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Pancreatic Neoplasms: HELP
Articles by Yu Zhang
Based on 28 articles published since 2010
(Why 28 articles?)
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Between 2010 and 2020, Yu Zhang wrote the following 28 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review TGF-β in pancreatic cancer initiation and progression: two sides of the same coin. 2017

Shen, Wei / Tao, Guo-Qing / Zhang, Yu / Cai, Bing / Sun, Jian / Tian, Zhi-Qiang. ·Department of General Surgery, Wuxi People's Hospital Affiliated Nanjing Medical University, 299 Qingyang Road, Wuxi, 214000 Jiangsu China. · 0000 0004 1775 8598 · grid.460176.2 ·Cell Biosci · Pubmed #28794854.

ABSTRACT: Pancreatic cancer is highly lethal malignant tumor with characterised rapid progression, invasiveness and resistance to radiochemotherapy. Transforming growth factor-β (TGF-β) signaling plays a dual role in both pro-tumorigenic and tumor suppressive of pancreatic cancer, depending on tumor stage and microenvironment. TGF-β signaling components alteration are common in pancreatic cancer, and its leading role in tumor formation and metastases has received increased attention. Many therapies have investigated to target TGF-β signaling in the preclinical and clinical setting. In this review, we highlight the dual roles of TGF-β and touch upon the perspectives on therapeutic target of TGF-β signaling in pancreatic cancer.

2 Clinical Trial Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer. 2010

Zhao, Hong / Yang, Guowang / Wang, Daoyuan / Yu, Xiangrong / Zhang, Yu / Zhu, Junqiu / Ji, Yongle / Zhong, Baoliang / Zhao, Wenshuo / Yang, Zhong / Aziz, Fahad. ·Clinical HIFU Therapy Center, Huadong Hospital affiliated to Fudan University, No. 221 West Yan'an Road, Shanghai, People's Republic of China. drhong.zhao.md@gmail.com ·Anticancer Drugs · Pubmed #20075714.

ABSTRACT: This phase II trial was conducted to evaluate the safety and efficacy of concurrent gemcitabine and high-intensity focused ultrasound (HIFU) therapy in patients with locally advanced pancreatic cancer. Patients with localized unresectable pancreatic adenocarcinoma in the head or body of the pancreas received gemcitabine (1000 mg/m) intravenously over 30 min on days 1, 8, and 15, and concurrent HIFU therapy on days 1, 3, and 5. The treatment was given every 28 days. Thirty-seven (94.9%) of the 39 patients were assessable for response, and two cases of complete response and 15 cases of partial response were confirmed, giving an overall response rate of 43.6% [95% confidence interval (CI), 28.0-59.2%]. The median follow-up period was 16.5 months (range: 8.0-28.5 months). The median time to progression and overall survival for all patients were 8.4 months (95% CI, 5.4-11.2 months) and 12.6 months (95% CI, 10.2-15.0 months), respectively. The estimates of overall survival at 12 and 24 months were 50.6% (95% CI, 36.7-64.5%) and 17.1% (95%CI, 5.9-28.3%), respectively. A total of 16.2% of patients experienced grade 3/4 neutropenia. Grade 3 thrombocytopaenia was documented in two (5.4%) patients. Grade 3 nausea/vomiting and diarrhea were observed in three (8.1%), and two (5.4%) patients, respectively. Grade 1 or 2 fever was detected in 70.3% of patients. Twenty-eight patients (71.8%) complained of abdominal pain consistent with tumor-related pain before HIFU therapy. Pain was relieved in 22 patients (78.6%). In conclusion, concurrent gemcitabine and HIFU is a tolerated treatment modality with promising activity in patients with previously untreated locally advanced pancreatic cancer.

3 Article Stress-induced phosphoprotein 1 promotes pancreatic cancer progression through activation of the FAK/AKT/MMP signaling axis. 2019

Jing, Yuanming / Liang, Wenqing / Liu, Jian / Zhang, Lin / Wei, Jianguo / Zhu, Yafang / Yang, Jianhui / Ji, Kewei / Zhang, Yu / Huang, Zongliang. ·Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, PR China. · Department of Orthopaedics, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, PR China. · Department of Hepatobiliary Surgery, Shanghai Oriental Hepatobiliary Hospital, Shanghai 200438, PR China. · Department of Endoscopy Center, Affiliated Hospital of Shaoxing College of Arts and Sciences (Shaoxing Municipal Hospital), Shaoxing 312000, Zhejiang Province, PR China. · Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China. Electronic address: zonglianghuang@tongji.edu.cn. ·Pathol Res Pract · Pubmed #31547977.

ABSTRACT: BACKGROUND: Dependent on the extent of adenosine triphosphate (ATP) hydrolysis and/or ATP/ADP exchange, the stress-induced phosphoprotein 1 (STIP1) mediates molecular interaction and complex formation between the molecular chaperones heat shock protein (Hsp)70 and Hsp90. The overexpression of STIP1 is increasingly being documented in various human malignancies, including ovarian, cholangiocellular, renal and gastric cancers. However, the role of STIP1 in pancreatic cancer (PANC) and probable molecular mechanism remains largely unexplored. METHODS & RESULTS: In the present study, using clinical samples (n = 88) and human PANC cell lines PANC-1, Capan-2, SW1990, and BxPC-3, we demonstrated that STIP1 is aberrantly expressed in human PANC tissues or cell lines compared to adjacent non-tumor pancreas samples or human pancreatic duct epithelial cells (HPDEC), respectively. Clinicopathological correlation studies revealed significant positive correlation between high STIP1 expression and lymph node involvement (p = 0.001), cancer metastasis (p = 0.002), microvascular invasion (p = 0.002), advance TNM stage (p = 0.024), perineural invasion (PNI; p = 0.013), and cancer-related death (p = 0.002) among patients with PANC. Univariate and multivariate analyses indicate that STIP1overexpression is an independent prognostic factor of PANC. Furthermore, STIP1 knockdown significantly inhibit the migration and invasive ability of PANC-1 and SW1990 cells, while downregulating N-cadherin and Vimentin, but upregulating E-cadherin mRNA expression levels, concurrently. We also demonstrated that STIP1 knockdown suppressed p-FAK, p-AKT, MMP2, MMP9, and Slug protein and mRNA expression levels, thus, indicating, at least in part, a role for STIP1 in the activation of FAK/AKT/MMP signaling. CONCLUSION: Taken together, our results demonstrate a critical role for STIP1 in cancer metastasis, disease progression and poor prognosis, as well as, provide evidence suggestive of the therapeutic efficacy of STIP1-mediated targeting of the FAK/AKT/MMP signaling axis in patients with PANC.

4 Article Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. 2019

Riquelme, Erick / Zhang, Yu / Zhang, Liangliang / Montiel, Maria / Zoltan, Michelle / Dong, Wenli / Quesada, Pompeyo / Sahin, Ismet / Chandra, Vidhi / San Lucas, Anthony / Scheet, Paul / Xu, Hanwen / Hanash, Samir M / Feng, Lei / Burks, Jared K / Do, Kim-Anh / Peterson, Christine B / Nejman, Deborah / Tzeng, Ching-Wei D / Kim, Michael P / Sears, Cynthia L / Ajami, Nadim / Petrosino, Joseph / Wood, Laura D / Maitra, Anirban / Straussman, Ravid / Katz, Matthew / White, James Robert / Jenq, Robert / Wargo, Jennifer / McAllister, Florencia. ·Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Integrative Biology, Faculty of Science, Universidad Mayor, Santiago, Chile. · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Engineering, Texas Southern University, Houston, TX, USA. · Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Departments of Medicine, Oncology and Molecular Microbiology & Immunology, Johns Hopkins University School of Medicine and the Bloomberg School of Public Health, Baltimore, MD, USA. · Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. · Department of Pathology and The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Resphera Biosciences, Baltimore, MD, USA. · Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: fmcallister@mdanderson.org. ·Cell · Pubmed #31398337.

ABSTRACT: Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.

5 Article Effect of prior cancer on survival outcomes for patients with pancreatic adenocarcinoma: a propensity score analysis. 2019

He, Chaobin / Zhang, Yu / Cai, Zhiyuan / Lin, Xiaojun. ·Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. · State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China. · Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. linxj@sysucc.org.cn. ·BMC Cancer · Pubmed #31142278.

ABSTRACT: BACKGROUND: With the increase in cancer survivors, more pancreatic ductal adenocarcinomas (PDACs) are developing as second primary cancers. Whether a prior cancer has an inferior impact on survival outcomes in patients with PDAC remains unknown, and the validity of criteria used to exclude patients with prior cancers in clinical trials needs to be determined. The aim of this study was to evaluate the prognostic factors and assess the survival impact of a prior cancer in patients with second primary PDAC. METHODS: Patients with PDAC were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific mortality rates were compared between patients with and those without prior cancer. RESULTS: The data of 9235 patients with PDAC from 2004 to 2015 were retrieved from the SEER database, consisting of 438 (4.74%) patients with a prior cancer and 8797 (95.26%) patients without a prior cancer, the patients were then pair-matched using propensity score matching (PSM) analysis. The median OS rates were 7 months for both groups of patients with PDAC with and without prior cancer. These two groups of patients had similar survival rates and cancer-specific mortalities before and after the PSM analysis. In the multivariate analysis, a history of prior cancer was not a significant prognostic factor of OS in patients with PDAC. CONCLUSIONS: Patients with PDAC who had a prior cancer had similar OS and cancer-specific mortality rates as those of patients without a prior cancer. The inclusion of patients with a prior cancer in the clinical trials of PDAC should be considered.

6 Article Codelivery Nanosystem Targeting the Deep Microenvironment of Pancreatic Cancer. 2019

Chen, Xinli / Zhou, Wenxi / Liang, Chen / Shi, Si / Yu, Xianjun / Chen, Qinjun / Sun, Tao / Lu, Yifei / Zhang, Yujie / Guo, Qin / Li, Chao / Zhang, Yu / Jiang, Chen. ·Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Research Center on Aging and Medicine, Department of Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China. · Department of Pancreatic and Hepatobiliary Surgery , Fudan University Shanghai Cancer Center , 270 Dongan Road , Shanghai 200032 , China. · Department of Oncology, Shanghai Medical College , Fudan University , Shanghai 200032 , China. ·Nano Lett · Pubmed #31058513.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is considered as one of the most aggressive malignancies due to its unique microenvironment of which the cardinal histopathological feature is the remarkable desmoplasia of the stroma, taking up about 80% of the tumor mass. The desmoplastic stroma negatively affects drug diffusion and the infiltration of T cells, leading to an immunosuppressive microenvironment. However, this unique microenvironment can limit the physical spread of pancreatic cancer via a neighbor suppression effect. Here, a tumor central stroma targeting and microenvironment responsive strategy was applied to generate a nanoparticle coloading paclitaxel and phosphorylated gemcitabine. The designed nanoparticle disrupted the central stroma while preserving the external stroma, thereby promoting the antitumor effectiveness of chemotherapeutics. Additionally, the resulting nanoparticle can modulate the tumor immunosuppressive microenvironment by augmenting the number of cytotoxic T cells and restraining the percentage of T regulatory cells. The relatively intact external stroma can effectively maintain the neighbor suppression effect and prevent tumor metastasis. Combining stroma targeting with the delivery of stimuli-responsive polymeric nanoparticles embodies an effective tumor-tailored drug delivery system.

7 Article Irreversible electroporation versus radiotherapy after induction chemotherapy on survival in patients with locally advanced pancreatic cancer: a propensity score analysis. 2019

He, Chaobin / Wang, Jun / Sun, Shuxin / Zhang, Yu / Lin, Xiaojun / Lao, Xiangming / Cui, Bokang / Li, Shengping. ·Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. · Department of Ultrasonics, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. · State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China. · Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. lishp@sysucc.org.cn. ·BMC Cancer · Pubmed #31029111.

ABSTRACT: BACKGROUND: Locally advanced pancreatic cancer (LAPC) represents more than one third of pancreatic cancers and owns poor survival after the standard chemotherapy. Irreversible electroporation (IRE) is a novel method and has been recently used in LAPC. The aim of this study was to compare the efficacy of IRE and radiotherapy after induction chemotherapy for patients with LAPC. METHODS: From August 2015 to August 2017, a total of 76 patients with biopsy proven LAPC and who had received IRE or radiotherapy after chemotherapy were included. Thirty-two pairs of patients were selected through propensity score matching (PSM) analysis and the efficacy of two treatments was compared. RESULTS: Before PSM analysis, after induction chemotherapy, patients with LAPC benefited more in terms of overall survival (OS) and progression free survival (PFS) from IRE, compared with radiotherapy (2-year OS rates, 53.5% vs 26.9%, p = 0.039; 2-year PFS rates, 28.4% vs 13.3%, p = 0.045). After PSM analysis, the survival benefits of OS and PFS of patients after induction chemotherapy followed by IRE were more obvious than those of patients treated with radiotherapy (2-year OS rates, 53.5% vs 20.7%, p = 0.011; 2-year PFS rates, 28.4% vs 5.6%, p = 0.004). Multivariate Cox regression analysis indicated that IRE after induction chemotherapy was identified as a significant favourable factor for both OS and PFS in both the whole and matched cohort. CONCLUSIONS: Induction chemotherapy followed by IRE is superior to induction chemotherapy followed by radiotherapy for treating LAPC. A randomized clinical trial comparing the efficacy of IRE and radiotherapy after the induction chemotherapy is therefore considerable.

8 Article [A Retrospective Study of 42 Lung Cancer Patients with Pancreatic Metastases]. 2019

Zhang, Yu / Chen, Minjiang / Zhao, Jing / Zhong, Wei / Xu, Yan / Wang, Mengzhao. ·Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China. ·Zhongguo Fei Ai Za Zhi · Pubmed #31014441.

ABSTRACT: BACKGROUND: A number of patients with lung cancer have distant metastases at the time of diagnosis. The most common sites for metastases are liver, brain, etc. However pancreatic metastasis is relatively rare, with an insidious onset and poor prognosis. There are no sufficient recognition and attention of lung cancer with pancreatic metastasis. The aim of this study was to summarize the pathological characteristics, clinical manifestations, therapies and prognosis of pancreatic metastases of lung cancer, thus further exploring better managements for the best prolonged survival or quality of life. METHODS: 42 patients of lung carcinoma with confirmed pancreatic metastases hospitalized at the Peking Union Medical College Hospital from January 1998 to December 2018 were identified. We reviewed all medical documentations for complete information including diagnosis, treatment, prognosis features. RESULTS: 24 (57%) patients were asymptomatic or presented with non-specific symptoms. 18 (43%) patients had symptoms related to pancreatic metastases, such as acute pancreatitis, obstructive jaundice or pain of lumber back. The median overall survival (OS) was 8.8 months. Multivariate analysis suggested patients with symptoms had a poor prognosis compared with patients without pancreatic symptoms [(hazard ratio, HR)=2.645, 95%CI: 1.013-6.910, P=0.047]. Patients received chemotherapy had better prognosis versus those who did not [HR=0.158, 95%CI: 0.049-0.512, P=0.002]. CONCLUSIONS: Pancreatic metastasis of lung cancer is rare and the prognosis is poor. Chemotherapy can prolong survival significantly. Local radiotherapy of the pancreas may alleviate local symptoms, improve quality of life, facilitate further systemic chemotherapy for patients to prolong survival. Patients with symptoms related to pancreatic metastases can benefit from the comprehensive treatment of chemotherapy combined with local pancreatic radiotherapy.

9 Article Grape seed proanthocyanidins inhibit proliferation of pancreatic cancer cells by modulating microRNA expression. 2019

Wang, Weihua / Zhan, Leilei / Guo, Dongqi / Xiang, Yanju / Tian, Muxing / Zhang, Yu / Wu, Hong / Wei, Yaxun / Ma, Ganglong / Han, Zhanjiang. ·College of Life Science, Tarim University, Alar, Xinjiang 843300, P.R. China. · Xinjiang Production and Construction Corps Key Laboratory of Deep Processing of Agricultural Products in South Xinjiang, Alar, Xinjiang 843300, P.R. China. · Center for Genome Analysis, ABLife Inc., Wuhan, Hubei 430075, P.R. China. · Xinjiang Production and Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Alar, Xinjiang 843300, P.R. China. ·Oncol Lett · Pubmed #30854052.

ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs of 18-25 nucleotides that modulate gene expression at the post-transcriptional level. Grape seed proanthocyanidins (GSPs), which are biologically active components in grape seeds, have been demonstrated to exhibit anticancer effects. The current study investigated whether GSPs can regulate miRNA expression and the possible anticancer molecular mechanisms of GSPs. Pancreatic cancer (PC) cell samples, SS3, SS12 and SS24, were treated with 20 µg/ml GSPs for 3, 12 and 24 h, respectively. Control samples, SC3, SC12 and SC24, were also prepared. Using miRNA-seq, transcriptome analysis identified 24, 83 and 83 differentially expressed (DE) miRNAs in SS3 vs. SC3, SS12 vs. SC12 and SS24 vs. SC24, respectively. This indicated that treatment with GSPs could modulate the expression of miRNAs. Subsequently, 74, 598 and 1,204 target genes for the three sets of DE miRNAs were predicted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that multiple target genes were associated with the proliferation and apoptosis of PC cells. In addition, a network was constructed of the DE miRNAs and the target genes associated with PC. The associations identified suggested that treatment with GSPs may inhibit the proliferation of PC cells through the modulation of miRNA expression.

10 Article Transcriptome analysis of pancreatic cancer cell response to treatment with grape seed proanthocyanidins. 2019

Wang, Weihua / Zhan, Leilei / Guo, Dongqi / Xiang, Yanju / Zhang, Yu / Tian, Muxing / Han, Zhanjiang. ·Department of Food Science, College of Life Sciences, Tarim University, Alar, Xinjiang 843300, P.R. China. · Xinjiang Production and Construction Corps Key Laboratory of Deep Processing of Agricultural Products in South Xinjiang, Alar, Xinjiang 843300, P.R. China. · Center for Genome Analysis, ABLife Inc., Wuhan, Hubei 430075, P.R. China. · Xinjiang Production and Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Alar, Xinjiang 843300, P.R. China. ·Oncol Lett · Pubmed #30675233.

ABSTRACT: Grape seed proanthocyanidins (GSPs) have been demonstrated to exhibit potential chemotherapeutic efficacy against various cancer types. To determine the underlying molecular mechanisms involved in GSP-induced apoptosis, the present study prepared pancreatic cancer (PC) cells samples, S3, S12 and S24, which were treated with 20 µg/ml GSPs for 3, 12 and 24 h, respectively. Control cell samples, C3, C12 and C24, were also prepared. Using RNA-sequencing, transcriptome comparisons were performed, which identified 966, 3,543 and 4,944 differentially-expressed genes (DEGs) in S3 vs. C3, S12 vs. C12 and S24 vs. C24, respectively. Gene Ontology analysis of the DEGs, revealed that treatment with GSPs is associated with disruption of the cell cycle (CC) in PC cells. Additionally, disruption of transcription, DNA replication and DNA repair were associated with GSP-treatment in PC cells. Network analysis demonstrated that the common DEGs involved in the CC, transcription, DNA replication and DNA repair were integrated, and served essential roles in the control of CC progression in cancer cells. In summary, GSPs may exhibit a potential chemotherapeutic effect on PC cell proliferation.

11 Article Combined Volumetric and Density Analyses of Contrast-Enhanced CT Imaging to Assess Drug Therapy Response in Gastroenteropancreatic Neuroendocrine Diffuse Liver Metastasis. 2018

Wang, Yi / Huang, Kun / Chen, Jie / Luo, Yanji / Zhang, Yu / Jia, Yingmei / Xu, Ling / Chen, Minhu / Huang, Bingsheng / Ni, Dong / Li, Zi-Ping / Feng, Shi-Ting. ·National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China. · Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. · Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. · Faculty of Medicine and Dentistry, University of Western Australia, Perth 6009, Australia. ·Contrast Media Mol Imaging · Pubmed #30510495.

ABSTRACT: Objective: We propose a computer-aided method to assess response to drug treatment, using CT imaging-based volumetric and density measures in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and diffuse liver metastases. Methods: Twenty-five patients with GEP-NETs with diffuse liver metastases were enrolled. Pre- and posttreatment CT examinations were retrospectively analyzed. Total tumor volume (volume) and mean volumetric tumor density (density) were calculated based on tumor segmentation on CT images. The maximum axial diameter (tumor size) for each target tumor was measured on pre- and posttreatment CT images according to Response Evaluation Criteria In Solid Tumors (RECIST). Progression-free survival (PFS) for each patient was measured and recorded. Results: Correlation analysis showed inverse correlation between change of volume and density (Δ( Conclusion: The changes of volume and density derived from CT images of all lesions showed a good correlation with PFS and may help assess treatment response.

12 Article Response of patients with locally advanced pancreatic adenocarcinoma to high-intensity focused ultrasound treatment: a single-center, prospective, case series in China. 2018

Ji, Yongshuo / Zhang, Yu / Zhu, Junqiu / Zhu, Linglin / Zhu, Yanfei / Hu, Kaimeng / Zhao, Hong. ·HIFU Center of Oncology Department, Huadong Hospital Affiliated to Fudan University, Shanghai 200000, China, hongzhhdyy@163.com. · Marketing Department, Shanghai A&S Science Technology Development Co., Ltd, Shanghai 200000, China. ·Cancer Manag Res · Pubmed #30349376.

ABSTRACT: Purpose: Patients with unresectable locally advanced pancreatic cancer (LAPC) are still in dire need of effective therapies. We performed this cohort study in order to assess the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treating patients with unresectable LAPC. Patients and methods: Eighty-seven cases with unresectable LAPC from January 2014 to December 2016 were finally recruited according to the inclusion criteria. The primary end point of our study was OS of all the cases, and the secondary end points included 6-month and 12-month survival rate, tumor response rate, carbohydrate antigen (CA) 19-9 response rate, VAS, quality of life, and safety. Results: All the 87 patients received HIFU ablation successfully, and were included in the efficacy and safety analysis. With a median follow-up of 16 months, median OS was estimated to be 12.2 months, with 95 % CI of 11.1-12.7 months. The 6-month and 12-month survival rates were 94.25% (95% CI =86.74-97.57) and 50.85% (95% CI =38.17-62.21), respectively. Multivariate analysis revealed that patients with VAS <4, Karnofsky performance status ≥80, and tumor size <3 cm have a significant improvement in their OS (adjusted HR [aHR] =0.26 [95% CI =0.12-0.57], Conclusion: HIFU ablation might be a potentially effective and safe therapeutic option for the patients with unresectable LAPC.

13 Article Integrin β1 promotes gemcitabine resistance in pancreatic cancer through Cdc42 activation of PI3K p110β signaling. 2018

Yang, Dejun / Tang, Yuan / Fu, Hongbing / Xu, Jiapeng / Hu, Zunqi / Zhang, Yu / Cai, Qingping. ·Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, China. · Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, China. Electronic address: caiqingping@smmu.edu.cn. ·Biochem Biophys Res Commun · Pubmed #30243721.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignancies with very poor prognosis due to its broad resistance to chemotherapy. Our previous study showed that integrin β1 expression is upregulated in PDAC and confers gemcitabine resistance in PDAC cells via the signaling pathway including Cdc42 and AKT activation. But the accurate signal transductions are not clear. Here, we aimed to illuminate the signal transductions of integrin β1 in the acquisition of gemcitabine resistance in PDAC. Drug-resistance (DR) cells from AsPC-1 parent cell line (PCL) were selected. Integrin β1 expression was determined using western blot assay. Changes in drug response and the activity of phosphatidylinositol 3-kinase (PI3K) signaling after knockdown of integrin β1, Cdc42 or p110β were evaluated using MTT, cleaved caspase-3 immunofluorescence and western blot assay. Western blot assays also detected the variations in Cdc42 activity and p110β expression after integrin β1 knockdown. The interaction between Cdc42 and p110β was determined by Glutathione S-transferase (GST) pull-down assay. The results showed that integrin β1 expression was upregulated in DR-AsPC-1 cells, and integrin β1 knockdown significantly decreased the activity of Cdc42, a target molecule of integrin β1, and p110β expression. Knockdown of anyone of integrin β1, Cdc42 and p110β inhibited the activity of PI3K signaling, and sensitized DR-AsPC-1 cells to gemcitabine. GST pull-down assay showed that GTP-Cdc42 interacted with p110β. Collectively, these data indicated that integrin β1 promoted gemcitabine resistance in PDAC through Cdc42 activation of PI3K p110β signaling. In vivo experiments also confirmed this conclusion. These findings contribute to a better understanding the molecular mechanism of chemoresistance and facilitate the development of more targeted and effective treatment strategy for PDAC.

14 Article Double-sided effect of tumor microenvironment on platelets targeting nanoparticles. 2018

Chen, Xinli / Wang, Qingbing / Liu, Lisha / Sun, Tao / Zhou, Wenxi / Chen, Qinjun / Lu, Yifei / He, Xi / Zhang, Yu / Zhang, Yujie / Ruan, Chunhui / Guo, Qin / Li, Chao / Jiang, Chen. ·Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 200032, China. · Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. · Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 200032, China. Electronic address: jiangchen@shmu.edu.cn. ·Biomaterials · Pubmed #30179776.

ABSTRACT: The cancer cells and stromal cells in tumor microenvironment secrete cytokines and recruit "homing" cells (macrophage, lymphocytes, platelets, etc.). Platelets can interact with tumor microenvironment and specifically aggregate at tumor sites. Surprising, we observed different "homing" effects of activated platelets in breast cancer model and pancreatic cancer model which is highly related with the blood supply of tumors. Besides, platelets targeting magnetic nanoparticles (MNPs) can home to breast cancer but be repelled from pancreatic cancer. We observed the targeting effect of MNPs is highly related with the expressions of collagen Ⅰ (marker of extracellular matrix) and CD34 (marker of tumor neovascularization). The homing nanoparticles such as platelets targeting MNPs could realize the tumor targeting ability, photo-thermal effect and tumor immunotherapeutic ability in the accessible tumor (e.g. breast cancer) but not the hypovascular tumor (e.g. pancreatic cancer).

15 Article Cordycepin induces apoptosis in human pancreatic cancer cells via the mitochondrial-mediated intrinsic pathway and suppresses tumor growth in vivo. 2018

Zhang, Yu / Zhang, Xiao Xi / Yuan, Rui Yan / Ren, Tai / Shao, Zi Yu / Wang, Hong Fei / Cai, Wei Long / Chen, Li Tian / Wang, Xu An / Wang, Ping. ·Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, People's Republic of China, chenlitian@xinhuamed.com.cn. · Department of General Surgery, Hangzhou First People's Hospital, Hangzhou 310006, People's Republic of China. · Shanghai Health Development Research Center, Shanghai 200040, People's Republic of China. · Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, People's Republic of China, chenlitian@xinhuamed.com.cn, wangxuan@xinhuamed.com.cn. · Department of General Surgery, Huzhou Central Hospital, Zhejiang 313000, People's Republic of China. ·Onco Targets Ther · Pubmed #30122940.

ABSTRACT: Background: Cordycepin, the main active ingredient of a traditional Chinese herbal remedy - extracted from Methods: The antitumor viability of cordycepin on human pancreatic cancer MIAPaCa-2 and Capan-1 cells was determined by colony formation assays. Annexin V/PI double staining and flow cytometry assay were used to investigate whether cordycepin induced apoptosis and cell cycle arrest. The mitochondrial membrane potential (ΔΨm) was analyzed by Rhodamine 123 staining, and expression of related proteins evaluated by Western blot and immunohistochemistry, both on pancreatic cancer cells and tumor xenografts to reveal the potential mechanism for the effect of cordycepin. Furthermore, the in vivo efficacy was examined on nude mice bearing MIAPaCa-2 cell tumors treated by intraperitoneal injection of cordycepin (0, 15, and 50 mg/kg/d) for 28 days. Results: Cordycepin inhibited cell viability, proliferation and colony formation ability and induced cell cycle arrest and early apoptosis of human pancreatic cancer cells (MIAPaCa-2 and Capan-1) in a dose- and time-dependent manner. The same effect was also observed in vivo. Decrease of ΔΨm and upregulation of Bax, cleaved caspase-3, cleaved caspase-9, and cleaved PARP as well as downregulation of Bcl-2 both in vitro and in vivo indicated that the mitochondria-mediated intrinsic pathway was involved in cordycepin's antitumor effect. Conclusion: Our data showed that cordycepin inhibited the activity of pancreatic cancer both in vitro and in vivo by regulating apoptosis-related protein expression through the mitochondrial pathway and suggest that cordycepin may be a promising therapeutic option for pancreatic cancer.

16 Article Loss of expression and prognosis value of alpha-internexin in gastroenteropancreatic neuroendocrine neoplasm. 2018

Wang, Yuhong / Chen, Yuanjia / Li, Xiaoxing / Hu, Wanming / Zhang, Yu / Chen, Luohai / Chen, Minhu / Chen, Jie. ·Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China. · Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China. · State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. · Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China. · Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China. chenminhu@mail.sysu.edu.cn. · Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China. chen0jie@hotmail.com. ·BMC Cancer · Pubmed #29940892.

ABSTRACT: BACKGROUND: The neuronal intermediate filament alpha-internexin (α-internexin) is a cytoskeleton protein which is involved in the tumor initiation and progression. In this study, we examined the expression and prognosis value of α-internexin in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). METHODS: α-internexin was detected with immunohistochemical staining in 286 tumor specimens from patients with GEP-NENs. Methylation status of α-internexin was evaluated by bisulfite genomic sequencing. We assessed the prognostic value of α-internexin and its correlation with relevant clinicalpathological characteristics. RESULTS: The reduced/loss of expression rate of α-internexin in GEP-NEN was 73.4% (210/286), while the positive expression rate was 26.6% (76/286). The difference of α-internexin deficiency was not statistically significant between gastrointestinal NENs (GI-NENs) and pancreatic NENs (pNENs). However, we found significant difference of reduced/loss of α-internexin expression among different sites of GI-NENs (χ CONCLUSIONS: The expression of α-internexin was highly heterougeneous in different sites of GEP-NENs. The reduced/loss of expression of α-internexin was closely related to tumors with aggressiveness and patient's adverse prognosis. The hypermethylation of the regulatory region examined may be an important epigenetic regulation mechanism of α-internexin deficiency in subtype of GI-NENs.

17 Article Immune Cell Production of Interleukin 17 Induces Stem Cell Features of Pancreatic Intraepithelial Neoplasia Cells. 2018

Zhang, Yu / Zoltan, Michelle / Riquelme, Erick / Xu, Hanwen / Sahin, Ismet / Castro-Pando, Susana / Montiel, Maria Fernanda / Chang, Kyle / Jiang, Zhengyu / Ling, Jianhua / Gupta, Sonal / Horne, William / Pruski, Melissa / Wang, Huamin / Sun, Shao-Cong / Lozano, Guillermina / Chiao, Paul / Maitra, Anirban / Leach, Steven D / Kolls, Jay K / Vilar, Eduardo / Wang, Timothy C / Bailey, Jennifer M / McAllister, Florencia. ·Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Engineering, Texas Southern University, Houston, Texas. · Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York. · Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas. · Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. · Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Texas Health Science Center, Houston, Texas. · Department of Immunology, University of Texas Health Sciences Center, Houston, Texas. · Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: fmcallister@mdanderson.org. ·Gastroenterology · Pubmed #29604293.

ABSTRACT: BACKGROUND & AIMS: Little is known about how the immune system affects stem cell features of pancreatic cancer cells. Immune cells that produce interleukin 17A (IL17A) in the chronically inflamed pancreas (chronic pancreatitis) contribute to pancreatic interepithelial neoplasia (PanIN) initiation and progression. We investigated the effects that IL17A signaling exerts on pancreatic cancer progenitor cells and the clinical relevance of this phenomena. METHODS: We performed studies with Mist1Cre;LSLKras;Rosa26mTmG (KC RESULTS: PanIN cells from KC CONCLUSIONS: In studies of mouse and human pancreatic tumors and precursors, we found that immune cell-derived IL17 regulated development of tuft cells and stem cell features of pancreatic cancer cells via increased expression of DCLK1, POU2F3, ALDH1A1, and IL17RC. Strategies to disrupt this pathway might be developed to prevent pancreatic tumor growth and progression.

18 Article MicroRNA‑720 inhibits pancreatic cancer cell proliferation and invasion by directly targeting cyclin D1. 2017

Zhang, Yu / Su, Yueying / Zhao, Yabing / Lv, Guoqiang / Luo, Ying. ·Department of General Surgery, Yongcheng City People's Hospital, Yongcheng, Henan 476600, P.R. China. · Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China. ·Mol Med Rep · Pubmed #28990111.

ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer‑associated deaths in Western countries, and ranks sixth among cancer‑associated diseases, with the highest mortality rate in China. Deregulation of micro (miR) RNA may contribute to the occurrence and progression of numerous cancers, including pancreatic cancer. In particular, deregulation of microRNA‑720 (miR‑720) has been reported in various types of human cancer. However, the expression and biological role of miR‑720 in pancreatic cancer remains to be elucidated. The present study aimed to investigate the expression and functional role of miR‑720 in pancreatic cancer and determine the underlying regulatory mechanism. The results demonstrated that miR‑720 was expressed at low levels in pancreatic cancer tissue samples and cell lines. Upregulating miR‑720 suppressed pancreatic cancer cell proliferation and invasion in vitro. Additionally, cyclin D1 (CCND1) was identified as the direct target gene of miR‑720 in pancreatic cancer. Furthermore, CCND1 was significantly upregulated in pancreatic cancer tissues and inversely correlated with miR‑720 expression. Furthermore, CCND1 re‑expression partially abrogated the inhibitory effects of miR‑720 on pancreatic cancer cells. Overall, miR‑720 may act as a tumor suppressor by directly targeting CCND1 in pancreatic cancer.

19 Article Nomogram individually predicts the overall survival of patients with gastroenteropancreatic neuroendocrine neoplasms. 2017

Fang, Cheng / Wang, Wei / Feng, Xingyu / Sun, Jian / Zhang, Yu / Zeng, Yujie / Wang, Junjiang / Chen, Huishan / Cai, Muyan / Lin, Junzhong / Chen, Minhu / Chen, Ye / Li, Yong / Li, Shengping / Chen, Jie / Zhou, Zhiwei. ·Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. · State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China. · Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. · Department of General Surgery, Guangdong General Hospital, Guangzhou, People's Republic of China. · Guangdong Academy of Medical Science, Guangzhou, People's Republic of China. · Department of Biliopancreatic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. · Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, People's Republic of China. · Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. · Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. · Department of Gastroenterology, Nanfang Hospital of Southern Medical University, Guangzhou, People's Republic of China. · Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou, People's Republic of China. · Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. · Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. · Department of Hepatopancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. ·Br J Cancer · Pubmed #28949958.

ABSTRACT: BACKGROUND: The current study aimed to establish a novel nomogram to predict the overall survival of individual Chinese patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Furthermore, this study sought to externally validate this nomogram using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The records of 1183 patients with GEP-NENs treated at five high-capacity institutions in China between 2005 and 2015 were retrospectively analysed. In addition, 10 236 GEP-NEN cases from the SEER database were included as an external validation set. RESULTS: A multivariate analysis using Cox proportional hazards (PHs) regression was performed, and a nomogram was constructed. Discrimination, calibration, and external validation were performed using the SEER data set. The multivariate Cox model indicated that age, tumour size, differentiation, lymph node metastases, and distant metastases were independent covariates associated with survival. With respect to the training set, the nomogram exhibited better discrimination power than TNM classification (Harrell's concordance index (C-index): 0.837 vs 0.784, P=0.006). Discrimination was also excellent and superior to that of TNM classification for the SEER-based validation set (C-index: 0.808 vs 0.717, P<0.001). The calibrated nomogram predicted a survival rate that closely corresponded to the actual survival rate. CONCLUSIONS: We developed a nomogram that predicted the 3- and 5-year overall survival rates of patients with GEP-NENs. Validation revealed excellent discrimination and calibration for this nomogram, suggesting that it exhibits satisfactory clinical utility that might improve individualised predictions of survival risks and lead to the creation of additional clinical therapies.

20 Article [Prognostic value of carcinoembryonic antigen, alpha fetoprotein, carbohydrate antigen 125 and carbohydrate antigen 19-9 in gastroenteropancreatic neuroendocrine neoplasms]. 2017

Chen, Luohai / Zhang, Yu / Chen, Minhu / Chen, Jie. ·Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. chen0jie@hotmail.com. ·Zhonghua Wei Chang Wai Ke Za Zhi · Pubmed #28900990.

ABSTRACT: OBJECTIVE: To study the rate of elevated common biomarkers of digestive tumors, including carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9), in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) and their prognostic values in GEP-NEN. METHODS: Clinicopathological data of patients with GEP-NEN treated in The First Affiliated Hospital, Sun Yat-sen University from January 2011 to December 2016 were retrospectively studied. The inclusion criteria were as follows: patients with complete clinicopathological data including AFP, CEA, CA125 and CA19-9 level before treatment; patients without previous or other concomitant cancer; patients diagnosed as sporadic but not familial NEN. Serum AFP level >30 μg/L, CEA level >7.5 μg/L, CA125 level >52.5 μg/L and CA19-9 level >52.5 kU/L were defined as elevation respectively. Kaplan-Meier analysis and Log-rank test were applied to investigate the prognostic role of these biomarkers. RESULTS: A total of 170 patients with GEP-NEN were enrolled, and 105 (61.8%) patients were male with median age of 52.5 years. Thirty-six (21.2%), 77 (45.3%) and 57 (33.5%) cases were gastric, intestinal and pancreatic NEN respectively. Elevated AFP, CEA, CA125 and CA19-9 were found in 3(1.8%), 19(11.2%), 22(12.9%) and 21(12.4%) patients. Elevated CEA was related with G3 disease (OR=4.78, 95%CI:1.28-17.85, P=0.020) and elevated CA125 was related with distant metastasis (OR=51.60, 95%CI:5.76-462.44, P=0.000) while elevated CA19-9 was related with both G3 disease (OR=3.81; 95%CI:1.21-11.99, P=0.022) and distant metastasis(OR=4.87; 95%CI:1.41-16.75, P=0.012). The median follow-up was 22.5 months. Forty-six patients (27.1%) died during the follow-up. Patients with elevated CEA, CA125 or CA19-9 had worse overall survival compared with their counterparts with the median survivals of 14 months (95%CI:5.4 to 22.6 months, χ CONCLUSIONS: Elevation of AFP, CEA, CA125 or CA19-9 is not common in GEP-NEN. Patients with elevation of these biomarkers have poor survival.

21 Article Clinicopathologic characteristics and prognosis of gastroenteropancreatic neuroendocrine neoplasms: a multicenter study in South China. 2017

Fang, Cheng / Wang, Wei / Zhang, Yu / Feng, Xingyu / Sun, Jian / Zeng, Yujie / Chen, Ye / Li, Yong / Chen, Minhu / Zhou, Zhiwei / Chen, Jie. ·Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China. · Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China. · Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, 510080, Guangdong, P. R. China. · Department of Biliopancreatic Surgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, 510120, Guangdong, P. R. China. · Department of Gastrointestinal Surgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, Guangdong, P. R. China. · Department of Gastroenterology, Nanfang Hospital of Southern Medical University, Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou, 510515, Guangdong, P. R. China. yechen@smu.edu.cn. · Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, 510080, Guangdong, P. R. China. yuan821007@126.com. · Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China. zhouzhw@sysucc.org.cn. · Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China. chen0jie@hotmail.com. ·Chin J Cancer · Pubmed #28637502.

ABSTRACT: BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of rare tumors. Many issues in terms of epidemiologic features, pathogenesis, and treatment of GEP-NENs are still under discussion. Our study aimed to analyze the clinicopathologic characteristics and prognosis of Chinese patients with GEP-NENs. METHODS: Complete clinicopathologic data and survival information of 1183 patients with GEP-NENs treated between 2005 and 2015 were collected from five medical centers in Guangdong Province, China. Patient survival was estimated using the Kaplan-Meier method and analyzed using the log-rank test; prognostic factors were analyzed using the Cox proportional hazards model. RESULTS: The most common tumor location was the rectum (37.4%), followed by the pancreas (28.1%), stomach (20.7%), small intestine (7.2%), appendix (3.4%), and colon (3.3%). After initial definitive diagnosis, 1016 (85.9%) patients underwent surgery. The 1-, 3-, and 5-year overall survival (OS) rates for the entire cohort were 87.9%, 78.5%, and 72.8%, respectively. The 3-year OS rates of patients with G1, G2, and G3 tumors were 93.1%, 82.7%, and 43.1%, respectively (P < 0.001). The 3-year OS rates of patients with stage I, II, III, and IV tumors were 96.0%, 87.3%, 64.0%, and 46.8%, respectively (P < 0.001). Patients with distant metastasis who underwent palliative surgery had a longer survival than those who did not (P = 0.003). Similar survival benefits of palliative surgery were observed in patients with neuroendocrine tumor (P = 0.031) or neuroendocrine carcinoma (P = 0.046). In multivariate analysis, age, grade, N category, M category, and surgery were found to be independent prognostic factors. CONCLUSIONS: Patients with GEP-NENs who are women, younger than 50 years old, have smaller tumor size, have lower tumor grade, have lower T/N/M category, and who undergo surgery can have potentially longer survival time. Our data showed that surgery can improve the prognosis of GEP-NEN patients with distant metastasis. However, randomized controlled trials need to be conducted to establish the optimal criteria for selecting patients to undergo surgery.

22 Article High Expression of Cell Division Cycle 42 Promotes Pancreatic Cancer Growth and Predicts Poor Outcome of Pancreatic Cancer Patients. 2017

Yang, Dejun / Zhang, Yu / Cheng, Yajun / Hong, Liang / Wang, Changming / Wei, Ziran / Cai, Qingping / Yan, Ronglin. ·Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China. · Outpatient Department, Yichuan Community Health Service Center, 43 Lishan Road, Shanghai, 200065, People's Republic of China. · Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China. caiqp1969@hotmail.com. · Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 FengYang Road, Shanghai, 200003, People's Republic of China. yanronglin@smmu.edu.cn. ·Dig Dis Sci · Pubmed #28181096.

ABSTRACT: BACKGROUND: Cell division cycle 42 (CDC42), an important member of the Rho family, is overexpressed in various human cancers. However, its expression and role in pancreatic cancer (PC) are not well understood. AIM: The present study was designed to investigate the expression patterns and underlying cellular mechanisms of CDC42 in PC. METHODS: First, immunohistochemical analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect CDC42 expression in clinical pancreatic carcinoma and adjacent tissues. Second, differential expression of CDC42 between PC cells and normal cells was evaluated by qRT-PCR and Western blotting. Third, the correlation between CDC42 expression as well as clinicopathological characteristics and patient survival was analyzed. Finally, CDC42 was knocked down to examine its role both in vivo and in vitro. RESULTS: The results showed significantly increased CDC42 expression in pancreatic tumor tissues compared with adjacent normal tissues, as revealed by qRT-PCR, Western blotting and immunostaining. Compared to PanC-1 cells, CDC42 expression was downregulated in HPDE6-C7 cells as shown by qRT-PCR and Western blotting. High CDC42 expression was observed in 69.2% (83/120) of pancreatic adenocarcinoma patients and was significantly associated with tumor differentiation (p = 0.013), median tumor size (p = 0.005), tumor infiltration (pT stage, p = 0.04), lymph nodal status (pN stage, p = 0.044) and TNM staging (p = 0.003). Multivariate Cox regression analysis revealed CDC42 expression to be an independent predictor of survival of PC patients (HR 3.0, 95% CI 1.60-5.61, p = 0.001). Finally, we found that CDC42 promoted the proliferation of PanC-1 cells both in vivo and in vitro. CONCLUSIONS: Our findings reveal that CDC42 might play an important role in promoting PC development, and the findings suggest that CDC42 might serve as a potential prognostic indicator of PC.

23 Article Inhibition of Cell Survival by Curcumin Is Associated with Downregulation of Cell Division Cycle 20 (Cdc20) in Pancreatic Cancer Cells. 2017

Zhang, Yu / Xue, Ying-Bo / Li, Hang / Qiu, Dong / Wang, Zhi-Wei / Tan, Shi-Sheng. ·Department of Oncology, Guizhou People's Hospital, Guizhou 550002, China. skyline_zyu@163.com. · Department of Oncology, Guizhou People's Hospital, Guizhou 550002, China. xueyingbo0619@163.com. · Department of Oncology, Guizhou People's Hospital, Guizhou 550002, China. lihang.sy@163.com. · Department of Oncology, Guizhou People's Hospital, Guizhou 550002, China. qiudcds@126.com. · Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. zwang6@bidmc.harvard.edu. · Department of Oncology, Guizhou People's Hospital, Guizhou 550002, China. tssh18018@126.com. ·Nutrients · Pubmed #28165402.

ABSTRACT: Pancreatic cancer is one of the most aggressive human tumors in the United States. Curcumin, a polyphenol derived from the

24 Article Magnetic mesoporous nanospheres anchored with LyP-1 as an efficient pancreatic cancer probe. 2017

Jiang, Yongjian / Liu, Shaojun / Zhang, Yu / Li, Hengchao / He, Hang / Dai, Juntao / Jiang, Tao / Ji, Weihang / Geng, Daoying / Elzatahry, Ahmed A / Alghamdi, Abdulaziz / Fu, Deliang / Deng, Yonghui / Zhao, Dongyuan. ·Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China. · Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, Shanghai 200433, China. · Department of Radiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: laijiangtaotao@163.com. · Institute for Complex Engineered Systems, Carnegie Mellon University, Pittsburgh, PA 15213, USA. · Materials Science and Technology Program, College of Arts and Sciences, Qatar University, Doha 2713, Qatar. · Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. · Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: surgeonfu@163.com. · Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, Shanghai 200433, China; State Key Lab of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China. Electronic address: yhdeng@fudan.edu.cn. ·Biomaterials · Pubmed #27871003.

ABSTRACT: Immobilization of a ligand that selectively interacts with cancer cells to nanomaterials can enhance their diagnostic and therapeutic efficiency. In this study, we firstly demonstrate the high expression of receptor for cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) in both mouse and human pancreatic cancer. Based on these findings, sub-50 nm multifunctional superparamagnetic mesoporous nanospheres with surface modified with LyP-1 are rationally designed. Theses nanospheres have a core of silica-protected magnetite nanoparticle and a shell of FITC-labeled mesoporous silica, and they are able to specifically recognize and conjugate with the pancreatic cancer cell in vitro, as verified by the combined techniques of fluorescent imaging and T2 weight magnetic resonance imaging. After systematic administration, these LyP-1 immobilized nanospheres are found to actively target to mouse orthotopic xenograft of pancreatic cancer, which opens up the door for applications in early probing and diagnosis of pancreatic cancer by the multimodal imaging.

25 Article Modified Staging Classification for Pancreatic Neuroendocrine Tumors on the Basis of the American Joint Committee on Cancer and European Neuroendocrine Tumor Society Systems. 2017

Luo, Guopei / Javed, Ammar / Strosberg, Jonathan R / Jin, Kaizhou / Zhang, Yu / Liu, Chen / Xu, Jin / Soares, Kevin / Weiss, Matthew J / Zheng, Lei / Wolfgang, Christopher L / Cives, Mauro / Wong, Joyce / Wang, Wei / Sun, Jian / Shao, Chenghao / Wang, Wei / Tan, Huangying / Li, Jie / Ni, Quanxing / Shen, Lin / Chen, Minhu / He, Jin / Chen, Jie / Yu, Xianjun. ·Guopei Luo, Kaizhou Jin, Chen Liu, Jin Xu, Quanxing Ni, and Xianjun Yu, Fudan University Shanghai Cancer Center · Chenghao Shao, Shanghai Changzheng Hospital · Wei Wang, Huadong Hospital, Fudan University, Shanghai · Yu Zhang, Minhu Chen, and Jie Chen, The First Affiliated Hospital, Sun Yat-Sen University · Wei Wang, Sun Yat-sen University Cancer Center · Jian Sun, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou · Huangying Tan, China-Japan Friendship Hospital · and Jie Li and Lin Shen, Peking University Cancer Hospital and Institute, Beijing, China · Ammar Javed, Kevin Soares, Matthew J. Weiss, Lei Zheng, Christopher L. Wolfgang, and Jin He, The Johns Hopkins University School of Medicine, Baltimore, MD · and Jonathan R. Strosberg, Mauro Cives, and Joyce Wong, Moffitt Cancer Center and Research Institute, Tampa, FL. ·J Clin Oncol · Pubmed #27646952.

ABSTRACT: Purpose The European Neuroendocrine Tumor Society (ENETS) and the American Joint Committee on Cancer (AJCC) staging classifications are two widely used systems in managing pancreatic neuroendocrine tumors. However, there is no universally accepted system. Methods An analysis was performed to evaluate the application of the ENETS and AJCC staging classifications using the SEER registry (N = 2,529 patients) and a multicentric series (N = 1,143 patients). A modified system was proposed based on analysis of the two existing classifications. The modified system was then validated. Results The proportion of patients with AJCC stage III disease was extremely low for both the SEER series (2.2%) and the multicentric series (2.1%). For the ENETS staging system, patients with stage I disease had a similar prognosis to patients with stage IIA disease, and patients with stage IIIB disease had a lower hazard ratio for death than did patients with stage IIIA disease. We modified the ENETS staging classification by maintaining the ENETS T, N, and M definitions and adopting the AJCC staging definitions. The proportion of patients with stage III disease using the modified ENETS (mENETS) system was higher than that of the AJCC system in both the SEER series (8.9% v 2.2%) and the multicentric series (11.6% v 2.1%). In addition, the hazard ratio of death for patients with stage III disease was higher than that for patients with stage IIB disease. Moreover, statistical significance and proportional distribution were observed in the mENETS staging classification. Conclusion An mENETS staging classification is more suitable for pancreatic neuroendocrine tumors than either the AJCC or ENETS systems and can be adopted in clinical practice.

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