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Pancreatic Neoplasms: HELP
Articles by X. Li
Based on 11 articles published since 2010
(Why 11 articles?)
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Between 2010 and 2020, X. Li wrote the following 11 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Clinical Trial VEGF remains an interesting target in advanced pancreas cancer (APCA): results of a multi-institutional phase II study of bevacizumab, gemcitabine, and infusional 5-fluorouracil in patients with APCA. 2012

Martin, L K / Li, X / Kleiber, B / Ellison, E C / Bloomston, M / Zalupski, M / Bekaii-Saab, T S. ·Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, USA. ·Ann Oncol · Pubmed #22767582.

ABSTRACT: BACKGROUND: We investigated the safety and efficacy of bevacizumab combined with gemcitabine followed by infusional 5-fluorouracil (5-FU) in patients with advanced pancreas cancer (APCA). DESIGN: Patients with untreated APCA received bevacizumab 10 mg/kg, gemcitabine 1000 mg/m(2) over 100 min, and 5-FU 2400 mg/m(2) over 48 h on days 1 and 15 of each 28-day cycle. The primary end point was the proportion of patients with progression-free survival (PFS) at 6 months from initiation of therapy. If PFS at 6 months was ≥41%, the regimen would be considered promising. RESULTS: Forty-two patients were enrolled in the study; of which, 39 were evaluable for primary end point. PFS at 6 months was 49% (95% CI 34% to 64%). Median PFS was 5.9 months (95% CI 3.5 to 8.1) and median overall survival (OS) was 7.4 months (95% CI 4.7 to 11.2). Partial response and stable disease occurred in 30% and 45% of patients, respectively. Treatment-related hypertension and normal baseline albumin correlated with an improved response rate, PFS and OS. Grade 3 to 4 toxicities included fatigue (14%), hypertension (5%), and venous thrombosis (5%). CONCLUSIONS: The study met its primary end point. Further investigation of anti-VEGF therapy in combination with fluoropyrimidine-based therapy is warranted in APCA. Treatment-related hypertension and normal baseline albumin may predict for the efficacy of bevacizumab and should be investigated in prospective studies.

2 Article [Effects of neoadjuvant therapy on postoperative complication of pancreatic cancer surgery]. 2018

Bai, X L / Su, W / Li, X / Liang, T B. ·Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Pancreatic Disease of Zhejiang Province, Hangzhou 310009, China. ·Zhonghua Wai Ke Za Zhi · Pubmed #30392298.

ABSTRACT: Pancreatic cancer is a fatal disease with low resectability, high recurrence rate and despairing prognosis.Neoadjuvant therapy has been proven to improve resectability, especially R0 resection rate, and extend overall survival.It has become the hotspot in the field of pancreatic cancer in the last decade.However, the concomitant adverse effects on surgery and postoperative complication also draw wide attention.In this reivew, the indication and the effects of neoadjuvant therapy on pancreas and body composition according the latest studies are summarized.Futhermore, the effects of neoadjuvant therapy on postoperative complication from multiple aspects are discussed.

3 Article Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer. 2018

Hessmann, E / Patzak, M S / Klein, L / Chen, N / Kari, V / Ramu, I / Bapiro, T E / Frese, K K / Gopinathan, A / Richards, F M / Jodrell, D I / Verbeke, C / Li, X / Heuchel, R / Löhr, J M / Johnsen, S A / Gress, T M / Ellenrieder, V / Neesse, A. ·Department Gastroenterology and Gastrointestinal Oncology, University Medical Centre Goettingen, Goettingen, Germany. · Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany. · Cancer Research UK Cambridge Institute, The University of Cambridge, Li Ka Shing Centre, Cambridge, UK. · Oncology iMED DMPK AstraZeneca UK Ltd, HODGKIN C/o B310 Cambridge Science Park, Cambridge, UK. · The University of Manchester, Cancer Research UK Manchester Institute, Manchester, UK. · Department of Oncology, University of Cambridge, Cambridge, UK. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden. · Department of Pathology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Department of Gastroenterology, Endocrinology and Metabolism, Philipps University Marburg, Marburg, Germany. ·Gut · Pubmed #28077438.

ABSTRACT: OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in RESULTS: Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%. CONCLUSIONS: Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.

4 Article Prolonged exposure to extracellular lumican restrains pancreatic adenocarcinoma growth. 2017

Li, X / Kang, Y / Roife, D / Lee, Y / Pratt, M / Perez, M R / Dai, B / Koay, E J / Fleming, J B. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Department of General Surgery, The University of Texas Health Science Center at Houston, Houston, Texas, USA. · Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ·Oncogene · Pubmed #28534517.

ABSTRACT: We previously demonstrated that pancreatic stellate cells within pancreatic ductal adenocarcinoma (PDAC) stroma secrete lumican and its presence is associated with prolonged survival of patients with localized PDAC. Here, we observed that extracellular lumican decreases PDAC tumour cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition of low-passage human PDAC cells in a species-specific manner. PDAC cells grown in variant culture conditions and exposed to extracellular lumican display typical characterizations of cancer cell in a quiescent state, such as growth inhibition, apoptosis, G0/G1 arrest and chemoresistance. Importantly, extracellular lumican is associated with diminished ERK1/2 phosphorylation and increased p38 phosphorylation within PDAC cells. We further demonstrated that extracellular lumican physically binds with EGFR to trigger EGFR internalization and downregulation of EGFR and its downstream signal molecule ERK. Lumican enhances casitas B-lineage lymphoma expression, which stabilized the TGFβ Type II receptor sensitizing PDAC cells to TGFβ-mediated activation of p38 and SMAD signals. These provide a mechanism for the shift in signalling and phenotypic changes we observed after prolonged exposure to lumican. Together, our findings demonstrate that stromal lumican restrains PDAC cell growth through mediating cell entry into a quiescent state.

5 Article Cancer-FOXP3 directly activated CCL5 to recruit FOXP3 2017

Wang, X / Lang, M / Zhao, T / Feng, X / Zheng, C / Huang, C / Hao, J / Dong, J / Luo, L / Li, X / Lan, C / Yu, W / Yu, M / Yang, S / Ren, H. ·Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin, China. · The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. · Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China. · Department of Gynaecology, Hepingqu Gynaecology and Obsterics Hospital, Tianjin, China. · Penn State College of Medicine, Hershey, PA, USA. ·Oncogene · Pubmed #27991933.

ABSTRACT: Forkheadbox protein 3 (FOXP3), initially identified as a key transcription factor for regulatory T cells (Treg cells), was also expressed in many tumors including pancreatic ductal adenocarcinoma (PDAC). However, its role in PDAC progression remains elusive. In this study, we utilized 120 PDAC tissues after radical resection to detect cancer-FOXP3 and Treg cells by immunohistochemistry and evaluated clinical and pathological features of these patients. Cancer-FOXP3 was positively correlated with Treg cells accumulation in tumor tissues derived from PDAC patients. In addition, high cancer-FOXP3 expression was associated with increased tumor volumes and poor prognosis in PDAC especially combined with high levels of Treg cells. Overexpression of cancer-FOXP3 promoted the tumor growth in immunocompetent syngeneic mice but not in immunocompromised or Treg cell-depleted mice. Furthermore, CCL5 was directly trans-activated by cancer-FOXP3 and promoted the recruitment of Treg cells from peripheral blood to the tumor site in vitro and in vivo. This finding has been further reinforced by the evidence that Treg cells recruitment by cancer-FOXP3 was impaired by neutralization of CCL5, thereby inhibiting the growth of PDAC. In conclusion, cancer-FOXP3 serves as a prognostic biomarker and a crucial determinant of immunosuppressive microenvironment via recruiting Treg cells by directly trans-activating CCL5. Therefore, cancer-FOXP3 could be used to select patients with better response to CCL5/CCR5 blockade immunotherapy.

6 Article Extracellular lumican augments cytotoxicity of chemotherapy in pancreatic ductal adenocarcinoma cells via autophagy inhibition. 2016

Li, X / Roife, D / Kang, Y / Dai, B / Pratt, M / Fleming, J B. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Oncogene · Pubmed #26876211.

ABSTRACT: Lumican, an extracellular matrix proteoglycan overexpressed by pancreatic stellate cells (PSCs) and pancreatic ductal adenocarcinoma cells (PDACs), drives the formation of a tumor-specific microenvironment. We recently showed that extracellular lumican inhibits pancreatic cancer cell growth and is associated with prolonged survival after surgery. Here we investigated the role of extracellular lumican in chemotherapy-mediated cancer therapy. Lumican secretion was increased by chemotherapeutic agents in PDAC, and especially in PSCs, and appeared to be linked to the extent of cells' response to chemotherapy-induced growth inhibition. In multiple PDAC models, including cell lines, patient-derived xenografts and lumican knockout mice, lumican significantly increased antitumor effect of chemotherapy. This effect was associated with DNA damage, apoptosis and inhibition of cell viability, glucose consumption, lactate production and vascular endothelial growth factor secretion. In PDAC cells, chemotherapeutic agents triggered autophagosome formation and increased LC3 expression through the reactive oxygen species-mediated AMP-activated kinase (AMPK) signaling pathway. Inhibition of gemcitabine-induced autophagy in cancer cells by treatment with AMPK inhibitor compound C, lysosomal inhibitor chloroquine or autophagy inhibitor 3MA enhanced gemcitabine-induced apoptosis, suggesting that autophagy is a protective cellular response to gemcitabine treatment. Importantly, lumican dramatically decreased AMPK activity, inhibiting chemotherapy-induced autophagy in both in vitro and in vivo PDAC models. Co-treatment of PDAC cells with lumican and gemcitabine increased mitochondrial damage, reactive oxygen species (ROS) production and cytochrome c release, indicating that lumican-induced disruption of mitochondrial function may be the mechanism of sensitization to gemcitabine. Together, our findings demonstrate that extracellular lumican augments cytotoxicity of chemotherapy in PDAC cells through inhibition of chemotherapeutic agent-induced autophagy.

7 Article Manganese superoxide dismutase expression is negatively associated with microRNA-301a in human pancreatic ductal adenocarcinoma. 2015

Pandit, H / Zhang, W / Li, Y / Agle, S / Li, X / Li, S P / Cui, G / Li, Y / Martin, R C G. ·Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA. · Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA. · Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China. · Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic/NB40, Cleveland, OH, USA. ·Cancer Gene Ther · Pubmed #26384137.

ABSTRACT: Manganese superoxide dismutase (MnSOD) expression has been found to be low in human pancreatic ductal adenocarcinoma (PDAC). Previously, we have reported that microRNA-301a (miR-301a) was found being upregulated via nuclear factor-κB (NF-κB) feedback loop in human PDAC. In this study, we investigate whether the miR-301a expression level is associated with MnSOD expression in human PDAC. We established a xenograft PDAC mouse model using transfected PanC-1 cells (miR-301a antisense or scrambled control) to investigate tumor growth and the interaction between MnSOD and miR-301a. The animal study indicated that miR-301a antisense transfection could significantly decrease the growth rate of inoculated PDAC cells, and this decrease in tumor growth rate is associated with increased MnSOD expression. To evaluate the MnSOD-miR-301a correlation in human PDAC, we have analyzed a total of 60 PDAC specimens, along with 20 normal pancreatic tissue (NPT) specimens. Human specimens confirmed a significant decrease of MnSOD expression in PDAC specimens (0.88±0.38) compared with NPT control (2.45±0.76; P<0.05), whereas there was a significant increase in miR-301a levels in PDAC specimens (0.89±0.28) compared with NPT control (0.25±0.41; P<0.05). We conclude that MnSOD expression is negatively associated with miR-301a levels in PDAC tissues, and lower miR-301a levels are associated with increased MnSOD expression and inhibition of PDAC growth.

8 Article Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc. 2015

Liu, Y / Li, X / Zhu, S / Zhang, J-g / Yang, M / Qin, Q / Deng, S-c / Wang, B / Tian, K / Liu, L / Niu, Y / Wang, C-y / Zhao, G. ·Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province, Wuhan City, China. · Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China. · Department of Gastroenterological Surgery, Peking University People's Hospital, Xicheng District, Beijing, China. ·Gene Ther · Pubmed #25965392.

ABSTRACT: Recent researches demonstrate that microRNAs (miRNAs) are deregulated in numerous cancers and involved in tumorigenesis, whereas their influences on pancreatic cancer (PC) still need further elucidation. The present research revealed that miR-494 was significantly decreased in PC cell lines and tissues. Functional study showed that overexpressed miR-494 could remarkably inhibit proliferation of PC cells both in vitro and in vivo, which was due to induction of apoptosis, G1-phase arrest and senescence. Moreover, upregulated miR-494 significantly prohibited invasion of PC cells. Meanwhile, both c-Myc and SIRT1 was identified as targets of miR-494 through dual luciferase assay and further confirmed by the reverse correlation between miR-494 and c-Myc/SIRT1 in PC samples. Furthermore, co-transfection with c-Myc-RNAi and SIRT1-RNAi synergistically reduced c-Myc and SIRT1 expression, and inhibited proliferation of PC, which simulated the effects of miR-494 overexpression. On the contrary, co-overexpression of c-Myc and SIRT1 effectively rescued inhibition of overexpressed miR-494 on PC cells. The clinical characteristics further revealed that low miR-494 correlated with larger tumor size, late tumor node metastasis stage, lymphatic invasion, distant metastasis and poor prognosis. In conclusion, the present study indicated that miR-494 might serve as predictor and inhibitor in PC by directy downregulating the loop of c-Myc and SIRT1.

9 Article WNT7B mediates autocrine Wnt/β-catenin signaling and anchorage-independent growth in pancreatic adenocarcinoma. 2014

Arensman, M D / Kovochich, A N / Kulikauskas, R M / Lay, A R / Yang, P-T / Li, X / Donahue, T / Major, M B / Moon, R T / Chien, A J / Dawson, D W. ·Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Howard Hughes Medical Institute, Department of Pharmacology, and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA, USA. · 1] Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA [2] Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · 1] Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA [2] Department of Surgery, Division of General Surgery, Institute for Molecular Medicine and Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Department of Cell Biology and Physiology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA. · 1] Howard Hughes Medical Institute, Department of Pharmacology, and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA, USA [2] Department of Medicine, Division of Dermatology, University of Washington School of Medicine, Seattle, WA, USA. ·Oncogene · Pubmed #23416978.

ABSTRACT: Developmental and cancer models show Wnt/β-catenin-dependent signaling mediates diverse phenotypic outcomes in the pancreas that are dictated by context, duration and strength of activation. While generally assumed to be pro-tumorigenic, it is unclear to what extent dysregulation of Wnt/β-catenin signaling impacts tumor progression in pancreatic adenocarcinoma (PDAC). In the present study, Wnt/β-catenin activity was characterized across a spectrum of PDAC cell lines and primary tumors. Reporter and gene expression-based assays revealed wide heterogeneity in Wnt/β-catenin transcriptional activity across PDAC cell lines and patient tumors, as well as variable responsiveness to exogenous Wnt ligand stimulation. An experimentally generated, pancreas-specific gene expression signature of Wnt/β-catenin transcriptional activation was used to stratify pathway activation across a cohort of resected, early-stage PDAC tumors (N=41). In this cohort, higher Wnt/β-catenin activation was found to significantly correlate with lymphvascular invasion and worse disease-specific survival (median survival time 20.3 versus 43.9 months, log-rank P=0.03). Supporting the importance of Wnt ligand in mediating autocrine Wnt signaling, Wnt/β-catenin activity was significantly inhibited in PDAC cell lines by WLS gene silencing and the small-molecule inhibitor IWP-2, both of which functionally block Wnt ligand processing and secretion. Transcriptional profiling revealed elevated expression of WNT7B occurred in PDAC cell lines with high levels of cell autonomous Wnt/β-catenin activity. Gene-knockdown studies in AsPC-1 and HPAF-2 cell lines confirmed WNT7B-mediated cell autonomous Wnt/β-catenin activation, as well as an anchorage-independent growth phenotype. Our findings indicate WNT7B can serve as a primary determinant of differential Wnt/β-catenin activation in PDAC. Disrupting the interaction between Wnt ligands and their receptors may be a particularly suitable approach for therapeutic modulation of Wnt/β-catenin signaling in PDAC and other cancer contexts where Wnt activation is mediated by ligand expression rather than mutations in canonical pathway members.

10 Article β2-AR-HIF-1α: a novel regulatory axis for stress-induced pancreatic tumor growth and angiogenesis. 2013

Shan, T / Ma, J / Ma, Q / Guo, K / Guo, J / Li, X / Li, W / Liu, J / Huang, C / Wang, F / Wu, E. ·Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China. ·Curr Mol Med · Pubmed #23745588.

ABSTRACT: The purpose of this study was to test the hypothesis that chronic stress in a negative social and psychological state plays a critical role in pancreatic cancer development and progression. In this study, we created a new stress model system to determine the effects of chronic stress on pancreatic cancer progression. Here, we show that chronic stress not only causes depression in mice, most likely attributed to an elevated level of epinephrine, but also induces pancreatic cancer progression. We provide evidence that the pancreatic cancer progression induced by chronic stress could be blocked to a significant degree by β2-AR inhibitor ICI118 551 or HIF-1α inhibitor 2-methoxyestradiol. Moreover, establishment of pancreatic cancer in mice exposed to chronic stress was accompanied by up-regulation of the expression of MMP-2, MMP-9, and VEGF, mediated by a HIF- 1α-dependent β-AR signaling pathway. Our data suggest that the β2-AR-HIF-1α axis regulates stress-induced pancreatic tumor growth and angiogenesis. This study may have a therapeutic or preventive potential for the patients with pancreatic cancer who are especially prone to psychosocial stress challenges.

11 Article Overexpression of CIAPIN1 inhibited pancreatic cancer cell proliferation and was associated with good prognosis in pancreatic cancer. 2012

Chen, X / Li, X / Chen, J / Zheng, P / Huang, S / Ouyang, X. ·Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, Fujian, China. cxzpc81@gmail.com ·Cancer Gene Ther · Pubmed #22677939.

ABSTRACT: Cytokine-induced antiapoptotic molecule (CIAPIN1), a newly identified apoptosis inhibitor, has been found to participate in the process of proliferation and tumorigenicity for several cancers. The aim of this study was to evaluate the prognostic value of CIAPIN1 in pancreatic cancer and to probe its function in pancreatic carcinogenesis. We found that CIAPIN1 protein was absent or reduced in pancreatic cancer cell lines. There was also a loss or decrease in CIAPIN1 expression in 118 cases of pancreatic cancer tissues as compared with that in 82 cases of normal pancreatic tissues. In a Cox proportional hazards model, CIAPIN1 expression independently predicted better survival (P<0.0001). Adenoviral-mediated restoration of CIAPIN1 expression greatly repressed the proliferation of pancreatic cancer cell in vitro and suppressed the tumorigenicity of pancreatic cancer cell in Balb/c nude mice. Our data also revealed that inhibition of pancreatic cancer cells proliferation by enforcing CIAPIN1 expression at least partly through delaying cell cycle progression and inducing cell apoptosis. In summary, our work revealed a novel function of CIAPIN1, which might possibly be used as an independent prognostic factor and a potential therapeutic target for pancreatic cancer.