Detecting and defeating cancer stem cells
Modeling disease
Discovering new drugs
These goals are both broad enough to encompass a variety of research initiatives yet focused upon the central mission of Boston Children’s Hospital. Three strategies have been developed to meet these goals. First, researchers seek to develop basic methods for creating customized stem cells that will permit these to be turned into any tissue in the body. Doing so provides the greatest degree of latitude to researchers and physicians working with children battling diseases or medical conditions. Second, researchers seek to apply those approaches to the diseases most likely to yield the first breakthrough treatments. Leukemia has been identified as a promising area, as research has been conducted in this area and the method for delivering the cells—blood transplantation—has already been established and is in use. Third and last, stem cells and other technologies developed at Boston Children’s Hospital are to be made available to colleagues worldwide in order to speed progress on a vast array of diseases. Doing so will permit rapid progress toward alleviating the suffering of the many children facing a variety of diseases and medical conditions.
To date, the progress achieved by Boston Children’s Hospital researchers has been impressive. George Q. Daley, for example, has worked to translate findings from stem cell biology into improved therapies for children facing genetic and malignant diseases. His laboratory has worked with human cell culture–based and murine models of human blood disease and has created customized stem cells to treat genetic immune deficiency in mice. Felix Engel and Mark Keating have also achieved breakthroughs for those children facing cardiovascular problems. Engel and Keating were able to have adult heart-muscle cells divide and multiply in mammals, which many view as the first step in regenerating heart tissue. In order to attack cardiovascular disease, Engel and Keating are now investigating whether this technique can improve heart function in animals suffering from cardiac problems.
Benowitz and members of his team have discovered a naturally occurring growth factor called oncomodulin. Oncomodulin stimulates regeneration in injured optic nerves. This research holds great promise for those hoping to treat blindness caused by optic-nerve damage and also has promise for achieving similar regeneration in the spinal cord and brain.
Boston Children’s Hospital has supported these and other research initiatives by providing first-rate facilities and resources to all involved in stem cell research. With nearly 700,000 square feet of research space, Boston Children’s Hospital has the largest research center located at a pediatric medical center. Employing over 1,100 scientists, Boston Children’s Hospital is the home to nine members of the National Academy of Sciences. Together with researchers at the Harvard University Medical School and the Howard Hughes Medical Institute, scientists at Boston Children’s Hospital continue to work on the cutting edge of stem cell research.
Stephen T. Schroth
Towson University
See Also: Clinical Trials, U.S.: Spinal Cord Injury; Harvard University; Howard Hughes Medical Institute; Rat Models to Study Stem Cells.
Further Readings
Blackburn, S. Ethics: A Very Short Introduction. New York: Oxford University Press, 2009.
Goodstein, J. R. Millikan’s School: A History of the California Institute of Technology. New York: W. W. Norton, 2006.
Park, A. The Stem Cell Hope: How Stem Cell Medicine Can Change Our Lives. New York: Plume, 2011.
Scott, C. T. Stem Cell Now: A Brief Introduction to the Coming Medical Revolution. New York: Plume, 2006.
Slack, J. Stem Cells: A Very Short Introduction. New York: Oxford University Press, 2012.
Brain Cancer
Brain Cancer
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Brain Cancer
An abnormal and uncontrolled division of cells in the brain can result in brain cancer. A clinically detectable tumor contains a heterogeneous population of cells, which originate from clonal growth of the progeny of a single cell. Brain cancers are of two types. Primary cancers are the tumors that arise within the brain parenchyma or the structures related to it. Secondary cancers metastasize from somewhere else in the body. These can be malignant (containing cancerous cells) or benign (containing noncancerous cells). Benign cancers grow slowly and have low mitotic activity, uniformity, well-defined borders, and rarely spread. Malignant cancers, on the other hand, grow rapidly and are invasive or infiltrative. However, the distinction between the benign and malignant lesion is less evident in the central nervous system (CNS). Brain cancers can cause a variety of symptoms by interfering with the normal functions of the brain. These symptoms mainly depend upon the type, location, and extent of the tumor. Different treatment modalities are available depending upon the grade, stage, and effects of the tumor.
Mechanism of Development
Progression through the cell cycle is necessary for the proliferation of both normal and cancer cells. The cell cycle consist of two functional phases (S phase and M phase) and two preparatory phases (G1 phase and G2 phase). These phases have multiple checkpoints to regulate, monitor, and prevent the cell cycle from progressing if certain requirements have not been met. Two main checkpoints are the G1/S checkpoint and the G2/M checkpoint. Tumor suppressor genes p53, p21, and p16 also regulate the cell cycle. Dysregulation of any part of the cycle results in uncontrolled growth. Other mechanisms involved in abnormal growth of cancer cells are the activation of cell growth by growth factors, inhibition of tumor suppressor genes, evasion of apoptosis, and upregulation of telomerase enzymes.
An image of a human brain using a magnetic resonance imaging (MRI) machine. In this patient, brain cancer has metastasized in the occipital lobe, shown in the darker gray mass at lower right. (Wikimedia Commons)
Brain cancer arises either from the transformation of progenitor cells or from the dedifferentiation of mature cells in response to genetic alteration. It has also been reported that some brain cancers possess a subpopulation of cancer stem-like cells having the capacity to initiate and sustain the tumor because of their ability to proliferate, self-renew, and be multi-potent. The self-renewal ability of these brain tumor stem cells correlates with increased malignancy (such as that seen in a medulloblastoma compared with a low-grade glioma). The origin of cancer stem cells is generally not known, but they may derive from a stem cell, a transient amplifying cell, or even a terminally differentiated cell that have acquired mutations that free them from the normal control on their proliferation and/or that give them stem cell characteristics, notably, by hijacking the capacity to self-renew and thereby creating a cancer cell that renews indefinitely.
Causes and Risk Factors
The exact mechanisms by which any given cancer has arisen are difficult to pinpoint. However, many studies have shown that primary cancer develops in the brain because cells, possibly stem cells, have acquired mutations in their DNA which allow them to undergo unchecked and uncontrollable division. Secondary cancers (cancers that develop elsewhere, for example,
