Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.

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“Salivary gland cancer (SGC) represents the most common malignancy in the head and neck region, and often metastasizes to the lungs. The helix-loop-helix ID1 protein has been shown to control metastatic progression in many types of cancers.

Using two different approaches to target the expression of ID1 (genetic knockdown and progesterone receptor introduction combined with progesterone treatment), we previously determined that the aggressiveness of salivary gland tumor ACCM cells in culture was suppressed. Here, using the same approaches to target ID1 expression, we investigated the ability of ACCM cells to generate lung metastatic foci in nude mice.

Moreover, since both approaches would be challenging for applications in humans, we added a third approach, i.e., treatment of mice with a non-toxic cannabinoid compound known to down-regulate ID1 gene expression.

All approaches aimed at targeting the pro-metastatic ID1 gene led to a significant reduction in the formation of lung metastatic foci.

Therefore, targeting a key transcriptional regulator using different means results in the same reduction of the metastatic spread of SGC cells in animal models, suggesting a novel approach for the treatment of patients with aggressive SGC.”

http://www.ncbi.nlm.nih.gov/pubmed/27087608

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells… CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells…  Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types…”  http://mct.aacrjournals.org/content/6/11/2921.long

http://www.thctotalhealthcare.com/tag/id-1/

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Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target.

Figure 2

“Glioblastoma (GBM) is the most common form of primary adult brain tumors…

It is, therefore, essential to discover master regulators that control GBM invasiveness and target them therapeutically.

We demonstrate here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of GBM cell lines and primary GBM cells.

Furthermore, we show that a non-toxic compound, cannabidiol, significantly down-regulates Id-1 gene expression and associated glioma cell invasiveness…

Our results suggest that Id-1 regulates multiple tumor-promoting pathways in GBM, and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of GBM patients.

We previously showed a strong correlation between Id-1 expression and the invasive and metastatic behavior of breast cancer cells.”

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells… CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells…  Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types…”  http://mct.aacrjournals.org/content/6/11/2921.long

“In this report, we show that Id-1 is a key regulator of brain tumor cell invasiveness and neurosphere growth, and that Id-1 expression is specifically up-regulated in tissues from patients with high-grade gliomas. Importantly, we demonstrate that targeting Id-1 expression using either genetic approaches or the non-toxic cannabinoid, cannabidiol (CBD), leads to a significant reduction in the invasion of both GBM cell lines and patient-derived primary GBM cultures. CBD also significantly inhibits GBM dispersal ex vivo, and reduces tumor growth and Id-1 expression in vivo.

Consistent with the breast cancer study, we found that the non-psychoactive cannabinoid CBD significantly down-regulated Id-1 expression in serum-derived and primary GBM cells. As expected, we observed robust inhibition of glioma cell invasiveness.

In conclusion, our results establish Id-1 as a key regulator of both invasion and stemness in GBM cells and demonstrate that the non-toxic cannabinoid compound CBD down-regulates Id-1 expression and tumor aggressiveness in culture and in vivo.

The data also shed light on some of the key pathways that control GBM cell dispersal and progression. A greater understanding of these pathways may lead to more effective therapies for cancer patients including the additional refinement of cannabinoid analogs targeting Id-1.

We expect our efforts to ultimately translate to the development of future clinical trials with nontoxic compounds that target the expression of Id-1, a master regulator of GBM aggressiveness.

With its lack of systemic toxicity and psychoactivity, CBD is an ideal candidate agent in this regard and may prove useful in combination with front-line agents for the treatment of patients with aggressive and high-grade GBM tumors.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594064/

“McAllister Lab… Cannabidiol inhibits tumor (glioblastoma) progression in mouse models of brain cancer. Mice bearing human brain tumors derived from glioblastoma were treated with the naturally occurring cannabinoid, cannabidiol (CBD).”  http://www.cpmcri-currents.org/our-people/discovery-investigators/mcallister-lab

“New Study Finds Cannabis Compound Could Have Even Greater Reach in Inhibiting Aggressive Cancer than Previously Thought. Researchers at California Pacific Medical Center Research Institute (CPMCRI, a Sutter Health affiliate) have found that a compound in cannabis previously shown to decrease metastatic breast cancer now shows promise in stopping aggressive brain cancer as well. The findings are particularly important given the safety of the cannabis compound and the fact that patients with advanced brain cancer have few options for treatment.”  http://www.cpmc.org/about/press/news2012/cannabis-brain.html

http://www.thctotalhealthcare.com/category/brain-cancer/

Glioblastoma progression in mouse models of brain cancer, after treatment with CBD

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Targeting multiple cannabinoid antitumor pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

“The psychoactive cannabinoid Δ9 -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol(CBD) can both reduce cancer progression each through distinct antitumor pathways.

Our goal was to discover a compound that could efficiently target both cannabinoid antitumor pathways.

KEY RESULTS:

CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogs that could co-target cannabinoid antitumor pathways (CBD- and THC-associated) and discovered the compound O-1663. This analog inhibited Id1, produced a marked stimulation of ROS, upregulated autophagy, and induced apoptosis. Of all compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo.

CONCLUSIONS AND IMPLICATIONS:

O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid antitumor pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/24910342

“Anti-cancer effects of resorcinol derivatives on ascitic and solid forms of Ehrlich carcinoma in mice.” http://www.ncbi.nlm.nih.gov/pubmed/13774935

“Ardisiphenol D, a resorcinol derivative identified from Ardisia brevicaulis, exerts antitumor effect through inducing apoptosis in human non-small-cell lung cancer A549 cells.” http://www.ncbi.nlm.nih.gov/pubmed/24392814

“Antitumor effect of resorcinol derivatives from the roots of Ardisia brevicaulis by inducing apoptosis.” http://www.ncbi.nlm.nih.gov/pubmed/21751842

“Resorcinol derivatives from Ardisia maculosa.”  http://www.ncbi.nlm.nih.gov/pubmed/17885843

“Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions.” https://www.ncbi.nlm.nih.gov/pubmed/28412918

http://www.thctotalhealthcare.com/category/breast-cancer/

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Marijuana Compound Shows Promise In Fighting Breast Cancer

“A compound found in cannabis may prove to be effective at helping stop the spread of breast cancer cells throughout the body.”

 

 
“The study, by scientists at the California Pacific Medical Center Research Institute, is raising hope that CBD, a compound found in Cannabis sativa, could be the first non-toxic agent to show promise in treating metastatic forms of breast cancer.”
 
 

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells”  http://mct.aacrjournals.org/content/6/11/2921.full

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Medical Marijuana Inc Announces Positive Developments in Recent Studies Using Cannabidiol (CBD) Compound; NBC News, ABC News and Huffington Post Report California Pacific Medical Center’s Findings That CBD Stops Metastasis in Aggressive Cancers – The Wall Street Journal

“Medical Marijuana Inc Announces Positive Developments in Recent Studies Using Cannabidiol (CBD) Compound; NBC News, ABC News and Huffington Post Report California Pacific Medical Center’s Findings That CBD Stops Metastasis in Aggressive Cancers

SAN DIEGO, May 28, 2013 (GLOBE NEWSWIRE) — Medical Marijuana Inc (OTC Pink:MJNA) is pleased to inform shareholders and the general public of recent developments in the research involving Cannabidiol (CBD) and other Phyto-cannabinoids.

The Following is taken from a Huffington Post interview with Dr. McAllister and Dr. Desprez:

A pair of scientists at California Pacific Medical Center in San Francisco has found that a compound derived from marijuana could stop metastasis in many kinds of aggressive cancer, potentially altering the fatality of the disease forever.

“It took us about 20 years of research to figure this out, but we are very excited,” said Pierre Desprez, one of the scientists behind the discovery, to The Huffington Post. “We want to get started with trials as soon as possible.”

The Daily Beast first reported on the finding, which has already undergone both laboratory and animal testing, and is awaiting permission for clinical trials in humans.

Desprez, a molecular biologist, spent decades studying ID-1, the gene that causes cancer to spread. Meanwhile, fellow researcher Sean McAllister was studying the effects of Cannabidiol, or CBD, a non-toxic, non-psychoactive chemical compound found in the cannabis plant. Finally, the pair collaborated, combining CBD and cells containing high levels of ID-1 in a petri dish.

“What we found was that his Cannabidiol could essentially ‘turn off’ the ID-1,” Desprez told HuffPost. The cells stopped spreading and returned to normal.

“We likely would not have found this on our own,” he added. “That’s why collaboration is so essential to scientific discovery.”

Desprez and McAllister first published a paper about the finding in 2007. Since then, their team has found that CBD works both in the lab and in animals. And now, they’ve found even more good news.

“We started by researching breast cancer,” said Desprez. “But now we’ve found that Cannabidiol works with many kinds of aggressive cancers–brain, prostate–any kind in which these high levels of ID-1 are present.”

Desprez hopes that clinical trials will begin immediately.

“We’ve found no toxicity in the animals we’ve tested, and Cannabidiol is already used in humans for a variety of other ailments,” he said. Indeed, the compound is used to relieve anxiety and nausea, and, since it is non-psychoactive, does not cause the “high” associated with THC.

While marijuana advocates will surely praise the discovery, Desprez explained that it’s not so easy as just lighting up.

“We used injections in the animal testing and are also testing pills,” he said. “But you could never get enough Cannabidiol for it to be effective just from smoking.”

Additional Information:

Dr. McAllister & CBD Research

Dr. Sean McAllister says that he is ready to begin testing CBD on humans to evaluate anti-cancer properties. Dr. McAllister and colleague Pierre Desprez, PhD from California Pacific Medical Center have previously mentioned, “Cannabidiol offers hope of a non-toxic therapy that could treat aggressive forms of cancer without any of the painful side effects of chemotherapy.” “We found that this one compound, CBD, had a specific effect on metastatic cancer cells, very aggressive tumor cells. CBD in animal studies has been used to ‘switch off’ a specific gene regulator.” Dr. McAllister explains: “We find when you treat with CBD, you down regulate the expression of this protein and that inhibits the disease process.” Dr. McAllister and Dr. Desprez have developed a synthetic version of CBD, which they say targets a specific gene in the body related to the spread of cancer (metastasis). Article: http://abclocal.go.com/kgo/story?section=news/health&id=9057615

Additional Cannabidiol Information

ABC News-

http://abclocal.go.com/kgo/story?section=news/health&id=9057615

Huffington Post-

http://www.huffingtonpost.com/2012/09/19/marijuana-and-cancer_n_1898208. html?ncid=edlinkusaolp00000003&ir=Weird%20News

US. National Cancer Institute

http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/p age4

Additional Dr. McAllister Publications

http://www.ncbi.nlm.nih.gov/pubmed/?term=Sean%20McAllister

Additional Published Material on Cannabidiol (CBD)

http://www.ncbi.nlm.nih.gov/gquery/?term=CANNABIDIOL”

More: http://online.wsj.com/article/PR-CO-20130528-906109.html

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Doctors utilise marijuana as pain relief

“A pair of scientists at California Pacific Medical Center in San Francisco has found that a compound derived from marijuana could stop metastasis in many kinds of aggressive cancer, potentially altering the fatality of the disease forever.

“It took us about 20 years of research to figure this out, but we are very excited,” said Pierre Desprez, one of the scientists behind the discovery. The finding, which has already undergone both laboratory and animal testing, and is awaiting permission for clinical trials in humans.

Desprez, a molecular biologist, spent decades studying ID-1, the gene that causes cancer to spread. Fellow researcher  Sean McAllister was studying the effects of Cannabidiol, or CBD, a non-toxic, non-psychoactive chemical compound found in the cannabis plant. Finally, the pair collaborated, combining CBD and cells containing high levels of ID-1 in a petri dish.

“What we found was that his Cannabidiol could essentially ‘turn off’ the ID-1,” Desprez told HuffPost. The cells stopped spreading and returned to normal.

“We likely would not have found this on our own,” he added. “That’s why collaboration is so essential to scientific discovery.”

Desprez and McAllister’s findings was first published in 2007. Since then, their team has found that CBD works both in the lab and in animals. And now, they’ve found even more good news.

“We started by researching breast cancer. But now we’ve found that Cannabidiol works with many kinds of aggressive cancers–brain, prostate–any kind in which these high levels of ID-1 are present.”

“We’ve found no toxicity in the animals we’ve tested, and Cannabidiol is already used in humans for a variety of other ailments,” he said. Indeed, the compound is used to relieve anxiety and nausea, and, since it is non-psychoactive, does not cause the “high” associated with THC.

While marijuana advocates will surely praise the discovery, Desprez explained that it’s not so easy as just lighting up. “We used injections in the animal testing and are also testing pills. But you could never get enough Cannabidiol for it to be effective just from smoking.”

Furthermore, the team has started synthesizing the compound in the lab instead of using the plant in an effort to make it more potent.”It’s a common practice. But hopefully it will also keep us clear of any obstacles while seeking approval.””

By Sola Ogundipe

http://www.vanguardngr.com/2013/01/doctors-utilise-marijuana-as-pain-relief/

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Marijuana compound could help fight breast cancer – ABC News

“There may be a new weapon in the fight against aggressive forms of breast cancer in the future, and it comes from an unlikely source: Marijuana. Researchers at California Pacific Medical Center in San Francisco believe a compound in marijuana may help.

The research funded by the California Breast Cancer Research Program builds on more than a decade of studies involving the genes responsible for the spread of cancer. Now scientists have found at the cellular level, a compound in cannabis inhibits the gene that controls the spread of cancer.

“The problem is not the cancer itself, the problem is the spread of the cancer,” said cancer researcher Yvez Desprez, Ph.D.

Cancer researcher Pierre Desprez points to the gene ID-1 as the trigger.

“When this type of gene is expressed, the cells basically go crazy and they’re very aggressive and they metastasize everywhere in the body,” said Desprez.

“We could expect that if we create really effective inhibitors against it, we could potentially treat many types of aggressive cancers,” said cancer researcher Sean McAllister, Ph.D.

Their research in breast cancer cell lines focused on using a non-toxic compound in cannabis to target the ID-1 gene.

“What we found was cannabidiol is a particularly good inhibitor of this gene that’s responsible for the ability of cancer cells to become very aggressive,” said McAllister.”

http://abclocal.go.com/kgo/story?section=news/health&id=5771385

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Scientists believe marijuana compound could fight cancer

“Scientists in California believe they may have discovered a compound in marijuana that can reduce the aggressiveness of some forms of cancer.

The San Francisco Gate reports on the data that has been years in the making. While marijuana has been shown to help reduce nausea and pain in cancer patients, scientists believe that a compound in marijuana has the ability to “turn off” the activity of a gene responsible for metastasis in breast and other types of cancers.

The research team is working out of San Francisco’s California Pacific Medical Center Research Institute and have been working for years on the study. The compound they’re focused on, called cannabidiol, does not produce the psychotropic high associated with marijuana.

Last year, the team published a small study showing the positive effects of cannabidiol on mice. New data is about to be released that expands upon the previous results that the researchers hope will help propel the study even further.

“The preclinical trial data is very strong, and there’s no toxicity. There’s really a lot of research to move ahead with and to get people excited,” said Sean McAllister, who is working alongside scientist Pierre Desprez in the study.

Desprez and McAllister believe that their merging of separate areas of study was serendipitous.

Desprez had been studying the protein ID-1, which he found to play an important role in how cancer could spread. McAllister, on the other hand, was focused on studying anabolic steroids in drug abuse. He soon became focused on with the role non-psychotropic cannabidiol, or CBD, interacts with cancer.

McAllister, after hearing an internal seminar from Desprez on his studies of ID-1, came up with the question “How effective would cannabidiol be on targeting metastatic cancer cells?”

The two then teamed up, with Desprez armed with ID-1 cancer-causing protein, and McAllister with CBD, his cancer-fighting compound.

For their experimentation, the doctors exposed ID-1 to CBD in a petri dish. In a shocking result, the ID-1, the cancer-causing protein, reverted to a normal state and stopped acting “crazy.”

“We thought we did the experiment the wrong way,” McAllister said of the overwhelming results.

However, their results proved to be consisted.

“I told Sean, ‘Maybe your drug is working through my gene,’ ” Desprez said.

What the researchers have discovered thus far in their research is that CBD turns off the overexpression of ID-1, which prevents it from traveling to foreign tissues. Thus, the metastasization – cancer’s fatal ability – is blocked.

In the wake of their positive results, the doctors were forced to emphasize that the CBD will only work in the presence of high levels of ID-1 and these do not include all cancerous tumors but, rather, aggressive, metastatic cells. High levels have been found in leukemia, colorectal, pancreatic, lung, ovarian, brain and other cancers.”
Read more: http://www.irishcentral.com/news/Scientists-believe-marijuana-compound-could-fight-cancer-170689736.html#ixzz29rQbc2oS

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Can Cannabidiol (CBD) Fight Metastatic Cancer? According to the latest research the answer is yes. Important news for Medical Marijuana, Inc.’s new line of high concentrate CBD health and wellness products.

“(OTC: MJNA), a leading hemp industry innovator, is pleased to report on a September 18 San Francisco Chronicle Article, “Pot compound seen as tool against cancer.” The article states that scientists at California Pacific Medical Center who have been researching marijuana’s compounds for the 20 years have found that Cannabidiol, or CBD, has the ability to “turn off” the DNA that causes “breast and other types of cancers” to metastasize. CBD is the second-most abundant cannabinoid within marijuana, but does not cause the psychotropic high of THC.

As stated in the article: “We started by researching breast cancer,” said scientist Pierre Desprez. “But now we’ve found that Cannabidiol works with many kinds of aggressive cancers–brain, prostate–any kind in which these high levels of ID-1 are present.” Desprez said he is hopeful clinical trials will begin immediately. He currently has grant funding through the National Institutes of Health, Susan G. Komen for the Cure, the U.S. Department of Defense and the California Breast Cancer Research Program.

As previously announced in the MJNA press release dated September 5, MJNA portfolio company, Red Dice Holdings, recently launched its Hemp-based high concentrate CBD health and wellness products, Dixie X, for over-the-counter sales. These Cannabidiol products represent the highest strength of CBD products on the market today, and this same concentrate will soon be used to launch the CanChew Biotechnologies line of CBD-enriched chewing gum. Click here for recent production news from PhytoSphere. Dixie X can currently be purchased in over 100 retail locations in Colorado, Arizona and New Mexico as well as on-line by anyone living in the U.S.

In short, MJNA and its portfolio company, PhytoSphere Systems, currently produces non-THC, high quality CBD enriched Hemp oil that according to this story, may fight the most aggressive forms of cancers we know of today.

Studies, such as those in this article and at Project CBD, have continually shown that these non-psychoactive CBD wellness products provide powerful relief for pain and anxiety sufferers, but without the euphoric effects provided by THC. The CBD health and wellness industry is estimated by MJNA to be a $5 billion market.”

http://www.cnbc.com/id/49117540/Can_Cannabidiol_CBD_Fight_Metastatic_Cancer_According_to_the_latest_research_the_answer_is_yes_Important_news_for_Medical_Marijuana_Inc_s_new_line_of_high_concentrate_CBD_health_and_wellness_products

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Marijuana Compound Fights Cancer; Human Trials Next

(NBC) “Research shows component in medical cannabis fights cancer.”

“The “medical” bit of medical marijuana may be legitimate after all: Turns out a component of cannabis fights cancer, according to research.

Scientists at California Pacific Medical Center found that cannabidiol, or CBD, has the ability to “turn off” the DNA that causes “breast and other types of cancers” to metastasize, according to the San Francisco Chronicle.

“If this plant were discovered in the Amazon today, scientists would be falling all over each other to be the first to bring it to market,” said Dr. Donald Abrams, chief of oncology at the University of California San Francisco, which has also found science behind marijuana’s efficacy.

The drug “has been shown to reduce pain and nausea” in cancer patients, the newspaper reported. AIDS patients also swear by cannabis for its ability to allow them to eat, sleep and otherwise function.

Turns out that cannabidiol has none of the psychotropic effects of marijuana as a whole, according to the newspaper. The researchers hope to move to clinical trials on humans soon.

Cancer cells exposed to cannabidiol lost their abilities to metastasize, according to the newspaper.”

http://www.nbcbayarea.com/news/local/Marijuana-Compound-Fights-Cancer-Human-Trials-Next-170406116.html

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