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 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

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: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>