scholarly journals Establishment and Characterization of Feline Mammary Tumor Patient-Derived Xenograft Model

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2380
Author(s):  
Hsiao-Li Chuang ◽  
Yi-Chih Chang ◽  
Yi-Ting Huang ◽  
Jiunn-Wang Liao ◽  
Pei-Ling Kao ◽  
...  
Keyword(s):  
Mammary Tumor ◽  
Xenograft Model ◽  
Cancer Therapies ◽  
Metastatic Progression ◽  
In Vivo Models ◽  
Tumor Patient ◽  
Nsg Mice ◽  
Patient Derived Xenograft

Feline mammary tumor is a relatively commonly diagnosed neoplasm in the cat. Development of new veterinary cancer therapies is limited by the shortage of in vivo models that reproduce tumor microenvironment and metastatic progression. Four feline mammary tumor orthotopic patient-derived xenograft model (PDX) successfully established in NOD-SCID gamma (NSG) mice. The overall success rate of PDX establishment was 36% (4/11). Histological, immunohistochemical, and short tandem repeat analysis showed a remarkable similarity between patient’s tumor and xenograft. The tumor grafts conserve original tumor essential features, including distant metastasis. Primary FMT-1807 cell line isolated from FMT-1807PDX tumor tissue. Tumorigenicity of FMT-1807 cells expanded from PDX was assessed by orthotopic injection into NSG mice. Mice yielded tumors which preserve the lung and liver metastasis ability. This work provides a platform for FMT translational investigation.

Establishment and Characterization of a Feline Mammary Tumor Patient-Derived Xenograft Model

2021 ◽  
Author(s):  
Hsiao-Li Chuang ◽  
Yi-Chih Chang ◽  
Yi-Ting Huang ◽  
Jiunn-Wang Liao ◽  
Yi-Lo Lin ◽  
...  
Keyword(s):  
Mammary Tumor ◽  
Xenograft Model ◽  
Cancer Therapies ◽  
Metastatic Progression ◽  
In Vivo Models ◽  
Tumor Patient ◽  
Pdx Model ◽  
Short Tandem

Abstract BackgroundFeline mammary tumor (FMT) is a relatively commonly diagnosed neoplasm in the cat. Development of new veterinary cancer therapies is limited by the shortage of in vivo models that reproduce tumor microenvironment and metastatic progression. ResultsFour FMT-patient‐derived xenografts (PDX) successfully established in NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ mice. The overall success rate of PDX establishment was 36% (4/11). Histological, immunohistochemical, and short tandem repeat analysis showed a remarkable similarity between patient's tumor and PDX.ConclusionsIn this study, FMT-PDX model were established. The tumor grafts conserve original tumor essential features, including distant metastasis. FMT-PDX represents an available resource for bridging the biology of FMT with preclinical studies of FMT in cats.

Establishment and characterization of an ovarian yolk sac tumor patient-derived xenograft model

2021 ◽  
Author(s):  
Manling Luo ◽  
Yuanqiao He ◽  
Baogang Xie ◽  
Shiyun Li ◽  
Fuqiang Gan ◽  
...  
Keyword(s):  
Xenograft Model ◽  
Yolk Sac ◽  
Yolk Sac Tumor ◽  
Tumor Patient ◽  
Patient Derived Xenograft

scholarly journals TMOD-15. EFFICACY OF THE MDM2 INHIBITOR KRT-232 IN GLIOBLASTOMA PATIENT-DERIVED XENOGRAFT MODELS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii231-ii231
Author(s):  
Rachael Vaubel ◽  
Ann Mladek ◽  
Yu Zhao ◽  
Shiv K Gupta ◽  
Minjee Kim ◽  
...  
Keyword(s):  
Target Genes ◽  
Xenograft Model ◽  
Culture Conditions ◽  
Patient Derived Xenograft ◽  
Fold Induction ◽  
Extended Survival ◽  
Mdm2 Amplification ◽  
Mdm2 Inhibitor

Abstract Non-genotoxic reactivation of p53 by MDM2 inhibitors represents a promising therapeutic strategy for tumors with wild-type TP53, particularly tumors harboring MDM2 amplification. MDM2 controls p53 levels by targeting it for degradation, while disruption of the MDM2-p53 interaction causes rapid accumulation of p53 and activation of the p53 pathway. We examined the efficacy of the small molecule MDM2 inhibitor KRT-232, alone and in combination with radiation therapy (RT), in MDM2-amplified and/or p53 wildtype patient-derived xenograft (PDX) models of glioblastoma in vitro and in vivo. In vitro, glioblastoma PDX explant cultures showed sensitivity to KRT-232, both tumors with MDM2 amplification (GBM108 and G148) and non-amplified but TP53-wildtype lines (GBM10, GBM14, and GBM39), with IC50s ranging from 300-800 nM in FBS culture conditions. A TP53 p.F270C mutant PDX (GBM43) was inherently resistant, with IC50 >3000 nM. In the MDM2-amplified GBM108 line, KRT-232 led to a robust (5-6 fold) induction of p53-target genes p21, PUMA, and NOXA, with initiation of both apoptosis and senescence. Expression of p21 and PUMA was greater with KRT-232 in combination with RT (25-35 fold induction), while stable knock-down of p53 in GBM108 led to complete resistance to KRT-232. In contrast, GBM10 showed lower induction of p21 and PUMA (2-3 fold) and was more resistant to KRT-232. In an orthotopic GBM108 xenograft model, treatment with KRT-232 +/- RT for one week extended survival from 22 days (placebo) to 46 days (KRT-232 alone); combination KRT-232 + RT further extended survival (77 days) over RT alone (31 days). KRT-232 is an effective treatment in a subset of glioblastoma pre-clinical models alone and in combination with RT. Further studies are underway to understand the mechanisms conferring innate sensitivity or resistance to KRT-232.

scholarly journals Development and Characterization of a Spontaneously Metastatic Patient-Derived Xenograft Model of Human Prostate Cancer

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Tobias Lange ◽  
Su Jung Oh-Hohenhorst ◽  
Simon A. Joosse ◽  
Klaus Pantel ◽  
Oliver Hahn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Xenograft Model ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Patient Derived Xenograft

scholarly journals Two Decades of Triazine Dendrimers

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4774
Author(s):  
Eric E. Simanek
Keyword(s):  
Genetic Material ◽  
Structural Complexity ◽  
Bioactive Molecules ◽  
Bioactive Materials ◽  
In Vivo Models ◽  
Tumor Subtypes ◽  
Gas Streams

For two decades, methods for the synthesis and characterization of dendrimers based on [1,3,5]-triazine have been advanced by the group. Motivated by the desire to generate structural complexity on the periphery, initial efforts focused on convergent syntheses, which yielded pure materials to generation three. To obtain larger generations of dendrimers, divergent strategies were pursued using iterative reactions of monomers, sequential additions of triazine and diamines, and ultimately, macromonomers. Strategies for the incorporation of bioactive molecules using non-covalent and covalent strategies have been explored. These bioactive materials included small molecule drugs, peptides, and genetic material. In some cases, these constructs were examined in both in vitro and in vivo models with a focus on targeting prostate tumor subtypes with paclitaxel conjugates. In the materials realm, the use of triazine dendrimers anchored on solid surfaces including smectite clay, silica, mesoporous alumina, polystyrene, and others was explored for the separation of volatile organics from gas streams or the sequestration of atrazine from solution. The combination of these organics with metal nanoparticles has been probed. The goal of this review is to summarize these efforts.

scholarly journals Characterization of the Potent, Selective Nrf2 Activator, 3-(Pyridin-3-Ylsulfonyl)-5-(Trifluoromethyl)-2H-Chromen-2-One, in Cellular and In Vivo Models of Pulmonary Oxidative Stress

2017 ◽  
Vol 363 (1) ◽  
pp. 114-125 ◽  
Author(s):  
John G. Yonchuk ◽  
Joseph P. Foley ◽  
Brian J. Bolognese ◽  
Gregory Logan ◽  
William E. Wixted ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Vivo Models ◽  
Nrf2 Activator

scholarly journals Induction of Acquired Resistance towards EGFR Inhibitor Gefitinib in a Patient-Derived Xenograft Model of Non-Small Cell Lung Cancer and Subsequent Molecular Characterization

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 740 ◽  
Author(s):  
Julia Schueler ◽  
Cordula Tschuch ◽  
Kerstin Klingner ◽  
Daniel Bug ◽  
Anne-Lise Peille ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Xenograft Model ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Ratio ◽  
Patient Derived Xenograft ◽  
Resistant Lines

In up to 30% of non-small cell lung cancer (NSCLC) patients, the oncogenic driver of tumor growth is a constitutively activated epidermal growth factor receptor (EGFR). Although these patients gain great benefit from treatment with EGFR tyrosine kinase inhibitors, the development of resistance is inevitable. To model the emergence of drug resistance, an EGFR-driven, patient-derived xenograft (PDX) NSCLC model was treated continuously with Gefitinib in vivo. Over a period of more than three months, three separate clones developed and were subsequently analyzed: Whole exome sequencing and reverse phase protein arrays (RPPAs) were performed to identify the mechanism of resistance. In total, 13 genes were identified, which were mutated in all three resistant lines. Amongst them the mutations in NOMO2, ARHGEF5 and SMTNL2 were predicted as deleterious. The 53 mutated genes specific for at least two of the resistant lines were mainly involved in cell cycle activities or the Fanconi anemia pathway. On a protein level, total EGFR, total Axl, phospho-NFκB, and phospho-Stat1 were upregulated. Stat1, Stat3, MEK1/2, and NFκB displayed enhanced activation in the resistant clones determined by the phosphorylated vs. total protein ratio. In summary, we developed an NSCLC PDX line modelling possible escape mechanism under EGFR treatment. We identified three genes that have not been described before to be involved in an acquired EGFR resistance. Further functional studies are needed to decipher the underlying pathway regulation.

Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer

Biomaterials ◽  
2018 ◽  
Vol 159 ◽  
pp. 229-240 ◽  
Author(s):  
Eliza Li Shan Fong ◽  
Tan Boon Toh ◽  
Quy Xiao Xuan Lin ◽  
Zheng Liu ◽  
Lissa Hooi ◽  
...  
Keyword(s):  
Liver Cancer ◽  
In Vivo Models ◽  
Patient Derived Xenograft
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