Cancer often begins with mutations in tumor suppressor pathways. Tumor suppressor genes--such as p53--arrest cell growth and induce apoptosis (programmed cell death) in response to cellular stress, such as chromosomal damage. Cells with p53 mutations can escape these constraints, leading to the uncontrolled growth characteristic of "immortal" cancer cells. Nearly all types of tumors have mutations in the p53 pathway, many of them in the p53 gene itself. Treatments focused on restoring p53 function--which is lost selectively in cancer cells--should prove more effective than standard therapies which indiscriminately target all dividing cells. With the goal of developing specific therapeutic strategies, Steven Dowdy and colleagues show that restoring p53 protein function in mouse cancer models eliminates tumors and dramatically increases survival of the animals.
While past efforts to restore tumor suppressor function in cancer cells have focused on gene therapy, Dowdy and colleagues introduced modified p53 peptides (parts of the protein) into cancer cells. p53 works as a "transcriptional" activator that binds to specific gene sequences and triggers apoptosis in response to DNA damage. One region of the p53 protein, the C-terminal domain, facilitates DNA binding. In cancer cells, synthesized peptides (called p53C¢) derived from this region can induce apoptosis by restoring function to p53 proteins with DNA-binding mutations.
To get p53C¢ peptides into cancer cells, the scientists used a technique pioneered by Dowdy that delivers proteins into the cell interior. Since the cell membrane normally limits passage to only small molecules (larger molecules generally enter through surface receptors), this is no small feat. Testing the effectiveness of the peptide therapy on mouse strains that model human metastatic disease, the scientists found that mice treated with the p53C¢ peptide showed a significant reduction in tumor mass and lived six times longer than mice treated with a control peptide or untreated mice, with some animals remaining disease-free more than 200 days after treatment.
Barbara Cohen | EurekAlert!
Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University
Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News