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PostPosted: Thu Mar 11, 2010 10:02 am 
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Reovirus May Be a Novel Approach to Prostate Cancer Treatment

ScienceDaily (Mar. 10, 2010) — Researchers in Canada have detected a novel oncolytic viral therapy against prostate cancer with use of a virus called the reovirus, according to study results published in Cancer Research, a journal of the American Association for Cancer Research.

The respiratory, enteric, orphan virus (commonly known as reovirus) is a non-attenuated, environmental virus that has shown oncolytic potential against many types of cancer, specifically lymphoid, ovarian, breast, pancreatic and high grade glioma cancer, according to the study. This is the first time the virus has been studied against prostate cancer.

"The reovirus is a very common, ubiquitous virus that most people are exposed to. As far as we know, it doesn't cause any significant illness in humans, even though when someone is exposed to it, it manifests, at most, as a mild respiratory infection or mild diarrhea," said researcher Don Morris, M.D., Ph.D., medical oncologist in the Department of Oncology at the Tom Baker Cancer Center in Alberta, Canada.

"For the treatment of localized prostate cancer, we found that the reovirus is safe and has evidence of specific tumor vs. normal prostate cell efficacy," added Morris.

Using preclinical and clinical settings, Morris and colleagues examined the efficacy of the reovirus as an experimental therapeutic for prostate cancer in vitro and in vivo. Among the six patients who participated in the study, all had early-stage, organ-confined prostate cancer. Each patient underwent a single intralesional virus injection into a suitable prostate cancer nodule via transrectal ultrasound guidance. Three weeks later, Morris and colleagues removed the prostate as part of the patient's standard treatment for correlative science analysis.

Findings showed safety and efficacy with minimal toxicity and no viral replication in the normal parts of the prostate, according to Morris. Cancer cell death was evident in the prostate. Studies to date have suggested that the virus' side effects are relatively modest, consisting of mild, self-limiting, flu-like symptoms.

"Our results are a stepping stone into future prostate cancer clinical trials with another category of cancer therapeutics," he said.

Robert Clarke, Ph.D., D.Sc., professor of oncology at Lombardi Comprehensive Cancer Center at Georgetown University and an editorial board member of Cancer Research, agreed, stating that he believes this study is worthy of subsequent clinical trials of the reovirus as a possible way of treating some prostate cancers.

"People have known of this application of the reovirus in trials, but no one to my knowledge has conducted studies in prostate cancer," said Clarke, who was not associated with this study. "I think this is an interesting approach. There is not a lot done in oncolytics, but clearly it is an area that is getting increasing attention, and we need everything we can get our hands on to make a difference in these patients."

http://www.sciencedaily.com/releases/20 ... 131754.htm


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PostPosted: Thu Mar 11, 2010 10:04 am 
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Common Virus Kills Cancer Stem Cells

ScienceDaily (Apr. 9, 2009) — Dalhousie Medical School cancer researcher Dr. Patrick Lee has proven that a common virus can infect and kill breast cancer stem cells. This breakthrough finding is published in the current issue of Molecular Therapy, the journal of the American Society of Gene Therapy.

It is only within the past few years that the scientific community has understood the full significance of cancer stem cells and the urgent need to find a means of eliminating them.

“Cancer stem cells are essentially mother cells,” explains Dr. Lee, Cameron Chair in Basic Cancer Research at Dalhousie Medical School. “They continuously produce new cancer cells, aggressively forming tumours even when there are only a few of them.”

Cancer stem cells are difficult to kill as they respond poorly to chemotherapy and radiation. As Dr. Lee notes, “You can kill all the regular cancer cells in a tumour, but as long as there are cancer stem cells present, disease will recur.”

Dr. Lee is optimistic that his team has found the key to destroying cancer stem cells. The researchers have recently shown that human reovirus, a common virus that does not cause disease, effectively targets and kills cancer stem cells in breast cancer tissue.

“We suspected that reovirus might be effective against cancer stem cells, because we have shown time and again how well it destroys regular cancer cells,” remarks Dr. Lee, who was the first in the world to discover that a benign and naturally occurring virus could selectively infect and kill cancer cells without harming healthy cells. A Calgary-based company, Oncolytics Biotech Inc., is testing reovirus in clinical trials to prove the treatments are safe and effective.

Unlike most cancer studies, which use cancer cell lines developed for laboratory use, this study used fresh breast cancer tissue. This cancer tissue was removed from a patient of Dr. Carman Giacomantonio, a Capital Health surgical oncologist who is working with Dr. Lee on the reovirus research, along with post-doctoral fellow Dr. Paola Marcato and research assistant Cheryl Dean.

In addition to its ability to kill cancer cells and cancer stem cells, reovirus stimulates the anti-cancer immune system. Since virus therapy also invokes an anti-virus response, Dr. Lee and post-doctoral fellow Dr. Shashi Gujar are working on a way to harness the immune system so it attacks cancer cells while allowing the virus to freely infect and destroy cancerous cells. “Refining this two-pronged approach to killing cancer is our next step,” says Dr. Lee. “We are taking advantage of the natural characteristics of reovirus and the immune system itself to create a powerful virus-based anti-cancer therapy."

Dr. Lee’s discovery that reovirus effectively targets breast cancer stem cells has captured the attention of LeadDiscovery, a UK-based organization dedicated to promoting drug discovery and development. LeadDiscovery has identified the finding to be of particular interest to the drug development sector and will feature it in its next update to the global scientific community and pharmaceutical industry.

http://www.sciencedaily.com/releases/20 ... 192134.htm


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PostPosted: Thu Mar 11, 2010 10:07 am 
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Patient Trial For Virus That Attacks Brain Cancer Cells

ScienceDaily (Apr. 16, 2008) — A common, naturally occurring virus that attacks cancer cells but appears to be harmless to normal cells is being studied as a possible treatment for malignant, highly aggressive and deadly brain tumors called gliomas. Researchers at Cedars-Sinai Medical Center are among a few in the United States evaluating this experimental therapy.

Over the course of a lifetime, most adults will be exposed to the virus in its natural state. It commonly infects the lungs and intestines but -- unlike most viruses -- causes few if any symptoms and is usually eliminated by the body within two weeks. But while the reovirus (respiratory enteric orphan virus) may be harmless to normal cells, it can specifically kill certain cancer cells.

Vulnerable cancer cells have a defect in a signaling pathway (the Ras pathway) that controls key cell functions. The reovirus is able to infect and kill cancer cells that have an "activated" Ras pathway, but the virus does not normally come into contact with cancer cells. Researchers at Oncolytics Biotech Inc., of Calgary, Canada, developed a therapeutic drug, REOLYSIN®, from the reovirus and are conducting multicenter clinical trials for a variety of cancers. Cedars-Sinai is participating only in the study on recurrent gliomas, the most common and deadly brain cancers.

Based on the fact that many types of cancer cells have an activated Ras pathway, the company estimates that up to two thirds of all human cancers are susceptible to reovirus induced cell death .

"Although not every glioma cell line has an activated Ras pathway, Ras activation is very common in these malignant brain cancers. In lab tests and animal studies, the reovirus appears to target Ras-activated tumor cells and leave normal cells alone," said neurosurgeon John S. Yu, M.D., director of Surgical Neuro-oncology at Cedars-Sinai's Department of Neurosurgery. Yu is principal investigator of the REOLYSIN® clinical trial at Cedars-Sinai.

According to the protocol of this open-label Phase I and II trial, patients will receive a single treatment of REOLYSIN®, infused over 72 hours and directed into the tumor under sophisticated guidance. Expected length of hospital stay is about five days, and patients' progress will be followed for at least 12 weeks.

Oncolytics published results of preclinical studies in the June 20, 2001 issue of the Journal of the National Cancer Institute. In an animal study, mice with gliomas that were treated with a single injection of reovirus survived significantly longer than untreated mice. Complete tumor regression was found in 20 of 23 mice treated with the virus.

In laboratory studies, widespread cell killing was seen in 19 of 24 established human glioma cell lines tested. Reovirus also infected and killed all nine of nine primary glioma cultures taken from brain tumor surgical specimens. "Primary" refers to gliomas originating in the brain, not metastasizing from other locations.

http://www.sciencedaily.com/releases/20 ... 091004.htm


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