Thursday, April 26, 2007

Pomegranate Juice May Slow Lung Cancer

Drinking pomegranate juice may help slow the progression of lung cancer, a University of Wisconsin-Madison study shows.

The researchers found that mice that drank the juice saw a greater reduction in tumor growth than those that didn't drink pomegranate juice. The reduction was 53.9% at 84 days and 61.6% at 140 days.

Previous studies have indicated that pomegranates might be beneficial in preventing a variety of other conditions, including heart disease and prostate cancer. The study is published in Cancer Research.

Hope For Cancer Patients

Alisa Gilbert always knew she was meant to help others. Surviving breast cancer showed her how.

Now in her mid-40s, Gilbert is the founder and executive director of the Office of Native Cancer Survivorship, a national nonprofit organization that provides support services to cancer patients.

At age 31, Gilbert was a cancer patient herself.

"I had a bilateral mastectomy when I was 31. I had chemotherapy and treatments and surgeries and such, and after that I ended up getting pregnant and having my first child, literally back to back with that treatment, and it was just an eye-opener. Everything that happened, all the people who came into my life at that time, really made such a difference and raised my awareness across the board to the issues that people face all over the country," Gilbert said.

The experience of surviving cancer led directly to her role as an activist and advocate for cancer patients and to the creation of ONCS.

"I've always been the kind of person that thought, 'I just know that I can make a difference.' It's not too hard to figure out what you need to do to actually make things change, so I've just been involved since then," Gilbert said.

Getting pregnant -- let alone getting pregnant so soon after being treated for cancer -- was a shock both to Gilbert and her doctors. Gilbert had gone through menopause during her cancer treatment; the doctors assumed she was incapable of getting pregnant and didn't supply her with birth control.

"I think my doctors were more terrified than anything because the hormones in your body can wreak all kinds of havoc and they weren't sure at the time if the pregnancy would bring on an occurrence of the disease, so they were really more concerned because they didn't think there would be any children," Gilbert said.

Gilbert said she was in "a kind of shock" at being pregnant.

"My husband and I hadn't planned it. My son was born on Christmas and it was pretty interesting; and not too long after that, our second child was born, too. We've got four children -- two from my husband's previous marriage and the two we've had. And after my second son was born, the doctors said, 'Absolutely not another one. This is too dangerous,'" Gilbert said.

Not very many studies have been done about breast cancer survivors having children, Gilbert said.

"There are so many survivor-related issues when you put all the data together; in my case, the fact of being 31, the fact of having an aggressive type of cancer and a tumor size that was humungous and had already metastasized, and they were treating me to shrink the tumor before surgery, which was pretty common back then but not practiced so much now. The bilateral mastectomy was not an option: that was the recommended therapy. If you put all that together and then the thought of getting pregnant not once but twice and the thought that re-occurrence could happen due to the hormone production rate during pregnancy. The last thing you want is to have somebody get pregnant and have cancer re-occur and they're not around long enough to see their children grow up," Gilbert said.

Against those odds, everything has turned out miraculously well for Gilbert and her family. She gave birth to two healthy children, has remained cancer-free and has dedicated her energy to helping others survive cancer and live healthy, productive lives.

"I've been doing great. My kids are healthy. We're very fortunate, we're very blessed," Gilbert said.

Antibody Effectives Against Cancer Hiked

PHILADELPHIA -- U.S. scientists have created a method of expanding the number of immune system "natural killer" cells, increasing antibody effectiveness against cancer.

The researchers at the Kimmel Cancer Center at Jefferson University in Philadelphia found adding such cells to anti-cancer therapies involving monoclonal antibody drugs is more effective in killing cancer cells, and perhaps someday might improve treatments.

The scientists, led by Dr. Takami Sato, showed in laboratory studies that adding such NK cells to a monoclonal antibody, Herceptin, which targets the HER2/neu protein on breast cancer cells, was more efficient at killing the cancer cells. The HER2/neu protein is expressed in approximately one-quarter of all breast cancers.

"It doesn't mean that the antibody and the NK cells will cure the cancer," Sato said, "but it shows that using an antibody that recognizes the cancer cell, along with added NK cells, can be very effective against the tumor."

The research was presented Wednesday in Los Angeles during the annual meeting of the American Association for Cancer Research.

Naturally Good: Make Like The Sailor Man

Popeye knew what he was talking about: Spinach packs a lot of punch. The green leafy vegetable is an excellent source of vitamins C and A (high concentration of beta-carotene) and folate. It is plentiful in vitamin K, manganese, magnesium, iron, calcium, potassium and vitamin B6 and is a good source of dietary fiber, copper, protein, phosphorus, zinc and vitamin E.

Spinach also offers omega-3 fatty acids, niacin and selenium. Its combination of vitamins and nutrients helps protect against osteoporosis, heart disease, colon cancer and arthritis.

Mold By-product Kills Multiple Myeloma

ROCHESTER, Minn. -- U.S. scientists have determined chaetocin, a by-product of a common wood mold, holds promise as a new anti-myeloma agent.

Mayo Clinic researchers demonstrated the by-product is more effective than currently used therapies at killing multiple myeloma cells.

"There were a number of fascinating findings," said Dr. Keith Bible, a Mayo Clinic oncologist and the study's lead investigator. "In addition to observing many favorable aspects of chaetocin, we discovered some avenues for further research into other possible anti-myeloma agents."

Multiple myeloma is an incurable bone marrow cancer that kills more than 11,000 people each year in the United States.

The research is detailed online in the journal Blood.

New Molecular Imaging Compound Pinpoints Cancer Spread in Mice

Researchers have created a new imaging compound in mice that selectively binds to certain cancer cells and glows, or fluoresces, only when processed by these cells. This cancer-specific fluorescence allowed the investigators to successfully visualize very small tumors in the peritoneum -- the tissue that lines the wall of the abdomen -- in mice with ovarian cancer. The sensitivity -- or ability to accurately detect small clusters of tumor cells -- of this approach was 92 percent. The study, conducted by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and colleagues, appears in the March 15, 2007 issue of Cancer Research. A second study** published in the April 15, 2007 issue of Cancer Research, showed even greater sensitivity with a compound designed to fluoresce while bound to the surface of cancer cells.


 

"The virtue of these studies is that other fluorescent compounds have been tested for the detection of small clusters of cancer cells that might otherwise be missed during surgery, but those have drawbacks, including being always fluorescent thereby making it difficult to distinguish tumor cells from normal tissue. These studies point to a potential solution to this problem," said NIH Director Elias A. Zerhouni, M.D.


 

"A fluorescent imaging compound that is specific for cancer cells holds great promise for the treatment of cancers, such as ovarian and pancreatic cancer, which often metastasize widely before diagnosis. In the coming years, as cancer research is increasingly based on an understanding of tumors down to a detailed molecular level, advanced imaging will be a key component of essentially every study," said NCI Director John E. Niederhuber, M.D.


 

The researchers, led by Hisataka Kobayashi, M.D., Ph.D., from NCI's Molecular Imaging Program in the Center for Cancer Research, first created a compound to be tested only in mice that consisted of the protein avidin, which binds to another protein commonly found on the surface of cancer cells that potentially can spread, or metastasize, to the peritoneum. They joined this compound to three molecules of the fluorescent compound rhodamine X. In this new compound, which they called Av-3ROX, the rhodamine X molecules are unable to fluoresce. However, when Av-3ROX is taken up by cancer cells after binding to them, it is broken down in sac-like compartments inside the cells called lysosomes. When enzymes in the lysosomes break the compound into smaller pieces, the rhodamine X is released and is able to fluoresce.


 

"Conventional imaging methods such as nuclear isotopes, MRI, or CT use contrast agents that make a signal whether they are bound or unbound to a cancer cell," said Kobayashi. "Our method will make a signal only from cancer cells. It's cancer-specific imaging."


 

When the researchers injected the 'always on' fluorescent molecule Av-0.5ROX into the peritoneum of tumor-bearing mice, fluorescence was immediately detectable and more intense than that produced by Av-3ROX immediately following its injection. However, Av-0.5ROX produced fluorescence in both tumor cells and the surrounding tissue, making it difficult to distinguish the tumor cells. In contrast, by three hours after Av-3ROX injection, the fluorescence intensity in normal tissues was less than with Av-0.5ROX , but the fluorescence intensity in tumor nodules was much higher than with Av-0.5ROX.


 

To confirm that Av-3ROX was primarily processed by tumor cells, the researchers performed a second experiment in mice, this time using cells that carried the gene for red fluorescent protein (RFP) to induce the initial tumors and peritoneal metastases. This approach allowed every metastasis to be detected using a camera and filter specific for RFP. The investigators then injected Av-3ROX into the peritoneum of the mice and captured fluorescent images of both Av-3ROX and RFP. Next, they compared the number of metastases identified using both compounds.


 

Out of 507 metastases, at least 0.8 millimeters in diameter, shown by RFP, Av-3ROX detected 465 of them, indicating a sensitivity of 92 percent. Only 2 percent of metastases identified by Av-3ROX turned out to be false positives, translating to a 98-percent tumor detection accuracy, or specificity, for this technique.


 

Although the data provide proof-of-concept for this type of molecular imaging technique, Av-3ROX cannot be used in people, because the avidin portion of the compound would cause an immune system reaction. Kobayashi and his colleagues are now working on a second-generation compound that joins the binding site of avidin -- the part that recognizes the cancer cells -- to human serum albumin. This compound "should not create a harmful immune response because it's based on a human protein," said Kobayashi.


 

In the second study**, the researchers designed a cancer cell-specific imaging compound that fluoresces while bound to a receptor on the outside of cancer cells. The imaging compound consists of two parts: a monoclonal antibody attached to more than 10 copies of a molecule called biotin, and a fluorescent molecule nAv-BDPfl, which glows approximately 10 times brighter when bound to biotin. A monoclonal antibody is a type of protein made in the laboratory that can locate and bind to substances on the surface of cancer cells.


 

The researchers designed a procedure to test the ability of this imaging compound to pinpoint small metastases in the peritoneum of mice with ovarian cancer. They found that the two-step imaging method had a sensitivity of 96 percent for metastases at least 0.8 millimeters in diameter, and a 98 percent tumor specificity. It is not yet known if this compound can be used "as is" in people.


 

Depending on the type of cellular receptor targeted in different cancers, a molecular imaging compound, once it attaches to its receptor, may be taken into the cell or remain bound to the surface. Therefore, Kobayashi and his colleagues are interested in developing different compounds that can fluoresce in either location. They believe that their approach to developing new imaging agents holds promise in optically enhancing surgical or endoscopic procedures, allowing for more complete surgical removal of metastatic disease.

Researchers Find That Childhood Sarcoma Increases Risk of Blood Clots

Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, have determined that children and young adults with a form of cancer called sarcoma are at increased risk of having a thromboembolic event (TE) in their veins. Thromboembolic events can be a blood clot in a vessel that can interfere with normal blood flow. Clots can sometimes break loose and travel through the blood stream to form new clots at locations in the body that are life-threatening. TEs are almost always treatable if detected early. Investigating the association between sarcoma and TE is important because the majority of children with sarcoma can be cured of their cancer, but the occurrence of TEs could adversely compromise this success.

The study investigators also found that pediatric patients whose cancer had spread beyond the original cancer site were more likely to develop a TE than those with localized cancer. These findings are from a study reported in the April 20, 2007 issue of the Journal of Clinical Oncology*. Researchers reviewed patient records for 122 children and young adults treated for sarcoma in the Pediatric Oncology Branch of the NCI between October 1980 and July 2002.

Cancer creates an environment that is conducive to thrombosis because of the propensity of tumor cells to promote coagulation as well the secretion of cytokines, or signaling compounds, that trigger inflammation. In addition, factors common to cancer patients, such as chemotherapy, surgery, immobilization, having a central venous access device (such as a central line), and having other diseases or conditions, all increase a person’s risk for blood clots.

The study results showed that, over the 22-year study period, 16 percent of children and young adults with sarcoma developed a TE. However, the researchers noted that this figure probably underestimates the true frequency of TEs in this pediatric patient population. Since this was a retrospective study of archival patient records, most of the original physicians may not have specifically looked for TEs, so some blood clots would have gone unrecorded. Also, TEs often are asymptomatic and early screening was less accurate. As the study observed, the rate at which TEs were detected in sarcoma patients increased from 7 percent before 1993 to 23 percent since 1993 -- an increase they attributed to improved screening techniques.

Children whose cancer had spread to other parts of the body were 2.5 times more likely to develop a TE than those whose disease was localized. The most common locations of the blood clots were in the deep veins of the legs and arms, the lungs (pulmonary embolism), and the inferior vena cava, which is the large vein that carries blood from the lower half of the body into the heart. Of the patients who developed a TE, 40 percent had no symptoms related to their blood clot. Thromboses were often detected around the same time as the cancer diagnosis.

Previous research had shown a link between cancer and TEs in adults, but data regarding TEs in adults may not be applicable to children with cancer. Children differ from adults in the types of cancer that occur, as well as in the number and types of co-morbid conditions. The researchers only looked at sarcomas (cancers of the bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue) in children, so not all pediatric cancer types were represented. Sarcomas account for 15 to 20 percent of pediatric cancers and include rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma. Approximately two-thirds of these cases can be cured.

A total of 23 TEs occurred in 19 of the 122 patients during the 22-year period of record keeping. Twenty-three percent of patients with metastatic cancer developed a TE, compared to 10 percent of patients with localized cancer, suggesting an association between tumor burden and the risk of TE.

Senior researcher Alan S. Wayne, M.D., Clinical Director of NCI’s Pediatric Oncology Branch at the Center for Cancer Research recommends, “Children and young adults with sarcoma should be closely monitored for thrombosis because these patients may not have any symptoms related to a TE and because thromboembolism is a potentially life-threatening complication that is almost always amenable to therapy.”

Decrease in Breast Cancer Rates Related to Reduction in Use of Hormone Replacement Therapy

The sharp decline in the rate of new breast cancer cases in 2003 may be related to a national decline in the use of hormone replacement therapy (HRT), according to a new report in the April 19, 2007, issue of the New England Journal of Medicine. The report used data from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (NCI), part of the National Institutes of Health.
Age-adjusted breast cancer incidence rates in women in the United States fell 6.7 percent in 2003. During this same period, prescriptions for HRT declined rapidly, following highly-publicized reports from the Women’s Health Initiative (WHI) study that showed an increased risk of breast cancer, heart disease, stroke, blood clots, and urinary incontinence among postmenopausal women who were using hormone replacement therapy that included both estrogen and progestin. The two most commonly prescribed forms of HRT in the United States, Premarin® and PremproTM, had their steepest declines starting in 2002-2003 -- from 61 million prescriptions written in 2001 to 21 million in 2004.
Led by senior investigator Donald Berry, PhD., of the University of Texas M.D. Anderson Cancer Center, Houston, Texas, the research team showed that the decrease in breast cancer incidence began in mid-2002 and leveled off after 2003. Comparing rates from 2001 and 2004 showed a decrease in annual age-adjusted incidence of 8.6 percent. The decrease occurred only in women over the age of 50 and was more evident in women with cancers that were estrogen receptor (ER) positive -- tumors that need estrogen in order to grow and multiply. The speed at which breast cancer rates declined after the WHI announcements may indicate that extremely small ER-positive breast cancers may have stopped progressing, or even regressed, after HRT was stopped.
“Breast cancer is the most frequently diagnosed cancer among women in the United States, and we have made great strides in its treatment,” said NCI Director John E. Niederhuber, M.D. “Still, we don’t know all the causes of breast cancer, and breast cancer rates had been increasing for two decades up to 2002. Finding the simple ways, such as limiting HRT use to decrease breast cancer risk, is a step forward.”
Preliminary findings of this report were presented at the 29th annual San Antonio Breast Cancer Symposium in 2006. Data from 2004, which was of great interest to those present for the meeting, were not available at that time. This report now includes the data from 2004, which show a leveling-off of breast cancer incidence from 2003 to 2004. This observation, combined with a stabilization of HRT use in 2004, further strengthens the association between breast cancer incidence and use of HRT.
Understanding the effect of cessation of HRT may be complex. Effects may vary depending on the type of HRT used and other factors specific to how the hormones affect the body. From the data in this report, it seems that the decline in breast cancer incidence that is related to a nationwide decline in use of HRT may have has run its course, and breast cancer incidence rates may stabilize or even begin to rise again. Researchers do not yet know if this reduction in HRT use will have a long-term effect on rates, or whether reduction in hormone levels simply slowed the growth of clinically detectable tumors, in which case as HRT use stabilizes, breast cancer incidence will begin to rise again.
Several other possibilities were considered to explain the sudden decrease in new breast cancer cases, including changes in reproductive factors, rates of mammography screening, environmental exposures, and changes in diet. HRT was the only risk factor that changed substantially from 2002 to 2003 and provides a possible explanation for this trend. “Recent reports have suggested a small decline in mammography use after 2000,” said Kathy Cronin, Ph.D., of the Surveillance Research Program at NCI. “Screening may play a role as well, and the contribution of mammography to the observed decline in incidence is currently being investigated.”
Because this analysis is based on population statistics, the study does not prove a link between HRT and breast cancer incidence. Only a randomized clinical trial could prove causation. When the link between breast cancer and HRT was first confirmed in the WHI, which was a randomized clinical trial, women in the study were asked to discontinue their study medications (either placebo or hormones), and were encouraged to continue undergoing annual mammography. These women are still being followed, and the WHI researchers are expected to release a follow-up report later this year about the group who received HRT (estrogen and progestin). This report will provide a much higher level of evidence about the influence of HRT (and cessation of HRT) on the incidence of breast cancer.
“The decision about use of HRT is complex,” says study researcher Christine Berg, M.D., from the National Cancer Institute. “While HRT provides relief from the symptoms of menopause, it may also increase one’s risk of breast cancer. It is important that women meet with their doctor to discuss what decision is right for them, particularly if they are at high risk for breast cancer.”
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*Ravdin M, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, Edwards BK, Berry DA. The Decrease in Breast Cancer Incidence in 2003 in the United States. NEJM. Vol. 356, No.16. April 19, 2007.
For information on NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, please go to http://seer.cancer.gov/
For more information about cancer, visit http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4 CANCER.