Detecting Single Cancer Molecules

A new test could predict prostate cancer recurrence much earlier.

1-Quanterix, a diagnostics startup in Cambridge, MA, has developed a highly sensitive new technologycapable of detecting a single, cancer-linked molecule in blood, to predict the recurrence of prostate cancer. In a new study of 30 men who had their prostates removed, the test could detect low levels of the molecule that commercial assays missed.

2-Quanterix's new detection technology counts the number of prostate specific antigen (PSA) molecules released by the cells of the prostate gland into the blood. In cancer patients who have had their prostates removed, PSA levels drop to below commercially detectable levels six weeks after surgery. An increase in PSA concentration over time is one indication that the prostate cancer has returned.

3-In this new method, PSA molecules are trapped on beads and isolated individually on arrays of tiny wells. A fluorescent enzyme added to the array lights up when it binds to PSA, revealing the number of PSA molecules in the sample.

4-According to the new study published in Nature Biotechnology, the test is 1,700 times more sensitive than other PSA detection methods used in clinical laboratories. Researchers found that while commercial assays detected no PSA in any of the blood samples, the Quanterix assay found PSA present in very tiny levels in all samples. Quanterix has yet to establish a cost for the test.

5-"I think we've made strides being able to decrease the threshold of detection, and I hope that we'll be able to extend this," saysHerbert Lepor, chairman of the department of urology at New York University Langone Medical Center. Though unconnected with the development of Quanterix's PSA test, Lepor says he plans to share his bank of blood samples with Quanterix to help standardize the assay. "I'm excited enough to commit our valuable resource of serum samples to give us a barometer of how this test will perform," he says.

6-Urologists typically screen their patients for cancer recurrence for several years following prostatectomy surgery, but the sensitive new test could pinpoint which patients are at higher risk of cancer recurrence and should therefore be monitored more frequently. With available PSA tests, Lepor waits three years following surgery before making predictions about which patients are at a higher risk of cancer recurrence. With a more sensitive assay, he hopes to make this call sooner.

7-There is a possibility that the test will be too sensitive, detecting PSA even in the absence of prostate cells. Lepor says that if this is the case, it may not be the absolute nadir that determines the probability of recurrence, but the rate of change of PSA levels over several weeks.

8-Researchers at Quanterix are working on applying their hypersensitive detection technology to Alzheimer's and Parkinson's disease. They hope to identify biomarkers linked to these diseases that are detectable at very low levels in blood. "It's just the tip of the iceberg for us," says David Duffy, senior director at Quanterix. "The ability to measure single molecules in blood is going to be applicable across a whole lot of other areas."

From:- MIT Technology Review

Systems Biology Helps to Understand Hematopoiesis

1-After blood loss, large amounts of the hormone Epo flood the hematopoietic system in the bone marrow. Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg and the University of Freiburg have now published an article in Science uncovering how a rapid turnover of Epo receptor molecules on hematopoietic cells ensures that these remain ready to react. Thus, our body can respond even to extreme increases of Epo levels with an adequate supply of red blood cells.

2-Our body reacts to blood loss by stimulating the production of red blood cells (erythrocytes). The cells of the hematopoietic (blood-forming) system in the bone marrow do so upon receipt of a signal by a hormone called erythropoietin, or Epo for short. This hormone is produced mainly by the kidney that increases the Epo level by up to a thousand-fold as a response to falling oxygen saturation of the blood.

3-The hematopoietic cells receive the Epo signal through Epo receptors on their surface. How do the blood progenitor cells that carry only few receptor molecules manage to react adequately to a high rise in the Epo level and to always provide the required amount of red blood cells? "If too much of the hormone floods too few receptor molecules, we would expect the saturation point to be reached soon. This would mean that the hematopoietic cell can no longer respond to a further increase in the hormone level," says Dr. Ursula Klingmüller of DKFZ.

4-Researchers in her department, who participate in the Helmholtz Alliance for Systems Biology and the MedSys Network LungSys funded by the Federal Ministry of Education and Research (BMBF), collaborated with colleagues of a working group headed by Professor Jens Timmer at Freiburg University to find out how hematopoietic cells can react in a linear way if Epo levels increase by several orders of magnitude. To do so, the researchers combined experimental data with mathematical models in a systems biology approach.

5-The research team was able to show that after binding of Epo to its receptor both molecules are rapidly taken up into the interior of the hematopoietic cells where they are broken down. During the process, the cell surface is continuously equipped with newly synthesized receptor molecules that are supplied from intracellular storage places. "This turnover of receptor molecules is a very rapid process," Jens Timmer explains who is a member of the Freiburg Institute for Advances Studies (FRIAS) as well as the excellence cluster BIOSS. "Thus, the cell keeps being able to recognize further hormone molecules in its environment and to react accordingly."

6-Genetically engineered Epo is an important medication for treating anemia, for example in dialysis patients who often suffer from low counts of red blood cells because these are destroyed during dialysis and, in addition, the failure of renal function leads to a lack of natural Epo. The results of the Heidelberg and Freiburg scientists may contribute to developing Epo variants with enhanced binding properties and thus increase the effectiveness of anemia treatment.

7-Verena Becker, Marcel Schilling, Julie Bachmann, Ute Baumann, Andreas Raue, Thomas Maiwald, Jens Timmer, Ursula Klingmüller: Covering a Broad Dynamic Range: Information Processing at the Erythropoietin Receptor. Science 2010, DOI: 10.1126/science.1184913

From- German Cancer Research Center Press release.