New drug targets for aggressive breast cancer

July 26, 2013 — Scientists at A*STAR’s Genome Institute of Singapore (GIS) led in a study that has identified genes that are potential targets for therapeutic drugs against aggressive breast cancer. These findings were reported in the July 2013 issue of PNAS.Out of the 1.5 million women diagnosed with breast cancer in the world annually, nearly one in seven of these is classified as triple negative. Patients with triple-negative breast cancer (TNBC) have tumours that are missing three important proteins that are found in other types of breast cancer. The absence of these three proteins make TNBC patients succumb to a higher rate of relapse following treatment and have lower overall survival rates. There is currently no effective therapy for TNBC.Using integrated genomic approaches, GIS scientists led by Dr. Qiang Yu, in collaboration with local and international institutions, set out to search for targets that can be affected by drugs. The scientists discovered that a protein tyrosine phosphatase[1], called UBASH3B, is overexpressed in one third of TNBC patients. UBASH3B controls the activity of an important breast cancer gene. The researchers found that deleting this gene expression markedly inhibits TNBC cell invasive growth and lung metastasis in a mouse model. They also showed that patients with TNBC tumours that have high levels of UBASH3B tend to be more likely to have early recurrence and metastasis.Lead author Dr Qiang Yu said, “The identification of target genes is always the most crucial first step towards treating a disease. …

Read more

Researchers generate long-lasting blood vessels from reprogrammed human cells

July 15, 2013 — Massachusetts General Hospital (MGH) researchers have used vascular precursor cells derived from human induced pluripotent stem cells (iPSCs) to generate, in an animal model, functional blood vessels that lasted as long as nine months. In their report being published in PNAS Early Edition, the investigators describe using iPSCs — reprogrammed adult cells that have many of the characteristics of embryonic stem cells — from both healthy adults and from individuals with type 1 diabetes to generate blood vessels on the outer surface of the brain or under the skin of mice.”The discovery of ways to bring mature cells back to a ‘stem-like’ state that can differentiate into many different types of tissue has brought enormous potential to the field of cell-based regenerative medicine, but the challenge of deriving functional cells from these iPSCs still remains,” says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and co-senior author of the study. “Our team has developed an efficient method to generate vascular precursor cells from human iPSCs and used them to create networks of engineered blood vessels in living mice.”The ability to regenerate or repair blood vessels could make a crucial difference in the treatment of cardiovascular disease — which continues to be the number one cause of death in the U.S. — and other conditions caused by blood vessel damage, such as the vascular complications of diabetes. In addition, providing a vascular supply to newly-generated tissue remains one of the greatest barriers facing efforts to build solid organs through tissue engineering.Several previous studies have generated from iPSCs the types of cells required to build blood vessels — endothelial cells that line vessels and connective tissue cells that provide structural support — but those cells could not form long-lasting vessels once introduced into animal models. “The biggest challenge we faced during the early phase of this project was establishing a reliable protocol to generate endothelial cell lines that produced great quantities of precursor cells that could generate strong, durable blood vessels,” says co-senior author Dai Fukumura, MD, PhD, also of the Steele Lab.The MGH team adapted a method originally used to derive endothelial cells from human embryonic stem cells (hESCs). But while that method used a single protein marker to identify vascular progenitors, the researchers sorted out iPSC-derived cells that expressed not only that protein but also two other protein markers of vascular potential. They then expanded that population using a culture system that team members had previously developed to differentiate endothelial cells from hESCs and confirmed that only iPSC-derived cells expressing all three markers generated endothelial cells with the full potential of forming blood vessels.To test the capacity of those cells to generate functional blood vessels, they implanted onto the surface of the brains of mice a combination of the iPSC-derived endothelial precursor cells expressing the three markers with the mesenchymal precursors that generate essential structural cells. Within two weeks, the implanted cells had formed networks of blood-perfused vessels that appeared to function as well as adjacent natural vessels and continued to function for as long as 280 days in the living animals. While implantation of the combined precursor populations under the skin of the animals also generated functional blood vessels, it required implantation of five times more cells, and the vessels were short-lived, an observation consistent with the team’s previous studies of vessel generation in these two locations.Because patients with type 1 diabetes (T1D), which can damage blood vessels, could benefit from the ability to make new blood vessels, the researchers wanted to determine whether iPSCs derived from the cells of such patients could help generate functional blood vessels. …

Read more

Utilizzando il sito, accetti l'utilizzo dei cookie da parte nostra. maggiori informazioni

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close