scholarly journals Lack of hotspot mutations other than TP53 R249S in aflatoxin B1 associated hepatocellular carcinoma

2020 ◽  
Vol 45 (4) ◽  
pp. 451-453
Author(s):  
Cemaliye B. Akyerli ◽  
Şirin K. Yüksel ◽  
M. Cengiz Yakıcıer
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Aflatoxin B1 ◽  
Low Frequency ◽  
Gene Mutations ◽  
Pathogenic Mutation ◽  
Liver Carcinoma ◽  
Major Health Problem ◽  
Hotspot Mutations

AbstractObjectiveDespite the recent advances in diagnosis and treatment of hepatocellular carcinoma (HCC), it is still a major health problem. Therefore, understanding the molecular mechanism is very important. Our aim is to investigate the molecular basis of aflatoxin B1 (AFB1) induced HCC other than the hotspot TP53 p.Arg249Ser (c.747G>T) (R249S) mutation.Methods525 genes previously reported to be involved in carcinogenesis with mutations in different cancer types were analyzed by next generation sequencing for 525 cancer-gene panel (Roche/NimbleGen) in one tumor sample (T29) and one cell line (MAHLAVU) carrying TP53 R249S mutation. Additionally, ARID2 and BCORL1 genes were analyzed by Sanger sequencing for MAHLAVU and Primary Liver Carcinoma/Poliomyelitis Research Foundation/5 (PLC/PRF/5) cell lines.ResultsNo other common gene mutations were found in the analyzed T29 and MAHLAVU samples and also no genetic variation possibly associated with AFB1 was detected in PLC/PRF/5 cell line and 68 COSMIC HCC samples. Likewise, no pathogenic mutation was detected in ARID2 and BCORL1 genes of MAHLAVU and PLC/PRF/5 cell lines.ConclusionNo fingerprint mutations were detected in the analyzed genes. To the best of our knowledge, other hotspot mutations appear to be absent if not at a very low frequency in HCC carrying TP53 R249S mutation.

SYNTHESIS AND CYTOTOXICITY OF POLYHYDROXYLATED CHOLESTEROL DERIVATIVES

2018 ◽  
Vol 56 (4) ◽  
pp. 467
Author(s):  
Thu Thuy Thi Tran ◽  
Ha Thi Dinh ◽  
Phương Lan Doan ◽  
Long Quoc Pham ◽  
Quang Dai Ngo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Addition Compound ◽  
Hep G2 ◽  
Physical Methods ◽  
Hepatocellular Carcinoma Cell Line ◽  
Human Hepatocellular Carcinoma Cell ◽  
Hepatocellular Carcinoma Cell

Eight polyhydroxylated cholesterol derivatives (1-8) were prepared from cholesterol, using oxidative reagents as SeO2, OsO4/NMO, HCOOH/H2O2 and BH3/ H2O2. Their structures were elucidated by using physical methods including NMR 1D and 2D. These compounds were evaluated against two cancer cell lines (Hep-G2, T98). Compounds 2, 4 and 8 inhibits human hepatocellular carcinoma cell line (Hep-G2) with IC50 4.69, 4.98 and 2.89 µg/mL, respectively. In addition, compound 8 exhibited strong cytotoxicity against T98 cell line (glioblastoma) with IC50 = 2.28 μM.

scholarly journals Animal model of intrahepatic metastasis of hepatocellular carcinoma: establishment and characteristic

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xuemei Li ◽  
Jike Hu ◽  
Baohong Gu ◽  
Maswikiti Ewetse Paul ◽  
Bofang Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Models ◽  
Cell Line ◽  
Cell Lines ◽  
Intrahepatic Metastasis ◽  
Model Systems ◽  
Large Tumor ◽  
Important Direction ◽  
Disease Study

Abstract One of the most important and striking characteristics of hepatocellular carcinoma (HCC) with intrahepatic metastasis, is that it results in extremely poor prognosis. Animal models have become a fundamental and very useful in research for disease study. However, some limitation has arisen from these model systems. We have therefore established a model of HCC with intrahepatic metastasis and noticed some differential appearances in different HCC cell lines. Luciferase-transfected HCC cell lines MHCC97-H and PLC/PRF/5 were inoculated into SCID mice via spleen. Observation the intrahepatic metastasis by bioluminescence imaging in vivo and comparing of the differential formation of metastatic lesions between different HCC cell lines by incorporating physical anatomy was done. Animal models for HCC intrahepatic metastasis were well established. However, there were some clearly noticed differences between MHCC97-H and PLC/PRF/5 cell lines. The group of MHCC97-H cell line readily metastasis in the liver, whereas group PLC/PRF/5 cell line developed extensive intrahepatic metastasis and formed large tumor in situ in the spleen. MHCC97-H and PLC/PRF/5 cell lines can be used to successfully establish a model of HCC intrahepatic metastasis with distinctive characteristics, which provides an important direction for the study of the mechanism of HCC intrahepatic metastasis, and may hopefully provide a basis for clinical treatment.

Hepatic oval cell lines generate hepatocellular carcinoma following transfection with HBx gene and treatment with aflatoxin B1 in vivo

2011 ◽  
Vol 311 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Chang-Hai Li ◽  
Yan-Jun Wang ◽  
Wei Dong ◽  
Shuai Xiang ◽  
Hui-Fang Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Aflatoxin B1 ◽  
Oval Cell ◽  
Hepatic Oval Cell

The role of HNF4A in GATA4-deficiency phenotypes of hepatocellular carcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 284-284
Author(s):  
Yu Bin Tan ◽  
Timothy Shuen ◽  
Han Chong Toh
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Correlation Analysis ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Transgenic Mouse ◽  
Cell Lines ◽  
Downstream Target ◽  
Cycle Arrest

284 Background: Hepatocellular carcinoma (HCC) is the 2nd leading global cause of cancer death. Recently, we have discovered previously undescribed deletion and germline mutation of GATA4 and showed that GATA4 is a key differentiation driver and metabolic regulator in HCC. However, as GATA4 is mostly deleted in HCC, targeting GATA4-downstream molecules is ideal. In this study, proof-of-concept experiments were conducted to show that introduction of HNF4A, which is a GATA4-regulated downstream target, could partially rescue the impaired phenotypes in GATA4-deficient HCC cell line. Methods: Correlation analysis using gene expression microarray of human HCC samples was conducted to identify the genes that are positively correlated with GATA4. A transgenic mouse model with a liver-specific conditional GATA4 knockout was designed to identify liver morphology and gene expression changes which are correlated with the loss of Gata4 in the mouse liver. CRISPR-mediated knockout of GATA4 and lentiviral HNF4A overexpression was carried out in a GATA4-deficient HCC cell lines, PLC/PRF/5 and Hep3B, followed by proliferation, apoptosis, cell cycle and senescence functional assays. Results: Pearson correlation analysis from human HCC samples showed that expression of HNF4A is positively correlated with that of GATA4. Livers from conditional Gata4 knockout mice had lower Hnf4a gene expression when compared to age-matched control mice. Loss of function analysis by CRISPR-mediated GATA4 knockout further showed downregulation of HNF4A in GATA4-deficient PLC/PRF/5 cell line. Lentiviral HNF4A overexpression in PLC/PRF/5 and Hep3B demonstrated reduced proliferation and increased apoptosis while PLC/PRF/5 also showed cell cycle arrest at G2/M phase when compared to control. However, no senescence induction was detected in HNF4A-overexpressing cells. Conclusions: Transgenic mouse data, CRISPR-mediated knockout and analysis of HCC samples showed that HNF4A is a key GATA4-downstream target. HNF4A overexpression decreases proliferation, increases apoptosis and cell cycle arrest in GATA4-deficient HCC cell lines, thus representing a possible therapeutic target for HCC.

scholarly journals Effects of LncRNA-HOST2 on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma cell line SMMC-7721

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Run-Tian Liu ◽  
Jing-Lin Cao ◽  
Chang-Qing Yan ◽  
Yang Wang ◽  
Cong-Jing An ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Line ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Human Hepatocellular Carcinoma ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Experimental Group

The present study explored the effect of long non-coding RNA-human ovarian cancer-specific transcript 2 (LncRNA-HOST2) on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma (HCC) cell line SMMC-7721. HCC tissues and adjacent normal tissues from 162 HCC patients were collected. The HCC cell lines were assigned into the control group (regular culture), negative control (NC) group (transfected with siRNA) and experimental group (transfected with Lnc-HOST2 siRNA). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of LncRNA-HOST2. Cell proliferation was detected by CCK-8 and colony-forming assays, cell apoptosis by flow cytometry and cell migration by Scratch test. Transwell assay was used to evaluate cell migration and invasion abilities. LncRNA-HOST2 expression in the HCC tissues increased 2–10 times than that in the adjacent normal tissues. Compared with the HL-7702 cell line, LncRNA-HOST2 expression in HepG2, SMMC-7721 and Huh7 cell lines was all up-regulated, but the SMMC-7721 cell had the highest Lnc-HOST2 expression. The LncRNA-HOST2 expression in the experimental group was down-regulated as compared with the control and NC groups. In comparison with the control and NC groups, cloned cells reduced, cell apoptosis increased, clone-forming ability weakened and inhibitory rate of colony formation increased in the experimental group. The cells migrating and penetrating into the transwell chamber were fewer in the experimental group than those in the control and NC groups. The experimental group exhibited slow wound healing and decreased cell migration area after 48 h. These findings indicate that LncRNA-HOST2 can promote cell proliferation, migration and invasion and inhibit cell apoptosis in human HCC cell line SMMC-7721.

scholarly journals Expression and biosynthetic variation of the epidermal growth factor receptor in human hepatocellular carcinoma-derived cell lines.

1988 ◽  
Vol 8 (1) ◽  
pp. 25-34 ◽  
Author(s):  
C R Carlin ◽  
D Simon ◽  
J Mattison ◽  
B B Knowles
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Cell Lines ◽  
Gene Amplification ◽  
Egf Receptor ◽  
Hepatoma Cell ◽  
Receptor Gene ◽  
Epidermal Growth

Expression of the epidermal growth factor (EGF) was analyzed in six human hepatocellular carcinoma-derived and one human hepatoblastoma-derived cell line, each of which retained the differentiated phenotype and functions of the parenchymal hepatocyte. The level of receptor expression of each hepatoma cell line was similar to that of the normal human fibroblast, approximately 10(5) molecules per cell. However, NPLC/PRF/5, a subline of the PLC/PRF/5 cell line obtained following reestablishment of a xenograft tumor in vitro, was found to express 4 x 10(6) high-affinity EGF receptor molecules per cell. Proliferation of the NPLC/PRF/5 cell line was inhibited in the presence of nanomolar quantities of ligand. Receptor overexpression was found to result from EGF receptor gene amplification without apparent rearrangement of the EGF receptor coding sequences. Although cell-specific variability in posttranslational processing of EGF receptor N-linked oligosaccharides in the hepatoma cell lines was found, no difference between the receptors in PLC/PRF/5 and NPLC/PRF/5 was observed and no aberrant receptor-related species were detected. EGF receptor gene amplification in the NPLC/PRF/5 cell line is probably a reflection of genome instability and selection of variants with augmented growth potential in limiting concentrations of EGF in vivo. When viewed in this light, EGF receptor overexpression could represent a manifestation of tumor progression in the EGF-responsive hepatocyte.

scholarly journals Increased ERp57 Expression in HBV-Related Hepatocellular Carcinoma: Possible Correlation and Prognosis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Miao Liu ◽  
Lingyao Du ◽  
Zhiliang He ◽  
Libo Yan ◽  
Ying Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Cell Line ◽  
Cell Lines ◽  
Liver Cell ◽  
Normal Liver ◽  
Hbv Infection ◽  
Altered Expression ◽  
Liver Cell Line ◽  
Liver Tissues

Aim.ERp57 is involved in virus induced endoplasmic reticulum stress (ERS) and plays an important role in tumorigenesis. This study aimed to find whether HBV infection altered ERp57 expression and whether ERp57 regulation was involved in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) genesis.Materials and Methods.HBV-HCC tissues, chronic hepatitis B (CHB) liver tissues, and normal liver tissues were acquired. ERp57 expressions in these tissues were detected through immunohistochemistry (IHC). And ERp57 expression in liver cell line L02, HBV replicative liver cell line L02-pHBV4.1, and HCC cell lines were detected through western blot for verification. Then medical data on patients providing HCC tissues were collected and analyzed along with ERp57 expression.Results.Higher ERp57 expression was found in HCC and CHB tissues (p<0.001). And HCC cell lines and L02-pHBV4.1 presented higher ERp57 expression as well. In patients, ERp57 expression showed significant differences between death and survival groups (p=0.037). And cumulative survival in patients with higher ERp57 (score⩾8.75) is significantly lower (p=0.009).Conclusion.Our study found increased expression of ERp57 in HBV-HCC. Such altered expression could be related to HBV infection and high ERp57 expression may lead to poor prognosis of HBV-HCC patients.

Expression and biosynthetic variation of the epidermal growth factor receptor in human hepatocellular carcinoma-derived cell lines

1988 ◽  
Vol 8 (1) ◽  
pp. 25-34
Author(s):  
C R Carlin ◽  
D Simon ◽  
J Mattison ◽  
B B Knowles
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Cell Lines ◽  
Gene Amplification ◽  
Egf Receptor ◽  
Hepatoma Cell ◽  
Receptor Gene ◽  
Epidermal Growth

Expression of the epidermal growth factor (EGF) was analyzed in six human hepatocellular carcinoma-derived and one human hepatoblastoma-derived cell line, each of which retained the differentiated phenotype and functions of the parenchymal hepatocyte. The level of receptor expression of each hepatoma cell line was similar to that of the normal human fibroblast, approximately 10(5) molecules per cell. However, NPLC/PRF/5, a subline of the PLC/PRF/5 cell line obtained following reestablishment of a xenograft tumor in vitro, was found to express 4 x 10(6) high-affinity EGF receptor molecules per cell. Proliferation of the NPLC/PRF/5 cell line was inhibited in the presence of nanomolar quantities of ligand. Receptor overexpression was found to result from EGF receptor gene amplification without apparent rearrangement of the EGF receptor coding sequences. Although cell-specific variability in posttranslational processing of EGF receptor N-linked oligosaccharides in the hepatoma cell lines was found, no difference between the receptors in PLC/PRF/5 and NPLC/PRF/5 was observed and no aberrant receptor-related species were detected. EGF receptor gene amplification in the NPLC/PRF/5 cell line is probably a reflection of genome instability and selection of variants with augmented growth potential in limiting concentrations of EGF in vivo. When viewed in this light, EGF receptor overexpression could represent a manifestation of tumor progression in the EGF-responsive hepatocyte.

scholarly journals ID: 1012 Cytotoxicity of Corchorus olitorius Linn. aqueous leaf extract against human carcinoma cells

2017 ◽  
Vol 4 (S) ◽  
pp. 86
Author(s):  
John Paul Tosoc
Keyword(s):  
Cell Viability ◽  
Cell Line ◽  
Cell Lines ◽  
Aqueous Extract ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Liver Carcinoma ◽  
Human Carcinoma ◽  
Carcinoma Cell Lines ◽  
Viability Percentage

C. olitorius are used as herbal medicine and eaten as vegetable by local people in Philippines.  The T’boli tribe commonly uses this plant to treat common illnesses such as pimples, wounds, boils, and inflammations. According to studies, the leaves of C. olitorius has properties to treat demulcent, diuretic, febrifuge, chronic cystitis, dysuria and even tumor. The aim of this study is to evaluate the cytotoxicity properties of the crude aqueous extract of C. olitorius leaf against colon (HCT116), breast (MCF-7), and liver (HepG2) carcinoma cell-lines using the MTT cell proliferation assay. The results showed that the aqueous extract has potential cytotoxicity activity against the three-carcinoma cell-lines. The aqueous extract was most bioactive in the colon carcinoma cell-line (HCT116) with cell viability percentage of 23.53 and 32.48 in 100 and 10 µg/mL, respectively. It was then followed by the breast carcinoma cell-line (MCF7) with cell viability percentage of 16.23 and 30.25 in 100 and 10 µg/mL, respectively. The extract was least but still bioactive in the liver carcinoma cell-line (HepG2) with cell viability percentage of 91.20 and 132.76 in 100 and 10 µg/mL, respectively. This study illustrates the importance of toxicological screening to confirm the safety and efficacy of the medicinal plant commonly used in the traditional medicine system in the treatment and management of illnesses by the T’boli tribe in South Cotabato

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