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151.
Ewa D. Micewicz Chun-Ling Jung Dorthe Schaue Hai Luong William H. McBride Piotr Ruchala 《International journal of peptide research and therapeutics》2011,17(3):247-257
Many lung cancer treatment regimens include radiotherapy. We sought to improve the efficacy of such treatment by invoking
the targeted delivery of a model radiosensitizer (nicotinamide) to malignant tissues. Ephrin receptors (Eph), which are often
overexpressed in lung cancers, were selected as the target of our delivery system. Molecular targeting was achieved utilizing
a small peptide derived from the C-terminal portion of azurin, a copper-containing redox protein (“cupredoxin”) that is capable
of binding to ephrin receptors. We prepared and screened a sub-library of peptides derived from the C-terminal region of azurin
and found several small analogues that bound ephrin receptors EphA2, EphB2, and EphB4. One such peptide, termed AzV36, was
selected for conjugation with nicotinic acid via an amide bond to form AzV36-NicL. The resulting linear peptide contains 15
residues (including unusual and d-amino acids), is very stable in human serum, and can be easily manufactured. AzV36-NicL conjugate was tested in vivo for
its ability to radiosensitize Lewis lung carcinoma (LCC) in artificial metastasis and solid tumor engraftment models. The
compound increased the efficacy of radiotherapy with tumor colonies being ~2–13 fold lower than with radiation alone depending
on experimental schedule. In contrast, equimolar amounts of unconjugated peptide (AzV36-L) or nicotinamide alone only marginally
improved radiation efficacy. The targeted delivery of radiosensitizer(s) to ephrin receptors may enhance the efficacy of radiation
treatment of lung cancer and of other cancers that overexpress ephrin receptor(s). 相似文献
152.
By use of small-angle X-ray scattering it is shown that addition of alkali halide salts in small amounts (0-200 mM) shifts the repeat spacing in multilamellar DC13PC vesicles and alters the anomalous swelling behaviour close to the main transition. Both effects follow the Hofmeister series of the ions. We suggest that the shift of repeat spacing can be explained by ion effects on the van der Waals attractive forces between the membranes and on the decay length of the repulsive hydration force. The anomalous swelling is explained in terms of a critical unbinding of the membranes. The proximity of the critical temperature of the unbinding to the main transition temperature can be tuned by varying the concentration and type of salt in the sample. 相似文献
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