Intramuscular transplantation improves engraftment rates for esophageal patient-derived tumor xenografts

Matthew Read, David Shi Hao Liu, Cuong Phu Duong, Carleen M Cullinane, William K Murray, Christina M Fennell, Jake Shortt, David A Westerman, Paul Robert Burton, Nicholas J Clemons, Wayne Allen Phillips

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

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. DISCUSSION: 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.
Original languageEnglish
Pages (from-to)305 - 311
Number of pages7
JournalAnnals of Surgical Oncology
Volume23
Issue number1
DOIs
Publication statusPublished - 2016

Cite this

Read, M., Liu, D. S. H., Duong, C. P., Cullinane, C. M., Murray, W. K., Fennell, C. M., ... Phillips, W. A. (2016). Intramuscular transplantation improves engraftment rates for esophageal patient-derived tumor xenografts. Annals of Surgical Oncology, 23(1), 305 - 311. https://doi.org/10.1245/s10434-015-4425-3
Read, Matthew ; Liu, David Shi Hao ; Duong, Cuong Phu ; Cullinane, Carleen M ; Murray, William K ; Fennell, Christina M ; Shortt, Jake ; Westerman, David A ; Burton, Paul Robert ; Clemons, Nicholas J ; Phillips, Wayne Allen. / Intramuscular transplantation improves engraftment rates for esophageal patient-derived tumor xenografts. In: Annals of Surgical Oncology. 2016 ; Vol. 23, No. 1. pp. 305 - 311.
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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. DISCUSSION: 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.",
author = "Matthew Read and Liu, {David Shi Hao} and Duong, {Cuong Phu} and Cullinane, {Carleen M} and Murray, {William K} and Fennell, {Christina M} and Jake Shortt and Westerman, {David A} and Burton, {Paul Robert} and Clemons, {Nicholas J} and Phillips, {Wayne Allen}",
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Read, M, Liu, DSH, Duong, CP, Cullinane, CM, Murray, WK, Fennell, CM, Shortt, J, Westerman, DA, Burton, PR, Clemons, NJ & Phillips, WA 2016, 'Intramuscular transplantation improves engraftment rates for esophageal patient-derived tumor xenografts', Annals of Surgical Oncology, vol. 23, no. 1, pp. 305 - 311. https://doi.org/10.1245/s10434-015-4425-3

Intramuscular transplantation improves engraftment rates for esophageal patient-derived tumor xenografts. / Read, Matthew; Liu, David Shi Hao; Duong, Cuong Phu; Cullinane, Carleen M; Murray, William K; Fennell, Christina M; Shortt, Jake; Westerman, David A; Burton, Paul Robert; Clemons, Nicholas J; Phillips, Wayne Allen.

In: Annals of Surgical Oncology, Vol. 23, No. 1, 2016, p. 305 - 311.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Intramuscular transplantation improves engraftment rates for esophageal patient-derived tumor xenografts

AU - Read, Matthew

AU - Liu, David Shi Hao

AU - Duong, Cuong Phu

AU - Cullinane, Carleen M

AU - Murray, William K

AU - Fennell, Christina M

AU - Shortt, Jake

AU - Westerman, David A

AU - Burton, Paul Robert

AU - Clemons, Nicholas J

AU - Phillips, Wayne Allen

PY - 2016

Y1 - 2016

N2 - 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. DISCUSSION: 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.

AB - 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. DISCUSSION: 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.

UR - http://link.springer.com/article/10.1245%2Fs10434-015-4425-3

U2 - 10.1245/s10434-015-4425-3

DO - 10.1245/s10434-015-4425-3

M3 - Article

VL - 23

SP - 305

EP - 311

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

SN - 1068-9265

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