TMZ is FDA approved for GBM in humans but its overall effectiveness is limited. In intracranial mouse xenografts of run-of-the mill GBM cell lines like U87, how well does TMZ perform?
I.e. is it possible to "cure" intracranial tumor bearing mice, where treatment results in complete disappearance of the tumor, without recurrence even after the drug is discontinued.
I was using TMZ as "negative control" i.e. a drug that is not supposed to work well, and I am surprised to find that it leads to profound tumor regression (by T2-MRI) in an intracranial xenograft of an established ATCC-type glioma cell line. Is this typical of what's observed in the pre-clinical literature?
And also these two ones ...
But I do not think that TMZ can really cure an intracranial model of GBM in rodents.
Robert
Thank you, that's what I was looking for. Good science. Very helpful.
In other words, run of the mill xenografts are in fact highly responsive to TMZ. Is there any hint as to whether intracranial xenografts of the same line are more sensitive than S.C. xenografts?
Did you and your team ever stain for microglial markers (Iba1, CD11b,...) in TMZ treated tumors? I.e. does TMZ lead to microgliosis or any other sort of immune activation?
Did you guys ever do small animal T2-MRI images? To see what the regression looks like and what the residual tumor after treatment.
Dear Florian,
No we did not perform the experiments you suggest.
And as GBM from patients grow i.c., we did not compare s.c. versus i.c. TMZ sensitivity of a given model for TMZ.
We did some of the experiments you suggest but when studying the effects of galectin-1 (+/- TMZ) on GBM growth (see the attached artiles).
Robert
Dear Professor Muller. Yes, the treatment of GBM is particular difficult and yes the efficacy of TMZ is very limited clinically. We have isolated GBM samples directly from patients that showed medium to poor response to TMZ in cell based assay. We found that in several cases the samples containing cancer stem-like cells of GBM that make them resistant to therapy. Interestingly, we found that strategy that introduce cluster miRNA-302-367 destroy the stemness property of GBM as well as propagation and so on. Please see the attach file for exemple. So please be very careful if you found TMZ alone is effective in your glioma model!
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