Project title predicting human tumor response by 31P MRS

on the exact solution for a sphere. This method, along with a more general virtual source procedure will directly utilize structural information from the MR/images do deduce optical properties. The analytic approaches will be sensitive to optical properties for objects of order 0.5 cm in diameter. Other imaging algorithms that do not rely on MRI images will also be employed. To achieve optimal sensitivity/specificity in breast tumor detection we will evaluate and apply comparative weights to the several optical criteria and to the imaging algorithms. Thesaurus Terms: breast neoplasm/cancer diagnosis, diagnosis design/evaluation, imaging/visualization, magnetic resonance imaging, method development, optics, tomography computer assisted diagnosis, infrared radiation, light scattering bioimagingfoiomedical imaging, clinical research, female, human subject

Institution:

Fiscal Year: Department: Project Start: Project End: ICD: IRG:

University of Pennsylvania Philadelphia, PA 19104-6380 1998 Radiology 06-AUG-93 31-AUG-00 National Cancer Institute ZRG7

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PREDICTING HUMAN TUMOR RESPONSE BY 31P MRS Grant Number: PI Name:

5U01CA62554-05 Charles, Hal C.

Abstract: DESCRIPTION: This application is from DU. The overall goal of this proposal is to evaluate the ability of parameters derived from 31-P magnetic resonance spectroscopy (MRS) and 1H magnetic resonance imaging (MR/) to assess prognosis and monitor therapeutic effectiveness in patients with neoplastic disease. The applicants will study locally advanced breast cancer treated with preoperative chemotherapy and radiation + hyperthermia. To accomplish this goal, the applicants propose to investigate 1H MR1 image guided 31-P MRS in a study design which incorporates serial studies with robust three dimensional spectral localization with spatial correlation to MR images. This study will be undertaken as a prospective, cooperative clinical research trial incorporating well defined clinical endpoints and technical quality control. With 31-P MRS, the applicants will measure tumor phosphometabolite levels, pH and derive appropriate metabolic indicators. With 1H MR1, the applicants will measure tumor T@ and estimate initial tu-

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mor necrosis as the volume percent which does not enhance with a paramagnetic contrast agent, e.g. Magnevist or Prohance. Serial MR1 and MRS will be performed prior to initiation of chemotherapy, 0-48 hours prior to the first radiation treatment, 0-48 hours following the first hyperthermia treatment, and 24-96 hours prior to surgery. The MRAS and MR1 data will be correlated with clinical and histologic response to therapy. The working hypotheses are that pretherapy and proximal posththerapy 31-P MRS metabolite levels, pH, and t2 values will be prognostic of treatment outcome. Thesaurus Terms: human therapy evaluation, neoplasm/cancer, neoplasm/cancer therapy, nuclear magnetic resonance spectroscopy, prognosis breast neoplasm, clinical trial, cooperative study, metabolism, necrosis, neoplasm/cancer chemotherapy, neoplasm/cancer surgery, neoplasm/cancer thermotherapy, radiation therapy female, human subject

Institution: Fiscal Year: Department: Project Start: Project End: ICD: IRG:

Duke University Durham, NC 27706 1999 Radiology 21-JUL-95 29-FEB-00 National Cancer Institute SRC

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INTERFERONS AND CELL GROWTH REGULATION Grant Number: PI Name:

5R29CA69031-04 Choubey, Divaker

Abstract: The interferons (IFNs) are a family of multifunctional cytokines that are part of the human body's defenses against infections and some cancers. IFNs act primarily by inducing the synthesis of effector proteins. Although IFNs are used in the treatment of various human cancers, including hairy cell leukemia, chronic myelogenous leukemia, and Kaposi's sarcoma, the mechanisms by which they act as antiproliferative agents are poorly understood.

Previously, we characterized a 52-kDa nuclear phosphoprotein (p202) whose level rises 20-fold in cells following IFN treatment. Constitutive expression of p202 in transfected cells inhibits growth, p202 has been found to bind to the retinoblastoma tumor suppressor protein (pRb). This finding indicates a potential role for p202 in regulating the cell cycle. This notion is further supported by tide observations that p202 associated with the transcription factor E2F (E2F-1/DP-1) in vitro and in vivo and inhibited E2F-mediated transcription in transient transfection assays. Thus, p202 might mediate the growth-inhibitory activities of the IFNs by inhibiting E2F activity.