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https://www.readbyqxmd.com/read/29232549/stressing-out-panin-nrf2-pushes-over-the-edge
#1
Laura Torrente, Gina M DeNicola
The mechanisms by which chronic stress promote the development of pancreatic ductal adenocarcinoma (PDAC) are poorly defined. In this issue of Cancer Cell, Todoric et al. discover a role for impaired autophagy in the development of PDAC through p62-mediated activation of NRF2.
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29228654/lack-of-chemopreventive-effects-of-p2x7r-inhibitors-against-pancreatic-cancer
#2
Altaf Mohammed, Naveena B Janakiram, Venkateshwar Madka, Gopal Pathuri, Qian Li, Rebekah Ritchie, Laura Biddick, Hannah Kutche, Yuting Zhang, Anil Singh, Hariprasad Gali, Stan Lightfoot, Vernon E Steele, Chen S Suen, Chinthalapally V Rao
Pancreatic cancer (PC) is an almost uniformly lethal disease with inflammation playing an important role in its progression. Sustained stimulation of purinergic receptor P2X7 drives induction of NLRP inflammasome activation. To understand the role of P2X7 receptor and inflammasome, we performed transcriptomic analysis of p48Cre/+-LSL-KrasG12D/+ mice pancreatic tumors by next generation sequencing. Results showed that P2X7R's key inflammasome components, IL-1β and caspase-1 are highly expressed (p < 0.05) in pancreatic tumors...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29195018/dendron-grafted-polylysine-based-dual-modal-nanoprobe-for-ultra-early-diagnosis-of-pancreatic-precancerosis-via-targeting-a-urokinase-type-plasminogen-activator-receptor
#3
Hui Li, Ping Wang, Wenyu Gong, Qi Wang, Jia Zhou, Wei-Hong Zhu, Yingsheng Cheng
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. Early detection of precancerous pancreatic intraepithelial neoplasia (PanIN) tissues is an urgent challenge to improve the PDAC prognosis. Here, a urokinase-type plasminogen activator receptor (uPAR)-targeted magnetic resonance (MR)/near-infrared fluorescence (NIRF) dual-modal nanoprobe dendron-grafted polylysine (DGL)-U11 for ultra-early detection of pancreatic precancerosis is reported. Because of its good biocompatibility and biodegradability, globular architecture, and well-defined reactive groups, the DGL is chosen as the platform to load with a pancreatic tumor-targeting peptide U11, a magnetic resonance contrast agent Gd3+ -diethylene triamine pentaacetic acid, and a near-infrared fluorescent cyanine dye Cy5...
December 1, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29190947/thioredoxin-system-mediated-regulation-of-mutant-kras-associated-pancreatic-neoplasia-and-cancer
#4
Michelle A Schultz, Andrew M Diaz, Sharon Smite, Anna R Lay, Brian DeCant, Ronald McKinney, Windel E Mascarinas, Yinglin Xia, Carola Neumann, David Bentrem, David W Dawson, Paul J Grippo
Peroxiredoxin-1 (Prdx1), a member of the thioredoxin (Txn) system, is overexpressed and correlates with poor prognosis in pancreatic cancer patients and can suppress Kras signaling through redox-mediated inhibition of ERK and AKT in lung and breast cancer. Its redox function is maintained by Txn and sulfiredoxin (Srxn), and its tumor promoting functions are activated by post-translational modification. We studied the role of the Txn system in pancreatic neoplasia and cancer by determining how it regulates the phosphorylation of Kras effectors and by determining its association with patient survival...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29167399/protein-o-mannosyltransferases-affect-sensory-axon-wiring-and-dynamic-chirality-of-body-posture-in-the-drosophila-embryo
#5
Ryan Baker, Naosuke Nakamura, Ishita Chandel, Brooke Howell, Dmitry Lyalin, Vladislav M Panin
Genetic defects in protein O-mannosyltransferases, POMT1 and POMT2, underlie severe muscular dystrophies. POMT genes are evolutionarily conserved in metazoan organisms. In Drosophila, both male and female POMT mutants show a clockwise rotation of adult abdominal segments, suggesting a chirality of underlying pathogenic mechanisms. Here we described and analyzed a similar phenotype in POMT mutant embryos that show left-handed body torsion. Our experiments demonstrated that coordinated muscle contraction waves are associated with asymmetric embryo rolling, unveiling a new chirality marker in Drosophila development...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29161242/cadherin-1-and-cadherin-3-cooperation-determines-the-aggressiveness-of-pancreatic-ductal-adenocarcinoma
#6
Carole Siret, Aurélie Dobric, Anna Martirosyan, Chloé Terciolo, Sébastien Germain, Renaté Bonier, Thassadite Dirami, Nelson Dusetti, Richard Tomasini, Marion Rubis, Stéphane Garcia, Juan Iovanna, Dominique Lombardo, Véronique Rigot, Frédéric André
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an extensive tissue invasion and an early formation of metastasis. Alterations in the expression of cadherins have been reported in PDAC. Yet, how these changes contribute to tumour progression is poorly understood. Here, we investigated the relationship between cadherins expression and PDAC development. METHODS: Cadherins expression was assessed by immunostaining in both human and murine tissue specimens...
November 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29137350/il2rg-identified-as-overexpressed-by-rna-seq-profiling-of-pancreatic-intraepithelial-neoplasia-mediates-pancreatic-cancer-growth
#7
Michael Ayars, Eileen O'Sullivan, Anne Macgregor-Das, Koji Shindo, Haeryoung Kim, Michael Borges, Jun Yu, Ralph H Hruban, Michael Goggins
Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma (IL2RG) encoding the common gamma chain, IL2Rγ...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29121082/the-mouse-model-of-pancreatic-cancer-atlas-mmpca-for-classification-of-pancreatic-cancer-lesions-a-large-histological-investigation-of-the-ptf1acre-lsl-krasg12d-transgenic-mouse-model-of-pancreatic-cancer
#8
Michelle J Veite-Schmahl, Adam C Rivers, Daniel P Regan, Michael A Kennedy
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading forms of cancer related deaths in the United States. With limited treatment options and unreliable diagnostic methods, long-term survival rates following a diagnosis of pancreatic cancer remain poor. Pancreatic intraepithelial neoplasia (PanIN) are precancerous lesions that precede progression towards PDAC. PanIN occur in increasing complexity as the disease progresses and the description of PanIN plays a critical role in describing, staging and diagnosing PDAC...
2017: PloS One
https://www.readbyqxmd.com/read/29069604/duct-and-acinar-derived-pancreatic-ductal-adenocarcinomas-show-distinct-tumor-progression-and-marker-expression
#9
Rute M M Ferreira, Rocio Sancho, Hendrik A Messal, Emma Nye, Bradley Spencer-Dene, Richard K Stone, Gordon Stamp, Ian Rosewell, Alberto Quaglia, Axel Behrens
The cell of origin of pancreatic ductal adenocarcinoma (PDAC) has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs), duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions...
October 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/29059173/sox9-activity-is-induced-by-oncogenic-kras-to-affect-mdc1-and-mcms-expression-in-pancreatic-cancer
#10
H Zhou, Y Qin, S Ji, J Ling, J Fu, Z Zhuang, X Fan, L Song, X Yu, P J Chiao
SRY (sex determining region Y)-box 9 (SOX9) is required for oncogenic Kras-mediated acinar-to-ductal metaplasia (ADM), pancreatic intraepithelial neoplasias (PanINs) and ultimately pancreatic ductal adenocarcinoma (PDAC). However, how oncogenic Kras affects SOX9 activity is not yet understood, and SOX9-associated genes in PDAC are also unknown at all. Here, we investigated the mechanistic link between SOX9 and oncogenic Kras, studied biological function of SOX9, and identified SOX9-related genes and their clinical significance in patients with PDAC...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29050937/integrated-expression-profiling-of-potassium-channels-identifys-kcnn4-as-a-prognostic-biomarker-of-pancreatic-cancer
#11
Shuheng Jiang, Lili Zhu, Jianyu Yang, Lipeng Hu, Jianren Gu, Xin Xing, Yongwei Sun, Zhigang Zhang
Dysregulated potassium (K(+)) channels have previously been shown to promote the development and progression of many types of cancers. Meanwhile, K(+) channels are particularly important in regulating the endocrine and exocrine functions of pancreas. However, the expression pattern and prognostic significance of K(+) channels in pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, by screening a GEO dataset containing 36 microdissected PDAC and matching normal pancreatic tissue samples, four differentially expressed K(+) channels (KCNJ5, KCNJ16, KCNN4 and KCNK1) were identified in PDAC...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28986726/acute-pancreatitis-onset-carcinoma-in-situ-of-the-pancreas-with-focal-fat-replacement-diagnosed-using-serial-pancreatic-juice-aspiration-cytologic-examination-space
#12
Tatsunori Satoh, Masataka Kikuyama, Shinya Kawaguchi, Hideyuki Kanemoto, Hiroyuki Muro, Keiji Hanada
A 59-year-old woman was admitted for acute pancreatitis. Abdominal computed tomography and magnetic resonance imaging revealed a swollen pancreatic parenchyma with dilatation of the main pancreatic duct (MPD) of the pancreas tail, which was separated from the normal pancreas body side by a locally atrophic part of the pancreas. Magnetic resonance cholangiopancreatography showed MPD stricture in the pancreas tail with dilatation of the upstream MPD. Endoscopic ultrasonography revealed that the MPD stricture of the pancreas tail was surrounded by a blurred and hypoechoic area...
October 6, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28948203/increased-bcl-xl-expression-in-pancreatic-neoplasia-promotes-carcinogenesis-by-inhibiting-senescence-and-apoptosis
#13
Kenji Ikezawa, Hayato Hikita, Minoru Shigekawa, Kiyoshi Iwahashi, Hidetoshi Eguchi, Ryotaro Sakamori, Tomohide Tatsumi, Tetsuo Takehara
BACKGROUND & AIMS: Bcl-xL, an anti-apoptotic Bcl-2 family protein, is overexpressed in 90% of pancreatic ductal adenocarcinoma (PDAC) cases. However, Bcl-xL expression in pancreatic intraepithelial neoplasias (PanINs) and its significance in PDAC carcinogenesis remain unclear. The aim of this study was to elucidate the significance of Bcl-xL expression in PanINs. METHODS: We investigated the expression levels of Bcl-xL in pancreas-specific KrasG12D (P-KrasG12D) mice and human PanINs and PDAC...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28934293/generation-of-a-pancreatic-cancer-model-using-a-pdx1-flp-recombinase-knock-in-allele
#14
Jinghai Wu, Xin Liu, Sunayana G Nayak, Jason R Pitarresi, Maria C Cuitiño, Lianbo Yu, Blake E Hildreth, Katie A Thies, Daniel J Schilling, Soledad A Fernandez, Gustavo Leone, Michael C Ostrowski
The contribution of the tumor microenvironment to the development of pancreatic adenocarcinoma (PDAC) is unclear. The LSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-Cre (KPC) tumor model, which is widely utilized to faithfully recapitulate human pancreatic cancer, depends on Cre-mediated recombination in the epithelial lineage to drive tumorigenesis. Therefore, specific Cre-loxP recombination in stromal cells cannot be applied in this model, limiting the in vivo investigation of stromal genetics in tumor initiation and progression...
2017: PloS One
https://www.readbyqxmd.com/read/28895920/emt-and-treatment-resistance-in-pancreatic-cancer
#15
REVIEW
Nicola Gaianigo, Davide Melisi, Carmine Carbone
Pancreatic cancer (PC) is the third leading cause of adult cancer mortality in the United States. The poor prognosis for patients with PC is mainly due to its aggressive course, the limited efficacy of active systemic treatments, and a metastatic behavior, demonstrated throughout the evolution of the disease. On average, 80% of patients with PC are diagnosed with metastatic disease, and the half of those who undergo surgery and adjuvant therapy develop liver metastasis within two years. Metastatic dissemination is an early event in PC and is mainly attributed to an evolutionary biological process called epithelial-to-mesenchymal transition (EMT)...
September 12, 2017: Cancers
https://www.readbyqxmd.com/read/28886117/incidence-of-pancreatic-cancer-is-dramatically-increased-by-a-high-fat-high-calorie-diet-in-krasg12d-mice
#16
Hui-Hua Chang, Aune Moro, Kazuki Takakura, Hsin-Yuan Su, Allen Mo, Masako Nakanishi, Richard T Waldron, Samuel W French, David W Dawson, O Joe Hines, Gang Li, Vay Liang W Go, James Sinnett-Smith, Stephen J Pandol, Aurelia Lugea, Anna S Gukovskaya, Michael O Duff, Daniel W Rosenberg, Enrique Rozengurt, Guido Eibl
Epidemiologic data has linked obesity to a higher risk of pancreatic cancer, but the underlying mechanisms are poorly understood. To allow for detailed mechanistic studies in a relevant model mimicking diet-induced obesity and pancreatic cancer, a high-fat, high-calorie diet (HFCD) was given to P48+/Cre;LSL-KRASG12D (KC) mice carrying a pancreas-specific oncogenic Kras mutation. The mice were randomly allocated to a HFCD or control diet (CD). Cohorts were sacrificed at 3, 6, and 9 months and tissues were harvested for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28831506/-cystic-pancreatic-tumors-diagnostics-and-new-biomarkers
#17
REVIEW
A W Berger, T Seufferlein, A Kleger
Mortality due to pancreatic ductal adenocarcinoma (PDAC) will increase in the near future. The only curative treatment for PDAC is radical resection; however, even small carcinomas exhibit micrometastases leading to early relapse. Accordingly, detection of premalignant precursor lesions is important. In essence, PDAC develops from three precursor lesions: pancreatic intraepithelial lesions (PanIN), intraductal papillary-mucinous neoplasia (IPMN) and mucinous-cystic neoplasia (MCN). Together with serous cystic neoplasia (SCN) and solid pseudopapillary neoplasia (SPN), these cystic lesions constitute the most common cystic neoplasms in the pancreas...
November 2017: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
https://www.readbyqxmd.com/read/28821773/a-patterned-single-layer-graphene-resistance-temperature-sensor
#18
Benyamin Davaji, Hak Dong Cho, Mohamadali Malakoutian, Jong-Kwon Lee, Gennady Panin, Tae Won Kang, Chung Hoon Lee
Micro-fabricated single-layer graphenes (SLGs) on a silicon dioxide (SiO2)/Si substrate, a silicon nitride (SiN) membrane, and a suspended architecture are presented for their use as temperature sensors. These graphene temperature sensors act as resistance temperature detectors, showing a quadratic dependence of resistance on the temperature in a range between 283 K and 303 K. The observed resistance change of the graphene temperature sensors are explained by the temperature dependent electron mobility relationship (~T(-4)) and electron-phonon scattering...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28737163/plane-dependent-ml-scatter-scaling-3d-extension-of-the-2d-simulated-single-scatter-sss-estimate
#19
Ahmadreza Rezaei, Koen Salvo, Thomas Vahle, Vladimir Panin, Michael Casey, Fernando Boada, Michel Defrise, Johan Nuyts
Scatter correction is typically done using a simulation of the single scatter, which is then scaled to account for multiple scatters and other possible model mismatches. This scaling factor is determined by fitting the simulated scatter sinogram to the measured sinogram, using only counts measured along LORs that do not intersect the patient body, i.e. 'scatter-tails'. Extending previous work, we propose to scale the scatter with a plane dependent factor, which is determined as an additional unknown in the maximum likelihood (ML) reconstructions, using counts in the entire sinogram rather than only the 'scatter-tails'...
July 24, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28698299/neat1-is-a-p53-inducible-lincrna-essential-for-transformation-suppression
#20
Stephano S Mello, Carolyn Sinow, Nitin Raj, Pawel K Mazur, Kathryn Bieging-Rolett, Daniela Kenzelmann Broz, Jamie F Conklin Imam, Hannes Vogel, Laura D Wood, Julien Sage, Tetsuro Hirose, Shinichi Nakagawa, John Rinn, Laura D Attardi
The p53 gene is mutated in over half of all cancers, reflecting its critical role as a tumor suppressor. Although p53 is a transcriptional activator that induces myriad target genes, those p53-inducible genes most critical for tumor suppression remain elusive. Here, we leveraged p53 ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) and RNA-seq (RNA sequencing) data sets to identify new p53 target genes, focusing on the noncoding genome. We identify Neat1, a noncoding RNA (ncRNA) constituent of paraspeckles, as a p53 target gene broadly induced by mouse and human p53 in different cell types and by diverse stress signals...
June 1, 2017: Genes & Development
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