[Role of hepatic surgery in colorectal cancer multiple liver metastasis].

Colorectal cancer liver metastasis can be categorized as initially resectable and initially unresectable liver metastasis. Patients with initially resectable colorectal cancer liver metastases may benefit from hepatic surgery significantly,while those with initially unresectable metastases also have an opportunity to be treated radically by liver surgery after conversion therapy,so as to have a prolonged survival time. It is crucial to choose the right time and right way of surgical intervention. The timing depends on determination of tumor resectability,controlling of pre-operative systemic therapy and evaluation of liver function after systemic treatment. The selection of right way contains the election between synchronous operation and staged operation, resection margin and using of technologies such as laparoscope and associating liver partition and portal vein ligation for staged hepatectomy. This paper aims to explore the optimal timing for operation and the approaches of surgical method based on the research progress worldwide for prolonging the survival time of patients with colorectal cancer multiple liver metastases.

[Study on the clinical significance and correlation of arginase-1 and inducible nitric oxide synthase expression in hepatocellular carcinoma].

Objective: To investigate the clinical significance and correlation of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression in hepatocellular carcinoma (HCC). Methods: The expression of Arg-1and iNOS in 146 cases of hepatocellular carcinoma tissues and corresponding adjacent tissues was detected by immunohistochemistry. The clinicopathological characteristics and the correlation between the expressions and prognosis were determined by chi square test, Spearman's rank correlation, Kaplan-Meier survival analysis and Cox regression analysis. Results: The positive rates of Arg-1 and iNOS were 18.7% (23/123) and 37.0% (54/146), respectively, which was significantly lower than the adjacent tissues [100%(146/146) and 93.8% (137/146)] and the difference was statistically significant (χ (2) = 212.521, P < 0.01, χ (2) = 104.276, P < 0.01). There was a positive correlation between the both expression (r = 0.331, P < 0.01). Arg-1 low expression was correlated with preoperative serum alpha-fetoprotein (AFP) level, tumor size, differentiation degree, histological types and Edmondson's grade. iNOS low expression was correlated with the differentiation degree and Edmondson's grade (P < 0.05). Kaplan Meier survival analysis showed that in patients with recurrence-free survival (RFs), Arg-1 (+) group > Arg-1 (-) group and Arg-1 (+) iNOS (+) group > Arg-1 (+) iNOS (-) group > Arg-1 (-) iNOS (-) group (P < 0.05). Cox multivariate analysis showed that age, tumor size, Edmondson's grade, vascular tumor emboli were significantly correlated with RFs (P < 0.05). Conclusion: There is a positive correlation between Arg-1 and iNOS expressions in HCC, and both may reflect the HCC malignant degree. The reduced/absent expression of both may participate in the occurrence and development of HCC. The combined detection of Arg-1 and iNOS on HCC may have certain significance for the judgment of differentiation degree and prognosis.

[Synergistic lethal effect of combined treatment of arsenic trioxide and aclacinomycin on human acute myeloid leukemia cell line KG-1a].

Objective: To investigate the synergistic lethal effect and mechanism of arsenic trioxide (ATO) and aclacinomycin (ACM) on human acute myeloid leukemia cell line KG-1a. Methods: Colony-forming assay was used to detect the proliferation of KG-1a cells treated with different concentration of ATO and ACM. Compusyn software was used to analyze the synergistic effect of ATO and ACM. Flow cytometry and Wright's staining were used to analyze the apoptotic rate of KG-1a cells induced by combined treatment of ATO and ACM. Western blot was used to determine the expression of proteins associated with apoptosis. Results: The cytotoxicity of arsenic trioxide or aclacinomycin alone was in a dose-dependent manner. Flow cytometry analysis showed that the apoptotic rate of KG-1a cells treated with both 0.4 µmol/L ATO and 10 nmol/L ACM was (34.5±3.1)%, significantly higher than (7.6±1.1)% of 0.4 µmol/L ATO treatment or (18.7±2.3) % of 10 nmol/L ACM treatment alone (P<0.05). The apoptotic rate of KG-1a cells treated with both 1.5 µmol/L ATO and 37.5 nmol/L ACM was (52.5±4.7)%, significantly higher than (19.1±3.2)% of 1.5 µmol/L ATO treatment or (27.7±2.2)% of 37.5 nmol/L ACM treatment alone (P<0.05). The apoptotic rate of KG-1a cells treated with both 3.0 µmol/L ATO and 75 nmol/L ACM was (61.3±4.5)%, significantly higher than (29.5±2.5)% of 3.0 µmol/L ATO treatment or (28.6±3.4) % of 75 nmol/L ACM treatment alone (P<0.05). In addition, the result of Wright's staining showed that combined treatment of ATO and ACM induced a more apparent phenotype of apoptosis when compared with single agent treatment. Compusyn software analysis showed that the combination index (CI) value of combined treatment group was less than 1, which indicated the synergistic effect of these two agents. Conclusions: Combined treatment of ATO and ACM shows a synergistic lethal effect on human acute myeloid leukemia cell line KG-1a via activating the apoptotic pathway, which inhibits cell growth and induces apoptosis.

Activated natural killer cells accelerate liver damage in patients with chronic hepatitis B virus infection.

Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV-infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV-infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune-clearance (IC) patients, 36 immune-tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3-4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients.