A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma

Background and objective Mesothelioma is an incurable cancer with a rising global incidence. Intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus has been used clinically to induce pleurodesis. We investigate if this bacterial compound has...

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Veröffentlicht in:Respirology (Carlton, Vic.) Vic.), 2014-10, Vol.19 (7), p.1025-1033
Hauptverfasser: Lansley, Sally M., Varano della Vergiliana, Julius F., Cleaver, Amanda L., Ren, Shaohua H., Segal, Amanda, Xu, Ming Yan, Lee, Y.C. Gary
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container_end_page 1033
container_issue 7
container_start_page 1025
container_title Respirology (Carlton, Vic.)
container_volume 19
creator Lansley, Sally M.
Varano della Vergiliana, Julius F.
Cleaver, Amanda L.
Ren, Shaohua H.
Segal, Amanda
Xu, Ming Yan
Lee, Y.C. Gary
description Background and objective Mesothelioma is an incurable cancer with a rising global incidence. Intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus has been used clinically to induce pleurodesis. We investigate if this bacterial compound has anti‐tumoural activities against pleural malignancies, in addition to its pleurodesing effect. Methods The effects of the treatment on mesothelioma cells were evaluated in vitro and further tested in two validated murine models. Results This S. aureus bio‐product mixture effectively kills mesothelioma cells and induces the release of interleukin (IL)‐8, monocyte chemotactic protein (MCP)‐1 and vascular endothelial growth factor from primary human mesothelial cells but not malignant pleural mesothelioma cells in vitro. Intratumoural delivery of the treatment in BALB/c mice induced tumour necrosis and local activation of T cells. Tumour growth was significantly inhibited in the treatment group during and after the treatment period (size of tumour 58.8 ± 10.3 mm2 vs 118.3 ± 6.7 mm2 from saline controls at day 23, n = 9–12 per group), P 
doi_str_mv 10.1111/resp.12351
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Gary</creator><creatorcontrib>Lansley, Sally M. ; Varano della Vergiliana, Julius F. ; Cleaver, Amanda L. ; Ren, Shaohua H. ; Segal, Amanda ; Xu, Ming Yan ; Lee, Y.C. Gary</creatorcontrib><description>Background and objective Mesothelioma is an incurable cancer with a rising global incidence. Intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus has been used clinically to induce pleurodesis. We investigate if this bacterial compound has anti‐tumoural activities against pleural malignancies, in addition to its pleurodesing effect. Methods The effects of the treatment on mesothelioma cells were evaluated in vitro and further tested in two validated murine models. Results This S. aureus bio‐product mixture effectively kills mesothelioma cells and induces the release of interleukin (IL)‐8, monocyte chemotactic protein (MCP)‐1 and vascular endothelial growth factor from primary human mesothelial cells but not malignant pleural mesothelioma cells in vitro. Intratumoural delivery of the treatment in BALB/c mice induced tumour necrosis and local activation of T cells. Tumour growth was significantly inhibited in the treatment group during and after the treatment period (size of tumour 58.8 ± 10.3 mm2 vs 118.3 ± 6.7 mm2 from saline controls at day 23, n = 9–12 per group), P &lt; 0.001. Tumour growth resumed on cessation of treatment, confirming the inhibition was treatment related. Treatment benefits were further validated in an orthotopic peritoneal model of mesothelioma and the compound significantly reduced the mesothelioma load (P &lt; 0.05 vs saline controls). Mice in the treatment group had a significant increase in the percentage of activated CD4+ and CD8+ T cells in tumour‐draining lymph nodes. No histological side‐effects were observed with the treatment. Conclusions This proof‐of‐principle study demonstrates promising antitumoural activity of a commercially available compound of S. aureus bio‐products against mesothelioma. This proof‐of‐principle study investigated the efficacy of inhibiting mesothelioma growth by a compound consisting of Staphylococcus aureus bio‐products. Treatment killed mesothelioma cells in vitro and retarded tumour growth in vivo. Given this product has been used as a pleurodesing agent in humans, its antitumoural activity against mesothelioma warrants clinical validation. 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Gary</creatorcontrib><title>A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma</title><title>Respirology (Carlton, Vic.)</title><addtitle>Respirology</addtitle><description>Background and objective Mesothelioma is an incurable cancer with a rising global incidence. Intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus has been used clinically to induce pleurodesis. We investigate if this bacterial compound has anti‐tumoural activities against pleural malignancies, in addition to its pleurodesing effect. Methods The effects of the treatment on mesothelioma cells were evaluated in vitro and further tested in two validated murine models. Results This S. aureus bio‐product mixture effectively kills mesothelioma cells and induces the release of interleukin (IL)‐8, monocyte chemotactic protein (MCP)‐1 and vascular endothelial growth factor from primary human mesothelial cells but not malignant pleural mesothelioma cells in vitro. Intratumoural delivery of the treatment in BALB/c mice induced tumour necrosis and local activation of T cells. Tumour growth was significantly inhibited in the treatment group during and after the treatment period (size of tumour 58.8 ± 10.3 mm2 vs 118.3 ± 6.7 mm2 from saline controls at day 23, n = 9–12 per group), P &lt; 0.001. Tumour growth resumed on cessation of treatment, confirming the inhibition was treatment related. Treatment benefits were further validated in an orthotopic peritoneal model of mesothelioma and the compound significantly reduced the mesothelioma load (P &lt; 0.05 vs saline controls). Mice in the treatment group had a significant increase in the percentage of activated CD4+ and CD8+ T cells in tumour‐draining lymph nodes. No histological side‐effects were observed with the treatment. Conclusions This proof‐of‐principle study demonstrates promising antitumoural activity of a commercially available compound of S. aureus bio‐products against mesothelioma. This proof‐of‐principle study investigated the efficacy of inhibiting mesothelioma growth by a compound consisting of Staphylococcus aureus bio‐products. Treatment killed mesothelioma cells in vitro and retarded tumour growth in vivo. Given this product has been used as a pleurodesing agent in humans, its antitumoural activity against mesothelioma warrants clinical validation. See Editorial, page 948</description><subject>Animals</subject><subject>Antigens, Bacterial - therapeutic use</subject><subject>bacterial toxin</subject><subject>Cell Culture Techniques</subject><subject>Cell Line, Tumor</subject><subject>cytokines</subject><subject>Disease Models, Animal</subject><subject>Enterotoxins - therapeutic use</subject><subject>Humans</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - pathology</subject><subject>malignant mesothelioma</subject><subject>Mesothelioma - drug therapy</subject><subject>Mesothelioma - pathology</subject><subject>Mesothelioma, Malignant</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - immunology</subject><subject>superantigen</subject><subject>T cells</subject><issn>1323-7799</issn><issn>1440-1843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkctuFDEQRVsIREJgwwcgL9l0sNt2P5YhCglSEhBJYGlVu2sYg93u-EGYf-Cj8WRC1tSmSlXnXlm-VfWa0UNW6l3AuByyhkv2pNpnQtCa9YI_LTNveN11w7BXvYjxB6WUSyqfV3uNLDjv5H7154ho7xwGbcDaDYFfYCyMFskScIEAyfiZ-BW5SrCsN9Zrr3WOBHLA0kbj6yX4KesUyeITzqmYmHltRlM2KTufA_ke_F1alzUB4nIwMxLnJ7RbX4fRpzVa4x28rJ6twEZ89dAPqpsPJ9fHZ_X5p9OPx0fntRGcslpPzdDIUQscOE6Dhr4Hrle6nzg0bbeiUkra6aGXgo8gOtmAxAGmfmgQNOP8oHq78y1Pv80Yk3ImarQWZvQ5Kibbthdtz-T_oGxoW8FFQd88oHl0OKklGAdho_59dgHYDrgzFjePd0bVNka1jVHdx6i-nFx9vp-Kpt5pTEz4-1ED4adqu2Kqvl2eqvdfmThr-YXi_C__vKI-</recordid><startdate>201410</startdate><enddate>201410</enddate><creator>Lansley, Sally M.</creator><creator>Varano della Vergiliana, Julius F.</creator><creator>Cleaver, Amanda L.</creator><creator>Ren, Shaohua H.</creator><creator>Segal, Amanda</creator><creator>Xu, Ming Yan</creator><creator>Lee, Y.C. Gary</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>7QL</scope><scope>C1K</scope></search><sort><creationdate>201410</creationdate><title>A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma</title><author>Lansley, Sally M. ; Varano della Vergiliana, Julius F. ; Cleaver, Amanda L. ; Ren, Shaohua H. ; Segal, Amanda ; Xu, Ming Yan ; Lee, Y.C. Gary</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i4301-cd2925bc4e93ed9ca88a3cfc8d3a267f055507c98543ba4752a5e9ad892eac133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antigens, Bacterial - therapeutic use</topic><topic>bacterial toxin</topic><topic>Cell Culture Techniques</topic><topic>Cell Line, Tumor</topic><topic>cytokines</topic><topic>Disease Models, Animal</topic><topic>Enterotoxins - therapeutic use</topic><topic>Humans</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - pathology</topic><topic>malignant mesothelioma</topic><topic>Mesothelioma - drug therapy</topic><topic>Mesothelioma - pathology</topic><topic>Mesothelioma, Malignant</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - immunology</topic><topic>superantigen</topic><topic>T cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lansley, Sally M.</creatorcontrib><creatorcontrib>Varano della Vergiliana, Julius F.</creatorcontrib><creatorcontrib>Cleaver, Amanda L.</creatorcontrib><creatorcontrib>Ren, Shaohua H.</creatorcontrib><creatorcontrib>Segal, Amanda</creatorcontrib><creatorcontrib>Xu, Ming Yan</creatorcontrib><creatorcontrib>Lee, Y.C. Gary</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Respirology (Carlton, Vic.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lansley, Sally M.</au><au>Varano della Vergiliana, Julius F.</au><au>Cleaver, Amanda L.</au><au>Ren, Shaohua H.</au><au>Segal, Amanda</au><au>Xu, Ming Yan</au><au>Lee, Y.C. Gary</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma</atitle><jtitle>Respirology (Carlton, Vic.)</jtitle><addtitle>Respirology</addtitle><date>2014-10</date><risdate>2014</risdate><volume>19</volume><issue>7</issue><spage>1025</spage><epage>1033</epage><pages>1025-1033</pages><issn>1323-7799</issn><eissn>1440-1843</eissn><abstract>Background and objective Mesothelioma is an incurable cancer with a rising global incidence. Intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus has been used clinically to induce pleurodesis. We investigate if this bacterial compound has anti‐tumoural activities against pleural malignancies, in addition to its pleurodesing effect. Methods The effects of the treatment on mesothelioma cells were evaluated in vitro and further tested in two validated murine models. Results This S. aureus bio‐product mixture effectively kills mesothelioma cells and induces the release of interleukin (IL)‐8, monocyte chemotactic protein (MCP)‐1 and vascular endothelial growth factor from primary human mesothelial cells but not malignant pleural mesothelioma cells in vitro. Intratumoural delivery of the treatment in BALB/c mice induced tumour necrosis and local activation of T cells. Tumour growth was significantly inhibited in the treatment group during and after the treatment period (size of tumour 58.8 ± 10.3 mm2 vs 118.3 ± 6.7 mm2 from saline controls at day 23, n = 9–12 per group), P &lt; 0.001. Tumour growth resumed on cessation of treatment, confirming the inhibition was treatment related. Treatment benefits were further validated in an orthotopic peritoneal model of mesothelioma and the compound significantly reduced the mesothelioma load (P &lt; 0.05 vs saline controls). Mice in the treatment group had a significant increase in the percentage of activated CD4+ and CD8+ T cells in tumour‐draining lymph nodes. No histological side‐effects were observed with the treatment. Conclusions This proof‐of‐principle study demonstrates promising antitumoural activity of a commercially available compound of S. aureus bio‐products against mesothelioma. This proof‐of‐principle study investigated the efficacy of inhibiting mesothelioma growth by a compound consisting of Staphylococcus aureus bio‐products. Treatment killed mesothelioma cells in vitro and retarded tumour growth in vivo. Given this product has been used as a pleurodesing agent in humans, its antitumoural activity against mesothelioma warrants clinical validation. See Editorial, page 948</abstract><cop>Australia</cop><pub>Blackwell Publishing Ltd</pub><pmid>25123375</pmid><doi>10.1111/resp.12351</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1323-7799
ispartof Respirology (Carlton, Vic.), 2014-10, Vol.19 (7), p.1025-1033
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source MEDLINE; Wiley Online Library All Journals
subjects Animals
Antigens, Bacterial - therapeutic use
bacterial toxin
Cell Culture Techniques
Cell Line, Tumor
cytokines
Disease Models, Animal
Enterotoxins - therapeutic use
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - pathology
malignant mesothelioma
Mesothelioma - drug therapy
Mesothelioma - pathology
Mesothelioma, Malignant
Mice
Mice, Inbred BALB C
Staphylococcus aureus
Staphylococcus aureus - immunology
superantigen
T cells
title A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma
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