Modulating the structure of EGFR with UV light: new possibilities in cancer therapy.

The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. EGFR is activated upon binding to e.g. epidermal growth factor (EGF), leading to cell survival, proliferation and migration. EGFR overactivation is associated with tumor progression. We have previously shown that low dose UVB illumination of cancer cells overexpressing EGFR prior to adding EGF halted the EGFR signaling pathway. We here show that UVB illumination of the extracellular domain of EGFR (sEGFR) induces protein conformational changes, disulphide bridge breakage and formation of tryptophan and tyrosine photoproducts such as dityrosine, N-formylkynurenine and kynurenine. Fluorescence spectroscopy, circular dichroism and thermal studies confirm the occurrence of conformational changes. An immunoassay has confirmed that UVB light induces structural changes in the EGF binding site. A monoclonal antibody which competes with EGF for binding sEGFR was used. We report clear evidence that UVB light induces structural changes in EGFR that impairs the correct binding of an EGFR specific antibody that competes with EGF for binding EGFR, confirming that the 3D structure of the EGFR binding domain suffered conformational changes upon UV illumination. The irradiance used is in the same order of magnitude as the integrated intensity in the solar UVB range. The new photonic technology disables a key receptor and is most likely applicable to the treatment of various types of cancer, alone or in combination with other therapies

Influence of Cr on structural, spectroscopic and magnetic'' properties CoFe2O4 grown by the wet Chemical method

The Cr doped CoFe2O4 nano crystalline ceramics are synthesized using wet chemical method. The structural, morphological, functional, spectroscopic and magnetic properties of pure CoFe2O4 and Cr doped CoFe2O4 are characterized by XRD, FESEM, FTIR, Raman, Mossbauer spectroscopy and M-H hysteresis loop. The X-ray diffraction (XRD) patterns of undoped (x = 0) and doped (x not equal 0) samples reveal the formation of single phase cubic spinel structure. The lattice parameters and cation distribution between tetrahedral (A) and octahedral (B) sites of the samples (AB(2)O(4)) were obtained by Rietveld refinement of XRD patterns. The FESEM micrographs exhibit dense micro structure with small voids. The energy dispersive x-ray studies confirm the presence of Cr in CoFe2O4. The FTIR spectrum confirms that the peaks corresponding to the metal-oxygen bonds have shiftedtowards higher wavelength region. Raman spectrum exhibits broad peaks which confirm the existence of local disorder due to the inter-site cation migration between tetrahedral and octahedral sites. The Mossbauer spectroscopy reveals that the magnitude of magnetic hyperfine field of tetrahedral site (H-A) and octahedral site (H-B) decreases with increase in Cr doping in CoFe2O4 and that the decrease is more rapid in tetrahedral site (H-A) compared to that in octahedral site (H-B). And also confirm that the magnetic hyperfine fields (B-hf) are smaller relative to pure cobalt ferrite representing that super exchange interaction which is decreases as the Cr concentration increases. The magnetization studies reveal a decrease in the saturation magnetization (M-s) of CoFe2O4 with increase in Cr substitution. A similar and non-monotonic variation of coercivity (H-c) and magneto crystalline anisotropy (K) suggests that H-c is mainly determined by K

Typical photoproducts generated upon UV illumination of the aromatic residues Trp and Tyr.

<p>Typical photoproducts generated upon UV illumination of the aromatic residues Trp and Tyr.</p

Time-resolved fluorescence measurements.

<p>Time-resolved intensity decay data, fitting curve and residuals obtained using the ISS routine for the control sEGFR sample (kept in the dark for 75 min, negative control, NC).</p