title: Intramuscular Transplantation Improves Engraftment Rates for Esophageal Patient-Derived Tumor Xenografts.
abstract: BACKGROUND
  Recently, there has been an increase in the availability of targeted molecular therapies for cancer treatment. The application of these approaches to esophageal cancer, however, has been hampered by the relative lack of appropriate models for preclinical testing. Patient-derived tumor xenograft (PDTX) models are gaining popularity for studying many cancers. Unfortunately, it has proven difficult to generate xenografts from esophageal cancer using these models. The purpose of this study was to improve the engraftment efficiency of esophageal PDTXs.
  
  
  METHODS
  Fresh pieces of esophageal tumors obtained from endoscopic biopsies or resected specimens were collected from 23 patients. The tumors were then coated in Matrigel and transplanted in immunocompromised mice subcutaneously (n = 6) and/or using a novel implantation technique whereby the tumor is placed in a dorsal intramuscular pocket (n = 18). They are then monitored for engraftment.
  
  
  RESULTS
  With the novel intramuscular technique, successful engraftment was achieved for all 18 patient tumors. Among these PDTXs, 13 recapitulated the original patient tumors with respect to degree of differentiation, molecular and genetic profiles, and chemotherapeutic response. Lymphomatous transformation was observed in the other five PDTXs. Successful engraftment was achieved for only one of six patient tumors using the classic subcutaneous approach.
  
  
  CONCLUSIONS
  We achieved a much higher engraftment rate of PDTXs using our novel intramuscular transplant technique than has been reported in other published studies. It is hoped that this advancement will help expedite the development and testing of new therapies for esophageal cancer.
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Read
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Liu
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.|Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
authors.forename: Cuong P
authors.initials: CP
authors.lastname: Duong
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Carleen
authors.initials: C
authors.lastname: Cullinane
authors.affiliation: Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: William K
authors.initials: WK
authors.lastname: Murray
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Fennell
authors.affiliation: Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.|School of Clinical Sciences at Monash Health, Melbourne, Australia.|Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, Australia.
authors.forename: Jake
authors.initials: J
authors.lastname: Shortt
authors.affiliation: Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia.|University of Melbourne, Melbourne, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Westerman
authors.affiliation: Monash University Centre for Obesity Research and Education, Alfred Hospital, Melbourne, Australia.|Cabrini Hospital, Melbourne, VIC, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Burton
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.|Department of Surgery (St. Vincent's Hospital), University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Clemons
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. wayne.phillips@petermac.org.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. wayne.phillips@petermac.org.|Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. wayne.phillips@petermac.org.|Department of Surgery (St. Vincent's Hospital), University of Melbourne, Melbourne, VIC, Australia. wayne.phillips@petermac.org.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Phillips
mesh_terms: D000818:Animals; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000601:surgery; D006085:Graft Survival; D006801:Humans; D007273:Injections, Intramuscular; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015375:Receptors, Interleukin-2 / Q000502:physiology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D015375:Receptors, Interleukin-2