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Huang C.,Shanghai JiaoTong University | Huang C.,Shanghai Key Laboratory of Pancreatic Disease | Li H.,Shanghai JiaoTong University | Li H.,Tongji University | And 4 more authors.
Oncology Reports | Year: 2013

In the present study, we investigated the effects of miR-155 on pancreatic cancer cell invasion and migration in vitro, underlying gene expression, expression of miR-155 and its target genes in pancreatic cancer tissues, and their association with metastasis and clinical stage. miR-155 mimics and an inhibitor were transfected into Panc-1 and Capan-2 cells in order to regulate the expression of miR-155. qPCR and western immunoblotting were performed in order to detect gene expression. Transwell assays were performed to characterize the invasion and migration of pancreatic cancer cells in vitro. Immunohistochemical analysis and in situ hybridization were used to detect the expression of protein and microRNA in pancreatic cancer tissue. miR-155 mimics and an inhibitor upregulated and downregulated, respectively, the expression of miR-155 in pancreatic cancer cells. The invasion and migration of pancreatic cancer cells increased or decreased along with miR-155 expression in vitro. Suppressor of cytokine signaling 1 (SOCS1) protein expression was upregulated when miR-155 was inhibited and downregulated when miR-155 was increased. However, the expression of P-signal transducer and activator of transcription-3 (STAT3) was synchronized with that of miR-155. Transcription of SOCS1 and STAT3 was unchanged by miR-155 regulation. miR-155 expression was high in pancreatic cancer tissues and SOCS1 expression was high in tumor-adjacent tissues. There was no relationship between these genes in cancer and tumor-adjacent tissues. In addition, miR-155 expression was associated with lymph node metastasis and clinical stage. In conclusion, miR-155 plays an important role in the regulation of pancreatic cancer cell invasion and migration by modulating the STAT3 signaling pathway and reducing SOCS1 expression in pancreatic cancer cells.


Hu H.,Shanghai JiaoTong University | Hu H.,Shanghai Key laboratory of Pancreatic Disease | Hang J.-J.,Shanghai JiaoTong University | Hang J.-J.,Shanghai Key laboratory of Pancreatic Disease | And 8 more authors.
Tumor Biology | Year: 2016

Macrophages play a critical role in the initiation and progression of various solid tumors. However, their prognostic significance in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. This study investigated the distribution patterns of macrophages in PDAC and possible association with the overall survival (OS). We found significant differences in macrophage density (identified by CD68 and CD163 immunopositivity; p < 0.001 for both) between primary cancer and paired adjacent normal tissues. Most macrophages in cancerous pancreatic tissues were located in the stroma rather than the islets (p = 0.032 and p < 0.001). We also demonstrated that a high total macrophage density (characterized by CD68 immunopositivity) correlated with an absence of jaundice before surgery (p = 0.03) and that a high density of M2 macrophages (characterized by CD163 immunopositivity) in the stroma strongly correlated with the tumors located in the tail and body of the pancreas (p = 0.04). In addition, OS was shorter in patients with high-density M2 macrophage infiltration than in those with low-density M2 macrophage infiltration (p = 0.012). Moreover, multivariate analysis revealed that dense M2 macrophage infiltration into the stroma was an independent prognostic factor for PDAC patients (p = 0.02). © 2016 International Society of Oncology and BioMarkers (ISOBM)


Hang J.,Shanghai JiaoTong University | Hang J.,Shanghai Key Laboratory of Pancreatic Disease | Hu H.,Shanghai JiaoTong University | Hu H.,Shanghai Key Laboratory of Pancreatic Disease | And 13 more authors.
Oncotarget | Year: 2016

Previous studies showed that celecoxib, a cyclooxygenase-2 (COX2) inhibitor, can inhibit angiogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC) via the suppression of specificity protein 1 (Sp1). In this study, we investigated the prognostic value of Sp1 and COX2 in 88 PDAC patients. Our study showed there was a positive correlation between Sp1 and COX2 expression (P=0.001) by using the Spearman's rank test. Pearson Chi-square test revealed that Sp1 and COX2 expression were positively associated with lymph node metastasis (P<0.05, both). In addition, the Kaplan-Meier analysis showed that patients with Sp1-or COX2-positive expression exhibited poorer overall survival (OS) than those with Sp1-or COX2-negative expression (P<0.05, all). Most importantly, Sp1-and COX2-negative patients had the best OS (P=0.01). In multivariate analysis, Sp1 expression (P=0.03), COX2 expression (P=0.04), and nuclear grade (P=0.009) were found to be independent predictors for OS. Moreover, we confirmed that Sp1 could upregulate the expression of COX2 in PDAC cell lines by western blot analysis, and both are of important prognostic value in PDAC.


PubMed | Shanghai Key Laboratory of Pancreatic Disease and Shanghai JiaoTong University
Type: | Journal: Oncotarget | Year: 2016

Pancreatic cancer (PC) is a highly lethal cancer. Thus, the immune molecular markers which help to select PC patients are especially important. In this study, we aimed at systematically analyzing the expression of MLH1, MSH2, PD-L1 and PD-1, investigate their clinical significance and prognostic value. We found that high expression of PD-L1 on cancer cell membranes correlated with lymph node metastasis (P = 0.033) and strongly correlated with poor-differentiation (P = 0.008); high expression of PD-1 on cell membranes of T-cells correlated with well-differentiation (P = 0.018) and strongly correlated with advanced T stage (P = 0.004); high PD-1 expression was associated with a significantly superior OS and was an independent prognostic factor (P = 0.031). Then we found an inverse correlation between MSH2 expression and PD-L1 expression (Spearman correlation coefficient r = -0.295, P = 0.004). In subgroup analyses, we observed that PD-1 expression level was associated with OS only at low PD-L1 expression subgroup (P = 0.021). Finally, when we stratified the cases into four subgroups based on PD-1 expression and stroma density, we found that patients with high PD-1 expression and dense stroma had a better OS, while patients with low PD-1 expression and moderate stroma showed a worst outcome. Our result may provide more effective molecular markers for immunotherapeutic strategies of PC patients in clinical practice.


Hang J.,Shanghai JiaoTong University | Hang J.,Shanghai Key Laboratory of Pancreatic Disease | Cai B.,Centers for Disease Control and Prevention | Xue P.,Shanghai JiaoTong University | And 15 more authors.
PLoS ONE | Year: 2015

Background: Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality. In previous epidemiologic studies, the respective correlation between lifestyle factors and comorbidity and CRC has been extensively studied. However, little is known about their joint effects on CRC. Methods: We conducted a retrospective case-control study of 1,144 diagnosed CRC patients and 60,549 community controls. A structured questionnaire was administered to the participants about their socio-demographic factors, anthropometric measures, comorbidity history and lifestyle factors. Logistic regression model was used to calculate the odds ratio (ORs) and 95% confidence intervals (95%CIs) for each factor. According to the results from logistic regression model, we further developed healthy lifestyle index (HLI) and comorbidity history index (CHI) to investigate their independent and joint effects on CRC risk. Results: Four lifestyle factors (including physical activities, sleep, red meat and vegetable consumption) and four types of comorbidity (including diabetes, hyperlipidemia, history of inflammatory bowel disease and polyps) were found to be independently associated with the risk of CRC in multivariant logistic regression model. Intriguingly, their combined pattern- HLI and CHI demonstrated significant correlation with CRC risk independently (ORHLI: 3.91, 95%CI: 3.13-4.88; ORCHI: 2.49, 95%CI: 2.11-2.93) and jointly (OR: 10.33, 95%CI: 6.59-16.18). Conclusions: There are synergistic effects of lifestyle factors and comorbidity on the risk of colorectal cancer in the Chinese population. © 2015 Hang et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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