scholarly journals Pathogenetic and Prognostic Significance of Inactivation of RASSF Proteins in Human Hepatocellular Carcinoma

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Diego F. Calvisi ◽  
Matthias Evert ◽  
Frank Dombrowski
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Human Liver ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Prognostic Significance ◽  
Dismal Prognosis ◽  
Human Liver Cancer ◽  
Cellular Inhibitors

Hepatocellular carcinoma (HCC) is one of the most frequent solid tumors worldwide, with limited treatment options and a dismal prognosis. Thus, there is a strong need to expand the basic and translational research on this deadly disease in order to improve the prognosis of HCC patients. Although the etiologic factors responsible for HCC development have been identified, the molecular pathogenesis of liver cancer remains poorly understood. Recent evidence has shown the frequent downregulation of Ras association domain family (RASSF) proteins both in the early and late stages of hepatocarcinogenesis. Here, we summarize the data available on the pathogenetic role of inactivation of RASSF proteins in liver cancer, the molecular mechanisms responsible for suppression of RASSF proteins in HCC, and the possible clinical implications arising from these discoveries. Altogether, the data indicate that inactivation of the RASSF1A tumor suppressor is ubiquitous in human liver cancer, while downregulation of RASSF2 and RASSF5 proteins is limited to specific HCC subsets. Also, the present findings speak in favour of therapeutic strategies aimed at reexpressing RASSF1A, RASSF2, and RASSF5 genes and/or inactivating the RASSF cellular inhibitors for the treatment of human liver cancer.

scholarly journals Treatment with low-dose sorafenib in combination with a novel benzimidazole derivative bearing a pyrolidine side chain provides synergistic anti-proliferative effects against human liver cancer

RSC Advances ◽  
2017 ◽  
Vol 7 (26) ◽  
pp. 16253-16263 ◽  
Author(s):  
Ming-Hua Hsu ◽  
Shih-Ming Hsu ◽  
Yu-Cheng Kuo ◽  
Chih-Yu Liu ◽  
Cheng-Ying Hsieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Human Liver ◽  
Low Dose ◽  
Benzimidazole Derivative ◽  
Side Chain ◽  
The World ◽  
Human Liver Cancer

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and deadliest cancers in the world.

scholarly journals The Role of Histone Acetylation-/Methylation-Mediated Apoptotic Gene Regulation in Hepatocellular Carcinoma

2020 ◽  
Vol 21 (23) ◽  
pp. 8894
Author(s):  
Pradeep Kumar Rajan ◽  
Utibe-Abasi Udoh ◽  
Juan D. Sanabria ◽  
Moumita Banerjee ◽  
Gary Smith ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histone Modification ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Nuclear Changes ◽  
New Perspective ◽  
Effective Diagnosis

Epigenetics, an inheritable phenomenon, which influences the expression of gene without altering the DNA sequence, offers a new perspective on the pathogenesis of hepatocellular carcinoma (HCC). Nonalcoholic steatohepatitis (NASH) is projected to account for a significant share of HCC incidence due to the growing prevalence of various metabolic disorders. One of the major molecular mechanisms involved in epigenetic regulation, post-translational histone modification seems to coordinate various aspects of NASH which will further progress to HCC. Mounting evidence suggests that the orchestrated events of cellular and nuclear changes during apoptosis can be regulated by histone modifications. This review focuses on the current advances in the study of acetylation-/methylation-mediated histone modification in apoptosis and the implication of these epigenetic regulations in HCC. The reversibility of epigenetic alterations and the agents that can target these alterations offers novel therapeutic approaches and strategies for drug development. Further molecular mechanistic studies are required to enhance information governing these epigenetic modulators, which will facilitate the design of more effective diagnosis and treatment options.

scholarly journals Histopathological analyses of the antitumor activity of anti-glypican-3 antibody (GC33) in human liver cancer xenograft models: The essential role of macrophages

2009 ◽  
Vol 8 (10) ◽  
pp. 930-938 ◽  
Author(s):  
Hirotake Takai ◽  
Atsuhiko Kato ◽  
Yasuko Kinoshita ◽  
Takahiro Ishiguro ◽  
Yayoi Takai ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Antitumor Activity ◽  
Human Liver ◽  
Essential Role ◽  
Human Liver Cancer ◽  
Xenograft Models

scholarly journals Identification of Ethyl Ferulate From Rubus corchorifolius L.F. Leaves and Its Inhibitory Effects on HepG2 Liver Cancer Cells

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 305-305
Author(s):  
Xuexiang Chen ◽  
Xian Wu ◽  
Guo Liu ◽  
Qun Wang ◽  
Wen Ouyang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Cell Morphology ◽  
Human Liver ◽  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Electrical Potential ◽  
Ethyl Ferulate ◽  
Liver Cancer Cells ◽  
Human Liver Cancer

Abstract Objectives Rubus corchorifolius L.f., also known as raspberry, March bubble, milk bubble, etc., belongs to the genus Rubus L. and the family Rosaceae. The tender leaves of Rubus corchorifolius L. f. have been made into herbal tea for drinking and relieving coughs in China since ancient times. In this study, we isolated a bioactive compound from the ethyl acetate extract of Rubus corchorifolius L.f. leaves and investigated its protective effects in HepG2 human liver cancer cell line and the underlying molecular mechanisms. Methods Structural analysis of the isolated compound was performed by spectroscopic methods and the compound was identified as ethyl ferulate. Efficacy and mechanisms of ethyl ferulate on the proliferation of HepG2 human liver cancer cells and LO2 normal human liver cells was determined by cell viability, cell morphology, apoptosis, mitochondrial membrane potential, Ca2 + release, and immunoblotting analyses. Results We found that ethyl ferulate significantly suppressed the cell proliferation of HepG2 cells (IC50 26.4 μM), while it did not cause cytotoxicity on LO2 cells. In addition, flow cytometry analysis demonstrated that ethyl ferulate inhibited HepG2 cell growth via inducing cellular apoptosis. Specifically, ethyl ferulate reduced the electrical potential of the mitochondrial membrane and increased the concentration of calcium ions inside cells. Moreover, these changes were accompanied by increases in the expression of the pro-apoptotic proteins, such as cleaved caspase-3 and Bax. In contrast, cell morphology and growth of LO2 cells remained unaffected. Conclusions In conclusion, our findings demonstrated, for the first time, that ethyl ferulate possesses great potential as an effective and safe antitumor agent for cancer chemoprevention in humans. Funding Sources This study was supported by the University of International Cooperation in Science and Technology Innovation Platform Project of Guangdong (2013gjhz0003). XC was partly supported by a scholarship from South China Agriculture University.

scholarly journals ImmunoPET as Stoichiometric Sensor for Glypican-3 in Models of Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Olivia J. Kelada ◽  
Nicholas T. Gutsche ◽  
Meghan Bell ◽  
Rose M. Berman ◽  
Kwamena E. Baidoo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Flow Cytometry ◽  
Liver Cancer ◽  
Cell Lines ◽  
Human Liver ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Human Liver Cancer ◽  
Gpc3 Expression

BackgroundHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. While conventional imaging approaches like ultrasound, CT, and MRI play critical roles in the diagnosis and surveillance of HCC, improved methods for detection and assessment of treatment response are needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography (immunoPET) imaging. Glypican-3 (GPC3) is a proteoglycan that is highly expressed in the majority of HCC tumors. GPC3-specific antibodies are used to diagnose HCC histopathologically, and have been proposed as a treatment of HCC. Here, we design, synthesize and demonstrate that our humanized immunoPET agent, [89Zr]Zr-DFO-TAB-H14, can stoichiometrically bind to models of human liver cancer with varied GPC3 expression. Methods: The GPC3-specific monoclonal humanized IgG1, TAB-H14, was used as a scaffold for engineering our immunoPET agent. Fluorescent and deferroxamine (DFO) chelate conjugates of TAB-H14 were characterized using mass spectrometry. Binding affinity of TAB-H14 and conjugates for GPC3 was determined in cell-free biolayer interferometry, and cell-based radioimmunoassays. GPC3-expression was assessed by flow cytometry and immunofluorescence using commercially available anti-GPC3 antibodies and TAB-H14 in GPC3−(A431) and GPC3+ cell lines including an engineered line (A431-GPC3+, G1) and liver cancer lines (HepG2, Hep3B, and Huh7). DFO-TAB-H14, was radiolabeled with Zr-89. Mice were subcutaneously engrafted with the aforementioned cell lines and in vivo target engagement of the immunoPET agent [89Zr]Zr-DFO-TAB-H14 was determined using PET/CT, quantitative biodistribution, and autoradiography. Results: TAB-H14 demonstrated subnanomolar to nanomolar affinity for human GPC3. Fluorescently tagged TAB-H14 was able to bind to GPC3 on cell membranes of GPC3-expressing lines by flow cytometry. These results were confirmed by immunofluorescence staining of A431, G1 HepG2, Hep3B, and Huh7 tumor sections. ImmunoPET imaging with [89Zr]Zr-DFO-TAB-H14 showed stoichiometric tumor uptake corresponding to the cell surface expression levels. Autoradiography and immunostaining confirmed in vivo findings. Conclusion: We systematically demonstrate that the humanized immnoPET agent [89Zr]Zr-DFO-TAB-H14 specifically and stoichiometrically binds to GPC3 in several models of human liver cancer, serving as a promising in vivo GPC3 sensor. This agent may provide utility in HCC diagnosis and surveillance, and the selection of candidates for GPC3-directed therapies.

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