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Journal of Hematology and Oncology

, 9:92

First Online: 21 September 2016Received: 13 July 2016Accepted: 03 September 2016DOI: 10.1186-s13045-016-0318-6

Cite this article as: Dong, R., Qiang, W., Guo, H. et al. J Hematol Oncol 2016 9: 92. doi:10.1186-s13045-016-0318-6

Abstract

BackgroundPatient derived xenografts PDX are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma HGSC is a deadly form of ovarian-fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient.

MethodsIn this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged from P0 to P4 and tumors were grafted orthotopically under the ovarian bursa or subcutaneously.

ResultsComparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted.

ConclusionOur findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC.

KeywordsHigh-grade serous carcinoma Patient-derived xenograft Intrabursal engraft histology Immunohistochemistry AbbreviationsPDXPatient derived xenografts

HGSCHigh-grade serous carcinoma

EOCEpithelial ovarian cancer

Taxol-CarboPaclitaxel and carboplatin

RINRNA integrity number

qPCRQuantitative real-time PCR

NODNonobese diabetic

SCSubcutaneous

IBIntrabursa

DABDiaminobenzidine

FFPEFormalin-fixation and paraffin-embedding

TMATissue microarray

SOESuccess of engraftment

N-C ratioNuclear cytoplasmic ratio

GVHDGraft-versus-host disease

CAMsCell adhesion molecules

SRSubrenal

IPIntraperitoneal

CSCCancer stem cell

Electronic supplementary materialThe online version of this article doi:10.1186-s13045-016-0318-6 contains supplementary material, which is available to authorized users.

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Autor: Ruifen Dong - Wenan Qiang - Haiyang Guo - Xiaofei Xu - J. Julie Kim - Andrew Mazar - Beihua Kong - Jian-Jun Wei

Fuente: https://link.springer.com/







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