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https://www.readbyqxmd.com/read/29222037/diabetes-as-risk-factor-for-pancreatic-cancer-hyperglycemia-promotes-epithelial-mesenchymal-transition-and-stem-cell-properties-in-pancreatic-ductal-epithelial-cells
#1
Sascha Rahn, Vivien Zimmermann, Fabrice Viol, Hendrike Knaack, Kerstin Stemmer, Lena Peters, Lennart Lenk, Hendrik Ungefroren, Dieter Saur, Heiner Schäfer, Ole Helm, Susanne Sebens
Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29221990/molecular-and-cellular-mechanisms-of-chemoresistance-in-pancreatic-cancer
#2
REVIEW
Aleksandra Adamska, Omar Elaskalani, Aikaterini Emmanouilidi, Minkyoung Kim, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available options are surgery, embolization, radiation, chemotherapy, immunotherapy and use of other more targeted drugs. In this review, we describe the cellular and molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE (nab-Paclitaxel), which have shown a survival benefit, although modest, for pancreatic cancer patients...
November 22, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29221926/plasma-protein-profiling-of-patients-with-intraductal-papillary-mucinous-neoplasm-of-the-pancreas-as-potential-precursor-lesions-of-pancreatic-cancer
#3
Maria Ilies, Praveen Kumar Sappa, Cristina Adela Iuga, Felicia Loghin, Manuela Gesell Salazar, Frank Ulrich Weiss, Georg Beyer, Markus M Lerch, Uwe Völker, Julia Mayerle, Elke Hammer
Efforts for the early diagnosis of the pancreatic ductal adenocarcinoma (PDAC) have recently been driven to one of the precursor lesions, namely intraductal papillary mucinous neoplasm of the pancreas (IPMN). Only a few studies have focused on IPMN molecular biology and its overall progression to cancer. Therefore, IPMN lacks comprehensive characterization which makes its clinical management controversial. In this study, we characterized plasma proteins in the presence of IPMNs in comparison to healthy controls, chronic pancreatitis, and PDAC by a proteomics approach using data-independent acquisition based mass spectrometry...
December 5, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29221879/surveillance-of-patients-with-intraductal-papillary-mucinous-neoplasm-with-and-without-pancreatectomy-with-special-reference-to-the-incidence-of-concomitant-pancreatic-ductal-adenocarcinoma
#4
Kenjiro Date, Takao Ohtsuka, So Nakamura, Naoki Mochidome, Yasuhisa Mori, Yoshihiro Miyasaka, Yoshinao Oda, Masafumi Nakamura
BACKGROUND: The presence of an intraductal papillary mucinous neoplasm (IPMN) is important in the detection of concomitant pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to elucidate the incidence and timing of development of concomitant PDAC in patients with and without pancreatectomy for IPMN. METHODS: We reviewed retrospectively the surveillance data for 22 patients who underwent pancreatectomy for PDAC concomitant with IPMN (PDAC-resection group), 180 who underwent pancreatectomy for IPMN (IPMN-resection group), and 263 whose IPMNs were left untreated (non-resection group)...
December 5, 2017: Surgery
https://www.readbyqxmd.com/read/29221789/pretherapy-neutrophil-to-lymphocyte-ratio-and-platelet-to-lymphocyte-ratio-do-not-predict-survival-in-resectable-pancreatic-cancer
#5
Akhil Chawla, Tiffany L Huang, Andrew M Ibrahim, Jeffrey M Hardacre, Christopher Siegel, John B Ammori
BACKGROUND: Pretherapy serum neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have both been identified as prognostic in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to identify the prognostic implication of pretherapy NLR and PLR in patients with resectable PDAC. METHODS: Data were collected retrospectively on patients operated at our institution between 2004 and 2014. A Cox proportional hazards model was used to investigate the relationship between clinical and pathological parameters, NLR and PLR to overall survival (OS)...
December 5, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/29221165/angiogenesis-in-adenosquamous-cancer-of-pancreas
#6
Nicola Silvestris, Katia Danza, Vito Longo, Oronzo Brunetti, Livia Fucci, Antonella Argentiero, Angela Calabrese, Ivana Cataldo, Roberto Tamma, Domenico Ribatti, Stefania Tommasi
Adenosquamous carcinoma of the pancreas (ASCP) is an uncommon variant of exocrine pancreatic malignancies, characterized by a histological admixture of adenomatous and squamous cell elements. This cancer is characterized by a poorly differentiated histology and a poorer clinical outcome compared to pancreatic ductal adenocarcinoma (PDAC). Unlike PDAC, that is characterized by a low microvascular density (MVD) and collapsed vasculature, no data are available about angiogenesis in ASPC. Immunohistochemical evaluation of MVD and trypatse-positive mast cells (MCs) were performed on a single case of ASCP compared to PDAC...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221133/endogenous-glutamine-decrease-is-associated-with-pancreatic-cancer-progression
#7
Cecilia Roux, Chiara Riganti, Sammy Ferri Borgogno, Roberta Curto, Claudia Curcio, Valeria Catanzaro, Giuseppe Digilio, Sergio Padovan, Maria Paola Puccinelli, Monica Isabello, Silvio Aime, Paola Cappello, Francesco Novelli
Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29216209/preliminary-study-of-tumor-heterogeneity-in-imaging-predicts-two-year-survival-in-pancreatic-cancer-patients
#8
Jayasree Chakraborty, Liana Langdon-Embry, Kristen M Cunanan, Joanna G Escalon, Peter J Allen, Maeve A Lowery, Eileen M O'Reilly, Mithat Gönen, Richard G Do, Amber L Simpson
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy...
2017: PloS One
https://www.readbyqxmd.com/read/29215586/investigation-of-polyamine-metabolism-and-homeostasis-in-pancreatic-cancers
#9
Chelsea Massaro, Jenna Thomas, Otto Phanstiel Iv
Pancreatic cancers are currently the fourth leading cause of cancer-related death and new therapies are desperately needed. The most common pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). This report describes the development of therapies, which effectively deplete PDAC cells of their required polyamine growth factors. Of all human tissues, the pancreas has the highest level of the native polyamine spermidine. To sustain their high growth rates, PDACs have altered polyamine metabolism, which is reflected in their high intracellular polyamine levels and their upregulated import of exogenous polyamines...
December 7, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29214453/neoadjuvant-therapy-versus-upfront-resection-for-pancreatic-cancer-the-actual-spectrum-and-clinical-burden-of-postoperative-complications
#10
Giovanni Marchegiani, Stefano Andrianello, Chiara Nessi, Marta Sandini, Laura Maggino, Giuseppe Malleo, Salvatore Paiella, Enrico Polati, Claudio Bassi, Roberto Salvia
BACKGROUND: Neoadjuvant therapy (NAT) is used for borderline-resectable or locally advanced pancreatic cancer (PDAC) and exhibits promising results in terms of pathological outcomes. However, little is known about its effect on surgical complications. METHODS: We analyzed 445 pancreatic resections for PDAC from 2014 to 2016 at The Pancreas Institute, Verona University Hospital. The Modified Accordion Severity Grading System and average complication burden (ACB) were used to compare patients treated with NAT with patients who underwent upfront surgery (UFS)...
December 6, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29213099/apparent-diffusion-coefficient-adc-predicts-therapy-response-in-pancreatic-ductal-adenocarcinoma
#11
M Trajkovic-Arsic, I Heid, K Steiger, A Gupta, A Fingerle, C Wörner, N Teichmann, S Sengkwawoh-Lueong, P Wenzel, A J Beer, I Esposito, R Braren, J T Siveke
Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211796/reprogramming-pancreatic-stellate-cells-via-p53-activation-a-putative-target-for-pancreatic-cancer-therapy
#12
Maya Saison-Ridinger, Kathleen E DelGiorno, Tejia Zhang, Annabelle Kraus, Randall French, Dawn Jaquish, Crystal Tsui, Galina Erikson, Benjamin T Spike, Maxim N Shokhirev, Christopher Liddle, Ruth T Yu, Michael Downes, Ronald M Evans, Alan Saghatelian, Andrew M Lowy, Geoffrey M Wahl
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely dense fibrotic stroma, which contributes to tumor growth, metastasis, and drug resistance. During tumorigenesis, quiescent pancreatic stellate cells (PSCs) are activated and become major contributors to fibrosis, by increasing growth factor signaling and extracellular matrix deposition. The p53 tumor suppressor is known to restrict tumor initiation and progression through cell autonomous mechanisms including apoptosis, cell cycle arrest, and senescence...
2017: PloS One
https://www.readbyqxmd.com/read/29209626/neovascular-prostate-specific-membrane-antigen-expression-is-associated-with-improved-overall-survival-under-palliative-chemotherapy-in-patients-with-pancreatic-ductal-adenocarcinoma
#13
Katharina Stock, Konrad Steinestel, Rebekka Wiesch, Jan-Henrik Mikesch, Anna Hansmeier, Marcel Trautmann, Nora Beller, Jan Rehkämper, Eva Wardelmann, Birthe Heitkötter, Wolfgang Hartmann, Jan Sperveslage, Sebastian Huss
Aims: Expression of PSMA (prostate-specific membrane antigen) has been demonstrated in various cancers, including pancreatic ductal adenocarcinoma (PDAC). However, PSMA expression in PDAC-associated neovasculature has so far not been systematically analyzed. Methods and Results: We analyzed PSMA expression in 81 PDAC tissue samples from 61 patients. Microvessel density (MVD) was assessed by software-based image analysis and showed a mean MVD of 63.7 microvessels/0...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29207609/reciprocal-regulation-of-dgcr5-and-mir-320a-affects-the-cellular-malignant-phenotype-and-5-fu-response-in-pancreatic-ductal-adenocarcinoma
#14
Sun Yong, Yu Yabin, Zhou Bing, Zhu Chuanrong, Gu Dianhua, Zhang Jianhuai, Yuan Weidong, Wang Shuming, Liu Ling
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Long non-coding microRNAs (lncRNAs) are a newly discovered type of regulatory molecule with both diagnostic and prognostic value, but the role of lncRNA in PDAC has not been well investigated until now. Here, we present evidence that shows that the lncRNA DGCR5 is significantly reduced in PDAC tissues as well as in PDAC cell lines and that the downregulation of DGCR5 predicts poor prognosis. Ectopic expression of DGCR5 inhibits the proliferation and migration, and promotes 5-FU resistances of PDAC cells...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29205349/perioperative-cytokine-levels-portend-early-death-after-pancreatectomy-for-ductal-adenocarcinoma
#15
Heather L Lewis, Jeff M Chakedis, Erin Talbert, Ericka Haverick, Priyani Rajasekera, Philip Hart, Mark Bloomston, Mary Dillhoff, Timothy M Pawlik, Denis Guttridge, Carl R Schmidt
BACKGROUND: Soluble signaling molecules may play an important role in malignant pathogenesis. We hypothesize that perioperative cytokine levels are associated with outcomes in patients with pancreatic adenocarcinoma (PDAC) undergoing surgical resection. METHODS: One hundered and eighteen patients with benign or malignant pancreatic disease were enrolled in a prospective study through a protocol for banking biologic samples. Peripheral blood was drawn at time of operation, and a multiplex cytokine assay was performed...
December 4, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29202869/prognostic-significance-of-hepatocyte-growth-factor-activator-inhibitor-type-1-hai-1-immunoreactivity-in-pancreatic-ductal-adenocarcinoma
#16
Chihiro Sakugawa, Yukihiro Haruyama, Hiroyuki Tanaka, Tsuyoshi Fukushima, Makiko Kawaguchi, Hiroaki Kataoka
OBJECTIVE: Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine protease inhibitor that is expressed on the surface of epithelial cells. Evidence has suggested that decreased cell surface HAI-1 in carcinoma cells results in enhanced invasiveness. However, little is known regarding the expression of HAI-1 in pancreatic ductal adenocarcinoma (PDAC). This study aimed to analyze HAI-1 expression in PDAC and its impact on patient prognosis. RESULTS: HAI-1 immunohistochemistry was performed on samples from 67 PDAC cases...
December 4, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29199604/mirna-a-diagnostic-and-therapeutic-tool-for-pancreatic-cancer
#17
Muhammad Imran Qadir, Arooj Faheem
Pancreatic ductal adenocarcinoma (PDAC) is fatal disease and one of the major causes of death among cancer patients. Diagnosis of PDAC during the early stages of cancer using ultrasounds and blood tests is difficult and chemotherapies alone for treating cancers are not very effective. MicroRNAs (miRNAs), small non-coding RNAs that alter the expression of genes in many processes, have been identified to play a significant role in pancreatic cancer regulation. miRNAs are classified as oncomiRs (tumor inducers) and tumor suppressor miRNAs...
2017: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29198002/staging-of-pancreatic-cancer-resectable-borderline-resectable-and-unresectable-disease
#18
Erik V Soloff, Atif Zaheer, Jeffrey Meier, Marc Zins, Eric P Tamm
Pancreatic ductal adenocarcinoma (PDAC) is a relatively common malignancy that carries an overall poor prognosis, with five-year survival below 10%. Despite ongoing research, surgical resection remains the only potentially curative treatment. Therefore, accurate identification of those patients who would benefit from surgical resection is of paramount importance. High-quality imaging and image interpretation is central to this process. Radiology helps in the determination of whether patients are resectable, borderline resectable, or unresectable and guides treatment planning...
December 2, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/29197396/new-laparoscopic-procedure-for-left-sided-pancreatic-cancer-artery-first-approach-laparoscopic-ramps-using-3d-technique
#19
Michihiro Yamamoto, Masazumi Zaima, Hidekazu Yamamoto, Hideki Harada, Junichiro Kawamura, Masahiro Yamada, Tekefumi Yazawa, Junya Kawasoe
BACKGROUND: For left-sided pancreatic ductal adenocarcinoma (PDAC), radical antegrade modular pancreatosplenectomy (RAMPS) is a reasonable surgical approach for tumor-free margin resection and systemic lymph node clearance. In pancreaticoduodenectomy for PDAC, the superior mesenteric artery (SMA)-first approach (or the "artery-first approach") has become the standard procedure. With improvements in laparoscopic instruments and techniques, some surgeons attempted to apply laparoscopic RAMPS (L-RAMPS) for carefully selected patients with left-sided PDAC...
December 2, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29197353/histone-profiling-reveals-the-h1-3-histone-variant-as-a-prognostic-biomarker-for-pancreatic-ductal-adenocarcinoma
#20
Monika Bauden, Theresa Kristl, Agata Sasor, Bodil Andersson, György Marko-Varga, Roland Andersson, Daniel Ansari
BACKGROUND: Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues...
December 2, 2017: BMC Cancer
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