Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Embryonic pathway critical to growth of digestive tract tumors

23.10.2003



The signal, called Hedgehog, tells cells when and where to grow during embryonic development and is turned on in primitive cells, or stem cells, in adult tissues to trigger tissue repair. Researchers at Hopkins and elsewhere have already linked Hedgehog and its signaling pathway to a non-fatal skin cancer (basal cell carcinoma), a deadly lung cancer and the most common childhood brain cancer (medulloblastoma).

"Blocking this signal may one day help treat cancers for which there are currently few or no mechanism-based therapies," says senior author Philip Beachy, Ph.D., professor of molecular biology and genetics in Hopkins’ Institute for Basic Biomedical Sciences and a Howard Hughes Medical Institute investigator. "For right now, the biggest question is whether it will pan out in people."


In experiments with cancer cell lines and tumor samples from patients, the scientists found that Hedgehog’s signal is required for the cancers’ growth. Moreover, a three-week course of a plant-derived chemical called cyclopamine, known to block Hedgehog, killed these cancers when grown in mice, causing no apparent harm to the animals.

"In mice, blocking the Hedgehog signal made the implanted tumors disappear," says the study’s first author, David Berman, M.D., Ph.D., assistant professor of pathology at Hopkins. "It’s been about three and a half months since we stopped the cyclopamine, and still the tumors haven’t returned."

Unfortunately, cyclopamine is unlikely to be useful for patients because there just isn’t enough of it, so the search is on to find Hedgehog blockers that could be made in quantities necessary for human studies, say the researchers.

The researchers checked for Hedgehog activation in cell lines and fresh samples of digestive tract tumors because the gut comes from the same part of the embryo -- the endoderm -- as the lung, says Anirban Maitra, MBBS, assistant professor of pathology. Earlier this year, a team from Hopkins linked Hedgehog activation to small cell lung cancer, providing reason to anticipate Hedgehog’s involvement in a variety of other cancers, notes Berman.

"Because of Hedgehog’s important roles in these tissues during development, we hypothesized that ’reactivation’ of the pathway occurs in adult life during cancer development in these organs," adds Maitra, whose procedure for obtaining fresh samples from surgically removed tumors provided the opportunity to analyze cancers unaltered by years of laboratory growth. "Our studies prove this hypothesis to be true."

The pathway’s link to another batch of cancers support the idea that cancer may arise -- in part -- from abnormal growth of stem cells inside mature organs.

The scientists speculate that primitive cells in the lining of the digestive tract may turn on the normal Hedgehog pathway to repair tissue damaged by long-term exposure to an environmental toxin or irritant, such as excess stomach acid chronically rising into the esophagus.

If the damaging environmental irritant is also carcinogenic, such as tobacco smoke, the chances go up that these long-lived primitive cells eventually may collect the right genetic mutations to trigger cancer development, suggests Beachy.

Authors on the study linking Hedgehog to digestive tract tumors are Berman, Maitra, Beachy, Sunil Karhadkar, Rocio Montes de Oca, Meg Gerstenblith, Antony Parker and James Eshleman of the Johns Hopkins School of Medicine; Kimberly Briggs and Neil Watkins of the Johns Hopkins Kimmel Cancer Center; and Yutaka Shimada of Kyoto University, Japan. The project was funded by the family of Margaret Lee and by grants from the National Institutes of Health.

A related paper, focusing on pancreatic cancer and written by researchers at the University of California at San Francisco and Harvard Medical School, appears in the same issue of the journal.


Under a licensing agreement between Curis Inc. and The Johns Hopkins University, Beachy and the University hold equity in Curis and are entitled to a share of royalties from sales of the products described in this article. Beachy also receives payment and equity for service as a consultant to Curis Inc. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.

Joanna Downer | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/
http://www.nature.com/nature

More articles from Health and Medicine:

nachricht Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>