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2012 Pilot Grants to Focus on Smoking Cessation, Breast and Ovarian Cancers, and Gender Differences in Aging

July 08, 2012

Our Pilot Project Program grants for 2012 target some of the most highly relevant areas of women’s health today. These include smoking cessation, which is more difficult for women than men; breast and ovarian cancers, the second and fifth leading causes of cancer deaths among American women; breast ultrasound screening, which is increasingly being used as supplemental screening in women with dense breast tissue, and neurodegenerative disorders, such as Alzheimer’s disease, which are more common in women than men.

“Smoking, breast and ovarian cancers, and Alzheimer’s disease exact a huge toll on the health of women. The investigations by this year’s awardees, like all of our previously funded studies, are designed with the goal of translating new scientific findings in these important areas into real-world benefits for women,” said Dr. Carolyn M. Mazure, Director of Women’s Health Research at Yale.

Our center’s annual pilot awards enable Yale investigators to generate previously unavailable data on important areas of women’s health. These pilot results are needed for investigators to apply for and obtain larger external grants to continue their research in these areas of women’s health. Since inception in 1998, our center has awarded more than $4.4 million in these “seed” grants, and the results from our pilot studies have generated nearly $50 million in new external grants – confirmation of the value of our research findings.

The four 2012 Women’s Health Research at Yale pilot grant recipients are:

Gender-Specific Mechanisms for Understanding Smoking Addiction

Irina Esterlis, Ph.D. Assistant Professor of Psychiatry

The Surgeon General has established that smoking quit rates for women have been lower than those for men in every single year for decades. And, importantly, the most commonly used treatments to aid quitting - nicotine replacement therapies - are not as effective for women as for men. Thus, in order to improve smoking cessation therapies for women, there is a critical need to investigate whether the neurobiology of smoking in women is different from that targeted by nicotine replacement therapies that affect nicotine receptors in the brain.

By using PET neuro scanning (a technology that produces visual images of the functioning of the brain at the cellular and molecular levels), Dr. Esterlis will take the first steps in investigating whether treatments targeting different receptors - called metabotropic glutamate receptors (mGluR5) - may be a better option for helping women quit smoking. She believes these glutamate receptors are excellent candidates because evidence from animal studies suggests gender differences in the role of mGluR5 in nicotine addiction, and glutamate, a key chemical messenger across nerve cells, has been shown to be compromised in mood disorders such as depression, one of the reasons that women smoke or relapse to smoking after quitting.

Current Research:

Enhancing Treatment of BRCA-Deficient Breast and Ovarian Cancers

Peter M. Glazer, M.D., Ph.D. Professor and Chair of Therapeutic Radiology

Inherited mutations in two particular genes, BRCA1 and BRCA2, are known to increase risk for breast and ovarian cancers. In addition, many non-familial breast and ovarian cancers are associated with cell-repair defects related to mutations in these two genes. Dr. Glazer discovered that a particular antibody (a protein made by immune cells to attack disease agents such as cancer cells) can increase the vulnerability of various types of cancer cells to radiation and chemotherapy treatment. Preliminary evidence shows that this effect is greater in breast and ovarian cancers related to BRCA1 and BRCA2 gene mutations.

Dr. Glazer’s pilot study will begin moving this important antibody, called 3E10, toward clinical application for improving breast and ovarian cancer treatments. The 3E10 antibody is distinguished from all other antibodies currently in use for cancer treatment by its abilities to penetrate cells and affect cell-repair. The ultimate goal is to provide new, more effective treatments for women with breast and ovarian cancers.

The Effectiveness of Breast Ultrasound Screening: Connecticut’s Experience Can Inform the Nation

Regina J. Hooley, M.D. Assistant Professor of Diagnostic Radiology

Early detection is the best strategy to reduce breast cancer mortality. Although early detection through mammography screening can reduce breast cancer mortality, it has limited ability to detect cancers in women with dense breast tissue. Because of this limitation, other screening methods, including breast ultrasound, have also been used to detect breast cancer. In 2009, Connecticut became the first state to adopt a law requiring radiologists to inform women with dense breast tissue that they may benefit from supplemental screening with ultrasound, after mammography. Two other states have now adopted legislation similar to that in Connecticut, yet a similar law was vetoed in California, primarily due to lack of data in the rates of false positive results, and concerns regarding rising healthcare costs.

Dr. Hooley will investigate the performance of breast ultrasound in women with dense breast tissue since the Connecticut law took effect. Through her review and analysis, Dr. Hooley and colleagues can determine the usefulness of ultrasound plus mammography in detecting tumors not revealed by mammography alone. As other states and the federal government continue to consider adoption of similar laws, the outcome of this study could inform the medical community, legislators, policymakers and women worldwide about the value and cost-effectiveness of breast ultrasound screening.

Understanding the Cellular Basis of Gender Differences in Neurodegenerative Disease

Flora M. Vaccarino, M.D. Professor of Neurobiology and in the Child Study Center

Compared with men, women have a greater incidence of disorders involving degeneration of brain nerve cells such as Alzheimer’s disease. Although studies have examined the role of estrogen in these neurodegenerative diseases, little research has focused on the cellular mechanisms underlying gender differences in aging. Further, no research has examined the role of cells called astroglial cells in gender differences and aging, despite a clear role for these cells in the generation and preservation of brain nerve cells, and evidence that these astroglial cells facilitate estrogen’s role in supporting healthy cells. Astroglial cells, the most abundant cells in the brain, play roles in key areas including maintenance of the blood-brain barrier, transmission of electrical signals, and repair of nerve cells.

Dr. Vaccarino will take initial steps toward understanding the cellular mechanisms that underlie gender differences in aging, and will identify genes expressed in astroglial cells involved in aging. Gene identification may enable the targeting of particular cellular genes that control growth and play roles in determining gender differences in neurodegenerative diseases and aging. Thus, this study represents first steps at identifying new targets in developing interventions for neurodegenerative diseases, particularly those which are more common in women.

Submitted by Geraldine Mancini on October 08, 2012