Scientists Identify Specific Markers That Trigger Aggressiveness Of Liver Cancer

Hepatocellular carcinoma (HCC) or primary liver cancer forms in the epithelial tissue of the liver and is most commonly caused by the hepatitis B virus (HBV) or hepatitis C virus (HCV). In the U.S., the National Cancer Institute (NCI) estimates that 15,000 men and 6,000 women are diagnosed with HCC each year. Worldwide, HCC accounts for 632,000 cases with the highest regions being Western Pacific and Africa according to a 2004 World Health Organization (WHO) report.

Researchers from Taipei Veterans General Hospital investigated the molecular mechanisms of HCC, one of the most common tumors found in Taiwan and largely caused by the high prevalence (15%-20%) of HBV in the country. The study, funded in part by a grant from the National Science Council, is the first to provide a comprehensive profile of multiple Epithelial-Mesenchymal Transition (EMT) markers and to demonstrate that Snail and Twist, but not Slug, are the major inducers of EMT in HCC. Results of the study are published in the November issue of Hepatology, a journal of the American Association for the Study of Liver Diseases.

EMT is critical in the development of invasiveness and metastatic potential of human cancers, and described as process where epithelial cells no longer adhere to one another, taking on fibroblastic properties. The EMT process is initiated by suppression of E-cadherin function through the major EMT regulators (Snail, Slug, and Twist). E-cadherin (calcium dependent adhesion molecules) is a type of protein found in the epithelial cells that ensure tissue cells bind together. When E-cadherin function is lost, cancer is able to progress and metastasize.

Professor Jaw-Ching Wu and colleagues obtained samples of primary HCC with adjacent non-tumorous liver tissues from 123 patients who had hepatic resection surgery between 1990 and 2002 at Taipei Veterans General Hospital. Reduced E-cadherin function was observed in 60.2% of patients. "We found a significant decrease in cancer-free intervals and overall survival for those patients who had a reduction in E-cadherin function," explained Dr. Wu. A downregulated expression of E-cadherin was also associated with large tumor size and multi-nodular tumors.

Results show that co-expression Snail and Twist (transcription factors or proteins that control when genes are switched on or off) indicates the worst prognosis for HCC patients. "Our research is the first to prove that the two proteins (Snail and Twist) work independently, but together promote EMT," noted Dr. Wu.

According to the study, overexpression of Twist is correlated with HCV-related HCC, partially explaining the highly invasive behavior and poor prognosis for patients with this form of liver cancer. Dr Wu added, "Our results provide essential information for determining HCC prognosis in patients and identifies possible new treatments for future HCC management."

Reference

1. Yang et al. Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma. Hepatology, 2009; DOI: 10.1002/hep.23221
2. Gianluigi Giannelli. The Epithelial Mesenchymal Transition: fact or fiction in cancer? Hepatology;, Published Online: October 29, 2009 DOI: 10.1002/hep.23329

High-Speed Test To Improve Pathogen Decontamination Developed

A chemist at NASA's Jet Propulsion Laboratory in Pasadena, Calif., has developed a technology intended to rapidly assess any presence of microbial life on spacecraft. This new method may also help the military test for disease-causing bacteria, such as a causative agent for anthrax, and may also be useful in the medical, pharmaceutical and other fields.

Adrian Ponce, the deputy manager for JPL's planetary science section, devised the new microscope-based method, which has the potential to quickly validate -- from days to minutes -- a spacecraft's cleanliness.

NASA adheres to international protocols by striving to ensure that spacecraft don't harbor life from Earth that could contaminate other planets or moons and skew science research. Microbes known as bacterial endospores can withstand extreme temperatures, ultraviolet rays and chemical treatments, and have been known to survive in space for six years. This resilience makes them important indicators for cleanliness and biodefense, Ponce said.

"Bacterial endospores are the toughest form of life on Earth," Ponce explained. "Therefore, if one can show that all spores are killed, then less-resistant, disease-causing organisms will also be dead."

The new technology works by looking for dipicolinic acid -- a major component of endospores and evidence of endospore growth -- by first applying terbium to a dime-sized area. Terbium is a chemical element used to generate the color green on television screens. That area is then illuminated under an ultraviolet lamp. Within minutes, one can see through a microscope aided by a digital camera whether live endospores are present. That's because they will literally glow: The terbium will show the endospores as bright green spots.

Ponce co-authored a paper on the new technology, called Germinable Endospore Biodosimetry, along with Pun To Young, a post-doctoral student at the California Institute of Technology in Pasadena, in the journal Applied and Environmental Microbiology. The research was also highlighted in Microbe, a magazine of the American Society for Microbiology.

The technology has piqued the interest of the U.S. Department of Homeland Security. The federal agency is funding development of a portable instrument based on Ponce's research that could quickly check for decontamination of pathogens after a biological attack. Ponce is working with the Department of Homeland Security and Advance Space Monitor, a company based in Falls River, Mass., to develop the instrument, which they plan to have ready for use by 2011. JPL and Caltech licensed the technology to Advance Space Monitor.

"As part of the Department of Homeland Security Science and Technology Directorate's near-term bioassays effort, the technology could enable the rapid assessment of facility sterilization. This could significantly reduce the time and cost of building restoration following a bio-contamination event," said James Anthony, chemical and biological research and development program manager at the Dept. of Homeland Security. A bioassay is an assessment of whether certain biological material is present on a surface being tested.

Anthony added that the technology could also be used in bio-containment facilities that have regularly scheduled decontamination requirements and rapidly reactivate important bio-defense research facilities.

Besides outer space and defense purposes, this new technology might also be applied in hospitals, child-care centers, dentists' offices and nursing homes.

"Given all the problems with hospital-acquired infections, assessing the sterility and hygiene of medical equipment and surfaces is becoming increasingly important," said Ponce.

Funding for Ponce's project was provided by NASA's Astrobiology Science and Instrument Development Program and Mars Technology Program, and the U.S. Department of Homeland Security's Chemical and Biological Research and Development division.

Courtesy: ScienceDaily