Chao Family Comprehensive Cancer Center
Message from Dr. Frank L. Meyskens, Director

CANCER
RESEARCH                                  Progress Brings Hope                                                  Fall 2009

Welcome Message from the Director

Welcome to the Fall 2009 version of Cancer Research, a newsletter that puts a spotlight on some of the best and brightest from among the members of the Chao Family Comprehensive Cancer Center. This is one of the few mechanisms we have to show off, and we want to take advantage of this opportunity to share some of the great things that are going on at the Cancer Center.

The next few editions will each feature one of our Shared Resources, or Core Facilities. These each focus on providing clinical, technical, laboratory or specialty support to Cancer Center members. Also highlighted are major grants awarded to our members, and high profile presentations and publications. This is a world-class Cancer Center and we are making an impact on cancer research, education and treatment in diverse ways.

Shared Resource Highlight: In Vivo Functional Onco-Imaging

Website: http://www.healthaffairs.uci.edu/cancer/IVFOI.html
Contacts: Director: Gultekin Gulsen, 949.824.6001, ggulsen@uci.edu
Financial Manager: Diane Huebner, 949.824.6001, dkhuebne@uc.edu

The In Vivo Functional Onco-Imaging Shared Resource provides clinical, epidemiologic, and basic science investigators with expertise, imaging instrumentation, and image analysis techniques. Imaging capabilities include three magnetic resonance imaging scanners, and a combined magnetic resonance imaging-diffuse optical tomography system. This hybrid system for small animal imaging was developed here at the University of California, Irvine. A two-dimensional fluorescence plus X-ray system is available, and a prototype system has been built that integrates three-dimensional fluorescence and bioluminescence tomography with micro-scale computed tomography imaging.

Optical imaging can provide in vivo hemoglobin and oxygen saturation imaging for assessment of angiogenesis and metabolism. Furthermore, it can monitor enhancement kinetics of an optical contrast agent. Currently, the systems are being upgraded to add fluorescence imaging capability. And, a new system is being developed for clinical breast imaging studies, which would be one of only five such systems in the country. The Shared Resource has a database of more than 900 breast magnetic resonance imaging scans!

Congratulations to the following grant awardees

Dr. Greg Weiss, co-leader of the Chemical and Structural Biology Program, was awarded $500,000 from the National Institutes of Health for “Purchase of a MALDTI-TOF Mass Spectrometer”. The mass spectrometer and associated equipment will support analytical chemistry research in several cancer-focused projects. In particular, Dr. Weiss will continue with his studies of cell regulation, control of cell activation, cell death and restoration of aging proteins, and development of synthetic antibodies using the new mass spectrometer.
Dr. Sabee Molloi, a member of the Onco-Imaging and Spectroscopy Program, was awarded $634,777 from the National Cancer Institute, for “Quantification of Breast Density Using Dual Energy Mammography”. His studies focus on development of quantitative techniques using diagnostic medical X-ray imaging technology. Breast density is an important yet underutilized risk factor in the development of breast cancer. Subjective visual assessment alone is inadequate to quantify breast density. The goal of this project is to develop a method to objectively and quantitatively measure the density of a woman’s breast using dual energy mammography. The method provides a volumetric measure of breast density and it has the potential to be incorporated into routine screening mammography.

Dr. Eva Lee, co-Leader of the Breast Cancer Translational Working Group, was awarded $634,950 from the National Cancer Institute to study “BRCA1 and progesterone receptors in breast cancer”. BRCA1 plays key roles in DNA damage response and cell cycle checkpoint control, important for tumor suppression. Dr. Lee has established a mouse model in which specific ablation of the BRCA1 and p53 genes occurs in mammary epithelial cells, leading to tumors that are similar to human breast cancers. Treatment of these mice with anti-progesterone significantly delays or prevents mammary tumorigenesis. The first aim of this project is to demonstrate the efficacy of a promising new anti-progesterone drug in preventing mammary carcinogenesis and in blocking tumor recurrence after chemotherapeutic treatment in the mouse model. The second aspect is to understand the detailed mechanism of how BRCA1 modulates progesterone receptor expression and cell proliferation. The long-term goals are to understand how mutations in BRCA1 cause mammary epithelial cells to be more sensitive to progesterone exposure, and to determine if development of breast cancer in women at high risk can be prevented or delayed with anti-progesterone therapeutics.

Recent high profile publication

Dr. Bradley Monk, co-leader of the Clinical Trials Protocol Review and Monitoring Committee, is lead author on a recent publication appearing in the Journal of Clinical Oncology (‘Phase III Trial of Four Cisplatin-Containing Doublet Combinations in Stage IVB, Recurrent, or Persistent Cervical Carcinoma: A Gynecologic Oncology Group Study’). Cervical cancer is preventable and generally curable if detected early. It affects over half a million women worldwide, and causes 4,000 deaths annually in the United States. This study represents a significant step forward in defining optimal therapy for advanced and recurrent cervical cancer. Dr. Monk and collaborators compared four cisplatin-based chemotherapy treatments (cisplatin plus paclitaxel, vinorelbine, gemcitabine or topotecan) in women with advanced or recurrent cervical cancer. The Phase III trial recruited 513 patients but was stopped at interim analysis, which showed no significant differences in terms of overall survival. However, the trends in relative risk, progression-free survival and overall survival favor the cisplatin-paclitaxel combination. The conclusion is that, although none of the tested combinations showed superiority, differences in chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing therapy. The analysis of the Quality of Life results from the study will be published separately. With all of the combinations, the relatively short overall survival remains disappointing, and the need to continue to study targeted and biologic therapies is obvious.

Thanks to outgoing Cancer Center Leaders

There have been several recent changes in our Cancer Center leadership. Tremendous thanks are owed to the following outgoing Senior Leaders and Program, Shared Resource and Translational Working Group Leaders for their extra efforts and leadership in these important positions:
Dr. John Butler, Deputy Director for Clinical Affairs
Dr. J. L. Redpath, Associate Director, Division of Education & Training AND Carcinogenesis Research Program co-Leader
Dr. Patrick Farmer and Dr. Alexander McPherson, Structural Molecular Biology Research Program co-Leaders
Dr. Orhan Nalcioglu, Onco-Imaging & Spectroscopy Research Program co-Leader
Dr. John Fruehauf and Dr. Michael Lilly, Translational Oncology Research Program co-Leaders
Dr. Susan Neuhausen, Population Sciences Research Program co-Leader
Dr. Arthur Lander, Transgenic Mouse Facility (TMF) Shared Resource Director
Dr. Lydia Su, In-Vivo Functional Onco-Imaging (IVFOI) Shared Resource Director
Dr. Randall Holcombe, GI Translational Working Group co-Leader

Thanks to incoming Cancer Center Leaders

Thanks as well to the incoming leaders listed below. Congratulations and good luck!
Dr. Hans-Ulrich Bernard, Carcinogenesis Research Program co-Leader
Dr. Tom Poulos, and Dr.Gregory Weiss, Chemical & Structural Biology Research Program co-Leaders
Dr. Lydia Su, Onco-Imaging & Spectroscopy Research Program co-Leader
Dr. Gultekin Gulsen, In-Vivo Functional Onco-Imaging (IVFOI) Shared Resource Director
Dr. Grant MacGregor, Transgenic Mouse Facility (TMF) Shared Resource Director
Dr. Timothy Morgan, GI Translational Working Group co-Leader

Comments and suggestions for future news items to Randy Berg (rberg@uci.edu).