Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find molecular pathway suspected in precancerous stomach lesions

05.04.2005


May lead to improved diagnosis and prevention of stomach-esophagus cancer



Researchers at Dana-Farber Cancer Institute have identified a chain of molecular signals that generate the specialized lining of the stomach during fetal development – a discovery that could lead to better diagnosis, treatment and prevention of stomach and esophageal cancer in adults.

Damage to the stomach lining, such as from acid reflux or helicobacter pylori (H. pylori) infections, might reactivate the newly found signaling pathway – but in this situation it would work in the opposite direction. As a result, the lining reverts to a more generic intestinal type of cells that form cancer-prone lesions.


Ramesh Shivdasani, MD, PhD, of Dana-Farber, senior author of a report in the April 4 issue of Developmental Cell, said the finding "opens a window that could help us eventually interfere with these pathways when they become abnormal. It should give us a list of potential therapeutic targets and could even help us to prevent the development of the precancerous lesions."

The lead author is Byeong-Moo Kim, PhD, also of Dana-Farber.

Patients with the increasingly common disorder known as Gastroesophageal Reflux Disease, or GERD, are at risk of developing precancerous lesions in the upper end of the stomach or the adjoining lower end of the esophagus. These lesions require intense frequent monitoring by endoscopy and sometimes prophylactic surgery to decrease the threat of this dangerous form of cancer. Cancer of the "gastroesophageal junction" has increased dramatically in the past two decades, especially in patients younger than 40 years.

Shivdasani’s laboratory studies the "rules" according to which body tissues develop their distinctive form and function at the beginning of life, because they may be reactivated, abnormally, when cancer arises later.

"Cancers of the stomach are almost always preceded by the conversion of the stomach type of lining to an intestinal type," says Shivdasani. In the developing fetus, the entire digestive tract is initially lined with intestinal-type cells. At a certain point, the activation of a molecular signaling pathway causes this layer to become more specialized, or differentiated, for the lining of the stomach and esophagus. Thereafter, the pathway falls silent, unless, many years later, damage to the lining sets it in motion again.

In the mouse fetus, the differentiation of intestinal lining into stomach lining happens rapidly, during a window of only one day, around the 12th and 13th days of gestation. (The corresponding period in the human fetus is during the 8th to 10th weeks.)

"We found that the epithelium [lining layer] is malleable, and depends completely on this pathway to instruct it to become stomach," says Shivdasani. "In the absence of this pathway, the epithelium would develop into the default intestinal state."

In experiments in mice, and with cultured mouse stomach and intestinal tissue, the scientists demonstrated that the signals that drive the differentiation of stomach lining are sent by a layer of cells, known as mesenchyme, that lie directly beneath the intestinal lining. The key player in the signaling pathway, they found, is a transcription factor – a protein that governs the expression of genes under its control – called Barx1. The main action of Barx1 in stomach lining formation is to block signaling through another pathway known as Wnt, the scientists found.

"Barx1 gives us a handle on what elements of the pathway might allow the stomach to differentiate abnormally into intestine as a result of injury to the stomach lining, setting the stage for cancer," Shivdasani says.

"These research findings offer the hope of identifying a protein marker that can be used to screen for these diseases and even to serve as a target for newly designed forms of therapy," said Robert Mayer, MD, director of Dana-Farber’s Center for Gastrointestinal Oncology, who was not involved in the study.

Bill Schaller | EurekAlert!
Further information:
http://www.dfci.harvard.edu

More articles from Life Sciences:

nachricht Historical rainfall levels are significant in carbon emissions from soil
30.05.2017 | University of Texas at Austin

nachricht 3D printer inks from the woods
30.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New Method of Characterizing Graphene

Scientists have developed a new method of characterizing graphene’s properties without applying disruptive electrical contacts, allowing them to investigate both the resistance and quantum capacitance of graphene and other two-dimensional materials. Researchers from the Swiss Nanoscience Institute and the University of Basel’s Department of Physics reported their findings in the journal Physical Review Applied.

Graphene consists of a single layer of carbon atoms. It is transparent, harder than diamond and stronger than steel, yet flexible, and a significantly better...

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

3D printer inks from the woods

30.05.2017 | Life Sciences

How circadian clocks communicate with each other

30.05.2017 | Life Sciences

Graphene and quantum dots put in motion a CMOS-integrated camera that can see the invisible

30.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>