scholarly journals NF-κB, JNK, and TLR Signaling Pathways in Hepatocarcinogenesis

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Shin Maeda
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Inflammatory Cell ◽  
Prognostic Markers ◽  
Tumor Promotion ◽  
Neoplastic Cell ◽  
Nuclear Factor ◽  
Tlr Signaling ◽  
The Third

Hepatocellular carcinoma (HCC) is the third largest cause of cancer deaths worldwide. The role of molecular changes in HCC have been used to identify prognostic markers and chemopreventive or therapeutic targets. It seems that toll-like receptors (TLRs) as well as the nuclear factor (NF)-κB, and JNK pathways are critical regulators for the production of the cytokines associated with tumor promotion. The cross-talk between an inflammatory cell and a neoplastic cell, which is instigated by the activation of NF-κB and JNKs, is critical for tumor organization. JNKs also regulate cell proliferation and act as oncogenes, making them the main tumor-promoting protein kinases. TLRs play roles in cytokine and hepatomitogen expression mainly in myeloid cells and may promote liver tumorigenesis. A better understanding of these signaling pathways in the liver will help us understand the mechanism of hepatocarcinogenesis and provide a new therapeutic target for HCC.

scholarly journals miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Gang Wu ◽  
Zhixi Li ◽  
Youyu Wang ◽  
Xueming Ju ◽  
Rui Huang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Hepg2 Cells ◽  
Hepatoma Cell ◽  
Luciferase Reporter ◽  
Hepatoma Cell Line ◽  
Novel Therapy ◽  
The Third ◽  
Direct Target

Hepatocellular carcinoma (HCC) is the most common type of malignancy of the liver and has been reported as the third most frequent cause of cancer associated death worldwide. Accumulating evidence showed that the expression of miR-34a was abnormal in HCC patients; however, the role of miR-34a in HCC is not clear. In this study, we have observed low expression of the miR-34a in both HCC tissues and hepatoma cell line as compared to normal control. Further to investigate the role of miR-34a in HCC development, HepG2 cells were transfected with miR-34a mimic. Following transfection, miR-34a expression was significantly increased, which further repressed proliferation of HepG2 cells. Bioinformatics, Luciferase Reporter, RT-qPCR, and western blotting assays indicated that special AT-rich sequence-binding protein-2 (SATB2) is a direct target of miR-34a in HCC cells. There was a negative correlation between the expression levels of SATB2 and miR-34a. Investigation into the molecular mechanism indicated that miR-34a regulated cell proliferation through inhibiting SATB2. Therefore, the results of the present study may improve understanding regarding the role of miR-34a in regulating cell proliferation and contribute to the development of novel therapy of HCC.

Liver Transplantation for Hepatocellular Carcinoma: An Update

2006 ◽  
Vol 4 (8) ◽  
pp. 762-767 ◽  
Author(s):  
Jean F. Botha ◽  
Alan N. Langnas
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Selection Criteria ◽  
Hepatic Cirrhosis ◽  
The United States ◽  
Treatment Modalities ◽  
Hepatic Malignancy ◽  
The Third ◽  
Small Hcc

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and the most common primary hepatic malignancy. It arises on a background of hepatic cirrhosis in approximately 95% of the cases in the United States. A wide variety of treatment modalities have been applied in the treatment of HCC. Liver transplantation has emerged as the preferred treatment for patients with small HCC. Transplantation for patients whose tumors do not exceed the Milan criteria yields results equivalent to those of transplantation for non-HCC indications. Controversy now exists regarding the use of living donors, expansion of selection criteria, and role of adjuvant therapy.

scholarly journals The molecular connection of histopathological heterogeneity in hepatocellular carcinoma: A role of Wnt and Hedgehog signaling pathways

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0208194 ◽  
Author(s):  
Anindita Tripathy ◽  
Sudhir Thakurela ◽  
Manoj Kumar Sahu ◽  
Kanishka Uthanasingh ◽  
Manas Behera ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Hedgehog Signaling

scholarly journals The Inflammatory Microenvironment in Hepatocellular Carcinoma: A Pivotal Role for Tumor-Associated Macrophages

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Daria Capece ◽  
Mariafausta Fischietti ◽  
Daniela Verzella ◽  
Agata Gaggiano ◽  
Germana Cicciarelli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factors ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Matrix Metalloproteases ◽  
Pivotal Role ◽  
M2 Macrophage ◽  
Tumor Associated Macrophages

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human cancers worldwide. HCC is an example of inflammation-related cancer and represents a paradigm of the relation occurring between tumor microenvironment and tumor development. Tumor-associated macrophages (TAMs) are a major component of leukocyte infiltrate of tumors and play a pivotal role in tumor progression of inflammation-related cancer, including HCC. Several studies indicate that, in the tumor microenvironment, TAMs acquire an M2-polarized phenotype and promote angiogenesis, metastasis, and suppression of adaptive immunity through the expression of cytokines, chemokines, growth factors, and matrix metalloproteases. Indeed, an established M2 macrophage population has been associated with poor prognosis in HCC. The molecular links that connect cancer cells and TAMs are not completely known, but recent studies have demonstrated that NF-κB, STAT-3, and HIF-1 signaling pathways play key roles in this crosstalk. In this paper, we discuss the current knowledge about the role of TAMs in HCC development, highlighting the role of TAM-derived cytokines, chemokines, and growth factors in the initiation and progression of liver cancer and outlining the signaling pathways involved in the interplay between cancer cells and TAMs.

Cinnamon Polyphenol Extract Exerts Neuroprotective Activity in Traumatic Brain Injury in Male Mice

2018 ◽  
Vol 17 (6) ◽  
pp. 439-447 ◽  
Author(s):  
Burak Yulug ◽  
Ertugrul Kilic ◽  
Serdar Altunay ◽  
Cenk Ersavas ◽  
Cemal Orhan ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathways ◽  
Intraperitoneal Administration ◽  
Neuroprotective Activity ◽  
Vehicle Group ◽  
Related Factor ◽  
Nuclear Factor ◽  
Male Mice

Background: Cinnamon polyphenol extract is a traditional spice commonly used in different areas of the world for the treatment of different disease conditions which are associated with inflammation and oxidative stress. Despite many preclinical studies showing the anti-oxidative and antiinflammatory effects of cinnamon, the underlying mechanisms in signaling pathways via which cinnamon protects the brain after brain trauma remained largely unknown. However, there is still no preclinical study delineating the possible molecular mechanism of neuroprotective effects cinnamon polyphenol extract in Traumatic Brain Injury (TBI). The primary aim of the current study was to test the hypothesis that cinnamon polyphenol extract administration would improve the histopathological outcomes and exert neuroprotective activity through its antioxidative and anti-inflammatory properties following TBI. Methods: To investigate the effects of cinnamon, we induced brain injury using a cold trauma model in male mice that were treated with cinnamon polyphenol extract (10 mg/kg) or vehicle via intraperitoneal administration just after TBI. Mice were divided into two groups: TBI+vehicle group and TBI+ cinnamon polyphenol extract group. Brain samples were collected 24 h later for analysis. Results: We have shown that cinnamon polyphenol extract effectively reduced infarct and edema formation which were associated with significant alterations in inflammatory and oxidative parameters, including nuclear factor-κB, interleukin 1-beta, interleukin 6, nuclear factor erythroid 2-related factor 2, glial fibrillary acidic protein, neural cell adhesion molecule, malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase. Conclusion: Our results identify an important neuroprotective role of cinnamon polyphenol extract in TBI which is mediated by its capability to suppress the inflammation and oxidative injury. Further, specially designed experimental studies to understand the molecular cross-talk between signaling pathways would provide valuable evidence for the therapeutic role of cinnamon in TBI and other TBI related conditions.

scholarly journals Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma

2017 ◽  
Vol 10 (10) ◽  
pp. 761-771 ◽  
Author(s):  
Shao-hang Cai ◽  
Shi-xun Lu ◽  
Li-li Liu ◽  
Chris Zhiyi Zhang ◽  
Jing-ping Yun
Keyword(s):  
Hepatocellular Carcinoma ◽  
Training Group ◽  
Tissue Microarrays ◽  
Favourable Outcome ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Kaplan Meier ◽  
Hepatocyte Nuclear Factor 4 ◽  
Prognostic Prediction

Background: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. Methods: A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry. The relationship between P2-HNF4α and clinical features of HCC patients were analysed. Kaplan–Meier analysis was conducted to assess the prognostic value of P2-HNF4α. Results: The results showed that the expression of P2-HNF4α in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4α expression was negatively correlated with P2-HNF4α expression ( p = 0.023). High P2-HNF4α expression was significantly associated with poor differentiation of HCC ( p = 0.002) and vascular invasion ( p = 0.017). Kaplan–Meier analysis showed that P2-HNF4α expression was closely correlated with overall survival in the training group ( p = 0.01), validation group ( p = 0.034), and overall group of patients with HCC ( p < 0.001). Conclusions: Our data show that the role of HNF4α in cancer development needs to be further refined. P2-HNF4α, different from P1-HNF4α, is markedly upregulated and serves as an oncogene-associated protein in HCC. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.

STAT3 and AKT signaling pathways mediate oncogenic role of NRSF in hepatocellular carcinoma

2020 ◽  
Vol 52 (10) ◽  
pp. 1063-1070
Author(s):  
Ming Ma ◽  
Yunhe Zhou ◽  
Ruilin Sun ◽  
Jiahao Shi ◽  
Yutong Tan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Zinc Finger Protein ◽  
Akt Signaling ◽  
Nervous System Development ◽  
Migration And Invasion ◽  
Tumor Type ◽  
Dependent Manner ◽  
Rnai Technology

Abstract Neuron-restrictive silencer factor (NRSF) is a zinc finger protein that acts as a negative transcriptional regulator by recruiting histone deacetylases and other co-factors. It plays a crucial role in nervous system development and is recently reported to be involved in tumorigenesis in a tumor type-dependent manner; however, the role of NRSF in hepatocellular carcinoma (HCC) tumorigenesis remains unclear. Here, we found that NRSF expression was up-regulated in 27 of 49 human HCC tissue samples examined. Additionally, mice with conditional NRSF-knockout in the liver exhibited a higher tolerance against diethylnitrosamine (DEN)-induced acute liver injury and were less sensitive to DEN-induced HCC initiation. Our results showed that silencing NRSF in HepG2 cells using RNAi technology significantly inhibited HepG2 cell proliferation and severely hindered their migration and invasion potentials. Our results demonstrated that NRSF plays a pivotal role in promoting DEN-induced HCC initiation via a mechanism related to the STAT3 and AKT signaling pathways. Thus, NRSF could be a potential therapeutic target for treating human HCC.

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