Navigation Links
Fluorescent probes may permit monitoring of chemotherapy effectiveness, Stanford study shows
Date:7/13/2009

STANFORD, Calif. Going out like a brilliant flame is one way to get attention. If physicians could watch tumor cells committing a form of programmed suicide called apoptosis, a desired effect of workhorse cancer treatments such as chemotherapy and radiotherapy, they could more quickly pick the most effective treatment. Now scientists at the Stanford University School of Medicine have found a way to do just that, by lighting up cells as they die.

Apoptosis is a carefully orchestrated sequence of intracellular events that leads to the cell's death. "The cell takes itself apart in a finite series of steps," said Matthew Bogyo, PhD, associate professor of pathology and of microbiology and immunology, and a member of the Stanford Cancer Center.

Bogyo is senior author of a study to be published online July 13 in Nature Medicine in which he and his Stanford colleagues demonstrated in mice that it is possible to noninvasively image the degree of apoptosis occurring in living animals' tumors, and thereby to gauge the effectiveness of apoptosis-inducing treatments. Several steps still remain before it can be determined whether this diagnostic method is safe for use in humans.

Apoptosis occurs all the time in healthy bodies. Cells have this suicide system in place to deal with viral infections, or just to complete their normal life cycle. Cells lining the gut, for example, or immune cells in the spleen and thymus are meant to live only a couple of days. "You lose three-quarters of a million cells per second in your body due to apoptosis," noted Guy Salvesen, PhD, director of the program on apoptosis and cell-death management at the Burnham Institute for Medical Research, in La Jolla, Calif.

But apoptosis is also a check against unwanted cell division, as occurs during tumor growth, said Salvesen, who collaborates with Bogyo on various research projects but did not participate in this study. "Cancer cells have to learn to do two things," Salvesen said. "First, they've got to learn to start dividing rapidly. But once they do that, they become very vulnerable to apoptosis. So they've got to learn to switch off this death mechanism. Chemotherapy and radiotherapy aim to turn it back on."

One way of determining whether they're succeeded is by monitoring key early players in apoptosis called caspases, a family of usually quiescent enzymes found inside every mammalian cell. Activated by various biochemical cues from within or outside of the cell, caspases commence a cascade of molecular steps that steer the cell to a clean, quiet, orderly death.

"Caspases have to be very tightly controlled, since they are regulating cell death. If they get turned on, the cell dies," said Bogyo. His team created probes by affixing fluorescent "tags" to small molecules that were engineered to bind and stay bound almost exclusively to caspases, and only when the caspases are in an active state. The resulting probes are excited by certain wavelengths of light that travel through skin without being absorbed. The probes respond by giving off their own light, which can be imaged by a special detector.

"Our probe can't bind to inactive caspases," Bogyo said. "It can go into cells, but it doesn't get stuck it just circulates back out. So the only cells that fluoresce are the ones approaching death."

In an early test of the probe, Bogyo and his colleagues gave mice a drug called dexamethosone, which preferentially induces apoptosis in certain immature immune cells residing primarily in the thymus. After systemically injecting a solution containing the probes, the investigators observed fluorescence in the thymus, as predicted. They confirmed by chemical methods that the fluorescent probes were indeed binding to caspases.

Next, the team performed experiments with a new, experimental monoclonal antibody that activates caspases, by a mechanism different from that of dexamethasone, and initiates apoptosis particularly in rapidly dividing cells such as those in tumors. In one such test, the researchers administered this antibody to mice onto which human tumors had been engrafted. After injecting these live mice at various time points with the fluorescent probes, Bogyo and his colleagues again saw the many tumor cells undergoing apoptosis light up, but not the healthy surrounding tissues.

The potential for practical payoffs is significant, Bogyo said. Radiotherapy and many chemotherapeutic selectively damage DNA in rapidly replicating cells, dramatically boosting the amount of apoptotic death happening in tumors. Some experimental models indicate that inducing apoptosis is the main way these treatments kill cancer cells.

"Different individuals respond differently to a given treatment. The quicker you can make a decision about whether a drug is working or not, the better," Bogyo said. Moreover, he said, new-generation drugs, some of them now in clinical trials, are designed specifically to turn on caspases.

Because caspase activation is a very early event in apoptosis, monitoring it could speed clinicians' ability to determine whether, how and when these new drugs work, said Bogyo. He has started a company, Akrotome, to speed the fluorescent probes' development and commercialization. Stanford has licensed this technology to Akrotome for a 4 percent ownership stake.

"The entire cancer chemotherapy field is very, very excited about probes like this," said the Burnham Institute's Salvesen, who has no financial ties to the current study or to Akrotome. The approach also holds promise for tracking unwanted apoptotic damage to tissues in disorders such as macular degeneration or traumas such as post-ischemic reperfusion injury.


'/>"/>

Contact: Bruce Goldman
goldmanb@stanford.edu
650-725-2106
Stanford University Medical Center
Source:Eurekalert

Related medicine news :

1. Naturally fluorescent molecules may serve as cancer biomarker
2. MBL scientist Osamu Shimomura wins Nobel Prize for discovery of green fluorescent protein
3. Fluorescent Retinal Cells Warn of Eye Disease
4. MEDRAD Multi Vendor Service Launches TotalRepair(SM) on Select Ultrasound Probes
5. Nanoscopic probes can track down and attack cancer cells
6. China Medical Technologies Announces the Receipt of SFDA Approval for Two of its FISH Probes and the Approval for the Hi-Tech Enterprise Status for its PRC Subsidiaries
7. Team probes why climbers die on Mount Everest
8. Study Probes Why Smokers Find It Hard to Quit
9. Study Probes Internet Health-Related Search Patterns
10. String probes for devastating childhood digestive disease
11. Matrix registry probes adherence to clopidogrel at 1 year
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2017)... ... January 20, 2017 , ... A new partnership between ... they no longer use or need, from clothes to couches to dressers and bicycles. ... and take them to the nearest Goodwill donation center through February 28th. , ...
(Date:1/20/2017)... Miami, Florida (PRWEB) , ... January 20, 2017 , ... ... in head lice cases in families with school-aged children since the holiday season. ... spend the holidays with their families, sharing hugs and taking photos, which is the ...
(Date:1/20/2017)... ... January 20, 2017 , ... ... its sugar-free alternative VW+ 002. The drinks have been produced in collaboration with ... to perform during your workout. , After a successful launch in Sweden last ...
(Date:1/20/2017)... ... 2017 , ... D R Burton Healthcare Products LLC, makers ... in a study indicating superior performance against competitive products in secretion clearance. ... Positive Expiratory Pressure Devices During Simulated Breathing“ was published in the winter issue ...
(Date:1/20/2017)... ... January 20, 2017 , ... “God's Miracle Man: Against All Odds”: an ... of published author, Keith C. A. Tucker, son of Minister Delores Pinnock and a ... by Reverend Mark Hardy , “While sitting up in bed, I felt a pounding ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... 19, 2017 Shire plc (LSE: ... U.S. Food and Drug Administration (FDA) has acknowledged receipt ... Application (NDA) for SHP465, a long-acting, triple-bead, mixed amphetamine ... once-daily treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). The FDA is ... 20, 2017, the designated Prescription Drug User Fee Act ...
(Date:1/19/2017)... 19, 2017 Pfizer joins ... Milner Therapeutics Consortium   Major research ... Cambridge   The Milner Therapeutics ... ) as a partner to the Milner Therapeutics Consortium. ... the efficient transfer of materials between industry and academia ...
(Date:1/19/2017)... Florida , January 19, 2017 ... Trump administration appears serious about reducing the FDA,s ... and innovation in the medical drug industry, many ... ahead with new clinical trials and development of ... companies forging ahead with recent developments include:  Moleculin ...
Breaking Medicine Technology: