miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma.

BACKGROUND/AIMS: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood. METHODS: We first investigated the expression level of miR-191 in human CCA tissues and cell lines with quantitative real-time PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter assays to verify the miR-191 target gene. RESULTS: We showed that miR-191 was up-regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled-related protein-1 (sFRP1) level was negatively correlated with that of miR-191. Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover, knockdown of miR-191 led to suppression of Wnt/ß-catenin signaling activation. Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re-activated the Wnt/ß-catenin signaling pathway as detected by an increased level of ß-catenin and phosphorylation of GSK-3ß, and restored the expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA with miR-191 inhibitor restored the colony formation ability and viability of RBE cells. CONCLUSION: Taken together, our results demonstrate a novel insight into miR-191 biological function in CCA. Our findings suggest that miR-191 is a potential therapeutic target of CCA treatment.

Impact of pancreatic margin status and lymph node metastases on recurrence after resection for invasive and noninvasive intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis.

BACKGROUND: Accurate information is currently lacking regarding the values of positive margins (M(+)) and lymph node (LN) metastases as independent predictors of postoperative recurrence in invasive and noninvasive intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: A comprehensive online literature search identified all types of primary studies that included M(+) and LN metastases as risk factors and defined recurrence as an outcome in patients with IPMNs. Suitable articles were also identified by manually researching references in qualifying articles. A meta-analysis of the result was performed using a random effects model. RESULTS: The recurrence rate in noninvasive IPMNs was 3.72% in patients with negative margin (M(-)) versus 9.56% in those with M(+) (odds ratio, OR = 0.37, 95% confidence interval, 95% CI: 0.17-0.78, p = 0.010). The recurrence rate in invasive M(-) IPMNs in was 33.85% compared to 53.66% in M(+) IPMNs (OR = 0.47, 95% CI: 0.25-0.88, p = 0.020). The recurrence rate in invasive IPMNs with positive LN was 76.92% compared to 30.86% with negative LN; OR = 0.15, 95% CI: 0.06-0.37, p < 0.0001). CONCLUSIONS: M(+) were associated with disease recurrence in all patients with IPMN, and nodal metastases were significantly associated with recurrence in invasive IPMN.

Radical modular pancreatoduodenectomy for pancreatic head cancer using a combination of multiple artery-first approaches technique.

The aim of this study was to describe and assess the efficacy of a combination of multiple artery-first approaches (CMAFA) in pancreatoduodenectomy (PD) depending on the tumor location from an embryonic point of view.Between January 2011 and December 2016, seventy-nine consecutive patients with pancreatic head cancer (PHC) underwent PD with curative intent. Patients were classified into two groups according to the surgical procedure: CMAFA-PD group (n = 38) and conventional PD (Co-PD) group (n = 41). Clinicopathlogical variables and clinical outcomes were compared among the two groups.The CMAFA technique demonstrated an improved rate of R0 resection (89.5% vs. 70.7%, P = .038) and a higher median lymph node yield (24 vs.20, P = .034). The CMAFA-PD group was associated with reduced blood loss (450 vs. 600 ml, P = .049), lower rate of blood transfusion (23.7% vs. 46.3%, P = .035), and shorter length of hospital stay (19 vs. 26 days, P < .001). The rates of 90-day mortality, major morbidity, and readmission were comparable among the two groups.This study demonstrates that CMAFA is a feasible and efficient technique with acceptable perioperative and oncological outcomes in treating patients with PHC.

Results of adjuvant radiation therapy for locoregional perihilar cholangiocarcinoma after curative intent resection.

PURPOSE: This study sought to define the role of adjuvant radiation therapy (RT) for patients with curative intent resection of perihilar cholangiocarcinoma (pCCA). PATIENTS AND METHODS: By using the Surveillance, Epidemiology and End Results (SEER) registry, 1,917 patients with non-metastatic pCCA who underwent surgical resection from 1988 to 2009 were included in this study. Propensity score methods were used to compare the survival outcomes of patients treated with and without adjuvant RT after controlling for selection bias. RESULTS: Of the 1,917 patients, 762 (39.7%) received adjuvant RT. In the unmatched population, median overall survival (OS) for patients receiving adjuvant RT compared with those undergoing surgery alone was 23 versus 22 months (P=0.651). Patients who received adjuvant RT were younger (65 vs 68 years, P<0.001), had more regional diseases (86.0% vs 76.7%, P<0.001), and had more positive lymph nodes (43.8% vs 32.2%, P<0.001). In the matched population, adjuvant RT did not show better OS (22 vs 23 months, P=0.978) or cancer-specific survival (CSS) (17 vs 18 months, P=0.554). CONCLUSION: Adjuvant RT is not associated with improved survival of patients with resected pCCA. These data suggest that adjuvant RT should not be routinely used to treat patients with pCCA outside research trials. Ideally, prospective randomized trials should be performed to verify the conclusion of this study.

Relationship between body mass index and incidence of breast cancer.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and the breast cancer incidence, so as to making contribution to breast cancer screening in high-risk groups, to adjustment from passive medical treatment to active treatment Methods: BMI status of 206 breast cancer patients and that of 210 healthy subjects at different ages were compared and analyzed. RESULTS: The mean BMI was significantly higher in breast cancer patients than in healthy subjects 24.45±3.50 vs. 23.80±3.10 kg/m(2), t=-2.189, P=0.001. When stratified by age, BMI were significantly higher in ≥60 age for breast cancer than that of control group (Z=-3.408, P=0.001) and no significant difference in <60 years old .Logistic regression analysis showed that BMI was a risk factor of breast cancer (OR=1.886, 95% CI: 1.122-3.009). CONCLUSION: BMI have a relationship with the occurrence of breast cancer, especially for ≥60 years old.