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Jefferson researchers uncover genetic signature that predicts colon cancer
April 05, 2006(PHILADELPHIA) Researchers at Jefferson Medical College in Philadelphia have uncovered a genetic "signature" that accurately identifies colon cancer-a key, they hope, to better understand how the cancer develops.
Colon cancer may begin when processes that regulate adult stem cells in the colon go awry. A handful of stem cells lie in the bottom of tiny tube-like "crypts" in the epithelium (or lining) of the colon. Stem cells produce daughter cells that proliferate, eventually making their way to the top of the crypt, where they become specialized colon cells. Simply put, mutations in the stem cells lead to mutant daughter cells and cancer.
To try to understand some of these processes, Bruce Boman, M.D., Ph.D., director of the Division of Genetic and Preventive Medicine at Jefferson Medical College of Thomas Jefferson University and at Jefferson's Kimmel Cancer Center, and his co-workers used a microarray chip to analyze the expression of microRNAs (miRNAs). MiRNAs are tiny pieces of genetic material discovered in recent years that are thought to be important in regulating gene expression and in the development of cancer. The chip carried complementary genetic "probes" for most of the known miRNAs in human and mouse.
The researchers first compared miRNA expression in the bottom tenth of normal colon crypts, which is where stem cells are located, to the other nine-tenths of the crypt, where daughter cells were proliferating. This approach was designed to tell the difference between stem cell and non-stem cell activity.
They also examined miRNA gene expression in colon cancer tissue, finding changes in expression between normal tissue and cancer. More specifically, they found a pattern of 16 miRNA genes that characterizes the crypt bottom. The pattern accurately predicted which colon tissues were normal and which were cancerous.
Dr. Boman, professor of medicine and director of Jefferson's Hereditary Cancer Center and Gastrointestinal Cancer Program at Jefferson's Kimmel Cancer Center, presents the team's findings April 4, 2006 at the annual meeting of the American Association for Cancer Research in Washington, D.C.
"This will not only give us insights into how tissue dynamics are regulated in normal colonic epithelium, but also in the development of cancer as well, where the normal steady state is disrupted," he says. "It might also help us better understand the stem cell origin of colon cancer.
"If a miRNA is binding to a gene product that is key to differentiation of a cell, and the miRNA is lost, maybe that cell won't be able to undergo differentiation and will become a cancer cell," he says. "We're now looking at the gene targets for the specific miRNAs.
"The exciting part," notes Dr. Boman, "is that by figuring out which of these molecules are lost in cancer, they can theoretically be replaced. This could have tremendous potential for the development of new drugs."
Thomas Jefferson University
The researchers first compared miRNA expression in the bottom tenth of normal colon crypts, which is where stem cells are located, to the other nine-tenths of the crypt, where daughter cells were proliferating. This approach was designed to tell the difference between stem cell and non-stem cell activity.
They also examined miRNA gene expression in colon cancer tissue, finding changes in expression between normal tissue and cancer. More specifically, they found a pattern of 16 miRNA genes that characterizes the crypt bottom. The pattern accurately predicted which colon tissues were normal and which were cancerous.
Dr. Boman, professor of medicine and director of Jefferson's Hereditary Cancer Center and Gastrointestinal Cancer Program at Jefferson's Kimmel Cancer Center, presents the team's findings April 4, 2006 at the annual meeting of the American Association for Cancer Research in Washington, D.C.
"This will not only give us insights into how tissue dynamics are regulated in normal colonic epithelium, but also in the development of cancer as well, where the normal steady state is disrupted," he says. "It might also help us better understand the stem cell origin of colon cancer.
"If a miRNA is binding to a gene product that is key to differentiation of a cell, and the miRNA is lost, maybe that cell won't be able to undergo differentiation and will become a cancer cell," he says. "We're now looking at the gene targets for the specific miRNAs.
"The exciting part," notes Dr. Boman, "is that by figuring out which of these molecules are lost in cancer, they can theoretically be replaced. This could have tremendous potential for the development of new drugs."
Thomas Jefferson University
Colon Cancer Current Events and Colon Cancer News RSSOther Illnesses, Body Weight Do Not Explain Racial Disparities in Colon Cancer Survival, UAB Researchers Say
A new study by University of Alabama at Birmingham (UAB) researchers shows that body-mass index (BMI) and co-existing medical conditions (co-morbidity) do not explain the decreased survival observed among African-Americans compared to Caucasians who also have colon cancer.
Paradoxical protein might prevent cancer
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Coffee break: Compound brewing new research in colon, breast cancer
A compound in coffee has been found to be estrogenic in studies by Texas AgriLife Research scientists.
Curry-cure? Spicing up the effectiveness of a potential disease-fighter
Scientists are reporting development of a nano-size capsule that boosts the body's uptake of curcumin, an ingredient in yellow curry now being evaluated in clinical trials for treatment of several diseases.
Colon cancer screening more effective earlier in day, UCLA study finds
The effectiveness of a screening colonoscopy may depend on the time of day it is performed. According to a new UCLA study, early-morning colonoscopies yielded more polyps per patient than later screenings, and fewer polyps were found hour by hour as the day progressed.
Study shows hormone replacement therapy decreases mortality in younger postmenopausal woman
Hormone replacement therapy (HRT) to treat menopausal estrogen deficiency has been in widespread use for over 60 years. Several observational studies over the years showed that HRT use by younger postmenopausal women was associated with a significant reduction in total mortality; available evidence supported the routine use of HRT to increase longevity in postmenopausal women.
Experts issue call to reconsider screening for breast cancer and prostate cancer
Twenty years of screening for breast and prostate cancer - the most diagnosed cancer for women and men - have not brought the anticipated decline in deaths from these diseases, argue experts from the University of California, San Francisco and the University of Texas Health Science Center at San Antonio in an opinion piece published in the "Journal of the American Medical Association."
Metals could forge new cancer drug
Drugs made using unusual metals could form an effective treatment against colon and ovarian cancer, including cancerous cells that have developed immunity to other drugs, according to research at the University of Warwick and the University of Leeds.
New data: Hospital imaging centers poised to pull back, hitting patients hardest in rural areas
Survivors and patients with cancers and heart disease, along with patient advocate organizations and physicians, today urged policymakers to enhance early diagnosis of deadly diseases by preserving access to advanced imaging, such as MRI and CT scans, in final health care reform legislation.
Whole-brain radiotherapy after surgery or radiosurgery not recommended for brain metastases
Whole-brain radiotherapy should not be given routinely to all patients whose cancer has spread to the brain, say researchers who found that using it after surgery or radiosurgery in patients with a limited number of brain metastases and stable cancer in the rest of the body did not extend lives or help patients remain functionally independent for longer.
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