Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.

Posted on January 17, 2015 by David

“Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance.

Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS).

In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator.

…we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion.

Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.”

http://www.ncbi.nlm.nih.gov/pubmed/25590811

http://www.thctotalhealthcare.com/category/gllomas/

The antitumor action of cannabinoids on glioma tumorigenesis.

Posted on December 5, 2014 by David

“Cannabinoids are a class of chemical compounds with a wide spectrum of pharmacological effects, mediated by two specific plasma membrane receptors (CB1 and CB2).

Recently, CB1 and CB2 expression levels have been detected in human tumors, including those of brain.

Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo in animal models, after local or systemic administration.

We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.”

http://www.ncbi.nlm.nih.gov/pubmed/25472761

http://www.thctotalhealthcare.com/category/gllomas/

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model.

Posted on November 16, 2014 by David

“High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful.

Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis.

In an attempt to improve treatment outcome, we have investigated the effect of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261).

Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS).

Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS.

…increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis.

These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation.

Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities.”

http://www.ncbi.nlm.nih.gov/pubmed/25398831

http://www.thctotalhealthcare.com/category/gllomas/

Distinctive pattern of cannabinoid receptor type II (CB2) expression in adult and pediatric brain tumors.

Posted on March 4, 2014 by David

“The efficacy of cannabinoids against high-grade glioma in animal models, mediated by two specific receptors, CB1 and CB2, raised promises for targeted treatment of the most frequent and malignant primary brain tumors.

Unlike the abundantly expressed CB1, the CB2 receptor shows a restricted distribution in normal brain. Although brain tumors constitute the second most common malignancy in children and the prevalence of histological types of brain tumors vary significantly between the adult and pediatric populations, cannabinoid receptor expression in pediatric tumors remains unknown.

In the present study, we compared the expression of the CB2 receptor in paraffin-embedded sections from primary brain tumors of adult and pediatric patients. Most glioblastomas expressed very high levels of CB2 receptors and the expression correlated with tumor grade.

Interestingly, some benign pediatric astrocytic tumors, such as subependymal giant cell astrocytoma (SEGA), which may occasionally cause mortality owing to progressive growth, also displayed high CB2 immunoreactivity.

The high levels of CB2 expression would predestine those tumors to be vulnerable to cannabinoid treatment.

In contrast, all examined cases of embryonal tumors (medulloblastoma and S-PNET), the most frequently diagnosed malignant brain tumors in childhood, showed no or trace CB2 immunoreactivity.

Our results suggest that the CB2 receptor expression depends primarily on the histopathological origin of the brain tumor cells and differentiation state, reflecting the tumor grade.”

http://www.ncbi.nlm.nih.gov/pubmed/17239827

Endocannabinoid system in cancer cachexia.

Posted on March 1, 2014 by David

Image result for current opinion in clinical nutrition & metabolic care

“More than 60% of advanced cancer patients suffer from anorexia and cachexia.

This review focuses on the possible mechanisms by which the endocannabinoid system antagonizes cachexia-anorexia processes in cancer patients and how it can be tapped for therapeutic applications.

Cannabinoids stimulate appetite and food intake…

Cannabinoid type 1 receptor activation stimulates appetite and promotes lipogenesis and energy storage.

Further study of cancer-cachexia pathophysiology and the role of endocannabinoids will help us to develop cannabinoids without psychotropic properties, which will help cancer patients suffering from cachexia and improve outcomes of clinical antitumor therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17563462

The endocannabinoid signaling system in cancer.

Posted on March 1, 2014 by David

“The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancerpathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/23602129

Spontaneous regression of septum pellucidum/forniceal pilocytic astrocytomas–possible role of Cannabis inhalation.

Posted on January 27, 2014 by David

“The purpose of this report is to document spontaneous regression of pilocytic astrocytomas of the septum pellucidum and to discuss the possible role of cannabis in promoting regression.

We report two children with septum pellucidum/forniceal pilocytic astrocytoma (PA) tumors… Neither patient received any conventional adjuvant treatment.

The tumors regressed over the same period of time that cannabis was consumed via inhalation, raising the possibility that the cannabis played a role in the tumor regression.”

http://www.ncbi.nlm.nih.gov/pubmed/21336992

Cannabinoid receptors in human astroglial tumors.

Posted on January 27, 2014 by David

“…cannabinoids are reported to inhibit the growth of tumors, including gliomas. These effects have been claimed to be mediated via cannabinoid receptors 1 and 2 (CB1, CB2).

We conclude that cannabinoid therapy of human gliomas targets not only receptors on tumor, but also on other cell types…”

http://www.ncbi.nlm.nih.gov/pubmed/16893424

5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid.

Posted on January 26, 2014 by David

“It has been recently reported that cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation.

…the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system…”

http://www.ncbi.nlm.nih.gov/pubmed/18028339

Cannabinoids induce glioma stem-like cell differentiation and inhibit gliomagenesis.

Posted on January 26, 2014 by David

“Glioma stem-like cells constitute one of the potential origins of gliomas, and therefore, their elimination is an essential factor for the development of efficient therapeutic strategies.

Cannabinoids are known to exert an antitumoral action on gliomas that relies on at least two mechanisms: induction of apoptosis of transformed cells and inhibition of tumor angiogenesis…

The discovery of an endogenous cannabinoid system, together with the great improvement in our understanding of the signaling mechanisms responsible for cannabinoid actions, has fostered the interest in the potential therapeutic applications of cannabinoids.

Several studies have demonstrated a significant antitumoral action of cannabinoid ligands in animal models. Thus, cannabinoid administration to nude mice curbs the growth of different tumors, including gliomas…

Cannabinoids are known to exert an antitumoral action against gliomas…

Overall, our results demonstrate that cannabinoids target glioma stem-like cells, promote their differentiation, and inhibit gliomagenesis, thus giving further support to their potential use in the management of malignant gliomas.

In conclusion, our results demonstrate the action of cannabinoids on glioma stem-like cells and thus may open new avenues for cannabinoid-based antitumoral strategies.”

http://www.jbc.org/content/282/9/6854.long