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Pancreatic Neoplasms: HELP
Articles by Gangqiang Li
Based on 22 articles published since 2010
(Why 22 articles?)
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Between 2010 and 2020, Gang Li wrote the following 22 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. 2011

Assifi, M Mura / Lu, Xuyang / Eibl, Guido / Reber, Howard A / Li, Gang / Hines, O Joe. ·Department of Surgery, UCLA School of Public Health, Los Angeles, CA, USA. ·Surgery · Pubmed #21878232.

ABSTRACT: BACKGROUND: Neoadjuvant treatment has proven beneficial for many gastrointestinal (GI) malignancies, but no phase III trials have been completed examining this approach in pancreatic cancer. This meta-analysis examines the best available phase II trials using neoadjuvant treatment for resectable and borderline/unresectable pancreatic adenocarcinoma. METHODS: Phase II trials were identified using a MEDLINE search, and the Cochrane Central Register of Controlled Trials from 1960 to July 2010. Patients were divided into 2 groups: Patients with initially resectable tumors (group A), and patients with borderline/unresectable tumors (group B). Primary outcome measures were rate of resection and survival. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. RESULTS: A total of 14 phase II clinical trials including 536 patients were analyzed. After treatment, resectability was 65.8% (95% CI, 55.4-75.6%) compared with 31.6% in group B (95% CI, 14.0-52.5%). A partial response was observed in patients with borderline/unresectable tumors; 31.8 (95% CI, 24.2-39.8%) in group B and 9.5% (95% CI, 2.9-19.4%) in group A (P = .003). Progressive disease was seen in 17.0% (95% CI, 11.9-22.7) of patients in group A versus 21.8% (95% CI, 10.1-36.5%) in group B (P = .006). Median survival in resected patients was 23 months for group A and 22 months for group B. CONCLUSION: Neoadjuvant treatment seems to have some activity in patients with borderline/unresectable pancreatic adenocarcinoma. Nearly one third of tumors initially deemed marginal for operative intervention were able to be ultimately resected after treatment. Until more effective targeted chemotherapeutics are developed, the only group of patients with pancreatic cancer that may benefit from neoadjuvant treatment are those with locally advanced disease.

2 Article Clinicopathological features and prognosis factors for survival in elderly patients with pancreatic neuroendocrine tumor: A STROBE-compliant article. 2019

Li, Gang / Tian, Mao-Lin / Bing, Yun-Tao / Tao, Lian-Yuan / Wang, Hang-Yan / Jiang, Bin / Yuan, Chun-Hui / Xiu, Dian-Rong. ·Department of General Surgery, Peking University Third Hospital, Haidian District, Beijing, People's Republic of China. ·Medicine (Baltimore) · Pubmed #30882623.

ABSTRACT: To investigate the features and prognosis of the elderly patients with pancreatic neuroendocrine tumor (pNET).The patients diagnosed with pNETs between 2004 and 2014 were identified from the Surveillance Epidemiology and End Results database. The ethical approval was waived because the present study was analysis of the data from Surveillance Epidemiology and End Results database.A total of 4608 patients with "one primary only" histologically pNETs were confirmed and 653 were older than 75 years. Cancer-specific survival (CSS) and overall survival (OS) were examined. The elderly patients (≥75 years) have disadvantage in CSS and OS compared with younger cohort. Multivariate logistic regression revealed that the elderly patients have increased poorly differentiated composition, and decreased proportion of Black patients, receipt of surgery, married status, and number of removed lymph node. Multivariate Cox regression analysis demonstrated worse differentiation. Patients of T3-4 and M1 stage were associated with poor CSS, while patients of being female, tumor locating at pancreatic body/tail, receipt of surgery, and being married were associated with better CSS in the elderly patients. Meanwhile, patients with higher histological grade and M1 stage have poor OS, while patients with the characteristics of female, being married, tumor location at pancreatic body/tail and tumor surgery have better OS. Distant metastatic elderly patients underwent primary site surgery had better CSS and OS than the patients without surgery.The elderly patients have increased possibility of poorly differentiated tumor, and decreased proportion of Black patients, surgery of primary site, number of removed lymph node and married status. Worse differentiation and tumor metastasis were independent risk factors for both CSS and OS, while primary tumor located in body/tail of pancreas, female patients, surgery of tumor primary site, and being married were protective factors.

3 Article Incidence of pancreatic cancer is dramatically increased by a high fat, high calorie diet in KrasG12D mice. 2017

Chang, Hui-Hua / Moro, Aune / Takakura, Kazuki / Su, Hsin-Yuan / Mo, Allen / Nakanishi, Masako / Waldron, Richard T / French, Samuel W / Dawson, David W / Hines, O Joe / Li, Gang / Go, Vay Liang W / Sinnett-Smith, James / Pandol, Stephen J / Lugea, Aurelia / Gukovskaya, Anna S / Duff, Michael O / Rosenberg, Daniel W / Rozengurt, Enrique / Eibl, Guido. ·Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. · Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. · Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States of America. · Pancreatic Research Group, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America. · Center for Molecular Oncology, UCONN Health, Farmington, CT, United States of America. · Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, United States of America. · Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States of America. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. · Department of Biostatistics, School of Public Health at UCLA, Los Angeles, CA, United States of America. · Department of Genetics and Genome Sciences, UCONN Health, Farmington, CT, United States of America. ·PLoS One · Pubmed #28886117.

ABSTRACT: Epidemiologic data has linked obesity to a higher risk of pancreatic cancer, but the underlying mechanisms are poorly understood. To allow for detailed mechanistic studies in a relevant model mimicking diet-induced obesity and pancreatic cancer, a high-fat, high-calorie diet (HFCD) was given to P48+/Cre;LSL-KRASG12D (KC) mice carrying a pancreas-specific oncogenic Kras mutation. The mice were randomly allocated to a HFCD or control diet (CD). Cohorts were sacrificed at 3, 6, and 9 months and tissues were harvested for further analysis. Compared to CD-fed mice, HFCD-fed animals gained significantly more weight. Importantly, the cancer incidence was remarkably increased in HFCD-fed KC mice, particularly in male KC mice. In addition, KC mice fed the HFCD showed more extensive inflammation and fibrosis, and more advanced PanIN lesions in the pancreas, compared to age-matched CD-fed animals. Interestingly, we found that the HFCD reduced autophagic flux in PanIN lesions in KC mice. Further, exome sequencing of isolated murine PanIN lesions identified numerous genetic variants unique to the HFCD. These data underscore the role of sustained inflammation and dysregulated autophagy in diet-induced pancreatic cancer development and suggest that diet-induced genetic alterations may contribute to this process. Our findings provide a better understanding of the mechanisms underlying the obesity-cancer link in males and females, and will facilitate the development of interventions targeting obesity-associated pancreatic cancer.

4 Article Bioactivity of a modified human Glucagon-like peptide-1. 2017

Xu, Fangfang / Wang, Kevin Yueju / Wang, Nan / Li, Gangqiang / Liu, Dehu. ·Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China. · Department of Natural Sciences, Northeastern State University, Broken Arrow, Oklahoma, United States of America. ·PLoS One · Pubmed #28152036.

ABSTRACT: Diabetes has become the third largest cause of death in humans worldwide. Therefore, effective treatment for this disease remains a critical issue. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis, and therefore represents a promising candidate to use for the treatment of diabetes. Native GLP-1, however, is quickly degraded in in the circulatory system; which limits its clinical application. In the present study, a chemically-synthesized, modified analogue of human GLP-1 (mGLP-1) was designed. Our analyses indicated that, relative to native GLP-1, mGLP-1 is more resistant to trypsin and pancreatin degradation. mGLP-1 promotes mouse pancreatic β-cell proliferation by up-regulating the expression level of cyclin E, CDK2, Bcl-2 and down-regulating Bax, p21, and stimulates insulin secretion. An oral glucose tolerance test indicated that mGLP-1 significantly improved glucose tolerance in mice. Intraperitoneal injections of mGLP-1 into streptozotocin (STZ)-induced type 2 diabetic mice significantly reduced blood sugar levels and stimulated insulin secretion. Oral gavages of mGLP-1 in diabetic mice did not result in significant hypoglycemic activity.

5 Article Preoperative neutrophil-to-lymphocyte ratio and tumor-related factors to predict lymph node metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). 2016

Tao, Lianyuan / Zhang, Lingfu / Peng, Ying / Tao, Ming / Li, Gang / Xiu, Dianrong / Yuan, Chunhui / Ma, Chaolai / Jiang, Bin. ·Department of General Surgery, Peking University Third Hospital, Beijing, China. ·Oncotarget · Pubmed #27494847.

ABSTRACT: As a poor prognosis indicator in patients with pancreatic ductal adenocarcinoma (PDCA), lymph node (LN) metastasis is of great importance in treatment. Present study was performed to evaluate the predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and possible clinical parameters on the LN metastasis in PDCA patients. A total of 159 operable patients with PDCA were enrolled in our study. The clinical utility of NLR and other clinical parameters was evaluated by receiver operating characteristic (ROC) curves. Overall survival analysis indicated that LN metastasis is an independent prognostic factor. The logistic analysis was used to determine the independent parameters associated with LN metastasis. Ideal cutoff values for predicting LN metastasis are 2.12 for NLR and 130.96 for PLR according to the ROC curve. Multivariate analyses indicate that NLR (HR 2.588; 95% CI 1.246-5.376; P = 0.011), CA125 (HR 6.348; 95% CI 2.056-19.594; P = 0.001) and CA19-9 (HR 2.738; 95% CI 1.151-6.515; P = 0.023) are associated significantly with LN metastasis independently. Preoperative NLR, CA125 and CA19-9 are useful biomarkers for the prediction of LN metastasis in PDCA patients.

6 Article Robust Early Inflammation of the Peripancreatic Visceral Adipose Tissue During Diet-Induced Obesity in the KrasG12D Model of Pancreatic Cancer. 2016

Hertzer, Kathleen M / Xu, Mu / Moro, Aune / Dawson, David W / Du, Lin / Li, Gang / Chang, Hui-Hua / Stark, Alexander P / Jung, Xiaoman / Hines, Oscar Joe / Eibl, Guido. ·From the Departments of *Surgery and †Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA, Los Angeles, CA; and ‡Department of Biostatistics, Fielding School of Public Health at UCLA, Los Angeles, CA. ·Pancreas · Pubmed #26495779.

ABSTRACT: OBJECTIVES: Obesity increases the incidence of multiple types of cancer. Our previous work has shown that a high-fat, high-calorie diet (HFCD) leads to visceral obesity, pancreatic inflammation, and accelerated pancreatic neoplasia in KrasG12D (KC) mice. In this study, we aimed to investigate the effects of an HFCD on visceral adipose inflammation with emphasis on potential differences between distinct visceral adipose depots. METHODS: We examined the weight and visceral obesity in both wild-type and KC mice on either control diet (CD) or HFCD. After 3 months, mice were killed for histological examination. Multiplex assays were also performed to obtain cytokine profiles between different adipose depots. RESULTS: Both wild-type and KC mice on an HFCD exhibited significantly increased inflammation in the visceral adipose tissue, particularly in the peripancreatic fat (PPF), compared with animals on a CD. This was associated with significantly increased inflammation in the pancreas. Cytokine profiles were different between visceral adipose depots and between mice on the HFCD and CD. CONCLUSIONS: Our results clearly demonstrate that an HFCD leads to obesity and inflammation in the visceral adipose tissue, particularly the PPF. These data suggest that obesity-associated inflammation in PPF may accelerate pancreatic neoplasia in KC mice.

7 Article Interplay between menin and Dnmt1 reversibly regulates pancreatic cancer cell growth downstream of the Hedgehog signaling pathway. 2016

Cheng, Peng / Wang, Yun-Feng / Li, Gang / Yang, Sheng-sheng / Liu, Che / Hu, Hao / Jin, Gang / Hu, Xian-Gui. ·Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. · Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. · Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai 200433, China. · Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: jingangjg@126.com. ·Cancer Lett · Pubmed #26454216.

ABSTRACT: Menin, the product of the Men1 gene, which is frequently mutated in pancreatic neuroendocrine tumors, acts as a chromatin-remodeling factor to modulate the transcription of cell cycle regulators by interacting with histone modification factors. However, the function of menin and its underlying mechanisms in pancreatic ductal adenocarcinoma remain unknown. Here, we found that menin inhibited pancreatic cancer cell growth in vitro and in vivo and that its expression was gradually lost during pancreatic carcinogenesis. Menin overexpression significantly activated the expression of the cyclin-dependent kinase (CDK) inhibitors p18 and p27, accompanied with a decrease in DNA methylation levels of p18 and p27 promoters. Mechanistically, we found that interaction of menin with DNA methyltransferase 1 (Dnmt1) competitively pulled down Dnmt1 from p18 and p27 promoters, leading to the downregulation of DNA methylation levels. Moreover, menin expression was suppressed by Dnmt1 downstream of the Hedgehog signaling pathway, and menin overexpression strongly antagonized the promotion effect of hedgehog signaling on pancreatic cancer cell proliferation. Taken together, the interaction between menin and Dnmt1 reversibly regulates pancreatic cancer cell growth downstream of Hedgehog pathways with complex mutual modulation networks, suggesting that the Hedgehog/Dnmt1/menin axis is a potential molecular target for pancreatic cancer therapy.

8 Article Downregulation of ASPP2 in pancreatic cancer cells contributes to increased resistance to gemcitabine through autophagy activation. 2015

Song, Bin / Bian, Qi / Zhang, Yi-Jie / Shao, Cheng-Hao / Li, Gang / Liu, An-An / Jing, Wei / Liu, Rui / Zhou, Ying-Qi / Jin, Gang / Hu, Xian-Gui. ·Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. smmusb@126.com. · Department of Nephrology, Changhai Hospital, Second Military Medical University, Changhai Road No.168, Shanghai, China. angelbq@126.com. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. yijie06@medmail.com.cn. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. schhao88@gmail.com. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. li_gang169@163.com. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. laa2001@163.com. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. jingwei7777@163.com. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. liuruichanghai@163.com. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. yingqizhou@163.com. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. jingang@sohu.com. · Department of Nephrology, Changhai Hospital, Second Military Medical University, Changhai Road No.168, Shanghai, China. jingang@sohu.com. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. xianguihu@163.com. · Department of Nephrology, Changhai Hospital, Second Military Medical University, Changhai Road No.168, Shanghai, China. xianguihu@163.com. ·Mol Cancer · Pubmed #26438046.

ABSTRACT: BACKGROUND: Apoptosis-stimulating of p53 protein 2 (ASPP2) is one of the ASPP family members and it has been reported to be associated with human cancer. However, the role of it in pancreatic cancer is still not clear. METHODS: We analyzed the expression level of ASPP2 in cancer tissue samples with RT-qPCR, Western Blotting assay and immunohistochemistry staining. We studied the biological function of ASPP2 and its mechanism with gene overexpression and gene silencing technologies. We determined the sensitivity of pancreatic cells with differential ASPP2 level to gemcitabine and whether autophagy inhibition affected the gemcitabine resistance, both in vitro and in vivo. RESULTS: Expression of ASPP2 was downregulated in cancerous tissues in comparison with para-cancerous tissues. ASPP2 expression was linked to clinical outcomes in patients and down-regulation of ASPP2 increased cell proliferation, autophagic flux, the activity of AMP Kinase of pancreatic cancer cells and vice versa. Knockdown of ASPP2 results in increased resistance to gemcitabine, which was attributed to the enhanced autophagy. CONCLUSIONS: ASSP2 expression is lower in cancerous tissues and decreased ASPP2 lead to higher cancer cells proliferation and autophagic flux, which contribute to the gemcitabine resistance.

9 Article Alternative splicing of NUMB, APP and VEGFA as the features of pancreatic ductal carcinoma. 2015

Zheng, Kai-Lian / He, Tian-Lin / Ji, Wei-Ping / Jiang, Hui / Shen, Ye / Li, Gang / Zhu, Si-Bo / Tong, Bing-Lei / Zhang, Yi-Jie. ·Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University Shanghai 200433, China. · R & D Department of Cinoasia Institute Shanghai 200437, China. · Department of General Surgery, Ao Young Hospital Suzhou 215617, China. ·Int J Clin Exp Pathol · Pubmed #26261495.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most common form of malignancy in pancreatic carcinoma. Here we report our discovery on the correlations between transcriptional alternative splicing (AS) of NUMB, APP, VEGFA and PDAC in patients. METHODS: The expression of NUMB, APP, VEGFA from patient samples was determined by qRT-PCR. AS of these genes was examined through laser induced fluorescence capillary electrophoresis. Correlation between the AS of the genes and results from clinical laboratory examinations were analyzed. Expression of NOTHC1 and NOTCH4 as downstream target genes was examined by qRT-PCR and Western blot. RESULTS: Quantitative results indicated that expression of NUMB was significantly lower in tumor tissues (TT) than in para-tumor tissues (TP) (P<0.05), while APP (P<0.01) and VEGFA (P<0.05) were significantly higher. AS transcript percentage of NUMB PRR(S) was lower in TT than TP (P<0.05). AS transcript percentage of VEGFA (105+185) was significantly lower in TT than TP (P<0.05) compared to higher expression of VEGFA (206+338) (P<0.05). Regression analysis indicated that AS transcript of NUMB PRR(L) correlated with tumor size (P<0.01), while AS transcripts of APP and VEGFA correlated with results of laboratory examinations. To reveal the correlation between AS and its downstream targets, NOTCH1 and NOTCH4 were selected as NUMB gene targets and detected to be significantly higher in TT than TP (P<0.05). CONCLUSION: Alternative splicing of APP, VEGFA and NUMB may play an important role in pathogenesis of pancreatic ductal adenocarcinoma. Among the 3 genes, PRR(L) form of NUMB gene is highly expressed in TT and positively correlated with tumor size, while PRR(S) is lacking in TT and negatively correlated with NOTCH expression suggesting that PRR(S) might be protective in tumorogenesis and shows NOTCH pathway down regulation ability.

10 Article miR-429 determines poor outcome and inhibits pancreatic ductal adenocarcinoma growth by targeting TBK1. 2015

Song, Bin / Zheng, Kailian / Ma, Hongyun / Liu, Anan / Jing, Wei / Shao, Chenghao / Li, Gang / Jin, Gang. ·Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. ·Cell Physiol Biochem · Pubmed #25833382.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) ranks fourth on the list of cancer-related causes of death and its prognosis has not improved significantly over the past decades. Deregulation or dysfunction of miRNAs contribute to cancer development. Previous data indicates that miR-429 is involved in the pathogenesis of PDAC. However, the role of miR-429 in PDAC remained unknown. METHODS: MiR-429 levels in sample tissues of 78 patients and in PANC1 and SW1990 cell lines were quantified by real-time PCR. MiR-429 expression was modulated using specific pre- and anti-miRNAs and cell growth was assayed by MTT analysis. Bioinformatics prediction of the miR-429 putative target genes was performed and luciferase assays confirmed TBK1 as a direct target gene. TBK1 levels in PDAC tissues were analyzed by immunohistochemistry. RESULTS: MiR-429 was remarkably decreased in PDAC tissues and cell lines. Lower miR-429 expression in PDAC tissues significantly correlated with shorter survival of PDAC patients. Overexpression of miR-429 inhibited PDAC cell lines growth in vitro and vice versa. TBK1 was found to be the direct target gene of miR-429. Higher TBK1 protein level in PDAC tissues correlated with shorter survival of PDAC patients. Overexpression of TBK1 partly restored cell proliferation. CONCLUSIONS: Low level of miR-429 and high level of TBK1 in PDAC promoted PDAC cells growth which might be related to the low survival rate of PDAC patients. MiR-429 play its role in PDAC by targeting TBK1.

11 Article MiR-940 inhibited pancreatic ductal adenocarcinoma growth by targeting MyD88. 2015

Song, Bin / Zhang, Chaoxiong / Li, Gang / Jin, Gang / Liu, Cong. ·Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. ·Cell Physiol Biochem · Pubmed #25766528.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an almost universally lethal disease. Deregulation or dysfunction of miRNAs contribute to cancer development. The role of miR-940 in PDAC remains unclear. METHODS: The level of miR-940 in PDAC tissues and cell lines was measured by qRT-PCR. MiR-940 was over-expressed by miRNAs mimics transfection and reduced by miRNAs antisense oligonucleotides (ASO) transfection. Cell proliferation was analyzed by MTT assay and cell apoptosis was evaluated by FACS analysis. Targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Myeloid differentiation primary response gene (88) (MyD88) protein level was assayed by immunohistochemistry and Western blot analysis. RESULTS: Low miR-940 level and high MyD88 protein level in PDAC tissues were both correlated with low survival rate. Up-regulation of miR-940 inhibited PDAC cell lines growth while down-regulation induced cell growth. The 3' UTR of MyD88 was targeted by miR-940. CONCLUSIONS: Low level of miR-940 and high level of MyD88 in PDAC promoted PDAC cells growth which might be related to the low survival rate of PDAC patients. MiR-940 exerted its effect by targeting MyD88.

12 Article miR-545 inhibited pancreatic ductal adenocarcinoma growth by targeting RIG-I. 2014

Song, Bin / Ji, Weiping / Guo, Shiwei / Liu, Anan / Jing, Wei / Shao, Chenghao / Li, Gang / Jin, Gang. ·Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. · Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: li_gang169@163.com. · Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: jingangjinggang@126.com. ·FEBS Lett · Pubmed #25315416.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) ranks fourth on the list of cancer-related causes of death. Deregulation or dysfunction of miRNAs contribute to cancer development. In this study, we found that low miR-545 level and high RIG-I protein in PDAC tissues were both correlated with low survival rate. MiR-545 up-regulation inhibited PDAC cell lines growth and vice versa. 3'UTR of RIG-I was targeted by miR-545. Thus we concluded that low miR-545 levels in PDAC promote tumor cells growth, and this is associated with reduced survival in PDAC patients. MiR-545 exerts its effects by directly targeting RIG-1.

13 Article The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma. 2014

Liu, Chen / Karam, Rachid / Zhou, YingQi / Su, Fang / Ji, Yuan / Li, Gang / Xu, GuoTong / Lu, LiXia / Wang, ChongRen / Song, MeiYi / Zhu, JingPing / Wang, YiRan / Zhao, YiFan / Foo, Wai Chin / Zuo, MingXin / Valasek, Mark A / Javle, Milind / Wilkinson, Miles F / Lu, YanJun. ·1] Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. [2] Tongji University School of Life Science and Technology, Shanghai, China. [3]. · 1] Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, California, USA. [2]. · 1] The Third General Surgery Department, Changhai Hospital, Second Military Medical University, Shanghai, China. [2]. · 1] Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. [2]. · 1] Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China. [2]. · The Third General Surgery Department, Changhai Hospital, Second Military Medical University, Shanghai, China. · Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Division of Anatomic Pathology, Department of Pathology, University of California San Diego, San Diego, California, USA. · 1] Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, California, USA. [2] Institute for Genomic Medicine, University of California San Diego, La Jolla, California, USA. ·Nat Med · Pubmed #24859531.

ABSTRACT: Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC.

14 Article Ellagic acid and embelin affect key cellular components of pancreatic adenocarcinoma, cancer, and stellate cells. 2013

Edderkaoui, Mouad / Lugea, Aurelia / Hui, Hongxiang / Eibl, Guido / Lu, Qing-Yi / Moro, Aune / Lu, Xuyang / Li, Gang / Go, Vay-Liang / Pandol, Stephen J. ·a Veterans Affairs Greater Los Angeles Healthcare System , Los Angeles , California , USA. ·Nutr Cancer · Pubmed #24127740.

ABSTRACT: Ellagic acid is a polyphenolic phytochemical present in many fruits and nuts with anticancer properties demonstrated in experimental tumor studies. Embelin is a benzoquinone phytochemical isolated from the Japanese herb Ardisiae Japonicae and has been shown to induce apoptosis in cancer cells. We found that ellagic acid and embelin each dose-dependently increased apoptosis and inhibited proliferation in human pancreatic cancer cells, MIA PaCa-2 and HPAF-II cells, and in pancreatic stellate cells, which are progenitors of pancreatic cancer desmoplasia. In each of these cell types, combinations of ellagic acid and embelin at low micromolar concentrations (0.5-3 μM) induced synergistic increases in apoptosis and decreases in proliferation. Ellagic acid decreased NF-κB transcriptional activity, whereas embelin decreased STAT-3 phosphorylation and protein expression of its downstream target survivin in cancer cells. In vivo dietary ellagic acid alone or in combination with embelin decreased tumor size and tumor cellularity in a subcutaneous xenograft mouse model of pancreatic cancer. These results show that ellagic acid and embelin interact with divergent intracellular signaling pathways resulting in augmentation of apoptosis and inhibition of proliferation at low micromolar concentrations for the key cellular components of pancreatic adenocarcinoma.

15 Article High-fat, high-calorie diet promotes early pancreatic neoplasia in the conditional KrasG12D mouse model. 2013

Dawson, David W / Hertzer, Kathleen / Moro, Aune / Donald, Graham / Chang, Hui-Hua / Go, Vay Liang / Pandol, Steven J / Lugea, Aurelia / Gukovskaya, Anna S / Li, Gang / Hines, Oscar J / Rozengurt, Enrique / Eibl, Guido. ·Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, 10833 LeConte Avenue, 72-236 CHS, Los Angeles, CA 90095. Geibl@mednet.ucla.edu. ·Cancer Prev Res (Phila) · Pubmed #23943783.

ABSTRACT: There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of the present study was to develop a model of diet-induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, for example, weight gain and metabolic disturbances. Offspring of Pdx-1-Cre and LSL-KrasG12D mice were allocated to either a high-fat, high-calorie diet (HFCD; ∼4,535 kcal/kg; 40% of calories from fats) or control diet (∼3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared with control animals, mice fed with the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of insulin-like growth factor I (IGF-I). The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T cells), elevated levels of several cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results show that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KrasG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity, as well as to evaluate dietary- and chemopreventive strategies targeting obesity-associated pancreatic cancer development.

16 Article The clinical efficacy and safety of modified Miwa's augmented regional pancreatoduodenectomy in the treatment of ductal adenocarcinoma of the pancreas in the uncinate process. 2013

Jing, Wei / He, Tianlin / Hu, Xiangui / Jin, Gang / Shao, Chenghao / Li, Gang / Song, Bin / Zhang, Yijie. ·Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. ·Hepatogastroenterology · Pubmed #23241422.

ABSTRACT: BACKGROUND/AIMS: En bloc resection of a tumor located in the uncinate process of the pancreas is a challenging problem. The aim of this study was to analyze outcomes of modified Miwa's augmented regional pancreatoduodenectomy for patients with pancreatic cancer in the uncinate process involving the root of the mesentery. METHODOLOGY: We analyzed by summarizing the 48 cases of ductal adenocarcinoma in the uncinate process of the pancreas during January 2004 to December 2010 with Miwa's augmented regional pancreatoduodenectomy in our hospital and examined the clinical effect and safety of this procedure. RESULTS: We performed extended pancreaticoduodenectomy combined with isolation of full-length superior mesentery artery (SMA) for 48 patients. Sixteen of the forty-eight patients were combined with PV/SMV resection and reconstruction. There was no operative death and 20 cases developed complications, including mild to severe diarrhea in 17 cases. During follow-up survey among all patients of 6 to 45 months (median 20 months), 9 died of liver metastasis, 10 died of local recurrence, and 5 died of non-tumor causes. The 1-, 2- and 3-year accumulated survival rates were 69.1%, 35.1% and 20.2%, respectively. CONCLUSIONS: Full-length SMA isolation and involved mesentery resection with extended pancreaticoduodenectomy is safe and effective.

17 Article The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo. 2013

Angst, Eliane / Park, Jenny L / Moro, Aune / Lu, Qing-Yi / Lu, Xuyang / Li, Gang / King, Jonathan / Chen, Monica / Reber, Howard A / Go, Vay Liang W / Eibl, Guido / Hines, Oscar J. ·Department of Surgery, Hirshberg Laboratories for Pancreatic Cancer Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. ·Pancreas · Pubmed #23000892.

ABSTRACT: OBJECTIVES: The flavonoid quercetin holds promise as an antitumor agent in several preclinical animal models. However, the efficacy of oral administration of quercetin in a pancreatic cancer mouse model is unknown. METHODS: The antiproliferative effects of quercetin alone or in combination with gemcitabine were tested in 2 human pancreatic cancer cell lines using cell count and MTT assays. Apoptosis was evaluated by flow cytometry. Tumor growth in vivo was investigated in an orthotopic pancreatic cancer animal model using bioluminescence. Quercetin was administered orally in the diet. RESULTS: Quercetin inhibited the growth of pancreatic cancer cell lines, which was caused by an induction of apoptosis. In addition, dietary supplementation of quercetin attenuated the growth of orthotopically transplanted pancreatic xenografts. The combination of gemcitabine and quercetin had no additional effect compared with quercetin alone. In vivo quercetin caused significant apoptosis and reduced tumor cell proliferation. CONCLUSIONS: Our data provide evidence that oral administration of quercetin was capable of inhibiting growth of orthotopic pancreatic tumors in a nude mouse model. These data suggest a possible benefit of quercetin in patients with pancreatic cancer.

18 Article Reduced levels of p15INK4b, p16INK4a, p21cip1 and p27kip1 in pancreatic carcinoma. 2012

Li, Gang / Ji, Yuan / Liu, Chen / Li, JingQi / Zhou, YingQi. ·The Third General Surgery Department, Zhanghai Hospital, Second Military Medical University, Shanghai, PR China. ·Mol Med Rep · Pubmed #22293850.

ABSTRACT: Pancreatic carcinoma is one of the leading causes of cancer mortality worldwide, although the molecular mechanisms of this disease are poorly understood. The aim of this study was to examine the expression of cyclin-dependent kinase inhibitors (CDKIs) and the epigenetic modifications in the promoters of these genes. We also evaluated the correlation between the methylation status of CDKI genes and smoking habit in clinical pancreatic carcinoma specimens. Western blotting and real-time PCR were performed to assess CDKI expression. Methylation-specific PCR was carried out to examine the methylation status of the promoters of CDKI genes. In this study, we revealed that reduced levels of the CDKI proteins, p15INK4b, p16INK4a, p21cip1 and p27kip1, are a prominent feature of pancreatic carcinoma patients. The DNA hypermethylation of the promoter was observed in 40% (2 of 5) of the p15INK4b genes, 60% (3 of 5) of the p16INK4a genes and 60% of the p21cip1 genes, which markedly correlated with their decreased mRNA expression. No hypermethylation was detected in the p27kip1 gene promoter in 5 pancreatic carcinoma patients with markedly decreased expression of p27kip1 mRNA, suggesting an alternative mechanism of p27kip in these patients. In this study, patients with a smoking habit displayed methylation of 2 CDKI genes in their pancreatic carcinoma specimens. We concluded that epigenetic modification via hypermethylation represents a critical mechanism for the inactivation of CDKI genes in pancreatic carcinoma.

19 Article Evidence for activation of mutated p53 by apigenin in human pancreatic cancer. 2012

King, Jonathan C / Lu, Qing-Yi / Li, Gang / Moro, Aune / Takahashi, Hiroki / Chen, Monica / Go, Vay Liang W / Reber, Howard A / Eibl, Guido / Hines, O Joe. ·Department of Surgery, David Geffen School of Medicine at UCLA, 72-107 CHS, 10833 LeConte Ave, Los Angeles, CA 90095, USA. ·Biochim Biophys Acta · Pubmed #22227579.

ABSTRACT: Pancreatic cancer is an exceedingly lethal disease with a five-year survival that ranks among the lowest of gastrointestinal malignancies. Part of its lethality is attributable to a generally poor response to existing chemotherapeutic regimens. New therapeutic approaches are urgently needed. We aimed to elucidate the anti-neoplastic mechanisms of apigenin-an abundant, naturally-occurring plant flavonoid-with a particular focus on p53 function. Pancreatic cancer cells (BxPC-3, MiaPaCa-2) experienced dose and time-dependent growth inhibition and increased apoptosis with apigenin treatment. p53 post-translational modification, nuclear translocation, DNA binding, and upregulation of p21 and PUMA were all enhanced by apigenin treatment despite mutated p53 in both cell lines. Transcription-dependent p53 activity was reversed by pifithrin-α, a specific DNA binding inhibitor of p53, but not growth inhibition or apoptosis suggesting transcription-independent p53 activity. This was supported by immunoprecipitation assays which demonstrated disassociation of p53/BclXL and PUMA/BclXL and formation of complexes with Bak followed by cytochrome c release. Treated animals grew smaller tumors with increased cellular apoptosis than those fed control diet. These results suggest that despite deactivating mutation, p53 retains some of its function which is augmented following treatment with apigenin. Cell cycle arrest and apoptosis induction may be mediated by transcription-independent p53 function via interactions with BclXL and PUMA. Further study of flavonoids as chemotherapeutics is warranted.

20 Article Fluorescence in situ hybridization and K-ras analyses improve diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses. 2011

Reicher, Sofiya / Boyar, Fatih Z / Albitar, Maher / Sulcova, Vladimira / Agersborg, Sally / Nga, Visal / Zhou, Ying / Li, Gang / Venegas, Rose / French, Samuel W / Chung, David S / Stabile, Bruce E / Eysselein, Viktor E / Anguiano, Arturo. ·Division of Gastroenterology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA. sreicher@sbcglobal.net ·Pancreas · Pubmed #21705950.

ABSTRACT: OBJECTIVES: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is the main diagnostic modality for pancreatic mass lesions. However, cytology is often indeterminate, leading to repeat FNAs and delay in care. Here, we evaluate whether combining routine cytology with fluorescence in situ hybridization (FISH) and K-ras/p53 analyses improves diagnostic yield of pancreatic EUS-FNA. METHODS: Fifty EUS-FNAs of pancreatic masses in 46 patients were retrospectively analyzed. Mean follow-up was 68 months. Thirteen initial cytologic samples (26%) were benign, 23 malignant (46%), and 14 atypical (28%). We performed FISH for p16, p53, LPL, c-Myc, MALT1, topoisomerase 2/human epidermal growth factor receptor 2, and EGFR, as well as K-ras/p53 mutational analyses. RESULTS: On final diagnosis, 11 (79%) of atypical FNAs were malignant, and 3 benign (21%). Fluorescence in situ hybridization was negative in all benign and all atypical samples with final benign diagnosis. Fluorescence in situ hybridization plus K-ras analysis correctly identified 60% of atypical FNAs with final malignant diagnosis. Combination of routine cytology with positive FISH and K-ras analyses yielded 87.9% sensitivity, 93.8% specificity, 96.7% positive predictive value, 78.9% negative predictive value, and 89.8% accuracy. CONCLUSIONS: Combining routine cytology with FISH and K-ras analyses improves diagnostic yield of EUS-FNA of solid pancreatic masses. We propose to include these ancillary tests in the workup of atypical cytology from pancreatic EUS-FNA.

21 Article Overexpression of CXCL5 is associated with poor survival in patients with pancreatic cancer. 2011

Li, Aihua / King, Jonathan / Moro, Aune / Sugi, Mark D / Dawson, David W / Kaplan, Jeffrey / Li, Gang / Lu, Xuyang / Strieter, Robert M / Burdick, Marie / Go, Vay Liang W / Reber, Howard A / Eibl, Guido / Hines, O Joe. ·Department of Surgery, Hirshberg Laboratories for Pancreatic Cancer Research, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-6904, USA. ·Am J Pathol · Pubmed #21356384.

ABSTRACT: Epithelial neutrophil-activating peptide-78 (CXCL5), a member of the CXC chemokine family, has been shown to be involved in angiogenesis, tumor growth, and metastasis. The objective of this study was to determine the relationship between CXCL5 expression and tumor progression in human pancreatic cancer and to elucidate the mechanism underlying CXCL5-mediated tumor angiogenesis and cancer growth. We report herein that CXCL5 is overexpressed in human pancreatic cancer compared with paired normal pancreas tissue. Overexpression of CXCL5 is significantly correlated with poorer tumor differentiation, advanced clinical stage, and shorter patient survival. Patients with pancreatic cancer and CXCL5 overexpression who underwent resection of cancer had a mean survival time 25.5 months shorter than that of patients who did not overexpress CXCL5. Blockade of CXCL5 or its receptor CXCR2 by small-interfering RNA knockdown or antibody neutralization attenuated human pancreatic cancer growth in a nude mouse model. Finally, we demonstrated that CXCL5 mediates pancreatic cancer-derived angiogenesis through activation of several signaling pathways, including protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and signal transducer and activator of transcription (STAT) in human endothelial cells. These data suggest that CXCL5 is an important mediator of tumor-derived angiogenesis and that it may serve as a survival factor for pancreatic cancer. Blockade of either CXCL5 or CXCR2 may be a critical adjunct antiangiogenic therapy against pancreatic cancer.

22 Article Incidence of pancreatic cancer in chinese patients with chronic pancreatitis. 2011

Wang, Wei / Liao, Zhuan / Li, Gang / Li, Zhao-Shen / Chen, Jie / Zhan, Xian-Bao / Wang, Luo-Wei / Liu, Feng / Hu, Liang-Hao / Guo, Yan / Zou, Duo-Wu / Jin, Zhen-Dong. ·Chronic Pancreatic Study Group, Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China. ·Pancreatology · Pubmed #21311209.

ABSTRACT: BACKGROUND AND AIM: It is suggested that patients with chronic pancreatitis (CP) have a markedly increased risk of pancreatic cancer compared with the general population. This study was designed to determine the rate of pancreatic cancer in CP patients in China. METHODS: This was a semiprospective, single-center study including 420 consecutive CP patients (285 males and 135 females, median age at onset 39.5 years), with the median follow-up time being 102.3 months (range 24-419 months). We calculated the standardized incidence ratio (SIR) based on the pancreatic cancer incidence in the general population of China. RESULTS: Four cases of pancreatic cancer (0.9% of patients) were observed in 3,591 patient-years (expected number of cases 0.15; SIR 27.2, 95% CI 7.4-69.6). Similar results were seen in alcoholics and non-alcoholics, and in smokers and non-smokers. When patients lost to follow-up were considered to be followed up until the end point without having developed pancreatic cancer (4,280 patient-years), SIR was 22.8 (CI 6.2-58.4). Based on the Cox model, with inserting factors being sex, age at the time of CP clinical onset, type of pancreatitis, and presence or absence of diabetes, calcification, alcohol use and smoking status, only age was found to correlate positively with the occurrence of pancreatic cancer (>50 years, hazard ratio, 1.8 ± 0.5; p = 0.044). CONCLUSION: The risk of pancreatic cancer is markedly increased in CP patients in China compared with the general population, especially in older patients. and IAP.