Takahiro Nakajima1, William Geddie2, Takashi Anayama3, Hyang Mi Ko2, Gilda da Cunha Santos2, Scott Boerner2, Tao Wang4, Yu-hui Wang5, Ming Li5, Nhu-An Pham5, Ming Sound Tsao4, Kazuhiro Yasufuku6. 1. Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. 2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. 3. Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. 4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Ontario Cancer Institute, Princess Margaret Cancer Center, University Health Network, Ontario, Canada. 5. Ontario Cancer Institute, Princess Margaret Cancer Center, University Health Network, Ontario, Canada. 6. Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: kazuhiro.yasufuku@uhn.ca.
Abstract
OBJECTIVES: There has been limited utility for laboratory tumor models to predict clinical performance of cancer drugs. Clinical drug trials usually recruit patients that have advanced disease, therefore preclinical tumor models that closely reflect this characteristic will be more reliable to test candidate drugs. We evaluated the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to sample metastatic lymph nodes in patients to establish patient-derived tumorxenograft (PDX) models of advanced lung cancer. MATERIALS AND METHODS: Cell suspensions from TBNA aspirates were implanted into the subcutaneous tissue of NSG (NOD scid) gamma) mice. The success rate of PDX establishment was associated with tumor histopathology and the cellularity and cytopathological diagnosis of the primary EBUS-TBNA samples. RESULTS: From December 2011 to June 2012, 19 patients were enrolled in this study. Successful engraftment was achieved in 8/19 cases (42.1%). The duration between inoculation and tumor formation averaged 62.4 days (13-144 days). The engrafted tumors included 3 adenocarcinomas (3/12: 25%), 2 squamous cell carcinomas (2/3: 67%), 1 large cell carcinoma (1/1: 100%), and 2 small cell carcinomas (2/3: 67%). CONCLUSION: EBUS-TBNA samples can be used for establishment of tumor xenograft model in immunodeficient mice.
OBJECTIVES: There has been limited utility for laboratory tumor models to predict clinical performance of cancer drugs. Clinical drug trials usually recruit patients that have advanced disease, therefore preclinical tumor models that closely reflect this characteristic will be more reliable to test candidate drugs. We evaluated the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to sample metastatic lymph nodes in patients to establish patient-derived tumorxenograft (PDX) models of advanced lung cancer. MATERIALS AND METHODS: Cell suspensions from TBNA aspirates were implanted into the subcutaneous tissue of NSG (NOD scid) gamma) mice. The success rate of PDX establishment was associated with tumor histopathology and the cellularity and cytopathological diagnosis of the primary EBUS-TBNA samples. RESULTS: From December 2011 to June 2012, 19 patients were enrolled in this study. Successful engraftment was achieved in 8/19 cases (42.1%). The duration between inoculation and tumor formation averaged 62.4 days (13-144 days). The engrafted tumors included 3 adenocarcinomas (3/12: 25%), 2 squamous cell carcinomas (2/3: 67%), 1 large cell carcinoma (1/1: 100%), and 2 small cell carcinomas (2/3: 67%). CONCLUSION: EBUS-TBNA samples can be used for establishment of tumor xenograft model in immunodeficientmice.
Authors: Matthew C Hernandez; John R Bergquist; Jennifer L Leiting; Tommy Ivanics; Lin Yang; Rory L Smoot; David M Nagorney; Mark J Truty Journal: J Gastrointest Surg Date: 2019-02-12 Impact factor: 3.452