Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc.

Recent researches demonstrate that microRNAs (miRNAs) are deregulated in numerous cancers and involved in tumorigenesis, whereas their influences on pancreatic cancer (PC) still need further elucidation. The present research revealed that miR-494 was significantly decreased in PC cell lines and tissues. Functional study showed that overexpressed miR-494 could remarkably inhibit proliferation of PC cells both in vitro and in vivo, which was due to induction of apoptosis, G1-phase arrest and senescence. Moreover, upregulated miR-494 significantly prohibited invasion of PC cells. Meanwhile, both c-Myc and SIRT1 was identified as targets of miR-494 through dual luciferase assay and further confirmed by the reverse correlation between miR-494 and c-Myc/SIRT1 in PC samples. Furthermore, co-transfection with c-Myc-RNAi and SIRT1-RNAi synergistically reduced c-Myc and SIRT1 expression, and inhibited proliferation of PC, which simulated the effects of miR-494 overexpression. On the contrary, co-overexpression of c-Myc and SIRT1 effectively rescued inhibition of overexpressed miR-494 on PC cells. The clinical characteristics further revealed that low miR-494 correlated with larger tumor size, late tumor node metastasis stage, lymphatic invasion, distant metastasis and poor prognosis. In conclusion, the present study indicated that miR-494 might serve as predictor and inhibitor in PC by directy downregulating the loop of c-Myc and SIRT1.

SIRT1 RNAi knockdown induces apoptosis and senescence, inhibits invasion and enhances chemosensitivity in pancreatic cancer cells.

The NAD(+)-dependent deacetylase, sirtuin 1 (SIRT1), has been recently been suspected to have a role in tumorigenesis. We investigated the expression of SIRT1 in pancreatic cancer and the effect of SIRT1-targeted RNA interference (RNAi) on cell proliferation and tumor formation in a pancreatic cancer cell line, PANC1. The expression of SIRT1 was investigated in 49 specimens of pancreatic cancer and adjacent normal pancreatic tissues. SIRT1 was overexpressed in pancreatic cancer tissues at both the mRNA and protein levels, with increased SIRT1 positivity associated with tumors from patients over 60 years old, tumors larger than 4 cm, higher TNM (extent of tumor (T), the extent of spread to lymph nodes (N), and presence of distant metastasis (M)) stage or the presence of lymph node or hepatic metastases. The PANC-1 was stably transfected with a SIRT1 small hairpin RNA (shRNA) expression plasmid and compared with untransfected and PANC-1-negative RNAi cells. Proliferation of PANC-1-SIRT1-RNAi cells was significantly reduced, accompanied by increased rates of apoptosis, G1 arrest and senescence. Furthermore, FOXO3a expression was markedly upregulated in PANC-1-SIRT1-RNAi cells, but no significant difference in p53 expression was observed. The invasive ability of PANC-1-SIRT1-RNAi cells was markedly reduced in vitro, which was linked to increased E-cadherin and reduced-MMP expression. Additionally, PANC-1-SIRT1-RNAi cells had a significantly reduced capacity to form tumors in vivo compared with untransfected and PANC-1-negative RNAi cells. These results suggest that SIRT1 may promote cell proliferation and tumor formation in pancreatic cancer, and downregulation of SIRT1 using shRNA could provide a novel therapeutic treatment.

Do antibacterial-coated sutures reduce wound infection in head and neck cancer reconstruction?

BACKGROUND: Surgical wound infection is a common complication, which increases the hospital stay and costs after surgery for head and neck cancer. In this study, we evaluated the effect of Triclosan-coated sutures on surgical wounds and analyzed the risk factors for wound infections in head and neck cancer surgery. PATIENTS AND METHODS: From January 2007 to December 2009, 253 consecutive patients underwent wide excision of a head or neck cancer and reconstructive procedures. All patient data were collected prospectively. Of these, 241 patients were included in this study, divided into two groups. The Triclosan group contained 112 patients, whose surgical wounds were closed with Triclosan-coated sutures (Vicryl Plus). The control group included the remaining 129 patients, whose surgical wounds were closed with conventional Vicryl sutures. We conducted a retrospective, multivariate analysis to determine independent risk factors for the cervical wound infection. RESULTS: The cervical wound infection rate was 14.9% (17/112) in the Triclosan group and 14.7% (19/129) in the control group, and these rates were not significantly different. Tumour stage and delayed intra-oral flap healing were independent risk factors for cervical wound infection. CONCLUSIONS: In this preliminary study, Triclosan-coated Vicryl sutures did not reduce the infection rate of cervical wounds after head or neck cancer surgery. The effectiveness of this suture material in head and neck cancer surgery should be considered with caution.

Assessment of the perforators of anterolateral thigh flaps using 64-section multidetector computed tomographic angiography in head and neck cancer reconstruction.

BACKGROUND: The anterolateral thigh (ALT) flap is a frequent choice for free flap transfer in head and neck cancer reconstruction because of its versatility. Preoperative mapping of the perforator pedicles of an ALT flap is still a challenge because of variations in vasculature. Although computed tomographic angiography (CTA) is used increasingly to evaluate the peripheral vasculature, the use of this method for evaluating the perforators of an ALT flap has not been described in detail. METHODS: From September 2008 to March 2009, 32 patients underwent preoperative CTA before free ALT flap transfer for head and neck cancer reconstruction. The perforators were marked on a 64-section multidetector CT image for each patient. The preoperatively mapped perforators were compared with the actual intraoperative findings. Flap success rates and associated morbidity and complications were recorded. RESULTS: Preoperative CTA identified major variations in perforators. Eighty-four were found by preoperative CTA; 64 of these were mapped to be explored during the operation, and 13 additional perforators were identified during surgery. The accuracy rate of identifying the branching origin of the ALT perforators was 98% (63/64). All of the ALT flaps survived except for one with necrosis (survival rate 97%). There was no donor site morbidity. CONCLUSIONS: Preoperative mapping of perforators by CTA proved valuable in free ALT flap transfer and shortened the operation time significantly. This modality provides useful information for head and neck cancer reconstruction in difficult cases, especially in patients with large or through-and-through defects that might need multiple perforators in flap design.