• Journal of Veterinary Science
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• v.24 no.3
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• pp.36.1-36.7
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• 2023

Platelet to lymphocyte ratio (PLR) is a prognostic marker in human hepatocellular carcinoma (HCC) however, its utility in canine HCC has not been explored. The aim of the study was to determine if PLR could predict survival outcomes in 42 dogs with HCC. PLR was not a significant predictive factor (p = 0.15) but lymphopenia alone was significantly correlated with a reduced probability of survival (p = 0.024). Further studies are needed to evaluate if peripheral lymphocyte count mirrors that of the tumor microenvironment in canine HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2655-2661
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• 2014

Background: Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. Materials and Methods: We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell ($LO_2$ cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. Results: Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and $LO_2$ cell line (p<0.05). Compared with the $LO_2$ cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05). Conclusions: High levels of Talin-1 expression are correlated with reduced invasion and migration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3915-3920
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• 2014

Background: Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. Materials and Methods: This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. Results: During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was $56.5{\pm}7.7years$. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. Conclusions: Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

• Journal of Digestive Cancer Research
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• v.4 no.2
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• pp.92-98
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• 2016

The barcelona clinic liver cancer (BCLC) staging systemis regarded as the optimal staging system to predict prognosis and guide treatmentfor hepatocellular carcinoma (HCC) .According to the BCLC classification, only patients with BCLC A stage should undergo liver resection. In contrast, patients with intermediate-advanced HCC should be scheduled for palliative therapies,such as transcatheter arterial chemoembolization (TACE) and target therapy, even if the lesion is resectable. More and more studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by radical resection and many patients benefited from curative resection. The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations. A revision of the BCLC algorithm should be proposed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3253-3256
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• 2015

Background: Chronic hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC) is a major health problem in the Asia-Pacific region including Thailand. Several factors have been proposed as contributing to hepatocarcinogenesis. This study was aimed to investigate the impact of CYP2C19 genotypic polymorphism in HCC related to chronic HBV infection in Thailand. Materials and Methods: A cross-sectional study was performed between April 2014 and January 2015. Chronic HBV patients with HCC (n=50) and without HCC (n=50) were included. Clinical information and blood samples of all patients were collected. The CYP2C19 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method, and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: The CYP2C19 genotype frequencies of RM, IM and PM in HBV patients were found to be 19/50 (38%), 25/50 (50%) and 6/50 (12%), respectively. The CYP2C19 genotype frequencies of RM, IM and PM in HBV with HCC patients were 21/50 (42%), 25/50 (50%) and 4/50 (8%), respectively. The distribution of CYP2C19 genotype was not different between patients with and without HCC. Interestingly, among HBV with HCC patients, the RM genotype of CYP2C19 tended to increase risk of aggressive manifestation (OR=2.89, 95%CI=0.76-11.25, P-value=0.07), compared with non RM genotype carriers. Conclusions: CYP2C19 genotype IM was the most common genotype in Thai patients with chronic HBV infection. In addition, genotype RM could be an associated factor for aggressive presentation in HCC related to chronic HBV infection.

• Journal of Yeungnam Medical Science
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• v.29 no.1
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• pp.48-53
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• 2012

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths in South Korea. To decrease its mortality rate, its early detection is very important. Screening for HCC detection has been accepted as the management modality for patients with chronic liver disease. Reported herein is a case involving the marked rapid growth of HCC detected at an advanced stage in a screening test with a 3 months interval. A 49-year-old male patient with chronic hepatitis B was admitted to the hospital due to a liver mass detected on CT scan. The patient underwent a first CT scan 3 months earlier, and no tumor was detected. Follow-up CT scan was performed and showed a 9.1 cm HCC with portal vein thrombosis. Percutaneous liver biopsy was performed, and the diagnosis of hepatocellular carcinoma was confirmed. In the pertinent guidelines, the recommended screening interval for HCC is 6-12 months, but the screening interval and additional diagnostic methods should be considered due to the variation in the HCC growth rate according to the patient's clinical characteristics.

• 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.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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4853-4856
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• 2016

Objective: Gimatecan is a new camptothecin (CPT) analogue that inhibits tumor growth by targeting DNA topoisomerase I (TOP I) and introducing strong and persistent DNA cleavage. Anti-tumor activity has been demonstrated with a wide range of solid tumors in previous preclinical and clinical studies. Here, we investigated for the first time the effects of gimatecan on the proliferation of hepatocellular carcinoma (HCC) cells both in vitro and in vivo. Methods: Anticancer efficacy of gimatecan were evaluated in a panel of HCC cell lines and corresponding mouse xenograft models. Inhibition of cell proliferation was measured by CellTiter-Glo cell viability assay. In vivo, gimatecan and control preparations were orally administered every four days, for a total of four times. Tumor volume and body weights of the mice were measured twice weekly. Results: In vitro cytotoxicity evaluation showed that gimatecan inhibited the proliferation of a large panel of HCC cell lines in a dose dependent manner, with IC50 values ranging between 12.1~1085.0 nM. In vivo evaluation in mouse xenograft models showed significant antitumor effects of gimatecan at 0.8mg/kg and 0.4mg/kg as compared to the control group. Conclusion: This study suggested that gimatecan may have the potential to be used as a chemotherapeutic agent for the treatment of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7871-7874
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• 2015

Background: There is no consensus regarding the selection of treatment options for hepatocellular carcinoma (HCC) after initial transarterial chemoembolization (TACE). This meta-analysis aimed to explore the survival benefit of hepatic resection after initial TACE for the treatment of HCC. Materials and Methods: We searched three major databases to identify all relevant papers comparing the outcomes of hepatic resection after initial TACE versus TACE alone for the treatment of HCC. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to evaluate the survival benefit of hepatic resection after initial TACE over TACE alone. Results: Three of 2037 initially identified papers were included. All of them were cohort studies from Asia. There was a significantly better overall survival (OS) in patients undergoing hepatic resection after initial TACE than in those undergoing TACE alone (HR=0.63, 95%CI=0.52-0.76, P<0.00001). The heterogeneity among studies was not statistically significant (P=0.96; I2=0%). Conclusions: Hepatic resection could improve the OS of HCC patients treated with initial TACE. Further randomized controlled trials should be necessary to identify the target population for the sequential use of hepatic resection after initial TACE and to compare the outcomes between patients undergoing hepatic resection after initial TACE session versus those undergoing TACE alone.