The SPORE in GI Cancer: Research

Cores

Administrative Core

The Administrative Core supports SPORE projects and investigators by managing SPORE resources and facilitating communication and interaction among SPORE components and collaborators, other SPORES, the community and the NCI. Management and support are accomplished through a series of oversight committees, as well as organized administrative and scientific meetings of SPORE investigators, institutional representatives and external advisors.

Tissue

The primary mission of the Vanderbilt GI SPORE Tissue Core is to provide high-quality human tissue and body fluid samples collected and processed according to standard protocols, research histology and research immunohistochemistry service to GI SPORE investigators and for interSPORE collaborations.

The specific aims of this proposal are:

  1. To collect, process, bank and distribute human colorectal neoplasms and matched normal tissue samples to investigators in the Vanderbilt GI SPORE and other GI SPORES;
  2. To collect and bank portions of polyps and biopsies of grossly normal colorectal mucosa to facilitate research in adenoma recurrence;
  3. To perform quality control to ensure that the relevant tissue is supplied to the researcher and that tissues are suitable for the planned;
  4. To protect patient confidentiality through use of an explicit consent form that specifically addresses use of extraneous tissue for research purposes and through de-identification of specimens;
  5. To work with the Biostatistics/Bioinformatics Core to establish an informatics strategy for networking of requests, specimen tracking, extraction of de-identified data relating to specimens of interest and linkage to research data;
  6. To provide laser capture microdissection services to the GI SPORE investigators;
  7. To provide tissue microarray services to the GI SPORE investigators and provide TMA slides to investigators at other institutions (such as the H. Lee Moffitt Cancer Center) and other GI SPOREs;
  8. To provide expertise in evaluation of histopathology of mouse models of colorectal neoplasia and correlation with human disease;
  9. To provide expertise in developing, performing and evaluating immunohistochemical stains for GI SPORE investigators.

Clinical Trials

The role of the Clinical Trials Core is to provide expertise in the development, implementation and coordination of the laboratory-clinical translational research trials performed in the SPORE. The ultimate goal is to develop improved therapies for patients with or at risk of developing gastrointestinal cancers through a better understanding of the biology of those cancers. To achieve this goal, the major responsibilities of the Clinical Trials Core will be:

  1. To provide expertise in the development and implementation of translational clinical trials related to the SPORE projects;
  2. To enhance accrual of patients to participate in SPORE-initiated trials;
  3. To coordinate the timely and accurate collection of data;
  4. To ensure accessibility of data for analysis by the various SPORE researchers at Vanderbilt University as well as researchers at other GI SPOREs.

During the first year there will be 3 trials open for accrual. These trials will serve to further the scientific knowledge regarding the roles of

  1. Combined blockade of the EGFR axis in the treatment of patients with advanced colorectal cancer;
  2. Combined use of EGFR- and Src-kinase inhibitors as neoadjuvant therapy in patients with colorectal cancer and potentially resectable liver metastases;
  3. Genetic and dietary risk factors for the development of colorectal adenomas.

Knowledge and insights gained from these trials will be used to design follow-up trials to be conducted within this SPORE and, when appropriate, assist in the development of larger, confirmatory trials to be conducted as inter-SPORE or cooperative group collaborations.

Biostatistics/Bioinformatics

The purpose of the Biostatistics/Bioinformatics Core is to provide professional expertise in statistics and bioinformatics for all Vanderbilt University GI Cancer SPORE projects, investigators and participants. Functions provided by this core include development of experimental designs, data acquisition and database development, data quality control, statistical analysis and interpretation of findings, and collaboration on presentation of results. To achieve these functions, the core directors and core biostatisticians are constantly available to investigators, and are in regular contact with the project and core leaders.

The primary objectives of the Biostatistics/Bioinformatics Core are:

  1. To provide study design and review all laboratory, animal and clinical studies including feasibility assessment, power analysis and sample size estimation;
  2. To collaborate in projects data analysis, interpretation of results and the writing of final study reports and manuscripts;
  3. To work with Clinical Trials Core and Tissue Core in the development of research project database, to maintain data quality control and to ensure timely data capture;
  4. To develop and evaluate statistical methods for experimental design and data analysis.

High Throughput Screening

High-throughput screening (HTS) is a means of rapidly assessing the ability of hundreds of thousands of chemical compounds to affect biological systems for the purpose of accelerating medical research. We propose an HTS core the goal of which is to enable GI SPORE investigators to discover chemical tools to promote better understanding of colorectal cancer physiology and potentially to help reveal novel targets and therapeutic opportunities through the following aims:

  1. To develop, validate, and implement a high-throughput screen (HTS) to discover modulators of E-cadherin expression;
  2. To develop, validate, and implement a high-throughput screen to discover compounds that modulate both axin and/or b-catenin stability;
  3. To develop, validate, and implement a high-throughput screen to discover compounds that modulate E-cadherin activity and adherens junction formation in the Colo205 cell line through actions on p120;
  4. To work with the VICB chemistry core to develop structure activity relationships (SAR) for compounds discovered in aims 1, 2 and 3 leading to improvements in their utility as tools to study GI cancer processes;
  5. To work with other GI SPORE cores and GI SPORE investigators to elucidate the targets and mechanisms of action of compounds discovered in aims 1, 2 and 3;
  6. To provide a knowledge-base and resources for GI SPORE investigators interested in using massively-parallel bioassay technologies to support the aims of the GI SPORE.

 


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