August 27, 2006, 7:01 PM CT

Tricking Cancer Cell To Self-destruction

Researchers have found a way to trick cancer cells into committing suicide. The novel technique potentially offers an effective method of providing personalized anti-cancer treatment.

Most living cells contain a protein called procaspase-3, which, when activated, changes into the executioner enzyme caspase-3 and initiates programmed cell death, called apoptosis. In cancer cells, however, the signaling pathway to procaspase-3 is broken. As a result, cancer cells escape destruction and grow into tumors.

"We have identified a small, synthetic compound that directly activates procaspase-3 and induces apoptosis," said Paul J. Hergenrother, a professor of chemistry at the University of Illinois at Urbana-Champaign and corresponding author of a paper to be posted online this week ahead of regular publication by the journal Nature Chemical Biology. "By bypassing the broken pathway, we can use the cells' own machinery to destroy themselves".

To find the compound, called procaspase activating compound one (PAC-1), Hergenrother, with colleagues at the U. of I., Seoul National University, and the National Center for Toxicological Research, screened more than 20,000 structurally diverse compounds for the ability to change procaspase-3 into caspase-3.

The scientists tested the compound's efficacy in cell cultures and in three mouse models of cancer. The testing waccording toformed in collaboration with William Helferich, a professor of food science and human nutrition at the U. of I., and Myung-Haing Cho at Seoul National University. The scientists also showed that PAC-1 killed cancer cells in 23 tumors obtained from a local hospital.........

Posted by: Janet      Permalink         Source

August 24, 2006, 10:12 PM CT

HIV Drug To Prevent Cervical Cancer

Scientists at the University of Manchester are in the process of developing a topical therapy against the human papilloma virus (HPV) which is responsible for pre-malignant and malignant disease of the cervix as well as other genital malignancies.

In the UK a number of thousands of women undergo surgery to remove premalignant lesions of every year. Instead they may be able to apply a simple cream or pessary to the affected area. The discovery may be even more significant in developing countries which lack surgical facilities and where HPV related cervical cancer is one of the most common forms of cancer in women.

Drs Ian and Lynne Hampson at the School of Medicine's Division of Human Development and Reproduction are in the process of developing the therapy from a type of drug that is given orally to treat HIV. This protease inhibitor can selectively kill cultured HPV infected cervical cancer cells and, since it is already available as a liquid formulation, it is possible it may work by direct application to the cervix.

The research, funded by the Humane Research Trust, is would be reported in the recent issue of the journal Anti-Viral Therapy (2006; 11(6): in press) and is also being presented at the International HPV meeting in Prague on 5 September.........

Posted by: Emily      Permalink         Source

August 24, 2006, 9:57 PM CT

Fungus A Potential Cancer Fighter

For the first time, scientists have developed a way to synthesize a cancer-killing compound called rasfonin in enough quantity to learn how it works.

Derived from a fungus discovered clinging to the walls of a New Zealand cave, the chemical tricks certain cancer cells into suicide while leaving healthy cells untouched.

"In 2000, researchers in Japan discovered that this compound might have some tremendous potential as a prototype anticancer agent, but no one has been able to study or develop it because it's so hard to get enough of it from natural sources," says Robert K. Boeckman, professor of chemistry.

"You either grow the fungus that makes it, or you go through a complicated chemical synthesis process that still yields only a minute amount," he says. "Now, after five years of effort, we've worked out a process that lets scientists finally produce enough rasfonin to really start investigating how it functions, and how we might harness it to fight cancer".

In 2000, scientists from Chiba University in Japan and the University of Tokyo simultaneously discovered a compound in certain fungi that selectively destroyed cells depending upon a gene called ras-one of the first known cancer-causing genes. They had found rasfonin, a compound that seemed tailor-made to knock out ras-dependent cancers like pancreas cancer.........

Posted by: Janet      Permalink         Source

August 24, 2006, 5:16 AM CT

Microcapsules Open in Tumour Cells

Treating cancerous tumours is difficult. Doctors have to destroy the tumour, but healthy tissue needs to be preserved. Chemotherapy tends to kill diseased cells, at the same time causing great damage to the body in general. So researchers are looking for ways to destroy only the rampant tumour cells. One way to achieve this is to transport substances inside of microcapsules into the tumour cells and release them there. Scientists led by Andre Skirtach and Gleb Sukhorukov at the Max Planck Institute of Colloids and Interfaces in Potsdam, Gera number of, along with Wolfgang Parak at Ludwig-Maximilian-University in Munich, have now used a laser as a means of opening microcapsules inserted into a tumour cell. The capsules subsequently release their contents, a fluorescent test substance, into the cell. The researchers used a light microscope to monitor how the luminous materials distribute themselves within the cell.

The vehicle that the scientists used was a polymer capsule only a few micrometres in diameter. The walls of the capsules were built from many layers of charged polymers, alternating positive and negative. In the laboratory, at least, this is an established way of producing transport containers for medicines, cosmetics, or nutrients, which can also pass through cell membranes. Andre Skirtach and colleagues equipped the capsules with a kind of "open sesame". But it didn't require any magic - just nanoparticles made of gold or silver atoms. The researchers mixed together charged metal nanoparticles along with the polymers composing the walls of the vesicle. The tumour cells absorbed the microcapsules and then the researchers aimed an infrared laser at them. Metal nanoparticles are especially good at absorbing the laser light and transmitting the heat further into their surroundings, heating up the walls. They became so hot that the bonds broke between the polymers and the shell and the capsules eventually opened.........

Posted by: Janet      Permalink         Source

August 24, 2006, 4:53 AM CT

PSA predicts treatment success

ANN ARBOR, Mich. -- A test used to detect prostate cancer can also help doctors know when therapy is working. A man's prostate specific antigen, or PSA, level after seven months of hormone treatment for advanced prostate cancer predicted how long he would survive, as per a new multicenter study conducted by the Southwest Oncology Group and led by scientists at the University of Michigan Comprehensive Cancer Center.

The study reviewed 1,345 men with prostate cancer that had spread to distant parts of the body. The men were treated with seven months of androgen deprivation treatment, a therapy designed to block the effects of hormones on the cancer. PSA levels were monitored throughout the therapy. The scientists observed that men whose PSA dropped below 4.0 ng/ml had a quarter the risk of dying in comparison to those whose PSA was more than 4.0.

Results of the study appear in the Aug. 20 issue of the Journal of Clinical Oncology.

"Our analysis showed that a low or undetectable PSA after seven months of androgen deprivation treatment is a powerful predictor of risk of death in patients with new metastatic prostate cancer. This could allow oncologists to identify patients who are unlikely to do well with this therapy long before they develop clinical signs of therapy resistance," says lead study author Maha Hussain, M.D., professor of internal medicine at the U-M Medical School.........

Posted by: Mark      Permalink         Source

August 23, 2006, 5:11 AM CT

Targeting Protein S14 In Breast Cancer Treatment

William Kinlaw, an associate professor of medicine at Dartmouth Medical School, has been working on a protein called S14 since 1990. Over the past few months, however, the news about S14 has picked up. Through a series of recently published academic studies, Kinlaw and colleagues are ready to pronounce S14 a potential drug target in treating breast cancer.

"Over the past three years, we've learned about S14 and its role in communicating information about the nutrient and energy supply to genes mandatory for fat metabolism in breast cancer cells," says Kinlaw, who is also affiliated with the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center. "With this knowledge has also come the understanding that most breast cancers have found a mechanism to turn on the S14 gene".

He explains that these tumors are 'addicted' to S14, because it is mandatory for the activation of a group of genes that allow the cancer cells to make fat. Kinlaw and his team have observed that breast cancer cells die if S14 is removed, and their analysis of human breast tumors indicates that S14 is critical for metastasis.

"This makes sense, as fat is a crucial fuel for breast cancers," he says. "We believe this is particularly so during a tumor cell's attempt to journey from the breast to other parts of the body, because the normal breast tissue supplies machinery that allows tumor cells to acquire fat from the bloodstream. Our data support the hypothesis that once the cells leave this metabolically friendly breast environment, the ability to manufacture their own fat becomes a make-or-break issue".........

Posted by: Janet      Permalink         Source

August 22, 2006, 9:49 PM CT

Is Tykerb better than Herceptin?

In reference to: Lapatinib In The Treatment Of Breast Cancer (April 4, 2006) Is Tykerb better than Herceptin? Maybe, for these reasons. Cells are the most basic structure of the body. Cells make up tissues, and tissues make up organs, such as the lungs or liver. Each cell is surrounded by a membrane, a thin layer that separates the outside of the cell from the inside. For a cell to perform necessary functions for the body and respond to its surroundings, it needs to communicate with other cells in the body. Communication occurs through chemical messages in a process called signal transduction. The purpose of these signals is to tell the cell what to do, such as when to grow, divide into two new cells, and die.

Targeted cancer therapies use drugs that block the growth and spread of cancer by interfering with specific molecules involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than current therapys and less harmful to normal cells. However, the monoclonal antibodies like Herceptin and Erbitux are \"large\" molecules. These very large molecules don\'t have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cells may pass small molecules back and forth. Exciting results have come from studies of multitargeted tyrosine kinase inhibitors, \"small\" molecules that act on multiple receptors in the malignant cells, like Tyberb and Sutent. Targeted \"small-molecule\" therapies ruled at the recent annual ASCO meeting of oncologists. The trend is away from the monoclonals to the small molecules, a trend in which a new predictive test may be able to hasten. The EGRFx (TM) assay is able to test molecularly-targeted anti-cancer drug therapies like Iressa, Tarceva, Tykerb, Sutent and possibly Nexavar, because of being small molecules.........

Posted by: Gregory D. Pawelski       Permalink         Source

August 22, 2006, 7:53 PM CT

Challenging Privately Funded Breast Cancer Research

New research by a Queen's University researcher questions the effectiveness of privately funded efforts to stop the epidemic of breast cancer among North American women.

"Breast cancer has been transformed into a market-driven industry," says Kinesiology and Health Studies researcher Samantha King. "It has become more about making money for corporate sponsors than funding innovative ways to treat breast cancer".

Dr. King's research, just published by University of Minnesota Press in a controversial new book, Pink Ribbons Inc., traces breast cancer's transformation from a stigmatized disease and individual tragedy to what she describes as "a market-driven industry that feeds off breast cancer survivors".

As per her research, only 64% of the money raised from one high-profile corporation's walk for breast cancer actually went to breast cancer organizations.

Dr. King documents how the event and its logo have become products brought and sold by North American corporate sponsors and "the extent to which fundraising for breast cancer has become a highly valued commodity in itself".

"Fundraising for breast cancer has developed into a highly competitive market in which large foundations and corporations compete with one another to attract the loyalty of consumers - in this case, well-intentioned members of the public wanting to do their part in the fight against the disease," she says.........

Posted by: Janet      Permalink         Source

August 21, 2006, 10:06 PM CT

Protein That Protect Breast Cancer Tumors

About half of women whose breast cancer is treated with standard chemotherapy have their cancer return within five years. Most chemotherapeutic drugs have undesirable side effects, but there has been no way to predict who would benefit and who wouldn't. Fortunately, new research findings at the University of Southern California could change that.

Scientists at the USC/Norris Comprehensive Cancer Center have discovered a new biological marker in tumors that can help indicate whether a woman's breast cancer will respond to the most usually prescribed chemotherapy drugs.

Amy S. Lee, Ph.D., professor of biochemistry and molecular biology in the Keck School of Medicine of the University of Southern California, isolated the gene for the GRP78 protein (78-kDA glucose-regulated protein) in 1980. It normally helps protect cells from dying, especially when they are under stress from a lack of glucose. In her current research, Lee finds that breast cancer tumors with high levels of GRP78 are protected from a common chemotherapy regimen based on Adriamycin, a topoisomerase inhibitor. Her findings are published as a "Priority Report" in the August 15 issue of Cancer Research.

"The importance of this study is in its potential to help clinicians who treat cancer," Lee says. "It will help sort out the patients who won't respond to particular therapy regimens and will have a higher chance of cancer recurrence."........

Posted by: Janet      Permalink         Source

August 21, 2006, 9:53 PM CT

Nicotine Withdrawal Begins Quickly

Smokers who have tried to quit are well aware of the symptoms of nicotine withdrawal: cravings for cigarettes, mood disturbances, appetite increase and sleep problems. However, it had not previously been known when withdrawal symptoms first appear. Thomas H. Brandon, Ph.D., Director of H. Lee Moffitt Cancer Center & Research Institute's Tobacco Research & Intervention Program and his research team from Moffitt and the University of South Florida study examined this and observed that within 30 minutes, the abstaining smokers reported greater cravings for cigarettes. Results have been reported in the most recent issue of Psychopharmacology, authored by Peter S. Hendricks, Joseph, W. Ditre, and David J. Drobes, and Brandon.

The team brought 50 pack-a-day smokers into the laboratory for four hours of testing. Half the smokers were randomly selected to continue smoking as usual, while the other half were asked to abstain from smoking for the four hours. Every half-hour these participants received a series of tests. Differences between the two groups were considered evidence of nicotine withdrawal.

Within 30 minutes, the abstaining smokers reported greater cravings for cigarettes. By one hour, they reported greater anger. Increases in anxiety, sadness, and difficulty concentrating all appeared within the first three hours. Results also show that in the first half-hour the abstaining smokers already performed more poorly on a task requiring sustained attention, and that their heart rate slowed within the first hour, another withdrawal symptom.........

Posted by: Janet      Permalink         Source