Navigation Links
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 ca ncer 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."
'"/>

Source:University of Texas M. D. Anderson Cancer Center


Related biology news :

1. Adding Radiation Therapy To Chemotherapy Improves Survival In Patients With High-risk Breast Cancer
2. Columbia research lifts major hurdle to gene therapy for cancer
3. Combination therapy boosts effectiveness of telomere-directed cancer cell death
4. Gene therapy converts dead bone graft to new, living tissue
5. Study identifies predictors of HIV drug resistance in patients beginning triple therapy
6. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
7. Muscle-targeted gene therapy reverses rare muscular dystrophy in mice
8. New therapy for HIV/AIDS eliminates needles and excessive toxicity
9. New Treatment Rivals Chemotherapy For Lymphoma, Study Finds
10. Gene therapy for Parkinsons disease moves forward in animals
11. Pulsating ultrasound enhances gene therapy for tumors

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:1/12/2017)... , Jan. 12, 2017  New research undertaken by ... office of the future.  1,000 participants were simply asked which ... months which we may consider standard issue.  Insights on what ... 2017 were also gathered from futurists and industry leaders including ... James Canton .  Some of ...
(Date:1/6/2017)... BOULDER, Colo. , Jan. 5, 2017 /PRNewswire/ ... join the "Digital Life Alliance" established by iCarbonX, ... in 2015 to build a "Global Digital Health ... based on a combination of individual,s biological, behavioral ... Under the agreement between the companies, SomaLogic will ...
(Date:12/22/2016)... , Dec. 20, 2016  As part of its longstanding ... leading personal genetics company, recently released its latest children,s book, ... The book focuses on the topics of inheritance and variation ... Standards (NGSS) taught in elementary school classrooms in the US. ... series by illustrator Ariana Killoran , whose previous book ...
Breaking Biology News(10 mins):
(Date:1/19/2017)... ... January 18, 2017 , ... LabRoots , the leading ... the world, was today awarded the "Best Science & Technology Social Networking Service ... and decided upon by a dedicated team of researchers and analysts. , The ...
(Date:1/19/2017)... ... January 19, 2017 , ... DaVita ... full spectrum of drug and device development, and Prism Clinical Research , ... clinicians, today announced Verified Clinical Trials (VCT) has been selected by ...
(Date:1/19/2017)... Md. , Jan. 18, 2017  Northwest Biotherapeutics, ... developing DCVax® personalized immune therapies for operable and inoperable ... Bosch , Chief Technical Officer of NW Bio, will ... January 19, 2017, at the Hyatt Regency Hotel in ... Bosch will chair the session entitled "New Therapeutic Approaches ...
(Date:1/19/2017)... 18, 2017 BD (Becton, Dickinson and Company) (NYSE: ... it will host a live webcast of its Annual Meeting of ... The webcast can be accessed from the BD corporate ... Tuesday, January 31, 2017. ... About BD BD is a global medical technology ...
Breaking Biology Technology: