RESUMO
We conducted a cross-sectional study on the clinical and mycological features of onychomycosis in patients in the dermatology ward of Iwate Medical University Hospital, an acute care hospital. Of the 226 hospitalized patients, 73 (32.3%) had onychomycosis and 61 (26.9%) were diagnosed after admission. The toenail was the most common site of onychomycosis (94.5%), while toenail plus fingernail and fingernail only sites were 4.1% and 1.4%, respectively. The most common clinical form of onychomycosis was distal and lateral subungual onychomycosis (79%) with Trichophyton rubrum (66.7%) and T. interdigitale (27.8%) as the main causative species. Patients who were older, or had neurological diseases, or needed stretcher transfer had onychomycosis significantly more frequently than those who were obese, had diabetes, cancer, needed an escort for moving, or could move independently. Our study suggests that there is likely to be a significant number of untreated and undiagnosed patients with onychomycosis in acute care hospitals. Therefore, it is necessary to increase awareness of onychomycosis in hospitals.
RESUMO
NAD(P)H quinone oxidoreductase 1 (NQO1)-dependent antitumor drugs such as ß-lapachone (ß-lap) are attractive candidates for cancer chemotherapy because several tumors exhibit higher expression of NQO1 than adjacent tissues. Although the association between NQO1 and ß-lap has been elucidated, the effects of a NQO1-inducer and ß-lap used in combination remain to be clarified. It has previously been reported that melanoma cell lines have detectable levels of NQO1 expression and are sensitive to NQO1-dependent drugs such as 17-allylamino-17-demethoxygeldanamycin. The present study was conducted to investigate the involvement of NQO1 in ß-lap-mediated toxicity and the utility of combination treatment with a NQO1-inducer and ß-lap in malignant melanoma cell lines. Decreased expression or inhibition of NQO1 caused these cell lines to become less sensitive to ß-lap, indicating a requirement of NQO1 activity for ß-lap-mediated toxicity. Of note was that carnosic acid (CA), a compound extracted from rosemary, was able to induce further expression of NQO1 through NF-E2 related factor 2 (NRF2) stabilization, thus significantly enhancing the cytotoxicity of ß-lap in all of the melanoma cell lines tested. Taken together, the data presented in the current study indicated that the NRF2-NQO1 axis may have potential value as a therapeutic target in malignant melanoma to improve the rate of clinical response to NQO1-dependent antitumor drugs.
Assuntos
Dermatite Perioral , Dermatite , Exantema , Criança , Doxiciclina/uso terapêutico , HumanosRESUMO
The KEAP1-NRF2 pathway regulates cellular redox homeostasis by transcriptional induction of genes associated with antioxidant synthesis and detoxification in response to oxidative stress. Previously, we reported that KEAP1 mutation elicits constitutive NRF2 activation and resistance to cisplatin (CDDP) and dacarbazine (DTIC) in human melanomas. The present study was conducted to clarify whether an HSP90 inhibitor, 17-AAG, efficiently eliminates melanoma with KEAP1 mutation, as the NRF2 target gene, NQO1, is a key enzyme in 17-AAG bioactivation. In melanoma and non-small cell lung carcinoma cell lines with or without KEAP1 mutations, NQO1 expression and 17-AAG sensitivity are inversely correlated. NQO1 is highly expressed in normal melanocytes and in several melanoma cell lines despite the presence of wild-type KEAP1, and the NQO1 expression is dependent on NRF2 activation. Because either CDDP or DTIC produces reactive oxygen species that activate NRF2, we determined whether these agents would sensitize NQO1-low melanoma cells to 17-AAG. Synergistic cytotoxicity of the 17-AAG and CDDP combination was detected in four out of five NQO1-low cell lines, but not in the cell line with KEAP1 mutation. These data indicate that 17-AAG could be a potential chemotherapeutic agent for melanoma with KEAP1 mutation or NQO1 expression.