Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.jcmgh.2020.12.009
DC Field | Value | |
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dc.title | Predicting HCC Response to Multikinase Inhibitors With In Vivo Cirrhotic Mouse Model for Personalized Therapy | |
dc.contributor.author | Huang, Daniel Q | |
dc.contributor.author | Muthiah, Mark D | |
dc.contributor.author | Zhou, Lei | |
dc.contributor.author | Jumat, Halisah | |
dc.contributor.author | Tan, Wan Xin | |
dc.contributor.author | Lee, Guan Huei | |
dc.contributor.author | Lim, Seng Gee | |
dc.contributor.author | Kow, Alfred | |
dc.contributor.author | Bonney, Glenn | |
dc.contributor.author | Shridhar, Iyer | |
dc.contributor.author | Lim, Yi Ting | |
dc.contributor.author | Wee, Aileen | |
dc.contributor.author | Pang, Yin Huei | |
dc.contributor.author | Soon, Gwyneth | |
dc.contributor.author | Chow, Pierce | |
dc.contributor.author | Dan, Yock Young | |
dc.date.accessioned | 2021-11-23T08:57:14Z | |
dc.date.available | 2021-11-23T08:57:14Z | |
dc.date.issued | 2021-01-01 | |
dc.identifier.citation | Huang, Daniel Q, Muthiah, Mark D, Zhou, Lei, Jumat, Halisah, Tan, Wan Xin, Lee, Guan Huei, Lim, Seng Gee, Kow, Alfred, Bonney, Glenn, Shridhar, Iyer, Lim, Yi Ting, Wee, Aileen, Pang, Yin Huei, Soon, Gwyneth, Chow, Pierce, Dan, Yock Young (2021-01-01). Predicting HCC Response to Multikinase Inhibitors With In Vivo Cirrhotic Mouse Model for Personalized Therapy. CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY 11 (5) : 1313-1325. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jcmgh.2020.12.009 | |
dc.identifier.issn | 2352345X | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/207536 | |
dc.description.abstract | Background & Aims: Hepatocellular carcinoma (HCC) arises in a cirrhotic, pro-angiogenic microenvironment. Inhibiting angiogenesis is a key mode of action of multikinase inhibitors and current non-cirrhotic models are unable to predict treatment response. We present a novel mouse cirrhotic model of xenotransplant that predicts the natural biology of HCC and allows personalized therapy. Methods: Cirrhosis was induced in NOD Scid gamma mice with 4 months of thioacetamide administration. Patient derived xenografts (PDXs) were created by transplant of human HCC subcutaneously into non-cirrhotic mice and intra-hepatically into both cirrhotic and non-cirrhotic mice. The applicability of cirrhotic PDXs for drug testing was tested with 16 days of either sorafenib or lenvatinib. Treatment response was evaluated by MRI. Results: 8 out of 19 (42%) human HCC engrafted in the cirrhotic model compared with only 3 out of 19 (16%) that engrafted in the subcutaneous non-cirrhotic model. Tumor vasculature was preserved in the cirrhotic model but was diminished in the non-cirrhotic models. Metastasis developed in 3 cirrhotic PDX lines and was associated with early HCC recurrence in all 3 corresponding patients (100%), compared with only 5 out of 16 (31%) of the other PDX lines, P =.027. The cirrhotic model was able to predict response and non-response to lenvatinib and sorafenib respectively in the corresponding patients. Response to lenvatinib in the cirrhotic PDX was associated with reduction in CD34, VEGFR2 and CLEC4G immunofluorescence area and intensity (all P ≤.03). Conclusions: A clinically relevant cirrhotic PDX model preserves tumor angiogenesis and allows prediction of response to multikinase inhibitors for personalized therapy. | |
dc.language.iso | en | |
dc.publisher | ELSEVIER INC | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Gastroenterology & Hepatology | |
dc.subject | Xenograft | |
dc.subject | Hepatocellular Carcinoma | |
dc.subject | Multikinase Inhibitors | |
dc.subject | HEPATOCELLULAR-CARCINOMA | |
dc.subject | LIVER | |
dc.subject | SORAFENIB | |
dc.subject | ESTABLISHMENT | |
dc.subject | MICROENVIRONMENT | |
dc.subject | PATHOGENESIS | |
dc.type | Article | |
dc.date.updated | 2021-11-21T13:38:35Z | |
dc.contributor.department | MEDICINE | |
dc.contributor.department | PATHOLOGY | |
dc.contributor.department | PHARMACY | |
dc.contributor.department | SURGERY | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.contributor.department | INST FOR HEALTH INNOVATION & TECHNOLOGY | |
dc.description.doi | 10.1016/j.jcmgh.2020.12.009 | |
dc.description.sourcetitle | CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | |
dc.description.volume | 11 | |
dc.description.issue | 5 | |
dc.description.page | 1313-1325 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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Predicting HCC Response to Multikinase Inhibitors With In Vivo Cirrhotic Mouse Model for Personalized Therapy.pdf | 5.7 MB | Adobe PDF | CLOSED | Published |
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