RESUMEN
By the recent introduction of molecular targeting drugs against BRAF mutation and immune checkpoint inhibitors, the prognosis of patients with melanoma in advanced stage is now improving, but still in the minority. Mucosal melanoma lacks the BRAF mutations, and hence conventional chemotherapeutic regimens must be improved. We have conventionally used dacarbazine (DTIC) for patients with metastatic mucosal melanoma. However, the efficacy of DTIC in patients with metastatic mucosal melanoma has been limited. Therefore, we explored other possibilities to improve the prognosis of patients suffering from metastatic mucosal melanoma. In this communication, we present a retrospective analysis of the sequential combination chemotherapy of DTIC with carboplatin and paclitaxel (CP) for metastatic mucosal melanoma of nasal cavity and paranasal sinuses. The objective response rate of seven patients is 14.3% by RECIST 1.1 and the overall survival (OS) is 12.5 months. These data indicate that the sequential combination chemotherapy of DTIC with CP could be an option for patients with metastatic mucosal melanoma of nasal cavity and paranasal sinuses who are currently ending into dismal prognosis.
RESUMEN
BACKGROUND: It is difficult to treat patients in the advanced stages of extramammary Paget disease (EMPD) because no effective treatment has yet been established. OBJECTIVE: To describe the experience of using combination chemotherapy (FECOM) in patients with metastatic EMPD. METHODS: Since we reported a case of metastatic EMPD that responded to FECOM, we have treated further patients with metastatic EMPD using FECOM at the National Cancer Center Hospital in Japan. FECOM consists of epirubicin 40 mg m(-2) , mitomycin C 3·5 mg m(-2) and vincristine 0·7 mg m(-2) on day 1, carboplatin 300 mg m(-2) on day 2 and 5-fluorouracil 350 mg m(-2) on days 2-6. To evaluate the efficacy of this combination therapy in patients with metastatic EMPD, data regarding patients given FECOM for the first-line treatment of metastatic EMPD were extracted retrospectively. RESULTS: Seven patients were eligible for this study. A partial response was noted in four evaluable patients (100%). The other three patients were not evaluable for clinical response. One of the three unevaluable patients showed a decrease in tumour size by 100%, the other two by about 20%. The median overall survival and progression-free survival were 9·4 months (7·6-17·3) and 6·5 months (2·6-7·9), respectively. The 1-year survival rate was 43% (three of seven). Three of the seven patients (43%) had grade 3 haematological toxicities. All treatment-related toxicities were reversible and there was no febrile neutropenia or treatment-related deaths. CONCLUSION: This study suggests that the combination chemotherapy FECOM may be a treatment option for patients with metastatic EMPD.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Ano/tratamiento farmacológico , Neoplasias de los Genitales Masculinos/tratamiento farmacológico , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Neoplasias de la Vulva/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/cirugía , Neoplasias Óseas/secundario , Carboplatino/administración & dosificación , Terapia Combinada , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Neoplasias de los Genitales Masculinos/cirugía , Humanos , Neoplasias Hepáticas/secundario , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Enfermedad de Paget Extramamaria/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/administración & dosificación , Neoplasias de la Vulva/cirugíaRESUMEN
BACKGROUND: Candesartan, an AT(1) receptor antagonist, has been reported to have no association with persistent cough in subjects with hypertension, but there has been no study on the safety of its administration to hypertensive patients with symptomatic asthma. The aim of this study was to compare the adverse effects of candesartan and calcium antagonists on cough, pulmonary function, and bronchial hyperresponsiveness in these patients. METHODS AND RESULTS: Sixty mildly to moderately hypertensive patients with bronchial asthma received either candesartan (n=30) or the calcium antagonists nifedipine or manidipine (n=30) for 6 months. The candesartan group included 5 subjects with a history of ACE inhibitor-induced cough. There were no differences between the 2 groups in patient characteristics, ACE gene polymorphism, pulmonary function, or bronchial hyperresponsiveness to methacholine. Control of hypertension was the primary end point; new cough detected by self-administrated questionnaire and an increase in cough frequency by visual analog scale were the second end point. No patient complained of persistent cough. Neither mean visual analog scale score nor pulmonary functions changed during this study. Bronchial hyperresponsiveness had a tendency to improve in the candesartan group, but there was no difference between the 2 groups. CONCLUSIONS: Incidence, frequency, and severity of persistent cough, pulmonary functions, and bronchial hyperresponsiveness did not change in either the candesartan or calcium antagonist group. It is suggested that candesartan is as effective and safe as calcium antagonists in the treatment of hypertension associated with symptomatic asthma.
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Antihipertensivos/administración & dosificación , Asma/tratamiento farmacológico , Bencimidazoles/administración & dosificación , Hiperreactividad Bronquial/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Tetrazoles/administración & dosificación , Adulto , Anciano , Asma/complicaciones , Asma/fisiopatología , Compuestos de Bifenilo , Presión Sanguínea/efectos de los fármacos , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/diagnóstico , Bloqueadores de los Canales de Calcio/administración & dosificación , Tos/diagnóstico , Tos/tratamiento farmacológico , Tos/etiología , Dihidropiridinas/administración & dosificación , Femenino , Pruebas Genéticas , Humanos , Hipertensión/complicaciones , Incidencia , Masculino , Cloruro de Metacolina , Persona de Mediana Edad , Nifedipino/administración & dosificación , Nitrobencenos , Dimensión del Dolor/efectos de los fármacos , Peptidil-Dipeptidasa A/genética , Piperazinas , Polimorfismo Genético , Pruebas de Función Respiratoria , Resultado del TratamientoRESUMEN
BACKGROUND: IL-18, identified as an IFN-gamma-inducing factor, is a proinflammatory cytokine that plays an important role in TH1 cell activation. Recently, it was reported that histamine induced IL-18 and that IL-18 might act as a coinducer of TH1 and TH2 cytokines. OBJECTIVE: The aim was to evaluate the contribution of IL-18 to asthma exacerbation. METHODS: Serum IL-18, soluble IL-2 receptor, eosinophil cationic protein, and plasma IFN-gamma levels, as well as peak expiratory flow were measured in patients with stable asthma (n = 28), acute mild or moderate asthma (n = 23), or pulmonary sarcoidosis (n = 35) and in healthy subjects (n = 26). We compared the serum IL-18 levels between patients with acute asthma and those in remission and examined the time course in acute exacerbation after asthma therapy. RESULTS: Significantly higher serum IL-18 levels were found in patients with acute asthma (215 +/- 33 pg/mL, mean +/- SE; P = .02) and pulmonary sarcoidosis (239 +/- 27 pg/mL, P = .008) than in control subjects (127 +/- 11 pg/mL), but the plasma IFN-gamma level was significantly elevated in only pulmonary sarcoidosis (P < .001). In pulmonary sarcoidosis the IL-18 values significantly correlated with the IFN-gamma levels (r = 0.61, P < .001), but in acute asthma they did not. The IL-18 levels during acute asthma exacerbation were significantly higher (P = .01) than on remission days. In acute asthma, circulating IL-18 levels significantly correlated with serum soluble IL-2 receptor levels (r = 0.77, P < .0001) but not with serum eosinophil cationic protein levels. The IL-18 level had a tendency to inversely correlate with peak expiratory flow. The elevated IL-18 levels in acute asthma quickly decreased on day 3 (P = .02) and day 7 (P = .002) after therapy. CONCLUSION: It was suggested that IL-18 may play a potential role to activate immunologic responses and may reflect disease activity in mild and moderate asthma exacerbation.
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Asma/sangre , Interleucina-18/sangre , Ribonucleasas , Enfermedad Aguda , Anciano , Proteínas Sanguíneas/análisis , Citocinas/metabolismo , Proteínas en los Gránulos del Eosinófilo , Femenino , Humanos , Interferón gamma/sangre , Enfermedades Pulmonares/sangre , Masculino , Persona de Mediana Edad , Ápice del Flujo Espiratorio , Receptores de Interleucina-2/sangre , Sarcoidosis/sangre , Solubilidad , Células Th2/metabolismoRESUMEN
BACKGROUND: The ratio of matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) may be a marker of the balance between airway tissue destruction and repair. TIMP-1 may potentially contribute to the pathogenesis of increased submucosal extracellular matrix deposition in asthma. OBJECTIVE: Our purpose was to assess the variation in sputum MMP-9 and TIMP-1 during acute asthma. METHODS: We evaluated the MMP-9 and TIMP-1 balance in sputa of 16 asthmatic patients admitted with spontaneous exacerbation, conducting measurement before (day 1) and after methylprednisolone infusion therapy (days 2, 3, 5, and 7), and on remission days. RESULTS: Peak expiratory flow and eosinophilic cationic protein levels were significantly (P <.05) improved within 7 days in all patients. Sputum MMP-9 levels on day 2 tended to be lower than on day 1, but not significantly. Zymography revealed that the main enzyme was identified immunologically as MMP-9, and gelatinase activity on day 1 had a tendency to decrease for the following 7 days. The TIMP-1 levels gradually increased until day 5, were significantly (P <.05) high on day 5, and decreased on day 7. The MMP-9/TIMP-1 molar ratios were significantly (P <.05) decreased on days 2, 3, 5, and 7 compared with day 1. Sputum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 molar ratios on day 1 were significantly higher (P <.02) than those on remission days. CONCLUSIONS: An imbalance between MMP-9 and TIMP-1 was present in acute asthma, with an excess of MMP-9 resulting in a high ratio of MMP-9/TIMP-1 before treatment, and over time with glucocorticosteroid the TIMP-1 levels rose, dropping the ratio of MMP-9/TIMP-1. It was suggested that overproduction of MMP-9 and TIMP-1 after asthma exacerbation might contribute significantly to airway tissue remodeling and that TIMP-1 production in acute asthma might not be suppressed by glucocorticosteroid.
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Metaloproteinasa 9 de la Matriz/aislamiento & purificación , Ribonucleasas , Esputo/enzimología , Enfermedad Aguda , Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Asma/metabolismo , Proteínas Sanguíneas/análisis , Líquido del Lavado Bronquioalveolar/química , Proteínas en los Gránulos del Eosinófilo , Eosinófilos/química , Femenino , Humanos , Mediadores de Inflamación/análisis , Masculino , Persona de Mediana Edad , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-1/análisisRESUMEN
Coenzyme B12 dependent diol dehydrase from Aerobacter aerogenes was immobilized by covalent binding to CNBr-activated Sepharose 4B. The Sepharose-bound enzyme exhibited a markedly high catalytic activity, viz., 75-95% of the specific activity of the original free enzyme. The apoenzyme acquired much greater stability to heat by immobilization. No significant difference between the immobilized and free enzymes was observed in the following properties: the affinity for coenzyme B12; the sensitivity to a sulfhydryl-modifying agent; the absolute requirement for a certain monovalent cation, such as K+, for catalysis; the susceptibility toward oxygen upon incubation with coenzyme B12 in the absence of substrate. These results suggest that the structure and function of the enzyme are not significantly influenced by immobilization on Sepharose. The immobilized enzyme was found to provide a convenient method for a study of ligand interaction with the enzyme. The subunit interaction between two dissimilar subunits, components F and S, was investigated using the component S immobilized on CNBr-activited Sepharose and free component F, and it was demonstrated that the substrate (1,2-propanedoil) promotes the hybrid formation between component F and component S, but K+ alone rather retarded the subunit association to some extent. Na+ markedly weakens the forces which bind the subunits together. The relationship between cobalamin binding and subunit structure is also discussed.
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Cobamidas/metabolismo , Enterobacter/enzimología , Enterobacteriaceae/enzimología , Hidroliasas/metabolismo , Propanodiol Deshidratasa/metabolismo , Apoenzimas/antagonistas & inhibidores , Apoenzimas/metabolismo , Estabilidad de Medicamentos , Calor , Sustancias Macromoleculares , Oxidación-Reducción , Potasio/farmacología , Propanodiol Deshidratasa/antagonistas & inhibidores , Unión Proteica , Sefarosa , Sodio/farmacologíaRESUMEN
Rubella hemagglutination inhibition (HI) antibodies in 266 children with rubella syndrome born in 1965 in the Ryukyu Islands and their mothers were followed for seven years. Titers of rubella HI antibody in the mothers declined slowly, while those in the children declined rapidly up to 40 months of age. Thereafter decline of titers became extremely slow and only seven cases (three per cent) became seronegative for rubella HI antibody. Rubella HI antibody titers seemed to have no particular correlation to the severity of clinical manifestations.