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https://www.readbyqxmd.com/read/28698299/neat1-is-a-p53-inducible-lincrna-essential-for-transformation-suppression
#1
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...
July 11, 2017: Genes & Development
https://www.readbyqxmd.com/read/28697176/hmga1-expression-levels-are-elevated-in-pancreatic-intraepithelial-neoplasia-cells-in-the-ptf1a-cre-lsl-krasg12d-transgenic-mouse-model-of-pancreatic-cancer
#2
Michelle J Veite-Schmahl, William C Joesten, Michael A Kennedy
BACKGROUND: Pancreatic cancer is currently the third leading cause of cancer deaths in the United States and it is predicted to become the second by the year 2030. High-mobility group A1 protein (HMGA1) is an oncogenic transcription factor, localised and active in cell nuclei, that is linked to tumour progression in many human cancers, including pancreatic cancer. Overexpression of HMGA1 renders cancer cells resistant to chemotherapy. Although the Ptf1a-Cre; LSL-KrasG12D transgenic mouse is perhaps the most widely utilised animal model for human pancreatic cancer, expression levels of HMGA1 in pancreata from this mouse model have not been characterised...
July 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28697132/overexpression-of-yes-associated-protein-1-an-independent-prognostic-marker-in-patients-with-pancreatic-ductal-adenocarcinoma-correlated-with-liver-metastasis-and-poor-prognosis
#3
Maria Teresa Salcedo Allende, Jorge Zeron-Medina, Javier Hernandez, Teresa Macarulla, Joaquim Balsells, Xavier Merino, Helena Allende, Josep Tabernero, Santiago Ramon Y Cajal Agüeras
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Overexpression of Yes associated protein 1 (YAP1), a downstream target of Hippo pathway, implicated in regulation of cell growth and apoptosis, has been reported in several human tumor types. The objective of this study was to investigate YAP1 expression in patients with PDAC and its prognostic values. METHODS: We evaluated YAP1 expression in 64 PDAC and 15 chronic pancreatitis (CP) cases and its related pancreatic intraepithelial neoplasia (PanIN) lesions and in 5 control subjects...
August 2017: Pancreas
https://www.readbyqxmd.com/read/28685935/gastric-gland-mucin-specific-o-glycan-expression-decreases-with-tumor-progression-from-precursor-lesions-to-pancreatic-cancer
#4
Ayumi Ohya, Kazuhiro Yamanoi, Hisashi Shimojo, Chifumi Fujii, Jun Nakayama
Pancreatic cancer is lethal, as it is often detected late. Thus novel biomarkers of precursor lesions are needed to devise timely therapies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) are major precursors of pancreatic cancer. In normal gastric mucosa, gastric gland mucin-specific O-glycans are unique in having α1,4-linked N-acetylglucosamine (αGlcNAc) residues attached to MUC6. Recently we reported that αGlcNAc functions as a tumor suppressor for differentiated-type gastric adenocarcinoma (Karasawa et al...
July 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28639725/targeting-nad-p-h-quinone-oxidoreductase-nqo1-in-pancreatic-cancer
#5
Anne M Lewis, Matthew Ough, Juan Du, Ming-Sound Tsao, Larry W Oberley, Joseph J Cullen
Quinone oxidoreductase (NQO1) functions as an important part of cellular antioxidant defense by detoxifying quinones, thus preventing the formation of reactive oxygen species. The aims of our study were to determine if NQO1 is elevated in pancreatic cancer specimens and pancreatic cancer cell lines and if so, would compounds previously demonstrated to redox cycle with NQO1 be effective in killing pancreatic cancer cells. Immunohistochemistry of resected pancreatic specimens demonstrated an increased immunoreactivity for NQO1 in pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) specimens versus normal human pancreas...
July 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28639428/relationship-between-pancreatic-intraepithelial-neoplasias-pancreatic-ductal-adenocarcinomas-and-single-nucleotide-polymorphisms-in-autopsied-elderly-patients
#6
Yoko Matsuda, Masashi Tanaka, Motoji Sawabe, Seijiro Mori, Masaaki Muramatsu, Makiko Naka Mieno, Toru Furukawa, Tomio Arai
A growing body of evidence shows that the presence of single nucleotide polymorphisms (SNPs) influences individual predisposition to pancreatic cancer. In the present study, we comparatively analyzed serially autopsied, elderly Japanese patients (n = 2,205) with pancreatic intraepithelial neoplasias (PanINs) and pancreatic ductal adenocarcinomas (PDACs) on the basis of their pancreatic lesions, clinical information, and SNPs. The incidence of PanIN-1, -2, -3, and PDACs in these patients was 55%, 12%, 1.4%, and 2...
June 22, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28627323/perspective-of-%C3%AE-v%C3%AE-6-integrin-imaging-for-clinical-management-of-pancreatic-carcinoma-and-its-precursor-lesions
#7
Katja Steiger, Anna-Melissa Schlitter, Wilko Weichert, Irene Esposito, Hans-Jürgen Wester, Johannes Notni
ß6-integrin immunohistochemistry analysis of a large number of pancreatic ductal adenocarcinoma (PDAC, 383 primary tumors, 7 lymph node, and 8 distant metastases) and 34 pancreatic intraepithelial neoplasia (PanIN) specimens revealed a high prevalence of αvß6-integrin expression in PDAC primaries (88%) and in almost all metastases, as well as in PanIN (57%). These findings underscore the high potential of a novel αvß6-integrin targeting positron emission tomography (PET) radiopharmaceutical, Ga-68-Avebehexin, for early diagnosis of pancreatic cancer...
January 1, 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28514653/the-presence-of-interleukin-13-at-pancreatic-adm-panin-lesions-alters-macrophage-populations-and-mediates-pancreatic-tumorigenesis
#8
Geou-Yarh Liou, Ligia Bastea, Alicia Fleming, Heike Döppler, Brandy H Edenfield, David W Dawson, Lizhi Zhang, Nabeel Bardeesy, Peter Storz
The contributions of the innate immune system to the development of pancreatic cancer are still ill defined. Inflammatory macrophages can initiate metaplasia of pancreatic acinar cells to a duct-like phenotype (acinar-to-ductal metaplasia [ADM]), which then gives rise to pancreatic intraepithelial neoplasia (PanIN) when oncogenic KRas is present. However, it remains unclear when and how this inflammatory macrophage population is replaced by tumor-promoting macrophages. Here, we demonstrate the presence of interleukin-13 (IL-13), which can convert inflammatory into Ym1+ alternatively activated macrophages, at ADM/PanIN lesions...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28419443/loss-of-natural-killer-t-nkt-cells-promotes-pancreatic-cancer-in-lsl-kras-g12d-mice
#9
Naveena B Janakiram, Altaf Mohammed, Taylor Bryant, Rebekah Ritchie, Nicole Stratton, Lydgia Jackson, Stan Lightfoot, Doris M Benbrook, Adam Asch, Mark L Lang, Chinthalapally V Rao
Role of unique T cell population, Natural Killer T (NKT) cells which have similar functions like NK cells in PC is not yet evaluated. In order to address the regulatory roles of NKT cells on tumor progression through tumor-associated macrophages (TAM) and their production of microsomal prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven pancreatic tumor (KPT) progression, we crossed CD1d(-/-) mice deficient in both iNKT and vNKT cells with the Kras(G12D) mice. Loss of NKT cells significantly increased pancreatic intraepithelial neoplasia lesions [PanINs] and also increased 5-LOX and mPGES-1 expressions in M2 type macrophages and cancer stem like cells in pancreatic tumors...
April 18, 2017: Immunology
https://www.readbyqxmd.com/read/28415794/micrornas-of-the-mir-17-92-cluster-regulate-multiple-aspects-of-pancreatic-tumor-development-and-progression
#10
Brian Quattrochi, Anushree Gulvady, David R Driscoll, Makoto Sano, David S Klimstra, Christopher E Turner, Brian C Lewis
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by resistance to currently employed chemotherapeutic approaches. Members of the mir-17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse models, we show that loss of mir-17~92 reduces ERK pathway activation downstream of mutant KRAS and promotes the regression of KRASG12D-driven precursor pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal exocrine tissue...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386018/panin-neuroendocrine-cells-promote-tumorigenesis-via-neuronal-cross-talk
#11
Smrita Sinha, Ya-Yuan Fu, Adrien Grimont, Maren Ketcham, Kelly Lafaro, Joseph A Saglimbeni, Gokce Askan, Jennifer M Bailey, Jerry P Melchor, Yi Zhong, Min Geol Joo, Olivera Grbovic-Huezo, In-Hong Yang, Olca Basturk, Lindsey Baker, Young Park, Robert C Kurtz, David Tuveson, Steven D Leach, Pankaj J Pasricha
Nerves are a notable feature of the tumor microenvironment in some epithelial tumors, but their role in the malignant progression of pancreatic ductal adenocarcinoma (PDAC) is uncertain. Here, we identify dense innervation in the microenvironment of precancerous pancreatic lesions, known as pancreatic intraepithelial neoplasms (PanIN), and describe a unique subpopulation of neuroendocrine PanIN cells that express the neuropeptide substance P (SP) receptor neurokinin 1-R (NK1-R). Using organoid culture, we demonstrated that sensory neurons promoted the proliferation of PanIN organoids via SP-NK1-R signaling and STAT3 activation...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28383565/diversity-of-precursor-lesions-for-pancreatic-cancer-the-genetics-and-biology-of-intraductal-papillary-mucinous-neoplasm
#12
Krushna C Patra, Nabeel Bardeesy, Yusuke Mizukami
Pancreatic ductal adenocarcinoma (PDA), one of the most lethal cancers worldwide, is associated with two main types of morphologically distinct precursors-pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). Although the progression of PanIN into invasive cancer has been well characterized, there remains an urgent need to understand the biology of IPMNs, which are larger radiographically detectable cystic tumors. IPMNs comprise a number of subtypes with heterogeneous histopathologic and clinical features...
April 6, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28369074/annexin-a10-is-a-candidate-marker-associated-with-the-progression-of-pancreatic-precursor-lesions-to-adenocarcinoma
#13
Jianhui Zhu, Jing Wu, Xiucong Pei, Zhijing Tan, Jiaqi Shi, David M Lubman
Annexins are a multigene family of calcium and phospholipid-binding proteins that play important roles in calcium signaling, cell motility, differentiation and proliferation. Our previous mass spectrometry-based proteomics study revealed that annexin A10 (ANXA10) was uniquely overexpressed in pancreatic CD24+ adenocarcinoma cells that were dissected from clinical PDAC tissues but was absent in CD24- adjacent normal cells. The correlation between ANXA10 expression and the progression of pancreatic cancer remains unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28368927/heterotopic-pancreas-of-the-gastrointestinal-tract-and-associated-precursor-and-cancerous-lesions-systematic-pathologic-studies-of-165-cases
#14
Sun-Young Jun, Dahye Son, Mi-Ju Kim, Sung Joo Kim, Soyeon An, Young Soo Park, Sook Ryun Park, Kee Don Choi, Hwoon-Yong Jung, Song Cheol Kim, Jeong Hwan Yook, Byung-Sik Kim, Seung-Mo Hong
Heterotopic pancreas (HP) can be detected by accompanying symptoms or incidentally during gastrointestinal (GI) tract tumor resection. We compared clinicopathologic features among 165 resected HPs (57 gastric [35%], 56 duodenal [34%], 30 omental [18%], and 22 jejunal [13%]). Symptomatic HPs (79/135 GI tract wall HPs, 59%) were larger (P=0.05), more common in younger patients and in a gastric location (both P<0.001), and more frequently associated with lymphoid cuffs (P=0.03) than incidentally found HPs. Gastric/jejunal HPs were more frequently symptomatic (P<0...
June 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28368414/tgf%C3%AE-engages-mek-erk-to-differentially-regulate-benign-and-malignant-pancreas-cell-function
#15
D R Principe, A M Diaz, C Torres, R J Mangan, B DeCant, R McKinney, M-S Tsao, A Lowy, H G Munshi, B Jung, P J Grippo
While TGFβ signals are anti-proliferative in benign and well-differentiated pancreatic cells, TGFβ appears to promote the progression of advanced cancers. To better understand dysregulation of the TGFβ pathway, we first generated mouse models of neoplastic disease with TGFβ receptor deficiencies. These models displayed reduced levels of pERK irrespective of KRAS mutation. Furthermore, exogenous TGFβ led to rapid and sustained TGFBR1-dependent ERK phosphorylation in benign pancreatic duct cells. Similar to results that our group has published in colon cancer cells, inhibition of ERK phosphorylation in duct cells mitigated TGFβ-induced upregulation of growth suppressive pSMAD2 and p21, prevented downregulation of the pro-growth signal CDK2 and ablated TGFβ-induced EMT...
July 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28367822/-autophagy-contributes-to-the-initiation-of-pancreatic-cancer
#16
Juan L Iovanna
The pancreatic adenocarcinoma initiation results from the interaction of genetic events combined with multiple other factors. Among the genetic alterations that contribute to the pathogenesis of this disease, the mutation of the KRAS oncogene is required but not sufficient to trigger this cancer. Pancreatitis, an inflammatory disease, facilitates and accelerates the transformation of pancreatic cells when the KRAS oncogene is mutated. Of note, the repertoire of molecular mediators of pancreatitis which are responsible of the promotion of KRAS-mediated transformation is not completely defined...
March 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28282719/pharmacogenetics-and-personalized-medicine-in-pancreatic-cancer
#17
REVIEW
Ali Hosseini Bereshneh, Fatemeh Morshedi, Mahsa Hematyar, Arastoo Kaki, Masoud Garshasbi
 Pancreatic cancer (PC) is a progressive, fatal disease with a high degree of malignancy. More than 40000 peoplediefrom this cancer annually in the United States. As a multifactorial condition, PC has a complex nature, and there are several genes and signalingpathwaysimplicated in PC pathogenesis and progression. There are diffèrent mutations in master genesincludingtumorsuppressors and oncogenesthat lead to Pancreaticintraepithelialneoplasia (PanIN) whichis the mostcommon non-invasive precursorlesion of pancreatic cancer...
March 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28272465/reconstituting-development-of-pancreatic-intraepithelial-neoplasia-from-primary-human-pancreas-duct-cells
#18
Jonghyeob Lee, Emily R Snyder, Yinghua Liu, Xueying Gu, Jing Wang, Brittany M Flowers, Yoo Jung Kim, Sangbin Park, Gregory L Szot, Ralph H Hruban, Teri A Longacre, Seung K Kim
Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28260136/cells-of-origin-of-pancreatic-neoplasms
#19
REVIEW
Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo, Tomoki Ebata, Masato Nagino
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease associated with poor prognosis, despite recent medical advances. It is of great importance to understand the initial events and cells of origin of pancreatic cancer to prevent the development and progression of PDAC. There are three distinct precursor lesions that develop into PDAC: pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs). Studies on genetically engineered mouse models have revealed that the initiation and development of these lesions largely depend on genetic alterations...
March 4, 2017: Surgery Today
https://www.readbyqxmd.com/read/28249896/lipocalin-2-promotes-pancreatic-ductal-adenocarcinoma-by-regulating-inflammation-in-the-tumor-microenvironment
#20
Sobeyda B Gomez-Chou, Agnieszka Katarzyna Swidnicka-Siergiejko, Niharika Badi, Myrriah Chavez-Tomar, Gregory B Lesinski, Tanios Bekaii-Saab, Matthew R Farren, Thomas A Mace, Carl Schmidt, Yan Liu, Defeng Deng, Rosa F Hwang, Liran Zhou, Todd Moore, Deyali Chatterjee, Huamin Wang, Xiaohong Leng, Ralph B Arlinghaus, Craig D Logsdon, Zobeida Cruz-Monserrate
Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation, and PDAC development. Mice with acinar cell-specific expression of Kras(G12D) were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content...
May 15, 2017: Cancer Research
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