Green Tea May Affect Prostate Cancer Progression

According to results of a study published in Cancer Prevention Research, a journal of the American Association for Cancer Research, men with prostate cancer who consumed the active compounds in green tea demonstrated a significant reduction in serum markers predictive of prostate cancer progression.

"The investigational agent used in the trial, Polyphenon E (provided by Polyphenon Pharma) may have the potential to lower the incidence and slow the progression of prostate cancer," says James Cardelli, professor and director of basic and translational research in the Feist-Weiller Cancer Center, LSU Health Sciences Center-Shreveport.

Green tea is the second most popular drink in the world, and some epidemiological studies have shown health benefits with green tea, including a reduced incidence of prostate cancer, according to Cardelli. However, some human trials have found contradictory results. The few trials conducted to date have evaluated the clinical efficacy of green tea consumption and few studies have evaluated the change in biomarkers, which might predict disease progression.

Cardelli and colleagues conducted this open-label, single-arm, phase II clinical trial to determine the effects of short-term supplementation with green tea's active compounds on serum biomarkers in patients with prostate cancer. The biomarkers include hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and prostate specific antigen (PSA). HGF and VEGF are good prognostic indicators of metastatic disease.

The study included 26 men, aged 41 to 72 years, diagnosed with prostate cancer and scheduled for radical prostatectomy. Patients consumed four capsules containing Polyphenon E until the day before surgery — four capsules are equivalent to about 12 cups of normally brewed concentrated green tea, according to Cardelli. The time of study for 25 of the 26 patients ranged from 12 days to 73 days, with a median time of 34.5 days.

Findings showed a significant reduction in serum levels of HGF, VEGF and PSA after treatment, with some patients demonstrating reductions in levels of greater than 30 percent, according to the researchers.

Cardelli and colleagues found that other biomarkers were also positively affected. There were only a few reported side effects associated with this study, and liver function remained normal.

Results of a recent year-long clinical trial conduced by researchers in Italy demonstrated that consumption of green tea polyphenols reduced the risk of developing prostate cancer in men with high-grade prostate intraepithelial neoplasia (HGPIN).

"These studies are just the beginning and a lot of work remains to be done, however, we think that the use of tea polyphenols alone or in combination with other compounds currently used for cancer therapy should be explored as an approach to prevent cancer progression and recurrence," Cardelli says.

Dr. William Nelson, V., M.D., professor of oncology, urology and pharmacology at the Johns Hopkins Kimmel Cancer Center, believes the reduced serum biomarkers of prostate cancer may be attributable to some sort of benefit relating to green tea components.

"Unfortunately, this trial was not a randomized trial, which would have been needed to be more sure that the observed changes were truly attributable to the green tea components and not to some other lifestyle change (better diet, taking vitamins, etc.) men undertook in preparation for surgery," adds Nelson, who is also a senior editor for Cancer Prevention Research. However, "this trial is provocative enough to consider a more substantial randomized trial."

In collaboration with Columbia University in New York City, the researchers are currently conducting a comparable trial among patients with breast cancer. They also plan to conduct further studies to identify the factors that could explain why some patients responded more dramatically to Polyphenon E than others. Cardelli suggested that additional controlled clinical trials should be done to see if combinations of different plant polyphenols were more effective than Polyphenon E alone.

Watch more breaking news now on our video feed:


Bookmark http://universeeverything.blogspot.com/ and drop back in sometime.

Researchers Find Physics, Math Provide Clues to Unraveling Cancer

Biology exists in a physical world. That's a fact cancer researchers are beginning to recognize as they look to include concepts of physics and mathematics in their efforts to understand how cancer develops -- and how to stop it.

The movement, led by researchers at the University of Michigan Comprehensive Cancer Center, has come to a head with a new section in one of the top cancer research journals and a new grant program from the National Cancer Institute.

Traditional cancer biology involves taking a sample of cells and holding them in time so they can be studied. Then the researchers look at that slice of cells to understand what signals and pathways are involved. But that doesn't capture the full picture, says Dr. Sofia Merajver, M.D., co-director of the Breast Oncology Program at the Comprehensive Cancer Center.

"The living cell is really a dynamic process. We need to consider the properties of physics to help us understand these data. In order to develop a drug directed against a given molecule that has real hope of treating cancer, we need to understand how that molecule is sitting in the cell, interacting with other molecules," says Merajver, professor of internal medicine at the U-M Medical School.

Merajver and her team have developed a sophisticated mathematical model to help researchers apply these concepts to cancer. The mathematical model is designed to help give researchers a complete picture of how a cell interacts with its surrounding environment. By understanding the full complexity of signaling pathways, researchers can better target treatments and identify the most promising potential new drugs.

Researchers have learned from this modeling that a well-known and major type of signaling pathway naturally transmits information not just in a forward direction, but also backwards. That implies new considerations for developing drugs to inhibit major growth and metastasis pathways in cancer.

This crosstalk was missed by conventional methods. Typically, when scientists begin to look at a cell, they must make assumptions to simplify the picture of what is happening in cells.

"When you make simplifying assumptions, you always run the risk of eliminating critical aspects of your system, but you have no way of knowing what was discarded. When you simplify, you don't know exactly what you're throwing away because you never looked at the complex case," Merajver says. Mathematical modeling allows researchers to look at the complex case more thoroughly.

"To understand how the laws of physics can be applied to biological systems is a new frontier," she says.

Merajver and her colleagues were successful in getting the journal Cancer Research to add a new regular section to the twice-monthly journal precisely focused on mathematical modeling. The journal has also added new editors to its board who have expertise in this discipline. Merajver and Trachette Jackson, professor of mathematics at U-M, will lead this effort as senior editors.

A review article about mathematical modeling appears in the Jan. 15 issue of Cancer Research, authored by Merajver, Jackson and Alejandra Ventura, a senior postdoctoral fellow in internal medicine at U-M.

Watch more breaking news now on our video feed:



Bookmark http://universeeverything.blogspot.com/ and drop back in sometime.

Study Finds Treatment With New Drug Might Make Tumor Cells More Sensitive to Therapy

Scientists at St. Jude Children's Research Hospital have shown that it might be possible to
make tumor cells more sensitive to irradiation and some types of chemotherapy by treating them with a drug that cripples their ability to repair DNA damage caused by these therapies.

The St. Jude researchers demonstrated in the laboratory that a molecule called CP466722 rapidly blocks the ATM protein's ability to orchestrate a series of biochemical events that culminate in the repair of DNA damaged by irradiation. The molecule exerted its effect in small quantities, and its effects rapidly ended after it was removed from cells, suggesting that such
a treatment in humans would not have significant or long-term side effects, the researchers say.

Results of the study were published in the Sept. 15 issue of the journal Cancer Research.

ATM plays a critical role in repairing a type of DNA damage called double-strand breaks, in which each of the two strands making up this molecule are cut, according to Dr. Michael Kastan, M.D., director of the St. Jude Comprehensive Cancer Center. This process protects cells from the potentially lethal or mutation-causing effects of free oxygen radicals and irradiation--both of which routinely threaten them, he added. Kastan is senior author of the report on these findings.
Children lacking the gene for ATM develop ataxia-teleangiectasia, a disease that causes several debilitating problems, such as neurodegeneration, cancer and sensitivity to irradiation that leads to irreparable, double-stranded DNA breaks.

"We found that inhibition of ATM activity with CP466722 produces cellular effects that are identical to those seen in cells that lack ATM," Kastan says. "It's as if we temporarily turned normal cells into cells indistinguishable from those of children with ataxia-teleangiectasia."

The protective role of ATM makes it a tempting target for researchers looking for a way to prevent cancer cells from repairing DNA damage caused by therapeutic irradiation, Kastan notes.

Previously Kastan's team found how ATM is activated by a signal from damaged DNA only seconds after the damage occurs. The activated ATM, in turn, activates other proteins by attaching a molecule called phosphate to them in a process called phosphorylation. This sets off a cascade of biochemical reactions that amplifies the initial ATM response leading to
repair of the double-stranded break.

"Our ability to rapidly and reversibly regulate ATM activity with CP466722 also gives us a new tool to study the function of this protein, which plays such a critical role in the ability of both normal and cancerous cells to repair their DNA," says Michael Rainey, a postdoctoral fellow in the St. Jude Department of Oncology. "This approach will help us learn more about the repair events triggered by ATM in response to DNA damage." Rainey is the report's first author.

Kastan also says that CP466722 provides his team with a basic chemical structure that they can build upon as they try to modify the molecule to enhance its potency and specificity and move studies from isolated cells to mouse models.

"Results of those mouse model studies would help us to determine if and how to proceed with studies in patients with cancer," Kastan says.

Watch more breaking news now on our video feed:



Bookmark http://universeeverything.blogspot.com/ and drop back in sometime.