Wednesday 18 November 2015

2015 abstracts from Society for Neuro-Oncology conference

The 2015 abstracts have been published.  I will use this post to summarize the most interesting abstracts, and will continue updating it as I read through them.

ATPS-59. IMPROVING EFFICACY OF BEVACIZUMAB
TREATMENT IN GLIOBLASTOMA BY TARGETING HIF1 ALPHA

 "GBM spheroids were implanted orthotopically in nude rats...

 Our results show that CBD treatment down-regulates HIF 1 alpha under hypoxic conditions in vitro and in vivo. Combination treatment with CBD and bevacizumab decreases tumor growth and intratumoral hypoxia in clinically relevant human GBM xenograft models."

CBD of course refers to cannabidiol, derived from the cannabis plant.  Bevacizumab is the generic name for Avastin.

ATPS-83. REPURPOSING MEBENDAZOLE AS A REPLACEMENT
FOR VINCRISTINE FOR THE TREATMENT OF BRAIN TUMORS

"We also have compared the therapeutic efficacies of mebendazole and vincristine against GL261 orthotopic [mouse glioma] tumors at their respective maximum tolerated doses (respectively 100 mg/kg/day and 1 mg/kg/week). We found that mebendazole showed a 61% increase in animal survival time, whereas vincristine failed to show any efficacy.However,we did observe significant neuropathy (as measured by sensory allodynia) induced by mebendazole treatment, similar to that caused by vincristine."


IMPS-44. S100B INHIBITION WITH DULOXETINE, A SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITOR, ALTERS MACROPHAGE POLARIZATION AND ABROGATES GLIOMA GROWTH IN MICE

"In vivo, duloxetine inhibited S100B production, altered polarization and trafficking of macrophages and abrogated the growth of intracranial GL261 gliomas." 

ATPS-13. AROMATASE EXPRESSION IN HIGH GRADE GLIOMAS: A POTENTIAL NEW TARGET FOR THERAPY

"HGGs (N = 35) had markedly higher aromatase expression (>50%) relative to LGGs (N = 19). It is important to note that all the GBMs (N = 21) showed high CYP19A1 [aromatase] expression, whereas the normal tissues and meningiomas had negligible expression. Secondly, letrozole, a widely used aromatase inhibitor in the treatment of ER+ breast tumors in post-menopausal women exhibited excellent brain and brain tumoral penetration and anti-tumor efficacy (assessed using mPET/CT) in rats orthotopically implanted C6 malignant glioma cells. Furthermore, glioma-bearing rats (N =10) treated with letrozole (4 mg/Kg;i.p.injections) had long term suppression with overall survival exceeding 65 days and no signs of overt toxicity. In contrast, control untreated rats (N = 6, 2ml/kg vehicle i.p. injections) developed significant morbidity/mortality in 15-20 days. Overall, our studies strongly suggest that aromatase is a new “druggable target” for treatment of HGGs and that letrozole can potentially be readily used for this purpose."


7 comments:

  1. Thank you for this.

    How many mg daily of CBD were ingested in the study? Unless this is referring to CBD oil being injected into the tumor cavity? I've heard they have also done studies that way as well.

    We've experimented with CBD/THC but I doubt we are anywhere near an amount that could be considered beneficial. Cannabis oil advocate Rick Simpson, who's real big on highly concentrated THC oil recommends building up to a gram a day. I can say we've never come near that amount as a 1:1 ratio of 15mg CBD/15mg THC was quite strong for my mom. Rick's tolerance is obviously insanely high lol. I realize this study is referring to CBD which does not produce a high like THC.

    Thanks Stephen!

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  2. This was a rat study, and no information is given in the abstract on dose or route of administration (oral? intraperitoneal?). Rodent doses can't be directly translated into human doses, even if we did know the rat dose, it would only give an approximation.

    Other rodent GBM studies with pure CBD have shown an antioxidant response mechanism coming into play leading to resistance (this study is summarized on the Supplements page on Astrocytoma Options). However I would be tempted to try it if it can make Avastin more effective. There are high CBD, very low THC blends available on the market.

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    1. Also some people are taking cannabis oil as a suppository, which apparently does not produce the same high that you would get taking it orally. See the "CBD" thread on this blog.

      http://btcocktails.blogspot.ca/2015/10/cbd.html

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  4. New abstract added to this post, on duloxetine, a SNRI antidepressant.

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  5. Another new abstract added to this post, showing letrozole, an aromatase inhibitor used in breast cancer therapy extends survival in the C6 rat glioma model.

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  6. A manuscript of the duloxetine study was just published online.

    https://www.sciencedirect.com/science/article/pii/S0304383518304981

    I've uploaded to the Brain Tumor Library. Folder 2 Therapies - preclinical -> Duloxetine

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