High Expression of Delta-Like Ligand 4 Predicts Poor Prognosis After Curative Resection for Pancreatic Cancer

Background

Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor angiogenesis, but its prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Our aim was to determine whether high DLL4 expression is correlated with poor prognosis after curative resection for PDAC.

Methods

Surgical specimens obtained from 89 patients with PDAC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Prognostic significance of DLL4 expression was evaluated by Kaplan–Meier method and Cox regression. The correlations of DLL4 expression with VEGFR-2 expression, tumor stage, and lymph node metastasis were examined by chi-square test and multivariate logistic regression.

Results

There were 38 (42.7%) and 51 patients who showed high and low DLL4 expression, respectively. Survival curves showed that patients with low DLL4 expression had a significantly better survival than those with high DLL4 expression (P < .001). Multivariate survival analysis demonstrated that high DLL4 expression was independently associated with both reduced overall survival (hazard ratio [HR] 2.24; 95% confidence interval [95% CI] 1.14–4.38) and reduced progression-free survival (HR 2.37; 95% CI 1.22–4.60). Multivariate logistic regression analyses showed that high DLL4 expression was independently associated with both advanced tumor stage (odds ratio [OR] 6.84; 95% CI 2.42–9.36) and lymph node metastasis (OR 3.27; 95% CI 1.04–10.34). We also found a positive correlation between DLL4 and VEGFR-2 expression (P < .001).

Conclusions

High DLL4 expression is significantly associated with poor prognosis for surgically resected PDAC, advanced tumor stage, and lymph node metastasis. Application of adjuvant therapy targeting DLL4-Notch signaling may improve prognosis.

     

Hepatic angiomyolipoma: A retrospective study of 25 cases

PURPOSE: We report our experience of diagnosing and treating hepatic angiomyolipoma (HAML), a rare benign mesenchymal tumor. METHODS: We analyzed retrospectively the clinicopathologic, radiological, and operative data of 25 patients who underwent surgery for HAML at our institute between November 2001 and May 2006. RESULTS: Most patients (20/25) were asymptomatic and had normal liver function. Ultrasonography (US) showed a heterogeneous hyperechoic mass in 13 of 23 patients, precontrast computed tomography (CT) showed that all of 12 lesions scanned were hypodense, and magnetic resonance imaging (MRI) showed hypointensity on T1-weighted images and hyperintensity on T2-weighted images in most (5/6) lesions. Marked enhancement in the arterial phase was seen in 10 of 12 lesions on CT scans and in 6 of 6 lesions on MRI scans. All tumors were composed of varying proportions of smooth muscle, adipose tissue, and blood vessels, and showed positive immunohistochemical staining for HMB-45. All patients underwent partial hepatectomy and there was no evidence of recurrence after a median follow-up of 43 months. CONCLUSION: The radiological features of HAML vary according to its histological components. The definitive diagnosis of HAML is challenging and depends on the presence of HMB-45-positive myoid cells. Hepatic angiomyolipoma is treated effectively with surgery and the prognosis is good.     

Papillary Thyroid Carcinoma: Factors Influencing Recurrence and Survival

Background The prognosis of patients with papillary thyroid carcinoma (PTC) is usually favorable; however, a subset of patients can develop local recurrence or distant metastases. The aim of this study was to evaluate the prognostic factors influencing the recurrence and the survival rate in 950 PTC patients. Materials and Methods From 1990 to 2005, 950 consecutive patients affected by PTC were operated on at our Department. We analyzed the prognostic role of the following parameters: gender, age at initial treatment, extent of thyroid surgery, node dissection, tumor size, node metastases, distant metastases, stage, and 131-I therapy. Results Seventy-nine patients (8.3%) developed locoregional or distant metastases after an average follow-up of 7.8 years (range 2–17 years); in particular local recurrence was observed in 25 cases and distant metastases in 54 cases. The global 10- and 15-year survival rates were 91.38% and 88.69%, respectively. At univariate analysis, all variables were significantly correlated with recurrence (P = .001) except gender (P = .3); moreover, gender (P = .2), node dissection (P = .5), and node metastases (P = .06) were not significant on 10- and 15-year survival. At multivariate analysis the age at first treatment, T4, M+, stage IV, the extent of thyroid surgery, and the 131-I therapy resulted to be significant and independent prognostic factors (P < .001). Conclusion Our data, in disagreement with other staging systems, suggest that gender does not play a significant role both in recurrence and survival. Moreover, the 131-I therapy was a statistically significant prognostic factor at univariate and multivariate analyses.     

Inhibitory Effects of Anti-sense PTTG on Malignant Phenotype of Human Ovarian Carcinoma Cell Line SK-OV-3

To construct eukaryotic expression vector expressing full length anti-sense pituitary tumor transforming gene (PTTG) mRNA and observe its blocking effect on the potential invasion of human ovarian carcinoma cell line SK-OV-3. PCR primers containing designed enzyme cut sites were used for cloning full-length PTTG gene fragment, and the resulting PCR product was inserted into the eukaryotic vector pcDNA3. 1 in the antisense direction. The recombinant vector was then transfected into SK-OV-3 by Lipofectamine. The positive cell clone was screened by G418, PTTG and bFGF at protein level expression were detected by Western blot. The biological behavior change of transfection positive cells was observed by colony formation in soft agar assay. Our results showed that SK-OV-3 clones stably expressing full-length recombinant pcDNA3. 1-PTTGas were obtained. The expressions of PTTG and bFGF protein in transfected cells were decreased by 61.5% and 52.3%, respectively as compared with non-transfected ones. The number of colony formation was reduced significantly in transfected cells as compared with empty vector transfected and non-transfected cells. It is concluded that the recombinant vector pcDNA3. 1-PTTGas is a novel tool and provides an alternative anti-sense gene therapy targeted at PTTG in human carcinoma.     

Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio Cannot Predict Lymph Node Metastasis and Prognosis in Patients with Early Gastric Cancer: a Single Institution Investigation in China

In the present study, we aimed at exploring the applied value of preoperative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in the prediction of lymph node metastasis (LNM) and prognosis in patients with early gastric cancer (EGC). We retrospectively analyzed a total of248 consecutive patients who underwent curative gastrectomy to be identified T1 stage gastric adenocarcinoma between January 1, 2010 and May 1, 2016 in a single institution. According to median preoperative NLR and PLR value, we divided the patients into four groups: high NLR >1.73 and low NLR <1.73, high PLR >117.78 and low PLR <117.78. Furthermore, to evaluate the relationship between preoperative NLR and PLR values, we categorized patients according to cutoff preoperative NLR-PLR score of 2 [high NLR (>1.73) and high PLR (>117.78)], 1 [either high NLR or high PLR], and 0 [neither high NLR nor high PLR], Statistical analyses were conducted using SPSS 20.0 software. The results showed that the preoperative NLR or PLR values, lower or higher, could not predict the LNM in patients with EGC (both P=0.544>0.05). The invasive depth of tumor was significantly correlated with LNM of EGC (P0.001). Kaplan-Meier plots illustrated that preoperative NLR and PLR values were not associated with overall survival (OS) in patients with EGC. It was concluded that the preoperative NLR and PLR may be the predictors for LNM and prognosis in patients with advanced gastric cancer; nevertheless, they cannot predict LNM and prognosis in patients with EGC.     

Value of Quantitative Tissue Velocity Imaging in the Detection of Regional Myocardial Function in Dogs with Acute Subendocardial Ischemia

This study evaluated the application of quantitative tissue velocity imaging （QTVI） in assessing regional myocardial systolic and diastolic functions in dogs with acute subendocardial ischemia. Animal models of subendocardial ischemia were established by injecting microspheres （about 300 μm in diameter） into the proximal end of left circumflex coronary artery in 11 hybrid dogs through cannulation. Before and after embolization, two-dimensional echocardiography, QTVI and real-time myocardial contrast echocardiography （RT-MCE） via intravenous infusion of self-made microbubbles,were performed, respectively. The systolic segmental wall thickening and subendocardial myocardial longitudinal velocities of risk segments before and after embolization were compared by using paired t analysis. The regional myocardial video intensity versus contrast time could be fitted to an exponential function： y=A·（1-exp-β·t）, in which the product of A and β provides a measure of myocardial blood flow. RT-MCE showed that subendocardial normalized A·β was decreased markedly from 0.99±0.19 to 0.35±0.11 （P〈0.05） in 28 left ventricular （LV） myocardial segments after embolization, including 6 basal and 9 middle segments of lateral wall （LW）, 8 middle segments of posterior wall （PW） and 5 middle segments of inferior wall （IW）. However, there was no statistically significant difference in subepicardial layer before and after embolization. Accordingly, the ratio of A·β of subendocardial myocardium to subepicardial myocardium in these segments was significantly decreased from 1.10±0.10 to 0.31±0.07 （P〈0.05）. Although the systolic wall thickening did not change 5 min after the embolization in these ischemic segments （29%±3% vs 31%±5%, P〉0.05）, the longitudinal peak systolic velocities （Vs） and early-diastolic peak velocities （Ve） recorded by QTVI were declined significantly （P〈0.05）. Moreover, the subendocardial velocity curves during isovolumic relaxation predominant     

Construction of Eukaryotic Expression Plasmid of Human PRX3 and Its Expression in HEK-293FT Cells

To construct the eukaryotic expression plasmid of human PRX3 and measure its expression in the HEK-293FT cells, the full-length coding region of human PRX3 was cloned by PCR and inserted into the eukaryotic expression vector pcDNA4-Xpress (A). HEK-293FT cells were transiently transfected with the recombinant plasmid. Western blot and immuofluorescence were used to detect the expression of the fusion protein. In the experiment, restriction analysis identified the construction of the recombinant plasmid and the inserted sequence was identical with that published on GenBank. Western blot and immunofluorescence confirmed the expression of the recombinant protein in transfected HEK-293FT cells. It was concluded that the eukaryotic expression plasmid of human PRX3 was constructed successfully and the recombinant could he expressed efficiently in HEK-293FT cells, which provides a sound basis for the further study on human PRX3.