- CORE A: BIOSPECIMEN / PATHOLOGY CORE
- CORE B: PRE-CLINICAL ANIMAL CORE
- CORE C: BIOSTATISTICS AND CLINICAL CORE
- CORE D: ADMINISTRATIVE CORE
CORE A: BIOSPECIMEN / PATHOLOGY CORE
The Brain Tumor SPORE Biospecimen/Pathology Core provides staff and technology dedicated to enhancing brain tumor biospecimen integrity and usability through use of optimized collection procedures; multi-modality preservation, processing, and analysis; histopathologic-molecular characterization; and computerized inventory and web-based request and tracking systems. All aspects of sample identification, processing and storage are performed with strict compliance to the College of American Pathologists (CAP) guidelines. In order to maximize sharing and integration of SPORE projects, the Tissue Core collects and makes available data derived from all distributed brain tumor biospecimens. Specific Aims of the SPORE Biospecimen/Pathology Core:
- A. To acquire brain tumor patient biospecimens from the operating room and SPORE Animal Core with optimized handling to maximize cell viability and/or minimize the warm-ischemic interval so as to meet the tissue accrual requirements for the Brain Tumor SPORE projects and clinical trials. This aim is essential for all Projects.
- B. To perform quality control assays on archived brain tumor biospecimens collected from the operating room and SPORE Animal Core, to ensure availability of adequate numbers of consistently handled specimens that will yield high quality data for SPORE projects and clinical trials.
- C. To provide routine and advanced tissue handling/processing and analytical techniques, including immunohistochemistry, fluorescence in situ hybridization (FISH), tissue microarray construction, DNA/RNA extraction, protein isolation, and preparation of viable cells that will advance project hypothesis development and goal attainment.
- D. To maintain a database containing demographic data, results from molecular analyses, and brain tumor patient biospecimen distributions (internal and external) that will be linked to relational clinical databases maintained by the Biostatistics and Clinical Core.
CORE B: PRE-CLINICAL ANIMAL CORE
Because of the translational requirement of SPORE research, it is essential that SPORE investigators have access to and assistance with animal models for therapeutic hypothesis testing. The UCSF Brain Tumor SPORE Animal Core addresses this need by using 3 types of rodent intracranial engraftment models, based on cell of origin: 1) human tumor cells; 2) chemically induced rodent brain tumor cell lines; and 3) tumor cells derived from genetically modified mouse models. Tumor cells are implanted in the brains of immunodeficient, and/or immunocompetent hosts, with therapeutic effect determined by bioluminescence monitoring of tumor growth, animal subject survival analysis, and immunohistochemical analysis of tumor biologic response indicators, especially proliferation and apoptotic response. In addition, the Core also conducts studies to assess therapeutic toxicity and biodistribution. These studies typically involve organ and tissue harvests at pre-determined timepoints, with specimens examined for drug content, and/or indication of abnormal pathology, and/or abnormal cell counts when blood samples are obtained. Finally, the Core serves as a source of tumor tissues, resulting from engraftment procedures, for biomarker investigation and assay development, and for in vitro investigation in instances involving the transfer of viable tissues or cells. These activities are carried out in association with the following specific aims:
- Aim 1: Propagate, analyze (histopathological and molecular), archive, and maintain up-to-date records on all tumor cell sources and tissues used in support of SPORE animal model research.
- Aim 2: Advise and assist all rodent model therapeutics testing, including optical imaging, survival benefit analysis, toxicity assessment, and molecular analyses of tumors for response to therapy.
- Aim 3: In association with the Tissue Core, utilize human xenograft tumor tissues to facilitate the development of immunohistochemical and FISH assays that can be applied to the investigation of biologic response indicators, therapeutic targets, and surrogate markers in patient tumors.
- Aim 4: Process, and distribute, within and outside of UCSF, xenograft tumor tissues and cell lines, as well as extracts from each, so as to promote intra- and inter-SPORE collaborations, as well as to support brain tumor research in general, through utilization of renewable tumor cell resources.
CORE C: BIOSTATISTICS AND CLINICAL CORE
The Biostatistics and Clinical Core will provide the leadership and expertise needed to support the laboratory and clinical research of the 4 Projects of this SPORE grant.
The Clinical component will be led by Dr. Prados, who will interact with Project leaders to develop clinical trials based upon laboratory investigations in Projects Three and Four in particular, as well as to discuss results in Projects One and Two that may lead to relevant biomarkers and potential stratification factors for future or potential clinical trials. The Clinical component will support the actual conduct of SPORE clinical trials, including providing clinicians, research nurses and data coordinators, and assist in all of the required regulatory reporting for those studies. Dr. Prados will support and facilitate the interactions of Project leaders with CTEP, cooperative groups, biopharmaceutical, and industry groups to obtain new therapeutic agents appropriate to the design of new studies that come from Projects Three and Four, as well as supporting the conduct of SPORE clinical trials to those groups as needed.
The Biostatistical component will be led by Dr. Molinaro, who will interact on an ongoing basis with the individual leaders from all four Projects to assess the statistical needs of each. The Biostatistical component will provide: advice on the design of experimental and clinical studies, including calculating sample sizes and power; data analysis support (either by performing the analyses within the core or advising qualified personnel within the projects), including the use of appropriate statistical models and applications of statistical test; and, when necessary, the development of novel methods to help interpret results from experiments. Additionally, a member of the Biostatistical component will participate in regularly scheduled project meetings to provide statistical/bioinformatics input and assist in preparing the necessary materials for presentation and publication.
CORE D: ADMINISTRATIVE CORE
The UCSF Brain Tumor SPORE proposal has 4 overall specific objectives: 1) to identify factors that contribute to the likelihood of surviving brain cancer; 2) to identify spectroscopic, non-invasively derived imaging parameters and linked tissue biomarkers that can help predict recurrence and outcome in patients with low grade glioma; 3) to develop improved therapies for pediatric brain tumors harboring BRAF mutations; and 4) to improve the immunotherapy of brain cancer. The Administrative Core of the UCSF Brain Tumor SPORE has been created to supervise the activities of the UCSF Brain Tumor SPORE and to provide fiscal management, administrative support, and the framework by which researchers can communicate and interact. The aims of the Core are: 1. To evaluate research progress. The Administrative Core, through the SPORE Executive Committee, the SPORE Steering Committee, and the SPORE External Advisory Board, will be responsible for evaluating the progress of projects and making decisions regarding the continuation/replacement of projects. 2. To provide fiscal management. The Administrative Core will distribute funds from the SPORE Award, the Career Development and Developmental Research Programs, SPORE Supplement Awards, and discretionary funds provided by the institution. The Administrative Core will also be responsible for the timely reporting of finances to Project Leaders and the SPORE PI/co-PIs. 3. To provide administrative support. The Administrative Core will be responsible for the daily operations of the SPORE, for the preparation of SPORE-related manuscripts, and for communications with NIH. 4. To facilitate communication between SPORE investigators. The Administrative Core will be responsible for the scheduling of all meetings, seminar series, and retreats, and for the distribution of the notices inviting participation in the Career Development Program and the Developmental Research Program. 5. To assist in compliance. The Administrative Core will be responsible for assuring compliance and scientific integrity of all components of the SPORE. The Administrative Core will be used by all Projects and Cores in the SPORE.