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Researchers identify new drug targets for cancer
January 02, 2007Solving a 100-year-old genetic puzzle, researchers at the University of California, San Diego (UCSD) School of Medicine have determined that the same genetic mechanism that drives tumor growth can also act as a tumor suppressor. Their findings could lead to new drug targets for cancer therapies.
In a study published in the January 1 issue of Cancer Cell, Don Cleveland, Ph.D., UCSD Professor of Medicine, Neurosciences and Cellular and Molecular Medicine and member of the Ludwig Institute for Cancer Research, looked at a common characteristic of cancer cells called aneuploidy. Aneuploidy - the occurrence of one or more extra or missing chromosomes - was first proposed as the cause of cancerous tumors nearly a century ago by German biologist Theodor Boveri, but his hypothesis had remained unproven.
"We questioned whether the wrong number of chromosomes contributed to tumor growth, or was a consequences of the accrued damage in cancerous cells," said Cleveland.
To find out, researchers in the Cleveland lab created and analyzed mouse models with cells having a highly variable number of chromosomes to discover if such aneuploidy made the mice more tumor-prone.
"We found that, with age, having cells which inherited the wrong composition of chromosomes resulted in a larger number of spontaneous tumors," said Cleveland. But the more unexpected feature of their findings was discovered when the research team added other genetic errors to mice with a high rate of aneuploidy - tumor development was slowed.
The UCSD researchers also studied mice that were missing a tumor suppressor gene, which is a gene that acts to prevent cell growth. If a mutation occurs in this gene, it makes the individual - or in this case, the mouse - more susceptible to the development of cancer in the tissue in which the mutation occurs.
"When we created mice missing a tumor suppressor gene that also had a high rate of aneuploidy, tumor development was actually sharply delayed," said Cleveland, adding that in tumors, "there is always a balance between uncontrolled growth and death."
The researchers hope that, in the future, they can develop what they are calling "aneuploidy therapy." Drugs that inhibit accurate delivery of the right number of chromosomes to each new cell, resulting in aneuploidy, would be used to destroy tumors caused by mutations in the tumor suppressors.
"This study opens up a whole series of potential therapeutic targets for cancer," said Beth A.A. Weaver, of the Ludwig Institute for Cancer Research and UCSD Department of Cellu
University of California - San Diego
To find out, researchers in the Cleveland lab created and analyzed mouse models with cells having a highly variable number of chromosomes to discover if such aneuploidy made the mice more tumor-prone.
"We found that, with age, having cells which inherited the wrong composition of chromosomes resulted in a larger number of spontaneous tumors," said Cleveland. But the more unexpected feature of their findings was discovered when the research team added other genetic errors to mice with a high rate of aneuploidy - tumor development was slowed.
The UCSD researchers also studied mice that were missing a tumor suppressor gene, which is a gene that acts to prevent cell growth. If a mutation occurs in this gene, it makes the individual - or in this case, the mouse - more susceptible to the development of cancer in the tissue in which the mutation occurs.
"When we created mice missing a tumor suppressor gene that also had a high rate of aneuploidy, tumor development was actually sharply delayed," said Cleveland, adding that in tumors, "there is always a balance between uncontrolled growth and death."
The researchers hope that, in the future, they can develop what they are calling "aneuploidy therapy." Drugs that inhibit accurate delivery of the right number of chromosomes to each new cell, resulting in aneuploidy, would be used to destroy tumors caused by mutations in the tumor suppressors.
"This study opens up a whole series of potential therapeutic targets for cancer," said Beth A.A. Weaver, of the Ludwig Institute for Cancer Research and UCSD Department of Cellu
University of California - San Diego
Aneuploidy Current Events and Aneuploidy News RSSA solution to Darwin's 'mystery of the mysteries' emerges from the dark matter of the genome
Biological species are often defined on the basis of reproductive isolation. Ever since Darwin pointed out his difficulty in explaining why crosses between two species often yield sterile or inviable progeny (for instance, mules emerging from a cross between a horse and a donkey), biologists have struggled with this question.
Protein helps cells duplicate correctly, avoid becoming cancer
A Purdue University researcher has discovered that the absence of certain proteins needed for proper cell duplication can lead to cancer.
When you've doubled your genes, what's 1 chromosome more or less?
An individual with Down syndrome and a male calico cat have one thing in common-each has an extra chromosome. For animals, most instances of an extra chromosome result in birth defects or even death, but plants are another matter entirely.
UGA researchers propose model for disorders caused by improper transmission of chromosomes
Parents of healthy newborns often remark on the miracle of life. The joining of egg and sperm to create such delightful creatures can seem dazzlingly beautiful if the chromosome information from each parent has been translated properly into the embryo and newborn.
New research finds possible genetic link to cause of pregnancy loss and disorders
Scientists at the University of Tennessee, Knoxville, and Lawrence Berkeley National Laboratory (LBNL) have published new findings about a cause of a condition at the root of genetic disorders such as Down Syndrome, pregnancy loss and infertility.
Research sheds light on cause of Down syndrome and other genetic disorders
Scientists have a better understanding of what causes an abnormal number of chromosomes in offspring, a condition called aneuploidy that encompasses the most common genetic disorders in humans, such as Down syndrome, and is a leading cause of pregnancy loss.
Chromosomal problems affect nearly all human embryos
For the first time, scientists have shown that chromosomal abnormalities are present in more than 90% of IVF embryos, even those produced by young, fertile couples.
New test can detect both genetic and chromosomal abnormalities in embryos
One-step screening for both genetic and chromosomal abnormalities has come a stage closer as scientists announced that an embryo test they have been developing has successfully screened cells taken from spare embryos that were known to have cystic fibrosis.
New blood test for Down syndrome
Howard Hughes Medical Institute researchers have developed a new prenatal blood test that accurately detected Down syndrome and two other serious chromosomal defects in a small study of 18 pregnant women.
Bladder cancer detected via amplified gene in cells found in urine
Counting the copies of a specific gene in cells gathered from a urine sample may provide a simple, noninvasive way to detect bladder cancer, a team led by researchers at The University of Texas M. D. Anderson Cancer Center reports in the Journal of the National Cancer Institute.
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Oncogenes, Aneuploidy, and AIDS: A Scientific Life and Times of Peter H. Duesberg by Harvey Bialy (Author) The author is an unabashed friend of Peter Duesberg and makes no bones about it in this personalized account of some of what the transformation of classical molecular biology into biotechnology has wrought. Most people, even many molecular biologists, will either not know or remember that two of the great themes of modern medicine, AIDS and cancer genes, both directly derive from the pioneering work on retroviruses of Peter Duesberg and a handful of others in the 1970s. Thus Duesberg's more than two decade, ongoing theoretical and experimental critiques of the dominant etiological explanations in each of these fields comes from substantial scientific contributions over a highly distinguished professional career that not only placed him in the US National Academy of Sciences at the young... |
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Aneuploidy:Etiology and Mechanisms (Basic Life Sciences) (Vol 36) by Vicki Dellarco (Editor) | |
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Aneuploidy (Oxford Monographs on Medical Genetics) by D. J. Bond (Author), A. C. Chandley (Author) | |
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Chromosome Segregation and Aneuploidy (Nato Asi Series H : Cell Biology, Vol 72) by Baldev K. Vig (Editor) Aneuploidy - the greatest genetic affliction of man - has its origin in many cellular processes. Its forerunner, chromosome non-disjunction, can result from malfunction of one of many processes involved in faithful segregation of chromosomes during mitosis or meiosis. Experts on chromosome biology, centromere, kinetochore, microtubules, spindle apparatus, biochemistry of mitosis and meiosis, developmental biology, and environmental mutagenesis discuss basic and applied aspects of how chromosomes malsegregate and how aneuplody originates. The most recent techniques employed to study chromosome segregation and also methods to determine aneugenic chemicals are described. | |
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Children and Young Adults with Sex Chromosome Aneuploidy : Follow-up, Clinical, and Molecular Studies by Ont.) International Workshop on Sex Chromosome Anomalies 1989 (Minaki (Author), John L. Hamerton (Author), Jane A. Evans (Author), Arthur Robinson (Author), Arthur Robinson (Editor), March of Dimes Birth Defects Foundation (Editor) Reports from the fifth workshop for investigators carrying out prospective longitudinal studies on children and young adults with sex chromosome anomalies are presented. Part I updates the studies and provides an unbiased summary of the prognosis for a fetus or newborn diagnosed with a sex chromosome anomaly. Part II deals with clinical and therapeutic observations and provides the first critical attempt at evaluating various therapeutic modes which may be useful for patients with the 45,X and 47,XXY karyotypes. There is also critical information concerning patients with Turner and Klinefelter syndromes. The book, the result of more than 20 years of international effort, will be of value to professionals who treat patients with sex chromosome anomalies and their families as well as to... | |
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Aneuploidies: Webster's Facts and Phrases by Icon Group International (Author) Ever need a fact or quotation on "aneuploidies"? Designed for speechwriters, journalists, writers, researchers, students, professors, teachers, historians, academics, scrapbookers, trivia buffs and word lovers, this is the largest book ever created for this word. It represents a compilation of "single sentences" and/or "short paragraphs" from a variety of sources with a linguistic emphasis on anything relating to the term "aneuploidies," including non-conventional usage and alternative meanings which capture ambiguities. This is not an encyclopedic book, but rather a collage of statements made using the word "aneuploidies," or related words (e.g. inflections, synonyms or antonyms). This title is one of a series of books that considers all major vocabulary words. The entries in each book... |
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