Nevada Cancer Institute

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$966,000.00 (Est.) for: Calendar Year 2007
Percent of funding associated with the use of human subjects: 100

Information on Use of Human Subjects:

This project does not involve the use of multiple protocols/subprojects.

Identifier or number: NVCI005s

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Nevada Cancer Institute
Most recent approval: 02/05/07
IRB approval number: 109650

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 800
Reporting period for number of human subjects: Fiscal Year 2007

Type(s) of Human Subjects Involvement:

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using bodily materials collected specifically for this project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

PURPOSE:

The overall goal of these studies is to develop biomarkers for the detection and characterization of specific cancers.

The studies in this project have the following aims:

1) To establish a specimen bank for testing new cancer biomarker assays and a bank of normal controls.
2) To characterize and isolate circulating tumor cells.
3) To test a specific subset of combination of antibodies to detect ovarian cancer.

OBJECTIVES:

To develop biomarkers that can be used for detection or prognostication for specific cancers.

METHODOLOGY:

Specimen banks of serum, plasma, DNA, and urine have been obtained and frozen. Each patient enrolled for treatment at Nevada Cancer Institute is asked to consent to having specimens stored. The appropriate protocol and consents were obtained. IRB approval was granted. Aliquots of the serum and plasma have been processed and stored at -80°. The specimens are linked to the electronic medical record. Control specimens from subjects without a history of cancer have been obtained and are in an unlinked specimen bank. These are consented under a separate IRB approved protocol.

Subsets of the repository have been used to study the coagulation parameters in plasma from patients with prostate cancer. The D-dimers, the prothrombin fragment F1-2, and the presence of phospholipid vesicles capable of supporting coagulation have been assessed.

We are presently analyzing these serum samples from prostate and breast cancer patients for the presence of stem cell markers and the RNA for the markers. Two of the markers we are assessing are SALL4 and BMI-1.

The blood samples from consented patients have been used to measure circulating tumor cells (CTC) in 150 prostate cancer patients. We are correlating these numbers with the classical serum markers as well as the clinical course.

We have studied the binding of fluorescent labeled folate to prostate cancer cells. The labeling may be important in determining whether folate conjugate labeled to chemotherapeutic agents or other toxic agents can be used to target tumor tissue. Aliquots of the blood have been placed into cell cultures in an effort to establish prostate cancer cell lines for further study.

We are in the process of developing methods to isolate CTC in order to perform detailed nucleic acid and antigenic analysis. We have acquired instrumentation for rapid image detection of cells labeled with fluorescent dyes and antibodies on slides, laser capture to isolate the labeled cells, and a rapid iCyte cell sorter to capture labeled CTCs.

In collaboration with Dr. Gil Mor and colleagues in the Department of Obstetrics and Gynecology at Yale University, Dr. Ward has continued to define an effective panel of biomarker proteins in blood for the detection of early stage ovarian cancer. In 2005, this group of investigators reported (Mor et al. PNAS 102, 7677, 2005) that a set of four proteins (leptin, prolactin, osteopontin, and IGF-1 insulin-like growth factor-1) could distinguish between the blood of healthy women and those with ovarian cancer. This test had a sensitivity of 95 percent and a specificity of 95 percent in a blinded study of 255 individuals. In 2007, the group identified macrophage inhibitory factor one (MIF-1) that was also differentially expressed in the blood of healthy women and women with ovarian cancer (Agarwal, R et al. Am. J. Obst. Gynecol. 196, 348, 2007). By adding CA-125, the only currently approved biomarker for ovarian cancer, to the previous five markers, a blood screening test was developed that had a 99.7 percent sensitivity and a 97.5 percent specificity in distinguished ovarian cancer patients from healthy controls in a blind study involving 562 women (Visintin et al. Clinical Cancer Research, 2007. In press). This blood test is by far the most accurate yet devised for the early detection of ovarian cancer.