November 16, 2005
Gene therapy curbs pancreatic cancerTopics: Medicine
Pancreatic cancer is the fifth leading cause of cancer deaths in the developed world, and is extremely difficult to treat. Only 3% of affected patients are still alive five years after diagnosis, a survival rate that has remained static for the past three decades. Currently, the only viable treatment is surgery. Radiotherapy and chemotherapy have little impact on the disease.
The research team investigated the potential of the protein vasostatin to suppress the development of new blood vessels and pancreatic tumour cells both in test tubes and in mice with pancreatic cancer. 'Solid' tumours, such as pancreatic cancer, are heavily dependent on a rich blood supply to enable them to grow rapidly and spread throughout the body. This process is known as angiogenesis.
The protein gene was incorporated into a virus (adenovirus), so that it would be able to penetrate the cells, acting as a vector. The test tube experiments showed that 72 hours after infection with the genetically modified virus, vasostatin was clearly active in the tissue. Tumour growth in the mice was also curbed, and when compared with mice which had not been infected with the virus, the difference between the two groups was highly significant.
The researchers then looked more closely at the pancreatic cells and the cell linings of the blood vessels (vascular endothelial cells).
They found that although vasostatin seemed to have little impact on the pancreatic cells, it blocked the formation of new blood vessels, effectively cutting off the supply of nutrients to the malignant cells. This effect was seen in both the test tube and animal experiments.
The authors conclude that this type of gene therapy "may be a potent strategy to treat many malignant tumours, including pancreatic cancer, and represents a promising therapeutic option for malignancy with a poor prognosis."
Background and related readings:
Targeted virus replication plus immunotherapy eradicates primary and distant pancreatic tumors in nude mice.
Researchers describe an adenovirus-based therapy for successfully managing pancreatic cancer, the cancer terminator virus (CTV), which is founded on targeted induction of viral replication from a cancer-specific progression elevated gene-3 (PEG-3) promoter (PEG-Prom) and immune modulation by IFN-gamma.
A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin.
The growth and persistence of solid tumors and their metastasis are angiogenesis-dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is a potent angiogenesis inhibitor. To investigate whether intramuscular administration of vasostatin gene has the antitumor activity in mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a control vector.
Adenovirus-mediated interferon alpha gene transfer induces regional direct cytotoxicity and possible systemic immunity against pancreatic cancer.
We previously demonstrated a characteristically high sensitivity of pancreatic cancer cells to interferon alpha (IFN-alpha) gene transfer, which induced a more prominent growth suppression and cell death in pancreatic cancer cells than in other types of cancers and normal cells. The IFN-alpha protein can exhibit both direct cytotoxicity and indirect immunological antitumour activity. Here, we dissected and examined the two mechanisms, taking advantage of the fact that IFN-alpha did not show any cross-species activity in its in vivo effect.
Posted by Richard at November 16, 2005 10:28 AM
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- Gene therapy curbs pancreatic cancer - Nov 16, 2005