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Newcastle and vanadyl sulfate-- Very Large responses in mouse melanoma (also prostate cancer)

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(@jcancom)
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Used intratumoral injection of vanadyl sulfate. IV administration of vanadyl sulfate is "acutely toxic".

"Vanadyl sulfate, an oxidative form of vanadium, is a commonly used body-building supplement."

"We observed extremely rapid tumor regression in mice treated with vanadyl sulfate (40 mg/kg) plus NDV (Figure 2B) that was preceded by the formation of a thick, rigid scab that eventually resolved, typically within 5 days of the last treatment (Figure S2). Regressions of tumors in all mice that received the combination therapy were complete within only 96 h of the initiation of treatment. Remarkably, all mice in the vanadyl sulfate plus NDV treatment group were cured of their disease, as demonstrated by their failure to re-grow tumors by 60 days after the initial regression."

"An intratumoral dose of 40 mg/kg vanadyl sulfate was chosen based on the fact that it was previously shown to significantly enhance tumor regression when used in combination with oncolytic VSVΔ51.21 While there was no evidence of toxicity when 40 mg/kg vanadyl sulfate was delivered intratumorally or intraperitoneally, IV administration of either 40 mg/kg or 20 mg/kg vanadyl sulfate was acutely toxic to mice."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868934/


   
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(@jcancom)
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vanadyl sulfate is a remarkably powerful anti-cancer agent especially in combination with oncolytic viruses (in mice at least). As the article above notes if this could be formulated properly then this treatment approach might have be broadly applicable as a cancer therapy.


   
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(@daniel)
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@jcancomHi J, very interesting. I did not know about vanadyl sulfate until now. I will look into teh details asap. Thank you.

Kind regards,

Daniel


   
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(@jcancom)
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D, this is a very powerful treatment. It is interesting that the authors immediately assumed that this is was an immune response; such rapid response makes me wonder whether this might be more of a metabolic response. We have seen in earlier posts that Newcastle virus has metabolic effects; perhaps vanadyl sulfate amplifies these effects. The article notes that this also helped in a prostate model. With the right formulation this might be a broadly applicable treatment. This is only the first generation of this therapy, the article reported that there are a range of amplifiers that could be considered for the next iteration. Possibly even now for melanoma, patients could consider vanadyl sulfate intratumoral injection along with another oncolytic virus TVEC.

"It is important to point out that vanadyl sulfate alone was able to induce significant tumor regression and enhance survival of B16-F10 tumor-bearing mice, with ~50% of mice being cured of their tumors. The mechanism behind this warrants further investigation, as well as dose escalation studies to determine whether greater survival rates are achievable. However, while vanadyl sulfate as a monotherapy significantly enhanced survival, it pales in comparison to the 100% survival observed when vanadyl sulfate was combined with NDV."

"The rapid nature with which tumors regressed suggested that the therapeutic effect of this combination therapy is mediated in large part by the innate immune system, as an effective adaptive immune response was unlikely to have been generated within this time frame."

 

 


   
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(@jcancom)
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The primary medical application of Vanadyl sulfate that is currently recognized is as an insulin mimic. One certainly wonders how large the metabolic consequences of injecting vanadyl sulfate directly into a tumor might be. Shutting down glucose processing in a tumor could produce rapid and profound effects. the idea that this might be more of an immune response perhaps could be incorrect.

Are there any studies that directly inject insulin into tumors? One would expect that that would also have very large anti-cancer effects. 


   
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