Reduced expression of Raf kinase inhibitor protein correlates with poor prognosis in pancreatic cancer.

AIM: Raf kinase inhibitory protein (RKIP) is an inhibitor of the Raf/MEK/MAP kinase signaling cascade and a suppressor of cancer metastasis. But its function in pancreatic cancer was not yet clarified completely. The aim of this study was to investigate the involvement of RKIP in pancreatic cancer. METHODS: RKIP expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumor tissue samples from a series (n = 99) of consecutive patients with pancreatic cancer. Survival was calculated using Kaplan-Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. RESULTS: RKIP expression was high in normal pancreatic epithelium and retained to varying degrees in pancreatic cancer tissues. However, in tumor tissues with lymph node metastasis (P = 0.008) and high UICC stage (P = 0.006), RKIP expression was highly significantly reduced or lost. Furthermore, the reduced expression of RKIP significantly correlated with both poor overall and disease-free survival (P = 0.008 and 0.01, respectively). Multivariate analyses revealed RKIP to be an independent prognosticator. CONCLUSION: These findings suggest that RKIP could be a promising marker for predicting a better prognosis in pancreatic cancer.

Expression of N-myc downstream-regulated gene 1 in primary gallbladder carcinoma and its correlation with clinicopathological features and clinical outcome.

N-myc downstream-regulated gene 1 (NDRG1), a member of the N-myc downstream-regulated gene family, is induced under a wide variety of stress and cell growth-regulatory conditions. In several cancers, recent studies have shown its association with inhibition of tumor metastasis and suggested it to be a tumor suppressor gene. However, its significance in primary gallbladder carcinoma (PGC) has not been studied. Therefore, the aim of this study was to investigate NDRG1 expression in PGC and its prognostic significance. We examined NDRG1 expression in tumor specimens from 138 patients with PGC by immunohistochemistry and analyzed the correlation between NDRG1 expression and clinicopathologic factors or survival. NDRG1 was expressed in 63.8% of PGC but not in the normal epithelium of the gallbladder, remarkably at the invasive front of the tumors. In addition, NDRG1 expression was significantly associated with high histologic grade, advanced pathologic T stage and clinical stage, positive nodal metastasis and venous/lymphatic invasion. Moreover, Kaplan-Meier curves showed that NDRG1 over-expression was significantly related to poor overall and disease-free survival (both P = 0.02). Furthermore, multivariate analyses showed that NDRG1 expression (hazard ratio, 3.338; P = 0.02) and clinical stage (hazard ratio, 3.128; P = 0.03) were independent risk factors for disease-free survival. Our data demonstrate for the first time that NDRG1 expression in PGC was significantly correlated with unfavorable clinicopathologic features and an independent poor prognostic factor for disease-free survival in patients. Taken together, our findings suggest that NDRG1 expression could be used as a novel prognostic factor for patient survival and might be a potential therapeutic target in PGC.

[HILIC-eLSD determination of five oligosaccharides contained in Morinda officinalis].

OBJECTIVE: To determine determinate five oligosaccharides, namely sucrose, 1-kestose, nystose, 1F-fructofurano-syinystose, bajijiasu contained in Morinda officinalis with an HILIC-ELSDI) method. METHOD: Waters XBridge Amide (4.6 mm x 150 mm, 3.5 microm) hilic column was adopted for gradient elution, with acetonitrile (A) and 0.2% triethylamine (B) as the mobile phase. The column temperature was set at 40 degrees C, with the flow rate of 0.8 mL x min. Waters 2424 evaporative light scattering detector (ESLD) was used as detector, with the gas flow of 275.79 kPa and drift tube temperature of 90 degrees C. RESULT: The detection range for the five oligosaccharides were 2.128-21.28 microg for sucrose (r = 0.999 3), 1.864-18.64 microg for 1-kestose (r = 0.999 6), 1.92-19.2 microg for nystose (r = 0.999 8), 1.912-19. 12 microg for 1F-fructofuranosyinystose (r = 0.999 5), 2.368-23.68 microg for bajijiasu (r = 0.999 4), respectively. The recovery of the five oligosaccharides ranged between 92.81%-102.8% (n = 6). CONCLUSION: The method is so simple, accurate and highly reproducible that it can be used as an analytical method for effective evaluation of the quality of M. officinalis herbs.

NDRG2 down-regulation and CD24 up-regulation promote tumor aggravation and poor survival in patients with gallbladder carcinoma.

Recent studies have demonstrated that N-Myc downstream-regulated gene 2 (NDRG2) may reduce the metastatic potential of breast cancer and hepatocellular carcinoma cells by regulating the expression of CD24, which is expressed in a large variety of solid tumors. The aim of this study was to clarify the clinical value of NDRG2 and CD24 expression in primary gallbladder carcinoma (GBC). One hundred and thirty GBC tissues were evaluated by immunohistochemistry for NDRG2 and CD24 expression. The associations of NDRG2 and CD24 expression with the clinicopathological characteristics and the overall survival of patients with GBC were analyzed. NDRG2 and CD24 were positively expressed in 49/130 (37.69%) and 107/130 (82.31%) of GBC tissues, respectively. In addition, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 more frequently had lymph node metastasis and lymphovascular invasion. Moreover, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 tended to show deeper invasion depth and higher TNM stage. There was a negative correlation between NDRG2 expression and CD24 expression in GBC tissues (r = -0.86, P < 0.001). The patients with NDRG2 negative expression correlated with poor prognosis of GBC (P = 0.01), as opposed to CD24 (P = 0.01). The survival rate of the patients with NDRG2-/CD24+ expression was the lowest (P < 0.001), and conjoined expression of NDRG2-/CD24+ was an independent prognostic indicator of GBC (P = 0.003). Our data suggest that NDRG2 down-regulation or CD24 up-regulation is an important feature of GBC. A combined detection of NDRG2/CD24 co-expression may benefit us in prediction of the prognosis in GBC.