Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice

Long Sheng Chang, Abraham Jacob, Mark Lorenz, Jonathan Rock, Elena M. Akhmametyeva, Georgeta Mihai, Petra Schmalbrock, Abhik R. Chaudhury, Raul Lopez, Jyoji Yamate, Markus R. John, Hannes Wickert, Brian A. Neff, Edward Dodson, D. Bradley Welling

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

OBJECTIVES: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. STUDY DESIGN AND METHODS: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. RESULTS: Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. CONCLUSIONS: This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.

Original languageEnglish (US)
Pages (from-to)2018-2026
Number of pages9
JournalLaryngoscope
Volume116
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Severe Combined Immunodeficiency
Acoustic Neuroma
Neurilemmoma
Heterografts
Growth
Magnetic Resonance Imaging
Sciatic Nerve
Thigh
Tumor Burden
Knockout Mice
Transgenic Mice
Neoplasms
Magnetic Resonance Spectroscopy
Animal Models
Immunohistochemistry

Keywords

  • Cystic
  • Gadolinium
  • Magnetic resonance imaging (MRI)
  • Malignant
  • Neurofibromatosis type 2 (NF2)
  • Severe combined immunodeficiency (SCID) mice
  • Vestibular schwannoma
  • Xenograft

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Chang, L. S., Jacob, A., Lorenz, M., Rock, J., Akhmametyeva, E. M., Mihai, G., ... Welling, D. B. (2006). Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice. Laryngoscope, 116(11), 2018-2026. https://doi.org/10.1097/01.mlg.0000240185.14224.7d

Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice. / Chang, Long Sheng; Jacob, Abraham; Lorenz, Mark; Rock, Jonathan; Akhmametyeva, Elena M.; Mihai, Georgeta; Schmalbrock, Petra; Chaudhury, Abhik R.; Lopez, Raul; Yamate, Jyoji; John, Markus R.; Wickert, Hannes; Neff, Brian A.; Dodson, Edward; Welling, D. Bradley.

In: Laryngoscope, Vol. 116, No. 11, 11.2006, p. 2018-2026.

Research output: Contribution to journalArticle

Chang, LS, Jacob, A, Lorenz, M, Rock, J, Akhmametyeva, EM, Mihai, G, Schmalbrock, P, Chaudhury, AR, Lopez, R, Yamate, J, John, MR, Wickert, H, Neff, BA, Dodson, E & Welling, DB 2006, 'Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice', Laryngoscope, vol. 116, no. 11, pp. 2018-2026. https://doi.org/10.1097/01.mlg.0000240185.14224.7d
Chang, Long Sheng ; Jacob, Abraham ; Lorenz, Mark ; Rock, Jonathan ; Akhmametyeva, Elena M. ; Mihai, Georgeta ; Schmalbrock, Petra ; Chaudhury, Abhik R. ; Lopez, Raul ; Yamate, Jyoji ; John, Markus R. ; Wickert, Hannes ; Neff, Brian A. ; Dodson, Edward ; Welling, D. Bradley. / Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice. In: Laryngoscope. 2006 ; Vol. 116, No. 11. pp. 2018-2026.
@article{3ee1ce0cec0f41dfa56551cf6db9a2bc,
title = "Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice",
abstract = "OBJECTIVES: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. STUDY DESIGN AND METHODS: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. RESULTS: Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. CONCLUSIONS: This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.",
keywords = "Cystic, Gadolinium, Magnetic resonance imaging (MRI), Malignant, Neurofibromatosis type 2 (NF2), Severe combined immunodeficiency (SCID) mice, Vestibular schwannoma, Xenograft",
author = "Chang, {Long Sheng} and Abraham Jacob and Mark Lorenz and Jonathan Rock and Akhmametyeva, {Elena M.} and Georgeta Mihai and Petra Schmalbrock and Chaudhury, {Abhik R.} and Raul Lopez and Jyoji Yamate and John, {Markus R.} and Hannes Wickert and Neff, {Brian A.} and Edward Dodson and Welling, {D. Bradley}",
year = "2006",
month = "11",
doi = "10.1097/01.mlg.0000240185.14224.7d",
language = "English (US)",
volume = "116",
pages = "2018--2026",
journal = "Laryngoscope",
issn = "0023-852X",
publisher = "John Wiley and Sons Inc.",
number = "11",

}

TY - JOUR

T1 - Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice

AU - Chang, Long Sheng

AU - Jacob, Abraham

AU - Lorenz, Mark

AU - Rock, Jonathan

AU - Akhmametyeva, Elena M.

AU - Mihai, Georgeta

AU - Schmalbrock, Petra

AU - Chaudhury, Abhik R.

AU - Lopez, Raul

AU - Yamate, Jyoji

AU - John, Markus R.

AU - Wickert, Hannes

AU - Neff, Brian A.

AU - Dodson, Edward

AU - Welling, D. Bradley

PY - 2006/11

Y1 - 2006/11

N2 - OBJECTIVES: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. STUDY DESIGN AND METHODS: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. RESULTS: Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. CONCLUSIONS: This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.

AB - OBJECTIVES: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. STUDY DESIGN AND METHODS: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. RESULTS: Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. CONCLUSIONS: This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.

KW - Cystic

KW - Gadolinium

KW - Magnetic resonance imaging (MRI)

KW - Malignant

KW - Neurofibromatosis type 2 (NF2)

KW - Severe combined immunodeficiency (SCID) mice

KW - Vestibular schwannoma

KW - Xenograft

UR - http://www.scopus.com/inward/record.url?scp=33750685043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750685043&partnerID=8YFLogxK

U2 - 10.1097/01.mlg.0000240185.14224.7d

DO - 10.1097/01.mlg.0000240185.14224.7d

M3 - Article

C2 - 17075413

AN - SCOPUS:33750685043

VL - 116

SP - 2018

EP - 2026

JO - Laryngoscope

JF - Laryngoscope

SN - 0023-852X

IS - 11

ER -