In vitro effect of chlorambucil on human glioma cell lines (SF767 and U87-MG), and human microvascular endothelial cell (HMVEC) and endothelial progenitor cells (ECFCs), in the context of plasma chlorambucil concentrations in tumor-bearing dogs

Autor: Deborah W. Knapp, Julie A. Mund, Kimberly M. Anderson, Michael J. Reese, Rebecca A. Packer, David R. Jones, Jamie Case
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Physiology
Cancer Treatment
lcsh:Medicine
Apoptosis
Cardiovascular Physiology
Epithelium
0302 clinical medicine
Animal Cells
immune system diseases
hemic and lymphatic diseases
Vasculogenesis
Medicine and Health Sciences
Morphogenesis
lcsh:Science
Neurological Tumors
Cells
Cultured
Endothelial Progenitor Cells
Mammals
Cultured Tumor Cells
Multidisciplinary
Cell Death
Pharmaceutics
Chemistry
Eukaryota
Glioma
3. Good health
Endothelial stem cell
medicine.anatomical_structure
Oncology
Neurology
Cell Processes
030220 oncology & carcinogenesis
Vertebrates
Biological Cultures
Cellular Types
Anatomy
Research Article
medicine.drug
Clinical Oncology
Endothelium
Cell Survival
Metabolic Clearance Rate
Context (language use)
Research and Analysis Methods
Cancer Chemotherapy
03 medical and health sciences
Dogs
Drug Therapy
Cell Line
Tumor
medicine
Animals
Chemotherapy
Humans
Progenitor cell
Antineoplastic Agents
Alkylating
Cell Proliferation
Dose-Response Relationship
Drug
Chlorambucil
lcsh:R
Organisms
Biology and Life Sciences
Endothelial Cells
Cancers and Neoplasms
Epithelial Cells
Cell Biology
Cell Cultures
Glioma Cells
medicine.disease
Biological Tissue
030104 developmental biology
Cell culture
Amniotes
Cancer research
lcsh:Q
Clinical Medicine
Developmental Biology
Zdroj: PLoS ONE, Vol 13, Iss 9, p e0203517 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endothelial cells, respectively. The in vitro LD50 and IC50 of chlorambucil were determined using human SF767 and U87-MG glioma cell lines, human microvascular endothelial cells (HMVECs) and human endothelial colony forming cells (ECFCs). Results were analyzed in the context of chlorambucil concentrations measured in the plasma of tumor-bearing dogs receiving 4 mg m-2 metronomic chlorambucil. The LD50 and IC50 of chlorambucil were 270 μM and 114 μM for SF767, and 390 μM and 96 μM for U87-MG, respectively. The IC50 of chlorambucil was 0.53 μM and 145 μM for the HMVECs and ECFCs, respectively. In pharmacokinetic studies, the mean plasma Cmax of chlorambucil was 0.06 μM. Results suggest that metronomic chlorambucil in dogs does not achieve plasma concentrations high enough to cause direct cytotoxic or growth inhibitory effects on either glioma or endothelial cells.
Databáze: OpenAIRE
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