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pancreatic cancer EMT

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https://www.readbyqxmd.com/read/27914516/leukotriene-b4-induces-emt-and-vimentin-expression-in-panc-1-pancreatic-cancer-cells-involvement-of-blt2-via-erk2-activation
#1
You Ri Kim, Mi Kyung Park, Gyeong Jin Kang, Hyun Ji Kim, Eun Ji Kim, Hyun Jung Byun, Moo-Yeol Lee, Chang Hoon Lee
Leukotriene B4 (LTB4) is a leukocyte chemoattractant and plays a major role controlling inflammatory responses including pancreatitis. LTB4 is known to be correlated with cancer progression. LTB4 induces keratin phosphorylation and reorganization by activating extracellular regulated kinase (ERK) in PANC-1 pancreatic cancer cell lines. However, the role of LTB4 in epithelial mesenchymal transition (EMT) and vimentin expression in pancreatic cancer cells is unknown. We examined whether LTB4 induces EMT and vimentin expression by Western blot, si-RNA, and RT-PCR...
December 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/27898661/methyl-cpg-binding-domain-3-inhibits-epithelial-mesenchymal-transition-in-pancreatic-cancer-cells-via-tgf-%C3%AE-smad-signalling
#2
Min Xu, Junbo He, Jie Li, Wen Feng, Hailang Zhou, Hong Wei, Meng Zhou, Ying Lu, Jian Zeng, Wanxin Peng, Fengyi Du, Aihua Gong
BACKGROUND: Methyl-CpG-binding domain 3 (MBD3) is an aberrant expression in human malignancies. However, the role of MBD3 in pancreatic cancer progression remains to be clarified. In this study, we investigated the effects of MBD3 on the epithelial-mesenchymal transition (EMT), and the underlying mechanism in pancreatic cancer cells. METHODS: The abilities of migration and invasion were examined by transwell and BD Matrigel invasion assays. EMT and TGF-β/Smad signalling were evaluated...
November 29, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27893715/tgf%C3%AE-promotes-mesenchymal-phenotype-of-pancreatic-cancer-cells-in-part-through-epigenetic-activation-of-vav1
#3
P-H Huang, P-J Lu, L-Y Ding, P-C Chu, W-Y Hsu, C-S Chen, C-C Tsao, B-H Chen, C-T Lee, Y-S Shan, C-S Chen
The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27889393/triple-amirna-vegfrs-inhibition-in-pancreatic-cancer-improves-the-efficacy-of-chemotherapy-through-emt-regulation
#4
Jianfei Huang, Haijun Mei, Zhiyuan Tang, Jieying Li, Xiaojing Zhang, Yixiang Lu, Fang Huang, Qin Jin, Zhiwei Wang
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal outcome. Both novel prognostic markers and therapeutic targets are needed to improve the overall outcome of patients. Although single or double VEGFRs have been studied in PDAC, little is known about the role of triple combination of VEGFRs (VEGFR1, 2, and 3) in prognosis and therapy. We determined VEGFRs protein expression in 241 pancreatic tissues by tissue microarray immunohistochemistry (TMA-IHC), and correlated with patients' clinical characteristics and overall survival...
November 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27878247/oridonin-inhibition-and-mir%C3%A2-200b%C3%A2-3p-zeb1-axis-in-human-pancreatic-cancer
#5
Zhifang Gui, Feng Luo, Yayang Yang, Can Shen, Shuquan Li, Jian Xu
The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition (EMT) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array. The expression of miR‑200b-3p was verified by using real-time PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice and immunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer...
November 18, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27878234/prometastatic-mechanisms-of-caf-mediated-emt-regulation-in-pancreatic-cancer-cells
#6
Tao Shan, Shuo Chen, Xi Chen, Wan Run Lin, Wei Li, Jiancang Ma, Tao Wu, Hong Ji, Yiming Li, Xijuan Cui, Ya'an Kang
Tumor metastasis are accompanied by the EMT (epithelial-mesenchymal transition)-MET (mesenchymal-epithelial transition) two-step process. In this study, we investigated the importance of cancer associated fibroblasts (CAF) in the process. First, the primary cultures of isolated pancreatic CAF, fibroblasts of normal pancreatic tissues (NF), and normal hepatic stellate cells (HSF) were identified and verified via the expression of α-SMA and vimentin. Using an indirect three-dimensional co-culture model, the morphological changes were observed by light microscopy and laser scanning confocal microscopy...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27825542/histopathological-tumor-invasion-of-the-mesenterico-portal-vein-is-characterized-by-aggressive-biology-and-stromal-fibroblast-activation
#7
Hryhoriy Lapshyn, Louisa Bolm, Ilona Kohler, Martin Werner, Franck G Billmann, Dirk Bausch, Ulrich T Hopt, Frank Makowiec, Uwe A Wittel, Tobias Keck, Peter Bronsert, Ulrich F Wellner
BACKGROUND: Mesenterico-portal vein resection (PVR) during pancreatoduodenectomy for pancreatic head cancer was established in the 1990s and can be considered a routine procedure in specialized centers today. True histopathologic portal vein invasion is predictive of poor prognosis. The aim of this study was to examine the relationship between mesenterico-portal venous tumor infiltration (PVI) and features of aggressive tumor biology. METHODS: Patients receiving PVR for pancreatic ductal adenocarcinoma of the pancreatic head were identified from a prospectively maintained database...
November 5, 2016: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/27822411/radiation-promotes-epithelial-to-mesenchymal-transition-and-invasion-of-pancreatic-cancer-cell-by-activating-carcinoma-associated-fibroblasts
#8
Doudou Li, Chao Qu, Zhouyu Ning, Haiyong Wang, Kun Zang, Liping Zhuang, Lianyu Chen, Peng Wang, Zhiqiang Meng
The tumor microenvironment is of crucial importance affecting treatment and prognosis. High degree of carcinoma-associated fibroblast (CAF) infiltration occurs in pancreatic cancer, though its effect on radiotherapy remains unclear. In this study, we demonstrated that radiation enhanced the migration- and invasion-promoting capacity of CAFs both in vitro and in vivo in a lung metastasis model. Radiation exposure increased the expression of CXCL12 by CAFs. CAF-derived CXCL12 promoted tumor cell EMT and invasion directly, acting through CXCR4 on pancreatic cancer cells...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27795830/advance-in-microrna-as-a-potential-biomarker-for-early-detection-of-pancreatic-cancer
#9
REVIEW
Jing Huang, Jianzhou Liu, Kevin Chen-Xiao, Xuemei Zhang, W N Paul Lee, Vay Liang W Go, Gary Guishan Xiao
Pancreatic cancer is characterized as a disease with low survival and high mortality because of no effective diagnostic and therapeutic strategies available in clinic. Conventional clinical diagnostic methods including serum markers and radiological imaging (CT, MRI, EUS, etc.) often fail to detect precancerous or early stage lesions. Development of effective biomarkers is unmet for reduction of mortality of pancreatic cancer. MicroRNAs (miRNAs) are a group of small non-protein-coding RNAs playing roles in regulation of cell physiology including tumorigenesis, apoptotic escape, proliferation, invasion, epithelial-mesenchymal transition (EMT), metastasis and chemoresistance...
2016: Biomarker Research
https://www.readbyqxmd.com/read/27793006/hs-173-a-novel-pi3k-inhibitor-suppresses-emt-and-metastasis-in-pancreatic-cancer
#10
Marufa Rumman, Kyung Hee Jung, Zhenghuan Fang, Hong Hua Yan, Mi Kwon Son, Soo Jung Kim, Juyoung Kim, Jung Hee Park, Joo Han Lim, Sungwoo Hong, Soon-Sun Hong
Pancreatic cancer is one of the most aggressive solid malignancies prone to metastasis. Epithelial-mesenchymal transition (EMT) contributes to cancer invasiveness and drug resistance. In this study, we investigated whether HS-173, a novel PI3K inhibitor blocked the process of EMT in pancreatic cancer. HS-173 inhibited the growth of pancreatic cancer cells in a dose- and time-dependent manner. Moreover, it significantly suppressed the TGF-β-induced migration and invasion, as well as reversed TGF-β-induced mesenchymal cell morphology...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27777765/epithelial-mesenchymal-transition-induction-is-associated-with-augmented-glucose-uptake-and-lactate-production-in-pancreatic-ductal-adenocarcinoma
#11
Menghan Liu, Lake-Ee Quek, Ghazal Sultani, Nigel Turner
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy with dismal prognosis. Metastatic spread and therapeutic resistance, the main causes of PDAC-related mortalities, are both partially underlined by the epithelial-mesenchymal transition (EMT) of PDAC cells. While the role of Warburg metabolism has been recognized in supporting rapid cellular growth and proliferation in many cancer types, less is known about the metabolic changes occurring during EMT, particularly in the context of PDAC...
2016: Cancer & Metabolism
https://www.readbyqxmd.com/read/27776346/highly-aligned-stromal-collagen-is-a-negative-prognostic-factor-following-pancreatic-ductal-adenocarcinoma-resection
#12
Cole R Drifka, Agnes G Loeffler, Kara Mathewson, Adib Keikhosravi, Jens C Eickhoff, Yuming Liu, Sharon M Weber, W John Kao, Kevin W Eliceiri
Risk factors for pancreatic ductal adenocarcinoma (PDAC) progression after surgery are unclear, and additional prognostic factors are needed to inform treatment regimens and therapeutic targets. PDAC is characterized by advanced sclerosis of the extracellular matrix, and interactions between cancer cells, fibrillar collagen, and other stromal components play an integral role in progression. Changes in stromal collagen alignment have been shown to modulate cancer cell behavior and have important clinical value in other cancer types, but little is known about its role in PDAC and prognostic value...
October 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27775688/inhibition-of-nf-kappa-b-pathway-leads-to-deregulation-of-epithelial-mesenchymal-transition-and-neural-invasion-in-pancreatic-cancer
#13
Alice Nomura, Kaustav Majumder, Bhuwan Giri, Patricia Dauer, Vikas Dudeja, Sabita Roy, Sulagna Banerjee, Ashok K Saluja
NF-κB has an essential role in the initiation and progression of pancreatic cancer and specifically mediates the induction of epithelial-mesenchymal transition and invasiveness. In this study, we demonstrate the importance of activated NF-κB signaling in EMT induction, lymphovascular metastasis, and neural invasion. Modulation of NF-κB activity was accomplished through the specific NF-κB inhibitor (BAY 11-7085), triptolide, and Minnelide treatment, as well as overexpression of IKBα repressor and IKK activator plasmids...
December 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27764163/targeting-epithelial-mesenchymal-transition-for-identification-of-inhibitors-for-pancreatic-cancer-cell-invasion-and-tumor-spheres-formation
#14
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
https://www.readbyqxmd.com/read/27750041/paracrine-il-6-signaling-mediates-the-effects-of-pancreatic-stellate-cells-on-epithelial-mesenchymal-transition-via-stat3-nrf2-pathway-in-pancreatic-cancer-cells
#15
Yuan Seng Wu, Ivy Chung, Won Fen Wong, Atsushi Masamune, Maw Shin Sim, Chung Yeng Looi
BACKGROUND: We previously showed that pancreatic stellate cells (PSC) secreted interleukin (IL)-6 and promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation via nuclear factor erythroid 2 (Nrf2)-mediated metabolic reprogramming. Epithelial-mesenchymal transition (EMT) is a key process for the metastatic cascade. To study the mechanism of PDAC progression to metastasis, we investigated the role of PSC-secreted IL-6 in activating EMT and the involvement of Nrf2 in this process...
October 14, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27733216/upregulation-of-microrna-935-promotes-the-malignant-behaviors-of-pancreatic-carcinoma-panc-1-cells-via-targeting-inositol-polyphosphate-4-phosphatase-type-i-gene-inpp4a
#16
Cuiyue Wang, Zhen Feng, Kaitong Jiang, Xiuli Zuo
Our goal was to determine the roles and regulatory mechanism of microRNA-935 (miR-935) in the progression of pancreatic cancer. The results showed that, compared with normal pancreatic tissues and cells, the expression of miR-935 was markedly upregulated while INPP4A expression was obviously downregulated in pancreatic cancer tissues and PANC-1 cells. After transfection with miR-935 inhibitor, miR-935 was significantly suppressed, and suppression of miR-935 significantly inhibited cell proliferation, suppressed cell migration, and induced cell apoptosis of pancreatic cancer cells...
October 11, 2016: Oncology Research
https://www.readbyqxmd.com/read/27726102/mirna-221-3p-desensitizes-pancreatic-cancer-cells-to-5-fluorouracil-by-targeting-rb1
#17
Lijun Zhao, Dongling Zou, Xueju Wei, Lanlan Wang, Yuanyuan Zhang, Siqi Liu, Yanmin Si, Hualu Zhao, Fang Wang, Jia Yu, Yanni Ma, Guotao Sun
Pancreatic cancer is a highly lethal disease due to its rapid dissemination and resistance to conventional chemotherapy. MicroRNAs (miRNAs) are emerging as novel regulators of chemoresistance, which modulate the expression of drug resistance-related genes. MiRNA-221 has been reported to be associated with chemoresistance in various types of cancer. But the detailed molecular mechanism about miR-221-3p regulating 5-fluorouracil (5-FU) resistance in human pancreatic cancer remains to be clarified. In this study, we investigated the association between miR-221-3p expression and 5-FU sensitivity...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27718126/suppression-of-cd26-inhibits-growth-and-metastasis-of-pancreatic-cancer
#18
Chunxiang Ye, Xiuyun Tian, Guanjun Yue, Liang Yan, Xiaoya Guan, Shan Wang, Chunyi Hao
CD26/DPPIV is a glycosylated transmembrane type II protein and has a multitude of biological functions, while its impact on the malignant phenotypes of cancer cells has not been fully understood. This study aimed to investigate the effect of CD26 on growth and metastasis of pancreatic cancer cells in vitro and in vivo. We found in this study that CD26 expression was higher in cell lines that derived from the metastatic sites than those from the primary tumor sites. In specimens of pancreatic cancer patients, CD26 expression was higher in cancerous tissues than in paired normal tissues...
October 7, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27713160/role-of-bcl9l-in-transforming-growth-factor-%C3%AE-tgf-%C3%AE-induced-epithelial-to-mesenchymal-transition-emt-and-metastasis-of-pancreatic-cancer
#19
Giuseppina Sannino, Nicole Armbruster, Mona Bodenhöfer, Ursula Haerle, Diana Behrens, Malte Buchholz, Ulrich Rothbauer, Bence Sipos, Christian Schmees
Pancreatic ductal adenocarcinoma (PDAC) has a low overall survival rate, which is approximately 20% during the first year and decreases to less than 6% within five years of the disease. This is due to premature dissemination accompanied by a lack of disease-specific symptoms during the initial stages. Additionally, to date there are no biomarkers for an early prognosis available.A growing number of studies indicate that epithelial to mesenchymal transition (EMT), triggered by WNT-, TGF-β- and other signaling pathways is crucial for the initiation of the metastatic process in PDAC...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27693633/hypoxia-induces-twist-activated-epithelial-mesenchymal-transition-and-proliferation-of-pancreatic-cancer-cells-in%C3%A2-vitro-and-in-nude-mice
#20
Shi Chen, Jiang-Zhi Chen, Jia-Qiang Zhang, Hui-Xin Chen, Mao-Lin Yan, Long Huang, Yi-Feng Tian, Yan-Lin Chen, Yao-Dong Wang
The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. TWIST activated by intra-tumoral hypoxia functions to promote the EMT. We hypothesized that TWIST and the downstream gene pathway could mediate PDAC progression under hypoxia. Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other proteins. Pancreatic cancer cell lines were used for in vitro experiments and nude mice were used to confirm the in vivo data...
September 28, 2016: Cancer Letters
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