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Results: 44
Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule.
Chiara Marchetti, Katherine G Zyner, Stephan A Ohnmacht, Mathew Robson, Shozeb M Haider, Jennifer P Morton, Giovanni Marsico, Tam Vo, Sarah Laughlin-Toth, Ahmed A Ahmed, Gloria Di Vita, Ingrida Pazitna, Mekala Gunaratnam, Rachael J Besser, Ana CG Andrade, Seckou Diocou, Jeremy A Pike, David Tannahill, R Barbara Pedley, TR Jeffry Evans, W David Wilson, Shankar Balasubramanian, Stephen Neidle
Mar 26, 2018
Human pancreatic ductal adenocarcinoma (PDAC) involves the dysregulation of multiple signaling pathways. A novel approach to the treatment of PDAC is described, involving the targeting of cancer genes in PDAC pathways having...
Animals Antimetabolites Antineoplastic Antineoplastic Agents Carcinoma Pancreatic Ductal Cell Line Tumor Computational Biology Computer Simulation DNA Damage Deoxycytidine Down-Regulation Drug Design Drug Resistance Neoplasm G-Quadruplexes Gene Expression Regulation Neoplastic Humans Mice Mice Nude Pancreatic Neoplasms Xenograft Model Antitumor Assays Gemcitabine
Magnetic Regulation of Thermo-Chemotherapy from a Cucurbit[7]uril-Crosslinked Hybrid Hydrogel.
The fabrication, characterization, and therapy efficiency of a noncovalent-bonded hydrogel network, which is assembled by utilizing cucurbit[7]uril as a supramolecular linker to "stick" superparamagnetic γ-Fe2 O3 nanoparticles...
cucurbit[7]uril drug release Hydrogels supramolecular chemistry thermotherapy Animals Antibiotics Antineoplastic Bridged-Ring Compounds Catechols Chitosan Cross-Linking Reagents Doxorubicin Drug Liberation HeLa Cells Humans Hydrogels hyperthermia Induced Imidazoles Magnetic Phenomena Magnetic Resonance Spectroscopy Magnetite Nanoparticles Mice Nude Xenograft Model Antitumor Assays
Establishing a Preclinical Multidisciplinary Board for Brain Tumors.
Birgit V Nimmervoll, Nidal Boulos, Brandon Bianski, Jason Dapper, Michael DeCuypere, Anang Shelat, Sabrina Terranova, Hope E Terhune, Amar Gajjar, Yogesh T Patel, Burgess B Freeman, Arzu Onar-Thomas, Clinton F Stewart, Martine F Roussel, R Kipling Guy, Thomas E Merchant, Christopher Calabrese, Karen D Wright, Richard J Gilbertson
Mar 23, 2018
Purpose: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies. It is extremely challenging to acquire...
A role for VEGF as a negative regulator of pericyte function and vessel maturation.
Joshua I Greenberg, David J Shields, Samuel G Barillas, Lisette M Acevedo, Eric Murphy, Jianhua Huang, Lea Scheppke, Christian Stockmann, Randall S Johnson, Niren Angle, David A Cheresh
Mar 13, 2020
Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth...
Angiogenesis Inhibitors Animals blood vessels Cell Line Cells Cultured Fibrosarcoma Humans Mice Mice Inbred C57BL Mice Nude Neovascularization Physiologic Pericytes Platelet-Derived Growth Factor Receptor Platelet-Derived Growth Factor beta Receptors Vascular Endothelial Growth Factor Signal Transduction Vascular Endothelial Growth Factor A
Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo.
TE Bapiro, KK Frese, A Courtin, JL Bramhall, B Madhu, N Cook, A Neesse, JR Griffiths, DA Tuveson, DI Jodrell, FM Richards
Nov 16, 2017
BACKGROUND: The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We...
Pyrazolo[1,5-a]pyrimidine TRPC6 antagonists for the treatment of gastric cancer.
Mingmin Ding, Hongbo Wang, Chunrong Qu, Fuchun Xu, Yingmin Zhu, Guangyao Lv, Yungang Lu, Qingjun Zhou, Hui Zhou, Xiaodong Zeng, Jingwen Zhang, Chunhong Yan, Jiacheng Lin, Huai-Rong Luo, Zixing Deng, Yuling Xiao, Jinbin Tian, Michael X Zhu, Xuechuan Hong
Jul 28, 2020
Transient receptor potential canonical 6 (TRPC6) proteins form receptor-operated Ca2+-permeable channels, which have been thought to bring benefit to the treatment of diseases, including cancer. However, selective antagonists...
anticancer Ca(2+) signaling Drug Discovery Nonselective cation channels TRPC channels Animals Antineoplastic Agents Apoptosis Calcium Cell Movement Cell Proliferation Gene Expression Regulation Neoplastic Humans Mice Mice Inbred BALB C Mice Nude Pyrazoles Pyrimidines Stomach Neoplasms TRPC6 Cation Channel Tumor Cells Cultured Xenograft Model Antitumor Assays
A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma.
Saiful E Syafruddin, Paulo Rodrigues, Erika Vojtasova, Saroor A Patel, M Nazhif Zaini, Johanna Burge, Anne Y Warren, Grant D Stewart, Tim Eisen, Dóra Bihary, Shamith A Samarajiwa, Sakari Vanharanta
Feb 21, 2019
Animals Carcinogenesis Carcinoma Renal Cell Cell Line Tumor Cell Proliferation Enhancer Elements Genetic Gene Expression Profiling Gene Expression Regulation Neoplastic Gene Regulatory Networks HEK293 Cells Humans Kidney Kidney Neoplasms Kruppel-Like Factor 6 Lipid Metabolism Male Mice Mice Inbred NOD Mice Nude Mice SCID Proto-Oncogene Proteins c-sis Signal Transduction Sterol Regulatory Element Binding Protein 1 Sterol Regulatory Element Binding Protein 2 TOR Serine-Threonine Kinases Xenograft Model Antitumor Assays
RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer.
C Cruz, M Castroviejo-Bermejo, S Gutiérrez-Enríquez, A Llop-Guevara, YH Ibrahim, A Gris-Oliver, S Bonache, B Morancho, A Bruna, OM Rueda, Z Lai, UM Polanska, GN Jones, P Kristel, L de Bustos, M Guzman, O Rodríguez, J Grueso, G Montalban, G Caratú, F Mancuso, R Fasani, J Jiménez, WJ Howat, B Dougherty, A Vivancos, P Nuciforo, X Serres-Créixams, IT Rubio, A Oaknin, E Cadogan, JC Barrett, C Caldas, J Baselga, C Saura, J Cortés, J Arribas, J Jonkers, O Díez, MJ O'Connor, J Balmaña, V Serra
Jul 16, 2018
BACKGROUND: BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging agents or to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their...
Animals BRCA1 Protein BRCA2 Protein Biomarkers Tumor Breast Breast Neoplasms Drug Resistance Neoplasm Female Germ-Line Mutation Humans Mice Mice Nude Poly(ADP-ribose) Polymerase Inhibitors Rad51 Recombinase Recombinational DNA Repair Retrospective Studies Treatment Outcome Xenograft Model Antitumor Assays
MET-EGFR dimerization in lung adenocarcinoma is dependent on EGFR mtations and altered by MET kinase inhibition.
Elena Ortiz-Zapater, Richard W Lee, William Owen, Gregory Weitsman, Gilbert Fruhwirth, Robert G Dunn, Michael J Neat, Frank McCaughan, Peter Parker, Tony Ng, George Santis
Apr 11, 2019
Advanced lung cancer has poor survival with few therapies. EGFR tyrosine kinase inhibitors (TKIs) have high response rates in patients with activating EGFR mutations, but acquired resistance is inevitable. Acquisition of the...
Adenocarcinoma Adenocarcinoma of Lung Animals Cell Line Tumor Cell Proliferation ErbB Receptors Extracellular Signal-Regulated MAP Kinases Focal Adhesion Protein-Tyrosine Kinases HEK293 Cells Humans Lung Neoplasms Mice Inbred BALB C Mice Nude Mutation Phosphorylation Protein Binding Protein Kinase Inhibitors Protein Multimerization Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-met Reproducibility of Results
Optoacoustics delineates murine breast cancer models displaying angiogenesis and vascular mimicry.
Isabel Quiros-Gonzalez, Michal R Tomaszewski, Sarah J Aitken, Laura Ansel-Bollepalli, Leigh-Ann McDuffus, Michael Gill, Lina Hacker, Joanna Brunker, Sarah E Bohndiek
Mar 08, 2018
BACKGROUND: Optoacoustic tomography (OT) of breast tumour oxygenation is a promising new technique, currently in clinical trials, which may help to determine disease stage and therapeutic response. However, the ability of OT to...
Animals Biological Mimicry Breast Neoplasms Cell Line Tumor Drug Monitoring Female Humans MCF-7 Cells Mammary Neoplasms Experimental Mice Mice Inbred BALB C Mice Nude Neoplasm Staging Neovascularization Pathologic Oxygen Consumption Photoacoustic Techniques Sensitivity and Specificity Tomography Tumor Hypoxia Xenograft Model Antitumor Assays
A PAX5-OCT4-PRDM1 developmental switch specifies human primordial germ cells.
Fang Fang, Benjamin Angulo, Ninuo Xia, Meena Sukhwani, Zhengyuan Wang, Charles C Carey, Aurélien Mazurie, Jun Cui, Royce Wilkinson, Blake Wiedenheft, Naoko Irie, M Azim Surani, Kyle E Orwig, Renee A Reijo Pera
Sep 11, 2018
Dysregulation of genetic pathways during human germ cell development leads to infertility. Here, we analysed bona fide human primordial germ cells (hPGCs) to probe the developmental genetics of human germ cell specification and...
Animals Cell Differentiation Cell Line Gene Editing Gene Expression Regulation Developmental Human Embryonic Stem Cells Humans Male Mice Nude Octamer Transcription Factor-3 PAX5 Transcription Factor Positive Regulatory Domain I-Binding Factor 1 Protein Binding SOXB1 Transcription Factors Signal Transduction Spermatozoa Testis Time Factors Transcription Genetic
Mutant p53 promotes RCP-dependent chemoresistance coinciding with increased delivery of P-glycoprotein to the plasma membrane.
Vinaya Phatak, Yannick von Grabowiecki, Justyna Janus, Leah Officer, Caron Behan, Lydia Aschauer, Lucia Pinon, Hannah Mackay, Sara Zanivan, Jim C Norman, Michael Kelly, John Le Quesne, Patricia AJ Muller
Feb 24, 2021
TP53 is the most frequently mutated gene in cancers. Mutations lead to loss of p53 expression or expression of a mutant protein. Mutant p53 proteins commonly lose wild-type function, but can also acquire novel functions in...
ATP Binding Cassette Transporter Subfamily B Adaptor Proteins Signal Transducing Animals Antineoplastic Agents Cell Membrane cisplatin Dose-Response Relationship Drug Drug Resistance Neoplasm Etoposide HCT116 Cells Humans Male Membrane Proteins Mice Inbred BALB C Mice Nude Mutation Neoplasms Tumor Burden Tumor Suppressor Protein p53 Xenograft Model Antitumor Assays
Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies.
David E Clark, Bohdan Waszkowycz, Melanie Wong, Peter M Lockey, Robert Adalbert, Jonathan Gilley, Jonathan Clark, Michael P Coleman
May 24, 2018
NAMPT may represent a novel target for drug discovery in various therapeutic areas, including oncology and inflammation. Additionally, recent work has suggested that targeting NAMPT has potential in treating axon degeneration....
axon degeneration Molecular docking NAMPT Similarity searching Virtual screening Animals Antineoplastic Agents Axons Caco-2 Cells Cell Line Tumor Cell Proliferation Crystallography X-Ray Cytochrome P-450 Enzyme System Cytokines Dose-Response Relationship Drug Drug Discovery Drug Screening Assays Antitumor Enzyme Inhibitors Humans Mice Mice Nude Models Molecular Molecular Structure Nicotinamide Phosphoribosyltransferase Structure-Activity Relationship
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds.
Sara Campinoti, Asllan Gjinovci, Roberta Ragazzini, Luca Zanieri, Linda Ariza-McNaughton, Marco Catucci, Stefan Boeing, Jong-Eun Park, John C Hutchinson, Miguel Muñoz-Ruiz, Pierluigi G Manti, Gianluca Vozza, Carlo E Villa, Demetra-Ellie Phylactopoulos, Constance Maurer, Giuseppe Testa, Hans J Stauss, Sarah A Teichmann, Neil J Sebire, Adrian C Hayday, Dominique Bonnet, Paola Bonfanti
Jan 25, 2021
The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because...
The CXCL12/CXCR4 Signaling Pathway
F Meuris, L Carthagena, A Jaracz-Ros, F Gaudin, P Cutolo, C Deback, Y Xue, F Thierry, J Doorbar, F Bachelerie
Mar 28, 2017
Imaging cell surface glycosylation in vivo using "double click" chemistry.
André A Neves, Henning Stöckmann, Yelena A Wainman, Joe C-H Kuo, Sarah Fawcett, Finian J Leeper, Kevin M Brindle
Nov 26, 2020
Dynamic alterations in cell surface glycosylation occur in numerous biological processes that involve cell-cell communication and cell migration. We report here imaging of cell surface glycosylation in live mice using double...
Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.
Johannes Bargehr, Lay Ping Ong, Maria Colzani, Hongorzul Davaapil, Peter Hofsteen, Shiv Bhandari, Laure Gambardella, Nicolas Le Novère, Dharini Iyer, Fotios Sampaziotis, Florian Weinberger, Alessandro Bertero, Andrea Leonard, William G Bernard, Amy Martinson, Nichola Figg, Michael Regnier, Martin R Bennett, Charles E Murry, Sanjay Sinha
May 16, 2019
p53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression.
Ivano Amelio, Mara Mancini, Varvara Petrova, Rob A Cairns, Polina Vikhreva, Sara Nicolai, Alberto Marini, Alexey A Antonov, John Le Quesne, Juvenal D Baena Acevedo, Kate Dudek, Gabriella Sozzi, Ugo Pastorino, Richard A Knight, Tak W Mak, Gerry Melino
Dec 04, 2018
HIF SWI/SNF Chromatin architecture microenvironment p53 Animals Carcinoma Non-Small-Cell Lung Cell Hypoxia Cell Line Tumor Extracellular Matrix Genes p53 Heterografts Humans Hypoxia-Inducible Factor 1 Lung Neoplasms Mice Mice Inbred BALB C Mice Nude Mutation Transcriptional Activation Tumor Microenvironment Tumor Suppressor Protein p53
In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer.
UNLABELLED: Fenofibrate, an agonist of PPAR-alpha, in doses above 25 microM, inhibits proliferation and induces apoptosis in Ishikawa endometrial cancer cells. We show that these effects are potentiated by retinoic acid, an...
Animals Antineoplastic Agents Apoptosis Cell Line Tumor Cell Proliferation Cyclin D1 Dose-Response Relationship Drug Endometrial Neoplasms Female Fenofibrate Gene Expression Profiling Gene Expression Regulation Humans Methionine Adenosyltransferase Mice Mice Nude Neoplasm Transplantation Oligonucleotide Array Sequence Analysis PPAR alpha RNA Interference RNA Messenger Tretinoin
Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.
Michal R Tomaszewski, Marcel Gehrung, James Joseph, Isabel Quiros-Gonzalez, Jonathan A Disselhorst, Sarah E Bohndiek
Sep 29, 2018
Measuring the functional status of tumor vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer...
Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3'-Deoxy-3'-[$^{18}$F]Fluorothymidine in Preclinical Models of Lung Cancer
S Schelhaas, A Held, L Wachsmuth, S Hermann, DJ Honess, K Heinzmann, DM Smith, JR Griffiths, C Faber, AH Jacobs
Jan 05, 2017
Animals Antineoplastic Agents Blotting Western Cell Line Tumor Deoxycytidine Dideoxynucleosides Diffusion Magnetic Resonance Imaging Disease Models Animal Female Flow Cytometry Humans Image Processing Computer-Assisted Immunohistochemistry Lung Neoplasms Mice Mice Nude Positron-Emission Tomography Radiopharmaceuticals Xenograft Model Antitumor Assays Gemcitabine
An Activatable Cancer-Targeted Hydrogen Peroxide Probe for Photoacoustic and Fluorescence Imaging.
Judith Weber, Laura Bollepalli, Ana M Belenguer, Marco Di Antonio, Nicola De Mitri, James Joseph, Shankar Balasubramanian, Christopher A Hunter, Sarah E Bohndiek
Aug 19, 2019
Reactive oxygen species play an important role in cancer, however, their promiscuous reactivity, low abundance, and short-lived nature limit our ability to study them in real time in living subjects with conventional noninvasive...
Absorption Radiation Adenocarcinoma Animals Cell Line Tumor Deoxyglucose Fluorescent Dyes Heterografts Humans Hydrogen Peroxide Liver Neoplasms MCF-7 Cells Mice Mice Nude Molecular Imaging Neoplasm Transplantation Optical Imaging Oxidative Stress Photoacoustic Techniques Piperazines Tissue Distribution
Mouse Papillomavirus L1 and L2 Are Dispensable for Viral Infection and Persistence at Both Cutaneous and Mucosal Tissues.
Sarah Brendle, Jingwei J Li, Nancy M Cladel, Debra A Shearer, Lynn R Budgeon, Karla K Balogh, Hannah Atkins, Marina Costa-Fujishima, Paul Lopez, Neil D Christensen, John Doorbar, Thomas T Murooka, Jiafen Hu
Oct 29, 2021
Papillomavirus L1 and L2, the major and minor capsid proteins, play significant roles in viral assembly, entry, and propagation. In the current study, we investigate the impact of L1 and L2 on viral life cycle and tumor growth...
IHC ISH L1 mutant L2 mutant RCA RNAscope TEM mouse papillomavirus qPCR tumor growth viral copy number viral production Animals Capsid Proteins Cell Transformation Viral DNA Viral Female Genome Viral Mice Mice Nude Mucous Membrane Mutation Oncogene Proteins Viral Papillomaviridae Skin Virus Replication
The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer.
Nour Ghaddar, Shuo Wang, Bethany Woodvine, Jothilatha Krishnamoorthy, Vincent van Hoef, Cedric Darini, Urszula Kazimierczak, Nicolas Ah-son, Helmuth Popper, Myriam Johnson, Leah Officer, Ana Teodósio, Massimo Broggini, Koren K Mann, Maria Hatzoglou, Ivan Topisirovic, Ola Larsson, John Le Quesne, Antonis E Koromilas
Aug 31, 2021
The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. Here we demonstrate that ISR is pivotal in lung adenocarcinoma (LUAD) development, the most...
adenine Adenocarcinoma Animals Carcinogenesis Cell Line Tumor Dual Specificity Phosphatase 6 Eukaryotic Initiation Factor-2 Female Humans Indoles Kaplan-Meier Estimate Lung Neoplasms Male Mice Nude Mitogen-Activated Protein Kinases Phosphorylation Proto-Oncogene Proteins p21(ras) Stress Physiological Xenograft Model Antitumor Assays
Phosphatidylinositide 3-kinase (PI3K) and PI3K-related kinase (PIKK) activity contributes to radioresistance in thyroid carcinomas.
Natalie Burrows, Joseph Williams, Brian A Telfer, Julia Resch, Helen R Valentine, Richard J Fitzmaurice, Amanda Eustace, Joely Irlam, Emily J Rowling, Cuong Hoang-Vu, Catharine M West, Georg Brabant, Kaye J Williams
May 26, 2021
Anaplastic (ATC) and certain follicular thyroid-carcinomas (FTCs) are radioresistant. The Phosphatidylinositide 3-kinase (PI3K) pathway is commonly hyperactivated in thyroid-carcinomas. PI3K can modify the PI3K-related kinases...
ATM ATR DNA-PKcs PI3K radioresistance Animals Carcinoma Carcinoma Papillary Cell Cycle Cell Cycle Proteins Cell Line Tumor DNA Damage DNA-Binding Proteins Dose-Response Relationship Radiation Enzyme Activation Female Histones Humans Hypoxia Indazoles Mice Mice Nude Neoplasm Transplantation Oxygen Phosphatidylinositol 3-Kinases Radiation Tolerance Signal Transduction Sulfonamides Thyroid Cancer Papillary Thyroid Neoplasms
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