Using a combination of a targeted cancer-fighting agent called DFMO and a low dose of an anti-inflammatory drug, UC Irvine researchers have reduced the risk of reoccurring colorectal polyps, an early sign of colon cancer, by as much as 95 percent with fewer toxic side effects.

The study marks a breakthrough in the effort to combat colon cancer, the third leading cause of cancer in men and fourth in women, according to Dr. Frank L. Meyskens Jr., the Daniel G. Aldrich Chair at UC Irvine and director of its Chao Family Comprehensive Cancer Center.

“There is a great hope that we will be able to prevent colon cancer effectively using this method,” said Meyskens, who led the clinical trial effort to test this drug combination. He presented his findings at the American Association for Cancer Research annual meeting in San Diego.

In earlier studies, Meyskens had established a safe and well-tolerated dose of DFMO (difluoromethylornithine) that was 1/50 of what would typically be used to treat advanced cancers. By combining this reduced dose of DFMO with a non-steroidal, anti-inflammatory drug called sulindac, researchers believed they could improve treatment and decrease the reoccurrence of potentially cancerous colon polyps with reduced toxic side effects.

DFMO is the basis of the drug eflornithine, which was initially developed as a cancer medication and is no longer manufactured commercially for that purpose. Sulindac is sold commercially as Clinoril and is used to treat arthritis and other inflammatory conditions.

The researchers enrolled 375 patients who had a history of at least one colorectal polyp, or adenoma, within the previous five years. Patients were randomly assigned to either a combination of 500 mg of daily DFMO and 150 mg of sulindac or placebos. Patients were followed for three years, and adenoma recurrence was measured by colonoscopy. Among the results:

* Overall risk for recurrent adenoma: 41.1 percent in placebo group to 12.3 percent in treated patients, a 79 percent reduction

* Risk for recurrent advanced adenomas: 8.5 percent in placebo group to 0.7 in treated patients, a 92 percent reduction

* Risk for adenomas larger than one centimeter: 7 percent in the placebo group to 0.7 percent in the treatment group, a 90 percent reduction.

* Rate of repeating adenoma among patients who had previously had more than one adenoma: 13.2 percent in the placebo group to with 0.7 percent in the treatment group, a 95 percent reduction.

The rate of reduction was so pronounced that the trial’s independent data and safety monitoring board stopped the trial early.

An analysis of side effects and toxicity found no difference between the treatment and placebo groups. There also was no difference in side effects requiring an overnight hospitalization, gastrointestinal side effects or cardiovascular side effects between the two groups.

“What we have shown here is that there is value in testing these agents at lower doses and in combination to determine if we can achieve the same effect without the damaging side effects,” Meyskens said.

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As our population ages and senior citizens become a larger demographic, cancer researchers are focusing on the links between aging and cancer. Studies presented at the 2008 Annual Meeting of the American Association for Cancer Research, April 12 – 16, highlight the biological aspects of aging that are key to greater risk and poorer prognosis, and surgical outcomes.

Surgical resection and survival in octogenarians and younger age cohorts of patients diagnosed with non-small cell lung cancer:

Although fewer of them undergo surgery, lung cancer patients in their 80s fare equally well following surgery as their younger counterparts, researchers report. The findings offer doctors potentially valuable guidance in treatment options for elderly patients, according to researchers.

A research team from the Hoag Cancer Center in Newport Beach, California, observed 1,293 patients with lung cancer, 482 of whom underwent surgical treatment. The oldest patients were more likely to be male. Older patients were also more likely to have localized disease.

Overall, the rate of surgery did not differ by age group. However, when primary lung cancer was considered separately, only 31.7 percent of patients older than 80 underwent surgery for their primary lung cancer compared with 38.5 percent of patients younger than 80. For patients with non-small cell lung cancer, the rate of surgery was 64 percent for those older than 80 and 83 percent for those younger than 80. For patients with regionally advanced disease, the rate of surgery for patients age 80 or older was 35 percent compared with 49 percent for those younger than 80 years old.

The five-year survival rate following surgery was 62 percent for those patients older than 80 compared with 53 percent for those aged 70 to 79 years. Among patients age 60 to 69 years and 50 to 59 years, the survival rate was 63 percent. For the youngest patients, those younger than 50, the survival rate was 79 percent.

“Although a smaller proportion of patients over the age of 80 underwent this type of surgery, their survival rate was comparable to the younger age groups,” said lead author Robert O. Dillman, M.D., medical director of the Hoag Cancer Center in Newport Beach, California.

Elevated interleukin-12 is a plasma marker of poor prognosis in stage III melanoma patients:

New research has established that elevated blood levels of interleukin-12, which rise as we age, independently predicts poor prognosis in patients with melanoma.

Interleukin-12 is a biological therapeutic agent that has been shown to act on the immune system and increase the body’s ability to fight disease. It has also previously been shown to interfere with blood flow to the tumors

However, the current study suggests that elevated interleukin-12 may play a role in poor prognosis for melanoma.

“This marker tends to increase with age, which could explain the link between age and poorer prognosis of this type of skin cancer,” said lead author Yun S. Chun, M.D., a surgical oncology fellow at the University of Texas M. D. Anderson Cancer Center.

Researchers measured blood levels of interleukin-12 in 658 patients. Of these patients, 445 had early stage disease, 150 had mid-stage disease and 63 had late stage disease.

As they predicted, Chun and colleagues found that blood levels of interleukin-12 rose with age. Among patients younger than 40, the average level of interleukin-12 was 75 pg/ml, those aged 40 to 59 had a average level of 84 pg/ml, those from 60 to 79 years had a level of 96 pg/ml and patients older than 80 had an average level of 112 pg/ml.

When researchers estimated risk factors for mortality among patients with melanoma, older age by itself did not predict risk. However, late stage disease and an elevated level of interleukin-12 did predict mortality. Specifically, for patients with late stage disease and an interleukin-12 level above 150 pg/ml, the risk of mortality was four times higher than that for patients with levels of interleukin-12 that were below 150 pg/ml.

“Among patients with melanoma, it is possible that elevated interleukin-12 may be a marker of a tumor promoting, rather than a tumor inhibiting, response,” Chun said.

Aging and DNA methylation in Alu and LINE-1 repeated elements:

An age-related decrease in DNA methylation, the process whereby genes are shut off and chromosomes packed up in complex strictures, could potentially lead to cancer development, according to researchers.

When a person does not have a proper rate of DNA methylation, chromosomes and DNA sequences become unstable, and therefore are more likely to contribute to cancer.

Approximately 55 percent of the human genome consists of repetitive elements, including approximately 500,000 long interspersed nucleotide elements (LINE) and 1.5 million repetitive elements of the Alu DNA sequences. Typically, these sequences undergo heavy methylation.

Previous human studies have linked a lack of methylation among LINE and Alu repetitive elements with disease. However, whether the unsteadiness of these elements is unrestrained with age had not yet been established.

For the current study, researchers from the Center of Molecular and Genetic Epidemiology at the University of Milan in Italy, in collaboration with investigators at the Harvard School of Public Health, Boston, MAmeasured DNA levels in 693 patients. Patients gave up to three blood samples, taken approximately three years apart from each other.

Overall, the older a patient grew, the less likely these elements were to methylate. Specifically, researchers found a 0.016 percent decrease for LINE-1 elements and a 0.015 percent decrease for Alu repetitive elements for each year of increased age.

“Such age-related decrease in methylation may increase the risk of mutational events potentially leading to cancer,” said lead author Laura Cantone, a researcher at the University of Milan.

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Millions of post-menopausal women use hormone replacement therapy (HRT) as a method to reduce symptoms associated with menopause. In a recent University of Missouri study, researchers found that one of the hormones used in HRT, a synthetic progestin, could be a major factor in promoting breast cancer. At the same time, the researchers have compelling evidence that using an antibody that prevents new blood vessel formation in tumors, or a small molecular drug, known as PRIMA, with similar properties as the antibody may be effective in treating or preventing the negative effects of progestin.

In a study published in the journal, Cancer Research, MU scientist Salman Hyder and his research team found that exposing tumor cells to progestin caused an increase in a growth factor that is involved in the formation of new blood vessels in tumors. Increasing the blood supply allows the tumors to expand as the availability of nourishment increases. However, when they used an antibody that inhibits the growth factor, the tumor shrank. Hyder’s team found similar results using PRIMA, which re-activated a protein known as p53. When p53 was activated within tumor cells, the number of breast cancer cells reduced significantly.

“As women age, many develop tiny lesions in their breasts,” said Hyder, professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center. “The majority of the time, these lesions never expand. We think this might be due to a specific protein, p53, that, under normal circumstances, prevents tumor cells from living. We found in our study that when the protein is active, it reduces the number of breast cancer cells in the body by inhibiting the growth factor that supplies blood vessels to the tumor. However, when the cells of these lesions are exposed to progestin in a body that does not have an active p53 protein, we found that the cells might start expanding and turn into tumors.”

The synthetic progestin Hyder’s team studied is known as medroxyprogesterone acetate (MPA), which is commonly used in HRT. Using an animal model, Hyder introduced MPA to the animals that were carrying human breast cancer cells. When the breast cancer cells were exposed to MPA, they began growing at an accelerated rate. Later, when the research team exposed the cells to the antibody known as 2C3, or PRIMA – both of which block formation of new blood vessels in tumors – the tumor cells failed to grow and spread in response to the MPA.

“Since MPA is a synthetic hormone, it stays in the body longer,” Hyder said. “Unfortunately, while the drug is used to protect the uterus from the harmful effects of estrogens in HRT formulations, it is hurting the breast.”

The Women’s Health Initiative estimated a 26 percent jump in the number of breast cancer cases among women ingesting estrogen and progestin. Hyder believes that a large number of these women might also have a p53 protein that is not active and, therefore, not able to inhibit MPA-induced growth factor that helps to proliferate the tumor cells. Hyder cautioned that these studies are at an early stage and a lot of work remains to link progestin use firmly with progression of breast cancers in women.

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The world’s top laser experts will gather in Kissimmee, FL, to share innovations in lasers and emerging technologies at the 28th Annual Scientific Conference of the American Society for Laser Medicine and Surgery (ASLMS). “LASER 2008” will be held on April 2-6, 2008, at the Gaylord PalmsTM Resort and Convention Center. Headlining the scientific program are acknowledged leaders in the field who will unveil the latest research developments and clinical studies in laser medicine, as well as present promising devices poised to enhance disease detection and management.

The ASLMS conference is traditionally regarded as the premier forum for the introduction of the newest breakthroughs in laser diagnostics and technology. Accordingly, some of the research and techniques presented at the meeting are only in the early stages of development. In addition to nearly 2,000 laser specialists in aesthetic medicine, dermatology, ophthalmology, oncology, urology, gynecology and dentistry, about 160 industry exhibitors will be on hand to showcase their latest products.

Scientific Highlights

This year’s “hot topics” include the following featured presentations:

* Groundbreaking Laser Research Aims to Get to the Root of Acne – Early research findings on the use of a tunable free electron laser that selectively targets the chemical bond structures of acne sebum will be presented. Until now, the current laser and light sources targeting acne only have had a secondary effect on sebaceous glands. The paper was named the ASLMS “Best Overall Basic Science Award” for the conference.
* Promising Research Uses Laser-Activated Gold Nanoparticles to Detect Breast Cancer Cells – Data from laboratory studies of a novel photoacoustic system that combines laser energy and nanotechnology to detect and quantify circulating breast cancer cells will be presented. Currently based on in vitro testing of human blood, this new technology could one day lead to better therapies for patients by fighting cancer at the single cell level, before cancer cells turn into tumors.
* Laser Eye Scanning Device for Detecting Alzheimer’s Disease Could Lead to Early Diagnosis, Better Treatment Outcomes for Patients – Promising new research will discuss a non-invasive laser eye scanning technology that combines laser-induced scatter and fluorescence measurements to detect the presence of a specific protein known to accumulate in the brain and eyes of Alzheimer’s patients. This ocular diagnostic tool is being tested in vitro, with plans for clinical trials to begin in the next 12 months.
* The Skinny on Non-Invasive Fat Reduction – A new concept of using cold to destroy fat cells based on animal experiments will be introduced. Leading researchers in fat removal, body contouring and cellulite reduction will present key insights on how a better scientific understanding of the biology and physiology of fat can lead to improved clinical treatments in the future.
* Innovations in Laser Hair Removal Expand Patient Base, Improve Results and Offer Gentler Treatments – Ongoing advances in laser hair removal technology have expanded the patient base, enhanced patient safety and improved clinical efficacy of this popular procedure. New approaches for reducing pain, safely treating darker skin patients who are taking a popular acne medication, and using a shorter pulsed laser for hair removal will be addressed.

Keynote Speaker

This year’s keynote speaker is laser pioneer R. Rox Anderson, MD, professor at Harvard Medical School, adjunct professor at MIT, and director of the Wellman Center for Photomedicine at Massachusetts General Hospital in Boston. Dr. Anderson’s lecture entitled “Innovation, Disruption and Suffering from Success” will be delivered on Saturday, April 5th.

Awards and Achievements

The ASLMS 2008 Leon Goldman Memorial Award will be bestowed to ASLMS Past-President Jerome M. Garden, MD, of Northwestern University Medical School in Chicago, IL, for his excellence in performing clinical laser research, maintaining a high standard of patient care and educating others in medical laser applications.

Jeffrey S. Dover, MD, of SkinCare Physicians in Chestnut Hill, MA, is this year’s recipient of the Ellet H. Drake Lectureship Award for his contributions to laser procedures and products, the scientific literature and his excellence in teaching.

The 2008 Nursing/Allied Health Excellence Award will be presented to Sharon K. Olson, RN, CMLSO, of Olympic Dermatology & Laser Clinic of Olympia, WA, in recognition of her exceptional nursing/allied health contributions to ASLMS and the advancement of joint practice in laser medicine and surgery.

Richard E. Fitzpatrick, MD, of La Jolla Cosmetic Surgery Centre in La Jolla, CA, will receive the 2008 Caroline and William Mark Memorial Award for outstanding contributions to laser technology.

The ASLMS is pleased to announce a new award this year – the Dr. Horace Furumoto Innovations Award, created to memorialize and honor Dr. Furumoto’s genius and leadership in the development of laser technology. Dieter Manstein, MD, of the Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School of Boston is the recipient of this year’s inaugural award for demonstrating a potential for contributing to the education and creativity required to expand the development of lasers in health care.

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