Study identifies another strategy for normalizing tumor blood supply

In an upcoming issue of the journal Nature Medicine, researchers from the Steele Laboratory of Radiation Oncology at Massachusetts General Hospital (MGH) report an experiment in which NO production was selectively suppressed in tumor cells while being maintained in blood vessels. The result was a significant improvement in the appearance and function of the tumor’s blood supply.

“Our finding suggest that the creation of perivascular NO gradients – differences between the levels produced in blood vessels and those found in tumor tissue – may be able to normalize tumor vasculature,” says Dai Fukumura, MD, PhD, of the Steele Laboratory, who led the study. “Combining the use of angiogenesis inhibitors, which normalize vasculature through a different mechanism, with the blockade of nonvascular NO production may produce even greater improvement in therapeutic outcomes.”

The blood vessels that develop around and within tumors are leaky and disorganized, interfering with delivery of chemotherapy drugs and with radiation treatment, which requires an adequate oxygen supply. Combining angiogenesis inhibitors, drugs that suppress the growth of blood vessels, with traditional anticancer therapies has improved patient survival in some tumors. That success supports a theory developed by Rakesh K. Jain, PhD, director of the Steele Laboratory, that the agents temporarily ‘normalize’ blood vessels, creating a period during which other treatments can be more effective.

Since angiogenesis is one of many physiologic activities mediated by NO, the MGH research team hypothesized that restricting NO production to blood vessels also could improve tumor vasculature. Using cancer cells from human brain tumors, they suppressed the enzyme that controls NO production in nonvascular tissue. When the modified tumor cells were implanted into mice, analysis of the resulting tumors showed that NO was present primarily in blood vessels, with significant reductions in tumor cells. Vessels in the growing tumors were more evenly distributed and less distorted than those in tumors grown from untreated tissue.

“Angiogenesis inhibitors block formation of new vessels by directly or indirectly inhibiting the proliferation and survival of vascular endothelial cells. But since their overall effect is to reduce the density of blood vessels, the ability of those agents to normalize tumor vasculature may not last long,” says Fukumura. “Blocking nonvascular NO production and maintaining NO levels around the vessels appears to keep endothelial cell function at the proper level.” An associate professor of Radiation Oncology at Harvard Medical School, Fukumura notes that the strategy now should be investigated in other types of tumors.

Source: Massachusetts General Hospital

Holey Nanoparticles Create New Tumor Imaging and Therapeutic Agent
Using a polymer that has both water-soluble and water-insoluble regions, a team of investigators from the Siteman Center of Cancer Nanotechnology Excellence has created a nanoparticle shaped like a bialy, a close relative of the bagel.
Could arthritis wonder drugs provide clues for all disease?
Drugs that have helped treat millions of rheumatoid arthritis sufferers may hold the key to many more medical conditions, including atherosclerosis – a leading cause of heart disease – says the researcher who jointly invented and developed them.
Researchers discover link between organ transplantation and increased cancer risk
Researchers have determined a novel mechanism through which organ transplantation often leads to cancer, and their findings suggest that targeted therapies may reduce or prevent that risk.
Vitamin A pushes breast cancer to form blood vessel cells
Researchers at Georgetown University Medical Center have discovered that vitamin A, when applied to breast cancer cells, turns on genes that can push stem cells embedded in a tumor to morph into endothelial cells. These cells can then build blood vessels to link up to the body's blood supply, promoting further tumor growth.
Tumor-inhibiting protein could be effective in treating leukemia
(PhysOrg.com) -- Angiocidin, a tumor-inhibiting novel protein discovered by Temple University researchers, may also have a role as a new therapeutic application in treating leukemia, according to a study by the researchers.
Nanomaterials Key to New Strategies for Blocking Metastasis
A new treatment strategy using targeted nanoparticles to block metastasis with anti-cancer drugs leads to good results using significantly lower doses of toxic chemotherapy, with less collateral damage to surrounding tissue, according to a collaborative team of researchers at the Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer at the University of California, San Diego. In designing this system, the investigators, led by David Cheresh, Ph.D., have identified what may become a generic method for using nanotechnology to target metastasis.
'Smart bomb' nanoparticle strategy impacts metastasis
A new treatment strategy using molecular "smart bombs" to target metastasis with anti-cancer drugs leads to good results using significantly lower doses of toxic chemotherapy, with less collateral damage to surrounding tissue, according to a collaborative team of researchers at the University of California, San Diego.
Bacterial peptide provides new insight into common tumor suppressor
Scientists have identified a new antitumor drug that might prove useful in developing treatments for a multiple human cancers. The research, published by Cell Press in the July 8 issue of the journal Cancer Cell, advances the understanding of one of the most frequently disrupted tumor suppressor proteins in human cancer and provides new insight into the regulation of the complex process of cellular protein degradation under normal and pathological conditions.

Study identifies another strategy for normalizing tumor blood supply

Related stories:

News discussion: