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ABSTRACT: Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of patients with advanced liver cancer. However, acquisition of cisplatin resistance is common in patients with hepatocellular carcinoma (HCC), and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-130a levels were significantly increased in HCC patients treated with cisplatin-based chemotherapy. miR-130a levels were also higher in cisplatin-resistant Huh7 cells than in Huh7 cells. Overexpression of miR-130a contributed to cisplatin resistance in Huh7 cell, whereas knockdown of miR-130a overcame cisplatin resistance in cisplatin-resistant Huh7 cell. We further demonstrated that upregulated miR-130a directly inhibited expression of tumor suppressor gene RUNX3, which resulted in activation of Wnt/β-catenin signaling and increased drug resistance. These data suggest that miR-130a/RUNX3/Wnt signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.
Biochemical and Biophysical Research Communications 07/2012; 425(2):468-72. · 2.48 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.
Biochemical and Biophysical Research Communications 06/2012; 423(4):826-31. · 2.48 Impact Factor
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ABSTRACT: There is no large-cohort report on living donor liver transplantation (LDLT) for biliary atresia (BA) patients from the mainland of China. This single-center study describes our initial experience with 43 LDLTs for BA patients aged two years or younger.
In this study, the eligibility criteria were BA as the primary diagnosis and two years of age or younger. From October 2006 to December 2010, the clinical data of 43 LDLTs, including pre-operative evaluations, surgical techniques, postoperative complications and outcomes of donors and recipients, were retrospectively analyzed.
Donor graft type was the left lateral segment with compatible ABO blood groups. Forty-three recipients were selected in this study. The median patient age at operation was 9 months (range 6-24), and the median body weight was 8 kg (range 5.7-12.5). Fourteen (32.6%) recipients received Kasai operations before liver transplantation. The overall one- and two-year cumulative survival rates for grafts and recipients were 81%, 81% and 76%, 76%, respectively. No donor mortality was encountered, with a minimal morbidity and no long-term sequelae. Nine out of 43 recipients died. Postoperative complications of recipients were biliary leakage and refluxing cholangitis (11/43, 25.6%), hepatic artery thrombosis (4, 9.3%), pulmonary infections (4, 9.3%), portal vein thrombosis (3, 7.0%), wound disruption (3, 7.0%), acute rejection (3, 7.0%), cytomegalovirus infection (2, 4.7%), and intra-abdominal bleeding (1, 2.3%).
Despite the relatively low survival rates due to lack of experience initially, LDLT still provides encouraging outcomes for pediatric recipients with BA, even small children under two years old.
Hepatobiliary & pancreatic diseases international: HBPD INT 06/2012; 11(3):250-5. · 1.08 Impact Factor
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ABSTRACT: Monitoring immune status in transplant recipients is essential for predicting the risk of infections. The aims of the study were to identify the correlation of a low ImmuKnow adenosine triphosphate (ATP) value with the development of invasive fungal infections (IFIs) and whether this is an independent risk factor for IFIs in liver recipients.
We followed up 248 liver recipients who developed 157 infectious episodes. Peripheral CD4(+) T cells were selected freshly for ATP detection. Percentages of T-helper (Th, CD3(+) CD4(+) ) and T-suppressor (Ts, CD3(+) CD8(+) ) lymphocyte subgroups were also examined.
Overall 44 patients (17.7%) were diagnosed as IFIs, of whom 9 (20.5%) died. The average ImmuKnow ATP value in the IFI patients (109 ± 78 ng/mL) was significantly lower than that in common bacterial infections (174 ± 106 ng/mL, P < 0.01) or stable liver recipients (314 ± 132 ng/mL, P < 0.01), while there was no difference in the Th/Ts ratio among each group. Logistic regression analysis showed ImmuKnow ATP value less than 100 ng/mL was an independent risk factor of IFI (OR = 3.44, P = 0.0237). ImmuKnow ATP values had no correlation with lymphocytes or their subgroups, but tended to correlate with the number of neutrophils and total white blood cells.
ImmuKnow assay monitoring has the potential to identify the patients at risk of developing IFI after liver transplantation (LT), which may provide a feasible measure for optimizing liver recipients' immune cellular function after transplantation.
Journal of Digestive Diseases 12/2011; 12(6):467-75. · 1.59 Impact Factor
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ABSTRACT: To identify the levels of functional immunity measured by the ImmuKnow assay in Chinese liver transplantation recipients and its application in monitoring the risk of posttransplant infection.
Forty-five apparent healthy Chinese and 106 adult liver transplant (LT) recipients were under investigation. LTs were grouped in stable status or infection according to their clinical diagnosis. Whole blood samples were collected freshly and cultured within 6 hr, the CD4(+) T cells were selected, and their adenosine triphosphate (ATP) value was assayed the next day. Before stimulation, we also examined the percentage of T-helper (Th; CD3(+) CD4(+)) and T-suppress (Ts; CD3(+) CD8(+)) lymphocyte subpopulations and the ratio of Th/Ts.
The average ImmuKnow assay in infectious LT recipients was 128 + or - 84 ng/mL, significantly lower (P<0.05) than that in stable LTs (305 + or - 149 ng/mL) or in normal adults (301+ or - 101 ng/mL). The ImmuKnow values in LTs had a good negative correlation to infection clinically (r = -0.6217, P<0.001). Infectious risk was high when the ImmuKnow value was less than 130 ng/mL (odds ratio=13, 95% confidence interval 6.0-29.4, P<0.01). The sensitivity of low ImmuKnow values in posttransplant infection was 85.2%, significantly higher than those of Th/Ts ratio and immunosuppressant trough levels (P<0.01); specificity was 76.3%, comparable with that of Th/Ts ratio (75.5%), but greatly higher than immunosuppressant trough levels (P<0.01). ImmuKnow ATP values had no correlation with Th/Ts ratio or immunosuppressant trough levels.
ImmuKnow ATP levels are lower in LT recipients with infection, which provides a new tool in monitoring posttransplant infection, and an index of tailoring immunosuppression clinically.
Transplantation 12/2009; 89(5):620-6. · 4.00 Impact Factor
