Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeted virus compels cancer cells to eat themselves

04.05.2006
Malignant glioma cells in mice die by autophagy

An engineered virus tracks down and infects the most common and deadly form of brain cancer and then kills tumor cells by forcing them to devour themselves, researchers at The University of Texas M. D. Anderson Cancer Center report this week in the Journal of the National Cancer Institute.

The modified adenovirus homed in on malignant glioma cells in mice and induced enough self-cannibalization among the cancer cells -- a process called autophagy -- to reduce tumor size and extend survival, says senior author Seiji Kondo, M.D., Ph.D., associate professor in the Department of Neurosurgery at M. D. Anderson.

’’This virus uses telomerase, an enzyme found in 80 percent of brain tumors, as a target,’’ Kondo says. ’’Once the virus enters the cell, it needs telomerase to replicate. Normal brain tissue does not have telomerase, so this virus replicates only in cancer cells.’’

Other cancers are telomerase-positive, and the researchers showed in lab experiments that the virus kills human prostate and human cervical cancer cells while sparing normal tissue.

In addition to demonstrating the therapeutic potential of the virus, called hTERT-Ad, Kondo says the international research team also clarified the mechanism by which such conditionally replicating adenoviruses (CRAs) infect and kill cancer cells.

Autophagy is a protective process that cells employ to consume part of themselves when nutrients are scarce or to destroy some of their organelles to recycle their components. A double membrane forms around the material to be consumed, then everything inside is digested.

Kondo and colleagues showed that hTERT-Ad (short for human telomerase reverse transcriptase promoter regulated adenovirus) infected the glioma cells and induced autophagy by inactivating a molecular pathway -- the mammalian target of rapamycin (mTOR) pathway -- that is known to prevent cellular self-cannibalization.

The result was a huge difference in tumor volume among mice with subcutaneous malignant glioma that got hTERT-Ad and those that received a different, non-replicating virus. Average tumor size in the hTERT-Ad group was 39 cubic millimeters, while those receiving the other virus had an average tumor volume of 200 cubic millimeters.

Among mice with malignant gliomas in the brain, those treated with three injections of hTERT-Ad on average lived 53 days. Those receiving the control adenoviruses lived on average 29 days. Two of the hTERT-Ad mice survived 60 days and had no detectable brain tumors.

Analyses of dead cancer cells showed telltale signs of autophagy: bits of virus in the cell nucleus and autophagic vacuoles -- cavities with residual digested material.

The cells showed no sign of having been killed by apoptosis -- a much better known process of programmed cell death. A normal biological defense mechanism that systematically kills defective cells, apoptosis is suppressed or dysfunctional in cancer cells. Many cancer therapies focus on restoring or enhancing apoptosis to combat the disease.

’’We believe that autophagy, but not apoptosis, mediates the principal anti-tumor effect of conditionally replicating adenoviruses,’’ Kondo says.

Cells killed by apoptosis show specific damage to the cell nucleus and DNA, with other cellular organelles preserved, Kondo explains. Cells killed by autophagy have little damage to the nucleus but heavy degradation of the cells’ organelles.

Apoptosis and autophagy should be viewed as type 1 and type 2 versions of programmed cell death, Kondo says. In a Nature Reviews Cancer paper last September, Kondo and colleagues reviewed therapies and molecules that cause or inhibit the self-cannibalization process and compared autophagy and apoptosis, which has been more heavily studied.

To improve cancer therapeutics, Kondo and colleagues concluded that it is vital to identify molecules that regulate autophagy in cancer cells and to understand how autophagy is associated with cell death, a relatively new field in cancer research.

The research group is following up the malignant glioma findings by studying ways to improve the efficiency of viral infection of cancer cells.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

nachricht How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>