Science Current Events | Science News | Brightsurf.com
 

Two known chemotherapy agents effectively target breast cancer stem cells

May 03, 2016

AUGUSTA, Ga. - Two existing chemotherapy drugs appear to be a powerful pair in targeting errant stem cells that are making breast cancer and enabling its spread and recurrence, scientists report.

A combination of the drugs, 5-azacytidine and the HDAC inhibitor butyrate, reduces the number of cancer stem cells and improves survival in an animal model of breast cancer, they report in the journal Cancer Research. Alone, neither was effective.

"Most current chemotherapy does not kill the stem cells, which are the cells of origin, only the tumor mass," said Dr. Muthusamy Thangaraju, biochemist in the Department of Biochemistry and Molecular Biology at the Medical College of Georgia and Georgia Cancer Center at Augusta University.

"This combination might need to be considered for all breast cancer patients because their common denominator is cancer stem cells," said Thangaraju, the study's corresponding author.

The two drugs are currently used together to boost the effectiveness of another agent, tamoxifen, which is commonly used to treat estrogen-receptor positive breast cancer. About 70 percent of breast cancers are positive for receptors for this sex hormone. Tamixofen reduces estrogen levels by blocking its receptor, and clinical experience indicates the additional drugs reduce recurrence in these women.

Thangaraju's lab has evidence that the two additional drugs directly affect at least two key ways that enable stem cells to make breast cancer, including the myoepithelial cells that enable it to spread to the bone, lung and beyond. They appear to help normalize the altered gene expression that occurs and block growth-promoting signals.

The drug 5-azacytidine is an inhibitor of the gene DNMT1. Thangaraju's research team had previously reported in the journal Nature Communications that gene is essential for maintaining both normal breast stem cells and healthy breast tissue as well as cancer stem cells. DNMT1 is much more highly expressed in breast cancer than in a healthy adult breast. High levels of DNMT1 reduce expression of the ISL1 gene, a natural tumor suppressor and control mechanism for stem cells. In fact, when the MCG scientists blocked the DNMT1 gene in a breast cancer model, it eliminated about 80 percent of breast tumors, particularly the most aggressive ones.

Also over-expressed in breast cancer are the signaling molecules RAD51AP1 and SPC25, which normally help repair the type of DNA damage that can cause cancer. But in the face of cancer and some cancer treatment, both molecules instead enable growth and spread of cancer cells. Butyrate, which is present at high levels in breast milk, blocks excessive levels of these molecules that cancer is now using to support its growth.

Their work was done in mouse models of breast cancer, and findings held up in a human breast cancer cell line.

The studies also provided more evidence -- at least in their animal models -- of why the stem cells are an important target. Normally, stem cells make progenitor cells, which make specific cells that comprise the breast. But the change in dynamics that can result in cancer, such as the change in gene expression, which can happen naturally, or in response to age, environmental factors like cigarette smoke and other carcinogens or disease, means that cancer stem cells can make both tumor as well as the myoepithelial cells that, in this scenario, instead enable metastasis. Progenitor cells did not directly make this errant form of the muscle-like cell.

Interestingly, vulnerability to these so-called epigenetic changes that enable cancer likely also make resulting cancer stem cells susceptible to the combination 5-azacytidine/butyrate therapy, Thangaraju said.

Recurrence occurs in about 20-45 percent of patients and can happen even decades after the initial diagnosis, Thangaraju said. Patients in whom recurrence risk is the most concerning are those whose breast cancer was diagnosed in the advanced stage and those with HER2 positive breast cancer, which means they have a growth factor receptor that further aids cancer growth.

###

The work was funded by the National Cancer Institute and the Department of Defense.

The study's first author, former graduate student Dr. Rajneesh Pathania, now a research fellow at the NIH's National Institute of Environmental Health Sciences, continues to collaborate with the MCG team on the studies.

Next steps include more work in human breast cancer cells and healthy breast cells with MCG breast pathologist Dr. Ravindra Kolhe, a study coauthor, and learning more about how the two drugs work against cancer stem cells.

Myoepithelial cells normally reside in the milk ducts where they help squeeze milk out of the breast. The milk ducts are the most common site for breast cancer. Healthy stem cells designed to help repopulate breast tissue are mostly small in number and inactive in adult women -- other than during pregnancy. Butyrate is a food source for some cells.

Medical College of Georgia at Augusta University


Related Stem Cells Current Events and Stem Cells News Articles


Amid terror threats, new hope for radiation antidote
University of Virginia School of Medicine researchers have identified promising drugs that could lead to the first antidote for radiation exposure that might result from a dirty bomb terror attack or a nuclear accident such as Chernobyl.

Zika virus infects human placental macrophages
One of Zika's mysteries is how the virus passes from an infected mother, through the placenta, to a developing fetus.

Faster, more efficient CRISPR editing in mice
University of California, Berkeley scientists have developed a quicker and more efficient method to alter the genes of mice with CRISPR-Cas9, simplifying a procedure growing in popularity because of the ease of using the new gene-editing tool.

Recent progress in tracking the viability of transplanted stem cells in vivo
Noninvasive cell-tracking methods are indispensable for assessing the safety and efficacy of stem-cell based therapy. Thus, the research of noninvasive cell-tracking methods for determining in vivo the translocation and long-term viability of the transplanted stem cells have received considerable attention.

Carnegie Mellon develops bio-mimicry method for preparing and labeling stem cells
Researchers led by Carnegie Mellon University Professor of Biological Sciences Chien Ho have developed a new method for preparing mesenchymal stem cells (MSCs) that not only leads to the production of more native stem cells, but also labels them with a FDA approved iron-oxide nanoparticle (Ferumoxytol).

Harnessing engineered slippery surfaces for tissue repair
Transplanting a preformed dense and coherent sheet of regenerative stem cells directly onto damaged heart, cartilage or bone tissue of ailing patients often is a more promising route to recovery than transplanting the cells just loosely mixed together.

Review finds fathers' age, lifestyle associated with birth defects
A growing body of research is revealing associations between birth defects and a father's age, alcohol use and environmental factors, say researchers at Georgetown University Medical Center. They say these defects result from epigenetic alterations that can potentially affect multiple generations.

Scientists identify protein which could improve treatments for recurrent miscarriages
Scientists at the University of Sheffield have identified a protein, involved in the development of the human placenta, may also help embryos implant in the womb - something which could improve treatments for recurrent miscarriages and pre-eclampsia.

Brazilian Zika virus strain causes birth defects in experimental models
Researchers at University of California San Diego School of Medicine, with colleagues in Brazil and Senegal, have described the first "direct experimental proof" that the Brazilian strain of Zika virus can actually cause severe birth defects.

Stem cells from diabetic patients coaxed to become insulin-secreting cells
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St. Louis and Harvard University have produced insulin-secreting cells from stem cells derived from patients with type 1 diabetes.
More Stem Cells Current Events and Stem Cells News Articles

Stem Cells: A Very Short Introduction

Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)


Embryonic stem cells have been hot-button topics in recent years, generating intense public interest as well as much confusion and misinformation. In this Very Short Introduction, leading authority Jonathan Slack offers a clear and informative overview of stem cells--what they are, what scientists do with them, what stem cell therapies are available today, and how they might be used in the future. Slack explains the difference between embryonic stem cells, which exist only in laboratory cultures, and tissue-specific stem cells, which exist in our bodies, and he discusses how embryonic stem cells may be used in the future to treat such illnesses as diabetes, Parkinson's disease, heart disease, spinal trauma, and retinal degeneration. But he stresses that, despite important advances, the...

Stem Cells: An Insider's Guide

Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)


Stem Cells: An Insider's Guide is an exciting new book that takes readers inside the world of stem cells guided by international stem cell expert, Dr. Paul Knoepfler. Stem cells are catalyzing a revolution in medicine. The book also tackles the exciting and hotly debated area of stem cell treatments that are capturing the public's imagination. In the future they may also transform how we age and reproduce. However, there are serious risks and ethical challenges, too. The author's goal with this insider's guide is to give readers the information needed to distinguish between the ubiquitous hype and legitimate hope found throughout the stem cell world. The book answers the most common questions that people have about stem cells. Can stem cells help my family with a serious medical problem...

The Stem Cell Revolution

The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)


The book describes the journey into the growing arena of clinical stem cell therapy by highlighting not only the road that brought a team of physicians together but also real stories from a number of their patients that were given their health back through the magic of stem cell therapy. Your fat is loaded with stem cells that can be used now to treat and reverse a large number of inflammatory and degenerative conditions. Most people have no idea that these magical cells actually exist right within our bodies. They think that they must wait until Big Pharma or a university PhD manufactures them from embryos. Yet the Cell Surgical Network, under the guidance of Drs. Berman and Lander, has been gathering investigational data that shows your cells are safe and effective in a large variety of...

Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives

Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)


Stem cells are the repair cells of your body.  When there aren’t enough of them, or they aren’t working properly, chronic diseases can manifest and persist. From industry leaders, sport stars, and Hollywood icons to thousands of everyday, ordinary people, stem cell therapy has helped when standard medicine failed. Many of them had lost hope. These are their stories.Neil H Riordan, author of MSC: Clinical Evidence Leading Medicine’s Next Frontier, the definitive textbook on clinical stem cell therapy, brings you an easy-to-read book about how and why stem cells work, and why they’re the wave of the future.

Stem Cells For Dummies

Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)


The first authoritative yet accessible guide to this controversial topic Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term. Explains the differences between adult stem cells and embryonic/umbilical cord stem cells Provides both sides of the political debate and the pros and cons of each side's opinions Includes medical success stories using stem cell therapy and its promise for the future Comprehensive and...

Stem Cells: Promise and Reality

Stem Cells: Promise and Reality
by Lygia V Pereira (Author)


Stem Cells: Promises and Reality will tell you everything you have always wanted to know about stem cells, but could not understand the field from elsewhere.Stem cells are the great therapeutic promise of the century, and this evolving field of research and medicine brings with it many legal, ethical and psychological issues that must be discussed by society as a whole.Written so as to be accessible to general readers as well as specialists, this book explains what stem cells are, and the different aspects of stem cell research and applications. The book will enable the reader to understand the field sufficiently to critically participate in the public debates regarding stem cell research and society and ethics. By the end of the book, the reader will also be able to judge news on the...

Stem Cells Are Everywhere

Stem Cells Are Everywhere
by Irv Weissman MD (Author)


An engaging introduction to stem cells for young scientists
 
How do you heal when you cut your skin or break a bone? How does your body keep making new blood or brain cells, or even second teeth? How does a plant keep growing larger? The answers lie in stem cells, which are found in every growing plant and animal. Keeping the subject simple enough for young readers, a pioneer of stem cell research explains cells, tissues, normal growth, what can go wrong, and how to fix it.

The Stem Cell Hope: How Stem Cell Medicine Can Change Our Lives

The Stem Cell Hope: How Stem Cell Medicine Can Change Our Lives
by Alice Park (Author)


A landmark book by the senior science writer at Time magazine introduces us to a medical breakthrough that can save our lives.

Few people know much about stem cell research beyond the ethical questions raised by using embryos. But in the last decade, stem cell research has made huge advances toward eliminating some of our most intractable diseases. Now this sweeping and accessible book introduces us to this cutting-edge science that will revolutionize medicine and change the way we think about and treat disease.

Alice Park takes us from stem cell's controversial beginnings to the recent electrifying promise of being able to create the versatile cells without using embryos at all. She shows us how stem cells give researchers an unprecedented ability to study disease...

A Buyer's Guide to Stem Cell Therapies: Safely Choose the Right Regenerative Treatment for You

A Buyer's Guide to Stem Cell Therapies: Safely Choose the Right Regenerative Treatment for You


The current array of "stem cell" therapies has been called the new wild west of medicine. Between fraudulent advertising, and confusing science, it's no wonder that even doctors are unsure of what to think about stem cell treatments. This book aims to educate lay people who may be interested in stem cell or other regenerative treatments as to what options are currently available, both at home and abroad, and what science exists to support their use.

Stem Cells Heal Your Eyes: Prevent and Help: Macular Degeneration, Retinitis Pigmentosa, Stargardt, Retinal Distrophy, and Retinopathy.

Stem Cells Heal Your Eyes: Prevent and Help: Macular Degeneration, Retinitis Pigmentosa, Stargardt, Retinal Distrophy, and Retinopathy.
by Damon P Miller II MD (Author), Carlyle Coash MA (Author), Adam Miller (Author)


A physician and pioneer in the integrative treatment of serious eye diseases such as Macular Degeneration, Retinitis Pigmentosa, Stargardt and other retinopathies reveals the best strategies used today to prevent and reverse these devastating diseases. Drawing on some of the hottest topics in modern medicine, the book discusses the surprising revelations from the research in Epigenetics and adult stem cells. Your genes are not your destiny. From our work with thousands of people, we understand that you might be fearful that you will lose your independence or your ability to do even the simplest tasks because serious eye disease is taking your sight. This book empowers you with simple tools that combat degenerative eye disease. Tools that support a healthy lifestyle and methods to remove...

© 2017 BrightSurf.com