Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New model to aid pancreatic cancer research

15.11.2006
Vanderbilt-Ingram Cancer Center researchers have developed a new animal model for pancreatic cancer that exhibits a high degree of similarity to human tumors.

Results from the genetically-engineered mice, published online Nov. 14 in the journal Genes and Development, suggest that the mice could provide new opportunities to investigate targeted chemotherapeutics and screening methods for one of the most deadly cancers.

With a 5-year survival rate of less than 5 percent, pancreatic cancer is one of the most lethal cancers. "Most cases are diagnosed at a late stage when it is incurable," said Hal Moses, M.D., the Hortense B. Ingram Professor of Molecular Oncology, professor of Cancer Biology and senior author on the study.

If appropriate, surgery is the most successful treatment option. However, surgery is usually unable to help patients with advanced disease, and there is currently no effective chemotherapy regimen.

Developing an animal model of pancreatic cancer is essential to identifying new treatment and screening options, but progress has been slow. The first realistic pancreatic cancer model, reported in 2003, involved a mutation in a single gene, called Kras. A mutation in this gene is among the earliest genetic changes observed in human pancreatic cancers. Yet the model does not mimic human disease closely.

"Kras mutation alone is not a very good model because it mainly gives a precursor condition," said Moses. This precursor condition called PanIN (pancreatic intraepithelial neoplasia) rarely progresses to the tumor type seen in humans, called PDAC (pancreatic ductal adenocarcinoma).

Kras mutation is considered a "tumor-initiating" event, but additional mutations in other genes are probably required for progression to a clinically relevant tumor. For the past few years, researchers have been searching for a combination of genetic mutations that recapitulates human pancreatic cancer in animals.

To hopefully improve upon previous models, Moses and colleagues have combined the Kras mutation with a "knock out" of the type II TGFƒÒ receptor (TGFBR2), a component of a signaling pathway that inhibits cell growth. Loss of TGFƒÒ signaling could remove the molecular "checks and balances" on cell growth, allowing unrestrained cell proliferation and tumor formation.

The researchers used a genetic manipulation that allowed them to control these genetic changes in pancreatic cells only. The resulting tumors were localized to the pancreas, with no extraneous tumor formation in other tissues ¡V a problem that has complicated previous models.

"Our model is more aggressive in terms of survival time," said Hideaki Ijichi, M.D., Ph.D., research fellow and lead author on the study. The mice survive approximately two months, reflecting the aggressiveness of human pancreatic tumors.

Also, the microscopic appearance of tumors in the new model more closely resembles that of human tumors.

"Combining the Kras mutation with the TGFBR2 knock-out resulted in 100 percent penetrance in developing tumors that histologically and clinically looks very much like human disease," said Moses.

"A certain percentage (of the previous models) have a sarcomatoid histology, which is very rare in humans," Ijichi said. "Our model has almost no sarcomatoid histology."

Ijichi and Moses are planning to use the new model to test targeted drug therapies and identify possible screening methods that could be used for early detection of pancreatic cancer ¡V something that is sorely lacking for humans.

Progress is indeed picking up in the field. Publishing in the same issue of the journal, a research group from Harvard University reports the development of another pancreatic cancer mouse model. Ronald DePinho, M.D., and colleagues combined the same Kras mutation with a "knockout" of a downstream component of the TGFƒÒ pathway, called Smad4.

While the Smad4 mutations are more commonly found in humans than mutations in the TGFBR2, the mice developed by DePinho and colleagues did not show the PDAC histology observed in Moses' mice.

Just why a mutation that is more common clinically would induce tumors that are unlike human cancers is unclear, Moses said.

"We really want to know the underlying mechanism of pancreatic carcinogenesis," said Ijichi. And these new animal models now provide researchers with two additional tools with which to investigate this problem.

Heather Newman | EurekAlert!
Further information:
http://www.vanderbilt.edu

Further reports about: KRAS Researchers pancreatic pancreatic cancer

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>