 |
|
Research shows cell's inactive state is critical for effectiveness of cancer treatment
January 12, 2009A new study sheds light on a little understood biological process called quiescence, which enables blood-forming stem cells to exist in a dormant or inactive state in which they are not growing or dividing. According to the study's findings, researchers identified the genetic pathway used to maintain a cell's quiescence, a state that allows bone marrow cells to escape the lethal effects of standard cancer treatments.
Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) found elevated levels of the tumor suppressor protein p53 in hematopoietic stem cells (HSCs) - immature cells in the bone marrow that have the capacity to differentiate into all types of mature blood cells. They showed that when chemotherapy or radiation is delivered to a cell that lacks both p53 and a gene called MEF, the cell not only becomes less quiescent, but also becomes more susceptible to being killed. These findings are published in the January 9, 2009, issue of Cell Stem Cell.
"This is the first time that anyone has established that p53 has a role in defining a cell's state of quiescence. Furthermore, it is surprising that some cells that lose p53 can actually be killed more readily than those that have p53 intact," said the study's senior author, Stephen Nimer, MD, Chief of the Hematology Service and Member of the Molecular Pharmacology and Chemistry Program at MSKCC. "Our findings have important implications for developing therapeutic strategies that could eliminate quiescent cancer stem cells."
The study builds on previous research in which Dr. Nimer and colleagues first identified the MEF gene and showed its ability to control the state of quiescence of HSCs as well as its critical role in determining the sensitivity of normal bone marrow cells to chemotherapy and radiation. They have now identified p53 as the pathway that MEF utilizes to maintain this enhanced quiescence.
It is known that when a cell experiences DNA damage as a result of cancer treatment, p53 plays a critical role in guarding the genomic integrity of the cell by either triggering it to die or by causing cells to stop growing so they can repair their DNA successfully. However, p53 has additional functions during the process of blood cell formation in the body - a process called hematopoiesis.
In the current study, investigators set out to determine whether the increased amount of p53 and enhanced expression of p53 target genes might contribute to the quiescence of cells and their ability to resist chemotherapy. They examined the function of p53 during hematopoiesis and found an important interdependency between p53 and its target gene, MEF, on HSC quiescence.
"Our findings suggest that by targeting those specific genes that control quiescence in cancer cells, we may enhance the anticancer effects of chemotherapy and radiotherapy, thereby promoting their effectiveness," said Dr. Nimer.
In addition, researchers identified two new targets of the p53 protein - Necdin and Gfi-1 - tumor growth suppressor genes that also regulate quiescence. Researchers lowered the expression of Necdin and Gfi-1 in hematopoietic stem cells lacking MEF and found a significant reduction in the quiescence of those cells. The results suggest that these p53 target genes are functionally responsible for the enhanced quiescence of HSCs in which MEF has been eliminated.
Memorial Sloan-Kettering Cancer Center
The study builds on previous research in which Dr. Nimer and colleagues first identified the MEF gene and showed its ability to control the state of quiescence of HSCs as well as its critical role in determining the sensitivity of normal bone marrow cells to chemotherapy and radiation. They have now identified p53 as the pathway that MEF utilizes to maintain this enhanced quiescence.
It is known that when a cell experiences DNA damage as a result of cancer treatment, p53 plays a critical role in guarding the genomic integrity of the cell by either triggering it to die or by causing cells to stop growing so they can repair their DNA successfully. However, p53 has additional functions during the process of blood cell formation in the body - a process called hematopoiesis.
In the current study, investigators set out to determine whether the increased amount of p53 and enhanced expression of p53 target genes might contribute to the quiescence of cells and their ability to resist chemotherapy. They examined the function of p53 during hematopoiesis and found an important interdependency between p53 and its target gene, MEF, on HSC quiescence.
"Our findings suggest that by targeting those specific genes that control quiescence in cancer cells, we may enhance the anticancer effects of chemotherapy and radiotherapy, thereby promoting their effectiveness," said Dr. Nimer.
In addition, researchers identified two new targets of the p53 protein - Necdin and Gfi-1 - tumor growth suppressor genes that also regulate quiescence. Researchers lowered the expression of Necdin and Gfi-1 in hematopoietic stem cells lacking MEF and found a significant reduction in the quiescence of those cells. The results suggest that these p53 target genes are functionally responsible for the enhanced quiescence of HSCs in which MEF has been eliminated.
Memorial Sloan-Kettering Cancer Center
Stem Cells Current Events and Stem Cells News RSSFirst reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
The use of stem cells in regenerative medicine may also be detrimental for health
The use of stem cells in regenerative medicine is not always beneficial for human health, it may even be harmful according to a work done by the University of Granada and University of León. Scientists have demonstrated that transplantation of human mononuclear cells isolated from umbilical cord blood exerted a deleterious effect in rats with liver cirrhosis.
Penn Study Provides First Clear Idea of How Rare Bone Disease Progresses
An international team of scientists, led by researchers at the University of Pennsylvania School of Medicine, is taking the first step in developing a treatment for a rare genetic disorder called fibrodysplasia ossificans progressiva (FOP), in which the body's skeletal muscles and soft connective tissue turns to bone, immobilizing patients over a lifetime with a second skeleton.
Iowa State University researcher discovers key to vital DNA, protein interaction
A researcher at Iowa State University has discovered how a group of proteins from plant pathogenic bacteria interact with DNA in the plant cell, opening up the possibility for what the scientist calls a "cascade of advances."
Scientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
More Stem Cells Current Events and Stem Cells News Articles
 |
Essentials of Stem Cell Biology, Second Edition by Robert Lanza (Editor), John Gearhart (Editor), Brigid Hogan (Editor), Douglas Melton (Editor), Roger Pederson (Editor), E. Donnall Thomas (Editor), James Thomson (Editor), Sir Ian Wilmut (Editor) First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners and students that are embracing the latest advances in stem cells. Representing the combined effort of seven editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world?s experts of the latest research information about specific organ systems. From basic biology/mechanisms, early development, ectoderm, mesoderm, endoderm, methods to application of stem cells to specific human diseases, regulation and... |
 |
Stem Cell Now by Christopher Thomas Scott (Author) The essential account of the most important scientific advance—and most volatile ethical debate—of our time While many believe stem cell research holds the key to curing a wide range of ailments, others see this research as opening a Pandora’s box that will devalue human life. In Stem Cell Now, Christopher Scott—executive director of Stanford University’s Stem Cells and Society Program—lays out the scientific and ethical issues surrounding this national dilemma. Scott guides readers through the latest advances in stem cell research in clear, accessible language, telling the stories of the researchers who are exploring the potential of stem cells to cure cancer, grow new organs, and repair the immune system. He also leads readers through a... |
 |
The Stem Cell Divide: The Facts, the Fiction, and the Fear Driving the Greatest Scientific, Political, and Religious Debate of Our Time by Michael Bellomo (Author) There has been much recent debate about the merits, dangers, and nature of stem cell research. Some see in it the answer to every debilitating disease known to man, while others see it as a step away from human cloning. While the battle has raged, research is moving ahead, and California has already passed a measure that will give $3 billion in support to stem cell research. But as politics, religion, and the media weigh in on this complex issue, more and more of the scientific reality of stem cell research is getting lost. In the search for the truth about stem cell science, the author has interviewed the scientists whose cutting-edge research is at the very heart of this hot-button issue. The book explains what they have accomplished so far, what they're currently doing, and what... |
 |
Human Stem Cell Manual: A Laboratory Guide by Jeanne F. Loring (Editor), Robin L. Wesselschmidt (Editor), Philip H. Schwartz (Editor) Stem cells are self-replicating and undifferentiated, meaning their function is not yet cell, tissue, or organ-specific. Due to the unique nature of these cells, research into their biology and function holds great promise for therapeutic applications through replacement or repair of diseased and damaged cells. This reader-friendly manual provides a practical "hands on" guide to the culture of human embryonic and somatic stem cells. By presenting methods for embryonic and adult lines side-by-side, the authors lay out an elegant and unique path to understanding the science of stem cell practice. The authors begin with a broad-based introduction to the field, and also review legal and regulatory issues and patents. Each experimental strategy is presented with an historical introduction,... |
 |
Stem Cell Research: Medical Applications And Ethical Controversy (The New Biology) by Joseph, Ph.D. Panno (Author) This is an informative reference to the technological advances, applications, and issues of stem cell research. The past few years have seen controversy and debate surrounding stem cell research. Because skin cells have the capability to divide - unlike most of the cells in our body - our skin can heal itself through the division of cells. Scientists have attempted to apply this concept to major organs, trying to see if stem cells can be used to make the repairs that post-mitotic cells cannot. "Stem Cell Research" is a comprehensive and interesting introduction to this popular new science for non-experts. Explaining how stems cells can be obtained from several places, including skin, bone marrow, and most usefully, embryos, this book covers all the fundamental aspects of stem cell... |
 |
Cell of Cells: The Global Race to Capture and Control the Stem Cell by Cynthia Fox (Author) Publication Date is March 26, 2007 |
 |
The Stem Cell Dilemma: Beacons of Hope or Harbingers of Doom? by Leo Furcht (Author), William Hoffman (Author) TodayÕs scientists are showing us how stem cells create and repair the human body. Unlocking these secrets has become the new Holy Grail of biomedical research. But behind that search lies a sharp divide. Stem cells offer the hope of creating or repairing tissues lost to age, disease, and injury. Yet because of this ability, stem cells hold the potential to incite an international biological arms race. THE STEM CELL DILEMMA will tell you everything you ever wanted to know about stem cells: what they are, how they work, and why their use has become so controversial. We are standing at a scientific crossroads, the likes of which the world has never seen. It is a moment that will change forever the practice of medicine and the future of life as we know it. |
 |
Mesenchymal Stem Cells: Methods and Protocols (Methods in Molecular Biology) by Darwin J. Prockop (Editor), Donald G. Phinney (Editor), Bruce A. Bunnell (Editor) For over forty years, mesenchymal stem cells (MSCs) have been scrutinized and studied, garnering much attention due to their broad therapeutic efficacy. In Mesenchymal Stem Cells: Methods and Protocols, leaders in the field were assembled to contribute detailed methodologies for the isolation and characterization of human and rodent MSCs. Recently, these vital cells have shown therapeutic benefits in the treatment of myocardial infarction, stroke, lung diseases, spinal cord injury and other neurological disorders, thus promising a boundless future in their study. Cutting edge and easy to use, Mesenchymal Stem Cells: Methods and Protocols is the perfect resource for scientists attempting to pursue this important and ever-developing field of research. |
 |
Stem Cell Wars: Inside Stories from the Frontlines by Eve Herold (Author), George Daley Dr. (Foreword) Americans have become the victims of misinformation about stem cell research. Over the last few years, the stem cell debate has been intensely political, religious, and confusing to many people. Now, Eve Herold explains what this science is all about, who is for and against it, and why it must go forward. She pulls together fascinating stories to highlight every aspect of this multifaceted field. She exposes the politics of stem cell research and demonstrates how the outcome of the debate could ultimately affect all of us. Packed with real-life stories of the people caught up in this groundbreaking struggle, Stem Cell Wars cuts through the noise and sets the standard for future debate. |
 |
Stem Cells For Dummies (For Dummies (Health & Fitness)) 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... |
| © 2009 BrightSurf.com |