Abstract
BackgroundWith 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.MethodsIn 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.ResultsIn 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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0319-0) contains supplementary material, which is available to authorized users.
Highlights
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
Patient-derived xenograft (PDX) models were prepared for eight brain tumor patients (Table 1) by implanting tiny tissue fragments biopsied from each patient into the brains of athymic mice (n = 3/group) using the two injection methods—cut-down syringe and pipette—described in “Methods” section
A dataset was obtained for each patient-derived xenograft (PDX) that included a pathological assessment and magnetic resonance imaging (MRI; T1 axial enhancement) of the corresponding donor, the injection method, the lifetime of the resulting PDX, and images of hematoxylin and eosin (H&E)-stained histological sections of PDX brain tissue (Fig. 2)
Summary
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. Several recent studies have reported innovative preclinical animal models generated by transplanting sectioned patient-derived tumor tissue fragments, rather than cell lines, into immunocompromised mice, such as athymic nude or non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice [7, 15,16,17,18], a concept generally referred to in the literature as patient-derived xenograft (PDX) [15, 18]. The propagation of tumors in successive generations of mouse hosts enables PDX cells to avoid the stressful conditions that possibly occur during cell culture [20] These advantages make PDXs biologically stable and enable them to maintain the molecular characteristics of the primary tumors from which they were derived [20, 21]. PDXs are useful for the preclinical testing of drugs, and to verify molecular changes and signaling pathways in oncology [1]
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