Source: Washington University School of Medicine
Cancer cells are sick, but they keep growing because they don't react to internal signals urging them to die. Now researchers at Washington University School of Medicine in St. Louis have found an efficient way to get a messenger into cancer cells that forces them to respond to death signals. And they did it using one of the most sinister pathogens around — HIV.
"HIV knows how to insert itself into many different types of cells," says senior author William G. Hawkins, M.D., assistant professor of surgery and a member of the Siteman Cancer Center at the School of Medicine and Barnes-Jewish Hospital. "A portion of the HIV protein called TAT can transport biologically active compounds into cells. TAT is small, but it can move massive molecules. You could almost hook TAT up to a train, and TAT would drag it inside a cell. So we've taken advantage of this ability."
来自Barnes-Jewish医院，医学校Siteman癌症中心的成员，外科学副教授，文章的高级作者，William G. Hawkins博士说：“HIV能够插入许多种不同类型的细胞，其TAT蛋白的一部分能够转运生物活性物质进入细胞。TAT本身很小，但它却能够转运大分子。你几乎可以给TAT挂一辆火车，TAT将把它拖进细胞内。因此，我们应用了它的这一能力。”
In an article published online in January 2007 in the Annals of Surgical Oncology, the researchers describe using TAT to pull a protein called Bim into cancer cells. TAT alone cannot cause AIDS and has no adverse health effects. Bim acts as a tumor suppressor and causes cancer cells to die through apoptosis, a process by which cells "commit suicide."
The research team found that the TAT-Bim compound activated apoptosis mechanisms in cancer cells and augmented the cell-killing effect of radiation. When mice with malignant tumors were treated with TAT-Bim, their tumors shrank, and they survived longer than mice that didn't get the treatment. After 40 days, 80 percent of mice receiving TAT-Bim were alive compared to 20 percent of mice that didn't get the treatment.
Hawkins asserts that this success marks the beginning of a very promising new approach to cancer therapy. "This is the tip of the iceberg," he says. "Now that we've proven we can do this, we've started creating a battery of proteins that can push cancer cells to die."
Hawkins says he thinks treatments that activate apoptosis mechanisms could provide new options for patients with the deadliest cancers — such as pancreatic cancer — which have very low rates of survival. He says he believes that clinical trials of these compounds could be just a few years away.
Hawkins began researching TAT-Bim after discussions with co-author Richard S. Hotchkiss, M.D., professor of anesthesiology, medicine and surgery and associate professor of molecular biology and pharmacology. Hotchkiss was seeking proteins that inhibit apoptosis in patients with life-threatening infections and found that TAT-Bim had the unwanted effect of increasing cell death. Hawkins wondered if TAT-Bim could be effective against cancer, and a productive scientific collaboration began between their labs to exploit the anticancer potential of TAT-Bim.
Hawkins 在与生物学和药理学副教授，麻醉学、内科学和外科学教授，文章的共同作者，Richard S. Hotchkiss博士讨论后，便开始研究TAT-Bim。Hotchkiss当时正在寻找能够抑制致命性感染患者凋亡的蛋白，他发现TAT-Bim有增加细胞死亡的效应。Hawkins想知道，TAT-Bim复合物是否能够有效的抑制癌症，从而在他们的实验室之间建立了有效的科学合作来探索TAT-Bim的潜在抗癌能力。
作者:admin@医学,生命科学 2011-03-05 05:27