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Pancreatic Neoplasms: HELP
Articles by Zi-Peng Lu
Based on 26 articles published since 2009
(Why 26 articles?)
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Between 2009 and 2019, Z. P. Lu wrote the following 26 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Role of CXCL12/CXCR4 signaling axis in pancreatic cancer. 2013

Wu, Peng-Fei / Lu, Zi-Peng / Cai, Bao-Bao / Tian, Lei / Zou, Chen / Jiang, Kui-Rong / Miao, Yi. ·Department of General Surgery, First Affiliated Hospital with Nanjing Medical University, Nanjing, China. ·Chin Med J (Engl) · Pubmed #24033967.

ABSTRACT: OBJECTIVE: This review focuses on the state-of-the-art of CXCL12/CXCR4 signaling axis in pancreatic cancer and its role in tumor progression. DATA SOURCES: Relevant articles published in English were identified by searching in Pubmed from 1997 to 2013, with keywords "CXCL12", "CXCR4" and "pancreatic cancer". Important references from selected articles were also retrieved. STUDY SELECTION: Articles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant mechanisms were selected. RESULTS: Pancreatic cancer has been one of the most lethal human malignancies, with median survival less than one year and overall 5-year survival only 6%. Tumor cells from pancreatic cancer express high level of CXCR4. CXCL12, the ligand for CXCR4, is extensively secreted by neighboring stromal cells and other distant organs. CXCL12 primarily binds to CXCR4, induces intracellular signaling through several divergent pathways, which are involved in progression and metastasis of pancreatic cancer. CONCLUSIONS: CXCL12/CXCR4 signaling axis may play an important role in the communication between pancreatic cancer cells and their microenvironment, which may have effect on tumor proliferation, invasion, angiogenesis, metastasis and chemoresistance. CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for pancreatic cancer.

2 Review Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma. 2013

Tang, Dong / Wang, Daorong / Yuan, Zhongxu / Xue, Xiaofeng / Zhang, Ye / An, Yong / Chen, Jianmin / Tu, Min / Lu, Zipeng / Wei, Jishu / Jiang, Kuirong / Miao, Yi. ·Department of Gastrointestinal Surgery, Subei People's Hospital of Jiangsu Province (Clinical Medical College of Yangzhou University), Yangzhou, People's Republic of China. ·Int J Cancer · Pubmed #22777597.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors with poor prognosis due to extremely high malignancy, low rate of eligibility for surgical resection and chemoradiation resistance. Increasing evidence indicate that the interaction between activated pancreatic stellate cells (PSCs) and PDAC cells plays an important role in the development of PDAC. By producing high levels of cytokines, chemotactic factors, growth factors and excessive extracellular matrix (ECM), PSCs create desmoplasia and a hypoxic microenvironment that promote the initiation, development, evasion of immune surveillance, invasion, metastasis and resistance to chemoradiation of PDAC. Therefore, targeting the interaction between PSCs and PDAC cells may represent a novel therapeutic approach to advanced PDAC, especially therapies that target PSCs of the pancreatic tumor microenvironment.

3 Article Insulin promotes invasion and migration of KRAS 2019

Wang, Guangfu / Yin, Lingdi / Peng, Yunpeng / Gao, Yong / Gao, Hao / Zhang, Jingjing / Lv, Nan / Miao, Yi / Lu, Zipeng. ·Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · Pancreas Institute, Nanjing Medical University, Nanjing, China. ·Cell Prolif · Pubmed #30838710.

ABSTRACT: OBJECTIVES: Hyperinsulinemia is a risk factor for pancreatic cancer, but the function of insulin in carcinogenesis is unclear, so this study aimed to elucidate the carcinogenic effects of insulin and the synergistic effect with the KRAS mutation in the early stage of pancreatic cancer. MATERIALS AND METHODS: A pair of immortalized human pancreatic duct-derived cells, hTERT-HPNE E6/E7/st (HPNE) and its oncogenic KRAS RESULTS: The migration and invasion ability of HPNE cells was increased after the introduction of the mutated KRAS gene, together with an increased expression of MMP-2. These effects were further enhanced by the simultaneous administration of insulin. The use of MMP-2 siRNA confirmed that MMP-2 was involved in the regulation of cell invasion. Furthermore, there was a concentration- and time-dependent increase in gelatinase activity after insulin treatment, which could be reversed by an insulin receptor tyrosine kinase inhibitor (HNMPA-(AM) CONCLUSIONS: Taken together, these results suggest that insulin induced migration and invasion in HPNE and HPNE-mut-KRAS through PI3K/AKT and ERK1/2 activation, with MMP-2 gelatinolytic activity playing a vital role in this process. These findings may provide a new therapeutic target for preventing carcinogenesis and the evolution of pancreatic cancer with a background of hyperinsulinemia.

4 Article Cytokine Profiling and Orthotopic Xenografing of Pancreatic Stellate Cells. 2019

Qian, Dong / Tian, Lei / Lu, Zipeng / Miao, Yi. ·Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. miaoyi@njmu.edu.cn. ·Methods Mol Biol · Pubmed #30378052.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most lethal human malignancies with a poor prognosis due to systemic metastasis and a high recurrence rate. Interactions between tumor and stromal cells play a critical role in tumor progression. However, the interaction between PSCs and pancreatic cancer cells (PCCs) and the underlying mechanisms are poorly understood. Coculture system with PSCs and PCCs is very useful technique platform for the in vitro and in vivo study of the interaction between these two cellular components. In this protocol, we aim to describe the cytokine profiling technique for in vitro study of PSC-PCC intercellular communication, and orthotopic xenografting animal model with coinjection of primary PSCs and PCC cell line.

5 Article Primary Cultures for Pancreatic Stellate Cells (PSCs). 2019

Tian, Lei / Lu, Zipeng / Miao, Yi. ·Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. miaoyi@njmu.edu.cn. ·Methods Mol Biol · Pubmed #30378051.

ABSTRACT: Primary cultures of pancreatic stellate cells (PSCs) remain an important basis for in vitro study. However, effective methods for isolating abundant PSCs are currently lacking. This purpose of this chapter is to report our novel approach to isolating PSCs from normal rat pancreas and human pancreatic ductal adenocarcinoma (PDAC) tissue. Normal PSCs were isolated with enzyme digestion and ladder centrifugation with Nycodenz solution. Isolated PSCs were cultured in DMEM/F12 containing 10% fetal bovine serum. Cancer-associated PSCs were obtained by an outgrow method from fresh human PDAC tissues. Isolated activated PSCs were cultured in DMEM/F12 containing 20% fetal bovine serum. With our modification, normal pancreas tissue yields an adequate number of PSCs (approximately 0.5-5 million/g pancreas) for in vitro studies, and the cell viability was about 90%. And a modified outgrowth method made tissue blocks attached more tightly and significantly shortened the outgrowth time of the activated cells. Our modification in PSC isolation methods significantly increased the isolation efficiency and shortened the culture period, thus facilitating future PSC-related research.

6 Article Therapies Targeting the Tumor Stroma and the VEGF/VEGFR Axis in Pancreatic Ductal Adenocarcinoma: a Systematic Review and Meta-Analysis. 2018

Lu, Zipeng / Weniger, Maximilian / Jiang, Kuirong / Boeck, Stefan / Zhang, Kai / Bazhin, Alexander / Miao, Yi / Werner, Jens / D'Haese, Jan G. ·Pancreas Center & Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. · Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians-University, Marchioninistraße 15, 81377, Munich, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Ludwig Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany. · Pancreas Center & Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. miaoyi@njmu.edu.cn. ·Target Oncol · Pubmed #30062609.

ABSTRACT: Abundant tumor stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and is suggested to play a role in the resistance of this deadly disease to systemic treatment. Despite promising results from preclinical studies, clinical trials with therapies targeting the tumor stroma and the vascular endothelial growth factor (VEGF) and its receptor VEGFR yielded conflicting results. With this systematic review and meta-analysis, we aim to summarize the existing evidence in this important field with a special focus on anti-VEGF/VEGFR therapy. A total of 24 clinical studies were included in the qualitative synthesis, and six randomized controlled trials (RCTs) investigating anti-VEGF/VEGFR agents were further included in the quantitative synthesis. The qualitative synthesis revealed a treatment advantage of combined therapy with nab-paclitaxel, while the meta-analysis on anti-VEGF/VEGFR drugs demonstrated marginal improvement of objective response rates and progression-free survival, but not overall survival. Stroma targeting is a promising and rapidly-developing treatment strategy in PDAC. However, novel drugs balancing stroma depletion and modulation are needed.

7 Article ALKBH5 Inhibits Pancreatic Cancer Motility by Decreasing Long Non-Coding RNA KCNK15-AS1 Methylation. 2018

He, Yuan / Hu, Hao / Wang, Yandong / Yuan, Hao / Lu, Zipeng / Wu, Pengfei / Liu, Dongfang / Tian, Lei / Yin, Jie / Jiang, Kuirong / Miao, Yi. ·Department of General Surgery, Pancreas Centre, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · Department of General Surgery, Heping Hospital, Changzhi Medical College, Changzhi, China. · Department of General Surgery, Huai'an People's Hospital Affiliated to Xuzhou Medical University, Huai'an, China. · Department of Hepatopancreatobiliary Center, The Third Hospital Affiliated to Nantong University, Nantong, China. · Department of General Surgery, The Second People's Hospital of Wuhu, Wuhu, China. ·Cell Physiol Biochem · Pubmed #30032148.

ABSTRACT: BACKGROUND/AIMS: Mounting evidence suggests that epitranscriptional modifications regulate multiple cellular processes. N6-Methyladenosine (m6A), the most abundant reversible methylation of mRNA, has critical roles in cancer pathogenesis. However, the mechanisms and functions of long non-coding RNA (lncRNA) methylation remain unclear. Pancreatic cancer resulted in 411,600 deaths globally in 2015. By the time of pancreatic cancer diagnosis, metastasis has often occurred in other parts of the body. The present study sought to investigate lncRNA m6A modification and its roles in pancreatic cancer. METHODS: Differential expression between cancer cells and matched normal cells was evaluated to identify candidate lncRNAs. The lncRNA KCNK15-AS1 was detected in cancer tissues and various pancreatic cells using RT-qPCR. KCNK15-AS1 was transfected into cells to explore its role in migration and invasion. Then, m6A RNA immunoprecipitation was performed to detect methylated KCNK15-AS1 in tissues and cells. Epithelial-mesenchymal transition (EMT) markers were used to evaluate KCNK15-AS1-mediated EMT processes. RESULTS: KCNK15-AS1 was downregulated in pancreatic cancer tissues compared with paired adjacent normal tissues. KCNK15-AS1 inhibited migration and invasion in MIA PaCa-2 and BxPC-3 cells. Furthermore, total RNA methylation in cancer cells was significantly enriched relative to that in immortalized human pancreatic duct epithelial (HPDE6-C7) cells. In addition, the m6A eraser ALKBH5 was downregulated in cancer cells, which can demethylate KCNK15-AS1 and regulate KCNK15-AS1-mediated cell motility. CONCLUSION: Our results have revealed a novel mechanism by which ALKBH5 inhibits pancreatic cancer motility by demethylating lncRNA KCNK15-AS1, identifying a potential therapeutic target for pancreatic cancer.

8 Article Long non-coding RNA lnc-PCTST predicts prognosis through inhibiting progression of pancreatic cancer by downregulation of TACC-3. 2018

Wang, Yandong / Ding, Xiangya / Hu, Hao / He, Yuan / Lu, Zipeng / Wu, Pengfei / Tian, Lei / Xia, Tianfang / Yin, Jie / Yuan, Hao / Shi, Guodong / Liu, Dongfang / Jiang, Kuirong / Miao, Yi. ·Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · Department of General surgery, The Second People's Hospital of Wuhu, Wuhu, China. · Department of Microbiology, Nanjing Medical University, Nanjing, China. · Department of Hepatopancreatobiliary Center, The Third Hospital Affiliated to Nantong University, Wuxi, China. · Department of General surgery, Huai'an Second People's Hospital, Huai'an, China. · Pancreas institute, Nanjing Medical University, Nanjing, China. · Department of General surgery, Huai'an First People's Hospital, Huai'an, China. ·Int J Cancer · Pubmed #29978472.

ABSTRACT: Pancreatic cancer (PC), which is one of the most lethal of malignancies and a major health burden, is associated with a dismal prognosis despite current therapeutic advances. Numerous long noncoding RNAs (lncRNA) have shown to be essential for PC tumorigenesis and progression. Nevertheless, the exact expression pattern of lnc-PCTST and its clinical significance still remain unclear. This study investigates the expression pattern of lnc-PCTST and its associated mRNA in three paired PC tissues and adjacent non-tumor tissues by Microarray-coarray approach. Briefly, our data demonstrated that lnc-PCTST expression is down-regulated in PC tissues. Also, lnc-PCTST has shown to be negatively correlated with transforming acidic coiled-coil 3 (TACC-3) expression. This expression pattern was further confirmed following qRT-PCR validation of 34 out of 48 paired cancer tissues. Furthermore, lnc-PCTST overexpression in PC cell lines inhibited cell proliferation and invasion in vitro, and tumorigenesis in vivo (using nude mice as animal model), but did not altered cell migration. Moreover, lnc-PCTST overexpression increased E-cadherin and repressed vimentin expression in vitro. Additionally, TACC-3 knockdown simulated the inhibiting effect of lnc-PCTST overexpression on PC cell lines, and the impaired proliferation, invasion effect and E-cadherin, vimentin expression on lnc-PCTST over-expressed cell lines can be rescued by overexpressed TACC-3. Significantly, the expression of lnc-PCTST was closely associated with its genomic neighboring gene TACC-3 and inhibited its promoter activity. In conclusion, lnc-PCTST is a potential tumor suppressor in PC, which inhibits cell proliferation, invasion, tumorigenesis and EMT by modulating TACC-3.

9 Article Plasma miRNAs in diagnosis and prognosis of pancreatic cancer: A miRNA expression analysis. 2018

Zhou, Xin / Lu, Zipeng / Wang, Tongshan / Huang, Zebo / Zhu, Wei / Miao, Yi. ·Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China. Electronic address: ivorchou@yeah.net. · Pancreas Center, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, Jiangsu Province, PR China. · Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China. · Department of Oncology, The Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi 214062, Jiangsu Province, PR China. · Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China. Electronic address: zhuwei@njmu.edu.cn. · Pancreas Center, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, Jiangsu Province, PR China. Electronic address: miaoyi@njmu.edu.cn. ·Gene · Pubmed #29913239.

ABSTRACT: The differential expression of microRNAs (miRNAs) in plasma of pancreatic cancer (PC) patients may act as a diagnostic biomarker. A four-stage study was performed to identify plasma miRNAs with potential in detecting PC. Exiqon panels (20 PC vs. 10 normal controls (NCs)) were applied in the screening phase to obtain miRNA profiling. The identified miRNAs were further assessed in the training (40 PC vs. 40 NCs) and testing stages (112 PC vs. 116 NCs) with qRT-PCR assays. A six-miRNA signature including up-regulated miR-122-5p, miR-125b-5p, miR-192-5p, miR-193b-3p, miR-221-3p and miR-27b-3p was identified. The signature could accurately discriminate PC patients from NCs with areas under the receiver operating characteristic curve of 0.848, 0.833 and 0.937 for the training, testing and the external validation stage (41 PC vs. 50 NCs), respectively. The multivariate Cox regression analyses showed that down-regulated plasma miR-125b-5p could predict worse OS independent from late tumor stage and high CA19-9. All the six miRNAs except miR-122-5p showed high expression levels in PC tissues than those in matched normal tissues. MiR-122-5p and miR-193b-3p were up-regulated, while miR-221-3p was down-regulated in plasma exosomes from PC patients. Bioinformatics analysis demonstrated that the miRNAs might involve in several molecular pathways closely related with PC such as p53 signaling pathway, pancreatic cancer, TGF-beta signaling pathway and so on. In conclusion, we identified a six-miRNA signature in plasma which could act as a non-invasive biomarker in diagnosis and prognosis of PC. Plasma miR-125b-5p might act as an independent biomarker in predicting OS of PC patients.

10 Article Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3. 2018

Hu, Hao / Wang, Yandong / Ding, Xiangya / He, Yuan / Lu, Zipeng / Wu, Pengfei / Tian, Lei / Yuan, Hao / Liu, Dongfang / Shi, Guodong / Xia, Tianfang / Yin, Jie / Cai, Baobao / Miao, Yi / Jiang, Kuirong. ·Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China. · Department of Hepatopancreatobiliary Center, The Third Hospital Affiliated to Nantong University, Wuxi, 214041, China. · Department of General Surgery, The Second People's Hospital of Wuhu, Wuhu, 241000, China. · Department of Microbiology, Nanjing Medical University, Nanjing, 211166, China. · Department of General Surgery, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, 223001, China. · Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China. · Department of General Surgery, Huai'an First Hospital Affiliated to Nanjing Medical University, Huai'an, 223001, China. · Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China. miaoyi@njmu.edu.cn. · Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China. miaoyi@njmu.edu.cn. · Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China. jiangkuirong@njmu.edu.cn. · Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China. jiangkuirong@njmu.edu.cn. ·Mol Cancer · Pubmed #29386037.

ABSTRACT: BACKGROUND: Long non-coding RNAs (lncRNAs) play an important role in the development and progression of various tumors, including pancreatic cancer (PC). Recent studies have shown that lncRNAs can 'act in cis' to regulate the expression of its neighboring genes. Previously, we used lncRNAs microarray to identify a novel lncRNA termed XLOC_000647 that was down-regulated in PC tissues. However, the expression and function of XLOC_000647 in PC remain unclear. METHODS: The expression of XLOC_000647 and NLRP3 in PC specimens and cell lines were detected by quantitative real-time PCR. Transwell assays were used to determine migration and invasion of PC cells. Western blot was carried out for detection of epithelial-mesenchymal transition (EMT) markers in PC cells. The effect of XLOC_000647 on PC cells was assessed in vitro and in vivo. The function of NOD-like receptor family pyrin domain-containing 3 (NLRP3) in PC was investigated in vitro. In addition, the regulation of NLRP3 by XLOC_000647 in PC was examined in vitro. RESULTS: Here, XLOC_000647 expression was down-regulated in PC tissues and cell lines. The expression level of XLOC_000647 was significantly correlated to tumor stage, lymph node metastasis, and overall survival. Overexpression of XLOC_000647 attenuated cell proliferation, invasion, and EMT in vitro and impaired tumor growth in vivo. Further, a significantly negative correlation was observed between XLOC_000647 levels and its genomic nearby gene NLRP3 in vitro and in vivo. Moreover, XLOC_000647 decreased NLRP3 by inhibiting its promoter activity. Knockdown of NLRP3 decreased proliferation of cancer cells, invasion, and EMT in vitro. Importantly, after XLOC_000647 was overexpressed, the corresponding phenotypes of cells invasion and EMT were reversed by overexpression of NLRP3. CONCLUSIONS: Together, these results indicate that XLOC_000647 functions as a novel tumor suppressor of lncRNA and acts as an important regulator of NLRP3, inhibiting cell proliferation, invasion, and EMT in PC.

11 Article YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway. 2018

Liu, Dongfang / Zhang, Jingjing / Wu, Yang / Shi, Guodong / Yuan, Hao / Lu, Zipeng / Zhu, Qicong / Wu, Pengfei / Lu, Cheng / Guo, Feng / Chen, Jianmin / Jiang, Kuirong / Miao, Yi. ·Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China. · Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China. ·Int J Cancer · Pubmed #29168185.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the malignant lethal tumors. It has been reported that the transcriptional regulator Yin Yang-1 (YY1) suppressed the invasion and metastasis of PDAC. However, the function of YY1 on proliferation and migration of pancreatic cancer remains to be clarified. In this study, we found that YY1 overexpression or knockdown can inhibit or promote the proliferation and migration of pancreatic cancer cells. Digital gene expression sequencing indicates that cyclin-dependent kinase inhibitor 3 (CDKN3) may be the candidate target gene of YY1. Then we found that YY1 can downregulate the expression of CDKN3 by directly binding to the promoter region of CDKN3. Silencing CDKN3 expression could inhibit the ability of cell proliferation and migration and overexpression of CDKN3 could restore the effects induced by YY1 overexpression in pancreatic cancer cells. The expression levels of YY1 and CDKN3 were negatively correlated in pancreatic cancer tissues and PDAC patients with higher levels of CDKN3 have poor prognosis. Vitro and vivo study show that CDKN3 can form a complex with MdM2-P53, thus leading to inhibiting the expression of P21, which is the target gene of P53, and finally facilitates the cell cycle to promote the proliferation of pancreatic cancer cells. Hence, YY1 can directly regulate the expression of CDKN3 and participate in the cycle of pancreatic cancer cells, which can inhibit the progression of pancreatic cancer. These results reveal that YY1-CDKN3-MDM2/P53-P21 axis is involved in pancreatic tumorigenesis, which may develop new methods for human pancreatic cancer therapy.

12 Article Radical antegrade modular pancreatosplenectomy for adenocarcinomaof the body of the pancreas in a patient with portal annular pancreas, aberrant hepatic artery, and absence of the celiac trunk: A case report. 2017

Yuan, Hao / Wu, Pengfei / Chen, Jianmin / Lu, Zipeng / Chen, Lei / Wei, Jishu / Guo, Feng / Cai, Baobao / Yin, Jie / Xu, Dong / Jiang, Kuirong / Miao, Yi. ·Department of General Surgery, Pancreas Center, The First Affiliated Hospital of Nanjing Medical University. · Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China. ·Medicine (Baltimore) · Pubmed #29310347.

ABSTRACT: RATIONALE: Portal annular pancreas is a rare anatomic variation, where the uncinated process of the pancreas connects with the dorsal pancreas and the pancreas tissue encases the portal vein (PV), superior mesenteric vein (SMV) or splenic vein (SV). Malignancies are quite uncommon in the patients, who have an annular pancreas especially portal annular pancreas. Ectopic common hepatic artery and absence of the celiac trunk (CT) are the other infrequent abnormalities. PATIENT CONCERNS: A 74-year-old man suffered from upper abdominal and back pain. DIAGNOSES AND INTERVENTIONS: Contrast enhanced computed tomography indicated a low-density mass in the body of the pancreas. Pathological report showed adenocarcinoma of the body of pancreas after radical antegrade modular pancreatosplenectomy (RAMPS). OUTCOMES: In the operation, we found the superior vein and portal vein was surrounded by the pancreatic tissue. The left gastric artery and splenic artery originated respectively from abdominal aorta, and celiac trunk was not viewed. In addition, the common hepatic artery was a branch from the superior mesenteric artery. LESSONS: In general, this is a novel clinical case of pancreatic carcinoma happening in the portal annular pancreas which was accompanied with aberrant hepatic artery and absence of the celiac trunk at the same time. Confronted with the pancreatic neoplasms, the possibility of coexistent annular pancreas and arterial variations should be considered.

13 Article Terminating the criminal collaboration in pancreatic cancer: Nanoparticle-based synergistic therapy for overcoming fibroblast-induced drug resistance. 2017

Wang, Liying / Liu, Xiangrui / Zhou, Quan / Sui, Meihua / Lu, Zipeng / Zhou, Zhuxian / Tang, Jianbin / Miao, Yi / Zheng, Min / Wang, Weilin / Shen, Youqing. ·Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China. · Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China. Electronic address: xiangrui@zju.edu.cn. · Center for Cancer Biology and Innovative Therapeutics, Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, China. · Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Medical School, Zhejiang University, China. · Department of Hepatobiliary and Pancreatic Interventional Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. ·Biomaterials · Pubmed #28837958.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a dismal overall prognosis mainly unchanged over the past decades. PDAC is generally refractory to conventional treatments, and thus novel therapies are urgently needed. Recently, accumulating evidence has indicated that human pancreatic stellate cells (PSCs) facilitate PDAC development and drug resistance through paracrine activation of hedgehog pathway. Here, we report that smart SN38 (active metabolite of irinotecan) polymeric prodrug-based nanoparticles effectively encapsulate the commercial hedgehog pathway inhibitor GDC-0449 for co-delivery. More intriguingly, we obtained size-tunable nanoparticles with increased GDC-0449 loading efficiency by simply extending the chain length of the hydrophobic SN38 block. To better evaluate the efficacy and investigate the synergistic mechanisms, we immortalized human PSCs and established fibroblast-containing models in vitro and in vivo. In PSCs, BxPC-3 cells and MIA PaCa-2 cells, GDC-0449 suppressed the co-culture induced up-regulations of the two drug resistance contributors: sonic hedgehog transcription factor glioma-associated protein1 (GLI-1) and UGT1A glucuronosyltransferase. Importantly, the nanoparticle-mediated co-delivery system exhibited potent antitumor efficacy with enhanced apoptosis and reduced collagen, α-SMA and GLI-1 expression in tumor tissues. These findings reveal a potential strategy to utilize nanoparticle-mediated drug co-delivery platform as an effective combination therapy for fibroblast-enriched PDAC.

14 Article [Laparoscopic pancreaticoduodenectomy with a novel artery first and uncinate process first approach through Treitz ligament]. 2017

Gao, W T / Xi, C H / Tu, M / Dai, X L / Guo, F / Chen, J M / Wei, J S / Lu, Z P / Wu, J L / Jiang, K R / Miao, Y. ·Pancreas Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China. ·Zhonghua Wai Ke Za Zhi · Pubmed #28464576.

ABSTRACT:

15 Article The clinical value, regulatory mechanisms, and gene network of the cancer-testis gene STK31 in pancreatic cancer. 2017

Zhang, Kai / Lu, Zipeng / Zhu, Yi / Tian, Lei / Zhang, Jingjing / Xi, Chunhua / Gao, Wentao / Jiang, Kuirong / Miao, Yi. ·Pancreatic Center & Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China. · Pancreas Institute of Nanjing Medical University, Nanjing 210029, Jiangsu, China. ·Oncotarget · Pubmed #28422722.

ABSTRACT: We aimed to identify STK31 as a cancer-testis (CT) gene and to explore its potential clinical value, regulatory mechanisms, and gene network in pancreatic cancer (PC). Gene expression data were generated from normal organ samples and pancreatic cancer samples from three public databases. STK31 expression patterns in normal and PC tissues were identified, and we explored its regulatory mechanisms. Gene ontology (GO) and pathway analyses of STK31-related genes were performed and an STK31 protein-protein interaction (PPI) network was constructed. STK31 was confirmed as a CT gene in PC and its expression was significantly higher in patients with new neoplasm compared with patients without new neoplasm (P = 0.046) and in more advanced pathologic stages than in earlier stages (P = 0.002); methylation level correlated negatively with STK31 expression. In total, 757 STK31-related genes were identified, and were significantly enriched in terms of polymorphisms and alternative splicings. The PPI network predicted that STK31 was physically associated with the PIWI (originally P-element Induced WImpy testis in Drosophila) and Tudor families.

16 Article Galectin-1-driven upregulation of SDF-1 in pancreatic stellate cells promotes pancreatic cancer metastasis. 2017

Qian, Dong / Lu, Zipeng / Xu, Qingcheng / Wu, Pengfei / Tian, Lei / Zhao, Liangtao / Cai, Baobao / Yin, Jie / Wu, Yang / Staveley-O'Carroll, Kevin F / Jiang, Kuirong / Miao, Yi / Li, Guangfu. ·Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China; Department of General Surgery, Affiliated Hospital of Nanjing University of TCM, Jiangsu Province Hospital of TCM, Nanjing 210029, China. · Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China. · Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China; Department of Gastroenterology, Subei People's Hospital, Clinical Medical School, Yangzhou University Affiliated Hospital, Yangzhou 225000, China. · Department of Surgery, University of Missouri, Columbia, MO 65212, USA; Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, USA; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA. · Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China. Electronic address: jiangkuirong@njmu.edu.cn. · Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China. Electronic address: miaoyi@njmu.edu.cn. · Department of Surgery, University of Missouri, Columbia, MO 65212, USA; Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, USA. Electronic address: liguan@health.missouri.edu. ·Cancer Lett · Pubmed #28336327.

ABSTRACT: Galectin-1, mainly expressed in activated pancreatic stellate cells (PSCs), is involved in many important cancer-related processes. However, very little is known how Galectin-1 modulates PSCs and subsequently impacts pancreatic cancer cells (PCCs). Our chemokine antibody array and in vitro studies demonstrates that Galectin-1 induces secretion of stromal cell-derived factor-1(SDF-1) in PSCs by activating NF-κB signaling. The secreted SDF-1 increases migration and invasion of PCCs. Knockdown of Galectin-1 and inhibitor-mediated blockade of SDF-1 as well as its ligand CXCR4 and NF-κB verifies the findings. In vivo experiment by knockdown of Galectin-1 in PSCs further demonstrates the conclusion. Collectively, the present studies demonstrate that Galectin-1-driven production of SDF-1 in PSCs through activation of NF-κB promotes metastasis in PDAC, offering a potential target in the treatment of pancreatic cancer.

17 Article Vasohibin 2 reduces chemosensitivity to gemcitabine in pancreatic cancer cells via Jun proto-oncogene dependent transactivation of ribonucleotide reductase regulatory subunit M2. 2017

Tu, Min / Li, Haifeng / Lv, Nan / Xi, Chunhua / Lu, Zipeng / Wei, Jishu / Chen, Jianmin / Guo, Feng / Jiang, Kuirong / Song, Guoxin / Gao, Wentao / Miao, Yi. ·Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People's Republic of China. · Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China. · Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People's Republic of China. gao11@hotmail.com. · Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People's Republic of China. miaoyi@njmu.edu.cn. ·Mol Cancer · Pubmed #28327155.

ABSTRACT: BACKGROUND: Vasohibin 2 (VASH2) has previously been identified as an agiogenenic factor and a cancer related protein. Here we investigated the association of VASH2 expression and chemoresistance in pancreatic cancer. METHODS: Immunohistochemical staining for VASH2 was performed on 102 human pancreatic cancer samples. Pancreatic cancer cell line models exhibiting overexpression or knockdown of VASH2 were generated. Gene expression analyses were carried out to determine genes differentially regulated by VASH2. Putative transcription factors that are downstream mediators of gene expression regulated by VASH2 were queried bioinformatically. Dual-luciferase reporter assays and ChIP assays were performed to confirm transactivation of target genes following VASH2 overexpression or knockdown. RESULTS: VASH2 protein expression was higher in human pancreatic cancer than in paired adjacent tissues and elevated VASH2 levels were associated with gemcitabine chemoresistance. In cell line models of pancreatic cancer, VASH2 expression induced gemcitabine chemoresistance in vitro and in vivo. It was discovered that expression of ribonucleotide reductase regulatory subunit M2 (RRM2) is regulated by VASH2; immunohistochemical analysis demonstrated a positive association of VASH2 expression and RRM2 expression in human pancreatic cancer tissues. Bioinformatics analyses revealed that induction of the Jun proto-oncogene (JUN) by VASH2 is responsible for upregulation of RRM2 expression; this JUN-dependent regulation of RRM2 by VASH2 was confirmed by chromatin immunoprecipitation and dual luciferase reporter assays, which demonstrated that JUN directly binds with the RRM2 promoter to activate transcription. CONCLUSIONS: These data suggest that VASH2 reduces the chemosensitivity to gemcitabine in pancreatic cancer cells via JUN-dependent transactivation of RRM2.

18 Article Association between ERCC2 Lys751Gln polymorphism and the risk of pancreatic cancer, especially among Asians: evidence from a meta-analysis. 2017

Wu, Yang / Lu, Zi-Peng / Zhang, Jing-Jing / Liu, Dong-Fang / Shi, Guo-Dong / Zhang, Chun / Qin, Zhi-Qiang / Zhang, Jian-Zhong / He, Yuan / Wu, Peng-Fei / Miao, Yi / Jiang, Kui-Rong. ·Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · Pancreas Institute, Nanjing Medical University, Nanjing, China. · Department of Digestive Diseases, Songjiang Branch Hospital of Shanghai First People's Hospital, Nanjing Medical University, Shanghai, China. · Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · Department of Gastrointestinal Surgery, Huai'an Affiliated to Xuzhou Medical University and Huai'an Second People's Hospital, Huai'an, China. ·Oncotarget · Pubmed #28223548.

ABSTRACT: Single nucleotide polymorphisms (SNPs) of Excision repair cross-complementing group 2 (ERCC2) gene are suspected to affect the risk of pancreatic cancer. Many studies have reported the association between ERCC2 Lys751Gln polymorphism (rs13181) and the susceptibility to pancreatic cancer, but the outcomes remained controversial. To comprehensively determine this association, we conducted a meta-analysis based on a total of eight studies. Evidence for this association was obtained from the PubMed, EMBASE, Web of Science and Chinese National Knowledge Infrastructure (CNKI) databases. In general, a significant association was found between ERCC2 rs13181 polymorphism and the susceptibility to pancreatic cancer in four genetic models [CC vs. AA: OR = 1.56, (95% CI: 1.28-1.90), P = 0.470; AC/CC vs. AA: OR=1.20, (95% CI: 1.06-1.36), P = 0.396; CC vs. AC/CC: OR = 1.50; (95% CI: 1.24-1.81), P = 0.530; C vs. A: OR=1.22, (95%CI:1.11-1.34), P = 0.159]. Furthermore, stratified analyses by ethnicity indicated a significant association only in the Asian population. Our results indicate that the ERCC2 Lys751Gln polymorphism might be important in stimulating the development of pancreatic cancer, especially for Asians.

19 Article [Surgical treatment for pancreatic neuroendocrine neoplasmas]. 2016

Wu, Junli / Guo, Feng / Wei, Jishu / Lu, Zipeng / Chen, Jianmin / Gao, Wentao / Li, Qiang / Jiang, Kuirong / Dai, Cuncai / Miao, Yi. ·Pancreas Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. ·Zhejiang Da Xue Xue Bao Yi Xue Ban · Pubmed #27045238.

ABSTRACT: Pancreatic neuroendocrine neoplasmas (PNENs) are classified into functioning & non-functioning tumors. The radical surgery is the only effective way for the cure & long-term survival. For the locoregional resectable tumors, the surgical resection is the first choice of treatment; the surgical procedures include local resection (enucleation) and standard resection. For the insulinomas and non-functioning tumors less than 2 cm, local resection (enucleation),distal pancreatectomy with spleen-preservation or segmental pancreatectomy are the commonly selected procedures. The radical resections with regional lymph nodes dissection, including pancreaticoduodenectomy, distal pancreatectomy and middle segmental pancreatectomy, should be applied for tumors more than 2 cm or malignant ones. For the locoregional advanced or unresectable functioning tumors, debulking surgery should be performed and more than 90% of the lesions including primary and metastatic tumors should be removed; for the non-functioning tumors, if complicated with biliary & digestive tract obstruction or hemorrhage, the primary tumors should be resected. The liver is the most frequent site of metastases for PNENs and three types of metastases are defined. For typeⅠmetastasis, patients are recommended for surgery if there are no contraindications; For type II metastasis, debulking surgery should be applied and at least 90% of metastatic lesions should be resected, and for patients with primary tumors removed and no extrahepatic metastases, or for patients with well-differentiated (G1/G2) tumors, liver transplantation may be indicated. For the unresectable type Ⅲ metastasis, multiple adjuvant therapies should be chosen.

20 Article Activation of pancreatic stellate cells involves an EMT-like process. 2016

Tian, Lei / Lu, Zi-Peng / Cai, Bao-Bao / Zhao, Liang-Tao / Qian, Dong / Xu, Qing-Cheng / Wu, Peng-Fei / Zhu, Yi / Zhang, Jing-Jing / Du, Qing / Miao, Yi / Jiang, Kui-Rong. ·Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China. ·Int J Oncol · Pubmed #26647741.

ABSTRACT: Pancreatic adenocarcinoma (PDAC) and chronic pancreatitis (CP) are characterized by a desmoplastic reaction involving activated pancreatic stellate cells (PSCs). However, the mechanisms of PSC activation remain poorly understood. We examined whether the epithelial-mesenchymal transition (EMT) process might play a role in PSC activation. PSCs were isolated from a rat pancreas and characterized using immunofluorescence and immunocytochemistry. We evaluated changes in cell motility and in the expression levels of a panel of EMT-related genes during the PSC activation process. Activation of PSCs occurred after 48 h of in vitro culture, as indicated by a morphological change to a myofibroblastic shape and a decrease in the number of cytoplasmic lipid droplets. After activation, PSCs showed enhanced cell migration ability compared to quiescent cells. In addition, the expression of epithelial markers (E-cadherin, BMP7 and desmoplakin) decreased, while expression of mesenchymal markers (N-cadherin, vimentin, fibronectin1, collagen1α1 and S100A4) increased in activated PSCs. EMT-related transcription factors (Snail and Slug) were also upregulated after PSC activation. The concurrent increase in cell migration ability and alterations in EMT-related gene expression suggests that the activation of PSCs involves an EMT-like process. The knowledge that PSC activation involves an EMT‑like process may help to identify potential new therapeutic targets to alleviate pancreatic fibrosis in diseases like CP and PDAC.

21 Article Elevation of MMP-9 and IDO induced by pancreatic cancer cells mediates natural killer cell dysfunction. 2014

Peng, Yun-Peng / Zhang, Jing-Jing / Liang, Wen-biao / Tu, Min / Lu, Zi-Peng / Wei, Ji-Shu / Jiang, Kui-Rong / Gao, Wen-Tao / Wu, Jun-Li / Xu, Ze-Kuan / Miao, Yi / Zhu, Yi. ·Department of General Surgery, The first Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People's Republic of China. miaoyi@njmu.edu.cn. ·BMC Cancer · Pubmed #25274283.

ABSTRACT: BACKGROUND: Natural killer (NK) cells play a key role in non-specific immune response in different cancers, including pancreatic cancer. However the anti-tumor effect of NK cells decreases during pancreatic cancer progression. The regulatory pathways by which NK cells facilitate tumor immune escape are unclear, therefore our purpose was to investigate the roles of the contributory factors. METHODS: NK cells isolated from fresh healthy peripheral blood were co-cultured with normal human pancreatic ductal cells hTERT-HPNE and human pancreatic cancer cell lines SW1990 and BxPc-3 in vitro. Then NK cell function was determined by Flow cytometric analysis of surface receptors and cytotoxic granules in NK cells, NK cell apoptosis and cytotoxicity, and Enzyme-linked immunosorbent assay of cytokines. Expression level of MMP-9, IDO and COX-2 in hTERT-HPNE and SW1990 cells were detected by quantitative RT-PCR. Statistical differences between data groups were determined by independent t-tests using SPSS 19.0 software. RESULTS: Our results showed that NK cell function was significantly downregulated following exposure to pancreatic cancer cells compared to normal pancreatic cells, as demonstrated by lower expressions of activating surface receptors (NKG2D, DNAM-1, NKp30 and NKp46) and cytotoxic granules (Perforin and Granzyme B); decreased secretion of cytokines (TNF-α and IFN-γ); and reduced cytotoxicity against myelogenous leukemia K562 cells. Further investigations revealed that MMP-9 and IDO may be implicated in SW1990 cell-induced NK cell dysfunction by facilitating tumor immune evasion. Blockade by TIMP-1 and/or 1-MT could partially restore NK function. CONCLUSIONS: Taken together, elevation of MMP-9 and IDO induced by pancreatic cancer cells mediates NK cell dysfunction. Our findings could contribute to the development of NK cell-based immunotherapy in patients with pancreatic cancer.

22 Article High expression of Galectin-1 in pancreatic stellate cells plays a role in the development and maintenance of an immunosuppressive microenvironment in pancreatic cancer. 2012

Tang, Dong / Yuan, Zhongxu / Xue, Xiaofeng / Lu, Zipeng / Zhang, Ye / Wang, Hui / Chen, Minyong / An, Yong / Wei, Jishu / Zhu, Yi / Miao, Yi / Jiang, Kuirong. ·Department of General Surgery, Nanjing Medical University, Nanjing, People's Republic of China. ·Int J Cancer · Pubmed #21780106.

ABSTRACT: Galectin-1 is implicated in making tumor cells immune privileged, in part by regulating the survival of infiltrating T cells. Galectin-1 is strongly expressed in activated pancreatic stellate cells (PSCs); however, whether this is linked to tumor cell immune escape in pancreatic cancer is unknown. Galectin-1 was knocked down in PSCs isolated from pancreatic tissues using small interfering RNA (siRNA), or overexpressed using recombinant lentiviruses, and the PSCs were cocultured with T cells. CD3(+) , CD4(+) and CD8(+) T cell apoptosis was detected by flow cytometry; T cell IL-2, IL-4, IL-5 and INF-γ production levels were quantified using ELISA. Immunohistochemical analysis showed increased numbers of PSCs expressed Galectin-1 (p < 0.01) and pancreatic cancers had increased CD3(+) T cell densities (p < 0.01) compared to normal pancreas or chronic pancreatitis samples. In coculture experiments, PSCs that overexpressed Galectin-1 induced apoptosis of CD4(+) T cells (p < 0.01) and CD8(+) T cells (p < 0.05) significantly, compared to normal PSCs. Knockdown of Galectin-1 in PSCs increased CD4(+) T cell (p < 0.01) and CD8(+) T cell viability (p < 0.05). Supernatants from T cells cocultured with PSCs that overexpressed Galectin-1 contained significantly increased levels of Th2 cytokines (IL-4 and IL-5, p < 0.01) and decreased Th1 cytokines (IL-2 and INF-γ, p < 0.01). However, the knockdown of PSC Galectin-1 had the opposite effect on Th1 and Th2 cytokine secretion. Our study suggests that the overexpression of Galectin-1 in PSCs induced T cell apoptosis and Th2 cytokine secretion, which may regulate PSC-dependent immunoprivilege in the pancreatic cancer microenvironment. Galectin-1 may provide a novel candidate target for pancreatic cancer immunotherapy.

23 Article Galectin-1 secreted by activated stellate cells in pancreatic ductal adenocarcinoma stroma promotes proliferation and invasion of pancreatic cancer cells: an in vitro study on the microenvironment of pancreatic ductal adenocarcinoma. 2011

Xue, Xiaofeng / Lu, Zipeng / Tang, Dong / Yao, Jie / An, Yong / Wu, Junli / Li, Qiang / Gao, Wentao / Xu, Zekuan / Qian, Zhuyin / Dai, Cuncai / Wei, Jishu / Miao, Yi / Jiang, Kuirong. ·Laboratory of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. ·Pancreas · Pubmed #21747316.

ABSTRACT: OBJECTIVES: This study aimed to clarify that the activated pancreatic stellate cells (PaSCs) are the origin of the highly expressed galectin-1 in the stroma of pancreatic ductal adenocarcinoma (PDAC) tissue and to evaluate the effect of the secreted galectin-1 on proliferation and invasion ability of pancreatic cancer cell line CFPAC-1 in vitro. METHODS: Different kinds of PaSCs were isolated from the normal or cancerous pancreatic tissues and cultured. Immunohistochemistry study, quantitative polymerase chain reaction, and Western blot were carried out to check the cellular origin of galectin-1 in PDAC tissue. By using modified Boyden chambers, in vitro coculture system of PaSCs was established with the pancreatic cancer cell line CFPAC-1 and based on which we assessed the proliferation and invasion ability of CFPAC-1 with or without galectin-1 antagonists. RESULTS: We identified PaSCs as the primary source of the highly expressed galectin-1 in PDAC stroma. Galectin-1 secreted by PaSCs increased CFPAC-1 proliferative rate in the proliferation assay and facilitated CFPAC-1 infiltration in the invasion assay. CONCLUSIONS: Under malignant circumstances, PaSCs express and secret galectin-1, which could further promote the proliferation and invasion of cancer cells.

24 Article Cyclopamine reverts acquired chemoresistance and down-regulates cancer stem cell markers in pancreatic cancer cell lines. 2011

Yao, Jie / An, Yong / Wie, Ji-shu / Ji, Zhen-ling / Lu, Zi-peng / Wu, Jun-li / Jiang, Kui-rong / Chen, Ping / Xu, Ze-kuan / Miao, Yi. ·Department of General Surgery, The First Affiliated Hospital of Yangzhou University, Yangzhou, P R China. ·Swiss Med Wkly · Pubmed #21630164.

ABSTRACT: BACKGROUND: The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that Hh plays an important role in maintaining the cancer stem cell (CSCs) pool. Gemcitabine-resistant pancreatic cancer cells highly express some of the CSCs markers. However, the expression level of Hh members in gemcitabine-resistant pancreatic cancer cells remains unknown. The aim of this study was to verify the expression of HH members, such as Shh, Ptc, SMO and Gli-1 in gemcitabine-resistant PDAC cell lines, and to explore a new strategy to overcome chemoresistance in PDAC. MATERIAL AND METHODS: Quantitative real-time RT-PCR (Q-PCR) and western blot were used to evaluate the relative expression level of HH members in SW1990, CFPAC-1 cells and gemcitabine-resistant SW1990, CFPAC-1 cells. The change of cancer stem cell markers and the expression level of HH members before and after cyclopamine treatment was evaluated using flow cytometry and Q-PCR, western blot, respectively. Cell apoptosis after cyclopamine treatment was measured by flow cytometry. RESULTS: CD44, CD133 and the expression level of HH members, including Shh, SMO, Gli-1, were found to be highly expressed in gemcitabine-resistant cells, which were significantly down-regulated by cyclopamine treatment. Flow cytometry analysis showed increased cell apoptosis after cyclopamine treatment. CONCLUSION: Gemcitabine-resistant pancreatic cancer cells highly express CSCs markers and some of the HH members, and inhibition of HH by cyclopamine is an effective method of reversing gemcitabine resistance in pancreatic cancer.

25 Article [Establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ and research the relationship between SW1990/GZ and pancreatic cancer stem cell]. 2010

An, Yong / Yao, Jie / Wei, Ji-Shu / Lu, Zi-Peng / Cai, Hui-Hua / Dai, Cun-Cai / Qian, Zhu-Yin / Xu, Ze-Kuan / Miao, Yi. ·Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China. ·Zhonghua Wai Ke Za Zhi · Pubmed #21054984.

ABSTRACT: OBJECTIVES: To establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ, and to explore the relationship between drug-resistant cell line SW1990/GZ and pancreatic cancer stem cell. METHODS: Gemcitabine-resistant pancreatic cancer cell line SW1990/GZ was obtained by treating parental cell line SW1990 in vitro with increasing dosage of gemcitabine in culture medium intermittently for 24 weeks. Stable cultures were obtained which were 77.2-fold increased in resistance relative to parental cells. Gene expressions of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP were determined by real-time PCR. Tumorigenic potential was performed by nude mice xenograft transplant experiments. Side population analysis and CD24CD44 positive cells explore were determined by flow cytometry to examine cancer stem cell proportion. RESULTS: Gemcitabine-resistant cell line SW1990/GZ underwent obvious morphological and functional changes. Compared with the parental cell line, SW1990/GZ cell was small and turned into round shape. SW1990/GZ had a higher gene expression level of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP than SW1990 (P < 0.01). Nude mice xenograft transplant experiments showed that only 1 × 10(5) SW1990/GZ cells were sufficient for tumor formation, whereas an injection of 1 × 10(5) SW1990 cells did not initiate tumors. Flow cytometry analysis showed that SP proportion in SW1990/GZ was (11.0 ± 1.0)%, whereas in parental SW1990 it was (4.6 ± 0.9)%, CD44CD24 positive cells was (8.73 ± 0.81)% in SW1990/GZ, whereas (1.1 ± 0.4)% in SW1990. CONCLUSIONS: Gemcitabine-resistant cell line SW1990/GZ has a higher proportion of pancreatic cancer stem cells compared to its parental cell line SW1990. CD44 is mainly responsible for acquired drug resistance, which can be a potential target to overcome acquired drug resistance in pancreatic cancer.

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