Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments.
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.
Department of Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Kyung-Min
KM
Kim
Department of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Jin-Kyoung
JK
Shim
Department of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Jong Hee
JH
Chang
Department of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Ji-Hyun
JH
Lee
Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Se-Hoon
SH
Kim
Department of Pharmacy, Yonsei University College of Pharmacy, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983 Republic of Korea.
Junjeong
J
Choi
Department of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Junseong
J
Park
Department of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Eui-Hyun
EH
Kim
Department of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Sun Ho
SH
Kim
Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Yong-Min
YM
Huh
Department of Life Science, Research Institute for Natural Sciences, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul, 04763 Republic of Korea.
Su-Jae
SJ
Lee
Department of Surgery, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Jae-Ho
JH
Cheong
Department of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea.
Seok-Gu
0000-0001-5676-2037
SG
Kang
Glioblastoma; Model failure; Patient-derived xenograft; Primitive neuro-ectodermal tumor; Tissue fragment