Safety and efficacy of a novel cannabinoid chemotherapeutic, KM-233, for the treatment of high-grade glioma

@article{Duntsch2005SafetyAE,
  title={Safety and efficacy of a novel cannabinoid chemotherapeutic, KM-233, for the treatment
of high-grade glioma},
  author={Christopher D. Duntsch and Murali Krishna Prasad Divi and Terreia S. Jones and Qihong Zhou and Mathangi Krishnamurthy and Peter Dipl Ing Boehm and G Christopher Wood and Allen K. Sills and Bob M. Moore Ii},
  journal={Journal of Neuro-Oncology},
  year={2005},
  volume={77},
  pages={143-152}
}
SummaryObjectiveTo test in vitro and in vivo the safety and efficacy of a novel chemotherapeutic agent, KM-233, for the treatment of glioma.MethodsIn vitro cell cytotoxicity assays were used to measure and compare the cytotoxic effects of KM-233, Δ8-tetrahydrocannabinol (THC), and bis-chloroethyl-nitrosurea (BCNU) against human U87 glioma cells. An organotypic brain slice culture model was used for safety and toxicity studies. A human glioma-SCID mouse side-pocket tumor model was used to test… 
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References

SHOWING 1-10 OF 57 REFERENCES
Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines
TLDR
Evaluating the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines suggests a possible application of CBD as an antineoplastic agent.
Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor.
TLDR
It is shown that local administration of the selective CB(2) agonist JWH-133 at 50 microg/day to Rag-2(-/-) mice induced a considerable regression of malignant tumors generated by inoculation of C6 glioma cells, and showed that selective activation of the CB( 2) receptor signaled apoptosis via enhanced ceramide synthesis de novo.
Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease.
TLDR
The current data demonstrate that CB2 cannabinoid receptors expressed on malignancies of the immune system may serve as potential targets for the induction of apoptosis, and because CB2 agonists lack psychotropic effects, they may Serve as novel anticancer agents to selectively target and kill tumors of immune origin.
Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors.
TLDR
It is shown that the CB(1) and theCB(2) receptor are expressed in normal skin and skin tumors of mice and humans and support a new therapeutic approach for the treatment of skin tumors.
Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway.
TLDR
One of the most intriguing findings was that THC-induced cell death was preceded by significant changes in the expression of genes involved in the mitogen-activated protein kinase (MAPK) signal transduction pathways.
Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability.
TLDR
There was no observed synergy between the effects of tamoxifen and the cannabinoids upon cell viability and Delta(9)-THC and cannabidiol, but not AEA produced a modest reduction in cell viability after 6 days of incubation in serum-free medium, whereas no effects were seen in 10% FBS-containing medium.
Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation
TLDR
It is shown that intratumoral administration of Δ9-tetrahydrocannabinol and the synthetic cannabinoid agonist WIN-55,212-2 induced a considerable regression of malignant gliomas in Wistar rats and in mice deficient in recombination activating gene 2.
Inhibition of rat C6 glioma cell proliferation by endogenous and synthetic cannabinoids. Relative involvement of cannabinoid and vanilloid receptors.
TLDR
The antiproliferative effects of the endocannabinoids upon C6 cells are brought about by a mechanism involving combined activation of both vanilloid receptors and to a lesser extent cannabinoid receptors, and leading to oxidative stress and calpain activation.
Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas
Cannabinoids inhibit tumor angiogenesis in mice, but the mechanism of their antiangiogenic action is still unknown. Because the vascular endothelial growth factor (VEGF) pathway plays a critical role
Antineoplastic activity of cannabinoids.
TLDR
Delta9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 times DBA/2)F1 (BDF1) mice hosting the L1210 murine leukemia, however, delta9- THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly.
...
1
2
3
4
5
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