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Gastrointestinal cancer
Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer
Jihoon Kang, Ji-Young Lee, Sunmin Lee, Danbee Kim, Jinyeong Lim, Ha Ra Jun, Seyeon Jeon, Young-Ae Kim, Hye Seon Park, Kyu-pyo Kim, Sung-Min Chun, Hee Jin Lee, Changhoon Yoo
Cancer Res Treat. 2023;55(1):219-230.   Published online April 6, 2022
DOI: https://doi.org/10.4143/crt.2021.1166
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC.
Materials and Methods
Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed.
Results
From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines.
Conclusion
We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

Citations

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  • Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
    Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
    Journal of Clinical Medicine.2024; 13(9): 2718.     CrossRef
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  • 194 Download
  • 1 Web of Science
  • 1 Crossref
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Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer
Lan Ying Li, Hee Jung Kim, Sun Ae Park, So Hyun Lee, Lee Kyung Kim, Jung Yun Lee, Sunghoon Kim, Young Tae Kim, Sang Wun Kim, Eun Ji Nam
Cancer Res Treat. 2019;51(3):1117-1127.   Published online November 6, 2018
DOI: https://doi.org/10.4143/crt.2018.405
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing.
Materials and Methods
To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA).
Results
Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25, HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845).
Conclusion
We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

Citations

Citations to this article as recorded by  
  • Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
    Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
    Journal of Clinical Medicine.2024; 13(9): 2718.     CrossRef
  • Uncovering miRNA–mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors
    Łukasz Biegała, Damian Kołat, Arkadiusz Gajek, Elżbieta Płuciennik, Agnieszka Marczak, Agnieszka Śliwińska, Michał Mikula, Aneta Rogalska
    Cells.2024; 13(10): 867.     CrossRef
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    Yihan Liu, Wantao Wu, Changjing Cai, Hao Zhang, Hong Shen, Ying Han
    Signal Transduction and Targeted Therapy.2023;[Epub]     CrossRef
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    Martina Muste Sadurni, Marco Saponaro
    Applied Biosciences.2023; 2(3): 459.     CrossRef
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    Genes.2023; 14(10): 1848.     CrossRef
  • Prediction of Chemoresistance—How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer
    Jacek Wilczyński, Edyta Paradowska, Justyna Wilczyńska, Miłosz Wilczyński
    Current Oncology.2023; 31(1): 229.     CrossRef
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    Journal of Personalized Medicine.2023; 14(1): 49.     CrossRef
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    Cancers.2021; 13(16): 4029.     CrossRef
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    Cancers.2020; 12(8): 2269.     CrossRef
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    Metallomics.2020; 12(10): 1542.     CrossRef
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    Bernd Nürnberg, Sandra Beer-Hammer
    Biomolecules.2019; 9(9): 427.     CrossRef
  • 10,554 View
  • 341 Download
  • 19 Web of Science
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Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models
Kyung Jin Eoh, Young Shin Chung, So Hyun Lee, Sun-Ae Park, Hee Jung Kim, Wookyeom Yang, In Ok Lee, Jung-Yun Lee, Hanbyoul Cho, Doo Byung Chay, Sunghoon Kim, Sang Wun Kim, Jae-Hoon Kim, Young Tae Kim, Eun Ji Nam
Cancer Res Treat. 2018;50(3):956-963.   Published online October 17, 2017
DOI: https://doi.org/10.4143/crt.2017.181
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients.
Materials and Methods
Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity.
Results
Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers.
Conclusions
Tumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

Citations

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  • TOWARDS Study: Patient-Derived Xenograft Engraftment Predicts Poor Survival in Patients With Newly Diagnosed Triple-Negative Breast Cancer
    Christos Vaklavas, Cindy B. Matsen, Zhengtao Chu, Kenneth M. Boucher, Sandra D. Scherer, Satya Pathi, Anna Beck, Kirstyn E. Brownson, Saundra S. Buys, Namita Chittoria, Elyse D'Astous, H. Evin Gulbahce, N. Lynn Henry, Stephen Kimani, Jane Porretta, Regina
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    Journal of the American College of Surgeons.2023; 237(3): 483.     CrossRef
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  • 238 Download
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Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies
Eun Jin Heo, Young Jae Cho, William Chi Cho, Ji Eun Hong, Hye-Kyung Jeon, Doo-Yi Oh, Yoon-La Choi, Sang Yong Song, Jung-Joo Choi, Duk-Soo Bae, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Woong-Yang Park, Byoung-Gie Kim, Jeong-Won Lee
Cancer Res Treat. 2017;49(4):915-926.   Published online January 4, 2017
DOI: https://doi.org/10.4143/crt.2016.322
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.
Materials and Methods
We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.
Results
Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor–overexpressing PDX with clear cell histology (p=0.023).
Conclusion
PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.

Citations

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    Tomohito Tanaka, Ruri Nishie, Shoko Ueda, Shunsuke Miyamoto, Sousuke Hashida, Hiromi Konishi, Shinichi Terada, Yuhei Kogata, Hiroshi Sasaki, Satoshi Tsunetoh, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
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