Zhao Yp

Induction, modulation and potential targets of miR-210 in pancreatic cancer cells.

BACKGROUND MiR-210 is induced by hypoxia and plays different roles in the development of certain cancers. However, little is known about its role in pancreatic cancer (PC). This study aimed to explore the induction and modulation of PC by miR-210 and its potential molecular targets. METHODS PC cells were cultured under normoxic and hypoxic conditions. Expression of miR-210 and hypoxia-inducible factor (HIF)-1alpha was detected using quantitative reverse-transcription polymerase chain reaction. Cancer cells were transiently transfected with HIF-1alpha small interfering RNA (siRNA) and miR-210 mimics, and cell proliferation was measured using the CCK-8 assay. Potential targets for miR-210 were then identified using a dual luciferase reporter assay. RESULTS Hypoxic conditions induced miR-210 expression in six PC cell lines (AsPC-1, BxPC-3, MIAPaCa-2, PANC-1, Su86.86 and SW1990), but not in Capan-1 or T3M4 cells. Transfection of HIF-1alpha siRNA into PANC-1 cells markedly inhibited HIF-1alpha expression, and subsequently down-regulated miR-210 expression under hypoxic conditions. MiR-210 had no observable impact on the proliferation of PANC-1 or Su86.86 cells and dual luciferase reporter assays showed significantly reduced luciferase activity in the wild-type E2F3, EFNA3, GIT2, MNT, ZNF462 and EGR3 constructs, compared to the corresponding mutants, but not in HOXA3. CONCLUSIONS These results suggest that miR-210 expression in PC cells is induced by hypoxia through a HIF-1alpha-dependent pathway, but does not influence PC cell proliferation. Also, E2F3, EFNA3, GIT2, MNT, ZNF462 and EGR3 may be potential miR-210 targets in PC.

Circulating microRNAs in cancer: diagnostic and prognostic significance

The involvement of microRNAs (miRs) in numerous pathological conditions is well established. In many kinds of cancer cells and animal models, various miRs have been shown to act as oncogenes or tumor suppressors. Recently, it was found that circulating miRs can be detected, and may be associated, with the clinicopathological features and prognosis of cancers, thus, providing potential novel diagnostic and prognostic markers for malignancies in humans. This review aims to address these issues based on recently published literature.

Laparoscopic distal pancreatectomy with or without splenectomy: spleen-preservation does not increase morbidity.

BACKGROUND The indications for laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and its morbidity compared with laparoscopic distal pancreatectomy with splenectomy (LDPS) are ill-defined. This study aimed to share the indications for spleen-preservation and investigate the safety and outcome of LSPDP at our institution. METHODS A retrospective review of patients who were scheduled to receive laparoscopic surgery for distal pancreatic lesions was conducted. The indications, surgical procedures, intra-operative data, and outcomes of the two procedures were collected and compared by statistical analysis. RESULTS LDPS and LSPDP were successfully performed in 16 and 21 patients respectively, whereas they were converted to open surgery in 9 patients. There were no significant differences in age, gender, operation time, blood loss, and conversion rate between the LDPS and LSPDP groups. The mean tumor size showed an inter-group difference (5.05 vs 2.53 cm, P<0.001). There were no significant differences in complication and morbidity rates between the two groups. All patients remained alive without recurrence during a follow-up of 9 to 67 months (median 35). CONCLUSION LSPDP has a morbidity and outcome comparable to LDPS.

NOP14 promotes proliferation and metastasis of pancreatic cancer cells

Pancreatic cancer (PC) is one of the most malignant cancers worldwide. We describe a novel gene, NOP14, which plays significant roles in PC cell proliferation and migration. Inhibition or overexpression of NOP14 expression in PC cells can reduce or promote motility, proliferation and metastatic capacity in vivo. In parallel, we observed changes in proteins related to migration, such as E-cadherin, vimentin, MMP9, RhoA and p53, along with proteins involved in proliferation, such as MAPK3 and CDK2. Taken together, our study provides new evidence for NOP14 in regulating PC cell proliferation and migration, and may provide new insights for clinical diagnosis and therapy.

Oncolytic vaccinia virus in combination with radiation shows synergistic antitumor efficacy in pancreatic cancer.

Combining oncolytic viruses with conventional therapy such as radiation is an innovative option for pancreatic cancer. We demonstrated that combination of GLV-1h151 and radiation yielded a synergistic cytotoxic effect, with the greatest effect achieved in the AsPC-1cell line. Combination treatment significantly increased apoptosis compared with either single treatment or the control group. In mice bearing human pancreatic tumor xenografts, combination treatment resulted in significantly enhanced inhibition of tumor growth. No evidence of toxicity was observed in mice. These results indicate that the combination of GLV-1h151 and radiation has great potential for translation into clinic practice.

Risk factors for postoperative pancreatic fstula in patients with insulinomas: analysis of 292 consecutive cases

BACKGROUND Pancreatic fistula (PF) remains the most challenging complication in pancreatic surgery, yet few published studies have focused on the risk factors for postoperative PF in patients undergoing surgery for insulinomas. METHODS From January 1990 to February 2010, a total of 292 patients with insulinomas underwent surgery at Peking Union Medical College Hospital. Demographic data, intraoperative procedures, and postoperative data were collected. Particular attention was paid to variables associated with PF as defined by the International Study Group of Pancreatic Fistula (ISGPF). Univariate and multivariate analyses were used to identify possible risk factors for PF. RESULTS PF was found in 132 (45.2%) patients, of whom 90 were classified into ISGPF grade A, 33 grade B, and 9 grade C. Multivariate analysis showed that male patients (OR=2.56; P=0.007) and operative time >180 minutes (OR=3.756; P<0.0001) were independent risk factors for clinical PF. Pancreatic resection with stapler was a protective factor for both total PF (OR=0.022; P=0.010) and clinical PF (OR=0.097; P=0.007). CONCLUSIONS Male gender and operative time >180 minutes were independent risk factors for clinical PF, while pancreatic resection with a stapler was a protective factor. Whether body mass index (BMI) and other variables during operation are risk factors of PF needs further study.

Activated mTOR/P70S6K signaling pathway is involved in insulinoma tumorigenesis

Insulinoma was a rare tumor and its pathogenesis was poorly understood. There had no study that focused on the role of mTOR signaling pathway in insulinoma tumorigenesis.

Medullary thyroid carcinoma with nodular goiter carries an excellent prognosis.

In our institution, patients with medullary thyroid carcinoma (MTC) concurrent with nodular goiter (NG) have a nearly 100% survival rate, but the reasons and characteristics are unclear.

Splenic preservation in laparoscopic distal pancreatectomy.

Laparoscopic spleen‐preserving distal pancreatectomy (LSPDP) is designed principally for the removal of benign and low‐grade malignant lesions in the left pancreas. The aims of this study were to compare LSPDP with laparoscopic distal pancreatectomy with splenectomy (LDPS), compare two splenic preservation techniques (splenic vessel preservation and Warshaw technique) and investigate factors that influence splenic preservation.

Clinical motivation and the surgical safety checklist

Although the surgical safety checklist (SSC) has been adopted worldwide, its efficacy can be diminished by poor clinical motivation. Systematic methods for improving implementation are lacking.