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Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation
BACKGROUND: The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models. METHODS: T...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Chinese Speaking Orthopaedic Society
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173097/ https://www.ncbi.nlm.nih.gov/pubmed/34136349 http://dx.doi.org/10.1016/j.jot.2021.04.004 |
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author | Yafei, Jiang Haoran, Mu Wenyan, Jiang Linghang, Xue Kai, Tian Gangyang, Wang Zhuoying, Wang Jing, Han Mengkai, Yang Yujie, Tang Yingqi, Hua Zhengdong, Cai |
author_facet | Yafei, Jiang Haoran, Mu Wenyan, Jiang Linghang, Xue Kai, Tian Gangyang, Wang Zhuoying, Wang Jing, Han Mengkai, Yang Yujie, Tang Yingqi, Hua Zhengdong, Cai |
author_sort | Yafei, Jiang |
collection | PubMed |
description | BACKGROUND: The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models. METHODS: Tumor samples obtained from a malignant GCTB was implanted in immunodeficient mice for the generation of PDX. Histological examination and short tandem repeat (STR) were used for inherited features analyses. An epigenetic/transcriptional targeted compound library was selected for drug screening. The in vivo effects of selected drug were validated in PDX model. RESULTS: We established the PDX model with recurrent malignant GCTB specimens, histological examination and STR analyses revealed that PDX and their corresponding parental patients shared the same STRs and histologic features, suggesting common origins. ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM. The results of the drug screening and in vivo PDX validation demonstrated that ITF-2357 might be a promising drug targeted H3F3A G34W mutation MGCTBs. CONCLUSION: Our study demonstrates that PDX model maintained the same histologic and genetic features as those in the original patient. targeting HDAC through ITF-2357 effectively overcomes malignant GCTB progression in vitro and in vivo. TRANSLATIONAL POTENTIAL STATEMENT: As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB. |
format | Online Article Text |
id | pubmed-8173097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Chinese Speaking Orthopaedic Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-81730972021-06-15 Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation Yafei, Jiang Haoran, Mu Wenyan, Jiang Linghang, Xue Kai, Tian Gangyang, Wang Zhuoying, Wang Jing, Han Mengkai, Yang Yujie, Tang Yingqi, Hua Zhengdong, Cai J Orthop Translat Original Article BACKGROUND: The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models. METHODS: Tumor samples obtained from a malignant GCTB was implanted in immunodeficient mice for the generation of PDX. Histological examination and short tandem repeat (STR) were used for inherited features analyses. An epigenetic/transcriptional targeted compound library was selected for drug screening. The in vivo effects of selected drug were validated in PDX model. RESULTS: We established the PDX model with recurrent malignant GCTB specimens, histological examination and STR analyses revealed that PDX and their corresponding parental patients shared the same STRs and histologic features, suggesting common origins. ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM. The results of the drug screening and in vivo PDX validation demonstrated that ITF-2357 might be a promising drug targeted H3F3A G34W mutation MGCTBs. CONCLUSION: Our study demonstrates that PDX model maintained the same histologic and genetic features as those in the original patient. targeting HDAC through ITF-2357 effectively overcomes malignant GCTB progression in vitro and in vivo. TRANSLATIONAL POTENTIAL STATEMENT: As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB. Chinese Speaking Orthopaedic Society 2021-06-01 /pmc/articles/PMC8173097/ /pubmed/34136349 http://dx.doi.org/10.1016/j.jot.2021.04.004 Text en © 2021 Department of Orthopaedic, Shanghai General Hospital, Shanghai JiaoTong Univeraity school of medicine https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Yafei, Jiang Haoran, Mu Wenyan, Jiang Linghang, Xue Kai, Tian Gangyang, Wang Zhuoying, Wang Jing, Han Mengkai, Yang Yujie, Tang Yingqi, Hua Zhengdong, Cai Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation |
title | Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation |
title_full | Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation |
title_fullStr | Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation |
title_full_unstemmed | Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation |
title_short | Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation |
title_sort | personalized medicine modality based on patient-derived xenografts from a malignant transformed gctb harboring h3f3a g34w mutation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173097/ https://www.ncbi.nlm.nih.gov/pubmed/34136349 http://dx.doi.org/10.1016/j.jot.2021.04.004 |
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