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GENTAUR Europe

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    Proteins found in soybeans could inhibit the growth of colon, liver and lung cancers.  Soybean meal is a bi-product following oil extraction from soybean seeds. It is rich in protein, which usually makes up around 40% of the nutritional components of the seeds and dependent on the line, and can also contain high oleic acid (a monounsaturated omega-9 fatty acid).

    The study looked at the role soybeans could have in the prevention of cancer. Using a variety of soybean lines which were high in oleic acid and protein, the researchers looked to monitor bioactivity between the peptides derived from the meals of soybean and various types of human cancer cells.

    The study showed that peptides derived from soybean meal significantly inhibited cell growth by 73% for colon cancer, 70% for liver cancer and 68% for lung cancer cells using human cell lines. This shows that the selected high oleic acid soybean lines could have a potential nutraceutical affect in helping to reduce the growth of several types of cancer cells.

    Published in News

    Researchers from Thomas Jefferson University's Kimmel Cancer Center have discovered that decorin, a naturally occurring protein that circulates in the blood, acts as a potent inhibitor of tumor growth modulating the tumor microenvironment.

    The study, published June 24 online in the Proceedings of the National Academy of Sciences, suggests it may be possible to harness the power of this naturally occurring anticancer agent as a way to treat cancer, including metastases.

    In several different publications it has been described the ability of decorin to affect a number of biological processes including inflammatory responses, wound healing, and angiogenesis.

    In this new article, the study's senior investigator, Renato Iozzo, M.D., Ph.D., has labeled decorin a "soluble tumor repressor" -- the first to be found that specifically targets new blood vessels, which are pushed to grow by the cancer, and forces the vessel cells to "eat" their internal components. This reduces their potential to feed the cancer overall causing an inhibition of tumor progression.

    "The tumor suppressors we all know are genes inside tumors that a cancer deletes or silences in order to continue growing. I call decorin a tumor repressor because its anti-tumor activity comes from the body, outside the cancer," says Dr. Iozzo, Professor of Pathology & Cell Biology, Biochemistry & Molecular Biology at Kimmel Cancer Center.

    "Decorin is a soluble compound that we found has a powerful, natural protective effect against cancer -- an exciting finding that we believe will open up a new avenue for both basic research and clinical application," Dr. Iozzo says. "Acting from the outside of the cells, decorin is able to modify the behavior of the cancer cells and of the normal cells in order to slow down the progression of the tumor. For this reason, decorin acts as a guardian of the matrix, the complicated structure built around the cells in our body."

    Absence of decorin promotes tumor growth

    Decorin has long been known to be involved in human development. It is so named because deposits of decorin "decorate" collagen fibrils after the human body forms.

    A second pool of decorin has been found circulating in blood after production by connective tissue throughout the body. This connective tissue is part of the extracellular matrix, which provides both structural support and biological regulation of tissue cells.

    But no one has understood the biological function of this second pool of decorin, according to Dr. Iozzo.

    The research team, including the two co-first authors, Simone Buraschi, Ph.D., and Thomas Neill, a graduate student, who work in the laboratory of Dr. Iozzo, decoded the function of soluble decorin. They found that addition of exogenous decorin to the tumor microenvironment induces autophagy, a mechanism by which cells discard unnecessary or damaged intracellular structures. "This process regulates a lot of cellular activities," says Dr. Iozzo.

    The researchers specifically found that decorin evoked autophagy in both microvascular and macrovascular endothelial cells -- cells that line the interior surface of blood vessels.

    "This matters because autophagy can exert a potential oncosupressive function by acting to discard critical cell components that would otherwise be involved in promotion of tumor growth through angiogenesis, the production of new blood vessels that can provide nutrition to the tumor," Dr. Iozzo says. "In contrast, absence of decorin permits tumor growth."

    Therefore, the presence of decorin in the surroundings of the tumor is essential to control tumorigenesis and formation of new blood vessels, he says. Moreover, Dr. Iozzo's laboratory has characterized for the first time Peg3, a known tumor-suppressor gene, as a master player in the autophagy process induced by decorin. "This discovery is important as it opens up to the study of new unexplored genes and signaling pathways in the field of autophagy," he says. 

    "Circulating decorin represents a fundamental cellular process that acts to combat tumor angiogenesis," Dr. Iozzo says. "Treatment based on systemic delivery of decorin may represent a genuine advance in our ongoing war against cancer."

    The study was funded by the National Institutes of Health grants R01 CA39481, R01 CA47282, and R01 CA120975.

    Collaborating researchers from LifeCell Corporation, in Branchburg, New Jersey, and Goethe University in Frankfurt, Germany, also contributed to the study.

    Published in News
    Thursday, 14 February 2013 10:22

    JX-594 Anti-Cancer Virus Found in Canada

    antibodies-jx-594 cancer-cellsRecent news suggests that Canadian Cancer Specialists have found what researchers have labelled a medical first, in that an engineered virus which is injected into the cancer patients blood stream targets cancer cells throughout the body killing them, or at least not letting them get any bigger. Out of 23 patients, who have highly metabolized cancer, which means that the cancer has spread throughout their body and doesn’t show signs of being decreased, have been injected with a cancer fighting virus which hopes to kill the cancer cells. This is not the first time that a cancer virus has been suggested to the public. However, normally with cancer viruses, the virus itself had to be administered and injected directly into the tumor. This is extremely difficult as, tumors are not always stationary within the human body. The anti-cancer virus JX-594 was injected into the blood of 23 patients. 8 out of the 23 patients had the JX-594 replicating itself inside the cancer tumors, and not spreading into other healthy non-cancer cells.

    "We are very excited because this is the first time in medical history that a viral therapy has been shown to consistently and selectively replicate in cancer tissue after intravenous infusion in humans.” Said, Professor John Bell, who is the lead research from the University of Ottawa. Professor Nick Lemoine, director of Barts Cancer Institute said, “Viruses that multiply in just tumor cells - avoiding healthy cells - are showing real promise as a new biological approach to target hard-to-treat cancers. This new study is important because it shows that a virus previously used safely to vaccinate against smallpox in millions of people can now be modified to reach cancers through the bloodstream - even after cancer has spread widely through the patient's body. "It is particularly encouraging that responses were seen even in tumors like mesothelioma, a cancer which can be particularly hard to treat."

    What happened to the other 15 patients who did not show sign of progress? Well...it’s not said. However, 6 of the patients did have infection which prevented the growth of any tumor progress. JX-594 was only given to the 23 patients at a small does, and only one does, because it is so early in the stages.
     

    Dose-Finding Results

    Oncolytic immunotherapies are designed to selectively replicate within cancer cells and, subsequently, to lyse them, Dr. Reid and colleagues explain. JX-594 is designed to induce virus-replication-dependent oncolysis and tumor-specific immunity, and to disrupt the "viral thymidine kinase gene for cancer selectivity and insertion of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) and beta-galactosidase transgenes for immune stimulation and replication assessment, respectively," they note.

    The complete response of bulky tumors and systemic efficacy was seen in phase 1 trials of JX-594.

    In this phase 2 trial, 30 patients with advanced HCC received 1 of 2 injections into liver tumors on days 1, 15, and 29: low-dose JX-594 (108 pfu) or high-dose JX-594 (109 pfu).

    Kaplan–Meier survival estimates were significantly longer in the high-dose group than in the low-dose group at 1 year (66% vs 23%) and at 18 months (35% vs 11%). Survival did not correlate with the origin of the tumor.

    In the 19 patients with multiple tumors at baseline (10 in the high-dose group and 9 in the low-dose group), median overall survival was longer in the high-dose group (13.6 vs 4.3 months; HR, 0.19; P = .018).

    Median survival in patients with multiple tumors was half that of patients with single tumors (8.8 vs 16.6 months). The authors note that there was no correlation between survival duration and the presence of detectable neutralizing antibodies to the vaccinia virus at baseline, compared with the absence of such antibodies (HR, 0.68)

    Both doses of JX-594 were generally well tolerated, Dr. Reid and colleagues report, and there were no treatment-related deaths. One patient in the high-dose group experienced a treatment-related serious adverse event (nausea and vomiting requiring prolonged hospitalization), and 8 patients (4 in each group) experienced nontreatment-related serious adverse events.

    Antiangiogenesis Results

    In the phase 2 antiangiogenesis trial, Dr. Breitbach and colleagues tested the hypothesis that a vaccinia virus engineered to target cells that activate the ras/MAPK signaling pathway would specifically infect and express transgenes (hGM-CSF, beta-galactosidase) in tumor-associated vascular endothelial cells in humans.

    Preclinical research in mice demonstrated that an intravenous infusion of JX-594 resulted in virus replication in tumor-associated endothelial cells, disruption of tumor blood flow, and hypoxia within 48 hours, and massive tumor necrosis within 5 days. In a phase 1 clinical trial, an intravenous infusion of JX-594 showed dose-dependent endothelial cell infection in tumors.

     

    Dr. Breitbach and colleagues found that JX-594 disrupted perfusion to the tumor as soon as 5 days after treatment in both VEGF-receptor inhibitor-naïve and -refractory patients with advanced HCC.

    This "technology opens up the possibility of multifunctional engineered vaccinia products that selectively target and infect tumor-associated endothelial cells, as well as cancer cells, resulting in transgene expression, vasculature disruption, and tumor destruction in humans systemically," they note.

    Funding for the dose-finding study was provided by Jennerex, Transgene SA, and the Green Cross Corporation. Several coauthors report receiving individual grants, as detailed in the paper.

    Published in News