CD64 Expression Is Increased in Patients with Severe Acute Pancreatitis: Clinical Significance

BACKGROUND/AIMS: Upregulated CD64 expression on neutrophils is the most useful marker for acute bacterial infections and systemic inflammation. However, it is unknown whether CD64 is involved in the pathogenesis of acute pancreatitis (AP). This study was designed to determine whether CD64 is implicated in severe acute pancreatitis (SAP), and thus, is a suitable marker for SAP. METHODS: SAP was induced in rats with an intraperitoneal injection of L-arginine. CD64 expression in the rat pancreas was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Additionally, the CD64 mRNA expression in peripheral blood leukocytes from 21 patients with mild acute pancreatitis (MAP) and 10 patients with SAP was investigated at the time of admission and during remission by qRT-PCR. RESULTS: CD64 mRNA and protein expression in the pancreas was significantly higher in rats with SAP, compared to the controls. The CD64 expression was higher in the patients with SAP than in the patients with MAP. During remission, CD64 mRNA decreased in both the MAP and SAP patients. The area under the curve of CD64 expression for the detection of SAP was superior to both the Ranson and the Acute Physiology and Chronic Health Evaluation II scores. CONCLUSIONS: The CD64 level was significantly increased in correlation with the disease severity in SAP and may act as a useful marker for predicting the development of SAP.

Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-beta in colorectal cells

Estrogen has anti-colorectal cancer effects which are thought to be mediated by mismatch repair gene (MMR) activity. Estrogen receptor (ER) expression is associated with microRNA (miRNA) expression in ER-positive tumors. However, studies of direct link between estrogen (especially estradiol E2), miRNA expression, and MMR in colorectal cancer (CRC) have not been done. In this study, we first evaluated the effects of estradiol (E2) and its antagonist ICI182,780 on the expression of miRNAs (miR-31, miR-155 and miR-135b) using COLO205, SW480 and MCF-7 cell lines, followed by examining the association of tissue miRNA expression and serum E2 levels using samples collected from 18 colorectal cancer patients. E2 inhibited the expressions of miRNAs in COLO205 cells, which could be reversed by E2 antagonist ICI 182.780. The expression of miR-135b was inversely correlated with serum E2 level and ER-beta mRNA expression in CRC patients' cancer tissues. There were significant correlations between serum E2 level and expression of ER-beta, miR-135b, and MMR in colon cancer tissue. This study suggests that the effects of estrogen on MMR function may be related to regulating miRNA expression via ER-beta, which may be the basis for the anti-cancer effect in colorectal cells.

Establishment of a cisplatin-induced multidrug resistance cell line SK-Hep1/DDP / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Multidrug resistance (MDR) is a major obstacle in the chemotherapy of cancer patients. The aim of this study was to establish a mutidrug-resistant cell line SK-Hep1/DDP and explore its molecular mechanism of the MDR.</p><p><b>METHODS</b>SK-Hep1/DDP cell line was induced by pulse treatment using a high concentration of cisplatin (DDP) in vitro. The chemoresistance indexes of cells were evaluated by CCK-8 assays. The protein of MDR1 (ABCB1), MRP1 (ABCC1), MRP2 (ABCC2) and Bax were detected by Western blotting, and the effect of MDR1 inhibitor cyclosporine A (CsA) on expression of MDR1 proteins in SK-Hep1 and SK-Hep1/DDP cell lines. Flow cytometry was performed to determine the distribution of the cell cycle and cell apoptosis ratio.</p><p><b>RESULTS</b>The SK-Hep1/DDP cells were 13.76 times more resistant to DDP in comparison with SK-Hep1 cells, and SK-Hep1/DDP cells also exhibited cross-resistance to many other chemotherapeutic agents (adramycin and 5-fuorouracil). MDR1, MRP1, and MRP2 protein expressions were significantly higher in the SK-Hep1/DDP than in the SK-Hep1 (P < 0. 01), but Bax was lower in the SK-Hep1/DDP than in the SK-Hep1(P < 0. 01). There was no obvious influence between SK-Hep1 and SK-Hep1/DDP cells in the expression of MDR1 by MDR1 inhibtor CsA (P > 0. 05). The percentages of cells in G(2)/M and S phase were significantly increased in SK-Hep1/DDP in comparison with those in SK-Hep1 [(20.67 +/- 5.69)% vs. (12.14 +/- 3.36)%; (42.20 +/- 2.65)% vs. (27.91 +/- 2.16)%; P < 0. 01]. After the cells were exposed to 10 μg/mL DDP for 24 h, the cell apoptosis rate of SK-Hep1/DDP was decreased in comparison with SK-Hep1, but it was increased in those with pretreatment of MDR1 inhibitor CsA as compared with those without pretreatment.</p><p><b>CONCLUSIONS</b>A reliable multi-drug resistant human hepatoma cell line SK-Hep1/DDP is successfully established. The MDR mechanisms of this cell lines are closely related to the over-expression of MDR1 MRP1 and MRP2, lower expression of Bax and the attenuated cell apoptosis induced by chemotherapeutic agents.</p>

The specific killing of human melanoma cells by replication selective adenovirus / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To construct replication selective adenovirus AdhepE1 targeting human melanoma and observe its specific killing of human melanoma cells in vitro.</p><p><b>METHODS</b>Adenovirus E1 region, the murine tyrosinase promoter and enhancer DNA sequences were acquired respectively by PCR cloning. The shuttle plasmid of replication-selective adenovirus targeting human melanoma was constructed by DNA recombination. Replication-selective adenovirus AdhepE1 was generated by homologous recombination. The human melanoma cell line SK-Mel-1 and hepatocellular carcinoma cell line HepG2 were attacked separately by lower dose of AdhepE1. Change of cell morphology was observed and the surviving cells were calculated. The expression of E1A was assayed by RT-PCR to verify the specific-replication of AdhepE1.</p><p><b>RESULTS</b>Replication selective adenovirus AdhepE1 targeting human melanoma was acquired by PCR. Human melanoma cell line SK-Mel-1 was sensitive to oncolytic killing of AdhepE1 whereas HepG2 was little responsive. The results of RT-PCR suggested that AdhepE1 replicated specifically in human melanoma cells.</p><p><b>CONCLUSION</b>AdhepE1 can selectively kill human melanoma cells.</p>

Relationship between mitochondrial DNA instability and interleukin-8 activity in gastric mucosa / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between mitochondrial DNA instability (mtMSI) and interleukin-8 (IL-8) activity in gastric mucosa of various lesions.</p><p><b>METHODS</b>IL-8 level in gastric mucosa was assayed using ELISA method. The mtMSI was detected by PCR-SSCP techniques.</p><p><b>RESULTS</b>mtMSI was observed in 11 out of 30 (36.7%) gastric cancers, 2 of 15 (13.3%) intestinal metaplasia, 2 of 10 dysplasia and 1 of 10 chronic atrophic gastritis. IL-8 level in mtMSI+ group [(76.8 +/- 3.8) pg/mg] was significantly higher than that in mtMSI- group [(48.3 +/- 3.6) pg/mg, P < 0.05].</p><p><b>CONCLUSION</b>mtMSI closely correlates with IL-8 level in gastric mucosa and is involved in gastric carcinogenesis.</p>