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  • American Association for Cancer Research (AACR)  (2)
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  • American Association for Cancer Research (AACR)  (2)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3196-3196
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3196-3196
    Abstract: BACKGROUND: Cells disseminated from primary epithelial tumors into peripheral blood, called circulating tumor cells (CTCs), can be monitored to assess metastases and to provide a surrogate marker of treatment response; indeed, the enumeration of fixed CTCs with the Johnson and Johnson Veridex CellSearch System is FDA-approved for assessment of patient prognosis in metastatic breast, prostate, and colorectal cancer. The opportunity to isolate viable CTCs using the Flexible Micro Spring Array (FMSA) device – a novel microfluidic device that enriches CTCs by two physical parameters: size and flexibility – offers the possibility of testing cancer treatments in real time and rapidly providing information back to clinicians regarding the best course of treatment. OBJECTIVES: In this study, we evaluated the possibility of isolating viable CTCs from human blood using the FMSA device, growing these cells in a mouse xenograft model, and determining successful treatments for metastatic disease. METHODS: GFP-labeled HCT-116 cells were spiked into samples of blood from healthy donors to mimic the blood of patients with metastatic disease. This spiked blood was filtered using the FMSA device, and the recovered cells were implanted into the flanks of immunodeficient mice for study. A series of in vivo experiments were carried out to investigate the effect of chemotherapy on the resulting tumors. These tumors were molecularly characterized, compared to tumors derived from non-filtered cells, and analyzed for potential differences resulting from FMSA enrichment. Studies are ongoing to further investigate the use of this model and approach to culture CTCs from patients. RESULTS & CONCLUSIONS: Cancer cells isolated from blood using the FMSA can proliferate when implanted subcutaneously into the flanks of immunodeficient mice – developing into tumors within two weeks. Although they grow at rates that depend on the number of cancer cells found in each mL of blood, these tumors provide a means for testing the effects of chemotherapy on CTCs in vivo. Using this model, treatments targeted towards CTCs could be assessed and provide real-time information to clinicians regarding treatment interventions for patients with metastatic cancer and detectable CTCs. It may also be possible to use this model as the primary mode for CTC culture as the in vivo environment may provide soluble factors, cell-to-cell interactions, and physical parameters that are not easily mimicked by in vitro culture. The approach has potential to help with efforts to develop personalized therapy options for patients with advanced cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3196. doi:1538-7445.AM2012-3196
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3187-3187
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3187-3187
    Abstract: Although technological advances in recent years have enabled isolatation of circulating tumor cells (CTCs), only the VeridexCellSearch System has been approved by the FDA for assessment of patient prognosis in metastatic breast, colon, and prostate cancers. A fundamental challenge with the CellSearch System is that the technique it uses to enrich and detect CTCs, EpCAM-basedimmunomagnetic isolation, fixates captured cells and prevents further molecular characterization by functional assays and primary cell culture. Progress in addressing these issues may help with progress with a variety of clinical needs including further characterization of the biology of individual patient tumors as well as their potential response top various therapeutics. In this study, we use the Flexible Micro Spring Array (FMSA) Device —a novel portable microfluidic device that captures and isolates viable CTCs by two physical parameters: size and flexibility—to capture, culture, and further characterize CTCs.GFP-labeled HCT-116 cells were spiked into healthy samples of donor blood to mimic blood samples of metastatic cancer patients. This spiked blood was filtered using the FMSA device, and the recovered cells were expanded in cell culture. A series of experiments were carried out to characterize these cells and investigate the effect of chemotherapy on the resulting cultures. Studies are ongoing to evaluate the potential of using this model to culture CTCs from patients and to evaluate the response of these cells to chemotherapies using high-throughput methodologies. The isolation of viable CTCs from human blood using the FMSA device provides a novel means for studying viable CTCs and for testing drug efficacy ex vivo. The analysis and identification of CTC-specific characteristics and their relation to chemotherapy susceptibility suggests a potential paradigm shift toward personalized and targeted cancer therapy based on the specific genetic defects of each patient's malignancy and CTCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3187. doi:1538-7445.AM2012-3187
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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