(Press-News.org) A promising new treatment for breast cancer being developed at Virginia Commonwealth University Massey Cancer Center and the VCU Institute of Molecular Medicine (VIMM) has been shown in cell culture and in animal models to selectively kill cancer stem cells at the original tumor site and in distant metastases with no toxic effects on healthy cells, including normal stem cells. Cancer stem cells are critical to a cancer's ability to recur following conventional chemotherapies and radiation therapy because they can quickly multiply and establish new tumors that are often therapy resistant.
The study, published in the International Journal of Cancer, focuses on a gene originally cloned in the laboratory of primary investigator Paul B. Fisher, M.Ph., Ph.D. The gene, melanoma differentiation associated gene-7 (mda-7), also known as interleukin (IL)-24, has been shown to directly impact two forms of cell suicide known as apoptosis and toxic autophagy, regulate the development of new blood vessels and also play a role in promoting cancer cell destruction by the immune system. In the present study, the researchers used a recombinant adenovirus vector, an engineered virus with modified genetic material, known as Ad.mda-7 to deliver the mda-7/IL-24 gene with its encoded protein directly to the tumor.
"Therapy with the mda-7/IL-24 gene has been shown to be safe in a phase I clinical trial involving patients with advanced cancers, and prior studies in my laboratory and with collaborators have shown that the gene could also be effective against breast, prostate, lung, colorectal, ovarian, pancreatic and brain cancers," says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics program at VCU Massey, chairman of VCU School of Medicine's Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine. "Our study demonstrates that this therapy may someday be an effective way to eradicate both early and advanced stage breast cancer, and could even be used to reduce the risk of cancer recurrence."
The researchers found that infection of human breast cancer cells with the adenovirus decreased the proliferation of breast cancer stem cells without affecting normal breast stem cells. It was also shown to induce a stress response in the cells that led to apoptosis by disrupting Wnt/B-catenin signaling, a process cells rely upon to transmit signals that initiate biological functions critical to survival. In mouse models, the therapy profoundly inhibited the growth of tumors generated from breast cancer stem cells and also killed cancer cells in distant, uninjected tumors.
Since discovering the mda-7/IL-24 gene, Fisher and his team have worked to develop better ways to deliver it to cancer cells, including two cancer "terminator" viruses known as Ad.5-CTV and Ad.5/3-CTV. Cancer terminator viruses are unique because they are designed to replicate only within cancer cells while delivering immune-modulating and toxic genes such as MDA-7/IL-24. Coupled with a novel stealth delivery technique known as ultrasound-targeted microbubble destruction (UTMD), researchers can now systemically deliver viruses and therapeutic genes and proteins directly to tumors and their surrounding tissue (microenvironment) at both primary and metastatic tumor sites. UTMD uses microscopic, gas-filled bubbles that can be paired with viral therapies, therapeutic genes and proteins, and imaging agents and can then be released in a site and target-specific manner via ultrasound. Fisher and his colleagues are pioneering this approach and have already reported success in experiments utilizing UTMD technology and mda-7/IL-24 gene therapy in prostate and colorectal cancer models.
"We are hopeful that this targeted gene therapy could be safely combined with conventional chemotherapies to significantly improve outcomes for patients with breast cancer and potentially a variety of other cancers," says Fisher. "When paired with promising new delivery techniques such as UTMD, physicians may one day be able to better target site-specific cancers and also monitor the effectiveness of these types of therapies in real time."
INFORMATION:
Fisher collaborated on this study with Paul Dent, Ph.D., member of the Developmental Therapeutics program at VCU Massey, professor in the Department of Neurosurgery at VCU School of Medicine and member of VIMM; Xiang-Yang Wang, Ph.D., member of the Cancer Molecular Genetics program at VCU Massey, associate professor in the Department of Human and Molecular Genetics and associate scientific director of immunology and infectious diseases of VIMM; Devanand Sarkar, M.B.B.S., Ph.D., Harrison Scholar and member of the Cancer Molecular Genetics program at VCU Massey, associate professor in the Department of Human and Molecular Genetics at VCU School of Medicine, and associate scientific director of cancer therapeutics at VIMM; Belal Azab, Ph.D., and Michelle E. Menezes, Ph.D., both postdoctoral scientists from the Department of Human and Molecular Genetics at VCU School of Medicine; and Sujit K. Bhutia, Ph.D., Department of Human and Molecular Genetics at VCU School of Medicine, now an assistant professor in the Department of Life Science, National Institute of Technology, Rourkela, India.
This study was supported by National Cancer Institute grants R01 CA097318 and P01 CA104177.
The full manuscript of this study is available at: http://onlinelibrary.wiley.com/doi/10.1002/ijc.28289/abstract;jsessionid=EAF95F3253E44B492D50B8E862E1F55E.d03t03
News directors: Broadcast access to VCU Massey Cancer Center experts is available through VideoLink ReadyCam. ReadyCam transmits video and audio via fiber optics through a system that is routed to your newsroom. To schedule a live or taped interview, contact John Wallace, (804) 628-1550.
About VCU Massey Cancer Center
VCU Massey Cancer Center is one of only 67 National Cancer Institute-designated institutions in the country that leads and shapes America's cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It has one of the largest offerings of clinical trials in Virginia and serves patients in Richmond and in four satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at http://www.massey.vcu.edu or call 877-4-MASSEY for more information.
About VCU and the VCU Medical Center
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 222 degree and certificate programs in the arts, sciences and humanities. Sixty-six of the programs are unique in Virginia, many of them crossing the disciplines of VCU's 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation's leading academic medical centers. For more, see http://www.vcu.edu.
Targeted viral therapy destroys breast cancer stem cells in preclinical experiments
2013-06-24
ELSE PRESS RELEASES FROM THIS DATE:
Rare pregnancy condition programs babies to become overweight in later life
2013-06-24
Babies born to mothers who suffer from a rare metabolic complication during pregnancy are programmed to be overweight, according to a study published today in the Journal of Clinical Investigation.
The study is the first to look at the long term effects on babies born to mothers with intrahepatic cholestasis of pregnancy (ICP), also called obstetric cholestasis, a rare complication of pregnancy characterised by the build-up of bile acids in the bloodstream.
The findings add to the strong evidence that the environment that babies are exposed to in the womb is a major ...
1 in 10 female German or British tourists holidaying in southern Europe suffers sexual harassment
2013-06-24
VIDEO:
One in 10 female German or British tourists holidaying in southern Europe suffers sexual harassment.
Click here for more information.
The European Institute of Studies on Prevention (Irefrea) surveyed more than 6,000 people in various airports in Mediterranean countries during summer 2009 to find out the levels of harassment and sex against one's will that had occurred. According to the experts, one in ten female English or German tourists has fallen victim to these ...
Study reveals uncertainty over the benefits of feeding birds in winter
2013-06-24
Wild bird populations are generally thought to benefit from being given additional food in winter but our understanding of the effects of such food provision is incomplete. The results of a new study, carried out by researchers at the University of Exeter and the British Trust for Ornithology (BTO), has found that feeding wild blue tits in winter resulted in less successful breeding during the following spring.
The research, just published in Scientific Reports, revealed that woodland blue tits that were provided with fat balls as a supplementary food during the winter ...
Pleasure response from chocolate: You can see it in the eyes
2013-06-24
PHILADELPHIA (June 24, 2013)— The brain's pleasure response to tasting food can be measured through the eyes using a common, low-cost ophthalmological tool, according to a study just published in the journal Obesity. If validated, this method could be useful for research and clinical applications in food addiction and obesity prevention.
Dr. Jennifer Nasser, an associate professor in the department of Nutrition Sciences in Drexel University's College of Nursing and Health Professions, led the study testing the use of electroretinography (ERG) to indicate increases in the ...
Action needed to help tobacco users quit across the globe
2013-06-24
More than half of the countries who signed the WHO 2005 Framework Convention on Tobacco Control have not formed plans to help tobacco users quit.
The World Health Organization Framework Convention on Tobacco Control (WHO FCTC) is a treaty developed to tackle the global tobacco epidemic that is killing 5 million people each year. It came into force in 2005 and is legally binding in 175 countries. The FCTC requires each country to develop plans to help tobacco users in their population to stop -- plans that should be based on strong scientific evidence for what works.
Two ...
New 'biowire' technology matures human heart by mimicking fetal heartrate
2013-06-24
TORONTO, Ontario (June 24, 2013) – A new method of maturing human heart cells that simulates the natural growth environment of heart cells while applying electrical pulses to mimic the heart rate of fetal humans has led researchers at the University of Toronto to an electrifying step forward for cardiac research.
The discovery, announced this week in the scientific journal Nature Methods, offers cardiac researchers a fast and reliable method of creating mature human cardiac patches in a range of sizes.
"You cannot obtain human cardiomyocytes (heart cells) from human ...
Brain cancer: Hunger for amino acids makes it more aggressive
2013-06-24
To fuel phases of fast and aggressive growth, tumors need higher-than-normal amounts of energy and the molecular building blocks needed to build new cellular components. Cancer cells therefore consume a lot of sugar (glucose A number of tumors are also able to catabolize the amino acid glutamine, an important building block of proteins. A key enzyme in amino acid decomposition is isocitrate dehydrogenase (IDH). Several years ago, scientists discovered mutations in the gene coding for IDH in numerous types of brain cancer. Very malignant brain tumors called primary glioblastomas ...
Massive Online Open Courses could revolutionize university education
2013-06-24
This news release is available in Spanish.
MOOCs are linked to the appearance of digital culture in all the areas of our lives, from the way we listen to music to the way we take photos, read the newspaper or watch movies. "Before, you had to have a radio, and a camera, go to the newsstand to buy the newspaper or go to the cinema, but now there are applications that enable us to do everything digitally," said the coordinator of the eMadrid network, Carlos Delgado Kloos, during the opening of this conference, dedicated to the transformational effect that the technology ...
Going to synagogue is good for health and happiness, Baylor researcher finds
2013-06-24
Two new Baylor University studies show that Israeli Jewish adults who attend synagogue regularly, pray often, and consider themselves religious are significantly healthier and happier than their non-religious counterparts. They also report greater satisfaction with life.
"These findings nicely reinforce the inherited Jewish folk wisdom that going to shul (synagogue) is 'good for you,'" said Baylor University researcher Jeff Levin, Ph.D.
Levin holds a distinguished chair at Baylor University, where he is University Professor of Epidemiology and Population Health and Director ...
Northwestern researchers examine mechanical bases for the emergence of undulatory swimmers
2013-06-24
How do fish swim? It is a simple question, but there is no simple answer.
Researchers at Northwestern University have revealed some of the mechanical properties that allow fish to perform their complex movements. Their findings, published on June 13 in the journal PLOS Computational Biology, could provide insights in evolutionary biology and lead to an understanding of the neural control of movement and development of bio-inspired underwater vehicles.
"If we could play God and create an undulatory swimmer, how stiff should its body be? At what wave frequency should ...