ABSTRACT
Epidermal growth factor receptor inhibitors (EGFRIs) frequently cause cutaneous adverse effects such as papulopustular eruptions. However, the mechanism of the reactions remains unclear. To assess the pathological mechanism of cutaneous adverse reactions caused by EGFRIs, we investigated whether EGFRIs have an influence on the innate immune response of the skin. Levels of human ß-defensins (hBDs), which serve as the first line of defence against infection by pathogenic microorganisms, in the stratum corneum samples of patients treated with EGFR. monoclonal antibodies were measured before and after starting therapy. There were no obvious trends in hBD production in patients without eruptions, whereas a significant decrease in hBD1 and hBD3 production and a nonsignficant decrease in hBD2 production were observed in patients who developed papulopustular eruptions. Our results suggest that a reduction in hBD contributes to the increased incidence of papulopustular eruptions.
Subject(s)
Antibodies, Monoclonal/adverse effects , Drug-Related Side Effects and Adverse Reactions/pathology , ErbB Receptors/antagonists & inhibitors , beta-Defensins/drug effects , Aged , Aged, 80 and over , Anti-Infective Agents/analysis , Anti-Infective Agents/metabolism , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Drug Eruptions/etiology , Drug Eruptions/immunology , Drug Eruptions/microbiology , Epidermis/drug effects , Epidermis/metabolism , Epidermis/pathology , ErbB Receptors/immunology , Female , Humans , Immunity, Innate/drug effects , Male , Middle Aged , Staphylococcal Skin Infections/chemically induced , Staphylococcal Skin Infections/epidemiology , beta-Defensins/analysisABSTRACT
In the current studies, we deposited ultra-thin hydroxyapatite films on a pure titanium substrate by pulsed laser deposition, and we examined the effects of these surfaces on rat bone marrow (RBM) cells. This method allowed deposition of 500-, 2,000-, and 5,000-A-thick hydroxyapatite films. X-ray diffraction showed that the amorphous films recrystallized to a hydroxyapatite crystal structure after annealing. The proliferation of RBM cells was unaffected by the hydroxyapatite films, but osteocalsin and alkaline phosphatase mRNA and protein levels were elevated in cells grown on 2,000- and 5,000-A-thick films. These results indicate that ultra-thin hydroxyapatite films generated by pulsed laser deposition are better at promoting osteogenesis than pure titanium surfaces.
Subject(s)
Calcium Phosphates/chemistry , Durapatite/chemistry , Alkaline Phosphatase/chemistry , Alkaline Phosphatase/metabolism , Animals , Bone Marrow Cells , Cell Differentiation , Cell Proliferation , Gene Expression Profiling , Lasers , Osteocalcin/chemistry , RNA, Messenger/metabolism , Rats , Tensile Strength , Titanium/chemistry , X-Ray DiffractionABSTRACT
In the current studies, we deposited ultra-thin hydroxyapatite films on a pure titanium substrate by pulsed laser deposition, and we examined the effects of these surfaces on rat bone marrow (RBM) cells. This method allowed deposition of 500-, 2000-, and 5000-Angstrom-thick hydroxyapatite films. X-ray diffraction showed that the amorphous films recrystallized to a hydroxyapatite crystal structure after annealing. The proliferation of RBM cells was unaffected by the hydroxyapatite films, but osteocalsin and alkaline phosphatase mRNA and protein levels were elevated in cells grown on 2000- and 5000-Angstrom-thick films. These results indicate that ultra-thin hydroxyapatite films generated by pulsed laser deposition are better at promoting osteogenesis than pure titanium surfaces.
