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https://www.readbyqxmd.com/read/29749431/expression-of-annexin-ii-and-stromal-tenascin-c-promotes-epithelial-to-mesenchymal-transition-and-correlates-with-distant-metastasis-in-pancreatic-cancer
#1
Naoko Yoneura, Shigetsugu Takano, Hideyuki Yoshitomi, Yasuyuki Nakata, Reiri Shimazaki, Shingo Kagawa, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Masaru Miyazaki, Masayuki Ohtsuka
The interaction between cancer cells and stromal components contributes to cancer invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). The present study investigated the role of the correlation between annexin II (ANX2) and stromal tenascin C (TNC) with the progression of PDAC. The functions of the expression ANX2 and TNC were assessed in in vitro experiments using mouse and human PDAC cells, and the clinical effect was analyzed using immunohistochemistry with surgically resected PDAC tissues...
May 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29748382/satellite-rna-increases-dna-damage-and-accelerates-tumor-formation-in-mouse-models-of-pancreatic-cancer
#2
Takahiro Kishikawa, Motoyuki Otsuka, Tatsunori Suzuki, Takahiro Seimiya, Kazuma Sekiba, Rei Ishibashi, Eri Tanaka, Motoko Ohno, Mari Yamagami, Kazuhiko Koike
Highly repetitive tandem arrays such as satellite sequences in the centromeric and pericentromeric regions of chromosomes, which were previously considered to be silent, are actively transcribed in various biological processes, including cancers. In the pancreas, this aberrant expression occurs even in Kras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are precancerous lesions. To determine the biological role of satellite RNAs in carcinogenesis in vivo, we constructed mouse major satellite (MajSAT) RNA-expressing transgenic mice...
May 10, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29732356/clinical-significance-of-pancreatic-intraepithelial-neoplasia-in-resectable-pancreatic-cancer-on-survivals
#3
Da-Young Yu, Young-Dong Yu, Wan-Bae Kim, Hyung-Joon Han, Sae-Byul Choi, Dong-Sik Kim, Sang-Yong Choi, Joo-Young Kim, Hyeyoon Chang, Baek-Hui Kim
Purpose: Noninvasive precursor lesions for pancreatic adenocarcinoma include pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. PanIN is often found synchronously adjacent to resected pancreatic ductal adenocarcinoma (PDAC) tumors. However, its prognostic significance on outcome after PDAC resection is unknown. The purpose of the current study was to determine if the presence of PanIN has a prognostic or predictive effect on survival after resection for PDAC with curative intent...
May 2018: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/29660164/high-grade-panin-presenting-with-localized-stricture-of-the-main-pancreatic-duct-a-clinicopathological-and-molecular-study-of-10-cases-suggests-a-clue-for-the-early-detection-of-pancreatic-cancer
#4
Masataka Yokode, Masayuki Akita, Kohei Fujikura, Mi-Ju Kim, Yukiko Morinaga, Seiichi Yoshikawa, Takuro Terada, Hiroshi Matsukiyo, Takuma Tajiri, Shiho Abe-Suzuki, Tomoo Itoh, Seung-Mo Hong, Yoh Zen
AIMS: This study aimed to identify the pathological features of high-grade PanIN that presents with imaging-detectable abnormalities. METHODS AND RESULTS: Ten cases of isolated, main-duct, high-grade PanIN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with 2 being associated with extensive upstream duct dilatation (>5 mm in diameter). Pancreatic juice cytology suggested adenocarcinoma in all 7 cases examined...
April 16, 2018: Histopathology
https://www.readbyqxmd.com/read/29658052/reduced-%C3%AE-glcnac-glycosylation-on-gastric-gland-mucin-is-a-biomarker-of-malignant-potential-for-gastric-cancer-barrett-s-adenocarcinoma-and-pancreatic-cancer
#5
REVIEW
Kazuhiro Yamanoi, Jun Nakayama
Gastric gland mucin secreted from pyloric gland cells, mucous neck cells, and cardiac gland cells of the gastric mucosa harbors unique O-glycans carrying terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc), which are primarily attached to the scaffold mucin core protein MUC6. αGlcNAc acts as an antibiotic against Helicobacter pylori (H. pylori), a microbe causing gastric cancer. In addition, mice deficient in A4gnt, which encodes the enzyme α1,4-N-acetylglucosaminyltransferase (α4GnT) that catalyzes αGlcNAc biosynthesis, spontaneously develop gastric differentiated-type adenocarcinoma, even if not infected by H...
April 16, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29621546/aberrant-upregulation-of-klk10-promotes-metastasis-via-enhancement-of-emt-and-fak-src-erk-axis-in-pdac
#6
Xiao-Yan Cao, Xiao-Xin Zhang, Min-Wei Yang, Li-Peng Hu, Shu-Heng Jiang, Guang-Ang Tian, Li-Li Zhu, Qing Li, Yong-Wei Sun, Zhi-Gang Zhang
Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC...
April 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29604293/immune-cell-production-of-interleukin-17-induces-stem-cell-features-of-pancreatic-intraepithelial-neoplasia-cells
#7
Yu Zhang, Michelle Zoltan, Erick Riquelme, Hanwen Xu, Ismet Sahin, Susana Castro-Pando, Maria Fernanda Montiel, Kyle Chang, Zhengyu Jiang, Jianhua Ling, Sonal Gupta, William Horne, Melissa Pruski, Huamin Wang, Shao-Cong Sun, Guillermina Lozano, Paul Chiao, Anirban Maitra, Steven D Leach, Jay K Kolls, Eduardo Vilar Sanchez, Timothy C Wang, Jennifer M Bailey, Florencia McAllister
BACKGROUND & AIMS: Little is known about how the immune system affects stem cell features of pancreatic cancer cells. Immune cells that produce interleukin 17 A (IL17A) in the chronically inflamed pancreas (chronic pancreatitis) contribute to PanIN initiation and progression. We investigated the effects of IL17A signaling exerts on pancreatic cancer progenitor cells and the clinical relevance of this phenomena. METHODS: We performed studies with Mist1Cre;LSLKras;Rosa26mTmG (KCiMist ;G) and Kras(G12D); Trp53(R172H); Pdx1-Cre (KPC) mice (which upon tamoxifen induction spontaneously develop pancreatic intraepithelial neoplasias, PanINs) and control littermates...
March 28, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29596465/homozygous-ksr1-deletion-attenuates-morbidity-but-does-not-prevent-tumor-development-in-a-mouse-model-of-ras-driven-pancreatic-cancer
#8
Elizabeth A Germino, Joseph P Miller, Lauri Diehl, Carter J Swanson, Steffen Durinck, Zora Modrusan, Jeffrey H Miner, Andrey S Shaw
Given the frequency with which MAP kinase signaling is dysregulated in cancer, much effort has been focused on inhibiting RAS signaling for therapeutic benefit. KSR1, a pseudokinase that interacts with RAF, is a potential target; it was originally cloned in screens for suppressors of constitutively active RAS, and its deletion prevents RAS-mediated transformation of mouse embryonic fibroblasts. In this work, we used a genetically engineered mouse model of pancreatic cancer to assess whether KSR1 deletion would influence tumor development in the setting of oncogenic RAS...
2018: PloS One
https://www.readbyqxmd.com/read/29533466/the-advanced-glycation-end-product-n-%C3%AF%C2%B5-carboxymethyllysine-promotes-progression-of-pancreatic-cancer-implications-for-diabetes-associated-risk-and-its-prevention
#9
Stefano Menini, Carla Iacobini, Luisa de Latouliere, Isabella Manni, Vittoria Ionta, Claudia Blasetti Fantauzzi, Carlo Pesce, Paola Cappello, Francesco Novelli, Giulia Piaggio, Giuseppe Pugliese
Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation...
June 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29462213/early-detection-of-pancreatic-cancer-in-mouse-models-using-a-novel-antibody-tab004
#10
Shu-Ta Wu, Chandra D Williams, Priyanka A Grover, Laura J Moore, Pinku Mukherjee
Pancreatic ductal adenocarcinoma (PDA) is the fourth-leading cause of cancer death in the United States with a 5-year overall survival rate of 8% for all stages combined. But this decreases to 3% for the majority of patients that present with stage IV PDA at time of diagnosis. The lack of distinct early symptoms for PDA is one of the primary reasons for the late diagnosis. Common symptoms like weight loss, abdominal and back pains, and jaundice are often mistaken for symptoms of other issues and do not appear until the cancer has progressed to a late stage...
2018: PloS One
https://www.readbyqxmd.com/read/29433879/expression-of-neuropeptide-y-and-its-receptors-y1-and-y2-in-pancreatic-intraepithelial-neoplasia-and-invasive-pancreatic-cancer-in-a-transgenic-mouse-model-and-human-samples-of-pancreatic-cancer
#11
Jens Waldmann, Volker Fendrich, Martin Reichert, Andreas Hecker, Detlef K Bartsch, Winfried Padberg, Julia P N Holler
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most dismal of human malignancies. Neuropeptides have shown to be implicated in angiogenesis, tumor growth, and formation of distant metastases in various solid tumors. In the present study, we used a genetically engineered mouse model of pancreatic cancer to evaluate the impact of neuropeptide Y (NPY) and its receptors 1 (Y1) and 2 (Y2) in preneoplastic lesions and pancreatic cancer as a potential target with antiproliferative properties...
March 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29388054/p16-p21-and-p53-proteins-play-an-important-role-in-development-of-pancreatic-intraepithelial-neoplastic
#12
Justyna Zińczuk, Konrad Zaręba, Katarzyna Guzińska-Ustymowicz, Bogusław Kędra, Andrzej Kemona, Anna Pryczynicz
BACKGROUND: Deregulation of cell cycle takes place during the development of many cancers as well as pancreatic ductal adenocarcinoma (PDA), which develops from precursor lesions, most frequently including pancreatic intraepithelial neoplasia (PanIN). AIMS: The aim of this study was to evaluate and compare the expression of p16, p21, and p53 proteins taking part in the regulation of the cell cycle in normal pancreatic ducts and pancreatic intraepithelial neoplasia at its various advancing stages...
February 1, 2018: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29367759/genetic-and-pharmacologic-abrogation-of-snail1-inhibits-acinar-to-ductal-metaplasia-in-precursor-lesions-of-pancreatic-ductal-adenocarcinoma-and-pancreatic-injury
#13
Volker Fendrich, Frederike Jendryschek, Saskia Beeck, Max Albers, Matthias Lauth, Farzad Esni, Kristin Heeger, Janina Dengler, Emily P Slater, Julia P N Holler, Aninja Baier, Detlef K Bartsch, Jens Waldmann
Pancreatic cancer (PDAC) is one of the most dismal of human malignancies. Inhibiting or delaying the progression of precursor lesions of PDAC, pancreatic intraepthial neoplasia (PanINs), to invasive cancer, would be a major step. In the present study, we used a transgenic murine model of pancreatic cancer to evaluate the impact of a conditional knockout of the transcription factor Snail1, a major factor in epithelial-to-mesenchymal transition, on acinar-to-ductal formation and on PanIN progression. By interbreeding conditional LsL-Snailfloxf/wt ; LsL-KrasG12D and Pdx1-Cre strains, we obtained LsL-KrasG12D ;Pdx1-Cre(KP) mice, Snail1 heterozygous knockout LsL-KrasG12D ; LsL-Snailflox/- ;Pdx1-Cre(KPShet ) mice or Snail1 homozygous knockout LsL-KrasG12D ;LsL-Snailflox/flox ;Pdx1-Cre(KPS) mice...
January 25, 2018: Oncogene
https://www.readbyqxmd.com/read/29352660/clinical-significance-of-muc13-in-pancreatic-ductal-adenocarcinoma
#14
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
#15
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...
March 2018: 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
#16
Ping He, Jong Won Yang, Vincent W Yang, Agnieszka B Bialkowska
BACKGROUND & AIMS: Activating mutations in KRAS (Kirsten rat sarcoma viral oncogene homolog) 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 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29232549/stressing-out-panin-nrf2-pushes-over-the-edge
#17
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
#18
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...
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
#19
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...
March 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29190947/thioredoxin-system-mediated-regulation-of-mutant-kras-associated-pancreatic-neoplasia-and-cancer
#20
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
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