Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model

Vaeteewoottacharn, Kulthida; Pairojkul, Chawalit; Kariya, Ryusho; Muisuk, Kanha; Imtawil, Kanokwan; Chamgramol, Yaovalux; Bhudhisawasdi, Vajarabhongsa; Khuntikeo, Narong; Pugkhem, Ake; Saeseow, O-tur; Silsirivanit, Atit; Wongkham, Chaisiri; Wongkham, Sopit; Okada, Seiji

doi:10.3390/cells8050496

Cited by 34 publications

(25 citation statements)

References 40 publications

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“…The duration of tumor establishment in mice differs among tumors, taking from a few days to a few months for the tumor nodule to be observed (first generation; F0). After serial transplantation, the duration of tumor growth becomes stable, with approximately 40–50 days required to obtain certain sized tumors [53,57]. The PDX samples should be stored together with the patient’s clinical data, gene-expression patterns, mutational statuses, drug responsiveness, and pathological analysis to generate a PDX library.…”

Section: Establishment Of Pdx Models Using Various Immunocompromismentioning

confidence: 99%

“…Since nude mice have benefits such as a relatively high engraftment ratios of gastrointestinal tumors, easy observation of subcutaneous tumors, and relatively low price, they remain an important resource for PDX establishment [31,53,62]. The BRJ mice have been used as alternative recipients of cholangiocarcinoma PDX, with a high engraftment ratio (75%) [57,63]. Other solid tumors, such as head and neck tumors, gastric cancers, and bladder cancers, are now under investigation.…”

Section: Establishment Of Pdx Models Using Various Immunocompromismentioning

confidence: 99%

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Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models

Okada

Vaeteewoottacharn

Kariya

2019

Cells

195

184

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Patient-derived xenograft (PDX) models are created by engraftment of patient tumor tissues into immunocompetent mice. Since a PDX model retains the characteristics of the primary patient tumor including gene expression profiles and drug responses, it has become the most reliable in vivo human cancer model. The engraftment rate increases with the introduction of Non-obese diabetic Severe combined immunodeficiency (NOD/SCID)-based immunocompromised mice, especially the NK-deficient NOD strains NOD/SCID/interleukin-2 receptor gamma chain(IL2Rγ)null (NOG/NSG) and NOD/SCID/Jak3(Janus kinase 3)null (NOJ). Success rates differ with tumor origin: gastrointestinal tumors acquire a higher engraftment rate, while the rate is lower for breast cancers. Subcutaneous transplantation is the most popular method to establish PDX, but some tumors require specific environments, e.g., orthotropic or renal capsule transplantation. Human hormone treatment is necessary to establish hormone-dependent cancers such as prostate and breast cancers. PDX mice with human hematopoietic and immune systems (humanized PDX) are powerful tools for the analysis of tumor–immune system interaction and evaluation of immunotherapy response. A PDX biobank equipped with patients’ clinical data, gene-expression patterns, mutational statuses, tumor tissue architects, and drug responsiveness will be an authoritative resource for developing specific tumor biomarkers for chemotherapeutic predictions, creating individualized therapy, and establishing precise cancer medicine.

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Section: Establishment Of Pdx Models Using Various Immunocompromismentioning

confidence: 99%

Section: Establishment Of Pdx Models Using Various Immunocompromismentioning

confidence: 99%

Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models

Okada

Vaeteewoottacharn

Kariya

2019

Cells

195

184

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“…This prolonged time should be considered as a negative factor when PDX models would be used as "Avatars" for therapy personalization. [56] iCCA NSG FGFR2-CCDC6 gene fusion [215] iCCA NGS DH1 R132C mutation [216] iCCA NOD/SCID Constitutive expression of FGFR 1-4 mRNA and FRS2 [217] iCCA CD1 immunodeficient nude NOTCH1 overexpression [219] iCCA B-NDG miceBALB/c (nu/nu) nude CDK7 overexpression [220] iCCA NOD/SCID YAP overexpression [204] iCCA Balb/c RJ mice Oct-3/4 or Sox2 expression [60] iCCA NOD/SCID Sodium-dependent vitamin C transporter 2 (SVCT-2) expression [221] eCCA Balb/c RJ mice Oct-3/4 or Sox2 expression [60] iCCA: intrahepatic cholangiocarcinoma; eCCA: extrahepatic cholangiocarcinoma; NOD/SCID: nonobese diabetic/severe combined immunodeficiency; NSG: NOD-scid IL2rγ null ; B-NDG; NOD-Prkdc scid IL2rg tm1 /Bcgen.…”

Section: Patient-derived Xenograft (Pdx)mentioning

confidence: 99%

Evolution of the Experimental Models of Cholangiocarcinoma

Massa

Varamo

Vita

et al. 2020

Cancers

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Cholangiocarcinoma (CCA) is a rare, aggressive disease with poor overall survival. In advanced cases, surgery is often not possible or fails; in addition, there is a lack of effective and specific therapies. Multidisciplinary approaches and advanced technologies have improved the knowledge of CCA molecular pathogenesis, highlighting its extreme heterogeneity and high frequency of genetic and molecular aberrations. Effective preclinical models, therefore, should be based on a comparable level of complexity. In the past years, there has been a consistent increase in the number of available CCA models. The exploitation of even more complex CCA models is rising. Examples are the use of CRISPR/Cas9 or stabilized organoids for in vitro studies, as well as patient-derived xenografts or transgenic mouse models for in vivo applications. Here, we examine the available preclinical CCA models exploited to investigate: (i) carcinogenesis processes from initiation to progression; and (ii) tools for personalized therapy and innovative therapeutic approaches, including chemotherapy and immune/targeted therapies. For each model, we describe the potential applications, highlighting both its advantages and limits.

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“…PDX models of CCA are still underdeveloped but also closely recapitulate the primary tumours. 88 Until recently, only a few PDX models of paediatric liver cancer had been developed. [89][90][91] More recently, 2 independent studies have established comprehensive cohorts of paediatric liver tumour PDXs.…”

Section: Patient-derived Xenograftsmentioning

confidence: 99%

Novel patient-derived preclinical models of liver cancer

Bresnahan

Ramadori

Heikenwälder

et al. 2020

Journal of Hepatology

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Preclinical models of cancer based on the use of human cancer cell lines and mouse models have enabled discoveries that have been successfully translated into patients. And yet the majority of clinical trials fail, emphasising the urgent need to improve preclinical research to better interrogate the potential efficacy of each therapy and the patient population most likely to benefit. This is particularly important for liver malignancies, which lack highly efficient treatments and account for hundreds of thousands of deaths around the globe. Given the intricate network of genetic and environmental factors that contribute to liver cancer development and progression, the identification of new druggable targets will mainly depend on establishing preclinical models that mirror the complexity of features observed in patients. The development of new 3D cell culture systems, originating from cells/tissues isolated from patients, might create new opportunities for the generation of more specific and personalised therapies. However, these systems are unable to recapitulate the tumour microenvironment and interactions with the immune system, both proven to be critical influences on therapeutic outcomes. Patient-derived xenografts, in particular with humanised mouse models, more faithfully mimic the physiology of human liver cancer but are costly and time-consuming, which can be prohibitive for personalising therapies in the setting of an aggressive malignancy. In this review, we discuss the latest advances in the development of more accurate preclinical models to better understand liver cancer biology and identify paradigm-changing therapies, stressing the importance of a bi-directional communicative flow between clinicians and researchers to establish reliable model systems and determine how best to apply them to expanding our current knowledge.

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Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model

Cited by 34 publications

References 40 publications

Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models

Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models

Evolution of the Experimental Models of Cholangiocarcinoma

Novel patient-derived preclinical models of liver cancer

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