Article
Biochemistry & Molecular Biology
Pei-Wei Shueng, Hui-Wen Chan, Wei-Chan Lin, Deng-Yu Kuo, Hui-Yen Chuang
Summary: Sorafenib is an effective drug for hepatocellular carcinoma, but resistance often occurs. This study found that resistance to sorafenib could be reversed by inhibiting fatty acid synthesis using orlistat, and this combination treatment enhanced cell killing in hepatocellular carcinoma by altering cell metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Letter
Biochemistry & Molecular Biology
Xiao-Dong Yang, Fan-En Kong, Ling Qi, Jia-Xin Lin, Qian Yan, Jane Ho Chun Loong, Shao-Yan Xi, Yue Zhao, Yan Zhang, Yun-Fei Yuan, Ning-Fang Ma, Stephanie Ma, Xin-Yuan Guan, Ming Liu
Summary: PARP1 plays important roles in stem cell pluripotency and HCC sorafenib treatment resistance. Overexpression of PARP1 is closely associated with poor clinical outcome in HCC patients. Olaparib suppresses DNA damage repair signaling and the global pluripotent transcriptional network, enhancing sorafenib in eliminating HCC residual tumors.
Article
Oncology
Zibo Chen, Tao Yuan, Fangjie Yan, Song Ye, Qin Xie, Bo Zhang, Nengmin Lin, Qiaojun He, Bo Yang, Hong Zhu
Summary: This study demonstrates that the intratumor hypoxia characteristic of advanced HCC is a major factor in sorafenib resistance, and the novel multi-kinase inhibitor CT-707 can sensitize hypoxic HCC cells to sorafenib. It was also found that CT-707 reverses the hypoxia-mediated sorafenib resistance by inhibiting YAP nuclear translocation.
Article
Pharmacology & Pharmacy
Zhengguang Zhang, Haitao Wu, Yajie Zhang, Cunsi Shen, Fuqiong Zhou
Summary: The natural product quercetin (QUE) can reverse the resistance of SOR-resistant cells to sorafenib (SOR), enhancing its efficacy by inhibiting proliferation, stimulating apoptosis, and suppressing tumor growth. This effect is possibly mediated through mechanisms involving EGFR tyrosine kinase inhibitor resistance, the PI3K-AKT signaling pathway, and HCC.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Cell Biology
Qiujie Wang, Cheng Bin, Qiang Xue, Qingzhu Gao, Ailong Huang, Kai Wang, Ni Tang
Summary: The study revealed that GSTZ1 enhances sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in HCC cells, and the combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Davide Gnocchi, Agata Kurzyk, Antonella Mintrone, Giovanni Lentini, Carlo Sabba, Antonio Mazzocca
Summary: Hepatocellular carcinoma (HCC) is a highly threatening tumor, and the current pharmacological treatments for HCC rely on protein kinase inhibitors. However, these approaches often result in side effects and drug resistance. This study reveals that LPAR6-mediated metabolic mechanism contributes to sorafenib resistance in HCC and proposes a pharmacological approach to overcome it.
Article
Oncology
Shusil K. Pandit, Giada Sandrini, Jessica Merulla, Valentina Nobili, Xin Wang, Alessia Zangari, Andrea Rinaldi, Dheeraj Shinde, Giuseppina M. Carbone, Carlo V. Catapano
Summary: Enhanced expression of mitochondrial ribosomal proteins and significant reprogramming of the mitochondrial network are associated with sorafenib resistance in human cell lines and hepatocarcinoma patients. This suggests potential actionable targets for improving therapeutic efficacy.
Article
Cell & Tissue Engineering
Sining Zhou, Yiming Liu, Qi Zhang, Huikang Xu, Yangxin Fang, Xin Chen, Jiamin Fu, Yin Yuan, Yifei Li, Li Yuan, Charlie Xiang
Summary: In this study, it was found that MenSCs reversed the sorafenib resistance in HCC-SR cells by upregulating the expression levels of BNIP3 and BNIP3L. In addition, MenSCs induced cell death in HCC-SR cells by regulating autophagy and mitochondrial function. Therefore, the combination therapy of sorafenib and MenSCs may be a promising strategy to overcome sorafenib resistance in HCC-SR cells.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Oncology
Chaoran Shi, Dora Lai-Wan Kwong, Xue Li, Xia Wang, Xiaona Fang, Liangzhan Sun, Ying Tang, Xin-Yuan Guan, Shan-Shan Li
Summary: Hepatocellular cancer (HCC) is a lethal subtype of liver cancer, and effective therapeutics are lacking. Understanding and targeting cancer stem cells (CSCs) can revolutionize cancer management. Maelstrom (MAEL) is implicated in the regulation of CSC phenotypes, and our study demonstrates that MAEL positively regulates cancer stem-cell-like properties in HCC. MAEL silencing enhances tumor cells' sensitivity to sorafenib. Our study also reveals the involvement of the MAEL-dependent PGST2/IL8/AKT/STAT3 signaling pathway in the regulation of stemness. Targeting the MAEL/PGST2 axis may be a potential therapeutic strategy against CSC and sorafenib resistance in HCC.
Article
Oncology
Jiali Zhao, En Lin, Zirui Bai, Yingbin Jia, Bo Wang, Yihua Dai, Wenfeng Zhuo, Guifang Zeng, Xialei Liu, Chaonong Cai, Peiping Li, Baojia Zou, Jian Li
Summary: Activated cancer-associated fibroblasts (CAFs) were found to be present in high levels in hepatocellular carcinoma (HCC) tissues but not in paracancerous tissues. CAFs induce sorafenib resistance in HCC cells by secreting CXCL12, which upregulates FOLR1 in HCC cells.
Article
Biochemistry & Molecular Biology
Zongqiang Hu, Yingpeng Zhao, Laibang Li, Jie Jiang, Wang Li, Yuanyi Mang, Yang Gao, Yun Dong, Jiashun Zhu, Chaomin Yang, Jianghua Ran, Li Li, Shengning Zhang
Summary: Metformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3, inhibiting the progression of HCC and sorafenib resistance.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Oncology
Bisha Ding, Chang Bao, Luqi Jin, Liang Xu, Weimin Fan, Weiyang Lou
Summary: The study demonstrated that CASK expression was positively associated with sorafenib resistance and poor prognosis in hepatocellular carcinoma (HCC) patients. Inhibition of CASK increased the sensitivity to sorafenib by promoting apoptosis and autophagy, while CASK overexpression led to the opposite effects. CASK may serve as a promising biomarker and potential therapeutic target for HCC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Yuchuan Jiang, Peng Chen, Kaishun Hu, Guanqi Dai, Jinying Li, Dandan Zheng, Hui Yuan, Lu He, Penghui Xie, Mengxian Tu, Shuang Peng, Chen Qu, Wenyu Lin, Raymond T. Chung, Jian Hong
Summary: This study found that persistent liver injury promotes the growth and metastasis of HCC, which is positively correlated with the degree of liver inflammation rather than the extent of liver fibrosis. Inflammatory cytokines in liver tissue were clearly increased after liver injury. The two indicated cytokines, TNF-α and IL-6, both promoted intrahepatic HCC progression via STAT3 activation.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Oncology
Yan Liao, Yue Yang, Di Pan, Youxiang Ding, Heng Zhang, Yuting Ye, Jia Li, Li Zhao
Summary: Hypoxia in solid tumors induces resistance to chemotherapy, and in this study, researchers established a hypoxia model to investigate Sorafenib resistance in Hepatocellular carcinoma (HCC). The study revealed that HSP90 alpha plays a crucial role in Sorafenib resistance under hypoxia by promoting chaperone-mediated autophagy degradation. The results suggest that HSP90 alpha inhibitor, Demethoxygeldanamycin (17-AAG), could potentially reverse Sorafenib resistance in liver cancer.
Article
Oncology
Lirong Chen, Chenhe Yi, Wenshuai Li, Yujen Tseng, Jun Zhang, Jie Liu
Summary: This study elucidated the significant mechanism of SPATS2-TRIM44-p-STAT3 in HCC and provided a new theoretical basis for targeted therapy, showing that high SPATS2 protein level is indicative of an unfavorable clinicopathological feature and poor prognosis in 112 HCC patients.
Review
Oncology
Sung-Hsin Kuo, Kun-Huei Yeh, Chung-Wu Lin, Jyh-Ming Liou, Ming-Shiang Wu, Li-Tzong Chen, Ann-Lii Cheng
Summary: The prevalence of HP-negative gastric MALT lymphoma has increased, while HP-positive gastric MALT lymphoma has decreased. Some case studies have shown that a first-line HP eradication therapy (HPE)-like regimen can result in complete remission for some patients with localized HP-negative gastric MALT lymphoma. Previous sporadic reports have also indicated that some patients with extragastric MALT lymphoma can respond to antibiotic treatment.
Article
Oncology
Yu-Yun Shao, Pai-Sheng Chen, Liang-In Lin, Bin-Shyun Lee, Andrew Ling, Ann-Lii Cheng, Chiun Hsu, Da-Liang Ou
Summary: This study identified miR-10b-3p as a potential biomarker for predicting sorafenib efficacy in advanced HCC patients and confirmed its mechanism of action.
BRITISH JOURNAL OF CANCER
(2022)
Review
Medicine, General & Internal
Tsung-Hao Liu, Ying-Chun Shen, Ann-Lii Cheng
Summary: In recent years, there has been a rapid expansion in systemic therapy options for advanced hepatocellular carcinoma (HCC), particularly in the use of single agent immune checkpoint inhibitors (ICI) and combinations with targeted therapies. These developments have shown significant efficacy and have shifted the treatment paradigm for advanced HCC.
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2022)
Review
Virology
Yi-Wen Huang, Albert Qin, Chan-Yen Tsai, Pei-Jer Chen
Summary: Ropeginterferon alfa-2b is a promising treatment option for MPN and chronic viral hepatitis due to its favorable pharmacokinetic profile and demonstrated efficacy in clinical studies. Administered once every two weeks, it has shown to be well-tolerated and effective in treating chronic hepatitis B, C, and D.
Review
Oncology
Chiao-Ling Li, Shiou-Hwei Yeh, Pei-Jer Chen
Summary: Cell-free tumor DNA (ctDNA) is a promising tumor marker that can reflect tumor burden, behavior, and prognosis. However, there are still challenges to be addressed before ctDNA can be used as a tumor marker. We propose using exogenous viral DNA integration to generate virus-host chimera DNA (vh-DNA) as a potential new biomarker. vh-DNA may overcome detection problems and serve as a universal marker for monitoring tumor expansion or burden related to oncogenic viruses.
Article
Oncology
Chia-Lun Hong, I-Shing Yu, Chen-Hsueh Pai, Jin-Shing Chen, Min-Shu Hsieh, Hua-Lin Wu, Shu-Wha Lin, Hsiang-Po Huang
Summary: CD248 maintains pericyte function in lung cancer through the Wnt signaling pathway and upregulates angiogenic factors, suggesting it as a potential therapeutic target.
Article
Oncology
Kuo-Hsing Chen, Chia-Lang Hsu, Yu-Li Su, Chang-Tsu Yuan, Liang-In Lin, Jia-Huei Tsai, Yi-Hsin Liang, Ann-Lii Cheng, Kun-Huei Yeh
Summary: This study found that the immune contexture in the tumor microenvironment is closely associated with prognosis in patients with metastatic BRAF V600E mutant colorectal cancer. High expression of immune genes and complement activation are correlated with poor prognosis, and the complement score is strongly correlated with tumor-associated macrophage M2 signatures.
BRITISH JOURNAL OF CANCER
(2023)
Article
Gastroenterology & Hepatology
Masatoshi Kudo, Richard S. Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Ann-Lii Cheng, Arndt Vogel, Francesco Tovoli, Kazuomi Ueshima, Hiroshi Aikata, Carlos Lopez Lopez, Marc Pracht, Zhiqiang Meng, Bruno Daniele, Joong-Won Park, Daniel Palmer, Toshiyuki Tamai, Kenichi Saito, Corina E. Dutcus, Riccardo Lencioni
Summary: The study aimed to validate objective response as an independent predictor of overall survival (OS) in individuals with unresectable hepatocellular carcinoma (HCC) receiving systemic anti-angiogenic therapy. The results showed that objective response assessed by investigator-assessed mRECIST could predict the survival of patients. Further studies are needed to confirm this finding.
JOURNAL OF HEPATOLOGY
(2023)
Article
Oncology
Yu-Yun Shao, Hung-Wei Hsu, Rita Robin Wo, Han-Yu Wang, Ann-Lii Cheng, Chih-Hung Hsu
Summary: CDK9 inhibitors have been found to have potent anti-proliferative and apoptosis-inducing activities against HCC cells, while inhibiting downstream signaling molecules' phosphorylation. Animal experiments have confirmed the inhibitory effects of CDK9 inhibitors on HCC. Overexpression of CDK9 reduced the efficacy of CDK9 inhibitors, while knockdown of CDK9 expression reduced the proliferative activities of HCC cells.
Article
Medicine, General & Internal
Chen-Hua Liu, Chun-Jen Liu, Tung-Hung Su, Shang-Chin Huang, Tai-Chung Tseng, Jo-Hsuan Wu, Pei-Jer Chen, Jia-Horng Kao
Summary: This study found a strong correlation between serum M2BPGi levels and the severity of hepatic fibrosis in patients with HCV infection, and identified specific cutoff values that can be used for accurate diagnosis.
Article
Gastroenterology & Hepatology
Chiao-Ling Tsai, Po-Sheng Yang, Feng-Ming Hsu, Ann-Lii Cheng, Wan-Ni Yu, Jason Chia-Hsien Cheng
Summary: This study investigated the effect of TOP1 inhibition and DNA-PKcs/RNF144A mechanism on radiosensitization mediated by natural killer (NK) cells in radiation therapy (RT). The results showed that TOP1 inhibitors and RT had a synergistic effect on hepatocellular carcinoma (HCC) cells, enhancing the anti-HCC effect of RT through increased DNA damage and DNA-PKcs signaling. RNF144A mediated DNA-PKcs ubiquitination and provided a reason for the difference in radiosensitization effect between HCC cells.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Article
Oncology
Yu-Chieh Tsai, Tzu-Yin Wang, Chia-Lang Hsu, Wei-Chou Lin, Jyun-Yu Chen, Jia-Hua Li, Yeong-Shiau Pu, Ann-Lii Cheng, Jason Chia-Hsien Cheng, Sheng-Fang Su
Summary: This study found that inhibiting HDAC6 can enhance the radiosensitivity of bladder cancer and reduce the expression of genes related to cell migration, angiogenesis, and metastasis induced by radiotherapy, thereby improving therapeutic efficacy.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Masatoshi Kudo, Richard S. Finn, Ann-Lii Cheng, Andrew X. Zhu, Michel Ducreux, Peter R. Galle, Naoya Sakamoto, Naoya Kato, Michitaka Nakano, Jing Jia, Arndt Vogel
Summary: This exploratory analysis examined the prognostic impact of baseline albumin-bilirubin (ALBI) score in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab + bevacizumab or sorafenib. The study found that atezolizumab + bevacizumab improved overall survival and progression-free survival compared to sorafenib in patients with ALBI score of 1, but not in patients with ALBI score of 2. ALBI grade appeared to be prognostic for outcomes in both treatment groups.
Article
Oncology
Philippe Merle, Masatoshi Kudo, Julien Edeline, Mohamed Bouattour, Ann-Lii Cheng, Stephen Lam Chan, Thomas Yau, Marcelo Garrido, Jennifer Knox, Bruno Daniele, Valeriy Breder, Ho Yeong Lim, Sadahisa Ogasawara, Stephane Cattan, Yee Chao, Abby B. Siegel, Ivan Martinez-Forero, Ziwen Wei, Chih-Chin Liu, Richard S. Finn
Summary: With extended follow-up, pembrolizumab demonstrated continued improvement in overall survival (OS) and progression-free survival (PFS) compared to placebo in advanced hepatocellular carcinoma (HCC) patients previously treated with sorafenib. The adverse event profile of pembrolizumab remained consistent with placebo.
Article
Radiology, Nuclear Medicine & Medical Imaging
Bang-Bin Chen, Po-Chin Liang, Tiffany Ting-Fang Shih, Tsung-Hao Liu, Ying-Chun Shen, Li-Chun Lu, Zhong-Zhe Lin, Chiun Hsu, Chih-Hung Hsu, Ann-Lii Cheng, Yu-Yun Shao
Summary: Sarcopenia and myosteatosis are independent prognostic factors in patients who received immunotherapy for advanced HCC.
EUROPEAN RADIOLOGY
(2023)