Evaluation of the therapeutic efficacy of a MEK inhibitor (TAK-733) using 18F-fluorodeoxyglucose-positron emission tomography in the human lung xenograft model A549
Reads0
Chats0
TLDR
18F-FDG-PET enabled early determination of late anti-tumor activity in response to TAK-733 treatment and showed dose-dependent inhibition of tumor growth and 18F- FDG uptake in tumor tissue.Abstract:
Objective
The aim of this study was to evaluate the potential of 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) for monitoring the therapeutic efficacy of TAK-733, an inhibitor of mitogen-activated protein kinase kinase, in nude rats bearing A549 (human lung carcinoma) xenografts.read more
Citations
More filters
Journal ArticleDOI
MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation.
Zuzanna Baranski,Tijmen H Booij,Marieke L. Kuijjer,Yvonne de Jong,Anne-Marie Cleton-Jansen,Leo S. Price,Bob van de Water,Judith V.M.G. Bovée,Pancras C.W. Hogendoorn,Erik H.J. Danen +9 more
TL;DR: MEK1/2 inhibition represents a candidate treatment strategy for osteosarcomas displaying high MEK activity as determined by ERK phosphorylation status, and western blot analysis ofERK activity revealed that sensitive lines had high constitutive ERK activity.
Journal ArticleDOI
A phase I dose-escalation study of TAK-733, an investigational oral MEK inhibitor, in patients with advanced solid tumors.
Alex A. Adjei,Alex A. Adjei,Patricia LoRusso,Antoni Ribas,Jeffrey A. Sosman,Anna C. Pavlick,Grace K. Dy,Xiaofei Zhou,Esha A. Gangolli,Esha A. Gangolli,Michelle Kneissl,Stephanie Faucette,Rachel Neuwirth,Viviana Bozon +13 more
TL;DR: TAK-733 had a generally manageable toxicity profile up to the maximum tolerated dose, and showed the anticipated pharmacodynamic effect of sustained inhibition of ERK phosphorylation, in patients with solid tumors.
Journal ArticleDOI
Simultaneous determination of five active alkaloids from Compound Kushen Injection in rat plasma by LC-MS/MS and its application to a comparative pharmacokinetic study in normal and NSCLC nude rats
TL;DR: Results indicated that the pharmacokinetic behaviors of oxymatrine, sophoridine and N-methylcytisine from CKI could be changed when it was intravenously administrated to the NSCLC model rats, and possible reasons have been proposed.
Journal ArticleDOI
Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models: evaluation of insulin and β3-adrenergic receptor agonist effects by 18F-FDG.
Seigo Ishino,Taku Sugita,Yusuke Kondo,Mika Okai,Kazue Tsuchimori,Masanori Watanabe,Ikuo Mori,Masaki Hosoya,Takashi Horiguchi,Hidenori Kamiguchi +9 more
TL;DR: The biodistribution method with 18F-FDG was confirmed to be useful for pharmacological evaluation of anti-diabetic or anti-obesity drugs using disease-model animals to detect clear differences in basal glucose uptake between disease- model animals and their corresponding controls.
Journal ArticleDOI
Preclinical Imaging in Targeted Cancer Therapies
TL;DR: Preclinical imaging can be considered as an integral part of the complex translational process that moves a newly developed targeted agent from laboratory to clinical application intervening in all clinically relevant steps including patient selection, early monitoring of drug effects and reversal of drug resistance.
References
More filters
Journal ArticleDOI
MAP kinase signalling pathways in cancer.
TL;DR: Recent findings and hypotheses on the role of MAPK pathways in cancer are discussed, with a focus on stress-activated pathways, which largely seem to counteract malignant transformation.
Journal ArticleDOI
Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials.
J. I. Johnson,S. Decker,Daniel W. Zaharevitz,Larry Rubinstein,J M Venditti,S Schepartz,S Kalyandrug,Michaele C. Christian,Susan G. Arbuck,Melinda G. Hollingshead,Edward A. Sausville +10 more
TL;DR: For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results.
Journal ArticleDOI
Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors
Rika Hoshino,Yuji Chatani,Takao Yamori,Takashi Tsuruo,Takashi Tsuruo,Hiroya Oka,Osamu Yoshida,Yutaka Shimada,Shigeki Arii,Hiromi Wada,Jiro Fujimoto,Michiaki Kohno +11 more
TL;DR: The results suggest that the constitutive activation of 41-/43-kDa MAP kinases in tumor cells is not due to the disorder of MAP kinase themselves, but is due toThe disorder of Raf-1, Ras, or some other signaling molecules upstream of Ras.
Journal ArticleDOI
Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development
Gary J. Kelloff,John M. Hoffman,Bruce E. Johnson,Howard I. Scher,Barry A. Siegel,Edward Y. Cheng,Bruce D. Cheson,Joyce O'Shaughnessy,Kathryn Z. Guyton,David A. Mankoff,Lalitha K. Shankar,Steven M. Larson,Caroline C. Sigman,Richard L. Schilsky,Daniel C. Sullivan +14 more
TL;DR: Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed and its potential as a surrogate of clinical benefit is addressed.
Journal ArticleDOI
Role of MAP kinase in tumor progression and invasion.
TL;DR: The potential role that MAPKs play in metastasis by regulating cell migration, proteinase-induction and apoptosis is discussed.