• Title/Summary/Keyword: Hepatocellular

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Alteration of Hepatic Drug Metabolizing Function after Traumatic Injury

  • Lee, Woo-Yong;Lee, Sang-Ho;Lee, Sun-Mee
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.301.1-301.1
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    • 2002
  • The aim of present study was to investigate effects of blunt trauma on alterations in cytochrome P-450 (CYP)-dependent drug metabolizing function and to determine the role of Kupffer cells in the hepatocellular dysfunction Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia. Control animals received only anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride (GdCl3) was injected intravenously via the tail vein at 7.5 mg/kg body wt. 1 and 2 days before surgery. (omitted)

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Tissue Microarray Immunohistochemical Profiles of p53 and pRB in Hepatocellular Carcinoma and Hepatoblastoma

  • Azlin, Abdul Hadi;Looi, Lai Meng;Cheah, Phaik Leng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3959-3963
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    • 2014
  • The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.

Soluble Expression of Recombinant Human Smp30 for Detecting Serum Smp30 Antibody Levels in Hepatocellular Carcinoma Patients

  • Zhang, Sheng-Chang;Huang, Peng;Zhao, Yong-Xiang;Liu, Shu-Yan;He, Shu-Jia;Xie, Xiao-Xun;Luo, Gou-Rong;Zhou, Su-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2383-2386
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    • 2013
  • Senescence marker protein 30 (SMP30), a hepatocellular carcinoma (HCC) associated antigen, was earlier shown by our research group to be highly expressed in HCC paracancerous tissues, but have low levels in HCC tissues. In order to detect anti-SMP30 antibody in serum of HCC patients, we established pET30a-SMP30 and pColdIII-SMP30 expression systems in Escherichia coli. However, the expression product was mainly in the form of inclusion bodies. In this research, we used several combinations of chaperones, four molecular chaperone plasmids with pET30a-SMP30 and five molecular chaperone plasmids with pColdIII-SMP30 to increase the amount of soluble protein. Results showed that co-expression of HIS-SMP30 with pTf16, combined with the addition of osmosis-regulator, and a two-step expression resulted in the highest enhancement of solubility. A total of 175 cases of HCC serum were studied by ELISA to detect anti-SMP30 antibody with recombinant SMP30 protein. Some 22 were positive and x2 two-sided tests all showed P>0.05, although it remained unclear whether there was a relationship between positive cases and clinical diagnostic data.

Three Treatment Methods via the Hepatic Artery for Hepatocellular Carcinoma - A Retrospective Study

  • Ma, Teng-Chuang;Shao, Hai-Bo;Xu, Yang;Xu, Ke
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2491-2494
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    • 2013
  • Background: To evaluate the relative effectiveness of different treatments of hepatocellular carcinoma (HCC) via the hepatic artery. Materials and Methods: The study sample group consisted of 418 patients who were randomly selected from 2008 to 2012 with a first diagnosis of HCC and treated with transcatheter arterial chemoembolization (TACE) or without (TAE) chemotherapy or transcatheter arterial infusion (TAI). We collected data including tumor size preoperative and one month thereafter to compare change in areas across the three groups, along with various laboratory indexes for comparison. Results: The overall average change of areas was $240.8{\pm}72.1mm^2$. In the three groups it was $265.0{\pm}58.0mm^2$ vs. $250.5{\pm}51.9mm^2$ vs. $123.7{\pm}26.2mm^2$. In groups TACE and TAE values were larger than in group TAI (p<0.01), but the difference between the two was not statistically significant (p= 0.191). Additionally, U/L change of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in groups TACE and TAE was greater than in the TAI cases ($24.0{\pm}13.5$ vs. $20.9{\pm}12.1$ vs. $5.47{\pm}8.20$ and $25.6{\pm}13.5$ vs.$23.2{\pm}12.28$ vs.$5.48{\pm}14.3$) on the preoperative day and two days thereafter (p<0.01). Between the two groups there was no significant cariation (p= 0.320 and p= 0.609). However, the AST and ALT recovered to normal levels one month later on therapy with liver protecting drugs. Conclusion: The groups TACE and TAE demonstrated more effective reduction of tumor size than group TAI. While lipiodol caused acute liver function damage, this proved reversible.

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
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    • v.16 no.16
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    • pp.7139-7142
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    • 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.

Association of MDR1 Gene Polymorphisms with Susceptibility to Hepatocellular Carcinoma in the Chinese Population

  • Ren, Yong-Qiang;Han, Ju-Qiang;Cao, Jian-Biao;Li, Shao-Xiang;Fan, Gong-Ren
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5451-5454
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    • 2012
  • Objective: The objective of this study was to evaluate the association of MDR1 gene polymorphisms with susceptibility to hepatocellular carcinoma (HCC). Methods: A total of 689 HCC patients and 680 cancer-free subjects were enrolled. Human MDR1 gene polymorphisms were investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Multiple logistic regression models were applied to estimate the association between MDR1 gene polymorphisms and susceptibility to HCC. Results: We detected a novel c.4125A>C polymorphism and our findings suggested that this variant was significantly associated with susceptibility to HCC. A significantly increased susceptibility to HCC was noted in the homozygote comparison (CC versus AA: OR=1.621, 95% CI 1.143-2.300, ${\chi}^2$=7.4095, P=0.0065), recessive model (CC versus AC+AA: OR=1.625, 95% CI 1.167-2.264, ${\chi}^2$=8.3544, P=0.0039) and allele contrast (C versus A: OR=1.185, 95% CI 1.011-1.389, ${\chi}^2$=4.4046, P=0.0358). However, no significant increase was observed in the heterozygote comparison (AC versus AA: OR=0.995, 95% CI 0.794-1.248, ${\chi}^2$=0.0017, P=0.9672) and dominant model (CC+AC versus AA: OR=1.106, 95% CI 0.894-1.369, ${\chi}^2$=0.8560, P=0.3549). Conclusions: These findings suggest that the c.4125A>C polymorphism of the MDR1 gene might contribute to susceptibility to HCC in the Chinese population. Further work will be necessary to clarify the relationship between the c.4125A>C polymorphism and susceptibility to HCC on larger populations of diverse ethnicity.

Associations Between Infiltrating Lymphocyte Subsets and Hepatocellular Carcinoma

  • Guo, Cun-Li;Yang, Hai-Chao;Yang, Xiu-Hua;Cheng, Wen;Dong, Tian-Xiu;Zhu, Wen-Jing;Xu, Zheng;Zhao, Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5909-5913
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    • 2012
  • Aims: We aimed to analyze the phenotype of tumor-infiltrating lymphocytes (TILs) and non-tumor infiltrating lymphocytes (NILs) in HCC and non-tumor tissues, and evaluate relationships between changes in these cells and the prognosis of HCC. Methods: Lymphocytes were isolated from HCC and corresponding non-tumor tissues and tested by flow cytometry. For comparison, clinical parameters were analyzed. Results: Compared with the non-tumor tissue, tumor tissue had a lower intensity of NK, NKT andCD8+T cell infiltration. TILs had higher intensity of CD4+CD25+Foxp3+regulatory T cell (Treg cells) infiltration compared with that in NILs. The prevalence of Treg cells was associated with fewer CD8 + T lymphocytes in the HCC immune microenvironment. The frequencies of NK cells and CD8+T cells in TILs of HCC patients with metastasis less than 12 months were lower than those without metastasis. However, the frequency of Treg cells was higher than those without metastasis. Conclusion: These results suggest that the frequencies of CD8+T, NK and NKT cells as well as Treg cells in the tumor tissue of HCC are significantly associated with patient survival, and could be applied as predictive indicators for HCC prognosis.

Evaluation of DNA Repair Gene XRCC1 Polymorphism in Prediction and Prognosis of Hepatocellular Carcinoma Risk

  • Li, Qiu-Wen;Lu, Can-Rong;Ye, Ming;Xiao, Wen-Hua;Liang, Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.191-194
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    • 2012
  • We conducted a case-control study in China to clarify the association between XRCC1-Arg399Gln polymorphism and HCC risk. A total of 150 cases and 158 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. A significantly increased risk was associated with the Arg/Gln genotype (adjusted OR 1.78, 95%CI=1.13-2.79) compared with genotype Arg/Arg. In contrast, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.69 (0.93-2.66). A significant association was found between positive HBsAg and Arg/Gln, with an OR of 3.43 (95% CI=1.45-8.13). Patients carrying Gln/Gln genotypes showed significantly lower median survival than Arg/Arg genotypes (HR=1.38, 95% CI=1.04-1.84). Further Kaplan-Meier analysis showed decreased median survival in Arg/Gln+Gln/Gln genotype carriers in comparison to Arg/Arg carriers (HR=1.33, 95% CI=1.02-1.76). In conclusion, we observed that XRCC1-Arg399Cln polymorphism is associated with susceptibility to HCC, and XRCC1 Gln allele genotype showed significant prognostic associations.

Polymorphisms of TERT and CLPTM1L and the Risk of Hepatocellular Carcinoma in Chinese Males

  • Su, Ling-Yan;Li, Xue-Lian;Shen, Li;Zhang, Yue;Zhao, Meng-Meng;Yin, Zhi-Hua;Su, Hong-Ying;Zhou, Bao-Sen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8197-8201
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    • 2014
  • Background: Telomerase reverse transcriptase (TERT) and cleft lip and palate trans-membrane 1 like (CLPTM1L) genes located on chromosome 5p15.33 are known to influence the susceptibility to various cancers. Here, we examined the association of TERT and CLPTM1L single nucleotide polymorphisms (SNPs) with hepatocellular carcinoma (HCC). Materials and Methods: Genotyping of TERT SNP rs2736098 and CLPTM1L SNP rs401681 was performed using TaqMan allelic discrimination assays in a case-control study of 201 HCC cases and 210 controls in a Chinese male population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analyses. Results: Both the rs2736098 T allele of TERT and the rs401681 T allele of CLPTM1L were associated with a significantly increased risk of HCC (adjusted odds ratio [OR]=1.605, 95% confidence interval [CI]=1.164-2.213; adjusted OR=1.399, 95%CI=1.002-1.955, respectively). Individuals carrying both TERT and CLPTM1L risk genotypes had an even higher risk of HCC (adjusted OR=4.420, 95%CI= 2.319-8.425). The TERT rs2736098 T allele was also significantly associated with the level of the HCC clinical indicator alpha-fetoprotein (P=0.026). Conclusions: Our results show that genetic variants of TERT and CLPTM1L may contribute to HCC susceptibility in Chinese males.