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Pancreatic ductal adenocarcinoma

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https://www.readbyqxmd.com/read/28529153/model-of-vascular-desmoplastic-multispecies-tumor-growth
#1
Chin F Ng, Hermann B Frieboes
We present a three-dimensional nonlinear tumor growth model composed of heterogeneous cell types in a multicomponent-multispecies system, including viable, dead, healthy host, and extra-cellular matrix (ECM) tissue species. The model includes the capability for abnormal ECM dynamics noted in tumor development, as exemplified by pancreatic ductal adenocarcinoma, including dense desmoplasia typically characterized by a significant increase of interstitial connective tissue. An elastic energy is implemented to provide elasticity to the connective tissue...
May 18, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28528374/pancreatic-cysts-and-guidelines
#2
REVIEW
James J Farrell
Pancreatic cysts, especially incidental asymptomatic ones seen on noninvasive imaging such as CT or MR imaging, remain a clinical challenge. The etiology of such cysts may range from benign cysts without any malignant potential such as pancreatic pseudocysts and serous cystadenomas to premalignant or frankly malignant cysts such as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, cystic degeneration associated with solid tumors such as pancreatic ductal adenocarcinoma or pancreatic endocrine neoplasms, and solid pseudopapillary neoplasms...
May 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28524160/stroma-regulated-hmga2-is-an-independent-prognostic-marker-in-pdac-and-aac
#3
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
#4
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
#5
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
#6
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/28516291/downstaging-in-stage-iv-pancreatic-cancer-a-new-population-eligible-for-surgery
#7
Isabella Frigerio, Paolo Regi, Alessandro Giardino, Filippo Scopelliti, Roberto Girelli, Claudio Bassi, Stefano Gobbo, Paolo Tinazzi Martini, Paola Capelli, Mirko D'Onofrio, Giuseppe Malleo, Laura Maggino, Elena Viviani, Giovanni Butturini
BACKGROUND: Recent papers consider surgery as an option for synchronous liver oligometastatic patients [metastatic pancreatic ductal adenocarcinoma (mPDAC)]. In this study, we present our series of resected mPDACs after neoadjuvant chemotherapy (nCT). PATIENTS AND METHODS: All patients resected after downstaging of mPDAC were included in this study. Downstaging criteria were disappearance of liver metastasis and a decrease in cancer antigen (CA) 19-9. The type and duration of nCT, last nCT surgery interval, histology, morbidity, and mortality were recorded, and overall survival (OS) and disease-free survival (DFS) were analyzed...
May 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28510280/modelling-the-iatrogenic-pancreatic-cancer-risk-after-islet-autotransplantation-in-mouse
#8
E Dugnani, V Pasquale, D Liberati, A Citro, E Cantarelli, S Pellegrini, P Marra, T Canu, G Balzano, M Scavini, A Esposito, C Doglioni, L Piemonti
Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk islets and/or pancreatic exocrine clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL-Kras(G12D/+) ;LSL-Trp53(R172H/+) ;Pdx-1-Cre, termed KPC mouse) were transplanted via the portal vein in syngeneic wild type (WT) severely diabetic recipients in the following treatment groups: group A (n=11) received KPC exocrine clusters in volume equal to 250 equivalent islets (IEQs); group B (n=12) received 250 WT IEQs mixed with KPC exocrine clusters (1:1 volume ratio); group C (n=5) received 250 KPC IEQs and group D (n=7) received 250 wild type IEQs...
May 16, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28507327/pde3-inhibitor-and-egcg-combination-treatment-suppress-cancer-stem-cell-properties-in-pancreatic-ductal-adenocarcinoma
#9
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
#10
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
#11
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
#12
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/28497169/homogeneous-pancreatic-cancer-spheroids-mimic-growth-pattern-of-circulating-tumor-cell-clusters-and-macrometastases-displaying-heterogeneity-and-crater-like-structure-on-inner-layer
#13
Hao Feng, Bao-Chi Ou, Jing-Kun Zhao, Shuai Yin, Ai-Guo Lu, Eva Oechsle, Wolfgang E Thasler
PURPOSE: Pancreatic cancer 3D in vitro models including multicellular tumor spheroid (MCTS), single cell-derived tumor spheroid (SCTS), tissue-derived tumor spheroid, and organotypic models provided powerful platforms to mimic in vivo tumor. Recent work supports that circulating tumor cell (CTC) clusters are more efficient in metastasis seeding than single CTCs. The purpose of this study is to establish 3D culture models which can mimic single CTC, monoclonal CTC clusters, and the expansion of macrometastases...
May 11, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28494747/new-diagnostic-and-therapeutic-aspects-of-pancreatic-ductal-adenocarcinoma
#14
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/28493831/multi-modality-imaging-monitored-creation-of-rat-orthotopic-pancreatic-head-cancer-with-obstructive-jaundice
#15
Zhibin Bai, Yaoping Shi, Jianfeng Wang, Longhua Qiu, Gaojun Teng, Feng Zhang, Xiaoming Yang
PURPOSE: To investigate the feasibility of using multi-modality imaging to monitor the creation of rat models with orthotopic pancreatic head cancer with obstructive jaundice. RESULTS: 27 of 52 rats (51.92%) developed pancreatic head cancer. The tumor formation rate was significantly higher in the animal group receiving bioluminescent tumor, compared to the group receiving non-bioluminescent donor tumors [78.1% (25/32 rats) vs 10.0% (2/20 rats), P = 0.0001]. Both ultrasound imaging and MRI clearly characterized the orthotopic tumors...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28493059/characterization-of-oatp1b3-and-oatp2b1-transporter-expression-in-the-islet-of-the-adult-human-pancreas
#16
Michelle Kim, Perri Deacon, Rommel G Tirona, Richard B Kim, Christopher L Pin, Henriette E Meyer Zu Schwabedissen, Rennian Wang, Ute I Schwarz
Organic anion-transporting polypeptides (OATPs) are membrane proteins that mediate cellular uptake of structurally diverse endogenous and exogenous compounds, including bile salts, thyroid and sex hormones, pharmacological agents, and toxins. Roles of OATPs in human liver are well established. Our recent report suggested the presence of the hepatic transporter OATP1B3 in human β cells. The aim of this study was to better characterize cellular localization and interindividual variation in OATP1B3 expression in human adult islets as a function of age, sex, and pancreatic disease, and to assess the expression of other OATPs...
May 10, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28489577/pancreatic-cancer-ascites-xenograft-an-expeditious-model-mirroring-advanced-therapeutic-resistant-disease
#17
Talia Golan, Chani Stossel, Michael Schvimer, Dikla Atias, Sharon Halperin, Ella Buzhor, Maria Raitses-Gurevich, Keren Cohen, Sara Pri-Chen, Julie Wilson, Robert E Denroche, Ilinca Lungu, John M S Bartlett, Faridah Mbabaali, Yosef Yarden, Nishanth Belugali Nataraj, Steven Gallinger, Raanan Berger
Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20-30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts.Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488580/germline-mutations-in-pancreatic-cancer-and-potential-new-therapeutic-options
#18
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
#19
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
#20
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
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