Marijuana Ingredient Inhibits VEGF Pathway Required for Brain Tumor Blood Vessels
August 16, 2004
Science Daily/American Association for Cancer Research
Cannabinoids, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).
According to a new study published in the August 15, 2004 issue of the journal Cancer Research, administration of cannabinoids significantly lowered VEGF activity in laboratory mice and two patients with late-stage glioblastoma.
"Blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available," said Manuel Guzmán, professor of biochemistry and molecular biology, with the Complutense University in Madrid, Spain, and the study's principal investigator.
"The present findings provide a novel pharmacological target for cannabinoid-based therapies."
Glioblastoma multiforme, the most aggressive form of glioma, strikes more than 7,000 Americans each year and is considered one of the most malignant and deadliest forms of cancer, generally resulting in death within one to two years following diagnosis.
The disease is usually treated with surgery, followed by conventional radiation alone or in combination with chemotherapy. However, the main tumor often evades total destruction, surviving and growing again, eventually killing the patient. For this reason, researchers are actively seeking other therapeutic strategies, some of which might be considered novel.
In this study, the investigators chose to work with cannabinoids which, in previous studies, have been shown to inhibit the growth of blood vessels, or angiogenesis, in laboratory mice. However, little was known about the specific mechanisms by which cannabinoids impair angiogenesis, or whether the chemical might do the same in human tumors.
To answer the first part of the question, the scientists induced gliomas in mice, which were subsequently inoculated with cannabinoids. Using DNA array analysis, the team examined 267 genes associated with the growth of blood vessels in tumors and found that cannabinoids lowered the expression of several genes related to the VEGF pathway, critical for angiogenesis.
The researchers also discovered that cannabinoids apparently worked by increasing the activity of ceramide, a lipid mediator of apoptosis, resulting in the functional inhibition of cells needed for VEGF production. The ability of cannabinoids to alter VEGF production was significantly stifled following the introduction of a ceramide inhibitor.
"As far as we know, this is the first report showing that ceramide depresses VEGF pathway by interfering with VEGF production," according to Guzmán.
To answer the second part of the question relating to clinical tests, the scientists obtained tumor biopsies from two patients with glioblastomas who had failed standard therapy, including surgery, radiotherapy and chemotherapy. The biopsied tissue was analyzed before and after local injection of a cannabinoid.
"In both patients, VEGF levels in tumor extracts were lower after cannabinoid inoculation," said Guzmán.
The results, he added, suggest a potential new approach toward the treatment of these otherwise intractable brain tumors.
"It is essential to develop new therapeutic strategies for the management of glioblastoma multiforme," the scientists wrote, "which will most likely require a combination of therapies to obtain significant clinical results."
Also participating in the study were Cristina Blázquez and Amador Haro, from Complutense University; Luis González-Feria, from University Hospital, Tenerife, Spain; Luis Álvarez, from La Paz University Hospital in Madrid; and M. Llanos Casanova, from the Project on Cellular and Molecular Biology and Gene Therapy, CIEMAT, also in Madrid.
https://www.sciencedaily.com/releases/2004/08/040816085401.htm
Patients with or without cancer use different forms of marijuana
March 26, 2019
NYU Langone Health / NYU School of Medicine
People with and without cancer are more likely, over time, to use a more potent form of medical marijuana with increasingly higher amounts of tetrahydrocannabinol (THC), a new study shows.
In a report publishing in the Journal of Palliative Medicine on March 26, researchers say that cancer patients were more likely to favor forms of medical marijuana with higher amounts of THC, which relieves cancer symptoms and the side effects of cancer treatment, including chronic pain, weight loss, and nausea.
By contrast, marijuana formulations higher in cannabidiol (CBD), which has been shown to reduce seizures and inflammation in other studies, were more popular among non-cancer patients, including those with epilepsy and multiple sclerosis, say the study authors.
Cancer patients were also more likely to prefer taking oil droplets containing medical marijuana under the tongue than "vaping."
"Although there is growing patient interest in medical cannabis, there is a scarcity of solid evidence about the benefits, risks, and patterns of use of marijuana products in various disease settings," says study lead investigator Arum Kim, MD, an assistant professor of medicine and rehabilitation medicine at NYU School of Medicine and director of the supportive oncology program at its Perlmutter Cancer Center. "Such information is important for delivering the best care."
Since 1996, 31 states, including New York in 2014, have legalized medical marijuana.
For the study, researchers analyzed data from 11,590 men and women in New York, of whom 1,990 (17.2 percent of the total patient cohort) were cancer patients who purchased and used cannabis products from Columbia Care LLC., a dispensary licensed in New York State, between January 2016 and December 2017.
The researchers caution that their data did not include the type of cancer the purchasers had, how much of what they bought was used, or whether marijuana was used for symptoms unrelated to the cancer. Nevertheless, the patterns of use among cancer patients were distinctly different from those of non-cancer patients.
Specifically, the study found that cancer and non-cancer patients used different dosages of cannabis formulations with dramatically different THC:CBD ratios. The two most common formulations contained THC and CBD, but one had twenty times more THC than CBD, whereas the other had the opposite ratio.
Over the two years of the study, the research team found that all types of patients increased their THC dose by approximately 0.20 milligrams per week.
"Our study provides valuable new information about how cancer patients are using marijuana," says study senior investigator Benjamin Han, MD, MPH, an assistant professor of medicine and population health at NYU School of Medicine. "In the absence of strong clinical research data for medical marijuana, identifying patterns of use offers some sense of how to guide patients who come in with questions for using medical marijuana, and what may or may not help them."
Researchers say they next plan to get more detailed information about how medical marijuana affects patient response to therapy and functional status at different stages of their disease, as well as the risks and side effects of treatment. Furthermore, the profiles of other cannabinoids besides THC and CBD in medical marijuana products warrant further research, according to the study authors.
Along with Kim and Han, another co-author from NYU School of Medicine and Perlmutter Cancer Center, which funded the study, was Zujun Li, MD. Other study authors include Christopher Kaufmann, PhD, MHS, at University of California San Diego; and Roxanne Ko, BA, BS, at the University of Hawaii.
https://www.sciencedaily.com/releases/2019/03/190326081343.htm
Cannabinoids may have a vast array of anti-cancer effects
July 18, 2018
Science Daily/Wiley
Previous research has shown that cannabinoids can help lessen side effects of anti-cancer therapies. Now a new British Journal of Pharmacology review has examined their potential for the direct treatment of cancer.
Phytocannabinoids are the most notable type of cannabinoid, and they occur naturally in the cannabis plant. Studies have shown that cannabinoids may stop cancer cells from dividing and invading normal tissue, and they may block the blood supply to tumors. Some studies also indicate that cannabinoids may enhance the body's immune response against the growth and spread of tumors.
"There is still a need for additional anti-cancer drugs. In this context accumulating data from preclinical models suggest that cannabinoids elicit anti-cancer effects on several levels of cancer progression," said author Prof. Burkhard Hinz, of Rostock University Medical Center, in Germany. "Clinical studies are now urgently needed to investigate the impact of cannabinoids on cancer growth and progression in patients."
https://www.sciencedaily.com/releases/2018/07/180718082143.htm
Can cannabinoids be used to treat cancer?
November 6, 2017
Science Daily/Mary Ann Liebert, Inc./Genetic Engineering News
When cannabinoids activate signaling pathways in cancer cells they can stimulate a cell death mechanism called apoptosis, unleashing a potent anti-tumor effect. Yet cannabinoids, which have also shown strong activity against human tumor tissue grown in animal models, have undergone minimal testing in patients. Their potential use as antitumor drugs and/or to boost the effectiveness of conventional cancer therapies is examined in an article published in The Journal of Alternative and Complementary Medicine (JACM).
In "A Review of the Therapeutic Antitumor Potential of Cannabinoids," scientists present the results of a detailed survey of the medical and scientific literature focused on the effects of cannabinoids on signaling pathways involved in tumor cell proliferation and death. The researchers review the mechanisms of anticancer activity of cannabinoids, discuss the similarities and differences between exogenous (plant-derived) and endogenous cannabinoids, report on the clinical studies conducted to date to assess the anti-tumor effects of these compounds, and consider the possible adjuvant properties of cannabinoids in cancer treatment.
"Although medical cannabis is well-supported in the literature for symptom reduction from cancer treatment or the disease itself, there are many claims that cannabis can treat cancer itself," says Leslie Mendoza Temple, MD, ABOIM, University of Chicago Pritzker School of Medicine and Medical Director, Integrative Medicine Program. "So far, this is based on only a handful of small human studies, anecdote, or laboratory research. This article nicely summarizes some of the work done in the lab for an understanding of cannabis' potential anti-cancer mechanisms, while pointing to the paucity of human trials." Dr. Temple adds, "Federal rescheduling of cannabis is critical so we can study its effects in humans and determine cannabis' direct or indirect effects on cancer cells."
https://www.sciencedaily.com/releases/2017/11/171106121300.htm