Experimental Pharmacology & Oncology GmbH
Ontology highlight
ABSTRACT:
PROVIDER: EGAO00000000749 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Organisation EGAO00000000883
| EGAO00000000883 | EGA
Project description:The multifunctional protein - tissue inhibitor of metalloproteinases-1 (TIMP-1) - has been associated with poor prognosis in several types of cancers including glioblastomas. Glioblastomas are the most common and malignant primary brain tumor known for being highly invasive and resistant to therapy. New treatment strategies are continuously being explored and currently vascular endothelial growth factor (VEGF) inhibitors administered in combination with Irinotecan is the most promising second line treatment. TIMP-1 has been associated with decreased response to chemotherapy in breast and colorectal cancer and especially the family of topoisomerase (TOP) inhibitors, such as Irinotecan, has been suggested to be affected by TIMP-1. In the present study, we investigated whether a high TIMP-1 expression in glioblastoma cells played a role in TOP inhibitor resistance. We established two TIMP-1 over-expressing cell lines and evaluated the sensitivity towards the TOP1 inhibitor SN-38 and the TOP2 inhibitor Epirubicin using a viability and a cytotoxicity assay. In addition, we investigated the invasive features of the cells in a brain slice culture model as well as in an orthotopic xenograft model. The results showed that TIMP-1 over-expressing U87MG cell line sub-clones were significantly more resistant than the controls when exposed to SN-38 and Epirubicin. The same tendency was seen for the TIMP-1 over-expressing A172 sub-clones. No significant differences in invasion patterns were observed for TIMP-1 over-expressing sub-clones when compared to controls. In conclusion, the present study suggests that TIMP-1 over-expression reduces the effect of TOP inhibitors in the glioblastoma cell line U87MG. There was no significant effect of TIMP-1 over-expression on tumor cell invasion. The association found between TIMP-1 cellular levels and the effect of TOP inhibitors needs to be validated in clinical patient material.
| S-EPMC3823891 | biostudies-literature
Project description:Numerous studies have documented that adolescents and young adults (AYAs) experience a significant cancer burden as well as significant cancer mortality compared with other age groups. The reasons for the disparate outcomes of AYAs and other age groups are not completely understood and are likely to be multifactorial, including a range of sociodemographic issues unique to these individuals as well as differences between adolescents, younger pediatric patients, and adults in the pharmacology of anticancer agents. Because adolescence is a period of transition from childhood to early adulthood, numerous physical, physiologic, cognitive, and behavioral changes occur during this time. In this review, we provide an overview of the unique developmental physiology of the adolescent and explain how these factors and the behavioral characteristics of adolescents may affect the pharmacology of anticancer agents in this patient population. Finally, we describe examples of studies that have assessed the relation between drug disposition and age, focusing on the AYA age group.
| S-EPMC3018345 | biostudies-literature
Project description:Organisation EGAO00000001000
| EGAO00000001000 | EGA
Project description:There is an increasing role for positron emission tomography (PET) in oncology, particularly as a component of early phase clinical trials. As a non-invasive functional imaging modality, PET can be used to assess both pharmacokinetics and pharmacodynamics of novel therapeutics by utilizing radiolabelled compounds. These studies can provide crucial information early in the drug development process that may influence the further development of novel therapeutics. PET imaging probes can also be used as early biomarkers of clinical response and to predict clinical outcome prior to the administration of therapeutic agents. We discuss the role of PET imaging particularly as applied to phase 0 studies and discuss the regulations involved in the development and synthesis of novel radioligands. The review also discusses currently available tracers and their role in the assessment of pharmacokinetics and pharmacodynamics as applied to oncology.
| S-EPMC3166688 | biostudies-literature
Project description:Organisation EGAO00000001153
| EGAO00000001153 | EGA
Project description:Organisation EGAO00000000994
| EGAO00000000994 | EGA
Project description:Organisation EGAO00000000426
| EGAO00000000426 | EGA
Project description:Organisation EGAO00000000999
| EGAO00000000999 | EGA
Project description:Organisation EGAO00000001196
| EGAO00000001196 | EGA