Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Dual gene therapy suppresses lung cancer in preclinical test

Combination gene therapy delivered in lipid-based nanoparticles drastically reduces the number and size of human non-small cell lung cancer tumors in mice, researchers at The University of Texas M. D. Anderson Cancer Center and the University of Texas Southwestern Medical Center report in the Jan. 15 edition of Cancer Research.

Two tumor-suppressing genes given intravenously reduced cancer separately but had their most powerful effect when administered together, cutting the number of tumors per mouse by 75 percent and the weight of tumors by 80 percent.

"In cancer treatment we have combination chemotherapy, and we also combine different modes of therapy - surgery, radiation and chemotherapy. Now you've got the possibility of combined targeted gene therapy," said Jack Roth, M.D., professor and chair of the M. D. Anderson Department of Thoracic and Cardiovascular Surgery and a senior researcher on the project.

The genes wrapped in the nanoparticles were p53, a well-known tumor suppressor that works by causing defective cells to commit suicide and is often shut down or defective in cancer cells, and FUS1, a tumor-suppressor discovered by the research group that is deficient in most human lung cancers. Each nanoparticle carried one of the two genes.

The Cancer Research paper reports that FUS1 works with p53 to force the lung cancer cells to kill themselves - a process known as apoptosis.

Further analysis showed that the combination achieved greater cell suicide because FUS1 suppresses a gene that expresses a protein known to rapidly degrade p53, says senior author Lin Ji, Ph.D., M. D. Anderson associate professor of thoracic and cardiovascular surgery.

The FUS1/p53 combination also activates a cell suicide pathway based in the cells' mitochondria, their energy powerhouse.

Lab experiments first showed that the gene combination cut the number of viable cells in four lines of human non-small cell lung cancer by 70 to 80 percent 48 hours after treatment while leaving a control group of normal cells unaffected. The cancer cell lines treated with the gene combination had 2 to 3 times more cells killed by apoptosis than either gene nanoparticle had individually. The research team then confirmed these findings in the mouse studies.

The nanoparticle delivery system, which the researchers have used for years, consists of a plasmid gene expression cassette loaded with DNA that encodes either the p53 or the FUS1 protein. This is wrapped tightly in a form of cholesterol to protect it from the body's defense mechanisms. "You can't deliver naked DNA for cancer therapy," Ji says.

The nanoparticles accumulate mainly in the lungs, particularly in the tumors, Ji says. The positively charged nanoparticles are delivered to the negatively charged cancer cell membrane and taken into the cell, where the genes repeatedly express either p53 or FUS1 tumor-suppressing proteins.

Roth expects the research team to advance combination therapies to clinical trials in the coming years, either of genes or of genes with other biologic or chemotherapy agents.

"We certainly hope this approach will be more effective but we also think it's likely to be much less toxic, with fewer side effects, than other types of combined cancer therapy," Roth says. "These genes don't have much effect on normal tissue or normal cells when they are overexpressed. It's really just cancer cells where they seem to have their effect. Ultimately, the usefulness of this approach has to be proven in clinical trials."

Scott Merville | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

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: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>