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https://www.readbyqxmd.com/read/29352660/clinical-significance-of-muc13-in-pancreatic-ductal-adenocarcinoma
#1
Sheema Khan, Nadeem Zafar, Shabia S Khan, Saini Setua, Stephen W Behrman, Zachary E Stiles, Murali M Yallapu, Peeyush Sahay, Hemendra Ghimire, Tomoko Ise, Satoshi Nagata, Lei Wang, Jim Y Wan, Prabhakar Pradhan, Meena Jaggi, Subhash C Chauhan
BACKGROUND: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. METHODS: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses...
January 15, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/29289465/investigating-the-role-of-transcription-factors-of-pancreas-development-in-pancreatic-cancer
#2
REVIEW
Ahmad Abu Turab Naqvi, Gulam Mustafa Hasan, Md Imtaiyaz Hassan
Pancreatic cancer (PC) is the seventh most common cause of cancer-related deaths worldwide that kills more than 300,000 people every year. Prognosis of PC is very poor with a five-year survival rate about 5%. The most common and highly observed type of PC is pancreatic ductal adenocarcinoma (PDAC). It is preceded by the progression of precursor lesions such as Pancreatic Intraepithelial Neoplasia (PanIN), Intraductal Papillary Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN). PanIN is the most common among these premalignant lesions...
December 24, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29248441/kr%C3%A3-ppel-like-factor-5-increased-in-pancreatic-ductal-adenocarcinoma-promotes-proliferation-acinar-to-ductal-metaplasia-pancreatic-intraepithelial-neoplasia-and-tumor-growth-in-mice
#3
Ping He, Jong Won Yang, Vincent W Yang, Agnieszka B Bialkowska
BACKGROUND & AIMS: Activating mutations in KRAS are detected in most pancreatic ductal adenocarcinomas (PDACs). Expression of an activated form of KRAS (KrasG12D) in pancreata of mice is sufficient to induce formation of pancreatic intraepithelial neoplasia (PanINs)-a precursor of PDAC. Pancreatitis increases formation of PanINs in mice that express KrasG12D by promoting acinar to ductal metaplasia (ADM). We investigated the role of the transcription factor Krüppel-like factor 5 (KLF5) in ADM and KRAS-mediated formation of PanINs...
December 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29232549/stressing-out-panin-nrf2-pushes-over-the-edge
#4
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
#5
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
#6
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
#7
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/29161242/cadherin-1-and-cadherin-3-cooperation-determines-the-aggressiveness-of-pancreatic-ductal-adenocarcinoma
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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