pyrophosphate and Glioma

Topics: Adenosine Triphosphate; Colorectal Neoplasms; Diphosphates; DNA Methylation; Glioma; Humans; Isocitrate Dehydrogenase; Janus Kinase 2; Mutation; Myeloproliferative Disorders; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Sequence Analysis, DNA; Templates, Genetic

Understanding the uptake of a drug by diseased tissue, and the drug's subsequent spatiotemporal distribution, are central factors in the development of effective targeted therapies. However, the interaction between the pathophysiology of diseased tissue and individual therapeutic agents can be complex, and can vary across tissue types and across subjects. Here, we show that the combination of mathematical modelling, high-resolution optical imaging of intact and optically cleared tumour tissue from animal models, and in vivo imaging of vascular perfusion predicts the heterogeneous uptake, by large tissue samples, of specific therapeutic agents, as well as their spatiotemporal distribution. In particular, by using murine models of colorectal cancer and glioma, we report and validate predictions of steady-state blood flow and intravascular and interstitial fluid pressure in tumours, of the spatially heterogeneous uptake of chelated gadolinium by tumours, and of the effect of a vascular disrupting agent on tumour vasculature.

Topics: Animals; Antineoplastic Agents; Blood Vessels; Cell Line, Tumor; Colorectal Neoplasms; Contrast Media; Diphosphates; Disease Models, Animal; Female; Gadolinium; Glioma; Humans; Hydrodynamics; Image Processing, Computer-Assisted; Mice; Mice, Inbred C57BL; Mice, Nude; Models, Theoretical; Regional Blood Flow; Stilbenes; Transplantation, Heterologous

Topics: Brain Neoplasms; Cell Nucleus; Dactinomycin; Diphosphates; Glioblastoma; Glioma; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Meningioma; Nucleotides; RNA Nucleotidyltransferases; RNA, Neoplasm; Tissue Extracts