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Pancreatic ductal adenocarcinoma

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https://www.readbyqxmd.com/read/28210844/elevated-interferon-induced-protein-with-tetratricopeptide-repeats-3-ifit3-is-a-poor-prognostic-marker-in-pancreatic-ductal-adenocarcinoma
#1
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
#2
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/28205343/association-of-chloride-intracellular-channel-4-and-indian-hedgehog-proteins-with-survival-of-patients-with-pancreatic-ductal-adenocarcinoma
#3
Qiong Zou, Zhulin Yang, Daiqiang Li, Ziru Liu, Yuan Yuan
Pancreatic cancer is the fourth most common cause of cancer-related mortality. Novel molecular biomarkers need to be identified for personalized medicine and to improve survival. The aim of this study was to examine chloride intracellular channel 4 (CLIC4) and Indian Hedgehog (Ihh) expression in benign and malignant lesions of the pancreas and to examine the eventual association between CLIC4 and Ihh expression, with clinicopathological features and prognosis of pancreatic cancer. A retrospective study of specimens collected from January 2000 to December 2011 at the Department of Pathology of the Second and Third Xiangya Hospitals, Central South University was undertaken to explore this question...
February 16, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28205147/identification-of-candidate-mirna-biomarkers-for-pancreatic-ductal-adenocarcinoma-by-weighted-gene-co-expression-network-analysis
#4
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
#5
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
#6
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/28197742/novel-biomarkers-for-pancreatic-cysts
#7
REVIEW
Harkirat Singh, Kevin McGrath, Aatur D Singhi
With increased utilization and ongoing advancements in cross-sectional abdominal imaging, the identification of a pancreatic cyst has become a frequent finding. While many pancreatic cysts are associated with a benign clinical course, others may transform into pancreatic ductal adenocarcinoma. However, distinguishing a benign from a malignant pancreatic cyst or pancreatic cyst with malignant potential on the basis of standard clinical findings, imaging parameters and ancillary studies can be challenging. Hence, a significant interest within the past decade has been the identification of novel biomarkers to accurately classify and prognosticate a pancreatic cyst...
February 14, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28196020/the-prevalence-and-clinicopathological-characteristics-of-high-grade-pancreatic-intraepithelial-neoplasia-autopsy-study-evaluating-the-entire-pancreatic-parenchyma
#8
Yoko Matsuda, Toru Furukawa, Shinichi Yachida, Makoto Nishimura, Atsuko Seki, Keisuke Nonaka, Junko Aida, Kaiyo Takubo, Toshiyuki Ishiwata, Wataru Kimura, Tomio Arai, Mari Mino-Kenudson
OBJECTIVE: We sought to identify clinicopathological characteristics of high-grade pancreatic intraepithelial neoplasia (PanIN)/carcinoma in situ to facilitate screening for pancreatic ductal adenocarcinoma. METHODS: We evaluated PanIN lesions in 173 consecutive autopsy cases with no evidence of pancreatic ductal adenocarcinoma and/or intraductal papillary mucinous neoplasm (mean age, 80.5 years) by submitting the entire pancreas for microscopic examination. RESULTS: PanIN-3 was found in 4% of examined cases, whereas PanIN-1 and PanIN-2 were present in 77% and 28%, respectively...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28196015/genomic-characterization-of-low-and-high-grade-pancreatic-mucinous-cystic-neoplasms-reveals-recurrent-kras-alterations-in-high-risk-lesions
#9
James R Conner, Adrián Mariño-Enríquez, Mari Mino-Kenudson, Elizabeth Garcia, Martha B Pitman, Lynette M Sholl, Amitabh Srivastava, Leona A Doyle
OBJECTIVES: Pancreatic ductal adenocarcinoma arises from the following 3 distinct precursor lesions: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm (MCN). Genetic abnormalities in the first 2 precursor lesions have been well characterized, but there are limited data on progression pathways in MCNs. This study aimed to characterize genomic differences between MCNs with low-grade (LG) and high-grade (HG) dysplasia or carcinoma...
February 14, 2017: Pancreas
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
#10
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/28194669/mir-143-targeting-tak1-attenuates-pancreatic-ductal-adenocarcinoma-progression-via-mapk-and-nf-%C3%AE%C2%BAb-pathway-in-vitro
#11
Feng-Ting Huang, Juan-Fei Peng, Wen-Jie Cheng, Yan-Yan Zhuang, Ling-Yun Wang, Chu-Qiang Li, Jian Tang, Wen-Ying Chen, Yuan-Hua Li, Shi-Neng Zhang
BACKGROUND: Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is one of the major regulators of inflammation-induced cancer cell growth and progression. MiR-143 dysregulation is a common event in a variety of human diseases including pancreatic ductal adenocarcinoma (PDA). AIMS: To identify the interaction between TAK1 and miR-143 in PDA. METHODS: Data mining of TAK1 expression in PDA patient gene profiling was conducted. QRT-PCR and western blot were performed to detect the expression of TAK1 in PDA tissues and cell lines...
February 13, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28194432/bet-inhibitors-block-pancreatic-stellate-cell-collagen-i-production-and-attenuate-fibrosis-in-vivo
#12
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/28191612/high-toll-like-receptor-tlr-9-expression-is-associated-with-better-prognosis-in-surgically-treated-pancreatic-cancer-patients
#13
Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H Kauppila, Joel Isohookana, Kirsi-Maria Haapasaari, Petri Lehenkari, Juha Saarnio, Tuomo J Karttunen
Pancreatic cancer remains one of the deadliest malignancies in the world. Inflammatory response and tumor environment are thought to play a major role in its pathogenesis. Knowledge on TLR expression and impact on patient survival in pancreatic cancer is limited. The study's aim was to clarify the role of different TLRs in pancreatic cancer. TLR2, TLR4, and TLR9 expression was investigated in 65 surgically resected pancreatic ductal adenocarcinoma specimens by immunohistochemistry. The association between TLR expression, clinical parameters, and local inflammatory response to the tumor was assessed using chi-square test...
February 12, 2017: Virchows Archiv: An International Journal of Pathology
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/28188630/genetic-analyses-of-isolated-high-grade-pancreatic-intraepithelial-neoplasia-hg-panin-reveal-paucity-of-alterations-in-tp53-and-smad4
#15
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/28187453/lack-of-association-between-the-pancreatitis-risk-allele-cel-hyb-and-pancreatic-cancer
#16
Koji Shindo, Jun Yu, Masaya Suenaga, Shahriar Fesharakizadeh, Koji Tamura, Jose Alejandro Navarro Almario, Aaron Brant, Michael Borges, Abdulrehman Siddiqui, Lisa Datta, Christopher L Wolfgang, Ralph H Hruban, Alison Patricia Klein, Michael Goggins
CEL-HYB is a hybrid allele that arose from a crossover between the 3' end of the Carboxyl ester lipase (CEL) gene and the nearby CEL pseudogene (CELP) and was recently identified as a risk factor for chronic pancreatitis. Since chronic pancreatitis is a risk factor for the development of pancreatic cancer, we compared the prevalence of the CEL-HYB allele in patients with pancreatic ductal adenocarcinoma to spousal controls and disease controls. The CEL-HYB allele was detected using Sanger and next generation sequencing...
February 7, 2017: Oncotarget
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/28180189/far-red-and-near-infrared-seminaphthofluorophores-for-targeted-pancreatic-cancer-imaging
#18
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
#19
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
https://www.readbyqxmd.com/read/28179331/preoperative-platelet-to-albumin-ratio-predicts-prognosis-of-patients-with-pancreatic-ductal-adenocarcinoma-after-pancreatic-resection
#20
Yoshihiro Shirai, Hiroaki Shiba, Koichiro Haruki, Takashi Horiuchi, Nobuhiro Saito, Yuki Fujiwara, Taro Sakamoto, Tadashi Uwagawa, Katsuhiko Yanaga
BACKGROUND: The aim of this study was to evaluate a novel prognostic value of preoperative platelet-to-albumin ratio (PAR) in patients resected for pancreatic cancer. PATIENTS AND METHODS: A total of 107 patients who underwent pancreatic resection for pancreatic cancer were studied. The patients were divided into two groups as PAR ≥46.4×10(3) or <46.4×10(3) Survival data were analyzed using the log-rank test for univariate analysis and Cox proportional hazards for multivariate analysis...
2017: Anticancer Research
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