Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Liver Cancer Linked to Cellular Repair Pathway

31.03.2006


The unchecked activity of a cell signaling pathway crucial in embryonic development and the liver’s response to injury leads to liver cancer, researchers from Duke University Medical Center and John Hopkins University School of Medicine have found.



Because the pathway, called Hedgehog, is present only in immature, stem-like liver cells, the discovery offers hope for targeted treatment of liver cancer, one of the leading causes of cancer-related death in the world. Laboratory experiments show that blocking the Hedgehog pathway kills cancer cells but leaves mature healthy liver cells intact, the researchers report. Treating patients with medications to interrupt the pathway would likely eliminate the cancer cells while sparing healthy liver tissue, said Jason Sicklick, M.D., a postdoctoral fellow at Duke and lead author of the study.

"Currently, there are no good chemotherapies for liver cancer, and many people with advanced liver disease are too ill for surgery to remove tumors," Sicklick said. "There is a desperate need for effective anticancer treatments that are safe for patients with liver disease."


The results will be published in the April 4, 2006, issue of Carcinogenesis. The research was funded by the National Institutes of Health.

Finding the overactivated Hedgehog pathway in liver cancer, but not in mature liver cells, opens the door for development of new diagnostic tests for the disease, Sicklick said. "Signs of excessive Hedgehog activity in cirrhotic patients could alert us to early stages of liver cancer, as well as provide valuable prognostic information for patients," he said.

Sicklick and colleagues also discovered a new Hedgehog pathway mutation in a patient with liver cancer that may lead to overactivation of Hedgehog and trigger abnormal cell growth, promoting cancer development. In test tube and cell culture experiments, blocking the Hedgehog pathway reduced growth of cancer cells by over 90 percent.

Liver cancer, or hepatocellular carcinoma, often develops in people with cirrhotic livers damaged by chronic infections, such as hepatitis, by alcohol abuse or other causes. It is rare in people with healthy livers. The cancer’s incidence is rising in the United States, with an estimated 17,550 new cases diagnosed in 2005 and 15,420 deaths. One reason for the rising rates is the increasing prevalence of obesity, which raises the risk of liver cancer five- to six-fold, said Anna Mae Diehl, M.D., chief of Duke’s gastroenterology division and senior author on the study.

The liver’s attempts to repair itself and regenerate new tissue after injury can trigger the Hedgehog pathway. During embryonic development, Hedgehog tells cells where and when to grow. In adult tissue, it signals the body to grow new tissue. "If the liver is injured badly, it uses some of the same mechanisms to repair itself as a fetus uses in growing a liver," Diehl said.

The Hedgehog pathway is linked to certain brain, skin and muscle cancers and has recently been implicated in cancers of the pancreas, esophagus, lungs and prostate. The work by the Duke and Johns Hopkins team now adds liver cancer to the growing body of evidence suggesting these cancerous tumors are generated by stem-like cells.

Stem-like cells in the liver require the Hedgehog pathway for survival, the researchers discovered. These primitive cells are similar to stem cells, but differ in basic ways involving cell reproduction. Hedgehog may lead to liver and other cancers because of over-activation of Hedgehog pathway’s components or genetic mutations that accumulate in these components during tissue repair.

"Ordinarily, the process is very tightly regulated, but apparently something goes wrong in these cells and the pathway is not turned off. That’s what conveys malignancy," Sicklick said.

Study co-authors include Yin-Xiong Li, Yi Qi, Kouros Owzar and Wei Chen of Duke University Medical Center; Aruna Jayaraman, Rajesh Kannangai, Perumal Vivekanandan and Michael Torbenson of the Johns Hopkins University School of Medicine; and John Ludlow of Vesta Therapeutics.

Becky Oskin | EurekAlert!
Further information:
http://www.duke.edu

More articles from Studies and Analyses:

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>