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.
Ivermectin, a potential anticancer drug derived from an antiparasitic drug
https://pubmed.ncbi.nlm.nih.gov/32971268/
Mingyang Tang 1, Xiaodong Hu 2, Yi Wang 3, Xin Yao 4, Wei Zhang 5, Chenying Yu 6, Fuying Cheng 7, Jiangyan Li 8, Qiang Fang 9
Affiliations expand
PMID: 32971268 PMCID: PMC7505114 DOI: 10.1016/j.phrs.2020.105207
Free PMC article
Abstract
Ivermectin is a macrolide antiparasitic drug with a 16-membered ring that is widely used for the treatment of many parasitic diseases such as river blindness, elephantiasis and scabies. Satoshi ōmura and William C. Campbell won the 2015 Nobel Prize in Physiology or Medicine for the discovery of the excellent efficacy of ivermectin against parasitic diseases. Recently, ivermectin has been reported to inhibit the proliferation of several tumor cells by regulating multiple signaling pathways. This suggests that ivermectin may be an anticancer drug with great potential. Here, we reviewed the related mechanisms by which ivermectin inhibited the development of different cancers and promoted programmed cell death and discussed the prospects for the clinical application of ivermectin as an anticancer drug for neoplasm therapy.
Keywords: avermectin(PubChem CID：6434889); cancer; doramectin(PubChem CID：9832750); drug repositioning; ivermectin; ivermectin(PubChem CID：6321424); moxidectin(PubChem CID：9832912); selamectin(PubChem CID：9578507).
Copyright © 2020 Elsevier Ltd. All rights reserved.
Thanks. Going down the Ivermectin / cancer rabbit hole is on my to-do list for 2022.
https://pubmed.ncbi.nlm.nih.gov/29511601/
The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug
Mandy Juarez 1, Alejandro Schcolnik-Cabrera 1, Alfonso Dueñas-Gonzalez 2
Affiliations expand
PMID: 29511601 PMCID: PMC5835698
Free PMC article
Abstract
Drug repositioning is a highly studied alternative strategy to discover and develop anticancer drugs. This drug development approach identifies new indications for existing compounds. Ivermectin belongs to the group of avermectins (AVM), a series of 16-membered macrocyclic lactone compounds discovered in 1967, and FDA-approved for human use in 1987. It has been used by millions of people around the world exhibiting a wide margin of clinical safety. In this review, we summarize the in vitro and in vivo evidences demonstrating that ivermectin exerts antitumor effects in different types of cancer. Ivermectin interacts with several targets including the multidrug resistance protein (MDR), the Akt/mTOR and WNT-TCF pathways, the purinergic receptors, PAK-1 protein, certain cancer-related epigenetic deregulators such as SIN3A and SIN3B, RNA helicase, chloride channel receptors and preferentially target cancer stem-cell like population. Importantly, the in vitro and in vivo antitumor activities of ivermectin are achieved at concentrations that can be clinically reachable based on the human pharmacokinetic studies done in healthy and parasited patients. Thus, existing information on ivermectin could allow its rapid move into clinical trials for cancer patients.
Keywords: Ivermectin; cancer; drug repurposing.
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Ivermectin, a potential anticancer drug derived from an antiparasitic drug.
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I betcha biden is going to claim he cured cancer by releasing this
Amazing therapeutic. Truly amazing. Thanks for posting.
Off label use will be banned because there are far more expensive drugs to use on cancer patients.
We can’t have people being cured quickly and easily, now can we?
No way. Big Pharma won’t let it happen.
“Amazing therapeutic. Truly amazing.”
*****
If it didn’t work, our government would not be restricting it’s availability.
Call it by its real name. Horse Paste. Horse Paste Cures Cancer! Fauci saddened……
where is the topics list page ?
How can I get this on extended news?
FR wouldn’t let me post it to that
“If it didn’t work, our government would not be restricting it’s availability.”
exactly ...
“..Amazing therapeutic. Truly amazing. ...”
That it is. Just ask the 200 or so CongressCritters that have been on it since the very start of the plandemic. They think it’s absolutely great.
Of course, they never said a word about it to anyone, never stood up for their constituencies to have it, etc.
IMHO, that makes em traitors. Their list of names was never publicly released, but they KNOW who they are...and so does God.
Yeah but that will cut into the cancer profits so it must be banned and if you oppose it, Neil Young will take his music off Spotify
So if this is accurate then we can start to consider that ivermectin has broad activity against certain mRNAs. Could this be the mechanism of action? And if so does can if be tweaked to a specific type of viral mRNA?
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.
I’m starting to see where the government hatred of Ivermectin is going. They don’t want it to help or cure Covid because they don’t truly want Covid helped or cured. It’s starting to snowball about all the ways Ivermectin can cure and help other diseases that they have made tons of money off of for years. A lot of money to lose if Ivermectin proves to be a cheap and efficient miracle drug.
Seems to work for blood cancers too. It is a miracle drug.
Now this is interesting.
I have no idea.
The only topics list I can find is when you go to post the article and you select them from the list.
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