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https://www.readbyqxmd.com/read/28230988/design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#1
Vibha Pathak, Corinne Elizabeth Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
Wnt/beta-Catenin signaling pathway has a very important role in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. This signaling pathway has been implicated in angiogenesis, maintenance of resistant CICs (cancer-initiating cells), metastasis, regulation of cell cycle, apoptosis and chemoresistance. We investigated the activity of a chemical series of phenyl benzimidazoles, small molecule inhibitors of Wnt signaling in LRP6-expressing HEK 293 cells against PDAC cells. Several benzimidazoles were designed, synthesized and screened under adherent and CIC conditions...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28220683/analysis-of-distinct-long-noncoding-rna-transcriptional-fingerprints-in-pancreatic-ductal-adenocarcinoma
#2
Xiang Yu, Yang Lin, Wu Sui, Yanfen Zou, Zhongchuan Lv
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies with the worst prognosis. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis and cancer progression. However, the expression pattern and roles of lncRNAs in the development of PDAC remain unknown. Herein, we globally analyzed the lncRNA expression profile in human PDAC and non-tumor tissues using four independent public microarray datasets from Gene Expression Omnibus (GEO)...
February 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28216975/negative-oncologic-impact-of-poor-postoperative-pain-control-in-left-sided-pancreatic-cancer
#3
Eun-Ki Min, Jae Uk Chong, Ho Kyoung Hwang, Sang Joon Pae, Chang Moo Kang, Woo Jung Lee
AIM: To investigate the association between postoperative pain control and oncologic outcomes in resected pancreatic ductal adenocarcinoma (PDAC). METHODS: From January 2009 to December 2014, 221 patients were diagnosed with PDAC and underwent resection with curative intent. Retrospective review of the patients was performed based on electronic medical records system. One patient without records of numerical rating scale (NRS) pain intensity scores was excluded and eight patients who underwent total pancreatectomy were also excluded...
January 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28215485/association-of-igg4-response-and-autoimmune-pancreatitis-with-intraductal-papillary-mucinous-neoplasms
#4
Amin A Hedayat, Mikhail Lisovsky, Arief A Suriawinata, Daniel S Longnecker
OBJECTIVES: Concurrent intraductal papillary-mucinous neoplasm (IPMN) and autoimmune pancreatitis (AIP) was observed in a patient (index case) at our institution. Cases of coincidental IPMN and type 1 AIP and concurrent ductal adenocarcinoma (PDAC) and AIP have been previously reported. In this study we evaluate the hypothesis that IPMN elicits an IgG4 response. METHODS: Twenty-one pancreases (including the index case) with IPMN resected at our institution were studied...
February 8, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28214673/duffy-antigen-receptor-for-chemokines-darc-expressing-in-cancer-cells-inhibits-tumor-progression-by-suppressing-cxcr2-signaling-in-human-pancreatic-ductal-adenocarcinoma
#5
Shintaro Maeda, Satoshi Kuboki, Hiroyuki Nojima, Hiroaki Shimizu, Hideyuki Yoshitomi, Katsunori Furukawa, Masaru Miyazaki, Masayuki Ohtsuka
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Chemokines play important roles in the progression of many malignancies; however, the role of chemokine receptor expression in clinical cases of PDAC is unclear. Moreover, little is known about DARC, a decoy receptor of CXC chemokines, in the regulation of tumor progression. METHODS: Functions of chemokine receptors were evaluated using surgical specimens collected from PDAC patients, and PDAC cell lines...
February 16, 2017: Cytokine
https://www.readbyqxmd.com/read/28210844/elevated-interferon-induced-protein-with-tetratricopeptide-repeats-3-ifit3-is-a-poor-prognostic-marker-in-pancreatic-ductal-adenocarcinoma
#6
Yue Zhao, Annelore Altendorf-Hofmann, Ioannis Pozios, Peter Camaj, Therese Däberitz, Xiaoyan Wang, Hanno Niess, Hendrik Seeliger, Felix Popp, Christopher Betzler, Utz Settmacher, Karl-Walter Jauch, Christiane Bruns, Thomas Knösel
PURPOSE: Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. METHODS: The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3...
February 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#7
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28205613/pak4-interacts-with-p85-alpha-implications-for-pancreatic-cancer-cell-migration
#8
Helen King, Kiruthikah Thillai, Andrew Whale, Prabhu Arumugam, Hesham Eldaly, Hemant M Kocher, Claire M Wells
It has been reported that p21-activated kinase 4 (PAK4) is amplified in pancreatic cancer tissue. PAK4 is a member of the PAK family of serine/threonine kinases, which act as effectors for several small GTPases, and has been specifically identified to function downstream of HGF-mediated c-Met activation in a PI3K dependent manner. However, the functionality of PAK4 in pancreatic cancer and the contribution made by HGF signalling to pancreatic cancer cell motility remain to be elucidated. We now find that elevated PAK4 expression is coincident with increased expression levels of c-Met and the p85α subunit of PI3K...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205147/identification-of-candidate-mirna-biomarkers-for-pancreatic-ductal-adenocarcinoma-by-weighted-gene-co-expression-network-analysis
#9
M Giulietti, G Occhipinti, G Principato, F Piva
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal prognosis which is, among others, due to a lack of suitable biomarkers and therapeutic targets. Previously, basic gene expression analysis methods have been used for their identification, but recently new algorithms have been developed allowing more comprehensive data analyses. Among them, weighted gene co-expression network analysis (WGCNA) has already been applied to several cancer types with promising results...
February 15, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28199010/immunohistochemical-hent1-expression-as-a-prognostic-biomarker-in-patients-with-resected-pancreatic-ductal-adenocarcinoma-undergoing-adjuvant-gemcitabine-based-chemotherapy
#10
REVIEW
N T E Bird, M Elmasry, R Jones, E Psarelli, J Dodd, H Malik, W Greenhalf, N Kitteringham, P Ghaneh, J P Neoptolemos, D Palmer
BACKGROUND: Human equilibrative nucleoside transporters (hENTs) are transmembranous proteins that facilitate the uptake of nucleosides and nucleoside analogues, such as gemcitabine, into the cell. The abundance of hENT1 transporters in resected pancreatic ductal adenocarcinoma (PDAC) might make hENT1 a potential biomarker of response to adjuvant chemotherapy. The aim of this study was to see whether hENT1 expression, as determined by immunohistochemistry, was a suitable predictive marker for subsequent treatment with gemcitabine-based adjuvant chemotherapy...
March 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28198398/microrna-155-controls-exosome-synthesis-and-promotes-gemcitabine-resistance-in-pancreatic-ductal-adenocarcinoma
#11
Manabu Mikamori, Daisaku Yamada, Hidetoshi Eguchi, Shinichiro Hasegawa, Tomoya Kishimoto, Yoshito Tomimaru, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Koichi Kawamoto, Kunihito Gotoh, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki
The cancer drug gemcitabine (GEM) is a key drug for treating pancreatic ductal adenocarcinoma (PDAC), but PDAC cells develop chemoresistance after long-term administration. Since the tolerance was immediately spread to every PDAC tissue in a patient, it is assumed that some certain efficient mechanisms underlay in the development of chemoresistance. Changes in the levels of particular microRNAs or alterations in intercellular communication play a dominant role in chemoresistance development, and recent data also suggest that exosomes play an important role in this process...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196013/prognostic-implications-of-expression-profiling-for-gemcitabine-related-genes-hent1-dck-rrm1-rrm2-in-patients-with-resectable-pancreatic-adenocarcinoma-receiving-adjuvant-chemotherapy
#12
Marek Sierzega, Radosław Pach, Piotr Kulig, Janusz Legutko, Jan Kulig
OBJECTIVES: The aim of this study was to examine the relevance of expression profiling of 4 genes involved in the action of gemcitabine among patients with pancreatic ductal-cell adenocarcinoma (PDAC). METHODS: A group of 100 patients who underwent pancreatic resections for PDAC and received adjuvant chemotherapy with gemcitabine between 2007 and 2010 was identified. Expression of mRNAs for human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunits (RRM1, RRM2), and deoxycytidine kinase (dCK) was examined by quantitative real-time polymerase chain reaction, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and dichotomized into groups of low and moderate/high expression levels grouped by tertiles...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28194432/bet-inhibitors-block-pancreatic-stellate-cell-collagen-i-production-and-attenuate-fibrosis-in-vivo
#13
Krishan Kumar, Brian T DeCant, Paul J Grippo, Rosa F Hwang, David J Bentrem, Kazumi Ebine, Hidayatullah G Munshi
The fibrotic reaction, which can account for over 70%-80% of the tumor mass, is a characteristic feature of human pancreatic ductal adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation of pancreatic stellate cells (PSCs), which are key regulators of collagen I production and fibrosis in vivo. In this report, we show that members of the bromodomain and extraterminal (BET) family of proteins are expressed in primary PSCs isolated from human PDAC tumors, with BRD4 positively regulating, and BRD2 and BRD3 negatively regulating, collagen I expression in primary cancer-associated PSCs...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28188806/role-of-ccl20-mediated-immune-cell-recruitment-in-nf-%C3%AE%C2%BAb-mediated-trail-resistance-of-pancreatic-cancer
#14
Claudia Geismann, Frauke Grohmann, Anita Dreher, Robert Häsler, Philip Rosenstiel, Karen Legler, Charlotte Hauser, Jan Hendrik Egberts, Bence Sipos, Stefan Schreiber, Andreas Linkermann, Zonera Hassan, Günter Schneider, Heiner Schäfer, Alexander Arlt
Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers. From a clinical view, the transcription factor NF-κB is of particular importance, since this pathway confers apoptosis resistance and limits drug efficacy. Whereas the role of the most abundant NF-κB subunit p65/RelA in therapeutic resistance is well documented, only little knowledge of the RelA downstream targets and their functional relevance in TRAIL mediated apoptosis in PDAC is available. In the present study TRAIL resistant and sensitive PDAC cell lines were analyzed for differentially expressed RelA target genes, to define RelA downstream targets mediating TRAIL resistance...
February 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28188746/context-dependent-epigenetic-regulation-of-nuclear-factor-of-activated-t-cells-1-in-pancreatic-plasticity
#15
Nai-Ming Chen, Albrecht Neesse, Moritz Lino Dyck, Benjamin Steuber, Alexander O Koenig, Clara Lubeseder-Martellato, Thore Winter, Teresa Forster, Hanibal Bohnenberger, Julia Kitz, Kirsten-Reuter Jessen, Heidi Griesmann, Jochen Gaedcke, Marian Grade, Jin-San Zhang, Wan-Chi Tsai, Jens Siveke, Hans-Ulrich Schildhaus, Philipp Ströbel, Steven A Johnsen, Volker Ellenrieder, Elisabeth Hessmann
BACKGROUND & AIMS: The ability of exocrine pancreatic cells to change the cellular phenotype is required for tissue regeneration upon injury but also contributes to their malignant transformation and tumor progression. We investigated context-dependent signaling and transcription mechanisms that determine pancreatic cell fate decisions toward regeneration and malignancy. In particular, we studied the function and regulation of the inflammatory transcription factor nuclear factor of activated T cells 1 (NFATC1) in pancreatic cell plasticity and tissue adaptation...
February 7, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28188630/genetic-analyses-of-isolated-high-grade-pancreatic-intraepithelial-neoplasia-hg-panin-reveal-paucity-of-alterations-in-tp53-and-smad4
#16
Waki Hosoda, Peter Chianchiano, James F Griffin, Meredith E Pittman, Lodewijk A A Brosens, Michaël Noë, Jun Yu, Koji Shindo, Masaya Suenaga, Neda Rezaee, Raluca Yonescu, Yi Ning, Jorge Albores-Saavedra, Naohiko Yoshizawa, Kenichi Harada, Akihiko Yoshizawa, Keiji Hanada, Shuji Yonehara, Michio Shimizu, Takeshi Uehara, Jaswinder S Samra, Anthony J Gill, Christopher L Wolfgang, Michael G Goggins, Ralph H Hruban, Laura D Wood
High-grade pancreatic intraepithelial neoplasia (HG-PanIN) is the major precursor of pancreatic ductal adenocarcinoma (PDAC) and is an ideal target for early detection. To characterize pure HG-PanIN, we analysed 23 isolated HG-PanIN lesions occurring in the absence of PDAC. Whole-exome sequencing of five of these HG-PanIN lesions revealed a median of 33 somatic mutations per lesion, with a total of 318 mutated genes. Targeted next-generation sequencing of 17 HG-PanIN lesions identified KRAS mutations in 94% of the lesions...
February 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28187218/reduced-expression-of-argininosuccinate-synthetase-1-has-a-negative-prognostic-impact-in-patients-with-pancreatic-ductal-adenocarcinoma
#17
Qingqing Liu, John Stewart, Hua Wang, Asif Rashid, Jun Zhao, Matthew H Katz, Jeffrey E Lee, Jason B Fleming, Anirban Maitra, Robert A Wolff, Gauri R Varadhachary, Sunil Krishnan, Huamin Wang
Argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme for arginine biosynthesis, is expressed in many types of human malignancies. Recent studies showed that ASS1 may have tumor suppressor function and that ASS1 deficiency is associated with clinical aggressiveness in nasopharyngeal carcinoma, myxofibrosarcomas and bladder cancer. The goal of this study was to evaluate the prognostic impact of ASS1 expression in patients with pancreatic ductal adenocarcinoma (PDAC). Our study included two independent cohorts: untreated cohort, which was comprised of 135 patients with PDAC who underwent pancreatoduodenectomy (PD) without pre-operative neoadjuvant therapy, and treated cohort, which was comprised of 122 patients with PDAC who have completed neoadjuvant therapy and PD...
2017: PloS One
https://www.readbyqxmd.com/read/28183138/overall-survival-and-clinical-characteristics-of-brca-mutation-carriers-with-stage-i-ii-pancreatic-cancer
#18
Talia Golan, Tal Sella, Eileen M O'Reilly, Matthew H G Katz, Ron Epelbaum, David P Kelsen, Ayelet Borgida, Hannah Maynard, Hedy Kindler, Eitan Friedmen, Milind Javle, Steven Gallinger
BACKGROUND: BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. METHODS: A larger multi-centre, case-control retrospective analysis was performed...
February 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28180189/far-red-and-near-infrared-seminaphthofluorophores-for-targeted-pancreatic-cancer-imaging
#19
Lei Wang, Connor W Barth, Martha Sibrian-Vazquez, Jorge O Escobedo, Mark Lowry, John Muschler, Haiyan Li, Summer L Gibbs, Robert M Strongin
Molecular probes that selectively highlight pancreatic cancer (PC) tissue have the potential to improve pancreatic ductal adenocarcinoma (PDAC) margin assessment through the selective highlighting of individual PC cells. Herein, we report a simple and unique family of systematically modified red and near-infrared fluorescent probes that exhibit a field-effect-derived redshift. Two of thirteen probes distributed to the normal mouse pancreas following systemic administration. One selectively accumulated in genetically modified mouse models of PDAC...
January 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28179576/kiaa1199-is-induced-by-inflammation-and-enhances-malignant-phenotype-in-pancreatic-cancer
#20
Shiro Kohi, Norihiro Sato, Atsuhiro Koga, Nobutaka Matayoshi, Keiji Hirata
BACKGROUND: Recent evidence suggests a critical role of hyaluronan (HA), especially low-molecular-weight HA (LMW-HA), in the aggressive tumor phenotype. Increased expression of KIAA1199, a newly identified protein involved in HA degradation, has been reported in various cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the functional significance of KIAA1199 in PDAC. METHODS: Using siRNA knockdown and forced expression models, we investigated the effects of KIAA1199 expression on malignant behaviors (proliferation, migration, and invasion) of PDAC cells...
February 4, 2017: Oncotarget
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