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https://www.readbyqxmd.com/read/29467942/-in-vitro-in-vivo-and-ex-vivo-demonstration-of-the-antitumoral-role-of-hypocretin-1-orexin-a-and-almorexant-in-pancreatic-ductal-adenocarcinoma
#1
Stéphanie Dayot, Daniela Speisky, Anne Couvelard, Pierre Bourgoin, Valérie Gratio, Jérôme Cros, Vinciane Rebours, Alain Sauvanet, Pierre Bedossa, Valérie Paradis, Philippe Ruszniewski, Alain Couvineau, Thierry Voisin
Pancreatic ductal adenocarcinoma (PDAC) is still the poorest prognostic tumor of the digestive system. We investigated the antitumoral role of orexin-A and almorexant in PDAC. We analyzed the orexin receptor type 1 (OX1R) expression by immunohistochemistry in human normal pancreas, PDAC and its precursor dysplastic intraepithelial lesions. We used PDAC-derived cell lines and fresh tissue slices to study the apoptotic role of hypocretin-1/orexin-A and almorexant in vitro and ex vivo . We analyzed in vivo the hypocretin-1/orexin-A and almorexant effect on tumor growth in mice xenografted with PDAC cell lines expressing, or not, OX1R...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467550/translational-pancreatic-cancer-research-a-comparative-study-on-patient-derived-xenograft-models
#2
Mercedes Rubio-Manzanares Dorado, Luis Miguel Marín Gómez, Daniel Aparicio Sánchez, Sheila Pereira Arenas, Juan Manuel Praena-Fernández, Juan Jose Borrero Martín, Francisco Farfán López, Miguel Ángel Gómez Bravo, Jordi Muntané Relat, Javier Padillo Ruiz
AIM: To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice. METHODS: This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations (intraperitoneal, subcutaneous and pancreatic)...
February 21, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29464529/prognostic-factors-and-the-role-of-adjuvant-treatment-in-periampullary-carcinoma-a-single-centre-experience-of-95-patients
#3
Saphalta Baghmar, Nikhil Agrawal, Guresh Kumar, Chhagan Bihari, Yashwant Patidar, Senthil Kumar, Tushar Kanti Chattopadhyay, Dipanjan Panda, Asit Arora, Viniyendra Pamecha
PURPOSE: The effect of adjuvant treatment on those undergoing pancreaticoduodenectomy (PD) for periampullary carcinomas (PAC) is not well studied. Most studies employed chemoradiation as the adjuvant modality. We aimed to analyse clinicopathological differences between types of PACs, the prognostic factors and the role of adjuvant therapy (chemotherapy in the majority). METHODS: Patients with PAC who underwent PD from Jan 2011 to Dec 2015 were retrospectively analysed...
February 21, 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29457531/shedding-new-light-on-rhoa-signalling-as-a-drug-target-in-vivo-using-a-novel-rhoa-fret-biosensor-mouse
#4
Max Nobis, David Herrmann, Sean C Warren, Douglas Strathdee, Thomas R Cox, Kurt I Anderson, Paul Timpson
The small GTPase RhoA is a master regulator of signalling in cell-extracellular matrix interactions. RhoA signalling is critical to many cellular processes including migration, mechanotransduction, and is often disrupted in carcinogenesis. Investigating RhoA activity in a native tissue environment is challenging using conventional biochemical methods; we therefore developed a RhoA-FRET biosensor mouse, employing the adaptable nature of intravital imaging to a variety of settings. Mechnotransduction was explored in the context of osteocyte processes embedded in the calvaria responding in a directional manner to compression stress...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29453806/cq-sensitizes-human-pancreatic-cancer-cells-to-gemcitabine-through-the-lysosomal-apoptotic-pathway-via-reactive-oxygen-species
#5
Zhiping Fu, Cheng Xi, Jie Kuang, Haoran Feng, Lingxie Chen, Juyong Liang, Xiaonan Shen, Stanley Yuen, Peng Chenghong, Shen Baiyong, Jin Zhijian, Weihua Qiu
As an established anti-cancer drug, gemcitabine (GEM) is an effective systemic treatment for advanced pancreatic cancer (PC). However, little is known about the potential effectors that may modify tumour cell sensitivity towards GEM. Autophagy, as a physiological cellular mechanism, is involved in both cell survival and cell death. In this study, we found that exposure to GEM induced a significant increase in autophagy in a dose-dependent manner in PANC-1 and BxPC-3 cells. Inhibition of autophagy by chloroquine (CQ) and ATG7 siRNA increased GEM-induced cytotoxicity, and CQ was more effective than ATG7 siRNA...
February 17, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29449689/current-and-emerging-therapies-for-pnets-in-patients-with-or-without-men1
#6
REVIEW
Morten Frost, Kate E Lines, Rajesh V Thakker
Pancreatic neuroendocrine tumours (PNETs) might occur as a non-familial isolated endocrinopathy or as part of a complex hereditary syndrome, such as multiple endocrine neoplasia type 1 (MEN1). MEN1 is an autosomal dominant disorder characterized by the combined occurrence of PNETs with tumours of the parathyroids and anterior pituitary. Treatments for primary PNETs include surgery. Treatments for non-resectable PNETs and metastases include biotherapy (for example, somatostatin analogues, inhibitors of receptors and monoclonal antibodies), chemotherapy and radiological therapy...
February 16, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29444910/the-neuroendocrine-phenotype-genomic-profile-and-therapeutic-sensitivity-of-gepnet-cell-lines
#7
Tobias Hofving, Yvonne Arvidsson, Bilal Almobarak, Linda Inge, Roswitha Pfragner, Marta Persson, Göran Stenman, Erik Kristiansson, Viktor Johanson, Ola Nilsson
Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not...
March 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29440233/comprehensive-characterisation-of-compartment-specific-long-non-coding-rnas-associated-with-pancreatic-ductal-adenocarcinoma
#8
Luis Arnes, Zhaoqi Liu, Jiguang Wang, Hans Carlo Maurer, Irina Sagalovskiy, Marta Sanchez-Martin, Nikhil Bommakanti, Diana C Garofalo, Dina A Balderes, Lori Sussel, Kenneth P Olive, Raul Rabadan
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease with limited therapeutic options. Genome and transcriptome analyses have identified signalling pathways and cancer driver genes with implications in patient stratification and targeted therapy. However, these analyses were performed in bulk samples and focused on coding genes, which represent a small fraction of the genome. DESIGN: We developed a computational framework to reconstruct the non-coding transcriptome from cross-sectional RNA-Seq, integrating somatic copy number alterations (SCNA), common germline variants associated to PDA risk and clinical outcome...
February 10, 2018: Gut
https://www.readbyqxmd.com/read/29438372/a-phase-i-trial-of-the-%C3%AE-secretase-inhibitor-mk-0752-in-combination-with-gemcitabine-in-patients-with-pancreatic-ductal-adenocarcinoma
#9
Natalie Cook, Bristi Basu, Donna-Michelle Smith, Aarthi Gopinathan, Jeffry Evans, William P Steward, Daniel Palmer, David Propper, Balaji Venugopal, Mirela Hategan, D Alan Anthoney, Lisa V Hampson, Michael Nebozhyn, David Tuveson, Hayley Farmer-Hall, Helen Turner, Robert McLeod, Sarah Halford, Duncan Jodrell
BACKGROUND: The Notch pathway is frequently activated in cancer. Pathway inhibition by γ-secretase inhibitors has been shown to be effective in pre-clinical models of pancreatic cancer, in combination with gemcitabine. METHODS: A multi-centre, non-randomised Bayesian adaptive design study of MK-0752, administered per os weekly, in combination with gemcitabine administered intravenously on days 1, 8 and 15 (28 day cycle) at 800 or 1000 mg m -2 , was performed to determine the safety of combination treatment and the recommended phase 2 dose (RP2D)...
February 13, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29434732/sustained-multiple-organ-ischaemia-after-transarterial-chemoembolization-with-drug-eluting-beads-for-hepatocellular-carcinoma
#10
Young Woon Kim, Jung Hyun Kwon, Soon Woo Nam, Jeong Won Jang, Hyun Suk Jung, Yu Ri Shin, Eun Su Park, Dong Jae Shim
Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads) may enhance drug delivery to tumours and reduce systemic toxicity. TACE with DC beads leads to significantly fewer serious side-effects compared with conventional TACE. A 66-year-old man with hepatocellular carcinoma (HCC) complained of continuous abdominal pain 1 month after TACE with DC beads. At the time of TACE, angiography revealed severe stenosis of both hepatic arteries. The diagnostic work up on admission suggested severe bile duct injury with regional bile duct dilatation, segmental liver and spleen infarction, necrotizing pancreatitis, as well as gastric and duodenal ulcers...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29433805/proactive-multi-modality-treatment-of-pancreatic-neuroendocrine-tumours-pnets-potential-survival-benefits
#11
L Tanno, D Mayo, S Mills, A Takhar, J Cave, L Nolan, B Stedman, F X Sundram, M Abu Hilal, H Connor, N Pearce, T Armstrong
BACKGROUND/OBJECTIVES: Primary and metastatic pancreatic neuroendocrine tumours (PNET) can be treated with combination of surgery, locoregional and systemic therapy. Survival benefits from individual treatments have been well reported, however, the combined outcome from multimodal treatments are not well described in the literature. We report outcomes in a cohort of PNET patients treated with proactive, multimodality therapy. METHODS: 106 patients were identified from a single tertiary referral centre prospective database...
December 14, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29408556/analysis-of-sialyl-lewis-x-on-muc5ac-and-muc1-mucins-in-pancreatic-cancer-tissues
#12
Meritxell Balmaña, Adrià Duran, Catarina Gomes, Esther Llop, Raquel López-Martos, M Rosa Ortiz, Sílvia Barrabés, Celso A Reis, Rosa Peracaula
Pancreatic adenocarcinoma (PDAC) lacks efficient biomarkers. Mucins are glycoproteins that can carry aberrant glycosylation in cancer. Our objective was to identify cancer-related glycan epitopes on MUC1 and MUC5AC mucins in PDAC as potential biomarkers. We have analysed the tumour-associated carbohydrate antigens sialyl-Lewis x (SLex) and sialyl-Tn (STn) on MUC1 and MUC5AC in PDAC tissues. The selected cohort for this study consisted of twenty-one PDAC tissues positive for SLex antigen and three normal pancreas specimens as controls...
February 1, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29402376/pet-panc-multicentre-prospective-diagnostic-accuracy-and-health-economic-analysis-study-of-the-impact-of-combined-modality-18fluorine-2-fluoro-2-deoxy-d-glucose-positron-emission-tomography-with-computed-tomography-scanning-in-the-diagnosis-and-management-of
#13
Paula Ghaneh, Robert Hanson, Andrew Titman, Gill Lancaster, Catrin Plumpton, Huw Lloyd-Williams, Seow Tien Yeo, Rhiannon Tudor Edwards, Colin Johnson, Mohammed Abu Hilal, Antony P Higginson, Tom Armstrong, Andrew Smith, Andrew Scarsbrook, Colin McKay, Ross Carter, Robert P Sutcliffe, Simon Bramhall, Hemant M Kocher, David Cunningham, Stephen P Pereira, Brian Davidson, David Chang, Saboor Khan, Ian Zealley, Debashis Sarker, Bilal Al Sarireh, Richard Charnley, Dileep Lobo, Marianne Nicolson, Christopher Halloran, Michael Raraty, Robert Sutton, Sobhan Vinjamuri, Jonathan Evans, Fiona Campbell, Jon Deeks, Bal Sanghera, Wai-Lup Wong, John P Neoptolemos
BACKGROUND: Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. OBJECTIVE: To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer...
February 2018: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/29399966/morphologically-invisible-proinsulin-secreting-adenoma-detected-by-ga-68-exendin-4-glp-1-receptor-positron-emission-tomography-ct
#14
Christoph Werner, Amelie Lupp, Robert Drescher, Martin Freesmeyer, Masoud Mireskandari, Christian Stoykow, Astrid Bauschke, Ulrich A Müller
This case report of a young man suffering from recurring hypoglycaemia illustrates a rare condition of a neuroendocrine tumour, predominantly secreting proinsulin and invisible to conventional imaging approaches. Only a GLP-1 receptor PET/CT using Exendin-4 visualized the pancreatic lesion and enabled curative therapy, confirming the diagnostic value of this tracer for detection of neuroendocrine tumours. As only few publications on this topic are available, an overview of the available data is also given. The known cut-off value of 60% for proinsulin level indicating malignancy is critically discussed...
February 5, 2018: Journal of Medical Imaging and Radiation Oncology
https://www.readbyqxmd.com/read/29398971/incidental-detection-of-asymptomatic-brain-metastases-on-18f-fluoride-positron-emission-tomography-computed-tomography-and-68ga-dotanoc-positron-emission-tomography-computed-tomography-in-a-patient-with-concomitant-breast-carcinoma-and-a-pancreatic-neuroendocrine
#15
Ruth Brown, Phei Shan Chuah, Emmanouil Panagiotidis, Sobhan Vinjamuri
A 54-year-old female treated for locally advanced ductal breast carcinoma was also diagnosed with a pancreatic neuroendocrine tumour. A staging 68Ga DOTANOC positron emission tomography/computed tomography (PET/CT) demonstrated somatostatin receptor-positive foci within the brain parenchyma. A whole body 18F-fluoride PET/CT also demonstrated several foci of low-grade tracer uptake in the brain. Magnetic resonance imaging confirmed several cerebral and cerebellar metastases. This case highlights the need to be aware of each tumor's metastatic profile and the careful attention required for thoroughly evaluating imaging in the presence of multiple pathologies...
January 2018: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29396463/the-mir-135b-bmal1-yy1-loop-disturbs-pancreatic-clockwork-to-promote-tumourigenesis-and-chemoresistance
#16
Weiliang Jiang, Senlin Zhao, Jia Shen, Lihong Guo, Yi Sun, Yuntian Zhu, Zhixiong Ma, Xin Zhang, Yangyang Hu, Wenqin Xiao, Kai Li, Sisi Li, Li Zhou, Li Huang, Zhanjun Lu, Yun Feng, Junhua Xiao, Eric Erquan Zhang, Lijuan Yang, Rong Wan
Circadian disruption has been implicated in tumour development, but the underlying mechanism remains unclear. Here, we show that the molecular clockwork within malignant human pancreatic epithelium is disrupted and that this disruption is mediated by miR-135b-induced BMAL1 repression. miR-135b directly targets the BMAL1 3'-UTR and thereby disturbs the pancreatic oscillator, and the downregulation of miR-135b is essential for the realignment of the cellular clock. Asynchrony between miR-135b and BMAL1 expression impairs the local circadian gating control of tumour suppression and significantly promotes tumourigenesis and resistance to gemcitabine in pancreatic cancer (PC) cells, as demonstrated by bioinformatics analyses of public PC data sets and in vitro and in vivo functional studies...
February 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29388052/imaging-of-non-neoplastic-duodenal-diseases-a-pictorial-review-with-emphasis-on-mdct
#17
REVIEW
Sergi Juanpere, Laia Valls, Isabel Serra, Margarita Osorio, Arantxa Gelabert, Albert Maroto, Salvador Pedraza
A wide spectrum of abnormalities can affect the duodenum, ranging from congenital anomalies to traumatic and inflammatory entities. The location of the duodenum and its close relationship with other organs make it easy to miss or misinterpret duodenal abnormalities on cross-sectional imaging. Endoscopy has largely supplanted fluoroscopy for the assessment of the duodenal lumen. Cross-sectional imaging modalities, especially multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI), enable comprehensive assessment of the duodenum and surrounding viscera...
January 31, 2018: Insights Into Imaging
https://www.readbyqxmd.com/read/29384525/mtor-inhibitor-based-combination-therapies-for-pancreatic-cancer
#18
Zonera Hassan, Christian Schneeweis, Matthias Wirth, Christian Veltkamp, Zahra Dantes, Benedikt Feuerecker, Güralp O Ceyhan, Shirley K Knauer, Wilko Weichert, Roland M Schmid, Roland Stauber, Alexander Arlt, Oliver H Krämer, Roland Rad, Maximilian Reichert, Dieter Saur, Günter Schneider
BACKGROUND: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. METHODS: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance...
January 2, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29382047/reviewing-the-utility-of-eus-fna-to-advance-precision-medicine-in-pancreatic-cancer
#19
REVIEW
William Berry, Joanne Lundy, Daniel Croagh, Brendan J Jenkins
Advanced pancreatic cancer (PC) is an aggressive malignancy with few effective therapeutic options. While the evolution of precision medicine in recent decades has changed the treatment landscape in many cancers, at present no targeted therapies are used in the routine management of PC. Only a minority of patients with PC present with surgically resectable disease, and in the remainder obtaining high quality biopsy material for both diagnosis and molecular testing can prove challenging. Endoscopic ultrasound-guided fine needle aspiration (EUS FNA) is a widely used diagnostic procedure in PC, and allows tumour sampling in patients with both early and late stage disease...
January 27, 2018: Cancers
https://www.readbyqxmd.com/read/29382042/extracellular-influences-molecular-subclasses-and-the-microenvironment-in-pancreatic-cancer
#20
REVIEW
Veronique L Veenstra, Andrea Garcia-Garijo, Hanneke W van Laarhoven, Maarten F Bijlsma
Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent form of pancreatic cancer and carries the worst prognosis of all common cancers. Five-year survival rates have not surpassed 6% for some decades and this lack of improvement in outcome urges a better understanding of the PDAC-specific features which contribute to this poor result. One of the most defining features of PDAC known to contribute to its progression is the abundance of non-tumor cells and material collectively known as the stroma. It is now well recognized that the different non-cancer cell types, signalling molecules, and mechanical properties within a tumor can have both tumor-promoting as well as -inhibitory effects...
January 27, 2018: Cancers
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