Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial
Abstract Background Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent becaus...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-022-02455-6 |
| _version_ | 1811340302239137792 |
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| author | Paola Muti Andrea Sacconi Claudio Pulito Giulia Orlandi Sara Donzelli Aldo Morrone James Jiulian Gerard P. Cox Martin Kolb Gregory Pond Peter Kavsak Mark Norman Levine Giovanni Blandino Sabrina Strano |
| author_facet | Paola Muti Andrea Sacconi Claudio Pulito Giulia Orlandi Sara Donzelli Aldo Morrone James Jiulian Gerard P. Cox Martin Kolb Gregory Pond Peter Kavsak Mark Norman Levine Giovanni Blandino Sabrina Strano |
| author_sort | Paola Muti |
| collection | DOAJ |
| description | Abstract Background Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set. Methods In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model. Results We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants. Conclusions We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma. Trial registration ClinicalTrials.gov, NCT02076672 . Registered 03/03/2014. |
| first_indexed | 2024-04-13T18:39:55Z |
| format | Article |
| id | doaj.art-881490acf3754d43aca0d1fbffd35fcd |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T18:39:55Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-881490acf3754d43aca0d1fbffd35fcd2022-12-22T02:34:46ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662022-08-0141111210.1186/s13046-022-02455-6Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trialPaola Muti0Andrea Sacconi1Claudio Pulito2Giulia Orlandi3Sara Donzelli4Aldo Morrone5James Jiulian6Gerard P. Cox7Martin Kolb8Gregory Pond9Peter Kavsak10Mark Norman Levine11Giovanni Blandino12Sabrina Strano13Department of Biomedical, Surgical and Dental Sciences, University of MilanBiostatistics and Bioinformatics, UOSD Clinical Trial Center, IRCCS Regina Elena National Cancer InstituteTranslational Oncology Research Unit, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS, Regina Elena National Cancer InstituteScientific Direction Office, IRCSS San Gallicano Dermatological InstituteTranslational Oncology Research Unit, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS, Regina Elena National Cancer InstituteScientific Direction Office, IRCSS San Gallicano Dermatological InstituteDepartment of Oncology, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Oncology, McMaster UniversityDepartment of Pathology and Molecular Medicine, McMaster UniversityDepartment of Oncology, McMaster UniversityTranslational Oncology Research Unit, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS, Regina Elena National Cancer InstituteSAFU Laboratory, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS Regina Elena National Cancer InstituteAbstract Background Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set. Methods In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model. Results We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants. Conclusions We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma. Trial registration ClinicalTrials.gov, NCT02076672 . Registered 03/03/2014.https://doi.org/10.1186/s13046-022-02455-6AsbestosisMalignant pleura mesotheliomaArtichokeBiomarkermiRNAMesothelin |
| spellingShingle | Paola Muti Andrea Sacconi Claudio Pulito Giulia Orlandi Sara Donzelli Aldo Morrone James Jiulian Gerard P. Cox Martin Kolb Gregory Pond Peter Kavsak Mark Norman Levine Giovanni Blandino Sabrina Strano Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial Journal of Experimental & Clinical Cancer Research Asbestosis Malignant pleura mesothelioma Artichoke Biomarker miRNA Mesothelin |
| title | Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial |
| title_full | Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial |
| title_fullStr | Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial |
| title_full_unstemmed | Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial |
| title_short | Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial |
| title_sort | artichoke phytocomplex modulates serum micrornas in patients exposed to asbestos a first step of a phase ii clinical trial |
| topic | Asbestosis Malignant pleura mesothelioma Artichoke Biomarker miRNA Mesothelin |
| url | https://doi.org/10.1186/s13046-022-02455-6 |
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