March 30, 2009, 5:20 AM CT

The new tumor suppressor gene

National Institutes of Health (NIH) scientists have identified a gene that suppresses tumor growth in melanoma, the deadliest form of skin cancer. The finding is reported today in the journal Nature Genetics as part of a systematic genetic analysis of a group of enzymes implicated in skin cancer and a number of other types of cancer.

The NIH analysis observed that one-quarter of human melanoma tumors had changes, or mutations, in genes that code for matrix metalloproteinase (MMP) enzymes. The findings lay the foundation for more individualized cancer therapy strategies where MMP and other key enzymes play a functional role in tumor growth and spread of the disease.

Tumor suppressor genes encode proteins that normally serve as a brake on cell growth. When such genes are mutated, the brake appears to be lifted, resulting in the runaway cell growth known as cancer. In contrast, oncogenes are genes that encode proteins involved in normal cell growth. When such genes are mutated, they also may cause cancer, but they do so by activating growth-promoting signals. Cancer therapies that target oncogenes commonly seek to block or reduce their action, while those aimed at tumor suppressor genes seek to restore or increase their action.

The newly released study may help to explain the disappointing performance of drugs designed to treat cancer by blocking MMP enzymes. Because members of the MMP gene family were believed to be oncogenes and a number of tumors express high levels of MMP enzymes, scientists have spent decades pursuing MMPs as promising targets for cancer therapies. However, when MMP inhibitors were tested in people with a wide range of cancers, the drugs failed to slow -- and in some cases even sped up -- tumor growth......... Posted by: Andria      Read more         Source

March 16, 2009, 8:12 PM CT

Switch May Prevent the Spread of Cancer

Scientists at the University of Pennsylvania School of Medicine have identified a master switch that might prevent cancer cells from metastasizing from a primary tumor to other organs. The switch is a protein that, when in the "on" position, maintains the normal character of cells that line the surface of organs and body cavities. These epithelial cells are the type of cell from which most solid tumors arise. However, when the switch is turned "off" or absent, epithelial cells acquire characteristics of another cell type, called mesenchymal cells, and gain the ability to migrate and move away from the primary tumor. The scientists report their findings in this month's issue of Molecular Cell.

Understanding how this switch works may one day lead to a drug that controls cancer cell metastasis and tissue fibrosis.

This change in cell motility is called the epithelial to mesenchymal transition, or EMT, and is an important process during the development of embryos. But when the transition is aberrantly reactivated in adults it can have dire physiological consequences, leading to cancer metastasis as well as other disease processes such as tissue fibrosis. Fibrotic tissue is a hallmark of organ failure, as in liver cirrhosis or kidney failure.

The master-switch is called the Epithelial Splicing Regulatory Protein, and comes in two closely related versions, ESRP1 and ESRP2. These proteins are able to change how RNAs that are produced from genes are spliced together. This is achieved by splicing different exons -- the sequence of DNA that codes information for protein synthesis -- together in different ways so that there can be more than one messenger RNA (mRNA) produced from the same gene. These mRNAs then go on to make different proteins......... Posted by: Andria      Read more         Source

March 16, 2009, 5:16 AM CT

Five-day radiation treatment of early stage prostate cancer

Preliminary results show that a shortened course of radiation treatment for prostate cancer called stereotactic body radiation treatment (SBRT) provides good PSA response for early-stage prostate cancer and has the same side effects as other therapys, as per a March 15 study in the International Journal of Radiation Oncology*Biology*Physics, the official journal of the American Society for Radiation Oncology (ASTRO). Study authors caution that further follow-up will be necessary to establish that SBRT is as effective in the long term as other proven therapys.

Radiation treatment is an effective way to treat localized prostate cancer. Proven successful therapys include brachytherapy (seed implants) where radiation sources are placed directly into the prostate and external beam radiation treatment where doctors give small daily doses of radiation to the prostate, five days a week, for eight weeks to give enough radiation to kill the cancer cells while sparing nearby healthy tissue.

External beam radiation treatment can be a very effective and minimally invasive therapy. However, the length of therapy can be burdensome for some patients, especially those who live very far from a therapy facility. Doctors have been investigating ways to shorten the course of the therapy through a technique called stereotactic body radiation treatment, where radiation oncologists give a higher dose of radiation every day for five days. Growing biologic evidence also suggests that delivering radiotherapy in this fashion might be more effective for prostate cancer than conventionally protracted courses......... Posted by: Andria      Read more         Source

February 25, 2009, 5:20 AM CT

Nanoscopic Changes to Pancreatic Cells

A team of scientists led by a Northwestern University biomedical engineer has developed a way to examine cell biopsies and detect never-before-seen signs of early-stage pancreas cancer, as per a new paper published online by the OSA journal Optics Letters.

Though the new technique has still not proven effective in double-blind clinical trials, it may one day help diagnose cancers of the pancreas and, potentially, other organs at their earliest and most treatable stages, before they spread.

A team from Northwestern and NorthShore University HealthSystem (NorthShore) describes the first application of the new technique, which they call "partial wave spectroscopic microscopy." This technique allows them to examine cell samples taken from people who have undergone screening for pancreas cancer to detect signs of the disease.

Pancreas cancer is typically diagnosed by hospital pathologists who look for telltale changes to the morphology of pancreatic cells when they examine cell biopsies under the microscope. The problem is that in the early stages of cancer, a number of early-stage cancer cells appear normal. By the time the malignant cells undergo observable changes, it appears to be too late in the disease progression for effective therapy.

In fact, only 7 percent of people with pancreas cancer are diagnosed in the earliest stages of the disease, when the cancer is still confined to its primary site. More than half of all people with the disease are not diagnosed until it has already metastasized......... Posted by: Andria      Read more         Source

February 20, 2009, 6:07 AM CT

When should you stop doing PSA testing?

Although widespread Prostate-Specific-Antigen (PSA) testing has undoubtedly decreased prostate cancer mortality, is there a point of diminishing returns? According to a research findings published in the April 2009 issue of The Journal of Urology, researchers found that in a subgroup of elderly men, among those who were 75 years old or older and had a PSA below 3 ng/ml (nanograms per milliliter), none subsequently died of prostate cancer. The discontinuation of routine PSA screening in these men may not increase the rates of undetected lethal disease, and could avoid potentially unnecessary treatments and reduce diagnostic costs.

Because PSA screening can find cancers that may become life-threatening in 5 to 25 years, there has been increased usage of the test in 40 to 50-year-olds. But the test can also discover cancers that never become life-threatening, perhaps in up to 30% of the cases. Many men who are older than 75 undergo continued PSA screening, potentially leading to unnecessary treatment since death from other causes is more likely than death from prostate cancer.

The study conducted by scientists from the Baltimore Longitudinal Study of Aging (National Institute on Aging, National Institutes of Health) and the Department of Urology at Johns Hopkins School of Medicine involved 849 men (122 with and 727 without prostate cancer) with serial PSA measurements. Researchers found that for men over 75 with PSA < 3ng/ml, none died of prostate cancer and only one developed high-risk prostate cancer. In contrast, men of all ages with a PSA ≥3.0 ng/ml had a continually rising probability of death from prostate cancer......... Posted by: Andria      Read more         Source

February 18, 2009, 6:20 AM CT

New method to predict colorectal cancer recurrence

A preliminary report shows that genetic testing may help identify a marker in lymph nodes that is linked to an increased risk of colorectal cancer recurrence among patients in whom conventional testing indicates that those lymph nodes show no evidence of cancer spread, as per a research studyin the February 18 issue of JAMA

Metastasis of tumor cells to regional lymph nodes is the single most important prognostic factor in patients with colorectal cancer. Recurrence rates increase from approximately 25 percent in patients with lymph nodes free of tumor cells as determined by biopsy (pN0 colorectal cancer) to approximately 50 percent in patients with four or more lymph nodes with metastases, as per background information in the article.

"Given the established relationship between lymph node metastasis and prognosis, recurrence in a substantial fraction of patients with pN0 colorectal cancer suggests the presence of occult [undetected] metastases (pN0 [mol+]) in regional lymph nodes that escape [biopsy] detection. On the other hand, patients with pN0 colorectal cancer who are free of lymph node metastases appears to be at lowest risk for developing recurrent disease. Thus, a more accurate evaluation of occult metastases in regional lymph nodes in patients with pN0 colorectal cancer could improve risk stratification in this clinically heterogeneous population," the authors write......... Posted by: Andria      Read more         Source

February 12, 2009, 5:46 AM CT

New culprit for prostate cancer?

Howard Hughes Medical Institute scientists have identified a new biological marker present in the urine of prostate cancer patients that indicates whether the cancer is progressing and spreading.

In experiments published in the February 12, 2009, issue of the journal Nature, the researchers identified 10 metabolites that become more abundant in prostate cells as cancer progresses. Their studies showed that one of these chemicals, sarcosine, helps prostate cancer cells invade surrounding tissue.

HHMI investigator Arul Chinnaiyan and his colleagues at the University of Michigan showed that as prostate cancer develops and progresses, sarcosine levels increase in both tumor cells and urine samples, suggesting that measurements of the metabolite could aid in non-invasively diagnosing the disease. Scientists might also be able to inhibit prostate cancer's spread by designing drugs that manipulate the sarcosine pathway.

The study is the first to analyze the levels of more than 1,000 different metabolites in human tumors. Researchers know that cells undergo complex changes as cancer develops and progresses to metastatic disease. Chinnaiyan's lab, which has extensively analyzed how genes and proteins in prostate cancer cells reflect these changes, thought that profiling cells' metabolites would offer an even more "holistic picture of the molecular alterations that occur," he said......... Posted by: Andria      Read more         Source

January 8, 2009, 9:23 PM CT

Why bladder cancer is deadlier for some

Bladder cancer is much more likely to be deadly for women and African-Americans, but the reasons long believed to explain the phenomenon account for only part of the differences for such patients in comparison to their white and male counterparts, as per results reported in the Jan. 1 issue of the journal Cancer

The results present a stark question for doctors and patients: If age, tumor type, and stage of the disease upon diagnosis don't account for all the increased lethality of the disease in women and African-Americans, then what does?

It's a gaping question facing scientists who have long confronted an irony of bladder cancer, the fifth-most-common type of cancer in America. The disease is more lethal in those patients who are less likely to get it.

Men are more than three times as likely as women to get the disease, and white people are nearly twice as likely to get the disease as African-Americans. Yet, once the disease is present, it's far deadlier in women and in African-Americans anywhere from 73 percent to 114 percent more deadly in the first year after diagnosis, depending on the group.

In the Cancer paper, researchers and physicians at the University of Rochester Medical Center show for the first time that the factors traditionally believed to be responsible for the differing course are responsible for only about one-third of the difference between white men and women, and up to two-thirds of the difference between African-Americans and their white counterparts......... Posted by: Andria      Read more         Source

December 23, 2008, 10:27 PM CT

Destabilizing cancer cells in kidney cancer

Kidney cancer is typically without symptoms until it has spread to other organs, when it is also the most difficult to treat. Newer chemotherapies show great promise for extending survival during later disease stages, but they can also be highly toxic.

In one of the first discoveries of its kind, UC Davis Cancer Center scientists have identified ways to block a cancer gene's own repair mechanism and, in so doing, help make chemotherapy for kidney cancer more effective and better tolerated. The outcome is reported in the current issue of Cancer Biology and Therapy

"Cancer cells are notorious in their ability to rapidly create copies of themselves. While the latest medications slow down that process, they do not tend to be curative and have a number of side effects," said Robert Weiss, a UC Davis professor of nephrology and chief of nephrology at the Sacramento VA Medical Center. "We wanted to find ways to help make chemotherapeutics as effective as possible at the lowest doses possible".

Newer medications work by destabilizing cancer cells at the DNA level, which reduces their ability to replicate. Knowing that the p21 gene has an important role in restoring cancer cell DNA and potentially circumventing the benefits of those therapys, Weiss sought to identify compounds that could interrupt this pathway......... Posted by: Andria      Read more         Source

December 22, 2008, 9:32 PM CT

E. coli engineered to produce anti-cancer drugs

Scientists from the UCLA Henry Samueli School of Engineering and Applied Science have taken a major step forward in the field of metabolic engineering, successfully using the bacterium Escherichia coli to synthesize a class of natural products known bacterial aromatic polyketides, which include important antibiotic and anticancer drugs.

Natural products are pharmacologically or biologically potent chemical compounds produced by living organisms; a number of are the active ingredients in pharmaceuticals. Bacterial aromatic polyketides include the antibiotic tetracycline and the compound doxorubicin, used in the therapy of breast and other cancers.

Because a number of of these natural products are synthesized by organisms that are difficult to collect, grow and maintain, scientists have sought to produce them using simpler organisms like E. coli, whose fast growth, variety of genetic tools and well-understood metabolism make it an ideal host for engineering and mass producing these compounds.

While turning E. coli into a microbial factory for natural products has been highly successful, resulting in the production of groups of drugs that include antibiotics like erythromycin and vancomycin, as well as terpenes and alkaloids, attempts to synthesize bacterial aromatic polyketides had previously been hindered by the compounds' complicated assembly process......... Posted by: Andria      Read more         Source