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【medical-news】犹太儿童医院宣布眼科癌症治疗新
St. Jude announces breakthrough in eye cancer treatment
Researchers use new, localized treatment to shrink retinoblastoma tumors, avoid chemo; treatment could be effective against some breast, lung, prostate and colon cancers
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Michael Dyer, Ph.D. is a Pew Scholar and an associate member of the Dept. of Developmental Neurobiology, St. Jude Children's Research Hospital.
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Scientists at St. Jude Children's Research Hospital have demonstrated in a mouse model a new, locally applied treatment for the eye cancer retinoblastoma that not only greatly reduces the size of the tumor, but does so without causing the side effects common with standard chemotherapy. The treatment also appears to be suitable for certain forms of breast, lung, prostate and colon cancer, and is simple enough for widespread use even in countries with limited resources.
A report on this work appears in the Nov. 2 issue of the journal Nature.
Retinoblastoma occurs in about 5,000 young children worldwide each year, arising from the immature retina, which is the part of the eye responsible for detecting light and color. The cancer is fatal if left untreated.
The new treatment holds promise for a simpler, more effective and less-toxic treatment for retinoblastoma that would eliminate the need for the current, complex therapy, according to senior author Michael Dyer, Ph.D., a Pew Scholar and associate member of the St. Jude Department of Developmental Neurobiology. The treatment is based on a discovery by Dyer's laboratory that overturned a widely held belief about the process of apoptosis (cell suicide) in retinoblastoma. Apoptosis is the way the body rids itself of abnormal cells that might become cancerous or cause other problems.
Until now, retinoblastoma experts thought that a mechanism called the p53 pathway triggered apoptosis in other types of cancer cells, but not in retinoblastoma. However, the St. Jude team proved not only that the p53 pathway was activated in early-stage retinoblastoma, but that excessive levels of a molecule called MDMX blocked it from triggering apoptosis in more advanced tumors. Based on this discovery, the St. Jude team used a molecule called nutlin-3 to block MDMX in retinoblastoma cells in test tube studies as well as in mouse models. The molecule was originally developed by
Roche Pharmaceuticals (Nutley, N.J.) for a similar use against a related target called MDM2 in adult cancer cells. The success in knocking out MDMX with nutlin-3 represents the first example of local delivery of a targeted chemotherapy drug for any childhood cancer, Dyer said.
Targeted therapy uses a customized drug to disable a specific molecule inside a growing cancer cell; local delivery is the placement of a drug at the site of disease, rather than systemic treatment. In systemic treatment, such as chemotherapy, a drug is infused into the body through a vein and then circulates, often causing toxic side effects that are especially challenging in children.
After demonstrating that nutlin-3 is effective when applied directly to the eye, the St. Jude team modified the treatment by combining this molecule with topotecan, a drug also being investigated in the treatment of retinoblastoma. Local delivery of this two-drug targeted treatment was even more effective, reducing tumor size significantly more than the most effective known combination of standard chemotherapy drugs.
"The findings suggest that this treatment not only could offer children with retinoblastoma more effective and less-toxic treatment," Dyer said. "It could also increase the chance that their vision can be preserved by eliminating the tumor and preventing its spread from the eye to the rest of the body."
The discovery that blocking MDMX releases the apoptosis response in retinoblastoma has important implications for certain forms of adult cancers as well. "Some forms of breast, lung, prostate and colon cancer are caused by abnormally large quantities of MDMX in the cells," Dyer explained. "So knocking out MDMX in those cancers might also dramatically reduce tumor size. And administering the drug directly to the site of the tumor could make the treatment especially effective while avoiding the toxicity caused by systemic exposure." This could mean the eventual elimination of all-body chemotherapy for certain cancers.
This work is likely to have its biggest impact on the care of children with retinoblastoma internationally, according to Dyer. Most children in the United States with retinoblastoma do not die from the disease because they benefit from early detection and advanced medical treatment. The complex treatment includes chemotherapy, radiation and laser therapy, as well as control of infections caused by treatment-related suppression of the immune system. However, most of the 5,000 children worldwide who are found to have retinoblastoma live primarily in countries with limited resources and have restricted access to medical treatment, according to Carlos Rodriguez-Galindo, M.D., an associate member of the St. Jude Oncology department.
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作者:admin@医学,生命科学 2010-11-08 17:11
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