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pancreatic cancer PANIN

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https://www.readbyqxmd.com/read/29161242/cadherin-1-and-cadherin-3-cooperation-determines-the-aggressiveness-of-pancreatic-ductal-adenocarcinoma
#1
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
#2
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
#3
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/29059173/sox9-activity-is-induced-by-oncogenic-kras-to-affect-mdc1-and-mcms-expression-in-pancreatic-cancer
#4
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
#5
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/28934293/generation-of-a-pancreatic-cancer-model-using-a-pdx1-flp-recombinase-knock-in-allele
#6
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
#7
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
#8
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/28698299/neat1-is-a-p53-inducible-lincrna-essential-for-transformation-suppression
#9
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
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
#10
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...
August 22, 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
#11
Maria Teresa Salcedo Allende, Jorge Zeron-Medina, Javier Hernandez, Teresa Macarulla, Joaquim Balsells, Xavier Merino, Helena Allende, Josep Tabernero, Santiago Ramon Y Cajal
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
#12
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...
September 2017: Cancer Science
https://www.readbyqxmd.com/read/28639725/targeting-nad-p-h-quinone-oxidoreductase-nqo1-in-pancreatic-cancer
#13
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
#14
Yoko Matsuda, Masashi Tanaka, Motoji Sawabe, Seijiro Mori, Masaaki Muramatsu, Makiko Naka Mieno, Toru Furukawa, Tomio Arai
We comparatively analyzed serially autopsied, elderly Japanese patients (n = 2205) with pancreatic intraepithelial neoplasias (PanINs) and pancreatic ductal adenocarcinomas (PDACs) on the basis of their pancreatic lesions, clinical information, and single nucleotide polymorphisms (SNPs). The incidence of PanIN-1, -2, -3, and PDACs in these patients was 55%, 12%, 1.4%, and 2.4%, respectively. The occurrence of PanINs was associated with female sex, increasing age, and lower body mass index. We did not identify any common SNPs between PanINs and PDACs...
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
#15
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
#16
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-cells-promotes-pancreatic-cancer-in-lsl-kras-g12d-mice
#17
Naveena B Janakiram, Altaf Mohammed, Taylor Bryant, Rebekah Ritchie, Nicole Stratton, Lydgia Jackson, Stan Lightfoot, Doris M Benbrook, Adam S Asch, Mark L Lang, Chinthalapally V Rao
The role of the unique T-cell population, natural killer T (NKT) cells, which have similar functions to NK cells in pancreatic cancer (PC), is not yet evaluated. To address the regulatory roles of NKT cells on tumour progression through tumour-associated macrophages (TAM) and their production of microsomal prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven pancreatic tumour (KPT) progression, we crossed CD1d(-/-) mice deficient in both invariant and variant NKT cells with the Kras(G12D) mice...
September 2017: Immunology
https://www.readbyqxmd.com/read/28415794/micrornas-of-the-mir-17-92-cluster-regulate-multiple-aspects-of-pancreatic-tumor-development-and-progression
#18
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
#19
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
#20
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
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