Posted on 02/07/2022 6:03:39 AM PST by RaceBannon
Abstract Relevance: Ivermectin, as an old anti-parasite drug, can suppress almost completely the growth of various human cancers, including ovarian cancer (OC). However, its anticancer mechanism remained to be further studied at the molecular levels. Ivermectin-related molecule-panel changes will serve a useful tool for its personalized drug therapy and prognostic assessment in OCs.
Purpose: To explore the functional significance of ivermectin-mediated lncRNA-EIF4A3-mRNA axes in OCs and ivermectin-related molecule-panel for its personalized drug therapy monitoring.
Methods: Based on our previous study, a total of 16 lncRNA expression patterns were analyzed using qRT-PCR before and after ivermectin-treated different OC cell lines (TOV-21G and A2780). Stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics was used to analyze the protein expressions of EIF4A3 and EIF4A3-binding mRNAs in ovarian cancer cells treated with and without ivermectin. A total of 411 OC patients from the Cancer Genome Atlas (TCGA) database with the selected lncRNA expressions and the corresponding clinical data were included. Lasso regression was constructed to examine the relationship between lncRNA signature and OC survival risk. The overall survival analysis between high-risk and low-risk groups used the Kaplan-Meier method. Heatmap showed the correlation between risk groups and clinical characteristics. The univariate and multivariate models were established with Cox regression.
Results: SILAC-based quantitative proteomics found the protein expression levels of EIF4A3 and 116 EIF4A3-binding mRNAs were inhibited by ivermectin in OC cells. Among the analyzed 16 lncRNAs (HCG15, KIF9-AS1, PDCD4-AS1, ZNF674-AS1, ZNRF3-AS1, SOS1-IT1, LINC00565, SNHG3, PLCH1-AS1, WWTR1-AS1, LINC00517, AL109767.1, STARD13-IT1, LBX2-AS1, LEMD1-AS1, and HOXC-AS3), only 7 lncRNAs (HCG15, KIF9-AS1, PDCD4-AS1, ZNF674-AS1, ZNRF3-AS1, SOS1-IT1, and LINC00565) were obtained for further lasso regression when combined with the results of drug testing and overall survival analysis. Lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565). The high-risk and low-risk groups based on the prognostic model were significantly related to overall survival and clinicopathologic characteristics (survival status, lymphatic invasion, cancer status, and clinical stage) in OC patients and remained independent risk factors according to multivariate COX analysis (p < 0.05).
Conclusion: Those findings provided the potential targeted lncRNA-EIF4A3-mRNA pathways of ivermectin in OC, and constructed the effective prognostic model, which benefits discovery of novel mechanism of ivermectin to suppress ovarian cancer cells, and the ivermectin-related molecule-panel changes benefit for its personalized drug therapy and prognostic assessment towards its predictive, preventive, and personalized medicine (PPPM) in OCs.
Keywords: EIF4A3; Ivermectin; Ovarian cancer; Personalized drug therapy; Predictive preventive personalized medicine (PPPM); Prognostic assessment; Prognostic model; TCGA; lncRNAs.
© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2020.
I used to take Synthroid but my doctor changed me to Levothyroxine and said we couldn’t get the Synthroid anymore. I wish I could find a natural med for thyroid but so far, no luck. The Levothyroxine hasn’t been working as well for the last year. She has changed the dosage several times and can’t figure out why my thyroid seems to be working better than it was. LOL I wish it would get so good that I could quit it altogether.
hmmm.
will reearch this.
note to self...the box in the fridge is ready to be replaced
He mixed it with olive oil and covered it with a bandage to keep it on.
P
Never give up?
It’s no wonder the India population is running outta control!
By the looks of the names and places of all the studies, Looks like biomedical research is another job americans don’t want to do.
ping - cancers and treatments!
I am interested id the real mechanism of action is anti mRNA. That also raises the specter of does long term use accumulate and disrupt normal human mRNA.
Clearly the drug has more than anti parasitic action but the question is how much and how relevant. Those are very big questions.
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Interesting indeed.
In the world in which we live, it may be difficult to get accurate data on these points. Plus like the Covid vax, not a lot of long term data.
Possibility that HIV virus is in Corona virus, intentional, man made
https://www.biorxiv.org/content/10.1101/2020.01.30.927871v1.full.pdf
Coronavirus far more likely than Sars to bond to human cells due to HIV-like mutation, scientists say
https://www.scmp.com/news/china/society/article/3052495/coronavirus-far-more-likely-sars-bond-human-cells-scientists-say
https://video.twimg.com/ext_tw_video/1490668730812141573/pu/vid/640x360/VR5b2qCP47m0K5tX.mp4?tag=12
I wonder how many ovarian cancers might be caused by a viral STD...
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