Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists announce long-sought mouse model of human pancreatic cancer

10.12.2003


Could yield advances in early diagnosis, treatment of lethal disease



Researchers at Dana-Farber Cancer Institute have created bioengineered mice that develop aggressive, fatal pancreatic cancer through the same genetic mishaps that cause the disease in humans. The findings are being posted online today by the journal Genes and Development.

Because the mouse-model cancers start and progress along a path that closely resembles the disease’s course in humans, the scientists believe it will be particularly useful in searching for telltale substances, or biomarkers, in the animals. These biomarkers could lead to a blood or urine screening test to catch the disease in an early and potentially curable stage in the mice and, ultimately, in humans.


Currently, nearly all the 30,000 cases of pancreatic cancer diagnosed annually are fatal within a matter of months because they are too advanced to remove surgically by the time they cause symptoms. Moreover, the standard treatments of chemotherapy and radiation are largely ineffective, for reasons that may become clearer as researchers study the biology of the disease in mice.

"This model shows great promise as a platform for rapid and efficient testing of novel therapeutic agents, and for the discovery of tumor stage-specific markers - both critical, unmet needs for the fourth-leading cause of cancer death in the United States," said Ronald A. DePinho, M.D., a senior author of the paper. The report, whose lead authors are Andrew J. Aguirre and Nabeel M. Bardeesy, Ph.D., will appear in the Dec. 15 print issue of Genes and Development.

DePinho, who is also a professor of medicine at Harvard Medical School, added that the new mouse model is the first to contain the two "critical lesions," or mutations, common to the human disease and "which faithfully recapitulates the rapid onset and lethal progression of the disease."

As in other solid tumors such as colon cancer, a series of genetic mutations underlies the conversion of normal cells in the pancreatic ducts to a precancerous series of stages termed PanIN-1, 2 and 3, and, finally, full-fledged, invasive cancer called adenocarcinoma. Only after the tumor has become a life-threatening adenocarcinoma does it cause symptoms by blocking bile ducts, causing jaundice and symptoms of pain, nausea and weight loss.

The genes mutate for various reasons: carcinogens such as tobacco smoke (smoking is a risk factor for pancreatic cancer), possibly dietary components and advancing age (mistakes in the DNA code of genes pile up and the body’s DNA repair mechanisms fail to keep pace). Several particular mutations have been identified in tissues taken from pancreatic cancer patients. Among them are KRAS - a growth signal stuck in the "on" position, resulting in unchecked cell growth - and several genes that normally suppress tumor formation, including INK4a/Arf, p53, and SMAD4.

Because the basic mechanisms of pancreatic cancer are so poorly understood, scientists have been trying for more than 15 years to create a mouse model that would mimic the human disease but which could be studied and used to identify potential drug targets. However, none of the models to date had produced cancer in mice that faithfully replicated what occurs in humans.

The team headed by Aguirre and Bardeesy used sophisticated bioengineering methods to control the activities of mutant genes in the pancreas. One, a mutant KRAS gene, was activated and kept switched on continuously as the mouse pancreas developed in the fetus. The other mutation inactivated the normally functional INK4a/Arf tumor suppressor gene. These two "signature mutations," the researchers showed, are both needed to convert normal cells into premalignant and then fully invasive pancreatic tumors. Mice that were given either of the mutations alone did not develop invasive cancers.

Bardeesy said that because the cancer-prone mice are all genetically identical and raised in a standard environment, it is possible to identify the biomarkers associated with early and late stages of the cancer. This will provide an entry point for the discovery of equivalent molecules useful in screening humans.


The research was supported by the Lustgarten Foundation for Pancreatic Research, which was established in the name of Marc Lustgarten, Vice Chairman of Cablevision Systems Corp. of New York, who died of the disease.

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

Contact: Richard Saltus, 617-632-5357.

Bill Schaller | EurekAlert!
Further information:
http://www.dfci.harvard.edu/

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>