Article
Oncology
Yuan-Hung Kuo, Yi-Hao Yen, Yen-Yang Chen, Kwong-Ming Kee, Chao-Hung Hung, Sheng-Nan Lu, Tsung-Hui Hu, Chien-Hung Chen, Jing-Houng Wang
Summary: This study compared the effectiveness of nivolumab and regorafenib as second-line therapies for hepatocellular carcinoma patients after sorafenib failure. The results showed similar treatment outcomes between nivolumab and regorafenib, with slightly better response rates in the nivolumab group. Despite differences in treatment-related adverse events, there were no significant disparities in time to progression and overall survival between the two groups.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Flavia Fondevila, Carolina Mendez-Blanco, Paula Fernandez-Palanca, Tania Payo-Serafin, Jos van Pelt, Chris Verslype, Javier Gonzalez-Gallego, Jose L. Mauriz
Summary: Early acquisition of sorafenib resistance in advanced hepatocarcinoma is a critical factor for poor prognosis. Autophagy, particularly regulated by FOXO3, is involved in modulating chemosensitivity. Targeting FOXO3-mediated autophagy may significantly improve the clinical efficacy of sorafenib in HCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Chong Zhang, Lin-Wen Wu, Zhi-Di Li, Man-Man Zhang, Jie Wu, Fei-Hua Du, Ling-Hui Zeng, Yang-Ling Li
Summary: The study revealed a link between hyperactivation of DYRK1A/HIF-1α signaling and increased risk of liver cancer. Knockdown of DYRK1A or treatment with harmine reduced HIF-1α expression levels in liver cancer cells under hypoxia, while DYRK1A overexpression had the opposite effect. DYRK1A was found to interact and activate STAT3 to regulate HIF-1α expression. Furthermore, harmine attenuated the proliferative ability of liver cancer cells under hypoxia, and DYRK1A knockdown enhanced the anti-liver cancer effects of regorafenib and sorafenib. Co-treatment with harmine and either regorafenib or sorafenib promoted cell death via the STAT3/HIF-1α/AKT signaling pathway.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Cell Biology
Ece Sariyar, Ozum Karpat, Sila Sezan, Sude Misra Baylan, Arda Kipcak, Kadriye Guven, Esra Erdal, Zeynep Firtina Karagonlar
Summary: This article describes a sorafenib resistant 3D tumor spheroid model for testing second-line treatment options in hepatocellular carcinoma (HCC). The study found that these resistant spheroids also exhibited resistance to other drugs, higher populations of cancer stem cells, upregulation of oncogenic kinases, and effective cell death induction with combined inhibition of EGFR and Lyn kinase. This model provides important insights into drug resistance and potential combinational therapies.
CELLULAR SIGNALLING
(2023)
Article
Medicine, Research & Experimental
Zu-Yau Lin, Ming-Lun Yeh, Ching-I. Huang, Po-Cheng Liang, Po-Yao Hsu, Shinn-Cherng Chen, Chung-Feng Huang, Jee-Fu Huang, Chia -Yen Dai, Ming -Lung Yu, Wan -Long Chuang
Summary: The advantage of combining colchicine with sorafenib or regorafenib in treating hepatocellular carcinoma (HCC) was investigated. The results showed that colchicine enhanced the anti-proliferative effects of sorafenib and regorafenib and regulated the expression of target genes and cancer stem cell markers.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Gastroenterology & Hepatology
Andrea Casadei-Gardini, Giulia Rovesti, Vincenzo Dadduzio, Caterina Vivaldi, Eleonora Lai, Sara Lonardi, Lorenzo Fornaro, Andrea Pretta, Vittorina Zagonel, Laura Bernardini, Giorgio Astara, Francesco E. D'Amico, Gianluca Masi, Margherita Rimini, Mario Scartozzi, Stefano Cascinu
Summary: The study findings suggest that the concomitant use of aspirin with sorafenib in patients with advanced HCC is associated with improved clinical outcomes, including longer overall survival and progression-free survival.
Article
Gastroenterology & Hepatology
Takeshi Terashima, Tatsuya Yamashita, Noboru Takata, Yasuhito Takeda, Hidenori Kido, Noriho Iida, Masaaki Kitahara, Tetsuro Shimakami, Hajime Takatori, Kuniaki Arai, Kazunori Kawaguchi, Kazuya Kitamura, Taro Yamashita, Yoshio Sakai, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
Summary: Sequential administration of sorafenib followed by regorafenib or lenvatinib is effective against advanced hepatocellular carcinoma, with similar safety profiles observed between sorafenib and regorafenib but differences in adverse events and anti-tumor effects between sorafenib and lenvatinib. The results provide insights for selecting sequential therapy for patients with advanced HCC.
HEPATOLOGY RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Massimo Iavarone, Federica Invernizzi, Tommy Ivanics, Stefano Mazza, Claudio Zavaglia, Marco Sanduzzi-Zamparelli, Miguel Fraile-Lopez, Carolin Czauderna, Giovanni Di Costanzo, Sherrie Bhoori, Matthias Pinter, Matteo Angelo Manini, Giuliana Amaddeo, Ainhoa Fernandez Yunquera, Federico Pinero, Maria Jose Blanco Rodriguez, Margarita Anders, Gabriel Aballay Soteras, Gerda Elisabeth Villadsen, Peter Daechul Yoon, Lucia Cesarini, Alvaro Diaz-Gonzalez, Maria Luisa Gonzalez-Dieguez, Raffaella Tortora, Arndt Weinmann, Vincenzo Mazzaferro, Mario Romero Cristobal, Gonzalo Crespo, Helene Regnault, Massimo De Giorgio, Maria Varela, Rebecca Prince, Luigia Scudeller, Maria Francesca Donato, Marcus-Alexander Worns, Jordi Bruix, Gonzalo Sapisochin, Pietro Lampertico, Maria Reig
Summary: This study demonstrates that regorafenib has a longer survival benefit in hepatocellular carcinoma patients after liver transplantation and sorafenib discontinuation, making it an effective second-line treatment option.
LIVER TRANSPLANTATION
(2021)
Article
Gastroenterology & Hepatology
Won Ick Chang, Byoung Hyuck Kim, Yoon Jun Kim, Jung-Hwan Yoon, Yong Jin Jung, Eui Kyu Chie
Summary: This study aimed to investigate the clinical benefits of locoregional radiation therapy (RT) before, after, and concurrent with sorafenib therapy for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. The results showed that locoregional RT was associated with significantly longer survival in BCLC stage C HCC patients who were treated with sorafenib, especially in patients treated with sorafenib for 12 weeks or more. Incorporating locoregional RT could improve the dismal prognosis for these patients.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Chemistry, Medicinal
Shuli Man, Chen Luo, Mengyao Yan, Ganggang Zhao, Long Ma, Wenyuan Gao
Summary: This article discusses the formation process and therapeutic targets of liver cancer, as well as the current development of natural products in anti-liver cancer treatment. It points out the potential advantages of natural products in intervening in the formation and development of liver cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Andrea Casadei-Gardini, Lorenza Rimassa, Margherita Rimini, Changhoon Yoo, Baek-Yeol Ryoo, Sara Lonardi, Gianluca Masi, Hyung-Don Kim, Caterina Vivaldi, Min-Hee Ryu, Mario Domenico Rizzato, Francesca Salani, Yeonghak Bang, Antonio Pellino, Silvia Catanese, Valentina Burgio, Stefano Cascinu, Alessandro Cucchetti
Summary: The study found no difference in overall survival between regorafenib and cabozantinib in HCC patients previously treated with sorafenib, but a greater benefit may be expected from cabozantinib treatment in faster progressing patients on prior sorafenib therapy.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Zhihui Dong, Zhuoshan Huang, Senlin Li, Ying Wang, Yandan Yao, Xianzhu Yang, Xiaoding Xu
Summary: Tumor microenvironment (TME) pH-responsive nanoparticles (NPs) were developed for systemic mRNA delivery to reverse trastuzumab resistance in breast cancer. These NPs, consisting of a pH-liable polymer and lipid, could efficiently deliver PTEN mRNA into tumor cells and up-regulate PTEN expression, ultimately blocking the PI3K/Akt signaling pathway and reversing trastuzumab resistance in breast cancer.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Chemistry, Medicinal
Chen Zhang, Wu Zhong, Ying Cao, Bohao Liu, Xiaojun Tao, Zhuan Li
Summary: Polylysine polymer nanoparticles modified with cholesterol and GSH-sensitive PEG (mPssPC) were constructed to load sorafenib (SOR) and the SIRT7 inhibitor 2800Z, forming dual-loaded NPs (S2@PsPCs) to reduce toxicity and increase efficacy of sorafenib in liver cancer treatment.
Article
Oncology
Yeonghak Bang, Changhoon Yoo, Sara Lonardi, Hyung-Don Kim, Caterina Vivaldi, Margherita Rimini, Giovanni Luca Frassineti, Sook Ryun Park, Mario Domenico Rizzato, Min-Hee Ryu, Francesca Salani, Ilario Giovanni Rapposelli, Baek-Yeol Ryoo, Zagonel Vittorina, Valentina Massa, Martina Valgiusti, Valentina Burgio, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini
Summary: A multicentre, retrospective study conducted in Italy and Korea revealed the superiority of sorafenib-regorafenib treatment sequence over sorafenib and physician's choice for patients with hepatocellular carcinoma (HCC). Survival analysis showed that patients treated with sorafenib-regorafenib had longer median overall survival and a reduced risk of death compared to those treated with sorafenib and physician's choice.
Article
Oncology
Hung-Wei Wang, Po-Heng Chuang, Wen-Pang Su, Jung-Ta Kao, Wei-Fan Hsu, Chun-Che Lin, Guan-Tarn Huang, Jaw-Town Lin, Hsueh-Chou Lai, Cheng-Yuan Peng
Summary: The study showed that albumin-bilirubin grade and alpha-fetoprotein level before regorafenib therapy can serve as predictors of disease control and survival rates in patients with unresectable hepatocellular carcinoma.
Article
Oncology
Justin H. Y. Yu, Stephanie Ma
Summary: Organoid culture is a valuable tool in cancer research, overcoming the limitations of previous models by recapitulating in vivo biology. HCC organoids, generated from human and murine tissue samples, retain key characteristics of parental tumor tissues and are useful in drug discovery and personalized medicine.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Lei Zhou, Ken H. O. Yu, Tin Lok Wong, Zhao Zhang, Chun Ho Chan, Jane H. C. Loong, Noelia Che, Hua Jian Yu, Kel Vin Tan, Man Tong, Elly S. Ngan, Joshua W. K. Ho, Stephanie Ma
Summary: This study utilized mouse models to investigate the heterogeneity and dynamics of Prom1+ cells in HCC, revealing their CSC-like properties and clonal expansion within tumors. Labelled Prom1+ cells showed increased tumorigenicity in 3D culture and allotransplantation, while depletion of these cells impeded tumor growth. Single-cell RNA sequencing analysis highlighted the heterogeneity of Prom1+ HCC cells and their potential role in disease progression.
Editorial Material
Oncology
Lei Zhou, Stephanie Ma
Review
Biochemistry & Molecular Biology
Ki-Fong Man, Stephanie Ma
Summary: This review provides a comprehensive summary of the intrinsic and extrinsic mechanisms of TKI resistance in liver CSCs, as well as potential strategies to overcome resistance.
ESSAYS IN BIOCHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Yin Tong, Priscilla S. W. Cheng, Chung Sze Or, Sarah S. K. Yue, Hoi Cheong Siu, Siu Lun Ho, Simon Y. K. Law, Wai Yin Tsui, Dessy Chan, Stephanie Ma, Siu Po Lee, Annie S. Y. Chan, April S. Chan, Shui Wa Yun, Ho Sang Hui, Siu Tsan Yuen, Suet Yi Leung, Helen H. N. Yan
Summary: Cell-cell and cell-matrix adhesions play a critical role in gastric cancer progression, especially in gastric cancer with dysregulated RHO signaling.
Review
Gastroenterology & Hepatology
Ka-Hei Lam, Stephanie Ma
Summary: Cancer stem cells (CSCs) are a major cause of treatment failure and tumor recurrence in hepatocellular carcinoma (HCC). In addition to intrinsic regulators, extrinsic regulators in the tumor microenvironment also play a crucial role in the regulation of CSCs.
Article
Gastroenterology & Hepatology
Tsz Lam Matthew Wong, Tin-Lok Wong, Lei Zhou, Kwan Man, James Purcell, Terence K. Lee, Jing-Ping Yun, Stephanie Ma
Summary: In this study, a kinase called protein tyrosine kinase 7 (PTK7) was identified as a significantly upregulated molecule in advanced and metastatic hepatocellular carcinoma (HCC). Functional and signaling studies revealed that PTK7 can enhance the metastatic potential of HCC cells by promoting epithelial-mesenchymal transition. These findings suggest that PTK7 could be a potential target for antimetastatic therapies.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dongdong Yan, Di Cui, Yun Zhu, Cecilia Ka Wing Chan, Chung Hang Jonathan Choi, Tengfei Liu, Nikki P. Y. Lee, Simon Law, Sai Wah Tsao, Stephanie Ma, Annie Lai Man Cheung
Summary: This study found that the expression of Cation-dependent mannose-6-phosphate receptor (M6PR) and ephrin type-B receptor 4 (EphB4) was significantly upregulated in exosomes derived from serglycin (SRGN)-overexpressing esophageal squamous cell carcinoma (ESCC) cells (SRGN Exo). SRGN Exo promoted ESCC cell invasion and tumor angiogenesis by upregulating M6PR, and enhanced ESCC cell invasion through upregulating EphB4. The expression levels of M6PR and EphB4 in the serum were positively correlated with SRGN expression levels in ESCC patients, and high serum M6PR levels were associated with poor overall survival rates.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yifei Wang, Man Tong
Summary: The posttranslational modifications (PTMs) of proteins play a critical role in protein regulation, enhancing proteome functional diversity and participating in complicated biological processes. In cancer biology, PTMs have been shown to interact with pro-tumorigenic signaling pathways, contributing to neoplastic transformation, tumor recurrence, and resistance to therapy. Cancer stemness, which maintains tumor cell self-renewal and differentiation, is essential in cancer development and therapy resistance. Understanding the PTM profile for modulating cancer stemness has shed light on the underlying mechanisms and potential therapeutic targets for gastrointestinal cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Zhixin Li, Kathy Nga-Chu Lui, Sin-Ting Lau, Frank Pui-Ling Lai, Peng Li, Patrick Ho-Yu Chung, Kenneth Kak-Yuen Wong, Paul Kwong-Hing Tam, Maria-Mercedes Garica-Barcelo, Chi-Chung Hui, Pak Chung Sham, Elly Sau-Wai Ngan
Summary: Using induced pluripotent stem cell-based models and single-cell transcriptomic analysis, the study identifies a set of 118 commonly dysregulated genes in enteric neural crest cells of Hirschsprung disease patients, and suggests HDAC1 as a key regulator of these genes. The study also reveals that upregulation of RNA splicing mediators and enhanced alternative splicing events are associated with severe form of the disease. Overall, the research defines various factors associated with Hirschsprung pathogenesis.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Tin-Lok Wong, Jia-Jian Loh, Shixun Lu, Helen H. N. Yan, Hoi Cheong Siu, Ren Xi, Dessy Chan, Max J. F. Kam, Lei Zhou, Man Tong, John A. Copland, Leilei Chen, Jing-Ping Yun, Suet Yi Leung, Stephanie Ma
Summary: By establishing 5FU+CDDP resistant organoid lines from gastric cancer patients, this study reveals that JAK/STAT signaling and its downstream target ADAR1 are upregulated, and ADAR1 contributes to chemoresistance and self-renewal through RNA editing. The study also finds hyper-edited lipid metabolism genes in the resistant lines, and ADAR1-mediated editing on SCD1 promotes lipid droplet formation, alleviating chemotherapy-induced ER stress and enhancing self-renewal. Inhibition of SCD1 reverses chemoresistance and reduces tumor-initiating cell frequency, and higher levels of ADAR1 and SCD1 or a high SCD1 editing/ADAR1 mRNA signature predict worse prognosis.
NATURE COMMUNICATIONS
(2023)
Article
Cell & Tissue Engineering
Kathy Nga-Chu Lui, Zhixin Li, Frank Pui-Ling Lai, Sin-Ting Lau, Elly Sau-Wai Ngan
Summary: This study used human pluripotent stem cells to generate human brainstem organoids, and found that mutations in the PHOX2B gene disrupt the formation of RTN neurons. The study further investigated the association between PHOX2B polyalanine repeat mutations and malformation of the respiratory center, demonstrating the potential toxic gain of function of PHOX2B-PARMs.
Article
Gastroenterology & Hepatology
Martina Mang Leng Lei, Carmen Oi Ning Leung, Eunice Yuen Ting Lau, Rainbow Wing Hei Leung, Victor Wan San Ma, Man Tong, Yin Ying Lu, Chen Yang Huang, Qiao Hua Zhu, Irene Oi Lin Ng, Stephanie Ma, Terence Kin Wah Lee
Summary: This study reveals that SCYL3 plays a critical role in promoting the progression of hepatocellular carcinoma (HCC). It is often overexpressed in HCC, especially in metastatic tumors, and is associated with worse patient survival. Suppression of SCYL3 attenuates cell proliferation, migration, and in vivo metastasis in HCC.
Article
Chemistry, Multidisciplinary
Yuan Gao, Man Tong, Tin-Lok Wong, Kai-Yu Ng, Yu-Nong Xie, Zhaowei Wang, Huajian Yu, Jia-Jian Loh, Meng Li, Stephanie Ma
Summary: This study investigates the role of long noncoding RNAs (lncRNAs) in sorafenib-induced ferroptosis in hepatocellular carcinoma (HCC) cells. URB1-antisense RNA 1 (AS1), a ferroptosis-related lncRNA, was found to be highly expressed in sorafenib-resistant HCC samples and predict poor survival in HCC. URB1-AS1 mitigates sorafenib-induced ferroptosis by inducing ferritin phase separation and reducing cellular free iron content.
Article
Biochemical Research Methods
Man Tong, Stephanie Ma
Summary: Three-dimensional organoids, resembling the original tissues in pathophysiology and structural architecture, are valuable in vitro models for studying metabolic activities in response to environmental or nutritional changes. This article provides a step-by-step protocol for establishing and culturing mouse and human hepatic tumor organoids, as well as two efficient approaches for investigating the effects of metabolites/drugs on the viability and metabolic functions of tumor organoids.