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（项目2 : 循环肿瘤细胞）
循环肿瘤细胞(CTC)技术已超过基本的研究阶段。那么，从此循环肿瘤细胞能学习到什么？大家要一起讨论各种已被应用的技术之作用吗？CTC的鉴定与分析朝向对基因型与细胞的高内涵（High Content）分析等分子等级的理解。采用此新技术能如何诱导患者治疗？能在此细胞上找到治疗的效果吗？原始肿瘤细胞群与循环细胞间有何差异？制药公司、生物技术企业、诊断药制造商、学术机关的专家们将在Circulating Tumor Cells会议上回应这些疑问。 RECOMMENDED SHORT COURSE* (SC2) Assay Development and Validation of Pharmacodynamic Biomarkers in Circulating Tumor Cells *Separate registration required
WEDNESDAY, SEPTEMBER 7 7:00 am Registration and Morning Coffee 8:30 Chairperson's Opening Remarks
ADVANCING TECHNOLOGIES 9:10 Microfiltration Devices to Improve CTC Enumeration and Isolation Siyang Zheng, Ph.D., Assistant Professor, Department of Bioengineering, Pennsylvania State University CTC enrichment is required for most of the CTC analysis procedures. Microfiltration devices enrich CTCs from blood based on size exclusion and independent of antigen expression on cell surface. The devices are optimized for recovery, enrichment, blood sample volume, processing time, and cell viability. Multiple ways of CTC characterization on device after enrichment have been demonstrated. Microfiltration device provides a versatile platform for CTC enumeration and analysis. 9:40 Microtentacles in CTCs are Promoted by Epithelial-to-Mesenchymal Transition Stuart S. Martin, Ph.D., Associate Professor, Physiology, Greenebaum NCI Cancer Center, University of Maryland School of Medicine Detached and circulating breast tumor cells generate dynamic membrane protrusions that we have named microtentacles, since they are composed of a unique kinesin-dependent coordination of detyrosinated microtubules and vimentin intermediate filaments. Microtentacles promote tumor cell aggregation and reattachment that increase the retention of CTCs in lung capillaries. Our recent studies show that induction of epithelial-to-mesenchymal transition (EMT) leads to tubulin detyrosination and stabilization in breast tumor cell lines. This EMT-induced increase in tubulin detyrosination promotes microtentacles and the reattachment of breast tumor cells to endothelial cell layers. In human breast tumors, tubulin detyrosination occurs in cells undergoing EMT at invasive tumor fronts and could prime these cells for metastatic success once entering the circulation. These findings provide a possible explanation for why increased levels of detyrosinated tubulin are associated with poor patient survival in breast cancer and a potential mechanism for how EMT in circulating tumor cells could promote metastasis. Since large epithelial tumor cells are crushed when pushed through narrow capillaries by blood flow, we are targeting microtentacles to reduce tumor cell reattachment and increase the fragmentation of circulating tumor cells. 10:10 Networking Coffee Break in the Exhibit Hall with Poster Viewing 10:50 Post Capture Enumeration and Molecular Analysis of CTCs: Oncocee TM-Brassay Development for the CLIA Laboratory Farideh Z. Bischoff, Ph.D., Vice President, Translational Research and CLIA Development, Biocept, Inc. The Biocept CEE TM (Cell Capture and Extraction) device centers on microfluidics and is designed to selectively capture and enrich target rare cells, including CTCs from blood. Because the Biocept CEE device is attached to the surface of a glass slide, the system is particularly suited for direct and immediate single CTC morphologic assessment, in addition to immunochemical and genetic analysis. The processing of blood samples from advanced stage cancer patients, including breast, prostate and lung, have been optimized for CTC capture, enumeration and post capture analysis of protein levels (ICC) as well as chromosomal/DNA content within Biocept's CLIA laboratory for commercialized testing. Study design for analytical validation of CTC-based CK-enumeration, HER2 FISH and ER/PR status determination by ICC for the OncoCEE TM-BR test will be discussed. Sponsored by
CLINICAL UTILITY & CASE STUDIES IN THE CLINIC 11:50 Expanding the Definition of Traditional CTCs: Cells Associated With Cancer in the Blood of Patients with Solid Tumors Jeffrey Chalmers, Ph.D., Professor, Chemical and Biomolecular Engineering, The Ohio State University The currently accepted definition of CTCs are cells that have: a nuclei, cytokeratin+ EpCAM+, and CD45-. Emerging evidence suggests that other rare, cancer associated circulating cells are present in the blood of metastatic cancer patients including CD45+ cytokeratin+ cells. A negative depletion process to isolate and quantify circulating tumor cells from the blood of head and neck cancer patients, using immunomagnetic separation was developed and is currently being validated on a number of solid tumors, including SCCHN and Breast Cancer. Correlation of number of CTCs, (tradition definition) tumor site, tumor stage, nodal status, smoking/alcohol abuse, histopathological characteristics, and clinical outcome was made with the SCCHN patients. 12:20 pm Clinical Application of CTCs in Lung Cancer & Malignant Effusions Steven M. Albelda, M.D., Vice Chief, Pulmonary, Allergy, and Critical Care Division; Director, Lung Research; Co-Director, Thoracic Oncology Laboratories, University of Pennsylvania Medical Center Unlike other tumors, such as breast, colon, and prostate cancers, it has been more difficult to apply CTC technology to lung cancer. Three areas relating to CTC technology in patients with thoracic malignancies will be discussed. These include: 1) studies to define why it has been difficult to detect CTC's in non-small cell lung cancer, 2) data describing the use of CTCs in small cell lung cancer to estimate tumor volume and to evaluate responses to chemotherapy, and 3) a new approach showing the utility of the Cell Search technology to diagnose malignant cells in pleural fluid. 12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
PROGNOSTIC VS. PREDICTIVE INDICATIONS 1:50 Chairperson's Remarks Gavin P. Robertson, Ph.D., Program Leader, Pharmacology, Pennsylvania State University 1:55 The Prognostic and Predictive Value of Enumeration and Molecular Characterization Massimo Cristofanilli, M.D., F.A.C.P., Professor, Chairman, Medical Oncology, G. Morris Dorrance Jr. Endowed Chair in Medical Oncology, Fox Chase Cancer Center 2:25 CTC Utility in Modern Drug Development Glen Clack, M.D., Clinical Director, Oncology: Early Phase, AstraZeneca
ESTABLISHING THE CTC-TUMOR RELATIONSHIP 2:55 CTCs and Lung Metastasis Development Gavin P. Robertson, Ph.D., Program Leader, Pharmacology, Pennsylvania State University Metastasis is a complex process requiring cell detachment from the primary tumor and CTC migration to secondary sites via lymphatic or blood circulatory systems. CTCs must survive blood flow shear forces and immune system challenges, finally becoming entrapped and extravasating into surrounding tissue to form metastases. Only a minority of CTCs trapped in the lung capillaries ever form metastases, mediated by chemokines secreted from CTCs that promote interaction with the extracellular environment. Entrapped CTCs in lungs produce and secrete chemokine IL-8, which attracts neutrophils to promote interaction with, and tethering to vascular endothelium enabling transendothelial CTC migration and metastasis development. 3:25 Networking Refreshment Break in the Exhibit Hall with Poster Viewing 4:00 Multiple Parameter Characterization of Circulating Tumor Cells Isolated Using a Microfluidic Vortex Generator Shannon Stott, Ph.D., Research Fellow, Surgery, Massachusetts General Hospital, Harvard Medical School 4:30 Detection of Circulating Tumor Cell Heterogeneity at the Single Cell Level and Determination of Defined Targets on These Cells for Individualized Therapy Katharina Pachmann, Ph.D., Professor, Experimental Hematology & Oncology, University of Jena Expression profiling could be successfully performed from more than 80% of all individually deposited isolated cells demonstrating the epithelial nature of these cells but also heterogeneity among the cells of individual patients with respect to other genes. Thus we show that circulating epithelial cells from breast cancer patients can be individually deposited and these single cells can subsequently be subject to expression profiling. 5:00-6:00 pm Interactive Breakout Discussion Groups 6:00-7:00 Welcome Reception in the Exhibit Hall with Poster Viewing
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