Thursday, May 14, 2015

catching liver cancer early

It’s always great to hear from my former postdoc colleagues who have gone out into the world to set up labs and do exciting research that I can then write about, just occasionally (most of the work I report comes from people I never met). So here is the latest news from the lab of Jenny Yang who arrived at the Oxford lab just a couple of months before me, back in the olden days. She used to work around 25 hours per day, and it’s good to see that her efforts have been rewarded, as she’s now a Distinguished University Professor and associate director of the Center for Diagnostics and Therapeutics at Georgia State University at Atlanta.


Jenny’s group at Georgia State developed a protein to bind gadolinium ions, which can then be used as contrast agents in magnetic resonance imaging of cancer in the liver. Other gadolinium-based products have been available, but due to their magnetic properties (low relaxivity) and other problems, they yielded poor contrast capability , which meant that they could only detect cancers that were already quite big. The new protein now enables the detection of liver tumours (both primary tumours and metastases from elsewhere, as quite a few cancers have the habit of establishing metastases in the liver) at a much earlier stage.

ProCA32, the researchers’ newly developed contrast agent allows for imaging liver tumours that measure less than 0.25 millimeters, compared to a current detection limit of 1 cm. Thus the method is more than 40 times more sensitive than today’s commonly used and clinically approved agents used to detect tumours in the liver. (Note that a tumour 40 times larger in diameter would have 40x40x40 = 64,000 more cancer cells, which is a scary thought.)

Specifically, ProCA32 widens the MRI detection window, which is found to be essential for obtaining high-resolution images of the liver. This application has important medical implications for imaging various liver diseases, the origin of cancer metastasis, monitoring cancer treatment and guiding therapeutic interventions, such as drug delivery.

“Our new agents can obtain both positive and negative contrast images within one application, providing double the accuracy and confidence of locating cancerous tumours,” Yang said. “These agents are also expected to be much safer with reduced metal toxicity.”

The researchers have shown proof-of-concept that ProCA32 can be used to detect cancerous liver tumours at an early stage with high sensitivity. In the study, they have also demonstrated that these new agents better facilitate the imaging of multiple organs, including the kidney and blood vessels, in addition to the liver and tumours.

“ProCA32 may have far-reaching implications in the diagnosis of other malignancies, which could facilitate development of targeted treatment, along with effective monitoring of tumour burden reduction,” Yang said. “Our agent and methodology can also be applied to study the brain and monitor treatment outcomes in a number of disorders, including stroke and recovery, Alzheimer’s disease, brain tumours and gliomas.”


Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging
Shenghui Xue, Hua Yang, Jingjuan Qiao, Fan Pu, Jie Jiang, Kendra Hubbard, Khan Hekmatyar, Jason Langley, Mani Salarian, Robert C. Long, Robert G. Bryant, Xiaoping Philip Hu, Hans E. Grossniklaus, Zhi-Ren Liu, and Jenny J. Yang
PNAS 2015 ; published ahead of print May 13, 2015, doi:10.1073/pnas.1423021112

This entry is based in part on the Georgia State press release.

Georgia State University researchers (left to right) Shenghui Xue, Jingjuan Qiao, Shanshan Tan, Mani Salarian and Jenny Yang developed the first robust and noninvasive detection of early stage liver cancer. Credit: Jingjuan Qiao, Georgia State University.

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