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catenin hepatocellular carcinoma

Vittoria Castiglioni, Enrico Radaelli
Murine hepatoblastoma (HB) is a rare spontaneous tumor with controversial histogenesis. It mainly occurs in aged males, frequently in close association with preexisting hepatocellular neoplasms. The present work describes a spontaneous HB arising within a hepatocellular carcinoma (HCC) in a 22-month-old male C57BL/6J mouse. The mouse also developed pulmonary co-metastases with either tumor components physically associated within the same metastatic foci. Microscopically, the HB consisted of a densely cellular neoplastic growth composed of palisades and perivascular pseudorosettes of poorly differentiated primitive cells, with a scant amount of cytoplasm, elongated hyperchromatic nuclei, and a high mitotic rate, whereas the hepatocellular carcinoma was composed of solid areas of neoplastic hepatocytes...
July 2018: Journal of Toxicologic Pathology
Limin Liu, Xingsheng Hu, Dangze Sun, Yao Wu, Zhanwei Zhao
The incidence and mortality of hepatocellular carcinoma (HCC) is high, but the mechanisms underlying the growth and progression of HCC have not been elucidated. Recently, the ZIC family member 5 (ZIC5) is emerging as an oncogene in various types of tumors. However, its expression and biological role in HCC have not been reported. This study first demonstrated that ZIC5 was up-regulated in HCC specimens, and high ZIC5 expression indicated poor prognosis of HCC patients. In addition, over-expressed ZIC5 promoted the proliferation, migration and invasion of HCC cell lines Huh7 and HepG2 in vitro and in vivo, while ZIC5 knockdown achieved the opposite effects...
August 4, 2018: Biochemical and Biophysical Research Communications
Dong-Yan Zhang, Xue-Jing Zou, Chuan-Hui Cao, Ting Zhang, Ling Lei, Xiao-Long Qi, Li Liu, De-Hua Wu
Long non-coding RNAs (lncRNAs) have recently been identified as critical regulators in tumor initiation and development. However, the function of lncRNAs in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of lncRNA MIR22HG in HCC. Methods: We evaluated MIR22HG expression in 52-patient, 145-patient, TCGA, and GSE14520 HCC cohorts. The effects of MIR22HG on HCC were analyzed in terms of proliferation, invasion, and metastasis, both in vitro and in vivo ...
2018: Theranostics
Chuan Xing Wu, Xiao Qi Wang, Siu Ho Chok, Kwan Man, Simon Hing Yin Tsang, Albert Chi Yan Chan, Ka Wing Ma, Wei Xia, Tan To Cheung
Rationale: Hepatocellular carcinoma (HCC) is an aggressive malignant solid tumor wherein CDK1/PDK1/β-Catenin is activated, suggesting that inhibition of this pathway may have therapeutic potential. Methods: CDK1 overexpression and clinicopathological parameters were analyzed. HCC patient-derived xenograft (PDX) tumor models were treated with RO3306 (4 mg/kg) or sorafenib (30 mg/kg), alone or in combination. The relevant signaling of CDK1/PDK1/β-Catenin was measured by western blot. Silencing of CDK1 with shRNA and corresponding inhibitors was performed for mechanism and functional studies...
2018: Theranostics
Anuj Verma, Munita Bal, Mukta Ramadwar, Kedar Deodhar, Prachi Patil, Mahesh Goel
BACKGROUND: Activation of Wnt/β-catenin pathway has been implicated as a mechanism of oncogenesis of hepatocellular carcinoma (HCC). CTNNB1 mutation, which encodes for β-catenin, has been found to be the most common underlying genetic alteration. In this study, we evaluated the frequency of aberrant β-catenin expression in our cohort of HCC cases and explored its correlation with clinicopathologic features. METHODS: Fifty-three cases of histologically proven HCC were included in this study...
October 2017: Indian Journal of Cancer
Sun Young Yim, Jae-Jun Shim, Ji-Hyun Shin, Yun Seong Jeong, Sang-Hee Kang, Sang-Bae Kim, Young Gyu Eun, Dong Jin Lee, Elizabeth A Conner, Valentina M Factor, David D Moore, Randy L Johnson, Snorri S Thorgeirsson, Ju-Seog Lee
Hepatocellular carcinoma (HCC) is a heterogeneous disease. Mouse models are commonly used as preclinical models to study hepatocarcinogenesis, but how well these models recapitulate molecular subtypes of human HCC is unclear. Here, integration of genomic signatures from molecularly and clinically defined human HCC (n=11) and mouse models of HCC (n=9) identified the mouse models that best resembled subtypes of human HCC and determined the clinical relevance of each model. Mst1/2 KO, Sav1 KO, and SV40 T antigen mouse models effectively recapitulated subtypes of human HCC with a poor prognosis, whereas the Myc transgenic model best resembled human HCCs with a more favorable prognosis...
August 6, 2018: Molecular Cancer Research: MCR
Alexandra Montagner, Laurent Le Cam, Hervé Guillou
No abstract text is available yet for this article.
August 4, 2018: Gut
Harshul Pandit, Yan Li, Xuanyi Li, Weizhong Zhang, Suping Li, Robert C G Martin
BACKGROUND: Hepatocellular carcinoma (HCC) is among the deadliest cancers due to its heterogeneity, contributing to chemoresistance and recurrence. Cancer stem-like cells (CSCs) are suggested to play an important role in HCC tumorigenesis. This study investigates the role of Wnt/β-catenin pathway in CSC enrichment and the capabilities of these CSCs in tumor initiation in orthotopic immunocompetent mouse model. METHODS: HCC-CSCs were enriched using established serum-free culture method...
August 3, 2018: BMC Cancer
Jian Zheng, Eran Sadot, Joana A Vigidal, David S Klimstra, Vinod P Balachandran, T Peter Kingham, Peter J Allen, Michael I D'Angelica, Ronald P DeMatteo, William R Jarnagin, Andrea Ventura
BACKGROUND: Hepatocellular adenomas (HCA) are benign liver tumors that may transform into hepatocellular carcinoma (HCC), but the molecular drivers of this transformation remain ill-defined. This study evaluates the molecular changes in HCA and HCC and in comparison to their adjacent non-neoplastic liver. METHODS: 11 patients with HCA and 10 patients with HCC without underlying hepatitis or cirrhosis were included in this pilot study. Tumor and non-tumor liver tissues were selected for immunohistochemical staining, small RNA sequencing, and targeted gene sequencing...
2018: PloS One
Stephanie Aicher, Athanasios Kakkanas, Lisette Cohen, Brigitte Blumen, Gabriela Oprisan, Richard Njouom, Eliane F Meurs, Penelope Mavromara, Annette Martin
Clinical studies have suggested association of some hepatitis C virus (HCV) subtypes or isolates with progression toward hepatocellular carcinoma (HCC). HCV core protein has been reported to interfere with host Wnt/β-catenin pathway, a cell fate-determining pathway, which plays a major role in HCC. Here, we investigated the impact of HCV core genetic variability in the dysregulation of Wnt/β-catenin pathway. We used both transient expression of core proteins from clinical isolates of HCV subtypes 1a (Cambodia), 4a (Romania) and 4f (Cameroon) and infection systems based on a set of engineered intergenotypic recombinant viruses encoding core from these various clinical strains...
July 25, 2018: Scientific Reports
Min Liu, Ke Jiang, Guibin Lin, Peng Liu, Yumei Yan, Tian Ye, Gang Yao, Martin P Barr, Dapeng Liang, Yang Wang, Peng Gong, Songshu Meng, Haozhe Piao
BACKGROUND: Aberrant activation of β-catenin and Yes-associated protein (YAP) signaling pathways has been associated with hepatocellular carcinoma (HCC) progression. The LIM domain protein Ajuba regulates β-catenin and YAP signaling and is implicated in tumorigenesis. However, roles and mechanism of Ajuba expression in HCC cells remain unclear. The E3 ligase Hakai has been shown to interact with other Ajuba family members and whether Hakai interacts and regulates Ajuba is unknown. METHODS: HCC cell lines stably depleted of Ajuba or Hakai were established using lentiviruses expressing shRNAs against Ajuba or Hakai...
July 24, 2018: Journal of Experimental & Clinical Cancer Research: CR
Yu-Feng Yang, Ying-Hua Pan, Qiu-Hong Tian, Dan-Chun Wu, Shu-Guang Su
Dysregulation of chromobox proteins contributes to the progression of human diseases. CBX1 has been implicated in epigenetic control of chromatin structure and gene expression, but its role in human cancers remains largely unknown. Here we show that CBX1 exhibits oncogenic activities in hepatocellular carcinoma (HCC) and indicates poor outcomes. The expression of CBX1 was noticeably increased, at both mRNA and protein levels, in HCC tissues and cell lines, compared with the nontumorous ones. High CBX1 expression was significantly associated with larger tumor size, poor tumor differentiation and tumor vascular invasion...
July 18, 2018: Translational Oncology
Junwei Song, Chan Xie, Lili Jiang, Geyan Wu, Jinrong Zhu, Shuxia Zhang, Miaoling Tang, Libing Song, Jun Li
It has been reported that the transcription factor activating enhancer-binding protein 4 (TFAP4) is upregulated and associated with an aggressive phenotype in several cancers. However, the precise mechanisms underlying the oncogenic role of TFAP4 remain largely unknown. Methods: TFAP4 expression levels in hepatocellular carcinoma (HCC) cells and tissues were detected by quantitative real-time PCR (qPCR) and immunohistochemistry (IHC). In vitro and in vivo assays were performed to investigate the oncogenic function of TFAP4 in the tumor-initiating cell (TIC)-like phenotype and the tumorigenic capability of HCC cells...
2018: Theranostics
Yang Yang, Yu-Chen Ye, Yan Chen, Jun-Long Zhao, Chun-Chen Gao, Hua Han, Wen-Chao Liu, Hong-Yan Qin
Tumor-associated macrophages (TAMs) are a major component of tumor microenvironment (TME) and play pivotal roles in the progression of hepatocellular carcinoma (HCC). Wnt signaling is evolutionarily conserved and participates in liver tumorigenesis. Several studies have shown that macrophage-derived Wnt ligands can activate Wnt signaling in tumor cells. However, whether Wnt ligands secreted by tumor cells can trigger Wnt signaling in macrophages is still elusive. In this study, we first verified that canonical Wnt/β-catenin signaling was activated during monocyte-to-macrophage differentiation and in M2-polarized macrophages...
July 18, 2018: Cell Death & Disease
Valeria Schinzari, Eleonora Timperi, Giulia Pecora, Francesco Palmucci, Daniela Gallerano, Alessio Grimaldi, Daniela Angela Covino, Nicola Guglielmo, Fabio Melandro, Emy Manzi, Andrea Sagnotta, Francesco Lancellotti, Luca Sacco, Piero Chirletti, Gian Luca Grazi, Massimo Rossi, Vincenzo Barnaba
In this study, we investigated the role of the Wnt/β-catenin signaling pathway in antitumor immune responses. We report that the concentration of secreted Wnt3a was significantly higher in conditioned medium from tumor or nontumor tissues obtained from all hepatocellular carcinoma or colorectal cancer patients tested, than in serum of healthy donors or patients. In addition, both Wnt3a and β-catenin were overexpressed by tumor-infiltrating and nontumor-infiltrating CD4+ or CD8+ T cells. The majority of these T cells expressed a dysfunctional effector memory Eomes+ T-bet- phenotype that we defined as partially exhausted, because they performed effector functions (in terms of interferon-γ and tumor necrosis factor-α production, as well as CD107a mobilization) despite their PD-1 expression...
August 2018: Cancer Immunology Research
Pei Hu, Changzheng Ke, Xingrong Guo, Pan Ren, Yaoyao Tong, Sen Luo, Yulin He, Zhiqiang Wei, Bin Cheng, Ruiming Li, Jie Luo, Zhongji Meng
AIM: The aim of this study is to investigate the role of glypican-3(GPC3)/wnt/β-catenin signaling pathway and autophagy in the regulation of hepatocellular carcinoma (HCC) growth mediated by curcumin. METHODS: HepG2 cells were treated with various concentrations of curcumin and/or GPC3-targeting siRNA in the presence or absence of 3-MA. Cell proliferation and apoptosis were determined by MTT and TUNEL assay, respectively. Expression of GPC3, β-catenin, c-myc, LC3, and Beclin1 was determined by western blotting...
June 21, 2018: Digestive and Liver Disease
Wei Chen, Jia You, Qi Zheng, Yue-Yong Zhu
Introduction: Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) by regulating gene expression. However, the identification of functional lncRNAs in HCC remains insufficient. Our study aimed to investigate the function of lncRNA OGFRP1, which has not been functionally researched before, in Hep3B and HepG2 cells. Methods: lncRNA OGFRP1 in HCC cells was down-regulated by using RNAi technology...
2018: Cancer Management and Research
Ningjia Cao, Liang Mu, Wei Yang, Li Liu, Liang Liang, Hong Zhang
MicroRNAs (miRNAs) are solid factors involved in the initiation and progression of hepatocellular carcinoma (HCC). Recently, miR-298 is recognized as a cancer-associated miRNA in breast, gastric and ovarian cancer. However, the functional role of miR-298 and its underlying mechanism are rarely reported in HCC. Herein, we found that the expression of miR-298 was down-regulated in HCC tissues and cell lines. The in vitro experiments showed that miR-298 overexpression inhibited cell proliferation, migration and invasion, and induced G1 arrest and apoptosis of HCC cells...
July 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ling Liu, Zile Huang, Jingjing Chen, Jiangang Wang, Shuying Wang
BACKGROUND: JS-K is a nitric oxide (NO) donor and could generate intracellularly high levels of NO. The study explores PP2A as a tumor suppressor is a major determinant mediating JS-K-caused apoptosis in human hepatocellular carcinoma (HCC) cells. METHODS: The human HCC cell lines (PLC5, Huh-7, Bel-7402, SMMC-7721 and HepG2) were used to assess effects of JS-K on cell viability, apoptosis induction and PP2A activation. Effects of JS-K on cell morphology, mitochondrial membrane potential, apoptosis and NO levels were determined in HCC cells expressing PP2A...
July 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
Ahmed M Khalaf, David Fuentes, Ali I Morshid, Mata R Burke, Ahmed O Kaseb, Manal Hassan, John D Hazle, Khaled M Elsayes
Hepatocellular carcinoma (HCC) is one of the most common primary hepatic malignancies and one of the fastest-growing causes of cancer-related mortality in the United States. The molecular basis of HCC carcinogenesis has not been clearly identified. Among the molecular signaling pathways implicated in the pathogenesis of HCC, the Wnt/β-catenin signaling pathway is one of the most frequently activated. A great effort is under way to clearly understand the role of this pathway in the pathogenesis of HCC and its role in the transition from chronic liver diseases, including viral hepatitis, to hepatocellular adenomas (HCAs) and HCCs and its targetability in novel therapies...
2018: Journal of Hepatocellular Carcinoma
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