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Pancreatic Neoplasms: HELP
Articles by Lei Zhou
Based on 17 articles published since 2010
(Why 17 articles?)
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Between 2010 and 2020, Lei Zhou wrote the following 17 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review LINE-1 methylation level and prognosis in pancreas cancer: pyrosequencing technology and literature review. 2017

Yamamura, Kensuke / Kosumi, Keisuke / Baba, Yoshifumi / Harada, Kazuto / Gao, Feng / Zhang, Xiaobo / Zhou, Lei / Kitano, Yuki / Arima, Kota / Kaida, Takayoshi / Takeyama, Hideaki / Higashi, Takaaki / Imai, Katsunori / Hashimoto, Daisuke / Chikamoto, Akira / Tan, Xiaodong / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. · Department of Pancreatic and Thyroidal Surgery, China Medical University Shengjing Hospital, Shenyang, 110004, People's Republic of China. · Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp. ·Surg Today · Pubmed #28536860.

ABSTRACT: PURPOSE: Global DNA hypomethylation plays an important role in genomic instability and carcinogenesis. The long interspersed nucleotide element-1 (LINE-1) methylation level is a good surrogate marker of the global DNA methylation level. Previously, we demonstrated a strong relationship between LINE-1 hypomethylation and poor prognosis in certain cancers. However, the relationship between the LINE-1 methylation level and the clinical outcome of pancreatic cancer (PC) remains unclear. METHODS: We used a pyrosequencing assay to measure LINE-1 methylation levels in 126 samples of resected PC and evaluated the prognostic value of the LINE-1 methylation level. RESULTS: LINE-1 methylation levels were significantly lower in PC tissues than in matched noncancerous pancreatic tissues (p = 0.039, n = 36). The tumoral LINE-1 methylation range was 41.3-92.8 (n = 126, mean 77.7, median 78.5, standard deviation 5.7). The LINE-1 methylation level was unrelated to clinical and pathological features. Moreover, LINE-1 hypomethylation was not significantly associated with overall survival, cancer specific survival, or disease-free survival (log-rank p = 0.30, p = 0.18 and p = 0.50, respectively). CONCLUSION: The LINE-1 methylation level appears not to be associated with poor prognosis in PC. The effect of the LINE-1 methylation level on the survival of PC patients needs to be confirmed in a larger-cohort study.

2 Review KRAS, BRAF, and PIK3CA mutations, and patient prognosis in 126 pancreatic cancers: pyrosequencing technology and literature review. 2016

Zhou, Lei / Baba, Yoshifumi / Kitano, Yuki / Miyake, Keisuke / Zhang, Xiaobo / Yamamura, Kensuke / Kosumi, Keisuke / Kaida, Takayoshi / Arima, Kota / Taki, Katsunobu / Higashi, Takaaki / Imai, Katsunori / Hashimoto, Daisuke / Yamashita, Yoichi / Chikamoto, Akira / Beppu, Toru / Tan, Xiaodong / Baba, Hideo. ·Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. · Department of Pancreatic and Thyroidal Surgery, China Medical University Shengjing Hospital, Shenyang, 110004, People's Republic of China. · Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp. ·Med Oncol · Pubmed #26927447.

ABSTRACT: The oncogenic hallmarks of pancreatic cancer (PC), such as the KRAS, BRAF, and PIK3CA mutations, have been widely investigated. However, almost all of the previous studies were limited by small sample sizes. In addition, previous data on the KRAS mutation and clinical outcomes in PC remain inconclusive. To clarify these data, we examined the mutation status of 126 PC patients and its relationship to clinical outcome. The frequencies of KRAS, BRAF, and PIK3CA mutations were determined from a non-biased database of 126 resected PCs and a high-throughput pyrosequencing assay. KRAS mutations were detected in 109 (86.5 %) of the 126 cases; the most common mutation was c.34G > T (p.G12C), which was present in 80 tumors, followed by c.35G > T (p.G12V) in 52 tumors. The KRAS mutation was not associated with any clinical or pathological features (p > 0.05 in all cases). In addition, the KRAS mutation was unrelated to overall survival (log rank p = 0.21) and cancer-specific survival (log rank p = 0.27). Importantly, the influence of KRAS mutation on patient outcome was not modified by any of the clinical or pathological variables (p for all interactions >0.05). Only one PIK3CA mutation (0.8 %) was detected on exon 9 RS3 (c.1633G > A, p.E545K). The BRAF mutation was not detected in PC. KRAS mutations appear to be unrelated to clinical outcome in PC. BRAF and PIK3CA mutations were extremely rare in PC, suggesting that they play a limited role in PC development.

3 Clinical Trial Dendritic Cell/Cytokine-Induced Killer Cell Immunotherapy Combined with S-1 in Patients with Advanced Pancreatic Cancer: A Prospective Study. 2017

Jiang, Ni / Qiao, Guoliang / Wang, Xiaoli / Morse, Michael A / Gwin, William R / Zhou, Lei / Song, Yuguang / Zhao, Yanjie / Chen, Feng / Zhou, Xinna / Huang, Lefu / Hobeika, Amy / Yi, Xin / Xia, Xuefeng / Guan, Yanfang / Song, Jin / Ren, Jun / Lyerly, H Kim. ·Department of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. · Department of Medicine, Duke University Medical Center, Durham, North Carolina. · Department of Surgery, Duke University Medical Center, Durham, North Carolina. · Department of Medicine, University of Washington, Seattle, Washington. · Geneplus-Beijing Institute, Beijing, China. · Department of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. jun.ren@duke.edu kim.lyerly@duke.edu. · Department of Surgery, Duke University Medical Center, Durham, North Carolina. jun.ren@duke.edu kim.lyerly@duke.edu. ·Clin Cancer Res · Pubmed #28611200.

ABSTRACT:

4 Article Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK signaling. 2020

Sheng, Weiwei / Shi, Xiaoyang / Lin, Yiheng / Tang, Jingtong / Jia, Chao / Cao, Rongxian / Sun, Jian / Wang, Guosen / Zhou, Lei / Dong, Ming. ·Department of Gastrointestinal Surgery, the First Hospital, China Medical University, Shenyang, 110001, China. · Department of General Surgery, the People's Hospital of Liaoning province, Shenyang, 110034, China. · Department of General Surgery, the First Hospital of Nanchang University, NanChang, 330006, China. · Department of General Surgery, the Central Hospital of JingZhou City, JingZhou, 434020, China. · Department of Gastrointestinal Surgery, the First Hospital, China Medical University, Shenyang, 110001, China. dongming@cmu.edu.cn. ·J Exp Clin Cancer Res · Pubmed #31952541.

ABSTRACT: BACKGROUND: Our previous study showed Musashi2 (MSI2) promoted chemotherapy resistance and pernicious biology of pancreatic cancer (PC) by down-regulating Numb and p53. We further explored the novel molecular mechanism involving its oncogenic role in PC development. METHODS: We investigated the potential role and mechanism of MSI2 in EGF-induced EMT in PC in vitro and vivo. RESULTS: EGF enhanced EGFR (epidermal growth factor receptor) phosphorylation, induced EMT and activated ZEB1-ERK/MAPK signaling in 2 PC cells. However, MSI2 silencing reversed EGF stimulated function, including inhibiting EGF-promoted EMT-like cell morphology and EGF-enhanced cell invasion and migration. Meanwhile, MSI2 silencing inhibited EGF-enhanced EGFR phosphorylation at tyrosine 1068 and reversed EGF-induced change of the key proteins in EMT and ZEB1-ERK/MAPK signaling (ZEB1, E-cad, ZO-1, β-catenin, pERK and c-Myc). Additionally, MSI2 was co-stained and co-immunoprecipitated with ZEB1, pERK and c-Myc in PC cells by IF and co-IP, implying a close interaction between them. In vivo, MSI2 silencing inhibited pancreatic tumor size in situ and distant liver metastases. A close relationship of MSI2 with EMT and ZEB1-ERK/MAPK signaling were also observed in vivo and human PC samples, which coordinately promoted the poor prognosis of PC patients. CONCLUSIONS: MSI2 promotes EGF-induced EMT in PC via ZEB1-ERK/MAPK signaling.

5 Article Histone deacetylase inhibition is synthetically lethal with arginine deprivation in pancreatic cancers with low argininosuccinate synthetase 1 expression. 2020

Kim, Stephanie S / Xu, Shili / Cui, Jing / Poddar, Soumya / Le, Thuc M / Hayrapetyan, Hovhannes / Li, Luyi / Wu, Nanping / Moore, Alexandra M / Zhou, Lei / Yu, Alice C / Dann, Amanda M / Elliott, Irmina A / Abt, Evan R / Kim, Woosuk / Dawson, David W / Radu, Caius G / Donahue, Timothy R. ·Department of Surgery, UCLA, Los Angeles, CA, 90095, USA. · Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Hubei 430022, China. · Ahmanson Translational Imaging Division, UCLA, Los Angeles, CA, 90095, USA. · Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, 90095, USA. · Department of Pancreatic and Thyroidal Surgery, Shengjing Hospital, China Medical University, Shenyang 110003, China. · Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA 90095, USA. · Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, 90095, USA. · David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA. ·Theranostics · Pubmed #31903153.

ABSTRACT: Arginine (Arg) deprivation is a promising therapeutic approach for tumors with low argininosuccinate synthetase 1 (ASS1) expression. However, its efficacy as a single agent therapy needs to be improved as resistance is frequently observed.

6 Article Immune correlates of clinical benefit in a phase I study of hyperthermia with adoptive T cell immunotherapy in patients with solid tumors. 2019

Qiao, Guoliang / Wang, Xiaoli / Zhou, Xinna / Morse, Michael A / Wu, Jiangping / Wang, Shuo / Song, Yuguang / Jiang, Ni / Zhao, Yanjie / Zhou, Lei / Zhao, Jing / Di, Yan / Zhu, Lihong / Hobeika, Amy / Ren, Jun / Lyerly, Herbert Kim. ·Department of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. · Department of Surgery, Duke University Medical Center, Durham, NC, USA. · Department of Gynecological Oncology, Beijing Gynecology Hospital, Capital Medical University, Beijing, China. ·Int J Hyperthermia · Pubmed #31795830.

ABSTRACT:

7 Article A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. 2019

Hu, Zishuo Ian / Bendell, Johanna C / Bullock, Andrea / LoConte, Noelle K / Hatoum, Hassan / Ritch, Paul / Hool, Hugo / Leach, Joseph W / Sanchez, James / Sohal, Davendra P S / Strickler, John / Patel, Ravindranath / Wang-Gillam, Andrea / Firdaus, Irfan / Yu, Kenneth H / Kapoun, Ann M / Holmgren, Eric / Zhou, Lei / Dupont, Jakob / Picozzi, Vincent / Sahai, Vaibhav / O'Reilly, Eileen M. ·Memorial Sloan Kettering Cancer Center, New York, New York. · Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · University of Wisconsin, Cancer Center, Madison, Wisconsin. · University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · Froedtert Hospital and Medical College of Wisconsin, Milwaukee, Wisconsin. · Torrance Memorial Physician Network, Redondo Beach, California. · Virginia Piper Cancer Institute, Minneapolis, Minnesota. · Comprehensive Cancer Centers of Nevada, Henderson, Nevada. · Cleveland Clinic, Cleveland, Ohio. · Duke University, Durham, North Carolina. · Comprehensive Blood and Cancer Center, Bakersfield, California. · Washington University School of Medicine, Saint Louis, Missouri. · Oncology Hematology Cancer, Inc., Cincinnati, Ohio. · David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York. · Department of Medicine, Weill Cornell Medical College, New York, New York. · Oncomed Pharmaceuticals Inc, Redwood City, California. · Virginia Mason Medical Center, Seattle, Washington. · University of Michigan, Ann Arbor, Michigan. ·Cancer Med · Pubmed #31347292.

ABSTRACT: PURPOSE: Notch signaling dysregulation is implicated in the development of pancreatic adenocarcinoma (PDAC). Tarextumab is a fully human IgG2 antibody that inhibits Notch2/3 receptors. PATIENTS AND METHODS: Aphase 2, randomized, placebo-controlled, multicenter trial evaluated the activity of tarextumab in combination with nab-paclitaxel and gemcitabine in patients with metastatic PDAC. Patients were stratified based on ECOG performance score and Ca 19-9 level and randomized 1:1 to nab-paclitaxel, gemcitabine with either tarextumab or placebo. Based on preclinical and phase Ib results suggesting a positive correlation between Notch3 gene expression and tarextumab anti-tumor activity, patients were also divided into subgroups of low, intermediate, and high Notch3 gene expression. Primary endpoint was overall survival (OS) in all and in patients with the three Notch3 gene expression subgroups (≥25th, ≥50% and ≥75% percentiles); secondary end points included progression-free survival (PFS), 12-month OS, overall response rate (ORR), and safety and biomarker investigation. RESULTS: Median OS was 6.4 months in the tarextumab group vs 7.9 months in the placebo group (HR = 1.34 [95% CI = 0.95, 1.89], P = .0985). No difference observed in OS in the Notch3 gene expression subgroups. PFS in the tarextumab-treated group (3.7 months) was significantly shorter compared with the placebo group (5.5 months) (hazard ratio was 1.43 [95% CI = 1.01, 2.01]; P = .04). Grade 3 diarrhea and thrombocytopenia were more common in the tarextumab group. CONCLUSIONS: The addition of tarextumab to nab-paclitaxel and gemcitabine did not improve OS, PFS, or ORR in first-line metastatic PDAC, and PFS was specifically statistically worse in the tarextumab-treated patients. CLINICAL TRIAL REGISTRY NO: NCT01647828.

8 Article Long Non-Coding RNA Differentiation Antagonizing Nonprotein Coding RNA (DANCR) Promotes Proliferation and Invasion of Pancreatic Cancer by Sponging miR-214-5p to Regulate E2F2 Expression. 2019

Yao, Zhichao / Chen, Qiyu / Ni, Zhonglin / Zhou, Lei / Wang, Yigeng / Yang, Yuetao / Huang, He. ·Department of General Surgery, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland). · Department of Surgery, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland). ·Med Sci Monit · Pubmed #31213582.

ABSTRACT: BACKGROUND Long non-coding RNA differentiation antagonizing nonprotein coding RNA (lncRNA DANCR) has been reported to act as an oncogene in various human cancers. The role of DANCR in development of pancreatic cancer (PC) is unknown. The aim of our research was to investigate the biological role of DANCR in PC. MATERIAL AND METHODS Expressions of DANCR, miR-214-5p, and E2F2 mRNA in PC tissues and cell lines were examined by qRT-PCR. Western blotting was carried out for detection of E2F2 protein expression in PC cells. Transwell assays were used to examine the metastatic ability of PC cells, while CCK-8 and colony formation assay were applied to evaluate cell proliferation. The effects of DANCR on PC cells were assessed by knockdown in vitro and in vivo. The regulatory mechanism of competitive endogenous RNAs were obtained from bioinformatics prediction and luciferase reporter assay. RESULTS DANCR was markedly upregulated in clinical tissues and cell lines of PC. High DANCR expression exhibited a significant correlation with poor prognosis. DANCR knockdown inhibited growth and metastasis of PC cells. Furthermore, DANCR acted as sponge to regulate miR-214-5p, and miR-214-5p inhibitor reversed the effects of DANCR knockdown on PC cells. Moreover, DANCR positively modulated E2F2 expression through miR-214-5p in PC cells. CONCLUSIONS Collectively, our findings demonstrated that lncRNA DANCR/miR-214-5p/E2F2 axis acts as an oncogene in PC development, which might provide a potential target for PC therapy.

9 Article Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion. 2019

Elliott, Irmina A / Dann, Amanda M / Xu, Shili / Kim, Stephanie S / Abt, Evan R / Kim, Woosuk / Poddar, Soumya / Moore, Alexandra / Zhou, Lei / Williams, Jennifer L / Capri, Joseph R / Ghukasyan, Razmik / Matsumura, Cynthia / Tucker, D Andrew / Armstrong, Wesley R / Cabebe, Anthony E / Wu, Nanping / Li, Luyi / Le, Thuc M / Radu, Caius G / Donahue, Timothy R. ·Department of Surgery, University of California, Los Angeles, CA 90095. · Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095. · Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095. · Department of Pancreatic and Thyroidal Surgery, Shengjing Hospital, China Medical University, Shenyang 110003, China. · Department of Surgery, Harbor-UCLA Medical Center, Torrance, CA 90502. · David Geffen School of Medicine, University of California, Los Angeles, CA 90095. · Department of Surgery, University of California, Los Angeles, CA 90095; cradu@mednet.ucla.edu TDonahue@mednet.ucla.edu. · Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095. ·Proc Natl Acad Sci U S A · Pubmed #30894490.

ABSTRACT: Functional lysosomes mediate autophagy and macropinocytosis for nutrient acquisition. Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit high basal lysosomal activity, and inhibition of lysosome function suppresses PDAC cell proliferation and tumor growth. However, the codependencies induced by lysosomal inhibition in PDAC have not been systematically explored. We performed a comprehensive pharmacological inhibition screen of the protein kinome and found that replication stress response (RSR) inhibitors were synthetically lethal with chloroquine (CQ) in PDAC cells. CQ treatment reduced de novo nucleotide biosynthesis and induced replication stress. We found that CQ treatment caused mitochondrial dysfunction and depletion of aspartate, an essential precursor for de novo nucleotide synthesis, as an underlying mechanism. Supplementation with aspartate partially rescued the phenotypes induced by CQ. The synergy of CQ and the RSR inhibitor VE-822 was comprehensively validated in both 2D and 3D cultures of PDAC cell lines, a heterotypic spheroid culture with cancer-associated fibroblasts, and in vivo xenograft and syngeneic PDAC mouse models. These results indicate a codependency on functional lysosomes and RSR in PDAC and support the translational potential of the combination of CQ and RSR inhibitors.

10 Article IRS-1 regulates proliferation, invasion and metastasis of pancreatic cancer cells through MAPK and PI3K signaling pathways. 2018

Huang, Yinpeng / Zhou, Lei / Meng, Xiangli / Yu, Boqiang / Wang, Huaitao / Yang, Yifan / Wu, Yunhao / Tan, Xiaodong. ·Department of General Surgery, Shengjing Hospital Affiliated to China Medical University Shengyang, China. ·Int J Clin Exp Pathol · Pubmed #31949598.

ABSTRACT: PC is one of the deadliest cancers, with unexpectedly high mortality. The main reason for poor prognosis is the high likelihood of invasion and metastasis of pancreatic cancer cells. Mechanism of exceptional protein phosphorylation that regulates cell invasion and metastasis in pancreatic cancer remain unclear. In our previous studies, we used high-throughput phosphorylation array to test two pancreatic cancer cell lines (PC-1 cells with a low potential, and PC-1.0 cells with a high potential, for invasion and metastasis). We noted that a total of 57 proteinsrevealed a differential expression (fold change 2.0). We supposed that insulin receptor substrate-1 (IRS-1) may play a significant role in pancreatic cancer invasion and metastasis. In this study, similar phosphorylation and protein expression levels together with morphological and functional characteristics were observed in PC-1.0 hamster pancreatic cancer cells and Aspc-1 human pancreatic cancer cells (similar to PC-1.0 in features) transiently transfected with IRS-1 siRNA. Our results indicated that proliferation, invasion and metastasis were reduced in both hamster and human pancreatic cancer cells. IRS-1 was found to regulate the target proteins involved in MAPK and PI3K signaling pathways, which include MEK1, MEK2 and AKT, at the protein and phosphorylation level. Low expression of IRS-1 in pancreatic cancer cells inhibited cell proliferation by targeting MEK1 and AKT, while inhibiting invasion and metastasis by targeting MEK2. Moreover, our results demonstrate that IRS-1 protein and phosphorylation expression levels are negatively controlled by LAR (protein tyrosine phosphatase, receptor type, F). LAR inhibited proliferation, invasion and metastasis of pancreatic cancer cells via a direct decrease of IRS-1 protein and phosphorylation expression levels. In summary, we demonstrate that IRS-1 regulates proliferation, invasion and metastasis of pancreatic cancer cells, and provides a new biomarker in an effort to develop novel therapeutic drug targets for pancreatic cancer treatment.

11 Article MicroRNA-221 induces autophagy through suppressing HDAC6 expression and promoting apoptosis in pancreatic cancer. 2018

Yang, Yifan / Sun, Yang / Wang, Huaitao / Li, Hansi / Zhang, Mingjie / Zhou, Lei / Meng, Xiangli / Wu, Yunhao / Liu, Peng / Liu, Xin / Zhang, Jun / Tan, Xiaodong. ·Department of Pancreatic and Thyroidal Surgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning 110000, P.R. China. · Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital Affiliated to Dalian Medical University, Dalian, Liaoning 116000, P.R. China. · Department of General Surgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning 110000, P.R. China. · Department of Gastroenterology Surgery, Liaoning Provincial Tumor Hospital, Shenyang, Liaoning 110000, P.R. China. · Department of Gastric Surgery, Liaoning Provincial Tumor Hospital, Shenyang, Liaoning 110000, P.R. China. ·Oncol Lett · Pubmed #30546469.

ABSTRACT: Pancreatic cancer is an aggressive type of cancer with a poor prognosis, short survival rate and high mortality. Therefore, understanding the molecular mechanism underlying the aggressive growth of pancreatic cancer is of importance. An increasing number of studies suggest that numerous microRNAs (miRNAs/miRs) are associated with the tumorigenesis, progression and prognosis of tumors. In a recent study by the present authors, it was revealed that the expression of miR-221 was significantly downregulated in highly aggressive pancreatic cancer cells compared with weakly aggressive pancreatic cancer cells. In addition, miR-221 has been suggested as a novel tumor-associated miRNA, as it is involved in apoptosis, invasion, metastasis and autophagy of tumor cells. However, the function of miR-221 in pancreatic cancer remains yet to be investigated. In the present study, it was revealed that transfection with miR-221 mimic was able to significantly induce apoptosis and autophagy in pancreatic cancer cells compared with the negative control. The protein deacetylase histone deacetylase-6 (HDAC6) has emerged to be an important component in the cellular management of protein aggregates. Studies suggest that HDAC6 serves a function in the clearance of aggresomes, thereby implying a functional association between HDAC6 and autophagy. In the present study, it was revealed that transfection with miR-221 mimic was able to suppress the protein expression of HDAC6 in pancreatic cancer cells compared with the negative control. Immunofluorescence data suggested that the inhibition of HDAC6 was able to induce autophagy in pancreatic cancer cells. Additionally, the results of the present study suggest that the downregulation of miR-221 expression may serve an oncogenic function in the apoptosis and autophagy of pancreatic cancer cells by inducing the expression of HDAC6.

12 Article Differential expression profiles of microRNAs in highly and weakly invasive/metastatic pancreatic cancer cells. 2018

Tan, Xiaodong / Zhou, Lei / Wang, Huaitao / Yang, Yifan / Sun, Yang / Wang, Zhaoping / Zhang, Xiaobo / Gao, Feng / Li, Hansi. ·Department of Pancreatic and Thyroidal Surgery, China Medical University Shengjing Hospital, Shenyang, Liaoning 110004, P.R. China. ·Oncol Lett · Pubmed #30333874.

ABSTRACT: Pancreatic cancer is the eighth-leading cause of cancer-associated mortality worldwide. To date, the cellular and molecular mechanisms associated with the invasion and metastasis of pancreatic cancer remain unclear. To examine these mechanisms, a microRNA (miRNA/miR) microarray with 1,965 genes was hybridized with labeled miRNA probes from invasive PC-1.0 and non-invasive PC-1 cells for molecular profiling analysis. In addition, reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was utilized to validate the microarray results. Online miRNA target prediction algorithms online were used to predict the target genes of the differentially expressed miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) term enrichment analysis were performed for the potential targets of the differentially expressed miRNAs. The results demonstrated that 54 miRNAs were differentially expressed, of which 33 were upregulated and 21 were downregulated in the PC-1.0 cell line compared with the PC-1 cell line. A total of 6 upregulated miRNAs (miR-31, -34a, -181a, -181b, -193a-3p, and -193b) and 4 downregulated miRNAs (miR-221, -222, -484, and -502-3p) were selected from these 54 miRNAs and validated by RT-qPCR. The differentially expressed miRNAs were further validated by RT-qPCR in the human pancreatic cancer cell lines AsPC-1 (highly invasive) and CAPAN-2 (less invasive). The results revealed that 2 upregulated miRNAs (miR-34a and -193a-3p) and 4 downregulated miRNAs (miR-221, -222, -484, and -502-3p) exhibited a consistent expression pattern between the PC-1.0/PC-1 and AsPC-1/CAPAN-2 pancreatic cancer cells. The GO and KEGG enrichment analysis indicated that the mRNAs potentially targeted by miRNAs were involved in a range of biological functions. These results suggest that different miRNA expression profiles occur between highly and weakly invasive and metastatic pancreatic cancer cell lines, and may affect a variety of biological functions in pancreatic cancer.

13 Article Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation. 2017

Qu, Kai / Zhang, Xing / Lin, Ting / Liu, Tian / Wang, Zhixin / Liu, Sushun / Zhou, Lei / Wei, Jichao / Chang, Hulin / Li, Ke / Wang, Zheng / Liu, Chang / Wu, Zheng. ·Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. · Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China. · Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, 810001, China. · Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China. · Department of Hepatobiliary Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, 256603, China. · Department of Hepatobiliary Surgery, Qingdao Municipal Hospital, Qingdao, 266011, China. · Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Xi'an, 710068, China. · Department of Central Laboratory, Liaocheng People's Hospital, Liaocheng, 252000, China. · Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. liuchangdoctor@126.com. · Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. wuzheng@126.com. ·Sci Rep · Pubmed #28490741.

ABSTRACT: Pancreatic cancer (PC) is a highly fatal disease worldwide and is often misdiagnosed in its early stages. The exploration of novel non-invasive biomarkers will definitely benefit PC patients. Recently, circulating miRNAs in body fluids are emerging as non-invasive biomarkers for PC diagnosis. In this study, we first conducted comprehensive robust rank aggregation (RRA) analysis based on 21 published miRome profiling studies. We statistically identified and clinically validated a miRNA expression pattern in PC patients. These miRNAs consisted of four up-regulated (hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-210-3p and hsa-miR-155-5p) and three down-regulated miRNAs (hsa-miR-217, hsa-miR-148a-3p and hsa-miR-375). Among them, hsa-miR-21-5p was one of the most highly expressed miRNAs in the serum of PC patients. Our validation test further suggested a relatively high accuracy of serum hsa-miR-21-5p levels in the diagnosis of PC, with a sensitivity of 0.77 and a specificity of 0.80. Finally, a diagnostic meta-analysis based on 9 studies also revealed favorable sensitivity and specificity of circulating hsa-miR-21-5p for the diagnosis of PC (pooled sensitivity and specificity were 0.76 and 0.74, respectively), which was consistent with our findings. Taken together, as one of the most aberrantly expressed miRNAs in PC, circulating hsa-miR-21-5p might be a promising serum biomarker in patients with PC.

14 Article UCA1 Regulates the Growth and Metastasis of Pancreatic Cancer by Sponging miR-135a. 2017

Zhang, Xiaobo / Gao, Feng / Zhou, Lei / Wang, Huaitao / Shi, Gang / Tan, Xiaodong. · ·Oncol Res · Pubmed #28315290.

ABSTRACT: Pancreatic cancer (PC) is a devastating malignant disease with a poor prognosis. This study aimed to investigate the role of urothelial carcinoma associated 1 (UCA1) in the progression of PC. Our results revealed that long noncoding RNA (lncRNA) UCA1 was overexpressed in PC tissues compared with adjacent histologically normal tissues. A downregulated level of UCA1 was also detected in five human PC cell lines (SW1990, BxPC-3, MiaPaCa-2, PANC-1, and CAPAN-1) compared with normal pancreatic duct epithelial HPDE cells. The proliferation of PC cells was inhibited after UCA1 was suppressed by a lentiviral vector. The cell apoptosis rate was largely promoted by downregulating UCA1. Further research revealed that microRNA (miRNA)-135a is a direct target of UCA1. The expression of miR-135a was decreased in PC tissues and cell lines compared with control groups. In addition, the decreased level of miR-135a was elevated by adding miR-135a mimic in SW1990 cells transfected with lncRNA UCA1. Similarly, an upregulated level of miR-135a was downregulated by adding miR-135a inhibitor in SW1990 cells transfected with UCA1 siRNA. Luciferase activity assay further confirmed the targeting relationship between UCA1 and miR-135a. Moreover, miR-135a reversed the effect of UCA1 on cell apoptosis rate and cell viability in SW1990 cells. The migration and invasion capacities of PC cells were suppressed by UCA1. siRNA was then enhanced by the miR-135a inhibitor. In vivo, UCA1 siRNA effectively suppressed tumor growth and the expression of migration markers. Taken together, our research revealed that UCA1 works as an oncogene by targeting miR-135a. The UCA1-miR-135a pathway regulated the growth and metastasis of PC, providing new insight in the treatment of PC.

15 Article Phosphoproteome Analysis of Invasion and Metastasis-Related Factors in Pancreatic Cancer Cells. 2016

Tan, Xiaodong / Liu, Peng / Huang, Yinpeng / Zhou, Lei / Yang, Yifan / Wang, Huaitao / Yu, Boqiang / Meng, Xiangli / Zhang, Xiaobo / Gao, Feng. ·Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P.R.China. ·PLoS One · Pubmed #27014871.

ABSTRACT: Mechanisms of abnormal protein phosphorylation that regulate cell invasion and metastasis in pancreatic cancer remain obscure. In this study, we used high-throughput phosphorylation array to test two pancreatic cancer cell lines (PC-1 cells with a low, and PC-1.0 cells with a high potential for invasion and metastasis). We noted that a total of 57 proteins revealed a differential expression (fold change ≥ 2.0). Six candidate proteins were further validated by western blot with results found to be accordance with the array. Of 57 proteins, 32 up-regulated proteins (e.g. CaMK1-α and P90RSK) were mainly involved in ErbB and neurotrophin signaling pathways as determined using DAVID software, while 25 down-regulated proteins (e.g. BID and BRCA1) were closely involved in apoptosis and p53 signaling pathways. Moreover, four proteins (AKT1, Chk2, p53 and P70S6K) with different phosphorylation sites were found, not only among up-regulated, but also among down-regulated proteins. Importantly, specific phosphorylation sites can affect cell biological functions. CentiScaPe software calculated topological characteristics of each node in the protein-protein interaction (PPI) network: we found that AKT1 owns the maximum node degrees and betweenness in the up-regulation protein PPI network (26 nodes, average path length: 1.89, node degrees: 6.62±4.18, betweenness: 22.23±35.72), and p53 in the down-regulation protein PPI network (17 nodes, average path length: 2.04, node degrees: 3.65±2.47, betweenness: 16.59±29.58). In conclusion, the identification of abnormal protein phosphorylation related to invasion and metastasis may allow us to identify new biomarkers in an effort to develop novel therapeutic drug targets for pancreatic cancer treatment.

16 Article Peptide tyrosine-tyrosine combined with its receptors exhibits an anti-cancer potential in pancreatic cancer MiaPaCa-2 cell. 2014

Li, Hongxia / Wang, Zhixin / Dong, Lei / Jiang, Jiong / Xu, Xinsen / Zhou, Lei / Wan, Yong. ·Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China. Email: diandianliu001@126.com. · Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China. · Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China. ·Chin Med J (Engl) · Pubmed #25533827.

ABSTRACT: BACKGROUND: Pancreatic cancer is a common malignant tumor of the digestive system. It is the fourth major cause of tumor-related death and its morbidity is increasing, and hence it is imperative to develop effective forms of therapy for pancreatic cancer. Peptide tyrosine-tyrosine (PYY) is an important gastrointestinal peptide hormone. According to previous literatures, PYY has been shown to inhibit tumor proliferation in cellular and animal models, but there has been limited research on the detailed mechanism of PYY in pancreatic cancer. This study was to observe the effects of PYY on pancreatic cancer cell and investigate the possible mechanism. METHODS: The expression of Y1, Y2, and Y5 receptors on pancreatic cancer cell lines were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The cytotoxicity of PYY toward the MiaPaCa-2 cell was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the cell morphology and structure changes were observed under inverted microscope and transmission electron microscope respectively. Apoptosis and cell cycle were evaluated by flow cytometry. The activity of caspase-3 was determined by activity assay kits and Western blotting. The expression of survivin, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were determined by RT-qPCR and Western blotting. RESULTS: Expression of Y2 receptor is the most abundant PYY receptor on pancreatic cancer cell. PYY inhibited MiaPaCa-2 cell proliferation, blocked it in G0/G1 phase, increased the proportion of apoptosis cells and caspase-3 activity, and reduced the expression of survivin, VEGF, and COX-2. CONCLUSIONS: PYY weakened the ability of the pancreatic MiaPaCa-2 cell viability through cell cycle blocking and apoptosis inducing. The inhibition effect of PYY may be mediated by the Y2 receptor. The increased caspase-3 activity and reduced expression of survivin, VEGF, and COX-2 may serve as a novel mechanism in PYY inhibition effect on MiaPaCa-2 cell.

17 Article MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells. 2010

Zhou, Lei / Tan, Xiaodong / Kamohara, Hidenobu / Wang, Wei / Wang, Baosheng / Liu, Jingang / Egami, Hiroshi / Baba, Hideo / Dai, Xianwei. ·Department of Hepato-pancreato-biliary Tumour Surgery, China Medical University Shengjing Hospital, Shenyang, PR China. ·Oncol Rep · Pubmed #20514469.

ABSTRACT: The mitogen-activated protein kinase kinase 1/2 (MEK1/2) signalling pathway plays a central role in tumour progression. Small molecules that inhibit MEK1/2 are therefore considered attractive candidates for anti-cancer drugs. However, the exact contributions of MEK1 and MEK2 to the development of pancreatic cancer remain to be established. To differentiate the functions of MEK1 and MEK2 in a cultured pancreatic cancer cell line, we utilised shRNA-mediated knockdown of their two mRNAs individually. We studied the effects of MEK1 and MEK2 knockdown on cell morphology, proliferation, mitotic arrest, and in vitro invasion capability in PC-1.0 cells. The results showed that inhibition of MEK1 expression was an effective and specific approach to inhibit cell proliferation and induce G0/G1 arrest. On the other hand, MEK2 knockdown specially altered cell morphology and inhibited the invasive ability of pancreatic cancer cells. Therefore, MEK1 and MEK2 mediate different biological responses in cultured pancreatic cancer cells. These proteins could become distinct targets for the inhibition of specific cellular functions in the treatment of pancreatic cancer.