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https://www.readbyqxmd.com/read/27895643/azithromycin-attenuates-pseudomonas-induced-lung-inflammation-by-targeting-bacterial-proteins-secreted-in-the-cultured-medium
#1
Teresinha Leal, Gabriella Bergamini, François Huaux, Nadtha Panin, Sabrina Noel, Barbara Dhooghe, Jeremy B Haaf, Pierluigi Mauri, Sara Motta, Dario Di Silvestre, Paola Melotti, Claudio Sorio
BACKGROUND: Pseudomonas aeruginosa airway infections are a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Azithromycin improves the related clinical outcomes, but its mechanisms of action remain poorly understood. We tested the hypothesis that azithromycin downregulates P. aeruginosa-induced pro-inflammatory responses by modifying release of bacterial proteins. METHODS: We monitored inflammatory markers in lungs of CF mutant mice and their littermate controls in response to conditioned media (CM) collected from the reference P...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27889647/activation-of-wnt-%C3%AE-catenin-signaling-enhances-pancreatic-cancer-development-and-the-malignant-potential-via-up-regulation-of-cyr61
#2
Makoto Sano, David R Driscoll, Wilfredo E DeJesus-Monge, Brian Quattrochi, Victoria A Appleman, Jianhong Ou, Lihua Julie Zhu, Nao Yoshida, Shintaro Yamazaki, Tadatoshi Takayama, Masahiko Sugitani, Norimichi Nemoto, David S Klimstra, Brian C Lewis
Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of WNT signaling is also commonly observed in PDAC. To ascertain the impact of postnatal activation of WNT-stimulated signaling pathways in PDAC development, we combined the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras(G12D), Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin(S37A) and WNT1 stimulated the progression of premalignant pancreatic intraepithelial neoplasias (PanIN) and PDAC development...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27888473/nasal-mucosa-healing-after-endoscopic-sinus-surgery-in-chronic-rhinosinusitis-of-elderly-patients-role-of-topic-alpha-tocopherol-acetate
#3
Domenico Testa, Giuseppina Marcuccio, Giorgio Panin, Andrea Bianco, Domenico Tafuri, Francesco Zappoli Thyrion, Michele Nunziata, Pasquale Piombino, Germano Guerra, Gaetano Motta
BACKGROUND: Chronic rhinosinusitis (CRS) in European country ranges in elderly patients from 4.5 to 12% of population and has a significant effect on quality of life. In these patients, rhinosinusitis is linked to immune functions changes with age and to mucosal paraphysiological alterations such as crusting formations with atrophic epithelium, variations of nasal airflow and modifications of the mucociliary clearance. Failure of medical treatments leads to surgery in patients with persistent symptoms and radiographic signs of CRS...
November 25, 2016: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/27816353/predisposing-factors-for-pancreatic-adenocarcinoma-what-is-the-role-of-imaging
#4
M-P Vullierme, M Lagadec
Early detection of pancreatic adenocarcinoma is the goal of imaging, enabling curative surgery. The identification of high-grade dysplastic precursor lesions is even more beneficial. Two forms are now better known: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). To detect these lesions with imaging, we need to know the patterns associated with them. A screening program could then be used to pinpoint them. This program could not be applied to the entire population...
December 2016: Diagnostic and Interventional Imaging
https://www.readbyqxmd.com/read/27795812/mucins-in-neoplasms-of-pancreas-ampulla-of-vater-and-biliary-system
#5
REVIEW
Dimitrios Moschovis, Giorgos Bamias, Ioanna Delladetsima
Tumors of the pancreas, the ampulla of Vater, and the extrahepatic and intrahepatic bile ducts have significant histological similarities due to the common embryonic origin of the pancreatobiliary system. This obviates the need for discovery of biomarkers with diagnostic and prognostic value for these tumors. Mucins, especially MUC-1, -2, -4 and -5AC, are important candidates for developing into such reliable biomarkers. Increased expression of MUC1 occurs in pancreatic ductal adenocarcinomas and is associated with increased degrees of dysplasia in pancreatic intraepithelial neoplasia (PanIN)...
October 15, 2016: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/27788482/reg-proteins-promote-acinar-to-ductal-metaplasia-and-act-as-novel-diagnostic-and-prognostic-markers-in-pancreatic-ductal-adenocarcinoma
#6
Qing Li, Hao Wang, George Zogopoulos, Qin Shao, Kun Dong, Fudong Lv, Karam Nwilati, Xian-Yong Gui, Adeline Cuggia, Jun-Li Liu, Zu-Hua Gao
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27788239/interaction-between-darunavir-and-etravirine-is-partly-mediated-by-cyp3a5-polymorphism
#7
Leïla Belkhir, Laure Elens, Francis Zech, Nadtha Panin, Anne Vincent, Jean Cyr Yombi, Bernard Vandercam, Vincent Haufroid
OBJECTIVES: To assess the impact of the loss-of-function CYP3A5*3 allele (rs776746, 6986A>G SNP) on darunavir (DRV) plasma concentrations. METHODS: 135 HIV-1 infected patients treated with DRV-based therapy were included in the study and plasma samples were obtained immediately before drug intake in order to determine DRV trough concentrations using an ultra performance liquid chromatography method (UPLC) with diode-array detection (DAD). Noteworthy is the fact that in 16 (11...
2016: PloS One
https://www.readbyqxmd.com/read/27783689/epithelial-to-stromal-re-distribution-of-primary-cilia-during-pancreatic-carcinogenesis
#8
Simon Schimmack, Sarah Kneller, Nigora Dadabaeva, Frank Bergmann, Andrew Taylor, Thilo Hackert, Jens Werner, Oliver Strobel
BACKGROUND: The Hedgehog (HH) pathway is a mediator in pancreatic ductal adenocarcinoma (PDAC). Surprisingly, previous studies suggested that primary cilia (PC), the essential organelles for HH signal transduction, were lost in PDAC. The aim of this study was to determine the presence of PC in human normal pancreas, chronic pancreatitis, and during carcinogenesis to PDAC with focus on both epithelia and stroma. METHODS: PC were analyzed in paraffin sections from normal pancreas, chronic pancreatitis, intraductal papillary-mucinous neoplasia, and PDAC, as well as in primary human pancreatic stellate cells (PSC) and pancreatic cancer cell lines by double immunofluorescence staining for acetylated α-tubuline and γ-tubuline...
2016: PloS One
https://www.readbyqxmd.com/read/27775692/quantitative-assessment-of-pancreatic-cancer-precursor-lesions-in-ihc-stained-tissue-with-a-tissue-image-analysis-platform
#9
Famke Aeffner, Nathan T Martin, Mirza Peljto, Joshua C Black, Justin K Major, Maryam Jangani, Michael O Ports, Joseph S Krueger, G David Young
Tissue image analysis (tIA) is emerging as a powerful tool for quantifying biomarker expression and distribution in complex diseases and tissues. Pancreatic ductal adenocarcinoma (PDAC) develops in a highly complex and heterogeneous tissue environment and, generally, has a very poor prognosis. Early detection of PDAC is confounded by limited knowledge of the pre-neoplastic disease stages and limited methods to quantitatively assess disease heterogeneity. We sought to develop a tIA approach to assess the most common PDAC precursor lesions, pancreatic intraepithelial neoplasia (PanIN), in tissues from Kras(LSL-G12D/+); Trp53(LSL-R172H/+); Pdx-Cre (KPC) mice, a validated model of PDAC development...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27764699/fbxw7-deletion-accelerates-kras-g12d-driven-pancreatic-tumorigenesis-via-yap-accumulation
#10
Qiang Zhang, Yaqing Zhang, Joshua D Parsels, Ines Lohse, Theodore S Lawrence, Marina Pasca di Magliano, Yi Sun, Meredith A Morgan
Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-Kras(G12D);Fbxw7(fl/fl) (KFC(fl/fl)) compound mice. We found that KFC(fl/fl) mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age...
November 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27752440/biomonitoring-of-selected-persistent-organic-pollutants-pcdd-fs-pcbs-and-pbdes-in-finnish-and-russian-terrestrial-and-aquatic-animal-species
#11
A Holma-Suutari, P Ruokojärvi, A A Komarov, D A Makarov, V V Ovcharenko, A N Panin, H Kiviranta, S Laaksonen, M Nieminen, M Viluksela, A Hallikainen
BACKGROUND: The Finnish and Russian animal species (semi-domesticated reindeer, Finnish wild moose, Baltic grey seal and Baltic herring) samples were biomonitored in terrestrial and aquatic environments for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs). RESULTS: Grey seal (Halichoerus grypus) was clearly the most contaminated species. The mean PBDE concentration in grey seal was 115 ng/g fat, and the highest WHO-PCDD/F-PCB-TEQ (toxic equivalent set by WHO) was 327 pg/g fat...
2016: Environmental Sciences Europe
https://www.readbyqxmd.com/read/27748943/c-fos-erk-promotes-the-progression-from-pancreatic-intraepithelial-neoplasia-to-pancreatic-ductal-adenocarcinoma
#12
Lei You, Xiaoxia Ren, Yongxing Du, Wenjing Zhao, Ming Cui, Ge Chen, Yupei Zhao
Pathogenesis of pancreatic ductal adenocarcinoma (PDAC) is thought to develop through the progression of precursor lesions, known as pancreatic intraepithelial neoplasias (PanIN). In the present study, we showed that c-Fos promoted proliferation, cell cycle and migration in pancreatic cancer cells. Caerulein was used to accelerate the pathogenesis of Pdx-cre; KrasG12D mice. During PanIN formation and development of PDAC, the expression of ERK and c-Fos increased concomitantly. When ERK activity was inhibited by U0126, the expression of c-Fos also decreased...
October 13, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27732578/a-renewed-model-of-pancreatic-cancer-evolution-based-on-genomic-rearrangement-patterns
#13
Faiyaz Notta, Michelle Chan-Seng-Yue, Mathieu Lemire, Yilong Li, Gavin W Wilson, Ashton A Connor, Robert E Denroche, Sheng-Ben Liang, Andrew M K Brown, Jaeseung C Kim, Tao Wang, Jared T Simpson, Timothy Beck, Ayelet Borgida, Nicholas Buchner, Dianne Chadwick, Sara Hafezi-Bakhtiari, John E Dick, Lawrence Heisler, Michael A Hollingsworth, Emin Ibrahimov, Gun Ho Jang, Jeremy Johns, Lars G T Jorgensen, Calvin Law, Olga Ludkovski, Ilinca Lungu, Karen Ng, Danielle Pasternack, Gloria M Petersen, Liran I Shlush, Lee Timms, Ming-Sound Tsao, Julie M Wilson, Christina K Yung, George Zogopoulos, John M S Bartlett, Ludmil B Alexandrov, Francisco X Real, Sean P Cleary, Michael H Roehrl, John D McPherson, Lincoln D Stein, Thomas J Hudson, Peter J Campbell, Steven Gallinger
Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently...
October 12, 2016: Nature
https://www.readbyqxmd.com/read/27725904/presentation-of-underglycosylated-mucin-1-in-pancreatic-adenocarcinoma-pdac-at-early-stages
#14
Su-Tang Lo, Pamela Pantazopouos, Zdravka Medarova, Anna Moore
Underglycosylated mucin 1 antigen (uMUC1) is a proven biomarker of cancer progression relevant to many malignancies including pancreatic ductal adenocarcinoma (PDAC). However, while ample evidence exists of the expression of total MUC1, little is known about the abundance of the underglycolsylated form of the antigen and its significance in disease progression. Such knowledge is important because the underglycosylated form of MUC1 is intimately linked to metastatic potential. Here, we investigated the expression uMUC1 at various stages of PDAC including pancreatic intraepithelial neoplasia (PanIN)...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27712835/utility-of-18-fludeoxyglucose-in-preoperative-positon-emission-tomography-computed-tomography-pet-ct-in-the-early-diagnosis-of-exocrine-pancreatic-cancer-a-study-of-139-resected-cases
#15
Francisco Sánchez-Bueno, Rocío García-Pérez, María Antonia Claver Valderas, Jesús de la Peña Moral, Laura Frutos Esteban, Eduardo Ortiz Ruiz, Matilde Fuster Quiñonero, Pascual Parrilla Paricio
INTRODUCTION: In pancreatic ductal adenocarcinoma (PDA), surgical resection is the only curative treatment, but due to its late clinical presentation only 15-25% patients are candidates for curative resection. The aim of this prospective, single-center study is to determine the diagnostic utility of preoperative PET-CT for early detection of PDA and early panIN lesions. METHODS: We studied the histopathological features of PDA and different panIN lesions in 139 surgical samples from patients undergoing pancreatic resection (from 2010-2014), comparing these results with preoperative PET-CT and MDCT study...
October 3, 2016: Cirugía Española
https://www.readbyqxmd.com/read/27672644/cystic-jejunal-duplication-with-heinrich-s-type-i-ectopic-pancreas-incidentally-discovered-in-a-patient-with-pancreatic-tail-neoplasm
#16
Simona Gurzu, Tivadar Bara, Tivadar Bara, Annamaria Fetyko, Ioan Jung
The aim of this study was to present a case of enteric duplication cyst and criteria for a proper differential diagnosis. A 51-year-old male was hospitalized for pancreatic tail neoplasm and distal pancreatectomy with splenectomy was performed. During surgery, a jejunal cystic lesion was incidentally detected and jejunectomy was performed. Microscopically, the cyst was observed to be covered by Keratin 7/Keratin 20 positive intestinal type epithelium and the muscularis layer was shared by the cyst and adjacent jejunum, without a cleavage plane between the cyst wall and jejunal muscularis propria...
September 16, 2016: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/27667193/satellite-rnas-promote-pancreatic-oncogenic-processes-via-the-dysfunction-of-ybx1
#17
Takahiro Kishikawa, Motoyuki Otsuka, Takeshi Yoshikawa, Motoko Ohno, Hideaki Ijichi, Kazuhiko Koike
Highly repetitive tandem arrays at the centromeric and pericentromeric regions in chromosomes, previously considered silent, are actively transcribed, particularly in cancer. This aberrant expression occurs even in K-ras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are precancerous lesions. To examine the biological roles of the satellite RNAs in carcinogenesis, we construct mouse PanIN-derived cells expressing major satellite (MajSAT) RNA and show increased malignant properties. We find an increase in frequency of chromosomal instability and point mutations in both genomic and mitochondrial DNA...
2016: Nature Communications
https://www.readbyqxmd.com/read/27617308/adipocytes-promote-pancreatic-cancer-cell-proliferation-via-glutamine-transfer
#18
Kevin A Meyer, Christopher K Neeley, Nicki A Baker, Alexandra R Washabaugh, Carmen G Flesher, Barbara S Nelson, Timothy L Frankel, Carey N Lumeng, Costas A Lyssiotis, Michelle L Wynn, Andrew D Rhim, Robert W O'Rourke
Adipocytes promote progression of multiple cancers, but their role in pancreatic intraepithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC) is poorly defined. Nutrient transfer is a mechanism underlying stromal cell-cancer crosstalk. We studied the role of adipocytes in regulating in vitro PanIN and PDAC cell proliferation with a focus on glutamine metabolism. Murine 3T3L1 adipocytes were used to model adipocytes. Cell lines derived from PKCY mice were used to model PanIN and PDAC. Co-culture was used to study the effect of adipocytes on PanIN and PDAC cell proliferation in response to manipulation of glutamine metabolism...
September 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/27610015/therapeutic-potential-of-targeting-acinar-cell-reprogramming-in-pancreatic-cancer
#19
REVIEW
Chi-Hin Wong, You-Jia Li, Yang-Chao Chen
Pancreatic ductal adenocarcinoma (PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRas(G12D) mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinar-to-ductal-metaplasia (ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia (PanIN) and eventually PDAC...
August 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27602757/pancreatic-stellate-cell-secreted-il-6-stimulates-stat3-dependent-invasiveness-of-pancreatic-intraepithelial-neoplasia-and-cancer-cells
#20
Nagaraj S Nagathihalli, Jason A Castellanos, Michael N VanSaun, Xizi Dai, Mahogany Ambrose, Qiaozhi Guo, Yanhua Xiong, Nipun B Merchant
Pancreatic ductal adenocarcinoma (PDAC) is a dynamic tumor supported by several stromal elements such as pancreatic stellate cells (PSC). Significant crosstalk exists between PSCs and tumor cells to stimulate oncogenic signaling and malignant progression of PDAC. However, how PSCs activate intercellular signaling in PDAC cells remains to be elucidated. We have previously shown that activated signal transducer and activator of transcription 3 (STAT3) signaling is a key component in the progression of pancreatic neoplasia...
September 1, 2016: Oncotarget
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