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https://www.readbyqxmd.com/read/28526679/succession-of-transiently-active-tumor-initiating-cell-clones-in-human-pancreatic-cancer-xenografts
#1
Claudia R Ball, Felix Oppel, Karl Roland Ehrenberg, Taronish D Dubash, Sebastian M Dieter, Christopher M Hoffmann, Ulrich Abel, Friederike Herbst, Moritz Koch, Jens Werner, Frank Bergmann, Naveed Ishaque, Manfred Schmidt, Christof von Kalle, Claudia Scholl, Stefan Fröhling, Benedikt Brors, Wilko Weichert, Jürgen Weitz, Hanno Glimm
Although tumor-initiating cell (TIC) self-renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long-term progression of PDAC in serial xenotransplantation is driven by a succession of transiently active TICs producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations...
May 19, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28524160/stroma-regulated-hmga2-is-an-independent-prognostic-marker-in-pdac-and-aac
#2
Carina Strell, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen, Arne Östman
BACKGROUND: The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. METHODS: We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. RESULTS: HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28521407/clinicopathological-implications-of-nqo1-overexpression-in-the-prognosis-of-pancreatic-adenocarcinoma
#3
Meiying Ji, Aihua Jin, Jie Sun, Xuelian Cui, Yang Yang, Liyan Chen, Zhenhua Lin
Nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase 1 (NQO1) protects cells from oxidative damage. NQO1 has been reported to be upregulated in numerous solid tumors, suggesting a role in carcinogenesis and tumor progression. The present study attempted to investigate the clinical prognostic significance of NQO1 overexpression in pancreatic ductal adenocarcinoma (PDAC). A total of 181 tissue specimens were studied, including 126 PDAC and 55 normal pancreas specimens, which were selected for immunohistochemical staining of NQO1 protein...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521289/role-of-transgelin-2-in-diabetes-associated-pancreatic-ductal-adenocarcinoma
#4
Yan Sun, Weiwei He, Man Luo, Yuhong Zhou, Guilin Chang, Weiying Ren, Kefen Wu, Xi Li, Jiping Shen, Xiaoping Zhao, Yu Hu
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Diabetes is a significant risk factor for PDAC and >50% of PDAC patients have concomitant diabetes. How diabetes influences the initiation and progression of PDAC remains elusive. Here, we show that transgelin-2 is dominantly expressed in PDAC tissues compared with adjacent normal tissues. The high level of transgelin-2 indicates poor survival of patients with PDAC. Remarkably, transgelin-2 expression is correlated with diabetic status...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28517236/effect-of-centralization-on-long-term-survival-after-resection-of-pancreatic-ductal-adenocarcinoma
#5
R Ahola, A Siiki, K Vasama, M Vornanen, J Sand, J Laukkarinen
BACKGROUND: Centralization of pancreatic surgery has resulted in improved short-term outcomes in a number of healthcare systems. The aim of this study was to see whether hospital volume influenced long-term prognosis, use of adjuvant therapy or histopathological evaluation of patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients undergoing surgical resection of PDAC in Finland between 2002 and 2008 were identified from national registers...
May 18, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28507327/pde3-inhibitor-and-egcg-combination-treatment-suppress-cancer-stem-cell-properties-in-pancreatic-ductal-adenocarcinoma
#6
Motofumi Kumazoe, Mika Takai, Shun Hiroi, Chieri Takeuchi, Maasa Yamanouchi, Takashi Nojiri, Hiroaki Onda, Jaehoon Bae, Yuhui Huang, Kanako Takamatsu, Shuya Yamashita, Shuhei Yamada, Kenji Kangawa, Takashi Takahashi, Hiroshi Tanaka, Hirofumi Tachibana
Recurrence following chemotherapy is observed in the majority of patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an efficient approach to targeting pancreatic CSCs remains to be established. Here we show that in cancer cells overexpressing the 67-kDa laminin receptor (67LR)-dependent cyclic GMP (cGMP) inducer, epigallocatechin-3-O-gallate (EGCG) and a phosphodiesterase 3 (PDE3) inhibitor in combination significantly suppressed the Forkhead box O3 and CD44 axis, which is indispensable for the CSC properties of PDAC...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507210/diabetes-pancreatogenic-diabetes-and-pancreatic-cancer
#7
Dana K Andersen, Murray Korc, Gloria M Petersen, Guido Eibl, Donghui Li, Michael R Rickels, Suresh T Chari, James L Abbruzzese
The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association's 76th Scientific Sessions in June 2016...
May 2017: Diabetes
https://www.readbyqxmd.com/read/28507102/foxo3-pgc-1%C3%AE-signaling-axis-is-essential-for-cancer-stem-cell-properties-of-pancreatic-ductal-adenocarcinoma
#8
Motofumi Kumazoe, Mika Takai, Shun Hiroi, Chieri Takeuchi, Mai Kadomatsu, Takashi Nojiri, Hiroaki Onda, Jaehoon Bae, Yuhui Huang, Kanako Takamatsu, Shuya Yamashita, Kenji Kangawa, Hirofumi Tachibana
In 95% of patients with pancreatic ductal adenocarcinoma (PDAC), recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anti-cancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knockin/knock down experiments and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)/PPAR-γ co-activator-1β (PGC- 1β)/pyruvate dehydrogenase -A1 (PDHA1) pathway is essential for CD44 expression and CSC properties...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28501471/comparison-of-endoscopic-ultrasound-guided-fine-needle-aspiration-and-pet-ct-in-preoperative-diagnosis-of-pancreatic-adenocarcinoma
#9
Jin-Ping Lai, Yong Yue, Wei Zhang, Yihua Zhou, David Frishberg, Laith H Jamil, James M Mirocha, Maha Guindi, Bonnie Balzer, Shikha Bose, Dengfeng Cao, Simon Lo, Xuemo Fan, Joanne K Rutgers
BACKGROUND: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the procedure of choice to investigate and sample pancreatic masses for the preoperative diagnosis of pancreatic ductal adenocarcinoma (PDAC). The role of (18)fluoro-deoxyglucose positron emission tomography/computed tomography (PET/CT) in PDAC is debated. This study evaluates the role of EUS-FNA as compared to PET/CT in the preoperative evaluation of PDAC. METHODS: Preoperative evaluation by PET/CT and EUS-FNA was performed on 25 patients with pancreatic solid lesions, who underwent a subsequent Whipple procedure or partial pancreatic resection...
April 13, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28499807/evaluation-of-insulin-like-growth-factor-igf-1-and-retinol-binding-protein-rbp-4-levels-in-patients-with-newly-diagnosed-pancreatic-adenocarcinoma-pdac
#10
Barbara Wlodarczyk, Anita Gasiorowska, Anna Borkowska, Ewa Malecka-Panas
BACKGROUND/OBJECTIVES: The elevation of insulin-like growth factor 1 (IGF-1) and adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the risk of many cancers. The aim of this study was to evaluate the serum concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis (CP). METHODS: The study included 43 patients with PDAC, 39 patients with CP and 10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA method (Corgenix UK Ltd R&D Systems)...
April 4, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28494747/new-diagnostic-and-therapeutic-aspects-of-pancreatic-ductal-adenocarcinoma
#11
Harald Mangge, Tobias Niedrist, Wilfried Renner, Stefan Lyer, Christoph Alexiou, Johannes Haybaeck
Pancreatic ductal adenocarcinoma (PDAC) is devastating. Because of its silent nature, the disease is often only diagnosed once it has reached an advanced, frequently inoperable stage. To date, we have no biomarkers that facilitate earlier diagnosis, leaving sufficient time for curative therapy that effectively lowers the very high mortality rate of this cancer entity. Because of this, the life expectancy of patients with PDAC is low (i.e. < 6% five-year survival rates). New data, including particular genetic signatures and features of the stromal architecture of PDAC tumors, may better explain their aggressiveness, their relatively long-lasting painless expansion, and why chemotherapy so frequently fails...
May 10, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28488580/germline-mutations-in-pancreatic-cancer-and-potential-new-therapeutic-options
#12
REVIEW
Rille Pihlak, Juan W Valle, Mairéad G McNamara
Due to short-lived treatment responses in unresectable disease, pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is availability of new information about germline and sporadic mutations in the deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and the expectation is that novel targeted therapies will thus be developed. A variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with the highest prevalence being BRCA1/2...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487490/differentiation-of-pancreatic-neuroendocrine-carcinoma-from-pancreatic-ductal-adenocarcinoma-using-magnetic-resonance-imaging-the-value-of-contrast-enhanced-and-diffusion-weighted-imaging
#13
Chuangen Guo, Xiao Chen, Zhongqiu Wang, Wenbo Xiao, Qidong Wang, Ke Sun, Xiaoling Zhuge
Pancreatic neuroendocrine carcinoma (PNEC) is often misdiagnosed as pancreatic ductal adenocarcinoma (PDAC). This retrospective study differentiated PNEC from PDAC using magnetic resonance imaging (MRI), including contrast-enhanced (CE) and diffusion-weighted imaging (DWI). Clinical data and MRI findings, including the T1/T2 signal, tumor boundary, size, enhancement degree, and apparent diffusion coefficient (ADC), were compared between 37 PDACs and 13 PNECs. Boundaries were more poorly defined in PDAC than PNEC (97...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28486750/stromal-spock1-supports-invasive-pancreatic-cancer-growth
#14
Veronique L Veenstra, Helene Damhofer, Cynthia Waasdorp, Anne Steins, Hemant M Kocher, Jan Paul Medema, Hanneke W van Laarhoven, Maarten F Bijlsma
Pancreatic ductal adenocarcinoma (PDAC) is marked by an abundant stromal deposition. This stroma is suspected to harbor both tumor-promoting as well as -suppressing properties. This is underscored by the disappointing results of stroma targeting in clinical studies. Given the complexity of tumor-stroma interaction in PDAC, there is a need to identify the stromal proteins that are predominantly tumor-promoting. One possible candidate is SPOCK1 that we previously identified in a screening effort in PDAC. We extensively mined PDAC gene expression datasets, and used species-specific transcript analysis in mixed-species models for PDAC to study the patterns and driver mechanisms of SPOCK1 expression in PDAC...
May 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28484232/inhibition-of-sp1-prevents-er-homeostasis-and-causes-cell-death-by-lysosomal-membrane-permeabilization-in-pancreatic-cancer
#15
Patricia Dauer, Vineet K Gupta, Olivia McGinn, Alice Nomura, Nikita S Sharma, Nivedita Arora, Bhuwan Giri, Vikas Dudeja, Ashok K Saluja, Sulagna Banerjee
Endoplasmic reticulum (ER) stress initiates an important mechanism for cell adaptation and survival, named the unfolded protein response (UPR). Severe or chronic/prolonged UPR can breach the threshold for survival and lead to cell death. There is a fundamental gap in knowledge on the molecular mechanism of how chronic ER stress is stimulated and leads to cell death in pancreatic ductal adenocarcinoma (PDAC). Our study shows that downregulating specificity protein 1 (Sp1), a transcription factor that is overexpressed in pancreatic cancer, activates UPR and results in chronic ER stress...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28477403/micro-rna-21-regulates-cancer-associated-fibroblast-mediated-frug-resistance-in-pancreatic-cancer
#16
Lulin Zhang, Jun Yao, Wenyao Li, Ce Zhang
Pancreatic adenocarcinoma (PDAC) is one of the leading cause of cancer death due to its highly aggressive biological nature and resistance to chemotherapies. Former study also indicated that miR-21 in cancer-associated fibroblasts (CAFs) is an important regulator of their activation. However, whether miR-21 in CAFs would regulate PDAC's tumor microenvironment and leading to drug resistance remain unknown. In this study, we evaluated the relationship among CAFs activation, miR-21 expression level and drug resistance using PDAC patient tumor samples...
May 5, 2017: Oncology Research
https://www.readbyqxmd.com/read/28476735/identification-of-targetable-alk-rearrangements-in-pancreatic-ductal-adenocarcinoma
#17
Aatur D Singhi, Siraj M Ali, Jill Lacy, Andrew Hendifar, Khanh Nguyen, Jamie Koo, Jon H Chung, Joel Greenbowe, Jeffrey S Ross, Marina N Nikiforova, Herbert J Zeh, Inderpal S Sarkaria, Anil Dasyam, Nathan Bahary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival of 8%. Current therapeutic regimens are largely ineffective and underscore the need for novel treatment strategies. Chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene have been identified in several neoplasms. In addition, ALK protein inhibitors have proven efficacy in patients with ALK-rearranged tumors. However, ALK translocations in PDAC have not been described. Through comprehensive genomic profiling of 3,170 PDACs, we identified 5 cases (0...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28473530/beta-blocker-drug-use-and-survival-among-patients-with-pancreatic-adenocarcinoma
#18
Ruzan Udumyan, Scott Montgomery, Fang Fang, Henrik Almroth, Unnur Valdimarsdottir, Anders Ekbom, Karin E Smedby, Katja Fall
Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register (n=2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register...
May 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28473229/atypical-flat-lesions-derive-from-pancreatic-acinar-cells
#19
Guido von Figura, Leonie Fahrenkrog-Petersen, Ana Hidalgo-Sastre, Daniel Hartmann, Norbert Hüser, Roland M Schmid, Matthias Hebrok, Nilotpal Roy, Irene Esposito
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is thought to derive from different precursor lesions including the recently identified atypical flat lesions (AFL). While all precursor lesions and PDAC share ductal characteristics, there is an ongoing debate about the cellular origin of the different PDAC precursor lesions. In particular, pancreatic acinar cells have previously been shown to display a remarkable plasticity being able to undergo ductal dedifferentiation in the context of oncogenic stimuli...
April 25, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28473189/a-tale-of-two-cancers-traveling-to-treat-pancreatic-and-thyroid-cancer
#20
Michael G White, Megan K Applewhite, Edwin L Kaplan, Peter Angelos, Dezheng Huo, Raymon H Grogan
BACKGROUND: Patients diagnosed with a malignancy must decide whether to travel for care at an academic center or receive treatment at a nearby hospital. Here we examine differences in demographics, treatment, and outcomes of those traveling to academic centers for their care vs those not traveling, as well as compare travel for an aggressive vs indolent malignancy. STUDY DESIGN: All patients with papillary thyroid carcinoma (PTC) or pancreatic ductal adenocarcinoma (PDAC) undergoing surgical resection and in the National Cancer Database were examined...
March 25, 2017: Journal of the American College of Surgeons
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