Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments

Kyung Min Kim, Jin Kyoung Shim, Jong Hee Chang, Ji Hyun Lee, Se Hoon Kim, Junjeong Choi, Junseong Park, Eui Hyun Kim, Sun Ho Kim, Yong Min Huh, Su Jae Lee, Jae Ho Cheong, Seok Gu Kang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: With the continuing development of new anti-cancer drugs comes a need for preclinical experimental models capable of predicting the clinical activity of these novel agents in cancer patients. However existing models have a limited ability to recapitulate the clinical characteristics and associated drug sensitivity of tumors. Among the more promising approaches for improving preclinical models is direct implantation of patient-derived tumor tissue into immunocompromised mice, such as athymic nude or non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In the current study, we attempted to develop patient-derived xenograft (PDX) models using tissue fragments from surgical samples of brain tumors. Methods: In this approach, tiny tissue fragments of tumors were biopsied from eight brain tumor patients-seven glioblastoma patients and one primitive neuroectodermal tumor patient. Two administration methods-a cut-down syringe and a pipette-were used to implant tissue fragments from each patient into the brains of athymic nude mice. Results: In contrast to previous reports, and contrary to our expectations, we found that none of these fragments from brain tumor biopsies resulted in the successful establishment of xenograft tumors. Conclusions: These results suggest that fragments of surgical specimens from brain tumor patients are unsuitable for implementation of brain tumor PDX models, and instead recommend other in vivo testing platforms for brain tumors, such as cell-based brain tumor models.

Original languageEnglish
Article number43
JournalCancer Cell International
Volume16
Issue number1
DOIs
StatePublished - 2016 Jun 10

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Heterografts
Brain Neoplasms
Neoplasms
Nude Mice
Primitive Neuroectodermal Tumors
SCID Mice
Syringes
Glioblastoma
Pharmaceutical Preparations
Theoretical Models
Biopsy
Brain

Keywords

  • Glioblastoma
  • Model failure
  • Patient-derived xenograft
  • Primitive neuro-ectodermal tumor
  • Tissue fragment

Cite this

Kim, K. M., Shim, J. K., Chang, J. H., Lee, J. H., Kim, S. H., Choi, J., ... Kang, S. G. (2016). Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments. Cancer Cell International, 16(1), [43]. https://doi.org/10.1186/s12935-016-0319-0
Kim, Kyung Min ; Shim, Jin Kyoung ; Chang, Jong Hee ; Lee, Ji Hyun ; Kim, Se Hoon ; Choi, Junjeong ; Park, Junseong ; Kim, Eui Hyun ; Kim, Sun Ho ; Huh, Yong Min ; Lee, Su Jae ; Cheong, Jae Ho ; Kang, Seok Gu. / Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments. In: Cancer Cell International. 2016 ; Vol. 16, No. 1.
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abstract = "Background: With the continuing development of new anti-cancer drugs comes a need for preclinical experimental models capable of predicting the clinical activity of these novel agents in cancer patients. However existing models have a limited ability to recapitulate the clinical characteristics and associated drug sensitivity of tumors. Among the more promising approaches for improving preclinical models is direct implantation of patient-derived tumor tissue into immunocompromised mice, such as athymic nude or non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In the current study, we attempted to develop patient-derived xenograft (PDX) models using tissue fragments from surgical samples of brain tumors. Methods: In this approach, tiny tissue fragments of tumors were biopsied from eight brain tumor patients-seven glioblastoma patients and one primitive neuroectodermal tumor patient. Two administration methods-a cut-down syringe and a pipette-were used to implant tissue fragments from each patient into the brains of athymic nude mice. Results: In contrast to previous reports, and contrary to our expectations, we found that none of these fragments from brain tumor biopsies resulted in the successful establishment of xenograft tumors. Conclusions: These results suggest that fragments of surgical specimens from brain tumor patients are unsuitable for implementation of brain tumor PDX models, and instead recommend other in vivo testing platforms for brain tumors, such as cell-based brain tumor models.",
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author = "Kim, {Kyung Min} and Shim, {Jin Kyoung} and Chang, {Jong Hee} and Lee, {Ji Hyun} and Kim, {Se Hoon} and Junjeong Choi and Junseong Park and Kim, {Eui Hyun} and Kim, {Sun Ho} and Huh, {Yong Min} and Lee, {Su Jae} and Cheong, {Jae Ho} and Kang, {Seok Gu}",
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Kim, KM, Shim, JK, Chang, JH, Lee, JH, Kim, SH, Choi, J, Park, J, Kim, EH, Kim, SH, Huh, YM, Lee, SJ, Cheong, JH & Kang, SG 2016, 'Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments', Cancer Cell International, vol. 16, no. 1, 43. https://doi.org/10.1186/s12935-016-0319-0

Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments. / Kim, Kyung Min; Shim, Jin Kyoung; Chang, Jong Hee; Lee, Ji Hyun; Kim, Se Hoon; Choi, Junjeong; Park, Junseong; Kim, Eui Hyun; Kim, Sun Ho; Huh, Yong Min; Lee, Su Jae; Cheong, Jae Ho; Kang, Seok Gu.

In: Cancer Cell International, Vol. 16, No. 1, 43, 10.06.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments

AU - Kim, Kyung Min

AU - Shim, Jin Kyoung

AU - Chang, Jong Hee

AU - Lee, Ji Hyun

AU - Kim, Se Hoon

AU - Choi, Junjeong

AU - Park, Junseong

AU - Kim, Eui Hyun

AU - Kim, Sun Ho

AU - Huh, Yong Min

AU - Lee, Su Jae

AU - Cheong, Jae Ho

AU - Kang, Seok Gu

PY - 2016/6/10

Y1 - 2016/6/10

N2 - Background: With the continuing development of new anti-cancer drugs comes a need for preclinical experimental models capable of predicting the clinical activity of these novel agents in cancer patients. However existing models have a limited ability to recapitulate the clinical characteristics and associated drug sensitivity of tumors. Among the more promising approaches for improving preclinical models is direct implantation of patient-derived tumor tissue into immunocompromised mice, such as athymic nude or non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In the current study, we attempted to develop patient-derived xenograft (PDX) models using tissue fragments from surgical samples of brain tumors. Methods: In this approach, tiny tissue fragments of tumors were biopsied from eight brain tumor patients-seven glioblastoma patients and one primitive neuroectodermal tumor patient. Two administration methods-a cut-down syringe and a pipette-were used to implant tissue fragments from each patient into the brains of athymic nude mice. Results: In contrast to previous reports, and contrary to our expectations, we found that none of these fragments from brain tumor biopsies resulted in the successful establishment of xenograft tumors. Conclusions: These results suggest that fragments of surgical specimens from brain tumor patients are unsuitable for implementation of brain tumor PDX models, and instead recommend other in vivo testing platforms for brain tumors, such as cell-based brain tumor models.

AB - Background: With the continuing development of new anti-cancer drugs comes a need for preclinical experimental models capable of predicting the clinical activity of these novel agents in cancer patients. However existing models have a limited ability to recapitulate the clinical characteristics and associated drug sensitivity of tumors. Among the more promising approaches for improving preclinical models is direct implantation of patient-derived tumor tissue into immunocompromised mice, such as athymic nude or non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In the current study, we attempted to develop patient-derived xenograft (PDX) models using tissue fragments from surgical samples of brain tumors. Methods: In this approach, tiny tissue fragments of tumors were biopsied from eight brain tumor patients-seven glioblastoma patients and one primitive neuroectodermal tumor patient. Two administration methods-a cut-down syringe and a pipette-were used to implant tissue fragments from each patient into the brains of athymic nude mice. Results: In contrast to previous reports, and contrary to our expectations, we found that none of these fragments from brain tumor biopsies resulted in the successful establishment of xenograft tumors. Conclusions: These results suggest that fragments of surgical specimens from brain tumor patients are unsuitable for implementation of brain tumor PDX models, and instead recommend other in vivo testing platforms for brain tumors, such as cell-based brain tumor models.

KW - Glioblastoma

KW - Model failure

KW - Patient-derived xenograft

KW - Primitive neuro-ectodermal tumor

KW - Tissue fragment

UR - http://www.scopus.com/inward/record.url?scp=84975508943&partnerID=8YFLogxK

U2 - 10.1186/s12935-016-0319-0

DO - 10.1186/s12935-016-0319-0

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AN - SCOPUS:84975508943

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JO - Cancer Cell International

JF - Cancer Cell International

SN - 1475-2867

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