Prognosis in patients with non-small cell lung cancer who received erlotinib treatment and subsequent dose reduction due to skin rash.

BACKGROUND: Severe skin rash as toxicity of erlotinib has been reported in relation to better response and survival. However, some patients require dose reduction due to skin toxicities, and their prognosis remains uncertain. We retrospectively evaluated the clinical course of non-small cell lung cancer patients receiving erlotinib at a reduced dose because of skin rash. PATIENTS AND METHODS: Among 76 patients treated with erlotinib, 55 patients who developed skin rash severer than grade 2 were divided into 2 groups: 24 patients treated with erlotinib with dose reduction because of skin rash (dose reduction group) and 31 patients without any dose reduction (non-dose reduction group). RESULTS: The median progression-free survival in the dose reduction and non-dose reduction groups was 341 and 70 days, respectively, and the median overall survival was 566 and 202 days, respectively (p < 0.001). In the dose reduction group, no smoking history, female sex, epidermal growth factor receptor gene mutation, and grade 3 skin rash were significant baseline factors. CONCLUSIONS: Patients who received erlotinib at a reduced dose following skin rash showed better survival than those without reduction. In cases of intolerable skin rash, patients may benefit from continuous treatment with a reduced dose of erlotinib.

In vitro antimicrobial activity of aminoreductone against the pathogenic bacteria methicillin-resistant Staphylococcus aureus (MRSA).

In this study, antimicrobial activity of aminoreductone (AR), a product formed during the initial stage of the Maillard reaction, against methicillin-resistant Staphylococcus aureus (MRSA) was evaluated. The significant growth inhibition of all 51 MRSA isolates irrespective of drug susceptibility by AR was observed. The minimum inhibitory concentration (MIC) of AR ranged from 13 to 26 mM. The bactericidal activity of AR was evaluated by a killing assay with multiples of MIC, and it was recognized to depend on its dose. The combined effects of AR and antibiotics frequently used for the treatment of infections caused by Gram-positive and Gram-negative bacteria, such as amikacin (AN), ciprofloxacin, imipenem and levofloxacin, were examined. As a result, AR did not interfere with these antibiotic activities against 12 MRSA isolates selected and showed the advanced effect of growth inhibition in combination with antibiotics. Moreover, the inhibitory effects of AR were similar to those of AN, an antibiotic with known adverse effects, some serious. These findings show that AR is a naturally formed antimicrobial agent present in thermally processed foods with potential health benefits in medical practice.

Demonstration of the presence of aminoreductone formed during the Maillard reaction in milk.

The Maillard reaction is a common chemical reaction that occurs in food and it generates multiple reaction products. Aminoreductone (AR) is one of the early-stage Maillard reaction products. At present the formation of AR has only been demonstrated in a model system consisting of a monosaccharide or disaccharide and an amino group-containing compound. There is no direct evidence to show the presence of AR in food. In this study, we demonstrated the formation and presence of AR in milk using a combination of 2,4-dinitrophenylhydrazine (DNP) and Cu(2+). A DNP derivative of AR oxidised by Cu(2+) was isolated and its detailed structure was identified by NMR analysis. We thus directly demonstrated the formation and presence of AR in milk.

Antimicrobial activity of aminoreductone against Helicobacter pylori.

Anti-Helicobacter pylori (H. pylori) effects of aminoreductone (AR), a Maillard reaction product, were evaluated in this study. AR effectively inhibited the growth of all 24 strains (19 clinical isolates and 5 isogenic mutants) irrespective of susceptibility to antibiotics and clinical manifestation. The minimum inhibitory concentration (MIC) of AR ranged from 0.5 to 5 mM. A killing assay with multiples of MIC was performed, demonstrating that the killing activity of AR was significantly higher than that of its derived melanoidin, an inhibitor of H. pylori urease-gastric mucin adherence, formed in the final stage of the Maillard reaction. These significant effects of AR on H. pylori were observed even in acidic conditions (pH 3). At most, 25 mM AR effectively exhibited bactericidal activity in all strains. These results rise up the possibility that foods containing AR, such as milk and dairy products, are valuable sources for preventing colonization of H. pylori in the stomach and its associated tissue damages.