APwzyHbegdplHmYHudmi6FNEp9gIDxtNPo0l_Y2aWDJqSfbY3t0-RRA63HZ-N8kvz4cHY5_zQ5v_i4mM_OJ1oSFiZFw6Hgma4LLbGQmgiZV5plUEoAmfM4sKIgpRaacaB5hSChEqxGqrOm5ifJy53vtrVejfnxihaUlJIJSSOx2BG1hbXaOrMBd60sGHWzYd1SgQtGt6iKTOscBcuxzDLBWEV4VmQ006WgVaMHr9MxWl9tsNbYBQftgenhSWdWammvVJbnIueDwZvRwNnfPfqgNsZrbFvo0PbDvUnJS06ZjOirf9D7XzdSS4gPMF1jY1w9mKpZxgrBOLkJO72HiqPGjdGxmBoT9w8Ebw8EkQn4Jyyh914tvn_7f_bi5yH7eo9dIbRh5W3bB2M7fwhmO1DHOvMOm7skU6KGXrjNhhp6QY29EGUv9j_oTnRb_PwvQzADEQ</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Takahara, Kiyoshi</creator><creator>Inamoto, Teruo</creator><creator>Minami, Koichiro</creator><creator>Yoshikawa, Yuki</creator><creator>Takai, Tomoaki</creator><creator>Ibuki, Naokazu</creator><creator>Hirano, Hajime</creator><creator>Nomi, Hayahito</creator><creator>Kawabata, Shinji</creator><creator>Kiyama, Satoshi</creator><creator>Miyatake, Shin-Ichi</creator><creator>Kuroiwa, Toshihiko</creator><creator>Suzuki, Minoru</creator><creator>Kirihata, Mitsunori</creator><creator>Azuma, Haruhito</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150901</creationdate><title>The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c802t-7f3a734cd7c8e78c0685bc24a98aa853535eb1a88c6c23a15bea8ab62de1c4fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>21st century</topic><topic>Abnormalities</topic><topic>Analysis</topic><topic>Androgens</topic><topic>Animals</topic><topic>Antiproliferatives</topic><topic>Apoptosis</topic><topic>Apoptosis - radiation effects</topic><topic>Blood-brain barrier</topic><topic>Body weight</topic><topic>Boron</topic><topic>Boron Compounds - pharmacology</topic><topic>Boron Neutron Capture Therapy - methods</topic><topic>Brain</topic><topic>Brain cancer</topic><topic>Brain research</topic><topic>Brain tumors</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - radiation effects</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Drugs</topic><topic>Gait</topic><topic>Head</topic><topic>Head & neck cancer</topic><topic>Head and neck cancer</topic><topic>Health aspects</topic><topic>Humans</topic><topic>In vivo methods and tests</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Medicine</topic><topic>Melanoma</topic><topic>Methods</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neurosurgery</topic><topic>Neutrons</topic><topic>Neutrons - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takahara, Kiyoshi</au><au>Inamoto, Teruo</au><au>Minami, Koichiro</au><au>Yoshikawa, Yuki</au><au>Takai, Tomoaki</au><au>Ibuki, Naokazu</au><au>Hirano, Hajime</au><au>Nomi, Hayahito</au><au>Kawabata, Shinji</au><au>Kiyama, Satoshi</au><au>Miyatake, Shin-Ichi</au><au>Kuroiwa, Toshihiko</au><au>Suzuki, Minoru</au><au>Kirihata, Mitsunori</au><au>Azuma, Haruhito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>10</volume><issue>9</issue><spage>e0136981</spage><epage>e0136981</epage><pages>e0136981-e0136981</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26325195</pmid><doi>10.1371/journal.pone.0136981</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-09, Vol.10 (9), p.e0136981-e0136981 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1710982681 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 21st century Abnormalities Analysis Androgens Animals Antiproliferatives Apoptosis Apoptosis - radiation effects Blood-brain barrier Body weight Boron Boron Compounds - pharmacology Boron Neutron Capture Therapy - methods Brain Brain cancer Brain research Brain tumors Cancer Cancer therapies Care and treatment Cell Line, Tumor Cell Proliferation - radiation effects Disease Models, Animal Dose-Response Relationship, Radiation Drugs Gait Head Head & neck cancer Head and neck cancer Health aspects Humans In vivo methods and tests Laboratory animals Male Medicine Melanoma Methods Mice Mice, Nude Neurosurgery Neutrons Neutrons - therapeutic use Nuclear capture Oncology Phenylalanine - analogs & derivatives Phenylalanine - pharmacology Physiological aspects Prostate cancer Prostatic Neoplasms - radiotherapy Radiation Radiation therapy Radiotherapy Skin cancer Studies Therapeutic applications Tomography Tumors Urology Xenograft Model Antitumor Assays - methods Xenografts |
| title | The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model |
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