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Adam Buckle, Ryu-Suke Nozawa, Dirk A Kleinjan, Nick Gilbert
Complex diseases, such as diabetes, are influenced by comprehensive transcriptional networks. Genome-wide association studies have revealed that variants located in regulatory elements for pancreatic transcription factors are linked to diabetes, including those functionally linked to the paired box transcription factor, Pax6. Pax6 deletions in adult mice cause rapid onset of classic diabetes, but the full spectrum of pancreatic Pax6 regulators is unknown. Using a regulatory element discovery approach we identified two novel Pax6 pancreatic cis-regulatory elements in a poorly characterised regulatory desert...
July 11, 2018: Human Molecular Genetics
Haoyi Jin, Peng Liu, Yunhao Wu, Xiangli Meng, Mengwei Wu, Jiahong Han, Xiaodong Tan
Pancreatic cancer is one of the deadliest cancers with rapid disease progression, requiring further elucidation of its underlying molecular mechanisms and novel biomarkers for early detection. Exosomes are small extracellular vesicles that are released by multiple cell types acting as message carriers during intercellular communication and are promising biomarker candidates. However, the role of pancreatic cancer cell-derived exosomes in cancer progression and the application of these vesicles as novel diagnostic biomarkers are still not fully studied...
July 14, 2018: Cancer Science
S Gasteiger, B Cardini, G Göbel, R Oberhuber, F Messner, T Resch, C Bösmüller, C Margreiter, S Schneeberger, M Maglione
BACKGROUND: Pancreas retransplantation is still a controversial option after loss of a pancreatic graft. This article describes the experience of pancreas retransplantation at a high-volume centre. METHODS: This was a retrospective observational study of all pancreas retransplantations performed in a single centre between 1997 and 2013. Pancreatic graft loss was defined by the return to insulin dependence. Risk factors for graft loss as well as patient and graft survival were analysed using logistic and time-to-event regression models...
July 14, 2018: British Journal of Surgery
Susanna Hegewisch-Becker, Ali Aldaoud, Thomas Wolf, Beate Krammer-Steiner, Hartmut Linde, Renate Scheiner-Sparna, David Hamm, Martina Jänicke, Norbert Marschner
Pancreatic cancer is a highly lethal malignancy. Developments in recent years have broadened our therapeutic armamentarium. Novel drugs such as nab-paclitaxel, liposomal irinotecan and chemotherapy regimens such as FOLFIRINOX have been successfully tested in clinical trials. Data on patients outside of clinical trials are scarce but necessary to assess and improve the standard of care. We present data on treatment and survival of 1,174 patients with locally advanced, inoperable or metastatic pancreatic ductal adenocarcinoma...
July 14, 2018: International Journal of Cancer. Journal International du Cancer
O V Kokorev, V N Khodorenko, S G Anikeev, V E Gunter
The dynamics of the development of the pancreatic islet cells in the porous TiNi scaffold was studied by electron microscopy. Changes in the metabolism of glucose and glycosylated hemoglobin and parameters of the peripheral blood and bone marrow were shown after transplantation of pancreatic islet cells on porous permeable TiNi scaffold during alloxan-induced diabetes. The cells administered on the porous biocompatible scaffold produced more prolonged anti-diabetic effect and normalized hemopoiesis parameters in comparison with their intraperitoneal administration...
July 13, 2018: Bulletin of Experimental Biology and Medicine
Arne Bokemeyer, Dina Gross, Markus Brückner, Tobias Nowacki, Dominik Bettenworth, Hartmut Schmidt, Hauke Heinzow, Iyad Kabar, Hansjoerg Ullerich, Frank Lenze
BACKGROUND: Treatment of biliary strictures is challenging. Digital single-operator cholangioscopes (SOCs) equipped with an improved imaging quality, were recently introduced and may be useful for selective guidewire placement in difficult biliary strictures. METHODS: A total of 167 digital SOC procedures performed between 2015 and 2018 were retrospectively analyzed for successful guidewire placements across biliary strictures. Only cases with previous failed conventional guidewire placement approaches were included...
July 13, 2018: Surgical Endoscopy
Benish Fida, Fabrizio Cutolo, Gregorio di Franco, Mauro Ferrari, Vincenzo Ferrari
Augmented reality (AR) has been successfully providing surgeons an extensive visual information of surgical anatomy to assist them throughout the procedure. AR allows surgeons to view surgical field through the superimposed 3D virtual model of anatomical details. However, open surgery presents new challenges. This study provides a comprehensive overview of the available literature regarding the use of AR in open surgery, both in clinical and simulated settings. In this way, we aim to analyze the current trends and solutions to help developers and end/users discuss and understand benefits and shortcomings of these systems in open surgery...
July 13, 2018: Updates in Surgery
Dalveer Singh, Roslyn Horneman, Navjot Kaur Nagra
OBJECTIVE: Prostate specific membrane antigen (PSMA) positron emission tomography diagnostic computed tomography (PET/CT) is gaining an increasing role in the staging of prostate cancer and restaging in cases of biochemical recurrence. Our understanding of PSMA affinity for incidental pathological and non-pathological entities is also maturing although certain cases do present as diagnostic and management dilemmas. SUBJECT AND METHODS: We present a case of a 55 years old man with prostate adenocarcinoma, with incidentally found pancreatic and thyroid lesions showing PSMA avidity...
July 12, 2018: Hellenic Journal of Nuclear Medicine
Alessandro Agnarelli, Marco Natali, Mercedes Garcia-Gil, Rossana Pesi, Maria Grazia Tozzi, Chiara Ippolito, Nunzia Bernardini, Robert Vignali, Renata Batistoni, Anna Maria Bianucci, Silvia Marracci
The natural alkaloid berberine has several pharmacological properties and recently received attention as a potential anticancer agent. In this work, we investigated the molecular mechanisms underlying the anti-tumor effect of berberine on glioblastoma U343 and pancreatic carcinoma MIA PaCa-2 cells. Human dermal fibroblasts (HDF) were used as non-cancer cells. We show that berberine differentially affects cell viability, displaying a higher cytotoxicity on the two cancer cell lines than on HDF. Berberine also affects cell cycle progression, senescence, caspase-3 activity, autophagy and migration in a cell-specific manner...
July 13, 2018: Scientific Reports
Anello Marcello Poma, Liborio Torregrossa, Rossella Bruno, Fulvio Basolo, Gabriella Fontanini
The disruption of the Hippo pathway occurs in many cancer types and is associated with cancer progression. Herein, we investigated the impact of 32 Hippo genes on overall survival (OS) of cancer patients, by both analysing data from The Cancer Genome Atlas (TCGA) and reviewing the related literature. mRNA and protein expression data of all solid tumors except pure sarcomas were downloaded from TCGA database. Thirty-two Hippo genes were considered; for each gene, patients were dichotomized based on median expression value...
July 13, 2018: Scientific Reports
Jennifer A Salati, Victoria H J Roberts, Matthias C Schabel, Jamie O Lo, Christopher D Kroenke, Katherine S Lewandowski, Jonathan R Lindner, Kevin L Grove, Antonio E Frias
BACKGROUND: In a Japanese macaque model of diet-induced obesity, we have previously demonstrated that consumption of a high-fat, "Western-style" diet (WSD) is associated with placental dysfunction and adverse pregnancy outcomes, independent of an obese maternal phenotype. Specifically, we have reported decreased uterine placental blood flow and increased inflammation with maternal WSD consumption. We also previously investigated the use of a promising therapeutic intervention that mitigated the adverse placental effects of a WSD but had unexpected detrimental effects on fetal pancreatic development...
July 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Vince Kornél Grolmusz, Annamária Kövesdi, Katalin Borka, Peter Igaz, Attila Patocs
Objective Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the endocrine pancreas, however their prognosis differs significantly upon their proliferative state which is characterized by histopathological grading. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to identify miRNAs with altered expression upon proliferation which can be used as prognostic biomarkers in PanNENs. Methods MiRNA expression profiles of 40 PanNENs were downloaded from Gene Expression Omnibus and were reanalyzed upon tumor grades (discovery cohort)...
July 13, 2018: European Journal of Endocrinology
Hiroki Fujieda, Masakazu Kogami, Masao Sakairi, Noriyasu Kato, Mitsuhiro Makino, Naoki Takahashi, Toshiyuki Miyazawa, Satoko Harada, Tokuyuki Yamashita
Glucokinase (GK) is an enzyme that plays an important role as a glucose sensor while maintaining whole body glucose homeostasis. Allosteric activators of GK (GKAs) have the potential to treat type 2 diabetes mellitus. To identify novel GKAs, a series of compounds based on a thiophenyl-pyrrolidine scaffold were designed and synthesized. In this series, compound 38 was found to inhibit glucose excursion in an oral glucose tolerance test (OGTT) in mice. Optimization of 38 using a zwitterion approach led to the identification of the novel GKA 59...
June 26, 2018: European Journal of Medicinal Chemistry
Kjetil Søreide, Thomas G Weiser, Rowan W Parks
BACKGROUND: Pancreatic injury is rare and optimal diagnosis and management is still debated. The aim of this study was to review the existing data and consensus on management of pancreatic trauma. METHODS: Systematic literature review until May 2018. RESULTS: Pancreas injury is reported in 0.2-0.3% of all trauma patients. Severity is scored by the organ injury scale (OIS), with new scores including physiology needing validation. Diagnosis is difficult, clinical signs subtle, and imaging by ultrasound (US) and computed tomography (CT) non-specific with <60% sensitivity for pancreatic duct injury...
July 11, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
Teresa Macarulla, Alfredo Carrato, Rafael Díaz, Adelaida García, Berta Laquente, Javier Sastre, Rafael Álvarez, Andres Muñoz, Manuel Hidalgo
Data regarding management of frail patients with pancreatic ductal adenocarcinoma practice is currently very scarce. Randomized clinical trials usually exclude these subgroup of patients and the majority of the publications only consider chronological age and ECOG performance status for their classification. Therefore, the current available data do not reflect daily clinical practice. Only data from a phase two study (FRAGANCE study), designed to select a tolerable dose-schedule of nab-placitaxel + gemcitabine (Phase oneNCT02382263) and to evaluate the efficacy of the selected regimen (Phase two) in patients with ECOG-2 and previously untreated advanced PDAC, are currently available...
July 10, 2018: Journal of Geriatric Oncology
Mengmeng Wang, Lili Song, Charlie Strange, Xiao Dong, Hongjun Wang
To assess the potential therapeutic effects of adipose tissue-derived mesenchymal stem cells (ASCs) for the treatment of type 2 diabetes (T2D), we compared the phenotype and functionality of ASCs isolated from high-fat diet and streptozotocin (STZ)-induced T2D and the leptin receptor-deficient (db/db) mice with cells from healthy C57BL/6 mice. ASCs from T2D or db/db mice showed similar expression patterns of cellular markers and abilities to differentiate into adipocytes, osteoblasts, and chondrocytes. However, the rate of proliferation was reduced...
June 19, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Xiaoxia Guo, Xiaoxi Ling, Fang Du, Qingbing Wang, Wei Huang, Zhongmin Wang, Xiaoyi Ding, Mingfeng Bai, Zhiyuan Wu
Imaging probes targeting type 2 cannabinoid receptor (CB2 R) overexpressed in pancreatic duct adenocarcinoma (PDAC) tissue have the potential to improve early detection and surgical outcome of PDAC. The aim of our study was to evaluate the molecular imaging potential of a CB2 R-targeted near-infrared (NIR) fluorescent probe (NIR760-XLP6) for PDAC. CB2 R overexpression was observed in both PDAC patient tissues and various pancreatic cancer cell lines. In vitro fluorescence imaging indicated specific binding of NIR760-XLP6 to CB2 R in human PDAC PANC-1 cells...
July 9, 2018: Translational Oncology
Benjamin Leroy Freschini, Pietro Addeo, Gerlinde Averous, Bernard Goichot, Philippe Bachellier, Alessio Imperiale
We report the case of a 54-year-old woman with a nonfunctioning paraganglioma arising from the gastroepiploic pedicle demonstrated by F-FDOPA PET/CT. Because gastroepiploic arcade can be assimilated to the gastric mesentery, this tumor has been classified as a mesenteric paraganglioma (PGL). Neural crest cells are a multipotent population of cells characterized by effective migratory properties potentially explaining PGL atypical localization as in the mesentery. Mesenteric PGLs are often nonfunctioning and can mimic gastric, colic, or pancreatic primary tumor because of their anatomical boundaries, making more difficult the diagnosis on preoperative imaging...
July 12, 2018: Clinical Nuclear Medicine
Elisa Bannone, Stefano Andrianello, Giovanni Marchegiani, Gaia Masini, Giuseppe Malleo, Claudio Bassi, Roberto Salvia
OBJECTIVE: The aim of the study is to characterize postoperative acute pancreatitis (POAP). SUMMARY BACKGROUND DATA: A standardized definition of POAP after pancreaticoduodenectomy (PD) has been recently proposed, but specific studies are lacking. METHODS: The patients were extracted from the prospective database of The Pancreas Institute of Verona. POAP was defined as an elevation of the serum pancreatic amylase levels above the upper limit of normal (52 U/L) on postoperative day (POD) 0 or 1...
July 12, 2018: Annals of Surgery
Bo Xu, Jia Liu, Xin Xiang, Shunhai Liu, Pingyong Zhong, Fei Xie, Tinggang Mou, Liang Lai
OBJECTIVE: To analyze the expression of micro-RNA 143 (miRNA-143) in the patients with pancreatic cancer and to explore the influence of overexpression of miRNA-143 on pancreatic cancer cells. METHODS: Twenty-five patients with pancreatic cancer that received treatment in their hospital were included in this study. Pancreatic cancer tissues of the patients were surgically removed, and cancer-adjacent tissues were taken for control. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expressions of miRNA-143 and its target gene Kirsten rat sarcoma (KRAS) in pancreatic cancer tissues and cancer-adjacent tissues...
July 13, 2018: Cancer Biotherapy & Radiopharmaceuticals
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