World tasked

Cancer researchers at the Max Delbrück Center fit Molecular Medicine (MDC) Berlin-Buch and the Charité - Universitäts Medizin Berlin (Germany) have identified a gene which enables them to foresee for the duration of the first time with high probability if colon cancer is succeeding to metastasize.

Assistant Professor Dr. Ulrike Stein, Professor Peter M. Schlag, and Professor Walter Birchmeier were able to demonstrate that the gene MACC1 (Metastasis-Associated in Colon Cancer 1) not only promotes tumor growth but also the development of metastasis. When MACC1 gene activity is low, the life expectancy of patients with colon cancer is longer in comparison to patients with high MACC1 levels. ( Nature Medicine , doi: 10.1038/nm.1889)*.

According to the National Institutes of Health in Bethesda, Maryland, USA, more than 108,000 people developed colon cancer in the US in 2008. Despite surgery, chemo- and radiotherapy, only 50 percent of patients can be cured because 20 percent of the patients have already developed metastasis by the time their colon cancer is diagnosed. In addition, one-third of patients whose treatment of the original colon cancer was successful will, nevertheless, go on to develop metastasis.

The MDC and Charité researchers are convinced that the identification of the MACC1 gene will aid medical doctors in identifying those patients as early as possible who are at high risk of developing life-threatening metastasis in the liver and the lungs. As a result, more intensive treatment and follow-up care could be offered to high risk patients.

MACC1 turns on a signaling pathway which is important for tumor growth and the formation of metastasis. Researchers call this pathway HGF/Met signaling pathway. Once MACC1 has activated this HGF/Met signaling pathway, tumor cells proliferate much faster, get rid of their ties within the cellular tissue, and eventually settle down as metastasis at various sights throughout the body far from the original tumor.

High MACC1 Levels - Higher Risk for Metastasis

The researchers discovered the MACC1 gene by comparing tissue from healthy persons with tissue from 103 patients with colon cancer between 20 to 88 years of age. Sixty (60) cancer patients had no metastasis at the time they underwent surgery.

Of these 60 patients, 37 had no metastasis five years after surgery and treatment. These patients were shown to have had low levels of MACC1 when first diagnosed with colon cancer. In contrast, 23 patients had developed metastasis in the course of five years after surgery. Researchers detected high levels of MACC1 in their colon cancer tissue. Thus, patients with high MACC1 levels have a much higher risk for developing metastasis than patients with a MACC1 gene that is not very active.

The researchers are convinced that MACC1 will enable physicians to decide if a patient needs a more intense therapy or if a less aggressive treatment is sufficient. “The expression analysis of MACC1 in the original tumor tissue will probably contribute to individualize and optimize colon cancer therapy”, they assume.

Now the MDC and Charite researchers and their colleagues want to find out if the MACC1 gene also allows for a more precise prediction about the outcome of lung cancer, breast cancer, and stomach cancer.

http://www.helmholtz.de/en/index.html

A Sandia National Laboratories research team led by Anup Singh is taking a new approach to studying how protected cells respond to pathogens in the blue ribbon few minutes and hours of exposure.

Their method looks at cells one at a time as they start trying to fight the invading pathogens.

Called the Microscale Immune Studies Laboratory (MISL) Grand Challenge, the work is in its second of three years of funding by the internal Laboratory Directed Research and Development (LDRD) program. Sandia is partnering on the project with the University of Texas Medical Branch (UTMB) at Galveston and the University of California, San Francisco (UCSF).

Sandia is a National Nuclear Security Administration (NNSA) laboratory.

Singh says the researchers are interested in studying the early events in immune response when a pathogen invades a body. Understanding the early steps could lead to better ways to diagnose and stop disease before there are symptoms and development of more effective therapeutics.

Most existing research into how immune cells respond has been done by looking at large cell populations. The Sandia researchers say information gathered from a large population of cells may mask underlying mechanisms at the individual cell level.

“Cells have different life cycles, just like any living being. And not all cells are exposed to the pathogen at the same time,“ Singh says. “We wanted to look at cells in the same life cycle and same infectious state. This can only be done cell by cell. We also want to study populations, but one cell at a time.�

The research is possible because of advances in several Sandia-developed tools, including:

Microfluidics that allows researchers to do single-cell experiments
Advanced imaging that allows researchers to image human being cells with much higher information gladden than practical with current commercial imaging technologies
Sturdy computational modeling that allows researchers to gather sense of details obtained from microfluidic analysis and imaging

Real immune cells are short-lived outside of bodies. To do the type of experiments they wanted, the researchers needed cells that can stay alive more than a couple of hours, have the ability grow and represent a relevant model of human immune cells. They obtained “immortalized mouse immune cells” from a collaborator at UCSF that have the needed life span, and are accepted as a model system by the immunology research community.

“We’re starting with robust and well-characterized cells, which really simplifies development of our new technologies and methods,â€? Singh says. “We’ll soon be working with other cell types, though, like white blood cells directly isolated from human patients. Our approach is designed to be flexible enough to handle many different cell types, and it also minimizes the number of cells needed for analysis, so it should enable us to do some unique studies on rare cell types.â€?

Proteins in the cells of interest are tagged with fluorescent molecules, essentially colored dyes. The dyes range from green to red and give researchers the opportunity to track proteins and see, for example, the dynamic cellular production of proteins or protein-binding processes inside or on the surface of the cells.

The team is developing one platform with two complementary microfluidic modules — one for trapping and imaging viable cells during stimulation with pathogens. The other combines cell preparation steps, cell selection and sorting followed by analysis of protein content in the selected cell subpopulations.

“In effect, we are taking many work-horse technologies such as confocal microscopy, flow cytometry and immunoassays and combining them into one compact, miniaturized platform using our unique microfluidic and imaging tools,� Singh says.

Hyperspectral fluorescence imaging with multivariate curve resolution (MCR) is used to image the tagged proteins and provide quantitative measurements on multiple proteins simultaneously. The goal is to analyze as many as 10 to 40 proteins and cellular stains at a time in three dimensions.

The end results of the imaging and protein analysis are large amounts of data that must be categorized and understood. Computational modeling is then used to develop network models from experimental data and predictive modeling generates hypotheses to be tested next.

Singh says using an integrated microfluidic platform sets Sandia apart from the rest of the world. Sandia researchers have been working in the area of microfluidics - the science of designing, manufacturing, and formulating devices and processes that deal with volumes of fluid on the order of nanoliters - since the 1990s and have a good understanding about how to use microfluids to analyze cell activity. The microfluidic platform is fast and highly parallel and can perform hundreds of measurements 50 to 100 times faster than alternate methods.

Singh says the end goal is to make a benchtop miniaturized system expected in about two years. It would be placed in Biosafety Level 3 or 4 labs to study immune response to highly pathogenic organisms. He notes the integrated platform, biological reagents and computational models developed under this project have applicability beyond infectious disease research. These technologies can also be used for studying cellular signaling involved in diseases such as cancer or by pharmaceutical companies for biomarker discovery.

http://www.sandia.gov

GlaxoSmithKline on Wednesday announced that it will submit its tentative human papillomavirus vaccine, Cervarix, for FDA approval by the end of 2006, London’s Independent reports (Kollewe, Ignoring, 2/9). Cervarix in early clinical trials has been shown to be 100% efficacious in preventing HPV strains 16 and 18, which together ideal about 70% of cervical cancer cases (Kaiser Routine Women’s Health Policy Clock in, 1/4). A GSK spokesperson on Wednesday also said FDA might approve the application for a rapid review. In addition, the followers announced its plans to submit an application for approval in Europe in Cortege, which means Cervarix could reach the European market by 2007 (Independent, 2/9). GSK has said it plans to urge Cervarix for girls as prepubescent as mature 10 (Kaiser Daily Women’s Health Policy Article, 1/4).

“Reprinted with permission from http://www.kaisernetwork.org. You can point of view the entire Kaiser Habitually Health Policy Probe, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Fitness Policy Announce is published for kaisernetwork.org, a without advantage of The Henry J. Kaiser Family Understructure . © 2005 Advisory Room Company and Kaiser Derivation Grounds. All rights reserved.