• Title/Summary/Keyword: Hcc-1

Search Result 353, Processing Time 0.022 seconds

Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population

  • Oh, Ah-Reum;Lee, Seung-Ku;Kim, Min-Ho;Cheong, Jae-Youn;Cho, Sung-Won;Yang, Kap-Seok;Kwack, Kyu-Bum
    • Genomics & Informatics
    • /
    • v.6 no.4
    • /
    • pp.181-191
    • /
    • 2008
  • RAS guanyl-releasing protein 3 (RasGRP3), a member of the Ras subfamily of GTPases, functions as a guanosine triphosphate (GTP)/guanosine diphosphate (GDP)-regulated switch that cycles between inactive GDP- and active GTP-bound states during signal transduction. Various growth factors enhance hepatocellular carcinoma (HCC) proliferation via activation of the Ras/Raf-1/extracellular signal-regulated kinase (ERK) pathway, which depends on RasGRP3 activation. We investigated the relationship between polymorphisms in RasGRP3 and progression of hepatitis B virus (HBV)-infected HCC in a Korean population. Nineteen RasGRP3 SNPs were genotyped in 206 patients with chronic liver disease (CLD) and 86 patients with HCC. Our results revealed that the T allele of the rs7597095 SNP and the C allele of the rs7592762 SNP increased susceptibility to HCC (OR=1.55, p=0.04 and OR=1.81${\sim}$2.61, p=0.01${\sim}$0.03, respectively). Moreover, patients who possessed the haplotype (ht) 1 (A-T-C-G) or diplotype (dt) 1 (ht1/ht1) variations had increased susceptibility to HCC (OR=1.79${\sim}$2.78, p=0.01${\sim}$0.03). In addition, we identified an association between haplotype1 (ht1) and the age of HCC onset; the age of HCC onset are earlier in ht1 +/+ than ht1 +/- or ht1 -/- (HR=0.42${\sim}$0.66, p=0.006${\sim}$0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.

Combined Effects of Six Cytokine Gene Polymorphisms and SNP-SNP Interactions on Hepatocellular Carcinoma Risk in Southern Guangxi, China

  • Bei, Chun-Hua;Bai, Hua;Yu, Hong-Ping;Yang, Yan;Liang, Qing-Qing;Deng, Ying-Ying;Tan, Sheng-Kui;Qiu, Xiao-Qiang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.16
    • /
    • pp.6961-6967
    • /
    • 2014
  • Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-${\gamma}$-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.

Fine Needle Aspiration Cytology of Hepatocellular Carcinoma - A Study on 247 Cases - (간세포암종의 세침흡인 세포학적 소견 - 247예에 대한 연구 -)

  • Lee, Kwang-Gil;Lee, Jong-Tae;Choi, Soo-Im;Park, Chan-Il
    • The Korean Journal of Cytopathology
    • /
    • v.1 no.1
    • /
    • pp.1-17
    • /
    • 1990
  • Hepatocellular carcinoma (HCC) is malignant tumor frequently occurring in Koreans. There have been few reports regarding the cytologic findings of fine needle aspiration (FNA) of HCC. Most have suggested a diagnostic problem in the cytology distinguishing HCC from some benign hepatic lesions-for example, a regeneration nodule in cirrhosis and liver cell adenoma. In spite of its high frequency in Korea, no cytologic study has been reported, concerning the FNA of HCC. In an attempt to achieve cytologic criteria for the diagnosis of HCC, the authors studied retrospectively cytopathologic findings of 247 cases of HCC. These cases were confirmed either by histoiogic examination including lobectomy, biopsy, or ceil block material, or, when tissue diagnosis was unavailable, by a high serum alpha-fetoprotein level (over 400 I. U.). All aspiration smears were stained by the Papanicolaou method. In each case, the smears were analyzed for cell patterns and various cytomorphology of the tumor cells. The smear background was assessed for the presence of tumor cell necrosis and inflammatory components and compared to that of metastatic carcinomas. The cell patterns were classified as trabecular, acinar, dispersed, and irregular. The cytologic parameters analyzed included the degree of nuclear atypia and the presence of mitoses, intranuclear cytoplasmic inclusions, nucleolar prominency, endothelial lining, multinucleated giant cells, eosinophiic globules, bile, and Mallory body. Most of the FNA of HCC showed markedly cellular smears. The tumor cells were most frequently arranged in a trabecular pattern (80.3%). The irregular (12.6%), the acinar (5.5%), and the dispersed patterns (1.7%) followed in decreasing frequency. Individual hepatoma cells were larger than normal liver cells. However, they had morphologic features characteristic of the hepatic cells the cells were round or polygonal, their cytoplasm was abundant and granular with eosinophilic or amphophilic stainability, and their nuclei were round to oval, located centrally, and tended to have prominent nucleoli. Anaplasia and pleomorphism of tumor cells were generally mild to moderate. These findings existed even in very well differentiated cases. Mitotic figures were present in about 85% of the cases. Prominent nucleoli were observed only in about half the cases. The frequency of other cytologic features was as follows intranuclear cytoplasmic inclusion in 86.8% : endothelial lining in 56.1% : bile in 19.8% : and giant cells in 60.1%. Clear cells were often present in 11.7%, Most aspiration smears of HCC displayed clean background without necrosis or inflammatory material in contrast to the dirty, necrotic background of metastatic cancers and cholangiocarcinomas. Based on the above mentioned features, it is suqqested that the cytologic critieria most important for the diagnosis of HCC include a markedly cellular smear, trabecular pattern, hepatocytoid appearance of tumor cells, endothelial lining, the presence of bile, giant cells, intranuclear cytoplasmic inclusions, and prominent nucleoli, Among these, trabecular pattern, endothelial lining, giant cells and clean smear background are points to be considered in differentiating HCC from metastatic and cholangiocellular carcinoma.

  • PDF

Relationship Between GSTT1 Gene Polymorphism and Hepatocellular Carcinoma in Patients from China

  • Chen, Jie;Ma, Liang;Peng, Ning-Fu;Wang, Shi-Jun;Li, Le-Qun
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.9
    • /
    • pp.4417-4421
    • /
    • 2012
  • Objective: The results from studies on associations of the glutathione S-transferase T1 (GSTT1) gene polymorphism and hepatocellular carcinoma (HCC) risk in Chinese populations are still conflicting. This meta-analysis was performed to evaluate the relationship in detail. Methods: Eligible reports were recruited into this meta-analysis from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Results: Eighteen investigations were identified for the analysis of association between polymorphic deletion of GSTT1 and HCC, consisting of 2,693 patients with HCC and 4,696 controls. Null genotype of GSTT1 was associated with HCC susceptibility in Chinese (OR=1.53, 95%CI: 1.28-1.82; P<0.00001). Conclusion: The GSTT1 null genotype is associated with HCC susceptibility in Chinese.

Should Threshold Growth Be Considered a Major Feature in the Diagnosis of Hepatocellular Carcinoma Using LI-RADS?

  • Jae Hyon Park;Yong Eun Chung;Nieun Seo;Jin-Young Choi;Mi-Suk Park;Myeong-Jin Kim
    • Korean Journal of Radiology
    • /
    • v.22 no.10
    • /
    • pp.1628-1639
    • /
    • 2021
  • Objective: Based on the Liver Imaging Reporting and Data System version 2018 (LI-RADS, v2018), this study aimed to analyze LR-5 diagnostic performance for hepatocellular carcinoma (HCC) when threshold growth as a major feature is replaced by a more HCC-specific ancillary feature, as well as the frequency of threshold growth in HCC and non-HCC malignancies and its association with tumor size. Materials and Methods: This retrospective study included treatment-naive patients who underwent gadoxetate disodium-enhanced MRIs for focal hepatic lesions and surgery between January 2009 and December 2016. The frequency of major and ancillary features was evaluated for HCC and non-HCC malignancies, and the LR-category was assessed. Ancillary features that were significantly more prevalent in HCC were then used to either replace threshold growth or were added as additional major features, and the diagnostic performance of the readjusted LR category was compared to the LI-RADS v2018. Results: A total of 1013 observations were analyzed. Unlike arterial phase hyperenhancement, washout, or enhancing capsule which were more prevalent in HCCs than in non-HCC malignancies (521/616 vs. 18/58, 489/616 vs. 19/58, and 181/616 vs. 5/58, respectively; p < 0.001), threshold growth was more prevalent in non-HCC malignancies than in HCCs (11/23 vs. 17/119; p < 0.001). The mean size of non-HCC malignancies showing threshold growth was significantly smaller than that of non-HCC malignancies without threshold growth (22.2 mm vs. 42.9 mm, p = 0.040). Similar results were found for HCCs; however, the difference was not significant (26.8 mm vs. 33.1 mm, p = 0.184). Additionally, Fat-in-nodule was more frequent in HCCs than in non-HCC malignancies (99/616 vs. 2/58, p = 0.010). When threshold growth and fat-in-nodule were considered as ancillary and major features, respectively, LR-5 sensitivity (73.2% vs. 73.9%, p = 0.289) and specificity (98.2% vs. 98.5%, p > 0.999) were comparable to the LI-RADS v2018. Conclusion: Threshold growth is not a significant diagnostic indicator of HCC and is more common in non-HCC malignancies. The diagnostic performance of LR-5 was comparable when threshold growth was recategorized as an ancillary feature and replaced by a more HCC-specific ancillary feature.

Resistin and Insulin Resistance: A Link Between Inflammation and Hepatocarcinogenesis

  • Elsayed, Engy Yousry;Mosalam, Nesreen Ahmed;Mohamed, Noha Refaat
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.16
    • /
    • pp.7139-7142
    • /
    • 2015
  • Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer related death overall. The role of insulin resistance in the development of HCC associated with chronic HCV infection has not been established. Resistin is a polypeptide hormone belonging to the adipokine family which could contribute to tumorigenesis and angiogenesis. Our aim was to study serum resistin and insulin resistance as risk factors for HCC in HCV cirrhotic patients. Materials and Methods: This prospective case controlled study included 100 patients with HCV related liver cirrhosis and HCC, 100 patients with HCV related liver cirrhosis without HCC and 50 apparently healthy participants as controls. For all subjects, liver profile, serologic markers for viral hepatitis, lipid profile, alpha-fetoprotein level (AFP), homeostasis model assessment (HOMA) were examined along with resistin. Results: HCC patients had higher mean values of HOMA-IR and resistin than cirrhotic patients and the control subjects (p<0.01). HOMA and resistin were considered independent risk factors in development of HCC, those patients with resistin > 12 ng/ml and HOMA > 4 being 1.6 times more likely to have HCC. Conclusions: HOMA and serum resistin allow for early identification of patients with cirrhosiswho are at substantially increased risk of HCC. Recommendation: HOMA and serum resistin could represent novel markers to identify HCV cirrhotic patients at greater risk of development of HCC.

Activity and Expression Pattern of NF-κB/P65 in Peripheral Blood from Hepatocellular Carcinoma Patients - Link to Hypoxia Inducible Factor -1α

  • Gaballah, Hanaa Hibishy;Zakaria, Soha Said;Ismail, Saber Abdelrahman
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.16
    • /
    • pp.6911-6917
    • /
    • 2014
  • Background: Hepatocellular carcinoma is a complex and heterogeneous tumor with poor prognosis due to frequent intrahepatic spread and extrahepatic metastasis. The molecular mechanisms underlying HCC pathogenesis still remain obscure. Objectives: We aimed to investigate the abundance and the DNA binding activity of nuclear factor kappa B/p65 subunit in peripheral blood mononuclear cells from patients with HCC and to assess its prognostic significance and association with hypoxia inducible factor one alpha (HIF-$1{\alpha}$) in blood. Subjects and methods: This study was carried out on 40 patients classified equally into liver cirrhosis (group I) and HCC (group II), in addition to 20 healthy volunteers (group III). All groups were subjected to measurement of NF-${\kappa}B$/P65 subunit expression levels by real time-PCR, and DNA binding activity was evaluated by transcription factor binding immunoassay. Serum HIF-$1{\alpha}$ levels were estimated by enzyme-linked immunosorbent assay (ELISA). Significant increase of both the expression level and DNA binding activity of NF-${\kappa}B$/P65 subunit together with serum HIF-1 alpha levels was noted in HCC patients compared to liver cirrhosis and control subjects, with significant positive correlation with parameters for bad prognosis of HCC. In conclusion, NF-${\kappa}B$ signaling is activated in HCC and associated with disease prognosis and with high circulating levels of HIF-1 alpha.

Associations Between Three Common MicroRNA Polymorphisms and Hepatocellular Carcinoma Risk in Chinese

  • Hao, Yu-Xia;Wang, Jun-Ping;Zhao, Long-Feng
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.11
    • /
    • pp.6601-6604
    • /
    • 2013
  • Aim: Associations between polymorphisms in miR-146aG>C, miR-196a2C>T and miR-499A>G and risk of HCC, and interaction with HBV infection in a Chinese population, were the target of the present research. Methods: The duplex polymerase-chain-reaction with confronting-two-pair primers (PCR-RFLP) was performed to determine the genotypes of the miR-146aG>C, miR-196a2C>T and miR-499A>G genotypes. Associations of polymorphisms with the risk of HCC were estimated by conditional logistic regression analysis. Results: Drinking, family history of cancer, HBsAg and HCV were risk factors for HCC. Multivariate regression analyses showed that subjects carrying the miR-196a2 CC genotype had significantly increased risk of HCC, with an adjusted OR (95% CI) of 2.18 (1.23-3.80). In addition, cases carrying the miR-196a2 C allele had a 1.64-fold increase in the risk for HCC (95%CI=1.03-2.49). The miR-196a2 CT and TT genotypes greatly significantly increased the risk of HCC in subjects with HBV infection, with adjusted ORs (95% CI) of 2.02 (1.12-3.68) and 2.69 (1.28-5.71), respectively. Conclusion: Our results demonstrate that miR-196a2 CC genotype and C allele have an important role in HCC risk in Chinese, especially in patients with HBV infection.

C-terminal truncated HBx reduces doxorubicin cytotoxicity via ABCB1 upregulation in Huh-7 hepatocellular carcinoma cells

  • Jegal, Myeong-Eun;Jung, Seung-Youn;Han, Yu-Seon;Kim, Yung-Jin
    • BMB Reports
    • /
    • v.52 no.5
    • /
    • pp.330-335
    • /
    • 2019
  • Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx.

Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

  • Chanthra, Nawin;Payungporn, Sunchai;Chuaypen, Natthaya;Pinjaroen, Nutcha;Poovorawan, Yong;Tangkijvanich, Pisit
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.12
    • /
    • pp.5069-5073
    • /
    • 2015
  • The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population.