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HCC signaling pathway

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https://www.readbyqxmd.com/read/28548966/targeting-shp-1-stat3-signaling-a-promising-therapeutic-approach-for-the-treatment-of-cholangiocarcinoma
#1
Ming-Hung Hu, Li-Ju Chen, Yen-Lin Chen, Ming-Shen Tsai, Chung-Wai Shiau, Tzu-I Chao, Chun-Yu Liu, Jia-Horng Kao, Kuen-Feng Chen
Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548956/dalbinol-a-rotenoid-from-amorpha-fruticosa-l-exerts-anti-proliferative-activity-by-facilitating-%C3%AE-catenin-degradation-in-hepatocellular-carcinoma-cells
#2
Xiaohui Zhu, Xin Wu, Jing Cheng, Hongbo Liao, Xiaoqing Di, Lili Li, Rong Li, Yanfang Zhou, Xiangning Zhang
Hepatocellular carcinoma (HCC) is a highly malignant tumor, and the main cause of treatment failure is malignant proliferation. Aberrations in Wnt/β-catenin signaling are associated with HCC development. Despite the improvements in overall survival made over the past decade from the advent of molecularly targeted therapies, these treatments do not have efficacy in all patients with different pathogeneses. Therefore, there is a demand for novel chemotherapeutic agents for HCC. To this end, we built a natural compound library and screened out a rotenoid named dalbinol from the seeds of Amorpha fruticosa L...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548306/zanthoxylum-avicennae-extract-enhances-gsk-3%C3%AE-to-attenuate-%C3%AE-catenin-via-phosphatase-2a-to-block-metastatic-effects-of-ha22t-cells-and-hepatocellular-carcinoma-xenografted-nude-mice
#3
Hsi-Chin Wu, Ing-Shiow Lay, Marthandam Asokan Shibu, Tsung-Jung Ho, Shiu-Min Cheng, Chih-Hao Lin, Tran Duc Dung, Long-Bin Jeng, Vijaya Padma Viswanadha, Chih-Yang Huang
Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/β-catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on β-catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock-down assays and co-immunoprecipitation assay...
May 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28547581/gender-disparity-in-hepatocellular-carcinoma-hcc-multiple-underlying-mechanisms
#4
REVIEW
Bo Zheng, Yan-Jing Zhu, Hong-Yang Wang, Lei Chen
On the global scale, hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of inflammation-driven HCC in males is three times as high as in females. Recent studies suggest that sex hormones have a crucial role in the pathogenesis and development of HBV-induced HCC. We found that the estrogen/androgen signaling pathway is associated with decreased/increased transcription and replication of HBV genes and can promote the development of HBV infections by up/downregulating HBV RNA transcription and inflammatory cytokines levels, which in turn slow down the progression of HBV-induced HCC...
May 23, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28545193/synthesis-characterization-and-cytotoxic-evaluation-of-graphene-oxide-nanosheets-in-vitro-liver-cancer-model
#5
Samah A Loutfy, Taher A Salaheldin, Marwa A Ramadan, Khaled Yehia Farroh, Zeinab F Abdallah, Tareq Youssef
Background: Graphene nanosheets have a broad spectrum of biomedical applications. Hepatocellular cancer (HCC) is a major health problem in the Egyptian population. Currently, treatment strategies are invasive and have several adverse side effects. Thus, other approaches are required for managing this aggressive type of cancer. Our objective here was to prepare and characterize graphene oxide nanosheets and evaluate cytotoxic effect at the molecular level in an in vitro human liver cancer cell model (HepG2)...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28544403/serine-protease-inhibitor-kazal-type-1-spink1-downregulates-e-cadherin-and-induces-emt-of-hepatoma-cells-to-promote-hepatocellular-carcinoma-metastasis-via-the-mek-erk-signaling-pathway
#6
Ying Hai-Yan, Gong Chao-Jie, Feng Yi, Jing Da-Dao, Lun-Gen Lu
OBJECTIVE: To investigate serine protease inhibitor Kazal type 1(SPINK1) expression and its influence on the prognosis of human hepatocellular carcinoma(HCC) and to explore the underlying molecular mechanisms involved. METHODS: Eighty patients with HCC who underwent curative resection were followed-up with a median observation time of 58.6 months.SPINK1expression was detected in the primary HCC samples by immunohistochemistry . Its role in tumor invasion and metastasis was evaluated in vitro by gene silence using siRNA-mediated approach, rSPINK1 and U0126(an inhibitor of MEK/ERK)...
May 23, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28537930/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#7
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533482/cd147-functions-as-the-signaling-receptor-for-extracellular-divalent-copper-in-hepatocellular-carcinoma-cells
#8
Pengfei Ding, Xin Zhang, Shujuan Jin, Bo Duan, Pengxiang Chu, Yufei Zhang, Zhi-Nan Chen, Bin Xia, Fei Song
Elevated copper levels in tumor microenvironment are directly correlated to cancer progression in a variety of malignancies. Copper is required in angiogenesis, and promotes the proliferation and metastasis of cancer cells. However, the molecular mechanism of copper in promoting cancer progression remains elusive. Here we report that CD147 serves as a signaling receptor for extracellular Cu2+ in hepatocellular carcinoma (HCC) cells. Cu2+ binds to the extracellular membrane-proximal domain of CD147 and mediates its self-association...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533225/multi-functional-effects-of-a-small-molecule-stat3-inhibitor-on-nash-and-hcc-in-mice
#9
Kwang Hwa Jung, Wonbeak Yoo, Heather L Stevenson, Dipti Deshpande, Hong Shen, Mihai Gagea, Suk-Young Yoo, Jing Wang, Thomas Kris Eckols, Uddalak Bharadwaj, David J Tweardy, Laura Beretta
The incidence of hepatocellular carcinoma (HCC) is increasing in the United States and liver cancer is the second leading cause of cancer-related mortality worldwide. Non-alcoholic steatohepatitis (NASH) is becoming an important risk for HCC and most patients with HCC have underlying liver cirrhosis and compromised liver function, which limit treatment options. Thus, novel therapeutic strategies to prevent or treat HCC in the context of NASH and cirrhosis are urgently needed. <br /><br />Experimental Design: Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently detected in HCC tumors...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28531143/a-4-phenoxyphenol-derivative-exerts-inhibitory-effects-on-human-hepatocellular-carcinoma-cells-through-regulating-autophagy-and-apoptosis-accompanied-by-downregulating-%C3%AE-tubulin-expression
#10
Wen-Tsan Chang, Wangta Liu, Yi-Han Chiu, Bing-Hung Chen, Shih-Chang Chuang, Yen-Chun Chen, Yun-Tzh Hsu, Mei-Jei Lu, Shean-Jaw Chiou, Chon-Kit Chou, Chien-Chih Chiu
Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines...
May 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28526827/activated-hepatic-stellate-cells-secrete-periostin-to-induce-stem-cell-like-phenotype-of-residual-hepatocellular-carcinoma-cells-after-heat-treatment
#11
Rui Zhang, Rong-Rong Yao, Jing-Huan Li, Gang Dong, Min Ma, Qiong-Dan Zheng, Dong-Mei Gao, Jie-Feng Cui, Zheng-Gang Ren, Rong-Xin Chen
Some evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525379/pdz-binding-kinase-regulated-by-foxm1-enhances-malignant-phenotype-via-activation-of-%C3%AE-catenin-signaling-in-hepatocellular-carcinoma
#12
Yu-Feng Yang, Ying-Hua Pan, Yun Cao, Jia Fu, Xia Yang, Mei-Fang Zhang, Qiu-Hong Tian
Deregulation of serine/threonine kinase contributes to the development and progression of human diseases. PDZ-binding kinase (PBK) has been implicated in the malignant process of cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) remains unclear. Here we show that PBK expression is increased and associated with larger tumor size, presence of vascular invasion, lymph node metastasis and poor overall and disease-free survivals in two independent cohorts of 879 patients with HCC...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522590/notch-inhibitor-pf-03084014-inhibits-hepatocellular-carcinoma-growth-and-metastasis-via-suppression-of-cancer-stemness-due-to-reduced-activation-of-notch1-stat3
#13
Chuan Xing Wu, Aimin Xu, Cathy C Zhang, Peter Olson, Lin Chen, Terence K Lee, Tan To Cheung, Chung Mau Lo, Xiao Qi Wang
Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma (HCC), indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in HCC. HCC spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28518144/microrna-23b-functions-as-an-oncogene-and-activates-akt-gsk3%C3%AE-%C3%AE-catenin-signaling-by-targeting-st7l-in-hepatocellular-carcinoma
#14
Likun Zhuang, Xin Wang, Zusen Wang, Xiang Ma, Bing Han, Hao Zou, Zehua Wu, Sheng Dong, Zhiqiang Qu, Yunjin Zang, Liqun Wu
Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life worldwide, whereas the etiology and pathogenesis of HCC have not been fully determined. In the past few years, many microRNAs (miRNAs) have been proved to have important roles in tumorigenesis of HCC. In this study, we found that miR-23b was significantly upregulated in tumor tissues of HCC patients. Functional tests showed that miR-23b could promote HCC cell proliferation and metastasis in vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a direct target of miR-23b and involved in the promotion effects of miR-23b on HCC tumorigenesis and metastasis...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28515912/accelerated-carcinogenesis-following-liver-resection-in-chronically-inflamed-livers-a-window-of-opportunity-for-treatment
#15
Amir Sonnenblick, Tamar Zahavi
The long-term prognosis following resection of hepatocellular carcinoma (HCC) remains unsatisfactory as a result of a high incidence of recurrence. Prevention of recurrence is the most important strategy to improve the long-term survival results. The role of hepatectomy itself, as an accelerator of carcinogenesis, has not been adequately evaluated in HCC patients. Studies in animal models have revealed a link between liver regeneration under chronic inflammation and hepatic tumorigenesis. Inhibiting different signal transduction pathways during liver regeneration without compromising the ability of the liver to regenerate appears to be a rational strategy and may decrease HCC development and recurrence...
May 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28509806/advances-in-management-of-hepatocellular-carcinoma
#16
Manon Allaire, Jean-Charles Nault
PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is one of the leading causes of death by cancer worldwide due to a dismal prognosis. The aim of this review is to summarize the main advances in the pathophysiology and management of HCC. RECENT FINDINGS: Genomic analysis has recently delineated the key signaling pathways aberrantly deregulated in HCC (telomere maintenance, cell cycle gene, Wnt/β-catenin, epigenetic modifier, oxidative stress etc.). Major advances in the clinical care of patients with HCC are helping to refine the diagnosis algorithm and tumor staging...
May 15, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28508871/non-cell-autonomous-activation-of-il-6-stat3-signaling-mediates-fgf19-driven-hepatocarcinogenesis
#17
Mei Zhou, Hong Yang, R Marc Learned, Hui Tian, Lei Ling
Hepatocellular carcinoma (HCC), a primary malignancy of the liver, is the second leading cause of cancer mortality worldwide. Fibroblast Growth Factor 19 (FGF19) is one of the most frequently amplified genes in HCC patients. Moreover, mice expressing an FGF19 transgene have been shown to develop HCC. However, the downstream signalling pathways that mediate FGF19-dependent tumorigenesis remain to be deciphered. Here we show that FGF19 triggers a previously unsuspected, non-cell-autonomous program to activate STAT3 signalling in hepatocytes through IL-6 produced in the liver microenvironment...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507442/aberrant-promoter-methylation-profiles-and-association-with-survival-in-patients-with-hepatocellular-carcinoma
#18
Dani Zhong, Hong Cen
The aim of this study was to investigate the prognostic and diagnostic value of genes with promoter methylation in hepatocellular carcinoma (HCC) patients. On the basis of The Cancer Genome Atlas data, we identified genes with differentially methylated promoters in HCC tissues and adjacent non-tumor tissues, using the linear models for microarray data approach. Cox proportional hazard regression analysis was applied to access the prognostic value of identified differentially methylated genes. The diagnostic value of the genes was evaluated through receiver operating characteristic...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28507277/notch1-regulates-the-jnk-signaling-pathway-and-increases-apoptosis-in-hepatocellular-carcinoma
#19
Chengxu Sui, Chengjun Zhuang, Deguang Sun, Li Yang, Liang Zhang, Lei Song
Notch1-induced pathways are involved in cell growth, apoptosis, motility, and invasion in many cancers. In the present study, the expression of Notch1 and NICD1 was detected in hepatocellular carcinoma (HCC) tissues using in-vitro assays. And then, we explored cell biology and signaling pathways using Notch1 siRNA or plasmids. Here, the expression of Notch1 and NICD1 was significantly decreased in HCC tissues. In-vitro, Notch1 plasmids inhibited cell proliferation, migration and invasion, but enhanced apoptosis of HepG2 and Hep3B cells...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28506857/foxk2-regulted-by-mir-1271-5p-promotes-cell-growth-and-indicates-unfavorable-prognosis-in-hepatocellular-carcinoma
#20
Mei-Fang Lin, Yu-Feng Yang, Zhen-Peng Peng, Mei-Fang Zhang, Jin-Yu Liang, Wei Chen, Xu-Hui Liu, Yan-Ling Zheng
The forkhead transcription factor FOXK2 has been implicated in the progression of human cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) have not been explored. Here we showed that FOXK2 expression was increased and associated with tumor size, TNM stage and vascular invasion. High FOXK2 expression was correlated with poor overall and disease-free survival in two independent cohorts consisting of 864 patients with HCC. The prognostic value of FOXK2 was validated by stratified survival analyses in subgroups difined by factors contributing to worse survival...
May 12, 2017: International Journal of Biochemistry & Cell Biology
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