AI Article Synopsis
Article Abstract
Purpose: Integrin alpha(v)beta(3) and vascular endothelial growth factor receptor 2 (Flk-1) have been shown to be involved in tumor-induced angiogenesis. Selective targeting of upregulated alpha(v)beta(3) and Flk-1 on the neovasculature of tumors is a novel antiangiogenesis strategy for treating a wide variety of solid tumors. In the studies described here, we investigated the potential therapeutic efficacy of two three-component treatment regimens using two murine tumor models.
Methods And Materials: The treatment regimens used nanoparticle (NP) based targeting agents radiolabeled with (90)Y. The small molecule integrin antagonist (IA) 4-[2-(3,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]-benzoyl-2-(5)-aminoethylsulfonylamino-beta-alanine, which binds to the integrin alpha(v)beta(3), and a monoclonal antibody against murine Flk-1 (anti-Flk-1 MAb) were used to target the NPs. Murine tumor models K1735-M2 (melanoma) and CT-26 (colon adenocarcinoma) were used to evaluate the treatment efficacy.
Results: In K1735-M2 and CT-26 tumors, a single treatment with IA-NP-(90)Y (14.2 microg/g IA, 5 or 6 microCi/g (90)Y) caused a significant tumor growth delay compared to untreated control tumors, as well as tumors treated with IA, IA-NP, and NP-(90)Y, respectively (p < 0.025, Wilcoxon test). In K1735-M2 tumors, a single treatment with anti-Flk-1 MAb-NP-(90)Y (0.36 microg/g anti-Flk-1 MAb, 5 microCi/g (90)Y) also caused a significant tumor growth delay (p < 0.05, Wilcoxon test) compared to untreated tumors, as well as tumors treated with anti-Flk-1 MAb, anti-Flk-1 MAb-NP, and conventional radioimmunotherapy with (90)Y-labeled anti-Flk mAb. Anti-CD31 staining showed a marked decrease in vessel density in tumors treated with anti-Flk-1 MAb-NP-(90)Y, which was associated with a high level of apoptotic death in these tumors, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining.
Conclusions: The present studies provide proof of principle that targeted radiotherapy works using different targeting agents on a nanoparticle, to target both the integrin alpha(v)beta(3) and the vascular endothelial growth factor receptor. These encouraging results demonstrate the potential therapeutic efficacy of the IA-NP-(90)Y and anti-Flk-1 MAb-NP-(90)Y complexes as novel therapeutic agents for the treatment of a variety of tumor types.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijrobp.2003.10.057 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enhanced engraftment of human haematopoietic stem cells via mechanical remodelling mediated by the corticotropin-releasing hormone.
Nat Biomed Eng
December 2024
Department of Hematology, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Institute of Blood and Cell Therapy and Anhui Provincial Key Laboratory of Blood Research and Applications, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
The engraftment of haematopoietic stem and progenitor cells (HSPCs), particularly in cord-blood transplants, remains challenging. Here we report the role of the corticotropin-releasing hormone (CRH) in enhancing the homing and engraftment of human-cord-blood HSPCs in bone marrow through mechanical remodelling. By using microfluidics, intravital two-photon imaging and long-term-engraftment assays, we show that treatment with CRH substantially enhances HSPC adhesion, motility and mechanical remodelling, ultimately leading to improved bone-marrow homing and engraftment in immunodeficient mice.
View Article and Find Full Text PDFPeptide Nanocarriers for Targeted Delivery of Nucleic Acids for Cancer Therapy.
Bioconjug Chem
December 2024
State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Peptides have been extensively studied in nanomedicine with great bioactivity and biocompatibility; however, their poor cell-membrane-penetrating properties and nonselectivity greatly limit their clinical applications. In this study, tumor-targeting therapy was achieved by modifying our previously developed efficient peptide vector with the cancer-targeting peptide RGD, enabling it to specifically target tumor cells with a high expression of RGD-binding receptors. B-cell lymphoma-2 antisense oligonucleotides were selected as the target model to validate the effectiveness of the delivery carriers.
View Article and Find Full Text PDFThe novel ECM protein SNED1 mediates cell adhesion via the RGD-binding integrins α5β1 and αvβ3.
J Cell Sci
December 2024
Department of Physiology and Biophysics, University of Illinois Chicago, Illinois, 60612, USA.
The extracellular matrix (ECM) is a complex meshwork comprising over 100 proteins. It serves as an adhesive substrate for cells and, hence, plays critical roles in health and disease. We have recently identified a novel ECM protein, SNED1, and have found that it is required for neural crest cell migration and craniofacial morphogenesis during development and in breast cancer, where it is necessary for the metastatic dissemination of tumor cells.
View Article and Find Full Text PDFConformational response of αβ and αβ integrins to force.
Structure
December 2024
Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA; Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA; Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, USA. Electronic address:
As major adhesion receptors, integrins transmit biochemical and mechanical signals across the plasma membrane. These functions are regulated by transitions between bent and extended conformations and modulated by force. To understand how force on integrins mediates cellular mechanosensing, we compared two highly homologous integrins, αβ and αβ.
View Article and Find Full Text PDFFeline Adenovirus Isolate Shows Silent Nucleotide Alterations, Alternative Receptor/Coreceptor Binding, High Resistance to Disinfectants and Antiviral Drugs, as Well as Immunomodulation.
Animals (Basel)
December 2024
Department of Preventive Medicine and Public Health, Semmelweis University, 1085 Budapest, Hungary.
Adenovirus (AdV) infection has been rarely documented in cats and other felids. Partial sequences of the hexon and fiber genes of a Hungarian feline adenovirus isolate (FeAdV isolate) showed a close relationship to human AdV (HAdV) type C1. Further molecular and biological characterization is reported here.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!