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https://www.readbyqxmd.com/read/29760790/anticancer-properties-of-fenofibrate-a-repurposing-use
#1
REVIEW
Xin Lian, Gang Wang, Honglan Zhou, Zongyu Zheng, Yaowen Fu, Lu Cai
Cancer is a leading cause of death throughout the world, and cancer therapy remains a big medical challenge in terms of both its therapeutic efficacy and safety. Therefore, to find out a safe anticancer drug has been long goal for oncologist and medical scientists. Among clinically used medicines with no or little toxicity, fenofibrate is a drug of the fibrate class that plays an important role in lowering the levels of serum cholesterol and triglycerides while elevating the levels of high-density lipoproteins...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29603014/impact-of-formulation-on-the-iontophoretic-delivery-of-the-folfirinox-regimen-for-the-treatment-of-pancreatic-cancer
#2
James D Byrne, Mohammad R N Jajja, Adrian T O'Neill, Allison N Schorzman, Amanda W Keeler, J Christopher Luft, William C Zamboni, Joseph M DeSimone, Jen Jen Yeh
PURPOSE: Effective treatment of patients with locally advanced pancreatic cancer is a significant unmet clinical need. One major hurdle that exists is inadequate drug delivery due to the desmoplastic stroma and poor vascularization that is characteristic of pancreatic cancer. The local iontophoretic delivery of chemotherapies provides a novel way of improving treatment. With the growing practice of highly toxic combination therapies in the treatment of pancreatic cancer, the use of iontophoresis for local delivery can potentiate the anti-cancer effects of these therapies while sparing unwanted toxicity...
March 30, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29545922/mek-inhibition-leads-to-brca2-downregulation-and-sensitization-to-dna-damaging-agents-in-pancreas-and-ovarian-cancer-models
#3
Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29529470/biological-evaluation-of-water-soluble-arene-ru-ii-enantiomers-with-amino-oxime-ligands
#4
Isabel de la Cueva-Alique, Sara Sierra, Laura Muñoz-Moreno, Adrián Pérez-Redondo, Ana M Bajo, Isabel Marzo, Lourdes Gude, Tomás Cuenca, Eva Royo
New water soluble, enantiopure arene ruthenium compound SRu SN -(1R,4S)-[(η6 -p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a') has been synthesized. The novel compound along with that previously described RRu RN -(1S,4R)-[(η6 -p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a' was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa...
March 6, 2018: Journal of Inorganic Biochemistry
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
#5
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/29446180/pigs-expressing-the-human-inhibitory-ligand-pd-l1-cd-274-provide-a-new-source-of-xenogeneic-cells-and-tissues-with-low-immunogenic-properties
#6
Anna Buermann, Stoyan Petkov, Björn Petersen, Rabea Hein, Andrea Lucas-Hahn, Wiebke Baars, Antje Brinkmann, Heiner Niemann, Reinhard Schwinzer
BACKGROUND: The programmed cell death-1 (PD-1, CD279)/PD-Ligand1 (PD-L1, CD274) receptor system is crucial for controlling the balance between immune activation and induction of tolerance via generation of inhibitory signals. Expression of PD-L1 is associated with reduced immunogenicity and renders cells and tissues to an immune-privileged/tolerogenic state. METHODS: To apply this concept for clinical xenotransplantation, we generated human (h)PD-L1 transgenic pigs and characterized expression and biological function of the transgene at the cellular level...
February 15, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29348825/a-novel-anti-cd146-antibody-specifically-targets-cancer-cells-by-internalizing-the-molecule
#7
Marie Nollet, Jimmy Stalin, Anaïs Moyon, Waël Traboulsi, Amel Essaadi, Stéphane Robert, Nausicaa Malissen, Richard Bachelier, Laurent Daniel, Alexandrine Foucault-Bertaud, Caroline Gaudy-Marqueste, Romaric Lacroix, Aurélie S Leroyer, Benjamin Guillet, Nathalie Bardin, Françoise Dignat-George, Marcel Blot-Chabaud
CD146 is an adhesion molecule present on many tumors (melanoma, kidney, pancreas, breast, ...). In addition, it has been shown to be expressed on vascular endothelial and smooth muscle cells. Generating an antibody able to specifically recognize CD146 in cancer cells (designated as tumor CD146), but not in normal cells, would thus be of major interest for targeting tumor CD146 without affecting the vascular system. We thus generated antibodies against the extracellular domain of the molecule produced in cancer cells and selected an antibody that specifically recognizes tumor CD146...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#8
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
February 2018: Nature Medicine
https://www.readbyqxmd.com/read/29301827/thy1-targeted-microbubbles-for-ultrasound-molecular-imaging-of-pancreatic-ductal-adenocarcinoma
#9
Lotfi Abou-Elkacem, Huaijun Wang, Sayan M Chowdhury, Richard H Kimura, Sunitha V Bachawal, Sanjiv S Gambhir, Lu Tian, Jürgen K Willmann
Purpose: To engineer a dual human and murine Thy1-binding single-chain-antibody ligand (Thy1-scFv) for contrast microbubble-enhanced ultrasound molecular imaging of pancreatic ductal adenocarcinoma (PDAC). Experimental Design: Thy1-scFv were engineered using yeast-surface-display techniques. Binding to soluble human and murine Thy1 and to Thy1-expressing cells was assessed by flow cytometry. Thy1-scFv was then attached to gas-filled microbubbles to create MBThy1-scFv Thy1 binding of MBThy1-scFv to Thy1-expressing cells was evaluated under flow shear stress conditions in flow-chamber experiments...
April 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29229290/simple-detection-of-telomere-fusions-in-pancreatic-cancer-intraductal-papillary-mucinous-neoplasm-and-pancreatic-cyst-fluid
#10
Tatsuo Hata, Marco Dal Molin, Anne McGregor-Das, Tae Jun Song, Christopher Wolfgang, James R Eshleman, Ralph H Hruban, Michael Goggins
Telomere end-to-end fusions are an important source of chromosomal instability that arise in cells with critically shortened telomeres. We developed a nested real-time quantitative PCR method for telomere fusion detection in pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms (IPMNs), and IPMN cyst fluids. Ninety-one pancreatic cancer cell lines and xenograft samples, 93 IPMNs, and 93 surgically aspirated IPMN cyst fluid samples were analyzed. The association between telomere shortening, telomerase activity, and telomere fusion detection was evaluated...
January 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29157102/chk1-inhibitor-sch-900776-enhances-the-antitumor-activity-of-mln4924-on-pancreatic-cancer
#11
Jian-Ang Li, Chao Song, Yefei Rong, Tiantao Kuang, Dansong Wang, Xuefeng Xu, Jian Yuan, Kuntian Luo, Bo Qin, Somaira Nowsheen, Zhenkun Lou, Wenhui Lou
MLN4924 inhibits the cullin-RING ligases mediated ubiquitin-proteasome system, and has showed antitumor activities in preclinical studies, but its effects and mechanisms on pancreatic cancer (PC) remains elusive. We found that MLN4924 inhibited the proliferation and clonogenicity of PC cells, caused DNA damage, particularly double-strand breaks, and leaded to Chk1 activation and cell-cycle arrest. Chk1 inhibitor SCH 900776 alone exhibited minimal cytotoxicity, and caused no DNA damage on PC cells. But in the combination therapy, SCH 900776 enhanced the cytotoxicity and DNA damage caused by MLN4924, likely by abrogating G2/M arrest and promoting DNA re-replication...
2018: Cell Cycle
https://www.readbyqxmd.com/read/29156810/psc-derived-galectin-1-inducing-epithelial-mesenchymal-transition-of-pancreatic-ductal-adenocarcinoma-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#12
Dong Tang, Jingqiu Zhang, Zhongxu Yuan, Hongpeng Zhang, Yang Chong, Yuqin Huang, Jie Wang, Qingquan Xiong, Sen Wang, Qi Wu, Ying Tian, Yongdie Lu, Xiao Ge, Wenjing Shen, Daorong Wang
Galectin-1 has previously been shown to be strongly expressed in activated pancreatic stellate cells (PSCs) and promote the development and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms by which Galectin-1 promotes the malignant behavior of pancreatic cancer cells remain unclear. In this study, we examined the effects of Galectin-1 knockdown or overexpression in PSCs co-cultured with pancreatic cancer (PANC-1) cells. Immunohistochemical analysis showed expression of epithelial-mesenchymal transition (EMT) markers and MMP9 were positively associated with the expression of Galectin-1 in 66 human PDAC tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29143337/intraductal-papillary-mucinous-neoplasm-of-the-pancreas-rapidly-xenografts-in-chicken-eggs-and-predicts-aggressiveness
#13
Zhefu Zhao, Nathalie Bauer, Ewa Aleksandrowicz, Libo Yin, Jury Gladkich, Wolfgang Gross, Jörg Kaiser, Thilo Hackert, Oliver Strobel, Ingrid Herr
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a high risk of progressing to invasive pancreatic ductal adenocarcinoma (PDA), but experimental models for IPMN are largely missing. New experimental systems for the molecular characterization of IPMN and for personalized prognosis and treatment options for IPMN are urgently needed. We analyzed the potential use of fertilized chicken eggs for the culture of freshly resected IPMN tissue. We transplanted 49 freshly resected IPMN tissues into eggs and compared the growth characteristics to IPMN tissues transplanted into mice; this was followed by an analysis of histology, morphology, and marker expression...
April 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29073149/intrapancreatic-injection-of-human-bone-marrow-derived-mesenchymal-stem-stromal-cells-alleviates-hyperglycemia-and-modulates-the-macrophage-state-in-streptozotocin-induced-type-1-diabetic-mice
#14
Norimitsu Murai, Hirokazu Ohtaki, Jun Watanabe, Zhifang Xu, Shun Sasaki, Kazumichi Yagura, Seiji Shioda, Shoichiro Nagasaka, Kazuho Honda, Masahiko Izumizaki
Type 1 diabetes mellitus is a progressive disease caused by the destruction of pancreatic β-cells, resulting in insulin dependency and hyperglycemia. While transplanted bone marrow-derived mesenchymal stem/stromal cells (BMMSCs) have been explored as an alternative therapeutic approach for diseases, the choice of delivery route may be a critical factor determining their sustainability. This study evaluated the effects of intrapancreatic and intravenous injection of human BMMSCs (hBMMSCs) in streptozotocin (STZ)-induced type 1 diabetic mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28977862/identification-and-causes-of-metabonomic-difference-between-orthotopic-and-subcutaneous-xenograft-of-pancreatic-cancer
#15
Bohan Zhan, Shi Wen, Jie Lu, Guiping Shen, Xianchao Lin, Jianghua Feng, Heguang Huang
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. However, the methodological differences between orthotopic and subcutaneous xenograft (OX and SX) models will cause confusion in understanding its pathological mechanism and clinical relevance. In this study, SX and OX models were established by implanting Panc-1 and BxPC-3 cell strains under skin and on the pancreas of mice, respectively. The tumor tissue and serum samples were collected for(1)H NMR spectroscopy followed by univariate and multivariate statistical analyses...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893801/galectin-3-a-druggable-vulnerability-for-kras-addicted-cancers
#16
Laetitia Seguin, Maria F Camargo, Hiromi I Wettersten, Shumei Kato, Jay S Desgrosellier, Tami von Schalscha, Kathryn C Elliott, Erika Cosset, Jacqueline Lesperance, Sara M Weis, David A Cheresh
Identifying the molecular basis for cancer cell dependence on oncogenes such as KRAS can provide new opportunities to target these addictions. Here, we identify a novel role for the carbohydrate-binding protein galectin-3 as a lynchpin for KRAS dependence. By directly binding to the cell surface receptor integrin αvβ3, galectin-3 gives rise to KRAS addiction by enabling multiple functions of KRAS in anchorage-independent cells, including formation of macropinosomes that facilitate nutrient uptake and ability to maintain redox balance...
December 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28858862/pancreas-cancer-precision-treatment-using-avatar-mice-from-a-bioinformatics-perspective
#17
Javier Perales-Patón, Elena Piñeiro-Yañez, Héctor Tejero, Pedro P López-Casas, Manuel Hidalgo, Gonzalo Gómez-López, Fátima Al-Shahrour
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death among solid malignancies. Unfortunately, PDAC lethality has not substantially decreased over the past 20 years. This aggressiveness is related to the genomic complexity and heterogeneity of PDAC, but also to the absence of an effective screening for the detection of early-stage tumors and a lack of efficient therapeutic options. Therefore, there is an urgent need to improve the arsenal of anti-PDAC drugs for an effective treatment of these patients...
2017: Public Health Genomics
https://www.readbyqxmd.com/read/28793277/o-2-18-f-fluoroethyl-l-tyrosine-18-f-fet-uptake-in-insulinoma-first-results-from-a-xenograft-mouse-model-and-from-human
#18
Alessio Imperiale, Frédéric Boisson, Guillaume Kreutter, Bernard Goichot, Izzie Jacques Namer, Philippe Bachellier, Patrice Laquerriere, Laurence Kessler, Patrice Marchand, David Brasse
INTRODUCTION: Herein we have evaluated the uptake of O-(2-18 F-fluoroethyl)-l-tyrosine (18 F-FET) in insulinoma in comparison with those of 6-18 F-fluoro-3,4-dihydroxy-l-phenylalanine (18 F-FDOPA) providing first data from both murine xenograft model and one patient with proved endogenous hyperinsulinemic hypoglycemia. METHODS: Dynamic 18 F-FET and carbidopa-assisted 18 F-FDOPA PET were performed on tumor-bearing nude mice after subcutaneous injection of RIN-m5F murine beta cells and on a 30-year-old man with type-1 multiple endocrine neoplasia and hyperinsulinemic hypoglycemia defined by a positive fasting test...
October 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28761381/nmda-receptors-are-important-regulators-of-pancreatic-cancer-and-are-potential-targets-for-treatment
#19
William G North, Fuli Liu, Liz Z Lin, Ruiyang Tian, Bonnie Akerman
Pancreatic cancer, particularly adenocarcinoma of the pancreas, is a common disease with a poor prognosis. In this study, the importance of N-methyl-D-aspartate (NMDA) receptors for the growth and survival of pancreatic cancer was investigated. Immunohistochemistry performed with antibodies against GluN1 and GluN2B revealed that all invasive adenocarcinoma and neuroendocrine pancreatic tumors likely express these two NMDA receptor proteins. These proteins were found to be membrane components of pancreatic cancer cell lines, and both channel-blocker antagonist and GluN2B antagonist significantly reduced cell viability in vitro...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/28748183/neodymium-140-dota-lm3-evaluation-of-an-in-vivo-generator-for-pet-with-a-non-internalizing-vector
#20
Gregory W Severin, Lotte K Kristensen, Carsten H Nielsen, Jesper Fonslet, Andreas I Jensen, Anders F Frellsen, K M Jensen, Dennis R Elema, Helmut Maecke, Andreas Kjær, Karl Johnston, Ulli Köster
(140)Nd (t1/2 = 3.4 days), owing to its short-lived positron emitting daughter (140)Pr (t1/2 = 3.4 min), has promise as an in vivo generator for positron emission tomography (PET). However, the electron capture decay of (140)Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that an in vivo redistribution of the daughter (140)Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled (140)Pr affects preclinical imaging with (140)Nd...
2017: Frontiers in Medicine
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