Associations of SLCO1B1 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients / 药学学报

The study aims to investigate the associations of SLCO1B1 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 89 renal transplant recipients with tacrolimus treatment. CYP3A5*3 genotypes were detected by PCR-RFLP method and SLCO1B1 (rs2306283, rs4149032) genotypes were detected by Agena Bioscience Mass ARRAY ® system. Trough concentrations of tacrolimus on day 7 after renal transplantation were collected from clinical data. Correlations between genetic polymorphisms and tacrolimus concentrations were analyzed by SPSS. In CYP3A5 nonexpressers, the dose-adjusted concentration of tacrolimus in SLCO1B1 rs2306283 CC carriers was considerably higher than that in CT and TT carriers. The results illustrated that SLCO1B1 rs2306283 polymorphisms were associated with tacrolimus concentrations, and genotyping for this SNP may be usefulfo r individualized medicine of tacrolimus.

Efficacy of continuous blood purification on rescue therapy of the critically ill children with acute lung injury and acute respiratory distress syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of continuous blood purification(CBP) in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in children.</p><p><b>METHODS</b>One hundred and forty seven cases of ALI/ARDS were hospitalized to our pediatric intensive care unit, and 32 cases were treated with continuous blood purification (CBP) from June, 2006 to May, 2011. The model for CBP was continuous veno-venous hemofiltration dialysis (CVVHDF). CBP treatment persisted for at least 8 hours and replacement + dialysis fluid dose was 35 - 100 ml/(kg·h). The clinical outcome measures included the mortality rate at 28th day, respiratory index (FiO2/PO2), dynamic lung compliance (Cdyn), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), mechanical ventilation parameters, vasoactive drug dose and lung X-ray changes.</p><p><b>RESULTS</b>In totally 147 cases of ALI/ARDS, 89 cases (60.5%) were male and 58 (39.5%) were female, mean age was (43.4 ± 36.7) months. Death occurred in 54 cases, the total mortality was 36.7%. The cause of ALI/ARDS was mainly severe pneumonia, severe sepsis, and leukemia or tumor diseases. There were significant differences in severity of illness between the CBP treatment group and non-CBP treatment group on Pediatric risk of score mortality (PRISM) III score (15.3 vs. 12.7, P < 0.05) and pediatric critical illness score (66.8 ± 19.3 vs. 74.6 ± 17.7, P < 0.05). The average duration of CBP treatment was 52 hours (12 hours to 232 hours). PaO2/FiO2 and Cdyn were improved after 2 hours CBP treatment compared with those before CBP treatment (P < 0.05), mechanical ventilation parameters including fraction of inspired oxygen (FiO2), peak inspiratory pressure (PiP) and positive end expiratory pressure (PEEP) were reduced. The use of vasoactive drugs in patients with MODS and shock gradually declined. The average ventilator-free days of the two groups did not show significant difference (P > 0.05). The mortality on CBP treatment group and non-treatment group were 37.5% and 36.5%, respectively, the difference was not significant (P > 0.05).</p><p><b>CONCLUSION</b>CBP adjuvant treatment for ALI/ ARDS could reduce pulmonary edema, improve PaO2/FiO2 and Cdyn, and improve mechanical ventilation parameters. CBP may be a very promising treatment for ALI/ARDS in children.</p>

Analysis of differential gene expression in rat hepatic stellate cells activated by culture or hepatocellular carcinoma cell induction / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Hepatic stellate cells (HSC) in hepatocellular carcinoma (HCC) transdifferentiate into extracellular matrix-producing myofibroblasts. Activated HSC can promote invasion and metastasis of HCC. To understand the differences of HSC in normal liver and HCC, we compared the gene expression patterns in HCC cell induction-activated and culture-activated rat HSC.</p><p><b>METHODS</b>HSC were isolated by density centrifugation and exposed to conditioned medium from rat HCC cell line C5F. Expression of 22 012 genes in quiescent HSC, culture-activated HSC and HCC induction-activated HSC was analyzed by cDNA microarray and confirmed by real-time RT-PCR and Western blot.</p><p><b>RESULTS</b>1672 genes were differentially expressed in culture-activated HSC, including proinflammatory factors, cell adhesion molecules, cell surface receptors, signaling transduction molecules and immune factors. 711 genes were differentially expressed in HCC induction-activated HSC. Some of them were identical to those in culture-activated HSC. HCC Induction-activated HSC showed specific gene expression patterns, including Raf1, Rac2, Adam17, Wnt6, MMP-9 and TNF, suggesting that HCC cells can specifically induce HSC activation.</p><p><b>CONCLUSION</b>The gene expression patterns in HCC induction-activated HSC are different from those in culture-activated HSC. HCC induction-activated HSC may play a major role in the invasion and metastasis of HCC. In vivo activation should be considered as the standard for the study of HSC biology. HCC induction-activated HSC should be considered as the standard for HSC biology studies.</p>

Effect of siRNA targeted against survivin on the malignant behaviors of human hepatoma cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study survivin expression in human hepatoma cells and the effects of survivin siRNA on the malignant phenotypes of human hepatocellular cell line HCCLM6.</p><p><b>METHODS</b>Four hepatocellular carcinoma (HCC) cell lines were used. Semi-quantitative RT-PCR and Western blot were used to measure and compare their survivin expressions. The siRNA expression vector pshRNA-survivin targeting the mRNA of survivin and vector pGPU6/GFP/Neo-NC (as a control) were constructed, and then transfected into HCCLM6 cells. FQ-PCR was used to quantify the mRNA levels of survivin. The malignant phenotypes of transfected HCCLM6 cells, including invasive activities and adhesive capabilities, were analyzed.</p><p><b>RESULTS</b>Survivin expression gradually increased with the increase of the invasion and metastasis behaviors of the four HCC cell lines (P<0.05). The expression of survivin was highest in cell line HCCLM6. Survivin mRNA level was decreased by 93.500%+/-3.117% after the pshRNA-survivin transfection. The cell adhesion rates significantly decreased in the cells transfected with pshRNA-survivin (cell adhesion rates were 11.403%+/-1.256% vs 32.545%+/-1.367%, t=20.732, P<0.01). The migrating number of HCCLM6 cells (13.5+/-0.9) transfected with pshRNA-survivin was also significantly decreased (t=14.5, P<0.01) as compared with the control group (32.6+/-1.4).</p><p><b>CONCLUSION</b>The expression of survivin in HCC might have a close relationship to their invasion and metastasis properties. Sequence-specific shRNA can significantly reduce the survivin expression in the HCCLM6 cell line. Suppression of survivin expression in HCCLM6 cells transfected with pshRNA-survivin can reduce their invasive and adhesive capabilities.</p>

Osteopontin promotes the malignant phenotypes of human hepatocellular carcinoma cell line SMMC-7721 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effects of osteopontin (OPN) on the phenotypes of human hepatocellular carcinoma cell line SMMC-7721.</p><p><b>METHODS</b>Human hepatocellular carcinoma SMMC-7721 cells were transfected with plasmid pcDNA 3.1(-)/OPN and cells transfected with a mock plasmid served as controls. OPN expression was verified by RT-PCR and Western blot, and concentrations of OPN, MMP-2, MMP-9 and uPA were measured by ELISA. A series of functional assays in vitro were used to monitor the changes of SMMC-7721 malignant phenotypes.</p><p><b>RESULTS</b>OPN expression of SMMC-7721 cells was elevated after transfection. Concentrations of OPN, MMP-2 and uPA in the medium of SMMC-7721 cells after transfection were higher than those of the controls [(3.02+/-0.12) ng/ml vs (1.43+/-0.07) ng/ml, (43.04+/-3.06) ng/ml vs (22.15+/-4.34) ng/ml, and (4.78+/-0.70) ng/ml vs (1.61+/-0.34) ng/ml respectively, P less than 0.01], but MMP-9 concentration did not increase [(7.82+/-2.25) ng/ml vs (7.70+/-1.92) ng/ml]. Functional assays in vitro indicated that SMMC-7721 cells after transfection showed higher adhesive, migrant and invasive capabilities than those of the controls (cell adhesion rates were 75.33%+/-10.59% vs 57.34%+/-2.52%; number of outer surface cells in migrant assay was 14.33+/-2.51 vs 6.34+/-1.53; cell number in the invasive assay was 8.23+/-1.53 vs 4.12+/-1.29 respectively, P less than 0.05).</p><p><b>CONCLUSION</b>OPN might enhance the expression of MMP-2 and uPA to promote malignant phenotypes of SMMC-7721 cells.</p>

Different expressions of chemokine receptors in human hepatocellular carcinoma cell lines with different metastatic potentials / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare different expression profiles of all known chemokine receptors in human hepatocellular carcinoma (HCC) cell lines with different metastasis potentials.</p><p><b>METHODS</b>Eighteen pairs of chemokine receptor primers were designed using Premier software. Expression profiles of the 18 chemokine receptors on four HCC cell lines of lower to higher potentials of metastasis (SMMC-7721, MHCC97-L, MHCC97-H and HCCLM6) were analyzed by RT-PCR. Expression of CXCR4 was detected by RT-PCR.</p><p><b>RESULTS</b>Expression profiles of chemokine receptors on four HCC cell lines with different metastatic potentials had significant differences (P < 0.01), in which CCR10, CXCR4 and CXCR6 expressions decreased gradually as the metastatic potential of the cell lines increased. The expressions of CCR3, CCR4, CCR10, CCR12 and XCR1 on HCCLM6 were significantly reduced compared with SMMC-7721 (P < 0.01), whereas the expressions of CXCR1 (P = 0.006) and CXCR5 (P = 0.003) exceeded that of SMMC-7721. Except for CXCR2, CXCR6 and XCR1, most of chemokine receptors on MHCC97-H were expressed differently compared with MHCC97-L (P < 0.05), in which expressions of CCR1 (P = 0.002), CCR2 (P = 0.004) and CCR5 (P = 0.046) exceeded MHCC97-L. CXCR4 was detected only on the positive controls and SMMC-7721 when the template of total RNA was reduced one-half in RT-PCR.</p><p><b>CONCLUSION</b>Chemokine receptors are expressed very differently at mRNA level on HCC cell lines with different metastatic potentials. The different profiles of chemokine receptors in tumor microenvironment and the function of CXCR4 in HCC should be further studied. Our findings have important implications in understanding the relationship between chemokine receptors and the metastatic potential of HCC.</p>

Comparison of the results and therapies for hepatocellular carcinoma with tumor thrombosis in portal vein / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the clinical effects of different therapies on hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT), and to study the factors that affected the prognosis.</p><p><b>METHODS</b>One hundred and thirty eight HCC with PVTT patients, whose liver function was compensatory and both tumor and PVTT could probably be resected together as evaluated by preoperative examinations, were divided into four groups: 1. conservative treatment group (n = 14); 2. chemotherapy group (n = 41); 3. surgical resection group (n = 19); 4. surgical resection with postoperative chemotherapy group (n = 64).</p><p><b>RESULTS</b>The median survival periods in four groups were 3.5, 7.1, 10.1 and 13.4 months, respectively. The half a year-, 1-, 2-, 3-year survival rates in the surgical resection with postoperative chemotherapy group were 53.7%, 37.6%, 30.7% and 14.0%, respectively, which were significantly higher than those of the other three groups (P < 0.05). Univariate and multivariate analysis both revealed that the number of chemotherapy courses affected the effect of surgical resection.</p><p><b>CONCLUSIONS</b>1. If patients' liver function is compensatory and tumors with PVTT can be removed together, exploration should be done. Surgical resection followed by postoperative chemotherapy would produce the best clinical result. 2. If patients' liver function is permissible, multiple chemotherapeutic courses should be given after resection of HCC with PVTT.</p>