February 26, 2007, 7:00 PM CT

Genes That Can Slow Cell Division

Cancer cells differ from normal cells in, among other things, the way they divide. When a normal cell complies with a signal telling it to divide, it also begins to activate a "braking system" that eventually stops cell division and returns the cell to a resting state. When that braking system is faulty, uncontrolled cell division and the growth of cancer can result. Weizmann Institute researchers studied this system of brakes, and identified many the genes involved.

As per the study's findings, which appeared in Nature Genetics online on February 25, aberrations in the activities of these genes are tied to certain types of cancer, as well as to the relative aggressiveness of the cancer. These insights may, in the future, lead to the development of ways to restore the brakes on runaway cell division and halt the progression of cancer.

First, the researchers mapped the network of genes that is activated in normal cells upon receiving the order to divide. The "divide!" signal comes from outside the cell in the form of a chemical called a growth factor, and it initiates a chain of events inside the cell. The genes activated in this sequence produce proteins, some of which cause cell division and others that put the brakes on that division. To find which genes were responsible, the researchers needed to sift through a huge quantity of data on genes and their activities. To cope with this monumental task, a team of Weizmann Institute scientists from diverse fields pooled their knowledge and experience: Prof. Yosef Yarden of the Biological Regulation Department, Prof. Eytan Doa number of of the Physics of Complex Systems Department, Prof. Uri Alon of the Molecular Cell Biology Department, and Dr. Eran Segal of the Computer Science and Applied Mathematics Department. Working with them were Prof. Gideon Rechavi of the Sheba Medical Center and scientists from the M.D. Anderson Cancer Center in Houston, Texas, headed by Prof. Gordon B. Mills......... Posted by: Andria      Read more         Source

February 23, 2007, 5:08 AM CT

Opening And Closing The Genome

At any given time, most of the roughly 30,000 genes that constitute the human genome are inactive, or repressed, closed to the cellular machinery that transcribes genes into the proteins of the body. In an average cell, only about one in ten genes is active, or expressed, at any given moment, with its DNA open to the cell' transcriptional machinery.

A dynamic cast of gatekeeper enzymes controls this access to the DNA, adding and removing particular molecules to open or close the genome to transcription as needed. Fully explicating the complex interplay among these enzymes and the molecules they manage has been a primary goal for researchers seeking to understand the mechanisms governing gene control. These mechanisms are vital for health-- when they go wrong, diseases like cancer can result.

In study published online February 22 in Cell, scientists at The Wistar Institute identify an important new player in this gene-control system, an enzyme responsible for removing certain molecules, or marks, involved in opening or closing chromatin, the material that makes up chromosomes. The activity of this enzyme is believed to be widespread in the genome, likely affecting a number of genes.

"This enzyme removes methyl groups from a specific location where they facilitate opening of the chromatin for gene expression, and therefore this enzyme maintains a repressed state of gene expression," says Ramin Shiekhattar, Ph.D., a professor at The Wistar Institute and senior author on the Cell study. Currently, Shiekhattar is also a professor at the Center de Regulacio Genomica in Barcelona. "When the enzyme is not present, however, the marks are not removed, and the chromatin remains open for transcription"......... Posted by: Andria      Read more         Source

February 21, 2007, 9:21 PM CT

African American Women And Breast Cancer?

Why are African American women 1.5 to 2.2 times more likely than white women to die from breast cancer, despite their lower incidence of the disease? Is it solely because they have less access to medical care? Maybe not, according to a new analysis that will appear in an upcoming issue of the International Journal of Surgery. In a paper now available online, researchers propose that the excess mortality occurs partly because black women are more likely than white women to develop breast cancer before menopause, when surgery to remove the tumor may pose a higher risk of stimulating cancer growth.

The researchers, led by Michael Retsky, PhD in the Vascular Biology Program at Children's Hospital Boston, note that African American women are diagnosed with breast cancer at an average age of 46, versus 57 for white women, and that their excess mortality first appeared in the mid-1970s, just when mammography for early detection was introduced. Early breast cancer detection leads to earlier surgical removals, which may actually spur relapse in some premenopausal cancer patients, the researchers say.

"Looking at what's happening in African American women provides a research opportunity to learn how to better screen for and treat premenopausal breast cancer overall," says Retsky. "There's much to learn that might translate into improved outcomes for all premenopausal women"......... Posted by: Andria      Read more         Source

February 20, 2007, 7:52 PM CT

Chemotherapy Drug Packs A One-two Punch

Cancer can be wily, and those who treat the disease have amassed a wide array of weapons with which to fight it and kill tumors. Radiation therapy and various forms of chemotherapy were all thought to be separate but equal treatments. Now, however, new research is beginning to show that it's not just killing the cancer cells that matter. How they're killed may turn out to be just as important and could play a role in marshalling the body's immune response.

New research by Rockefeller University associate professor Madhav Dhodapkar, head of the Laboratory of Tumor Immunology and Immunotherapy, shows that one form of chemotherapy - a drug called bortezomib - kills tumor cells in such a way that it may allow the immune system to recognize them. In a first edition paper published online this week by the journal Blood, Dhodapkar, postdoctoral fellow Radek Spisek, and their colleagues show that unlike radiation or other chemical therapies, bortezomib can kill multiple myeloma cells in culture in such a way that it elicits a response by memory and killer T cells. The results suggest the drug has the potential to enhance patients' immunity to tumors, helping their bodies fight the disease more effectively.

Multiple myeloma is a cancer of immune cells in the bone marrow. Dhodapkar's experiments show that when treated with bortezomib in tissue culture, multiple myeloma cells die in such a way that a heat shock protein, called hsp90, migrate to their surface. When another group of immune cells, called dendritic cells, encounter hsp90 on the dying tumor cells, the protein acts as a signal for their activation. The dendritic cells then ingest them for presentation to memory and killer T cells, a progression that - in humans - could potentially lead to enhanced immunity. "If you could directly target the drug to these cells," Dhodapkar says, "it may be sufficient enough to create a vaccine. The exposure of heat shock proteins on dying cells represents an immunogenic form of cell death"......... Posted by: Andria      Read more         Source

February 19, 2007, 8:21 PM CT

Defense Mechanism Of Tumors Discovered

MIT scientists have identified a critical defense mechanism that tumor cells employ to survive the toxic effects of chemotherapy--knowledge that could very soon lead to more effective cancer therapys.

The findings, reported as the cover story in the Feb. 13 issue of Cancer Cell, show that after chemotherapy, a number of tumors resort to using a signaling pathway normally linked to the inflammatory response in order to survive.

Drugs that knock out this inflammatory defense mechanism would render tumors vastly more susceptible to chemotherapy, as per Michael Yaffe, MIT associate professor of biology and biological engineering, and leader of the research team. One such drug is already in the pipeline.

"In the clinic, we could use lower doses of chemotherapy and get a more profound reduction of the tumor with fewer side effects in patients by targeting this pathway," said Yaffe, who is affiliated with MIT's Cancer for Cancer Research, the Broad Institute of MIT and Harvard, and Beth Israel Deaconess Medical Center.

Knocking out the inflammatory pathway should be an effective tactic against most tumors--namely, tumors that lack p53, a protein known to protect normal cells from becoming malignant. (Cells with p53 don't rely on the pathway for survival.) Up to 80 percent of human tumors lack p53, making them susceptible to the new therapy......... Posted by: Andria      Read more         Source

February 15, 2007, 4:57 AM CT

ER and HER-2 status of breast tumors

Two critical characteristics of breast cancer that are important to treatment can be identified by measuring gene expression in the tumor, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports in Lancet Oncology online.

Researchers developed and validated a new genomic microarray test that identifies whether a tumor's growth is fueled by the female hormone estrogen and the role of a growth factor receptor known as HER-2 that makes a tumor vulnerable to a specific drug. The status of these factors is now determined by pathology tests.

"This is one important step towards personalized diagnosis and treatment planning based on an integrated genomic test of an individual tumor," said senior author W. Fraser Symmans, M.D., associate professor in the M. D. Anderson Department of Pathology. The Lancet Oncology paper results are the latest in an effort by the research team to develop a single test to quickly and efficiently determine the characteristics and vulnerabilities of a patient's breast cancer and ultimately to guide treatment.

About 70 percent of breast cancers are estrogen-receptor positive and another 15 to 25 percent are human epidermal growth factor receptor-2 (HER-2) positive. Each receptor status requires different types of treatment......... Posted by: Andria      Read more         Source

February 15, 2007, 4:32 AM CT

African-american Breast Cancer Survivors And Perceived Risk

A unique survey of African American breast cancer survivors at heightened risk for hereditary breast cancer has found the majority do not believe they have an increased chance of developing the cancer again.

Researchers from the University of Pennsylvania, reporting in the recent issue of Cancer Epidemiology, Biomarkers & Prevention, say these findings suggest it is important to ensure that African American women understand their risk of developing cancer, and genetic counseling to address cultural beliefs and values may be one way of doing so.

"Having a personal and family history of breast cancer are known risk factors for breast cancer, and it is surprising and worrisome that most of these women with such a history don't recognize that risk," said the study's lead author, Chanita Hughes Halbert, Ph.D., assistant professor of psychiatry and Director of the Community and Minority Cancer Control Program at the University of Pennsylvania's Abramson Cancer Center.

Halbert's research focuses on understanding the socio-cultural underpinnings of cancer prevention and control behaviors among ethnically diverse populations so that interventions can be designed that reduce cancer morbidity and mortality.

One such intervention is genetic counseling that often includes testing whether a woman has a mutation in one of two genes (BRCA1/BRCA2); women with these genes are at greater risk for developing breast cancer than women without alterations in those genes......... Posted by: Andria      Read more         Source

February 11, 2007, 9:24 PM CT

New Technology Guides Cancer Treatment

Researchers from Dana-Farber Cancer Institute and Broad Institute of the Massachusetts Institute of Technology and Harvard University in combination has created a new technology screening tumors for cancer-related gene abnormalities that might be treated with "targeted" drugs.

The findings, published on the Nature Genetics Web site, may help relieve a bottleneck between scientists' expanding knowledge of the genetic mutations associated with cancer and the still nascent ability of doctors to use that knowledge to benefit patients. The results constitute an important step toward the era of "personalized medicine," in which cancer therapy will be guided by the particular set of genetic mutations within each patient's tumor, the authors suggest.

"It's universally recognized that cancer is a disease of the genome, of mutations within genes responsible for cell growth and survival, and a great deal of effort has gone into finding those mutations, to the point where several hundred to a thousand are now known," said the study's senior author, Levi Garraway, MD, PhD, of Dana-Farber and the Broad Institute. "The challenge has been how to determine which of them are involved in each of the hundreds of kinds of cancer that occur in humans -- and to develop accurate, affordable methods of detecting key mutations in tumor samples. This study suggests that such a method is feasible on a large scale".........

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February 7, 2007, 4:51 AM CT

speed up radiation therapy

A new computer-based technique could eliminate hours of manual adjustment associated with a popular cancer treatment. In a paper published in the Feb. 7 issue of Physics in Medicine and Biology, researchers from Rensselaer Polytechnic Institute and Memorial Sloan-Kettering Cancer Center describe an approach that has the potential to automatically determine acceptable radiation plans in a matter of minutes, without compromising the quality of treatment.

"Intensity Modulated Radiation Therapy (IMRT) has exploded in popularity, but the technique can require hours of manual tuning to determine an effective radiation treatment for a given patient," said Richard Radke, assistant professor of electrical, computer, and systems engineering at Rensselaer. Radke is leading a team of engineers and medical physicists to develop a "machine learning" algorithm that could cut hours from the process.

A subfield of artificial intelligence, machine learning is based on the development of algorithms that allow computers to learn relationships in large datasets from examples. Radke and colleagues have tested their algorithm on 10 prostate cancer patients at Memorial Sloan-Kettering. They found that for 70 percent of the cases, the algorithm automatically determined an appropriate radiation therapy plan in about 10 minutes.........

Posted by: Andria      Read more         Source

January 30, 2007, 9:29 PM CT

Breast Cancer And Type Of Hormonal Drug

Aromatase inhibitors, a type of hormone therapy used to treat advanced breast cancer in postmenopausal women, result in a small but significant increase in overall survival when compared to other hormone treatments, according to a new systematic review of studies.

In addition, aromatase inhibitors -- drugs known as Arimidex, Aromasin and Femara -- are less likely to cause blood clots and vaginal bleeding than other hormone treatments, said review co-author Judith Bliss of the Institute of Cancer Research in London.

The review analyzed 30 studies involving the treatment of advanced breast cancer, encompassing more than 10,000 postmenopausal women.

Bliss and colleagues were surprised at how few of the reviewed studies presented data on overall survival for women taking aromatase inhibitors. "Survival data was only available for about half of the women," Bliss said.

The available data showed an 11 percent reduction in the risk of death compared to women not receiving aromatase inhibitors.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.........

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