A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

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A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

OdgovorNapisal/-a skorc » 29 Avg 2016, 16:54

British Journal of Cancer (2006) 95, 197–203. doi:10.1038/sj.bjc.6603236 www.bjcancer.com
Published online 27 June 2006

A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

Δ9-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans. Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration. We also evaluated THC action on the length of survival and various tumour-cell parameters. A dose escalation regimen for THC administration was assessed. Cannabinoid delivery was safe and could be achieved without overt psychoactive effects. Median survival of the cohort from the beginning of cannabinoid administration was 24 weeks (95% confidence interval: 15–33). Δ9-Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro and decreased tumour-cell Ki67 immunostaining when administered to two patients. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.


Keywords: cannabinoid; glioblastoma multiforme; pilot clinical study; antitumoral drug

http://www.nature.com/bjc/journal/v95/n ... 3236a.html

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Re: A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

OdgovorNapisal/-a skorc » 29 Avg 2016, 17:08

in problem, ki lahko nastane:

Glioma cells develop resistance to cannabinoid treatment due to the upregulation of Amphiregulin (EGFR family ligand) and the growth factor midkine (Mdk)

Prosim, ce lahko najdete vsebino kej na to temo?

Hvala

skorc
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Re: A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

OdgovorNapisal/-a skorc » 29 Avg 2016, 18:04

Mozna resitev:
Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival.
Abstract
The cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor agonist Delta(9)-tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived cannabinoids, which do not interact efficiently with CB(1) and CB(2) receptors, can modulate the actions of Delta(9)-THC. There are conflicting reports, however, as to what extent other cannabinoids can modulate Delta(9)-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Delta(9)-THC. We therefore tested cannabidiol, the second most abundant plant-derived cannabinoid, in combination with Delta(9)-THC. In the U251 and SF126 glioblastoma cell lines, Delta(9)-THC and cannabidiol acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species and apoptosis as well as specific modulations of extracellular signal-regulated kinase and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of cannabidiol to Delta(9)-THC may improve the overall effectiveness of Delta(9)-THC in the treatment of glioblastoma in cancer patients.

http://www.ncbi.nlm.nih.gov/pubmed/20053780


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