Jun 27, 2012
In brief: research round-up
Visualizing plaques sheds light on Alzheimer's progression
Swiss researchers have generated detailed three-dimensional images showing the distribution of amyloid plaques in the brains of mice with Alzheimer's disease. These plaques, which appear before the onset of symptoms, could prove valuable for early diagnosis or evaluating disease progression. The team, from the Paul Scherrer Institute (PSI), ETH Zurich and the École Polytechnique Fédérale de Lausanne, used phase contrast imaging to visualize plaque distribution in the brains of mice with different stages of Alzheimer's, enabling the development of the disease to be followed in detail (NeuroImage 61 1336).
Investigations were carried out using synchrotron X-rays from the Swiss Light Source at PSI. The researchers note that their imaging results showed excellent agreement with those obtained using the gold standard process of slicing and staining the brain. While the high radiation dose required for phase contrast imaging prevents its use in living animals, it should lead to a better understanding of Alzheimer's disease. Another goal is to use the phase contrast technique to help improve in vivo imaging methods such as PET, which are currently under development.
Radiation-prodrug combination targets pancreatic cancer
Combining irradiation with the prodrug TH-302 may provide an effective treatment for pancreatic cancer, according to results presented at the AACR's Pancreatic Cancer: Progress and Challenges conference, held earlier this month in Lake Tahoe, NV. Researchers from the Ontario Cancer Institute/Princess Margaret Hospital in Toronto, Canada, tested TH-302 in preclinical models of pancreatic cancer.
TH-302 is a tumour-selective, hypoxia-activated, cytotoxic prodrug that specifically targets the areas of extreme hypoxia found in solid tumours. Such hypoxic regions are less responsive to chemo- and radiotherapy, and the researchers hypothesized that targeting them with drugs may enhance treatment response. Mice received treatment with TH-302 alone, irradiation alone or a combination of the two. The combination approach reduced tumour growth in high- and medium-hypoxic xenografts; but had little effect on tumour growth in low- or non-hypoxic implants. The study showed that treatment efficacy was also dependent upon the tumour growth rate.
Why is PDT so painful?
Photodynamic therapy (PDT) provides an effective treatment for various forms of non-melanoma skin cancer; however, many patients suffer severe pain during treatment. The reason why PDT can be so painful has now been uncovered by researchers from the Ruhr-Universität-Bochum in Germany, findings that may provide a starting point for suppressing the pain. During PDT of the skin, aminolevulinic acid (ALA) is applied to the skin. Cancer cells have a higher metabolism than normal cells and take up considerably more of this substance. The ALA within the cancer cells is converted to protoporphyrin IX, which can be activated with red light to produce reactive oxygen species that destroy the cancer cells.
In a cell culture experiment, the team showed that pain-sensitive nerve cells in the skin also take up ALA, and subsequently fire when exposed to light, sending a pain stimulus to the brain. Without ALA, the pain-sensitive cells remained inactive under red light. They also showed that nerve cell activity is caused by sodium channels and voltage-gated calcium channels in the cell membrane, opening up the possibility of using a drug that targets these channels to suppress pain. The team found that pain is also generated when affected tumour cells secrete acetylcholine. This acts as a neurotransmitter in the nervous system, but induces pain when injected into the skin. The researchers are currently preparing the data for publication.
Tiny magnetic coils modulate neural activity
Deep brain stimulation (DBS) can reduce the symptoms of several neurological disorders, but the metallic DBS implants limit the future use of MRI and can elicit an immune system response. Now, investigators from Massachusetts General Hospital (MGH; Boston, MA) have shown that magnetic stimulation can generate similar neural activity to that elicited by the electrical impulses used for DBS. The team demonstrated that a magnetic coil, of 1 mm length and 0.5 mm diameter, could elicit neuronal signals in retinal cells when implanted into the brain directly above retinal tissue (Nature Communications doi: 10.1038/ncomms1914).
When the coil was oriented parallel to the retina, the induced field activated retinal bipolar cells. A coil oriented perpendicular to the retina produced responses indicative of ganglion cell activation. These results suggest that modifying the coil geometry may enable generation of specific neural responses. "This study provides a proof of concept that small coils can activate neurons, and much work still needs to be done," said corresponding author Shelley Fried. "We need to explore how to optimize coil properties and then evaluate the devices in animal models. We also hope to explore the use of these coils in non-DBS applications."
Engineered microvessels provide disease test bed
Bioengineers at the University of Washington (Seattle, WA) have developed a means to grow small human blood vessels, creating a three-dimensional test bed with which to study vascular phenomena such as angiogenesis and thrombosis. Researcher Ying Zheng built the structure from collagen, creating tiny channels and injecting them with human endothelial cells. Over two weeks, the endothelial cells grew throughout the structure and formed tubes. When brain cells were injected into the surrounding gel, the cells released chemicals that prompted the engineered vessels to sprout new branches, extending the network.
In this latest study, Zheng collaborated with the Puget Sound Blood Center to examine how the platform transported blood (PNAS 109 9342). The engineered vessels could transport human blood smoothly, even around corners. When treated with an inflammatory compound, the vessels developed clots, similar to the response of real vessels. The system also showed promise as a model for tumour progression. Adding a signalling protein for vessel growth caused new blood vessels to sprout from the originals. These new vessels were leaky, as in human cancers.
About the author
Tami Freeman is editor of medicalphysicsweb.