Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial

Our plain-English summary of Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial, by P. Muti, A. Sacconi, C. Pulito, et al (Journal of Experimental & Clinical Cancer Research, 2022).

The study

• Authors: P. Muti, A. Sacconi, C. Pulito, G. Orlandi, S. Donzelli, A. Morrone, J. Jiulian, G.P. Cox, M. Kolb, G. Pond, P. Kavsak, M.N. Levine, G. Blandino, S. Strano
• Journal: Journal of Experimental & Clinical Cancer Research
• Published: 2022;41(1):255
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2022. The Author(s).

In plain English

This was a small single-arm phase II trial, with no comparison group, testing an artichoke leaf product (AWPC) in men with non-malignant asbestos-related disease, mostly pleural plaques, in Hamilton, Ontario. AWPC contained 30% freeze-dried artichoke extract and 70% powdered artichoke leaf. Twenty-two men were recruited between November 2014 and July 2015, and 18 completed 90 days of treatment at 3000 mg a day. The main measure was a blood protein called mesothelin. Of the 18, 5 had a decrease, 7 no change and 6 an increase. The authors counted 4 of 18 (22%) as successes, including one man whose 23.1% drop fell short of the planned 25% threshold. They described the effect on mesothelin as small and not significant. Eleven of 2571 blood microRNAs changed significantly after treatment. Two of them, miR-181a-5p and miR-193a-5p, also appeared in earlier mesothelioma data. Of 21 men who took AWPC, 11 reported at least one adverse reaction. None were considered serious. AWPC was suspected as the cause in 3 men, all of whom withdrew. The COVID-19 pandemic halted the second stage. The authors concluded that much larger studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-arm phase II trial (Simon two-stage design); only the first stage was completed
• Who was studied: 22 men with asbestosis or benign pleural disease, recruited at the Firestone Clinic, St. Joseph's Hospital, Hamilton, Ontario, between November 2014 and July 2015. 18 were analyzed: 16 with pleural plaques and 2 with asbestosis.
• Exposure: The treatment studied was AWPC capsules, an artichoke leaf product containing 30% freeze-dried extract and 70% micronized leaf powder. The dose was 6 capsules (3000 mg) per day for 90 days. All participants had past asbestos exposure, with a median exposure time of 10 years; fiber types were not reported.
• Main results:
  • Among the 18 analyzed patients, serum mesothelin decreased in 5 (28%), did not change in 7 (39%) and increased in 6 (33%)
  • Only 3 patients met the planned success definition (a decrease of 25% or more). The authors also counted a patient with a 23.1% decrease, giving 4 of 18 (22%) successes.
  • The authors described the effect on mesothelin as small and not statistically significant
  • In the 18 patients, 11 of 2571 serum microRNAs were significantly changed between baseline and after three months of treatment
  • Two of these microRNAs, miR-181a-5p and miR-193a-5p, were the only ones also found in two other datasets: the authors' earlier tissue study (29 malignant pleural mesothelioma vs 12 benign mesothelial cyst specimens) and the TCGA mesothelioma dataset
  • Of 21 patients who took AWPC, 11 reported at least one adverse reaction (not necessarily caused by AWPC), and none were considered serious
  • AWPC was suspected as the cause of adverse reactions in 3 patients, all of whom withdrew: 2 with diarrhea and 1 with mild light-headedness. No drug-related reactions occurred in the 18 who completed the trial.
  • The second stage of the trial was halted by the COVID-19 pandemic
• The authors' conclusion: The authors concluded that the results may indicate AWPC could affect pathways connected to mesothelioma, and that much larger studies following asbestos-exposed workers are needed
• Limitations the authors state:
  • Serum mesothelin is a poor-performing biomarker, which may partly explain the weak main outcome result
  • The study used benign asbestos-related disease as a stand-in for mesothelioma, so it does not directly test the effect on mesothelioma; the sample size was also limited
  • Only the 18 patients from the first stage were reported, because enrollment closed at the start of the pandemic

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Clinical Trial, Pleural Mesothelioma, Asbestos Exposure, Mesothelioma, Prognosis, Latency, Mesothelin, Glycoprotein.

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