Targeting Platelet-Derived Growth Factor Receptor on Endothelial Cells of Multidrug-Resistant Prostate Cancer

Autor: Christopher J. Logothetis, Joseph E. Busby, Marva Maya, Toru Nakamura, Sertac Yazici, Isaiah J. Fidler, Junqin He, Kim Anh Do, Xuemei Wang, Sun Jin Kim, Dominic Fan, Hisanori Uehara, Paul Mathew
Rok vydání: 2006
Předmět:
Male
CD31
Cancer Research
Platelet-derived growth factor
medicine.medical_treatment
Fluorescent Antibody Technique
Apoptosis
Piperazines
Mice
Random Allocation
chemistry.chemical_compound
Antineoplastic Combined Chemotherapy Protocols
Tumor Cells
Cultured
Receptors
Platelet-Derived Growth Factor
Phosphorylation
Neovascularization
Pathologic
Reverse Transcriptase Polymerase Chain Reaction
Bone metastasis
Protein-Tyrosine Kinases
Immunohistochemistry
Drug Resistance
Multiple
Endothelial stem cell
Oncology
Paclitaxel
Lymphatic Metastasis
Benzamides
Imatinib Mesylate
medicine.drug
medicine.medical_specialty
Blotting
Western
Mice
Nude
Antineoplastic Agents
Bone Neoplasms
Internal medicine
In Situ Nick-End Labeling
medicine
Animals
Humans
Protein Kinase Inhibitors
Chemotherapy
Tibia
business.industry
Microcirculation
Endothelial Cells
Prostatic Neoplasms
Imatinib
medicine.disease
Antineoplastic Agents
Phytogenic
Pyrimidines
Imatinib mesylate
Endocrinology
chemistry
Drug Resistance
Neoplasm
Cancer research
business
Neoplasm Transplantation
Zdroj: JNCI: Journal of the National Cancer Institute. 98:783-793
ISSN: 1460-2105
0027-8874
Popis: Background: Inhibiting phosphorylation of platelet-derived growth factor receptor (PDGFR) by treatment with the PDGFR kinase inhibitor imatinib and the chemotherapeutic agent paclitaxel reduces the incidence and size of human prostate cancer bone lesions in nude mice. Because tumor cells and tumor-associated endothelial cells express activated PDGFR, the primary target for imatinib has been unclear. Methods: We selected multidrug-resistant human PC-3MM2 prostate cancer cells (termed PC-3MM2-MDR cells) by culturing them in increasing concentrations of paclitaxel. PC-3MM2-MDR cells were implanted into one tibia of 80 nude mice. Two weeks later, the mice were randomly assigned to receive distilled water (control group), paclitaxel, imatinib, or imatinib plus paclitaxel for 10 weeks (20 mice per group). Tumor incidence and weight, bone structure preservation and osteolysis, and the incidence of lymph node metastasis were determined. The phosphorylation status of PDGFR on tumor cells and tumor-associated endothelial cells and levels of apoptosis were examined with immunohistochemical analyses. Microvessel density was assessed as the number of cells expressing CD31/platelet endothelial cell adhesion molecule 1 (PECAM-1). All statistical tests were two-sided. Results: PC-3MM2-MDR cells were resistant to paclitaxel and imatinib in vitro. Treatment of implanted mice with imatinib plus paclitaxel led to statistically signifi cant decreases in bone tumor incidence (control = 19 mice with tumors of 19 mice total; imatinib plus paclitaxel = four of 18 mice; P
Databáze: OpenAIRE
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