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Research advances new cancer preventive strategies from myriad sources

American Association For Cancer Research (AACR) : 02 July, 2006  (Technical Article)
Promising new ways to prevent cancer emerge regularly from the laboratories of research institutions around the world. With every deposit to the scientific bank of knowledge about the human body and disease processes comes an opportunity to posit and test fresh theories. The results often suggest simple measures people can take to improve their chances of cheating cancer.
Promising new ways to prevent cancer emerge regularly from the laboratories of research institutions around the world. With every deposit to the scientific bank of knowledge about the human body and disease processes comes an opportunity to posit and test fresh theories. The results often suggest simple measures people can take to improve their chances of cheating cancer.

Among the studies presented this morning are two dealing with some of life's more common phenomena: Having babies and taking aspirin.

Two others show the possible anti-cancer benefit of compounds long- and widely used to treat other conditions.

Synthetic Peptide Shows Promise in Conveying Pregnancy-induced Protection Against Breast Cancer to All Women (Abstract #3503)

It's a benefit of childbirth generally not considered when the new arrival appears on the scene: Pregnancy seems to protect women from the onset of breast cancer later in life. The question before scientists is how.

A team of researchers at the Albany Medical College, led by Thomas T. Andersen, Ph.D., created a peptide with the same chemical characteristics as alpha-fetoprotein, a pregnancy-associated molecule they believe is among those responsible for reducing the risk of breast cancer among mothers. The synthetic peptide AFPep (cyclic 9-amino acid), administered by mouth, stopped the growth of human breast cancer cells implanted in one group of mice, and decreased the incidence and number of breast cancer tumors in a second cohort of mice that had been injected with a carcinogenic chemical.

When combined with the chemotherapy drug tamoxifen, AFPep reduced the number of tumor-bearing rats by 77 percent. AFPep alone yielded a 23 percent decrease in the cancer rate.

'We are heartened by our results, which found that oral administration of AFPep is safe and effective for the treatment and prevention of breast cancer in these animal models,' said Andersen. 'We believe we are making strides to help protect all women from developing breast cancer, and hopefully extend and save the lives of those who do.'

Naturally occurring alpha-fetoprotein is produced by the fetus and is apparent in the mother's blood at around the 12th week of gestation. AFP levels in women decrease soon after they give birth.

In the Albany study, the female mice with chemically induced carcinogenesis were given a one-time dose of either AFPep or tamoxifen, some orally and some by injection. The animals were palpated weekly for 100 days to assess the number of mice with tumors, and the number and size of tumors within each mouse. Mice with human breast cancer tissue were used to test the therapeutic value of AFPep, with 30 days considered the end point.

Even at very high doses, AFPep showed no signs of toxicity.

NSAIDS and Breast Cancer: Risk Varies Between Baby Aspirin, Regular-strength Aspirin and Ibuprofen (Abstract #3733)

It has been many years since baby aspirin supplanted the apple as the recommended daily dose for doctor avoidance. Millions of people take this most common of the non-steroidal anti-inflammatory drugs to help prevent heart attack and stroke. Now, studies suggest women who do so may also be minimizing their breast cancer risk.

Scientists at the Fred Hutchinson Cancer Research Center in Seattle compared the incidence of invasive breast cancer with the amount and frequency of NSAID use among participants in its Vitamins and Lifestyle Study. They found that women who took an average of four or more baby aspirins a week over the previous ten years experienced a 34 percent decreased risk of breast cancer compared to those who did not use NSAIDs.

Conversely, study participants who reported the same cumulative dose of regular or extra strength aspirin were at an increased risk for the disease. Regular-strength aspirin contains 325 milligrams of the active ingredient acetylsalicylic acid, versus 81 milligrams in low-dose or baby aspirin.

Ibuprofen and other, non-aspirin NSAIDs showed no association with breast cancer, at any dose.

'Based on the preliminary results of our study and previous studies, there is a suggestion that breast cancer risk may vary depending on NSAID type and/or dose,' said Ann Ready, N.D., who was lead investigator on the Hutchinson study. She added, 'However, due to the inconsistency of the evidence at this point, it would be premature to recommend NSAIDs for the prevention of breast cancer until further studies have been conducted.'

The VITAL Study is a prospective cohort study of the associations between lifestyle factors and supplement use with cancer risk in Washington. A total of 77,738 men and women in the western part of the state, aged 5076 years, entered the study between 2000 and 2002 by completing a detailed questionnaire on supplement use, diet and other cancer risk factors. Seventy percent also provided DNA self-collected DNA samples.

For the investigation of a relationship between NSAID use and breast cancer, the Hutchinson researchers reviewed data for 35,368 women enrolled in the VITAL Study. Participants completed a baseline questionnaire assessing their breast cancer risk factors, lifestyle factors and NSAID use. Breast cancer incidence among these women was monitored through the Western Washington Surveillance Epidemiology and End Results (SEER) cancer registry. The amount of NSAIDs used by the women was determined from their reports of the average number of days per week they had taken one of the drugs during the preceding ten years.

Vitamin D Compounds Show Promise for Prostate Cancer Prevention (Abstract #2315)

Researchers from Roswell Park Cancer Institute in Buffalo, N.Y., found that the active metabolite of vitamin D, calcitriol, and the vitamin D analogs, QW-1624-F2-2 and paricalcitol, are promising chemopreventive agents against prostate cancer.

Calcitriol is used clinically to treat a variety of disorders, including recently, in clinical trials for established cancer. A major obstacle to the clinical use of calcitriol is dose-limiting hypercalcemia, a condition characterized by abnormally high concentration of calcium in the blood. QW, developed at Johns Hopkins University, and paricalcitol (Zemplar) have been shown to reduce the levels of the hormones which regulate the metabolism of calcium and phosphorus in the body.

In vitro, researchers demonstrated that the three drugs inhibit cell growth, inhibit DNA synthesis, and promote cell cycle arrest. Additionally, the vitamin D compounds regulated several proteins that affect tumor growth.

The researchers then studied the effects of calcitriol and QW on the prevention of androgen-dependent prostate cancer in the transgenic adenocarcinoma of mouse prostate model, which develops prostate cancer as the mice age. Both calcitriol and QW slowed the progression of prostate cancer in intact TRAMP mice after 14 weeks of treatment as indicated by decreased reproductive tract and prostate weight. In addition, chronic treatment of mice with calcitriol markedly reduced tumor burden, although side effects were seen in some mice.

The effect of calcitriol and QW on hormone refractory prostate cancer was also investigated, using castrated TRAMP mice. Results showed that vitamin D had no effect on disease progression in castrated mice as measured by reproductive tract and prostate weight.

'Our pre-clinical data using the TRAMP mouse model, which mimics human prostate cancer, suggests that calcitriol and QW-1624-F2-2 are promising for prevention of androgen-dependent prostate cancer progression. Further studies are under way in our laboratory to better understand how these agents prevent prostate cancer,' said Adebusola Alagbala of Roswell Park Cancer Institute and lead author of the study. The studies, funded by the National Institutes of Health, were conducted in the laboratory of Dr. Barbara A. Foster at Roswell Park Cancer Institute.
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