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SAN DIEGO, CA — Green tea is high in the antioxidant EGCG (epigallocatechin-3- gallate) which helps prevent the body’s cells from becoming damaged and prematurely aged. Studies have suggested that the combination of green tea and EGCG may also be beneficial by providing protection against certain types of cancers, including breast cancer. A new study conducted by researchers at the University of Mississippi researchers now finds that consuming EGCG significantly inhibits breast tumor growth in female mice. These results bring us one step closer to better understanding the disease and potentially new and naturally occurring therapies.

The study was conducted by Jian-Wei Gu, Emily Young, Jordan Covington, James Wes Johnson, and Wei Tan, all of the Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS. Dr. Gu will present his team’s findings, entitled, Oral Administration of EGCG, an Antioxidant Found in Green Tea, Inhibits Tumor Angiogenesis and Growth of Breast Cancer in Female Mice, at the  121^st Annual Meeting of the American Physiological Society (APS; www.the-APS.org/press), part of the Experimental Biology 2008 scientific conference.

The Study

Epidemiological studies suggest that green tea and its major constituent, EGCG, can provide some protection against cancer. Because these studies were very limited, the anti-cancer mechanism of green tea and EGCG was not clear. As a result, the researchers examined whether drinking EGCG (just the antioxidant infused in water) inhibited the following: expression of VEGF (vascular endothelial growth factor, which is found in a variety of breast cancer types); tumor angiogenesis (thought to help tumors expand by supplying them with nutrients); and the growth of breast cancer in female mice.

Seven week old female mice were given EGCG (25 mg/50 ml) in drinking water for five weeks (approximately 50-100 mg/kg/day.) The control mice received regular drinking water. In the second week of the study mouse breast cancer cells were injected in the left fourth mammary glands of the mice. Tumor size was monitored by measuring the tumor cross section area (TCSA). Tumors were eventually isolated and measured for tumor weight, intratumoral microvessel (IM) density (using staining), and VEGF protein levels (using ELISA).

At the end of the five week period the researchers found that oral consumption of EGCG caused significant decreases in TCSA (66%), tumor weight (68%), IM density 155±6 vs.111±20 IM#mm^2) and VEGF protein levels (59.0±3.7 vs. 45.7±1.4 pg/mg) in the breast tumors vs. the control mice, respectively (N=8; P<0.01).  Further, VEGF plasma levels were lower in EGCG mice than in control mice (40.8±3.5 vs. 26.5±3.8 pg/ml P< 0.01).

Dr. Gu, the senior researcher for the study, hypothesized that the reason for the link between EGCG and the reductions in the cancer data was because EGCG directly targets both tumor blood vessels and tumor cells of breast cancer for suppressing the new blood vessels formation in breast tumor, the proliferation and migration of breast cancer cells.

Gu concluded by saying, “In this study we have demonstrated that the frequent ingestion of EGCG significantly inhibits breast tumor growth, VEGF expression and tumor angiogenesis in mice. We believe our findings will help lead to new therapies for the prevention and treatment of breast cancer in women.”

Physiology is the study of how molecules, cells, tissues and organs function to create health or disease. The American Physiological Society (APS; www.The-APS.org/press) has been an integral part of this discovery process since it was established in 1887.

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reporter Gavin Johnson (WEDNESDAY, March 19th, 2008)

Often known as the theory of faith healing, placebos have been around for generations. While a placebo may have no actual chemical or medical effect directly on the human body, the physical results on a patient’s health may show otherwise.

A recent study was conducted among 500 cancer patients earlier this year in Houston, Texas. Among the 500 patients, 250 were given a daily placebo in addition to their normal treatment, which was explained to contain new found minerals that attack malignant cells in the body, and have shown to dramatically slow the effects of cancer. The other group of patients was given no additional pills, and continued their regular treatment, typically including radiation or chemotherapy.

These pills however were nothing more than sugar pills, or light dosages of common painkillers. While the compositions of the pills were supposedly worthless on the body in any significant way, the result of the test showed different.

Out of the control group of 250 patients who did not receive any additional medication in addition to their normal routine, there was a 43% improvement on their condition. These were rather expected results for diseases of that severity. However of the group that had received the placebo, 83% of the patients begun to show improvement within the first week, continuing to the end of the experiment.

More clinical trials are expected to take place beginning later this month. Further investigation of this self healing technique is expected. Many believe that there is strong emphasis on the cognitive aspect of the healing of cancer. While it can not be said for certain, the results of this experiment certainly support that theory.

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by Dianne C. Witter

Dr. Aggarwal is conducting laboratory studies on the apparent anticancer activity of curcumin, which is the main ingredient of the curry spice turmeric.

Razelle Kurzrock, M.D., rigorously evaluates the laboratory data behind any new pharmaceutical agent she considers moving into clinical trials at M. D. Anderson Cancer Center. As a physician, she is cautious; as a scientist, she’s a skeptic; she wants unbiased, evidence-based information. And that, to her own surprise, is how she became interested in studying curcumin—the primary ingredient of the curry spice turmeric—as a possible anticancer agent in humans.

“Dr. Bharat Aggarwal, chief of the cytokine research laboratory in the Department of Experimental Therapeutics, came to me and said, ‘I want to show you some great results we’ve gotten in the lab with an exciting new agent,’” said Dr. Kurzrock. “But he wouldn’t tell me what the agent was—he wanted me to see the data first.”

Dr. Kurzrock, professor in and chair ad interim of M. D. Anderson’s Department of Investigational Cancer Therapeutics (formerly the Phase I Clinical Trials program), was impressed with the data. “It was clear that this agent was just as potent at killing tumor cells in the lab as any experimental drug I’d seen from pharmaceutical companies,” she said. When Dr. Aggarwal told her this active agent was curcumin, she was intrigued and began designing a clinical study to test curcumin’s efficacy in humans.

Shutting down the master switch

Curcumin’s anti-inflammatory properties have been valued in Eastern medicine for centuries, but its specific mechanism of action has only recently been identified. In 1995, Dr. Aggarwal and colleagues demonstrated that curcumin shuts down nuclear factor kappa B (NF-kB), which is involved in the regulation of inflammation and many other processes.

By blocking the activity of this “master switch,” curcumin appears to interfere with the cancer process at an early point, impeding multiple routes of development: reducing the inflammatory response, inhibiting the proliferation of tumor cells, inducing their self-destruction, and discouraging the growth of blood vessels feeding tumors. These effects can shrink tumors and inhibit metastasis. Furthermore, shutting down NF-kB can enable traditional chemotherapy drugs to destroy cancer cells more effectively.

Hundreds of laboratory studies by Drs. Aggarwal and Kurzrock and others have demonstrated that curcumin is biologically active against many types of cancer cells—melanoma, and breast, bladder, brain, pancreatic, and ovarian carcinomas, to name just a few. “In the lab, we haven’t yet found a type of cancer it doesn’t show activity against,” Dr. Aggarwal said.

While it’s a long road from lab to clinic, Dr. Aggarwal sees promise in curcumin both as a possible preventive agent and as a cancer treatment. As a medicinal agent, its potential extends far beyond cancer. Laboratory studies have demonstrated curcumin’s promise in a number of different diseases that are also affected by inflammation, including arthritis, inflammatory bowel disease, Alzheimer’s disease, diabetes, cardiovascular disease, autoimmune diseases, and others. In light of these findings, the number of clinical studies of curcumin has grown substantially in the past few years and continues to rise.

Studying activity in cancer patients

The clinical research on curcumin in cancer is new but promising. Early studies at M. D. Anderson and elsewhere have shown curcumin to be well tolerated and non-toxic at high oral doses.

Dr. Kurzrock is designing clinical trials of curcumin, based on promising lab results.

Dr. Kurzrock and colleagues recently conducted a trial of curcumin in 49 patients with advanced pancreatic cancer, which is notoriously resistant to treatment. Two of those patients had clinically meaningful responses and remained stable for 8 months and more than 22 months, respectively. Another had a brief but dramatic response (73% reduction in tumor size).

“In advanced pancreatic cancer, the response rate to the Food and Drug Administration-approved treatments is only about 5%, so we were very encouraged that we saw any activity at all in this group,” said Dr. Kurzrock. “That tells us curcumin does have biologic activity in pancreatic cancer—there was a true antitumor effect. It’s too soon to know if it will affect survival rates, but more study is definitely warranted.” The fact that some patients benefited is encouraging, since there were questions about whether therapeutic concentrations could be achieved with oral administration.

To address the issue of absorption, Dr. Kurzrock is leading the development of an intravenous, liposome-encapsulated delivery system for curcumin that she says has so far been “very potent” in the lab. Liposomal curcumin would be given intravenously, thereby circumventing the problem of poor absorption.

“The fact that the curcumin did show some activity in the study even though it was poorly absorbed suggests that if we can develop a more effective method to get it to the tumors, it may well have promise as an anticancer treatment,” said Dr. Kurzrock. She hopes to have the liposome-encapsulated delivery system ready to test in a phase I clinical trial for patients with a variety of cancers in 2008. Whether the intravenous formulation would have more side effects in patients because of the higher blood levels of the agent is not yet known, but preliminary testing in mice has shown no toxicity, even at maximum doses.

Currently under way at M. D. Anderson is a clinical trial of curcumin in multiple myeloma, and researchers are seeking funding for a trial in breast cancer. Trials of curcumin in colorectal cancer and in myelodysplastic syndrome are in progress at other institutions. Curcumin is also in clinical trials as a treatment for non-cancer diseases such as Alzheimer’s disease, arthritis, and psoriasis.

Food for thought

Dr. Aggarwal, for one, is not surprised at the evidence that curcumin may have efficacy in treating cancer. He feels curcumin has the potential to one day be an inexpensive and nontoxic alternative to harsher oncology drugs; a chemopreventive agent; and an adjunct to chemotherapy. But he notes that progress in developing curcumin for medical use is likely to be much slower than for pharmaceutical agents because curcumin can’t be patented on a broad scale and therefore is unlikely to attract the interest and the funding of pharmaceutical companies.

For his part, Dr. Aggarwal takes a curcumin tablet every day, and he offers this food for thought: “The combined rate of the four most common cancers in the United States—lung, prostate, breast, and colon—is at least 10 times lower in India, where curry is a staple in the diet.”

For more information, call Dr. Aggarwal at 713-794-1817 or Dr. Kurzrock at 713-794-1226.

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