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The Better Than Ever (BTE) training program is a fitness training and fundraising program designed to help make walking, running or biking a regular part life. The program also raises funds to support investigator-initiated clinical trials.
For 2013, the BTE research grants will supplement the NCI Cancer Center Support Grant pilot program. The grant review committee, and all of us at the University of Arizona Cancer Center are very grateful for the support of our BTE participants. This year's awards bring the 13-year grant distribution total to more than $1.8 million.
This year's funding goes to Guang Yao, PhD and Wenxin Zheng, MD who will study "Molecular Mechanism of Tubal Secretory Cell Expansion and Biomarkers for Ovarian Cancer Early Detection."
Women's pelvic serous cancer (PSC) constitutes serous carcinomas of the ovary, fallopian tube and peritoneum. It is now known that the majority of women's PSCs are derived from fallopian tubal epithelial cells. Such understanding has gradually shifted the research focus from the ovary or the ovarian surface epithelia to the tubal epithelial cells. Two different types of epithelial cells are present in tubal mucosa: one with cilia and the other one without. The overgrowth of the tubal cells without cilia serves as a latent precancer or a common pathway prior to the development into ovarian serous cancer.
The combined efforts from Drs. Yao and Zheng are expected to uncover the mystery of the growth advantages of the cells without cilia in the fallopian tubes of PSC patients. Such understanding will help us to develop a novel way of ovarian cancer early detection and prevention.
About the researchers:
A cell biologist whose expertise is cancer pathway and analysis at the molecular and system level.
A physician scientist and an internationally recognized gynecologic pathologist who has contributed multiple original research works in the field of gynecologic oncology and gynecologic pathology.
Mark D. “Marty” Pagel, PhD: Measuring tumor acidity in ovarian cancer patients using non-invasive CEST MRI
This study looks into a non-invasive method that uses magnetic resonance imaging to measure the acid content in tumors during pre-clinical studies. In this study, Dr. Pagel and his team of researchers aims to demonstrate that their clinical imaging method can diagnose tumors with high-acid and low-acid content in patients with ovarian cancer. Determining if a patient's tumor has a high acid content can help the patient and physician to select the best chemotherapy, leading to "personalized medicine" for each individual patient.
Kimberly McDermott, PhD: Dr. McDermott: Are primary cilia a predictive marker for hedgehog drug therapeutic efficacy?
The objective of this study is to determine if the presence of primary cilia on Basal Cell Carcinoma is predictive of responsiveness to treatment with an SMO Inhibitor called GDC-0449. This drug is currently in clinical trials for a number of different cancers including Basal Cell Carcinoma and if our study is successful the use of primary cilia as a marker to predict drug efficacy would allow physicians to target treatment specifically to patients that are most likely to respond positively to the drug.
Amanda Baker, PharmD, PhD
Investigating hypoxia in ovarian cancer using Hypoxyprobe(™)-1, a diagnostic biomarker for guiding hypoxia-targeted therapies
Hypoxia, a deficiency in the amount of oxygen reaching the tissues, is a common feature of many solid tumor types and is strongly associated with aggressive disease and chemotherapy and radiation resistance. The incidence of hypoxia in ovarian tumors has not been widely investigated.
In tumor tissues obtained from patients participating in this study, the investigator will assess the percentage of ovarian tumor cells that are growing in hypoxic conditions by using an investigational diagnostic chemical probe called Hypoxyprobe(™)-1. These results will be compared with a molecular biomarker of hypoxia called HIF-1α. The information gained from this new BTE study will provide evidence to guide the clinical investigation of hypoxia-directed therapies in ovarian cancer. The tumor tissue obtained as part of this study will also be a valuable resource for investigating how hypoxia contributes to traditional chemotherapy resistance.
In 2010, the five grants involved testing novel therapies, understanding biological processes, developing innovative diagnostic tools and using gene expression signatures to predict treatment response. The diseases of focus are ovarian cancer, cervical cancer and breast cancer.
This study will explore the therapeutic potential of a novel ovarian cancer treatment that exploits the secretion by tumor cells of a particular soluble molecule. The molecule, known as vascular endothelial cell growth factor (VEGF), plays an important role in the formation of the blood vessels that support tumor growth. Using genetic engineering techniques, we have generated an artificial receptor that causes cells to die upon binding of VEGF. A specially modified non-infectious virus will be used to introduce and express this receptor in ovarian tumors and the effect on tumor survival will be determined. Particular emphasis will be placed on ensuring that the approach is safe and that various normal cell types are not harmed as a result of treatment. Such studies are essential prior to the initiation of planned clinical trials.
Currently there is no way to detect early stage ovarian cancer and most cases are diagnosed at advanced stages when treatment options are limited and prognosis is poor. This study aims to develop a small and flexible endoscope that provides real-time cellular-level images of tissues inside the abdominal cavity. The device will image early-stage ovarian cancer on the surface of the ovary as well as inside the fallopian tube, where many ovarian cancers are thought to arise. Such a device would be used during a laparoscopic procedure to diagnose early-stage ovarian cancer and may provide an effective way to screen women at high risk of developing the disease.
Samuel K. Campos, PhD
Unraveling the Inhibitory Mechanisms of Bacitracin on HPV16 Infection
Human papillomavirus (HPV) infections are associated with more than 99 percent of all cervical cancers and therefore represent a significant cause of worldwide morbidity and mortality among women, especially in developing countries. Despite being the causative agents of cervical cancers, the molecular mechanisms involved in host cell invasion are poorly understood for oncogenic HPVs. We have observed that Bacitracin, an FDA approved antibiotic commonly available in over-the-counter ointments, blocks HPV infection perhaps by inhibiting a class of enzymes that may play a role in HPV-host cell invasion. Understanding the inhibitory mechanisms of this compound will expand our knowledge of HPV-host cell interactions and identify potential targets for the development of HPV antivirals and prophylactics.
Julie E. Lang, MD, FACS
Isolation and Gene Expression Profiling of Circulating Tumor Cells in Breast Cancer
Circulating tumor cells (CTCs) are rare cancer cells shed into the blood stream of breast cancer patients. In a prospective clinical study enrolling 120 newly diagnosed breast cancer patients, we will obtain a tube of blood and a small piece of tumor tissue from surgery. The purpose of our study is to determine if CTCs are cancer stem cells. We will use a novel technique we developed that permits isolating rare CTCs and studying their molecular biology. We will also study if a CTC gene expression signature may be defined for patients with locally advanced breast cancer that predicts for response to treatment. As CTCs may explain why disease recurs despite aggressive treatment of breast cancer, this novel approach has potential to determine if studying CTCs can help guide physicians in making treatment decisions for breast cancer patients.
Russell S. Witte, PhD
Spectroscopic Photoacoustic Imaging of Molecular Expression in Metastatic Breast Cancer
Our long-term goal is to develop novel imaging tools and complementary contrast agents to noninvasively monitor the tumor microenvironment and improve treatment strategies for breast cancer patients. Because detection of just one cell surface receptor is generally an incomplete diagnosis of metastatic breast cancer, we will develop a photoacoustic imaging system and targeted contrast agents to simultaneously map expression of multiple surface receptors. This will dramatically enhance our existing pre-clinical imaging platform already capable of tracking a tumor’s growth and vascular network in three dimensions. Photoacoustic imaging is a safe, highly sensitive real-time technology that potentially provides powerful diagnostic and theranostic capability during routine ultrasound breast exams.