Intratumoral sirolimus injection for prostate cancer

Unlike Rapamycin, injectable sirolimus forms a depot at the site of injection that results in increased tissue availability and sustained local delivery of the drug over time. The tumors in the injectable sirolimus weekly and biweekly treatment groups showed significant decrease in tumor burden compared to oral Rapamycin and vehicle treated groups in both 22Rv1 and PC3 cell generated tumors. Blood PSA in the injectable sirolimus treated groups also showed a faster decrease than treatment with Rapamycin. Immunohistochemistry showed a decrease in the phosphorylation of both mTOR targets, S6K and 4EBP with no change in the protein levels of mTOR confirming that injected sirolimus acts by inhibiting the mTOR activity. Proliferation marker Ki-67 showed a decrease while apoptosis marker cleaved caspase-3 showed an increase upon treatment with sirolimus substantiating the underlying molecular mechanism of the observed tumor shrinkage. Interestingly, anti-metastasis marker E-cadherin levels increased with sirolimus treatment as well.

These results show the clinical potential of local sirolimus injection for the treatment of prostate cancer and underscores the need for next stage human trials.

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Related, @MAC I’m assuming you’ve reviewed this already:

Disclosed herein is an aqueous, injectable rapamycin solution comprising 0.1 to 10 percent of a concentrate solution of rapamycin in N,N-dimethylacetamide, at concentrations of rapamycin ranging from 0.25 mg/ml to 100 mg/ml, in combination with a diluent solution consisting of 0.1 to 10 weight percent of one or more polyoxyethylene sorbitan esters, 10 to 60 weight percent of either polyethylene glycol 200 or 300 or both and 30 to 90 volume percent water, wherein the concentration of rapamycin in he combined solution ranges from 0.05 mg/ml to 5.0 mg/ml. Also disclosed is an aqueous, injectable solution of rapamycin, said solution comprising rapamycin in 0.1 to 10 weight percent N,N-dimethylacetamide, 0.09 to 7.5 weight percent of one or more polyoxyethylene sorbitan esters, 9 to 60 weight percent of either polyethylene glycol 200 or 300 or both and 30 to 90 volume percent of water, wherein the concentration of rapamycin in the solution ranges from 0.05 mg/ml to 5.0 mg/ml. Preferred aqueous, injectable rapamycin solutions are those wherein one polyoxyethylene sorbitan ester is present and the polyethylene glycol present is polyethylene glycol 300.

I’ve seen lots of injection sirolimus before in rodent studies…but don’t believe I’ve seen a reference to an actual intramuscular and intranasal “human” study/clinical trial?

Fyarro is a nanoparticle albumin sirolimus suspension for IV.

I am not after novelty or patentability…couldn’t care less.

I am n=1 risk taking trying to better translate rodent studies to unlock the full potential of rapamcyin to allow us to all live to 100+.

Oh I know that - I’m just thinking that some of these formulations might be perfect instructions / recipes for the biohackers in the room.

Hi,

I just found out my CRP value in my summary table was NOT hsCRP (my normal test), but regular CRP.

I already edited the share link with this correction.

Can you update the PDF download you have linked to the post?

This is revision.

https://drive.google.com/file/d/1CP-IUU5H3EzNHAyQMF3LQb6gotynT-et/view?usp=sharing

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