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!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy