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February 20, 2007, 9:14 PM CT

Gene profiling and resistance to Herceptin

Gene profiling and resistance to Herceptin
Using gene chips to profile tumors before therapy, scientists at Harvard and Yale Universities found markers that identified breast cancer subtypes resistant to Herceptin, the primary therapy for HER2-positive breast cancer. They say this advance could help further refine treatment for the 25 to 30 percent of patients with breast cancer with this class of tumor.

In the February 15 issue of Clinical Cancer Research, the scientists observed that HER2-positive tumors that did not respond to Herceptin expressed certain basal markers, growth factors and growth factor receptors. One of these, insulin-growth factor receptor 1(IGF-1R), was linked to a Herceptin response rate that was half that of tumors that did not express IGF-1R.

They also discovered that resistant tumors continue to over-express the HER2 growth factor protein -- an important finding given that a number of researchers had thought that loss of HER2 was likely responsible for Herceptin resistance.

"Herceptin has revolutionized the care of HER2-positive breast cancer for a number of patients, but unfortunately, not for some. This work demonstrates that digging deeper into the molecular subtypes of these tumors helps us understand why some tumors are resistant and may point to ways to remedy that," said the studys lead author, Lyndsay Harris, M.D., associate professor and Director of the Breast Cancer Disease Unit at Yale University Medical Center.........

Posted by: Emily      Read more         Source


February 20, 2007, 7:51 PM CT

Chemotherapy Drug Packs A One-two Punch

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 treatment and various forms of chemotherapy were all believed to be separate but equal therapys. 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: Janet      Read more         Source


February 20, 2007, 7:47 PM CT

Test Identifies Lymphoma Patients Likely to Respond

Test Identifies Lymphoma Patients Likely to Respond
Scientists at the Albert Einstein College of Medicine of Yeshiva University have discovered a genetic signature identifying cases of lymphoma that are uniquely susceptible to a newly developed molecular targeted treatment. As a result, physicians organizing clinical trials of the new treatment will be able to enroll patients who'll be most likely to benefit from it.

The research was led by Dr. Ari Melnick, assistant professor of developmental & molecular biology and medicine at Einstein, who also developed the new lymphoma treatment. The study appears in the February 20 issue of the Proceedings of the National Academy of Sciences.

Each year more than 60,000 Americans are diagnosed with B cell lymphomas-tumors of cells of the immune system that include Hodgkin's and non-Hodgkin's lymphomas. B cells are the immune-system cells that make antibodies. Genetic aberrations can cause B cells to multiply uncontrollably, causing B cell lymphomas.

Dr. Melnick's study focused on a gene called BCL6. The protein it codes for is a transcriptional repressor, which means that it can shut off the functioning of genes in B cells and other cells of the immune system and prevent them from being expressed. The BCL6 protein is normally produced only during a specific stage of B cell development and is never made again. But deregulation of BCL6 can cause the protein to be produced when it shouldn't be. The unwelcome presence of the BCL6 protein blocks the expression of important genes that normally protect cells from becoming malignant. As a result, cancerous B-cell lymphomas occur.........

Posted by: Janet      Read more         Source


February 19, 2007, 9:05 PM CT

New test for most virulent HPV strains

New test for most virulent HPV strains
A test for the two strains of human papillomavirus responsible for most cervical cancers is under study.

The molecular assay uses a cervical scraping, like that for a liquid-based Pap smear, to test for HPV types 16 and 18, responsible for 70 percent of cervical cancers, says Dr. Daron G. Ferris, family medicine doctor and director of the Gynecologic Cancer Prevention Center at the Medical College of Georgia.

"Data from a National Cancer Institute trial shows that if you have a genital infection with HPV types 16 or 18, your chance of getting moderate to severe premalignant cervical changes or cancer is much higher than if you have one of the other types," says Dr. Ferris, a principal investigator on the national study evaluating the assay.

The NCI study followed women infected with different types of the typically slow-acting virus over 10 years. It found women infected with type 18 had a 15 percent risk of malignant or pre-malignant changes after 10 years, those with type 16 had a 20 percent increased risk while those with the 11 other strains had a collective risk of 1-2 percent.

"Clearly, there is a big difference between HPV types 16 and 18 and all the other cancer-causing strains of HPV," says Dr. Ferris.

The type-specific assay, developed by Third Wave Technologies, Inc., in Madison, Wis., is being tested along with an assay that looks for the presence of 14 types of cancer-causing HPV. A test that detects 13 types of HPV already is commercially available, so the new test could become the second non-type-specific HPV test on the market.........

Posted by: Emily      Read more         Source


February 15, 2007, 4:31 AM CT

African-american Breast Cancer Survivors And Perceived Risk

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.

Scientists 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: Janet      Read more         Source


February 11, 2007, 9:05 PM CT

Technology To Captures Tumors'genetic Profile

Technology To Captures Tumors'genetic Profile
A study led by scientists at Dana-Farber Cancer Institute and Broad Institute of the Massachusetts Institute of Technology and Harvard University provides the first demonstration of a practical method of screening tumors for cancer-related gene abnormalities that might be treated with "targeted" drugs.

The findings, published online today on the Nature Genetics Web site, may help relieve a bottleneck between scientists' expanding knowledge of the genetic mutations linked to 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 treatment 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".........

Posted by: Janet      Read more         Source


February 8, 2007, 10:06 PM CT

Lung Cancer Rates Among Female Nonsmokers

Lung Cancer Rates Among Female Nonsmokers
Not all lung cancer is due to a lifetime of smoking cigarettes. Sometimes the diagnosis is a mystery, and the stigma surrounding the disease makes it hard for patients to talk about. Now, scientists at the Stanford University School of Medicine and the Northern California Cancer Center have taken the first steps toward analyzing why people who never smoked get lung cancer.

Their data, would be reported in the Feb. 10 issue of the Journal of Clinical Oncology, shows that never-smokers get lung cancer more often than thought, with women even more at risk than men.

"People tend to banter about this number of 10 to 15 percent of lung cancer cases being in people who have never smoked," explained lead author Heather Wakelee, MD, assistant professor of medicine at Stanford. "But when you actually try to find the hard data to show that, it's very limited".

The team of scientists used multiple collections of data from both the United States and Sweden that, in total, tracked the occurence rate of lung cancer in more than 1 million people from the ages of 40 to 79. They calculated the lung cancer incidence rates in terms of new cases per person-year, representing every year that someone was included in the study.

They observed that for women, the lung cancer incidence rate in never-smokers ranged from 14.4 to 20.8 cases per 100,000 person-years. In men, it ranged from 4.8 to 13.7 incidents. For current smokers, the rates were about 10 to 30 times higher. To put these numbers in perspective, Wakelee pointed out that the rates for cervical and thyroid cancer in women of the same age range are comparable, at 15.4 and 17.3 cases per 100,000 person-years, respectively.........

Posted by: Scott      Read more         Source


February 7, 2007, 4:50 AM CT

speed up radiation therapy

speed up radiation therapy The automatic radiation planning algorithm results in beamlet intensities that produce equal-dose contours.
Credit: Rensselaer/Richard Radk
A new computer-based technique could eliminate hours of manual adjustment linked to a popular cancer therapy. In a paper reported in the Feb. 7 issue of Physics in Medicine and Biology, scientists 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 therapy.

"Intensity Modulated Radiation Therapy (IMRT) has exploded in popularity, but the technique can require hours of manual tuning to determine an effective radiation therapy 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 his colleagues have tested their algorithm on 10 patients with prostate cancer at Memorial Sloan-Kettering. They observed that for 70 percent of the cases, the algorithm automatically determined an appropriate radiation treatment plan in about 10 minutes.........

Posted by: Janet      Read more         Source


February 6, 2007, 9:59 PM CT

Identifying Breast Cancer in Overweight Women

Identifying Breast Cancer in Overweight Women
Increasing the ability to identify sentinel nodes-the very first lymph nodes that trap cancer cells draining away from a breast lesion site-has a major impact in the therapy and outcome of patients with breast cancer, possibly eliminating the need for unnecessary and painful surgery. Scientists observed that using SPECT/CT imaging aids in sentinel node identification-particularly for overweight or obese women, as per a report in the recent issue of the Journal of Nuclear Medicine.

Lymphoscintigraphy (a usually performed nuclear medicine procedure that makes the lymphatic system visible to specialized cameras)-used with single photon emission computed tomography (SPECT)/computed tomography (CT) imaging-boosted sentinel node identification not only for the general population but also for those who were overweight. "The addition of SPECT/CT with lymphoscintigraphy enhanced sentinel node identification in overweight breast cancer patients," noted Hedva Lerman, vice chair of the nuclear medicine department at Tel-Aviv Sourasky Medical Center in Israel. Failure to identify sentinel nodes is more frequent in overweight or obese patients, and improved techniques are needed to guide surgeons to their location, said the co-author of "Improved Sentinel Node Identification by SPECT/CT in Overweight Patients With Breast Cancer." She explained, "While the identification of the sentinel node is an important part of surgical management approaches in breast cancer, obesity is a significant factor in why it fails and inevitably leads to occasional-and unnecessary-full axillary lymph node dissection (a more complex surgery that removes all lymph nodes in the armpit region)."........

Posted by: Janet      Read more         Source


February 6, 2007, 9:41 PM CT

Major Player in Cell Growth

Major Player in Cell Growth
When cells go about the business of dividing, they can get sidelined. Maybe there aren't enough nutrients. Maybe there aren't the right signals to resume multiplying. Either way, cells go quiet.

What can restart cell division - the process that drives the development of embryos, the renewal of hair, skin and blood, and the creation of cancer - is a single transcription factor called GABP, as per new research from The Warren Alpert Medical School of Brown University and Rhode Island Hospital.

The work, published online in Nature Cell Biology, introduces a new pathway that can be manipulated to control cell growth. Since cell growth is a fundamental biological process, the research may shed light on everything from miscarriages to muscular dystrophy. The main application, however, is cancer. Since a key characteristic of cancer cells is unchecked growth, the research identifies potential targets for new therapys.

"As a scientist and a physician, I am tremendously excited," said Alan Rosmarin, M.D., an associate professor in the Department of Medicine and the Department of Molecular Biology, Cell Biology and Biochemistry at Brown and director of clinical oncology research for Lifespan, Rhode Island's largest health care system. "This discovery not only adds to our basic understanding of cell division, it could lead to better cancer drugs. And they're needed. Cancer touches everyone".........

Posted by: Janet      Read more         Source



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Cancer
Cancer is a very common disease, approximately one out of every two American men and one out of every three American women will have some type of cancer at some point during the course of their life. Cancer is more common in the elderly and 77 percent of cancers occur in people above age 55 or older. Cancer is also common in children. Cancer incidence is said to have two peaks once during early childhood and then during late years in life. No age period is completely exempted from development of cancers. Some cancers occur predominantly in the elderly, other types occur in children, Cancer occurs in all ethnic races, however the cancer rates and rates of specific cancer types may vary from group to group. Late stages of cancer may be incurable in most cases, but with the advancement of medicine, more and more cancers are becoming curable.

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