Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dartmouth researchers advance fight against pancreatic cancer

17.05.2004


New studies show success in reducing tumor growth



Two Dartmouth medical studies have produced promising results in the fight against pancreatic cancer, one of the most deadly and aggressive forms of cancer, and may lead to the development of new, highly targeted therapies to manage previously untreatable tumors.

In two trials targeting some of the most challenging traits of pancreatic tumor cell growth, researchers from Dartmouth Medical School (DMS) and the Norris Cotton Cancer Center (NCCC) at Dartmouth-Hitchcock Medical Center (DHMC) have demonstrated success in slowing and preventing tumor development.


The NCCC research team was led by Dr. Murray Korc, a pioneer in early research on growth factor receptors in pancreatic cancer, and chair of the department of medicine at DMS and DHMC. An endocrinologist and cancer biologist, he focuses much of his research on the mechanisms that make pancreatic cancer so resilient and aggressive. Work reported in the May 15 issues of Clinical Cancer Research and Cancer Research addresses the team’s latest advances.

Pancreatic cancer is characteristic for its ability to spread quickly, while becoming increasingly resistant to traditional chemotherapy. Generally diagnosed in an advanced state, it is frequently inoperable. As a result, it is the fourth leading cause of cancer death in adults in the US, killing more than 30,000 Americans every year, says Korc.

"By the time the disease is diagnosed, pancreatic cancer cells have a huge growth advantage over normal cells, which enables them to grow and metastasize very quickly," said Korc. "Our research has focused on determining what factors enable the cells to grow at such a fast rate and then how to slow that rate down and actually suppress pancreatic tumor growth."

Korc likens the disease to speeding in a car with an accelerator that is stuck to the floor. "Naturally, you apply the brakes but they don’t work, so you begin pumping the brakes to slow the car down. The brakes are broken in pancreatic cancer but in addition, we found that the brake has been converted into an accelerator by the cancer cells. In essence, pumping the brakes gives you two accelerators."

In fact, said Korc, the inhibitory factors that have been proven to slow down the growth of normal cells, can often backfire and increase the spread of tumors in the pancreas, or in other words, change the brake into an accelerator.

In a feature article appearing in the May 15 edition of Clinical Cancer Research, Korc and Dr. Mitsuharu Fukasawa, a research associate in the department of medicine at DMS, reported a new, highly effective anti-angiogenic approach for treating pancreatic cancer. They focused on the over-expression of a molecule that hampers chemotherapeutic efforts in pancreatic cancer. The molecule, VEGF, is responsible for angiogenesis, a process that stimulates blood vessel formation. In pancreatic cancer cells, there is a 90-fold higher level of VEGF than in normal cells, which enables the cancer cells to grow and metastasize quickly and efficiently.

In this study, the researchers injected a protein sponge, VEGF-Trap, into mice bearing pancreatic tumors derived from four different human pancreatic cancer cells. They predicted the sponge would absorb most of the angiogenetic VEGF molecules, thereby slowing the blood vessel proliferation and suppressing tumor growth.

"The protein sponge completely suppressed pancreatic tumor growth," said Korc. "In all the tumors tested, there was a marked decrease in blood vessel formation, which is very exciting." The next step, he acknowledged, is to introduce this technology in humans, where it is desperately needed.

In the second study, published in Cancer Research, Korc and his research team, headed by his post-doctoral fellow Nicole Boyer Arnold, describe a novel mechanism for chemoresistance in pancreatic cancer. In their investigation, the team identified the pathways responsible for giving the pancreatic cancer cells a growth advantage and making them resistant to chemotherapeutic drugs. They focused on two molecules, Smad7 and thioredoxin, which are found in high quantities in many pancreatic tumors.

These molecules make signaling pathways abnormal so that when a drug is introduced to suppress cancer cell growth, these molecules allow the cancer cells to resist the drugs and to continue to grow. This chemo-resistance is a hallmark of aggressive cancers such as pancreatic cancer. "Now that we know this pathway exists, it will allow us and other investigators to try to figure out ways to interfere with this pathway to design new therapies for pancreatic cancer," said Korc. In future research, the research team will also introduce a molecular sponge to absorb certain over-expressed molecules that promote the expression of Smad7 and thioredoxin, in order to determine if this renders the cancer cells more responsive to therapy.

Although these studies are early, Korc is hopeful they will develop into clinical trials in the future. "The mortality rate (of pancreatic cancer) virtually equals incidence," he said. "Of the 31,000 people in the US that get it this year, 30,300 will die from it, and most patients die within six months. That is why we are excited about this research and hope that it will lead to more advances in the treatment of pancreatic cancer."


The studies were funded by the National Cancer Institute through two United States Public Health Service Grants awarded to Korc, and by a postdoctoral fellowship to DMS/NCCC researcher Nicole Boyer Arnold from the George E. Hewitt Foundation for Medical Research.

Andy Nordhoff | EurekAlert!
Further information:
http://www.dartmouth.edu/

More articles from Studies and Analyses:

nachricht Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>