PLK1, IDH1, and Genistein

Came across this study on sensitizing IDH1 mutant tumors to TMZ.  Inhibiting PLK1 sensitized mutant IDH1 gliomas to TMZ in mice.  

PLK1 INHIBITION ENHANCES TEMOZOLOMIDE EFFICACY IN IDH1 MUTANT GLIOMAS

They used the small molecule BI2536 which is not currently available outside of clinical trials.   However, I did find a 2016 study on Genistein (which is available retail) and its possible inhibition of PLK1.

 Sensitivity of TP53-Mutated Cancer Cells to the Phytoestrogen Genistein Is Associated with Direct Inhibition of Plk1 Activity.

Some more info on Genistein here as well.

Intranasal delivery

This post is a response to Joanne's post about the cerebellum, as I wanted to include a visual.  For tumors in the cerebellum, the method of delivery might be the most important factor.  According to one study,

"The cerebellar uptake of IN delivered neurotherapeutics is found to peak at 12h rapidly declining by 24h. IP delivery does not exhibit peak cerebellar uptake at any particular time point, rather it is observed to be at the same level at all time-points. Cerebellar uptake of neurotherapeutics after IN delivery is ~5 ± 2 times greater than that after IP delivery"

In other words intranasal delivery results in far higher drug levels in the cerebellum compared to intraperitoneal injection, which is the usual method for delivering drugs to lab animals.

Click on image above to enlarge.  The 4 lines at the top represent levels of therapuetics (including curcumin) in the cerebellum after intranasal delivery.  The 4 flat lines on the bottom are the same therapies after intraperitoneal injection to mice.  Quite an impressive difference.

From the study: Brain Uptake of Neurotherapeutics after Intranasal versus Intraperitoneal Delivery in Mice

The question from here is which therapies are formulated for intranasal delivery.  Perillyl alcohol and chlorotoxin (scorpion venom) are taken this way, though neither of them are easy to access.  As we've discussed recently there are curcumin nasal sprays on the market, though I haven't seen any clinical research published with them.

http://store.bioponic.com/curecumin2.html

Let's make this the "intranasal therapy" thread.