• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10713-10718
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• 2015

Purpose: To investigate the prognostic value of serum amyloid A (SAA) in patients with hepatocellular carcinoma (HCC) undergoing surgery. Materials and Methods: Preoperative serum samples of 328 patients with HCC who underwent curative resection and of 47 patients with benign liver lesion were assayed. Serum levels of SAA were measured by enzyme-linked immunosorbent assay and its correlations with clinicopathological characteristics and survival were explored. Results: Levels of SAA were significantly higher in patients with HCC than those with benign liver lesion. There were strong correlations between preoperative serum SAA level and tumor size and more advanced BCLC stage. On univariate analysis, elevated SAA was associated with reduced disease-free survival and overall survival (p=0.001 and 0.03, respectively). Multivariate analyses showed that serum SAA level was an independent prognostic factor for overall survival (hazard ratio 2.80, p=0.01). Conclusions: High SAA serum level is a novel biomarker for the prognosis of HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.775-780
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• 2014

Objectives: TCR-gamma-delta+T cells (${\gamma}{\delta}$ T cells) are non-conventional T lymphocytes that can recognize and eradicate tumor cells. Our previous studies showed that infiltration and function of ${\gamma}{\delta}$ T cells were substantially attenuated in hepatocellular carcinoma (HCC). However, their prognostic value was not clarified. Methods: The association between ${\gamma}{\delta}$ T cells and the clinical outcomes was determined by immunohistochemistry (IHC) in a HCC patient cohort (n = 342). Results:Immunohistochemistry showed decreased infiltration of ${\gamma}{\delta}$ T cells in tumoral tissues compared with paired peritumoral tissues. The counts of ${\gamma}{\delta}$ T cells in peritumoral tissues were negatively correlated with tumor size (P = 0.005). Survival analysis showed that the levels of peritumoral ${\gamma}{\delta}$T cells were related to both time to recurrence (TTR) and overall survival (OS) (P = 0.010 and P = 0.036, respectively) in univariate analysis, and related to TTR in multivariate analysis (P = 0.014, H.R. [95% CI] = 0.682 [0.502-0.927]). Furthermore, the level of peritumoral ${\gamma}{\delta}$ T cells showed independent prognostic value for TTR in Barcelona Clinic Liver Cancer (BCLC) stage A patients (P = 0.038, H.R. [95% CI] = 0.727 [0.537-0.984]). However, tumoral ${\gamma}{\delta}$ T cells did not show independent prognostic value for either TTR or OS in HCC patients. Conclusions: Low counts of ${\gamma}{\delta}$ T cells in peritumoral liver tissue are related to a higher incidence of recurrence in HCC and can predict postoperative recurrence, especially in those with early-stage HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3811-3816
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• 2015

Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10513-10524
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• 2015

Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.

• Korean Journal of Veterinary Pathology
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• v.2 no.2
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• pp.73-84
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• 1998

This study was carried out to investigate on the serum chemistry and the DNA ploidy changes in carcinogenesis of the rat liver and kidney. Sixty male Sprague-Dawley rats were divided into two groups. Group I was non-treated control. Group II was given initiators (2,2'-dihydroxy- di-N-propylnitrosamine, 0.1% in drinking water(d.w.) for 1 week and N-ethyl-N-hydroxy-ethylnitrosamine; 0.15% in d.w. for 1 week) and promoters (3'methyl-cholanthrene; 3'MC, l0mg/kg, intraperitoneally(i.p.) twice a week and DL-serine; 0.05% in d.w. for 5 weeks, from 3 to 8 weeks). All examinations were performed at 12 and 20 weeks RBC, HGBCp＜0.05) and PCVCp＜0.01) significantly decreased in Group II at 20 weeks. Activities of ALT, AST(p＜0.05) and GGT(p＜0.01) were significantly increased in Group II at 20 weeks. Flow cytometric analysis showed hepatocyte nuclei from normal livers were predominantly tetraploid(66~67%) and then diploid(28~30%). Most of hepatocyte nuclei from carcinogen-treated rats were diploid (52~68%) and less were tetraploid(28~42%). Neoplastic liver nodules and hepatocellular carcinoma contained almost exclusively diploid nuclei. Renal cell nuclei from normal kidney were predominantly diploid(88~93%), those from carcinogen-treated rats had an abnormal DNA-content peak(aneuploidy, 6-7%), near the tetraploidy area. These results suggest that diploidy may be an effective screening marker of the liver carcinogenesis. Aneuploidy may be an useful marker in assessment of the experimental renal carcinogenesis.

• Korean Journal of Veterinary Pathology
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• v.1 no.1
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• pp.13-25
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• 1997

The anticarcinogenic effects of dimethyl disulfide(DMDS, methyl disulfide)and diallyl disulfide(DADA, allyl disulfide) were studied in a 28 weeks rat multi-organ carcinogenesis model. neoplastic and preneoplastic lesions were observed in the liver kidney thyroid gland esophagus duodenum colon, rectum and adrenal gland. Tesults showed that neoplastic lesions in the kidney liver and thyroid gland were inhibited by DADS but those in the liver and colon were enhanced by DMDS when compared to positive control group. incidence of neoplastic lesions in the other organs were not changed by DMDS or DADS exposure. While GST-p positive foci in the liver were increased by DMDS, DADS had no effect. There was no significant histopathological lesion in DMDS or DADS treated group without pretreatment with carcinogens.

• Korean Journal of Veterinary Service
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• v.22 no.1
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• pp.61-70
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• 1999

This study is concerned with assessment of diethylnitrosamine(DEN) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate the changes of liver-specific enzyme activities in rats (Sprague-Dawley) by ad libitum feeding of DEN. And also, as another objective index in urine, the level of urinary biopterin was measured by high performance liquid chromatography(HPLC) method. The results were as follows ; 1. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 7 weeks after DEN administration. 2. The body and liver weights were significantly(p<0.05) decreased in rats 11 weeks after DEN administration. 3. The ratio of liver weight to body weight was rather stable and not significantly decreased in the all treatment groups. 4. The liver specific enzyme activities(AST, ALT,$\gamma$-GTP) were significantly(p<0.05) increased in all treatment groups compared to control group. 5. Compared to normal level, urine biopterin level was significantly (p<0.05) increased in all treatment groups(p<0.05). In conclusion, this result confirmed that the DEN was one of the potent hepatocarcinogens. In experimental model of rats exposed to DEN, the results indicated that values of liver specific enzyme activities(AST, ALT, $\gamma$-GTP) and urine biopterin level could be useful complementary tumor indices.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6455-6461
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• 2012

Objective: E-cadherin has been identified as a tumor suppressor in many types of carcinoma. However, some studies recently suggested that the role and expression of E-cadherin might be more complex and diverse. In the present study, we evaluated the prognostic value of E-cadherin expression with reference to levels in membranes and cytoplasm, and the membrane/cytoplasm ratio, in hepatocellular carcinomas (HCCs) after curative hepatectomy. Methods: The expression of E-cadherin was assessed by immunohistochemistry in HCC tissue microarrays from 125 patients, and its prognostic values and other clinicopathlogical data were retrospectively analyzed. Patients were followed for a median period of 43.7 months (range 1 to 126 months). Results: Univariate analysis demonstrated that a high membrane/cytoplasm (M/C) ratio of E-cadherin expression was associated with poor overall survival (OS) (P =0.001) and shorter time to recurrence (TTR) (P=0.038), as well as tumor size, intrahepatic metastasis, and TNM stage. In contrast, neither membrane nor cytoplasmic expression of E-cadherin was related with OS and TTR. Furthermore, multivariate analysis confirmed the M/C ratio to be an independent predictor of OS (P=0.031). ${\chi}^2$ tests additionally showed that the M/C ratio of E-cadherin expression was related with early stage recurrence (P=0.012), rather than later stage recurrence. Conclusion: The M/C ratio of E-cadherin expression is a strong predictor of postoperative survival and is associated with early stage recurrence in patients with HCC.

• Herbal Formula Science
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• v.22 no.1
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• pp.177-192
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• 2014

Objective : In order to investigate the effect of Curcumae Longae Rhizoma(CLR) extract on the hepatocellular carcinogenesis and acute liver damage induced by diethylnitrosamine(DENA) and $CCl_4$ in rats. Methods : Experimental groups were subdivided into four; normal group (Nor), acute liver damage and hepatocellular cancer inducing control group (Con), and CLR extract 200mg/kg/day (CAA) or 400mg/kg/day (CAB) administered groups to Con. Thereafter the changes of the body weight, the liver weight and the weight of liver/100g body weight, total cholesterol, HDL cholesterol, triglyceride, the activities of AST, ALT, ALP, LDH, AFP, SOD, catalase were measured. And we observed by optical and electron microscopy. Result : 1. The body weight was decreased in Con compared with Nor for 5 weeks, but increased in Con compared with Nor from 6 week to 9 week. During experimental period of total 9 weeks, CAA and CAB were increased compared with Con. 2. The liver weight was increased significantly (p<0.05) in Con compared with Nor. The weight of liver/100g body weight was increased significantly (p<0.05) in Con compared with Nor and decreased significantly (p<0.05) in CAB compared with Con. 3. The level of total cholesterol was increased in Con and CAA compared with Nor, but there was not statistically significant. The level of triglyceride was decreased in Con compared with Nor. But increased in CAA and CAB compared with Con. The level of HDL-cholesterol was significantly increased (p<0.05) in CAA and CAB compared with Con. 4. The activities of AST, ALT were increased in Con compared with Nor, but decreased in CAA compared with Con, significantly decreased (p<0.05) in CAB compared with Con. 5. The activities of ALP, LDH were increased in Con compared with Nor, but decreased in CAA and CAB compared with Con. 6. The activities of AFP was increased significantly (p<0.05) in Con compared with Nor, but decreased significantly (p<0.05) in CAA and CAB compared with Con. 7. The activities of SOD were increased in Con, CAA and CAB compared with Nor, but decreased in CAA and CAB compared with Con. The activities of Catalase was more increased in CAA and CAB compared than Con. 8. The results of light microscopical observation, a number of hepatocytes were damaged in Con compared with Nor and CAB. 9. According to the electron microscopical observation, irregular nuclear membrane, condensed nucleoplasm was observed in Con, the experimental group was observed in the nucleus of the well-preserved and evenly developed nucleoplasm. Conclusions : These results suggest that administration of CLR extract suppress or retard on the hepatocellular carcinogenesis and acute liver damage induced by DENA and $CCl_4$ in rats.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.39-40
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• 2001

The inhibition of carcinogenesis by tea has been demonstrated in animal models on many organ sites. These include cancers of the skin, lung, oral cavity, esophagus, stomach, liver, small intestine, pancreas, colon, bladder, prostate, and mammary glands. The most well studied sites are skin and lung.(omitted)