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1.
J Immunother Cancer ; 8(1)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32345624

RESUMO

BACKGROUND: The early response to treatment with immune-checkpoint inhibitors is difficult to evaluate. We determined whether changes in integrated [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/MRI (18F-FDG PET/MRI) parameters after the first 2 weeks of antiprogrammed death-1 antibody nivolumab therapy could predict the response of patients with non-small cell lung cancer (NSCLC). METHODS: Twenty-five patients with previously treated NSCLC were enrolled prospectively and underwent 18F-FDG PET/MRI before and at 2 weeks after nivolumab therapy. Changes in maximal standardized uptake value, total lesion glycolysis (ΔTLG) and apparent diffusion coefficient (ΔADC) between the two scans were calculated and evaluated for their associations with the clinical response to therapy. RESULTS: The disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLG, increased ADCmean (ie, negative ΔADCmean) and lower ΔTLG+ΔADCmean than patients with PD. Among the parameters tested, receiver operating characteristic curve analysis revealed that a cut-off value of 16.5 for ΔTLG+ΔADCmean had the highest accuracy (92%) for distinguishing between patients with non-PD and PD. A ΔTLG+ΔADCmean value <16.5 was significantly associated with longer median progression-free survival (9.0 vs 1.8 months, p<0.00001) and overall survival (23.6 vs 4.7 months, p=0.0001) compared with ΔTLG+ΔADCmean value ≥16.5. A multivariate Cox model revealed that ≥16.5 ΔTLG+ΔADCmean was an independent predictor of shorter progression-free survival (HR 37.7) and overall survival (HR 9.29). CONCLUSIONS: A combination of ΔTLG and ΔADCmean measured by integrated 18F-FDG PET/MRI may have value as a predictor of the response and survival of patients with NSCLC following nivolumab therapy. TRIAL REGISTRATION NUMBER: UMIN 000020707.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fluordesoxiglucose F18/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Nivolumabe/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/farmacologia , Resultado do Tratamento
2.
Eur Radiol ; 29(7): 3908-3917, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30972546

RESUMO

OBJECTIVES: Although hematological toxicities (HT) are the leading adverse events of systemic chemotherapy, the estimation of severe HT is challenging. Recently, 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) accumulation with PET has been considered a biomarker of the cell proliferation. This study aims to elucidate whether the vertebral accumulation of 18F-FLT could estimate severe HT during platinum-doublet chemotherapy. METHODS: In this Institutional Review Board-approved retrospective study, 50 patients with primary lung cancer underwent 18F-FLT PET scan before platinum-doublet chemotherapy. We evaluated the standardized uptake value, total vertebral proliferation (TVP), and TVP/body surface area (TVP/BSA) of the vertebral body (Th4, Th8, Th12, and L4), and then the associations between those parameters and frequency of severe HT during platinum-doublet chemotherapy were assessed. RESULTS: Severe HT (grade 3/4) was observed in 40.0% of patients during the first cycle. The ROC curve analyses revealed that the TVP/BSA of L4 was the most discriminative parameter among PET parameters for the prediction of severe HT. The multivariate logistic regression analysis revealed the TVP/BSA of L4 (odds ratio [OR], 0.94; p = 0.0036) and the frequency of the grade 3/4 hematological toxicity in previous clinical trials (OR, 1.03; p = 0.023) were independent predictors. Furthermore, the sensitivity, specificity, and accuracy of the TVP/BSA of L4 cut-off of 68.7 to predict grade 3/4 HT were 80.0%, 86.7%, and 84.0%, respectively. A low TVP/BSA of L4 (< 68.7) as a binary variable was a significant indicator of severe HT (OR, 26.0; p = 0.000026). CONCLUSIONS: The low 18F-FLT uptake in the lower vertebral body is a predictor of severe HT in patients with lung cancer who receive platinum-doublet chemotherapy. TRIAL REGISTRATION: Trial registration: UMIN000027540 KEY POINTS: • The vertebral 18 F-FLT uptake with PET is an independent predictor of the severe hematological toxicity during the first cycle of platinum-doublet chemotherapy. • The 18 F-FLT uptake in L4 vertebral body estimated hematological toxicities better than that in the upper vertebra (Th4, Th8, and Th12). • The evaluation of the amount and activity of hematopoietic cells in the bone marrow cavity using 18 F-FLT PET imaging could provide predictive data of severe hematological toxicities and help determine an appropriate drug combination or dose intensity in patients with advanced malignant diseases.


Assuntos
Antineoplásicos/efeitos adversos , Quimiorradioterapia/métodos , Radioisótopos de Flúor/metabolismo , Neoplasias Pulmonares/terapia , Adulto , Idoso , Proliferação de Células , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Platina/administração & dosagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
4.
Medicine (Baltimore) ; 96(51): e9320, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29390506

RESUMO

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX), which avoids toxicities associated with a vehicle used in solvent-based PTX, has already shown safety and efficacy in patients with non-small cell lung cancer (NSCLC). METHODS: A phase II study was performed to assess the safety and efficacy of nab-PTX monotherapy as second-line chemotherapy after cytotoxic anticancer drugs for previously treated advanced NSCLC. Thirty-two patients with advanced NSCLC who had previously undergone 1 regimen of cytotoxic anticancer drugs were enrolled. Nab-PTX was administered intravenously at a dose of 100 mg/m on days 1, 8, and 15 of a 28-day cycle. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and toxicity profile were evaluated. RESULTS: The ORR was 28.1%, the DCR was 71.9%, median PFS was 3.9 months (95% confidence interval [CI] 2.7-5.1 months), and median OS was 10.9 months (95% CI 9.5-12.3 months). The mean relative dose intensity of nab-PTX was 77%. Grade 3 or 4 neutropenia, and grade 3 febrile neutropenia were observed in 11 and 1 of 32 patients, respectively. As nonhematologic toxicities, grade 3 peripheral sensory neuropathy and pneumonitis were each observed in 2 of 32 patients. CONCLUSION: Nab-PTX is an active and well-tolerated regimen in patients with previously treated NSCLC.


Assuntos
Paclitaxel Ligado a Albumina/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anemia/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Pneumonia/induzido quimicamente , Terapia de Salvação
5.
Arerugi ; 65(2): 134-7, 2016 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-27086960

RESUMO

A 62-year-old man was admitted to our hospital because of wheezing and dyspnea. Chest computed tomography showed ground-glass opacity and some centrilobular nodules. Chronic eosinophilic pneumonia complicated with Mycoplasma pneumoniae infection was diagnosed on the basis of bronchoalveolar lavage eosinophilia and blood findings. However, based on the clinical course, the patient was suspected to have eosinophilic bronchiolitis. This case suggests the possibility that eosinophilic inflammation can occur concomitantly in the central airway and distal airway.


Assuntos
Asma/complicações , Bronquiolite/complicações , Eosinofilia/complicações , Eosinofilia Pulmonar/complicações , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Nucl Med ; 56(12): 1869-75, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26359263

RESUMO

UNLABELLED: The aim of this prospective study was to clarify whether dual-time-point (18)F-FDG PET imaging results are useful to predict long-term survival of idiopathic pulmonary fibrosis (IPF) patients. METHODS: Fifty IPF patients underwent (18)F-FDG PET examinations at 2 time points: 60 min (early imaging) and 180 min (delayed imaging) after (18)F-FDG injection. The standardized uptake value (SUV) at each point and retention index value (RI-SUV) calculated from those were evaluated, and then the results were compared with overall and progression-free survival. RESULTS: A multivariate Cox proportional hazards model showed higher RI-SUV and higher extent of fibrosis score as independent predictors of shorter progression-free survival. The median progression-free survival for patients with negative RI-SUV was better than that for those with positive RI-SUV (27.9 vs. 13.3 mo, P = 0.0002). On the other hand, multivariate Cox analysis showed higher RI-SUV and lower forced vital capacity to be independent predictors of shorter overall survival. The 5-y survival rate for patients with negative RI-SUV was better than that for those with positive RI-SUV (76.8% vs. 14.3%, P = 0.00001). In addition, a univariate Cox model showed that positive RI-SUV as a binary variable was a significant indicator of mortality (hazard ratio, 7.31; 95% confidence interval, 2.64-20.3; P = 0.0001). CONCLUSION: Our results demonstrate that positive RI-SUV is strongly predictive of earlier deterioration of pulmonary function and higher mortality in patients with IPF.


Assuntos
Fluordesoxiglucose F18 , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Intervalo Livre de Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Processamento de Imagem Assistida por Computador , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X
8.
J Asthma Allergy ; 7: 131-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25228816

RESUMO

BACKGROUND: Losing the sense of smell, which suggests eosinophilic rhinosinusitis, is a subjective symptom, sometimes reported in asthmatic patients taking controller medication. Upper abdominal symptoms, suggesting gastroesophageal reflux disease (GERD) or functional dyspepsia, occur also in these patients. However, the relationship between these symptoms, concomitant with asthma, and the intensity of eosinophilic airway inflammation remains obscure. OBJECTIVE: To assess the symptoms of asthma and rhinosinusitis, and to examine the relationship between the symptoms and bronchial inflammation, a new questionnaire, the G scale, was developed. To investigate the effects of GERD, dyspepsia, and rhinosinusitis on asthma symptoms and bronchial inflammation, the symptoms of asthma and rhinosinusitis obtained by the G scale, upper abdominal symptoms obtained by the modified F scale, a questionnaire for GERD and dyspepsia, and fractional exhaled nitric oxide (FeNO) were analyzed. METHODS: A prospective, observational study was performed in four hospitals in Gunma prefecture, and a retrospective analysis was done using data obtained from five hospitals in Gunma prefecture and Fukui prefecture, Japan. A total of 252 patients diagnosed as having asthma participated in the prospective study. RESULTS: The frequency of daytime phlegm or losing the sense of smell had a positive correlation with FeNO levels in asthmatic patients taking controller medication. Upper abdominal symptoms, as well as symptoms suggesting rhinitis, were well correlated with asthma symptoms. However, neither upper abdominal symptoms nor rhinitis symptoms increased FeNO levels, which reflect eosinophilic airway inflammation during treatment for asthma. On the other hand, the degree of upper abdominal symptoms or dyspepsia symptoms had a weak but significant negative correlation with FeNO levels. CONCLUSION: Daytime phlegm and losing the sense of smell suggest that eosinophilic airway inflammation persists, despite anti-inflammatory therapy, in patients with asthma. Although rhinitis and GERD made the subjective symptoms of asthma worse, they did not seem to enhance eosinophilic airway inflammation.

9.
Lung Cancer ; 85(1): 47-52, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24775095

RESUMO

OBJECTIVES: Recent advances in endobronchial ultrasonography with a guide sheath (EBUS-GS) have enabled better visualization of distal airways, while virtual bronchoscopic navigation (VBN) has been shown useful as a guide to navigate the bronchoscope. However, indications for utilizing VBN and EBUS-GS are not always clear. To clarify indications for a bronchoscopic examination using VBN and EBUS-GS, we evaluated factors that predict the diagnostic yield of a transbronchial biopsy (TBB) procedure for peripheral lung cancer (PLC) lesions. METHODS: We retrospectively reviewed the charts of 194 patients with 201 PLC lesions (≤3cm mean diameter), and analyzed the association of diagnostic yield of TBB with [(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron emission tomography and chest computed tomography (CT) findings. RESULTS: The diagnostic yield of TBB using VBN and EBUS-GS was 66.7%. High maximum standardized uptake value (SUVmax), positive bronchus sign, and ground-glass opacity component shown on CT were all significant predictors of diagnostic yield, while multivariate analysis showed only high (18)F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign as significant predictors. Diagnostic yield was higher for PLC lesions with high (18)F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign (84.6%) than for those with SUVmax <2.8 and negative bronchus sign (33.3%). High (18)F-FDG uptake was also correlated with tumor invasiveness. CONCLUSIONS: High (18)F-FDG uptake predicted the diagnostic yield of TBB using VBN and EBUS-GS for PLC lesions. (18)F-FDG uptake and bronchus sign may indicate for the accurate application of bronchoscopy with those modalities for diagnosing PLC.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Adenocarcinoma/patologia , Biópsia , Bronquíolos/patologia , Broncoscopia , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Pulmonares/patologia , Cintilografia , Estudos Retrospectivos
10.
Clin Lung Cancer ; 13(6): 458-63, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22402083

RESUMO

INTRODUCTION: Salvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non-small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies. MATERIALS AND METHODS: This study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non-small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate. RESULTS: Twenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% CI, 3.21-37.9) and 45% (95% CI, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% CI, 0.9-3.1 months) and 12.0 months (95% CI, 8.0-16.0 months), respectively. CONCLUSION: These results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Retratamento , Terapia de Salvação , Taxa de Sobrevida , Resultado do Tratamento
11.
Respir Med ; 105(12): 1931-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21903371

RESUMO

BACKGROUND: Relationships among clinical, physiological, imaging and pathological findings of small airway disease associated with Sjögren's syndrome have remained unclear. SUBJECTS AND METHODS: We retrospectively studied 14 patients who underwent surgical lung biopsy and who were diagnosed with small airway disease associated with primary or secondary Sjögren's syndrome. We compared clinical, bronchoalveolar lavage, physiological, imaging and pathological findings between primary and secondary Sjögren's syndrome. We scored HRCT and pathological abnormalities and investigated correlations among physiological, HRCT and pathological data, changes in physiological parameters and in HRCT scores after two years of treatment, as well as correlations between these values and pathological scores. RESULTS: Bronchoalveolar lavage fluid, physiological, imaging and pathological findings of the airways did not significantly differ between primary and secondary Sjögren's syndrome. Air trapping on HRCT negatively correlated with MEF50 and MEF25. Although lymphoid cell infiltration and peribronchiolar fibrosis were the most common pathologies, constrictive change scores correlated negatively with MEF50 and MEF25, positively with air trapping scores and negatively with improvements after therapy in MEF(50), MEF(25) and air trapping. CONCLUSIONS: Constrictive change was the most significant determinant of physiological and imaging presentations and of changes in these factors after therapy for small airway disease associated with Sjögren's syndrome.


Assuntos
Líquido da Lavagem Broncoalveolar , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Pulmão/patologia , Síndrome de Sjogren/diagnóstico por imagem , Síndrome de Sjogren/patologia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Biópsia , Feminino , Humanos , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Síndrome de Sjogren/imunologia
12.
Clin Lung Cancer ; 12(6): 387-92, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21729650

RESUMO

UNLABELLED: Efficacy of first-line gefitinib for elderly epidermal growth factor receptor mutated patients with lung adenocarcinoma is uncertain. This study was aimed to investigate efficacy of gefitinib for such population. The primary endpoint was response rate (RR) and at least 12 cases were needed. Overall RR was 59% (95% confidence interval, 33%-81%) and first-line gefitinib was effective for elderly patients. INTRODUCTION: Feasibility of gefitinib therapy in elderly patients with non-small-cell lung cancer is uncertain. This phase II study aimed to investigate the efficacy and usefulness of gefitinib therapy as a first-line treatment for elderly patients who have advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. PATIENTS AND METHODS: We enrolled chemotherapy-naïve advanced lung adenocarcinoma patients aged 75 years or older. Patients were administered gefitinib (250 mg) once daily until progression or unacceptable toxicity. The primary endpoint was response rate (RR), and secondary endpoints were disease control rate (DCR; defined as complete response [CR] plus partial response [PR] plus stable disease [SD]), progression-free survival (PFS), overall survival (OS), and toxicity profile. RESULTS: Between April 2008 and November 2009, 17 lung adenocarcinoma patients were enrolled. Overall RR was 59% (95% confidence interval [CI]: 33% to 81%), with 2 patients achieving CR and 8 PR. SD was noted in 5 patients, and DCR was 88% (95% CI: 62% to 98%). Median PFS was 12.9 months (95% CI: 2.2 to 23.6 months), and median OS had not yet been reached. Major grade 3 toxicities were skin rash (12%) and increased levels of aspartate aminotransferase or alanine aminotransferase (18%). CONCLUSION: First-line treatment with gefitinib was effective and well-tolerated in elderly patients with EGFR mutations.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Mutação/genética , Quinazolinas/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
13.
Respirology ; 16(4): 713-20, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21382131

RESUMO

BACKGROUND AND OBJECTIVE: The value of dual-time- point (18) F-FDG PET was investigated to predict the prognosis of patients with pulmonary sarcoidosis. METHODS: Twenty-one patients with pulmonary sarcoidosis underwent (18) F-FDG PET examinations at two time points: an early scan at 60min and a delayed scan at 180min after injection of (18) F-FDG. Standardized uptake values (SUVs) at the two time points and the retention index (RI-SUV) calculated from these were evaluated. To evaluate disease progression, all patients underwent chest CT 1year after (18) F-FDG PET. Using these results, the accuracy of (18) F-FDG PET parameters and (67) Ga uptake for predicting disease persistence were compared, and the correlations between those parameters and serum markers were assessed. RESULTS: RI-SUV was significantly higher in patients with increased or unchanged pulmonary lesions at follow-up CT (persistent group; 21.3±9.6%) than in patients with improved pulmonary lesions (improved group; -9.2±28.6%, P=0.0075). The diagnostic accuracy of RI-SUV in the persistent group was significantly greater than that of early SUV or (67) Ga uptake, and serum soluble IL-2 receptor showed a significant correlation with RI-SUV. CONCLUSIONS: RI-SUV showed better diagnostic accuracy compared with early SUV or (67) Ga uptake, in patients with persistent lung involvement at 1year. It may be a useful measure of persistent inflammation in patients with pulmonary sarcoidosis.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Sarcoidose Pulmonar/diagnóstico , Adulto , Feminino , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Radiografia Torácica/métodos , Receptores de Interleucina-2/sangue , Tomografia Computadorizada por Raios X/métodos
14.
Lung Cancer ; 73(3): 289-93, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21320735

RESUMO

In humans, aromatase (CYP19) gene expression is regulated via alternative promoters. Activation of each promoter gives rise to a CYP19 mRNA species with a unique 5'-untranslated region. Inhibition of aromatase has been reported to downregulate lung tumor growth. The genetic basis for CYP19 gene expression and aromatase activity in lung cancer remains poorly understood. We analyzed tissues from 15 patients with non-small cell lung cancer (NSCLC) to evaluate CYP19 promoter usage and promoter-specific aromatase mRNA levels in NSCLC tumor tissues and adjacent non-malignant tissues. CYP19 promoter usage was determined by multiplex RT-PCR and aromatase mRNA levels were measured with real-time RT-PCR. In non-malignant tissues, aromatase mRNA was primarily derived from activation of CYP19 promoter I.4. Although promoter I.4 usage was also dominant in tumor tissues, I.4 activation was significantly lower compared with adjacent non-malignant tissues. Activity of promoters I.3, I.1 and I.7 was significantly higher in tumor tissues compared with non-malignant tissues. In 4 of 15 cases of non-small cell lung cancer, switching from CYP19 promoter I.4 to the alternative promoters II, I.1 or I.7 was observed. In 9 cases, there were significantly higher levels of aromatase mRNA in lung tumor tissues compared with adjacent non-malignant tissues. These findings suggest aberrant activation of alternative CYP19 promoters that may lead to upregulation of local aromatase expression in some cases of NSCLC. Further studies are needed to examine the impact of alternative CYP19 promoter usage on local estrogen levels and lung tumor growth.


Assuntos
Aromatase/metabolismo , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Neoplasias Pulmonares/enzimologia , Pulmão/metabolismo , Regiões Promotoras Genéticas/genética , Adulto , Idoso , Processamento Alternativo , Aromatase/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Ativação Transcricional
15.
Intern Med ; 49(21): 2333-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21048370

RESUMO

We report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) after pandemic influenza (H1N1) vaccination. A 57-year-old man, who had been diagnosed with IPF in September 2008, was admitted to our hospital in December 2009 because of aggravation of dyspnea and fever two days after H1N1 vaccination. Chest computed tomography showed diffuse bilateral ground-glass opacities superimposed on preceding reticular opacities. We diagnosed AE-IPF. Corticosteroid and cyclophosphamide were effective. Although the efficacy of influenza vaccination in patients with chronic lung diseases is well established, physicians should keep in mind that influenza vaccination has the potential to cause AE-IPF.


Assuntos
Progressão da Doença , Fibrose Pulmonar Idiopática/diagnóstico , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/efeitos adversos , Doença Aguda , Humanos , Fibrose Pulmonar Idiopática/imunologia , Vacinas contra Influenza/imunologia , Masculino , Pessoa de Meia-Idade
16.
Eur J Radiol ; 73(3): 545-50, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19167853

RESUMO

BACKGROUND: To diagnose sputum smear-negative pulmonary tuberculosis (PTB) is difficult and the ability of high-resolution computed tomography (HRCT) for diagnosing PTB has remained unclear in the sputum smear-negative setting. We retrospectively investigated whether or not this imaging modality can predict risk for sputum smear-negative PTB. METHODS: We used HRCT to examine the findings of 116 patients with suspected PTB despite negative sputum smears for acid-fast bacilli (AFB). We investigated their clinical features and HRCT-findings to predict the risk for PTB by multivariate analysis and a combination of HRCT findings by stepwise regression analysis. We then designed provisional HRCT diagnostic criteria based on these results to rank the risk of PTB and blinded observers assessed the validity and reliability of these criteria. RESULTS: A positive tuberculin skin test alone among clinical laboratory findings was significantly associated with an increase of risk of PTB. Multivariate regression analysis showed that large nodules, tree-in-bud appearance, lobular consolidation and the main lesion being located in S1, S2, and S6 were significantly associated with an increased risk of PTB. Stepwise regression analysis showed that coexistence of the above 4 factors was most significantly associated with an increase in the risk for PTB. Ranking of the results using our HRCT diagnostic criteria by blinded observers revealed good utility and agreement for predicting PTB risk. CONCLUSIONS: Even in the sputum smear-negative setting, HRCT can predict the risk of PTB with good reproducibility and can select patients having a high probability of PTB.


Assuntos
Tomografia Computadorizada por Raios X/métodos , Tuberculose Pulmonar/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Regressão , Estudos Retrospectivos , Risco , Escarro/microbiologia , Teste Tuberculínico , Tuberculose Pulmonar/microbiologia
17.
Respir Res ; 10: 17, 2009 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-19267931

RESUMO

BACKGROUND: Hypoxia induces the proliferation of lung fibroblasts in vivo and in vitro. However, the subcellular interactions between hypoxia and expression of tumor suppressor p53 and cyclin-dependent kinase inhibitors p21 and p27 remain unclear. METHODS: Normal human lung fibroblasts (NHLF) were cultured in a hypoxic chamber or exposed to desferroxamine (DFX). DNA synthesis was measured using bromodeoxyuridine incorporation, and expression of p53, p21 and p27 was measured using real-time RT-PCR and Western blot analysis. RESULTS: DNA synthesis was increased by moderate hypoxia (2% oxygen) but was decreased by severe hypoxia (0.1% oxygen) and DFX. Moderate hypoxia decreased p21 synthesis without affecting p53 synthesis, whereas severe hypoxia and DFX increased synthesis of both p21 and p53. p27 protein expression was decreased by severe hypoxia and DFX. Gene silencing of p21 and p27 promoted DNA synthesis at ambient oxygen concentrations. p21 and p53 gene silencing lessened the decrease in DNA synthesis due to severe hypoxia or DFX exposure. p21 gene silencing prevented increased DNA synthesis in moderate hypoxia. p27 protein expression was significantly increased by p53 gene silencing, and was decreased by wild-type p53 gene transfection. CONCLUSION: These results indicate that in NHLF, severe hypoxia leads to cell cycle arrest via the p53-p21 pathway, but that moderate hypoxia enhances cell proliferation via the p21 pathway in a p53-independent manner. In addition, our results suggest that p27 may be involved in compensating for p53 in cultured NHLF proliferation.


Assuntos
Proliferação de Células , Fibroblastos/metabolismo , Pulmão/metabolismo , Oxigênio/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Ciclo Celular , Hipóxia Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27 , Replicação do DNA , Desferroxamina/farmacologia , Fibroblastos/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Quelantes de Ferro/farmacologia , Pulmão/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transfecção , Proteína Supressora de Tumor p53/genética
18.
Eur J Nucl Med Mol Imaging ; 36(7): 1121-30, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19247654

RESUMO

PURPOSE: Individual clinical courses of idiopathic interstitial pneumonia (IIP) are variable and difficult to predict because the pathology and disease activity are contingent, and chest computed tomography (CT) provides little information about disease activity. In this study, we applied dual-time-point [(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET), commonly used for diagnosis of malignant tumours, to the differential diagnosis and prediction of disease progression in IIP patients. METHODS: Fifty patients with IIP, including idiopathic pulmonary fibrosis (IPF, n = 21), non-specific interstitial pneumonia (NSIP, n = 18) and cryptogenic organizing pneumonia (COP, n = 11), underwent (18)F-FDG PET examinations at two time points: scan 1 at 60 min (early imaging) and scan 2 at 180 min (delayed imaging) after (18)F-FDG injection. The standardized uptake values (SUV) at the two points and the retention index (RI-SUV) calculated from them were evaluated and compared with chest CT findings, disease progression and disease types. To evaluate short-term disease progression, all patients were examined by pulmonary function test every 3 months for 1 year after (18)F-FDG PET scanning. RESULTS: The early SUV for COP (2.47 +/- 0.74) was significantly higher than that for IPF (0.99 +/- 0.29, p = 0.0002) or NSIP (1.22 +/- 0.44, p= 0.0025). When an early SUV cut-off value of 1.5 and greater was used to distinguish COP from IPF and NSIP, the sensitivity, specificity and accuracy were 90.9, 94.3 and 93.5%, respectively. The RI-SUV for IPF and NSIP lesions was significantly greater in patients with deteriorated pulmonary function after 1 year of follow-up (progressive group, 13.0 +/- 8.9%) than in cases without deterioration during the 1-year observation period (stable group, -16.8 +/- 5.9%, p < 0.0001). However, the early SUV for all IIP types provided no additional information of disease progression. When an RI-SUV cut-off value of 0% and greater was used to distinguish progressive IIPs from stable IIPs, the sensitivity, specificity and accuracy were 95.5, 100 and 97.8%, respectively. CONCLUSION: Early SUV and RI-SUV obtained from dual-time-point (18)F-FDG PET are useful parameters for the differential diagnosis and prediction of disease progression in patients with IIP.


Assuntos
Fluordesoxiglucose F18 , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Pneumonias Intersticiais Idiopáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Radiografia Torácica , Tórax/diagnóstico por imagem , Tórax/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios X
19.
Eur J Nucl Med Mol Imaging ; 36(4): 632-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19093113

RESUMO

PURPOSE: To evaluate the usefulness of (18)F-FDG PET in the imaging of pulmonary lesions related to disease activity and in monitoring responses to treatment in patients with pulmonary mycobacteriosis (PM). MATERIALS AND METHODS: We used high-resolution computed tomography (HRCT) and (18)F-FDG PET to evaluate 47 consecutive untreated patients with PM, 25 with tuberculosis (TB) and 22 with Mycobacterium avium-intracellulare complex (MAC), who presented with small peripheral pulmonary nodules

Assuntos
Fluordesoxiglucose F18/farmacologia , Pneumopatias/diagnóstico por imagem , Pneumopatias/diagnóstico , Infecções por Mycobacterium/diagnóstico por imagem , Infecções por Mycobacterium/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tuberculoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nódulo Pulmonar Solitário/patologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Tuberculoma/patologia
20.
J Nucl Med ; 50(1): 81-7, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19091887

RESUMO

UNLABELLED: The purpose of this study was to compare the efficacy of short-tau inversion-recovery (STIR) MRI and 18F-FDG PET/CT for the detection of metastasis in mediastinal and hilar lymph nodes in patients with lung cancer. METHODS: Ninety-three patients with known or suspected lung cancer with mediastinal and hilar lymph node swelling underwent STIR MRI and 18F-FDG PET/CT examinations. STIR MRI scans were obtained with a 2% copper sulfate phantom placed along the back of each patient, with the lymph node-to-phantom ratio calculated for quantitative analysis. For qualitative analysis, the results of all STIR MRI scans were evaluated using a 5-point visual scoring system. To evaluate the diagnostic capabilities of STIR MRI and 18F-FDG PET/CT, we used receiver-operating-characteristic curve analysis to determine the optimal thresholds for the lymph node-to-phantom ratio, visual score, and maximal standardized uptake value. Further, the capability of each to determine N-stage was compared in each patient using the McNemar test. RESULTS: A total of 137 lymph nodes (82 malignant lesions, 55 benign lesions) were analyzed. When optimal threshold values were adopted, the quantitative and qualitative sensitivity, specificity, and accuracy of STIR MRI were not significantly different from those of 18F-FDG PET/CT. However, 18F-FDG PET/CT in combination with qualitative STIR MRI analysis had a significantly higher capability to detect nodal involvement on an individual-patient basis (96.9% specificity, 90.3% accuracy) than did 18F-FDG PET/CT alone (65.6% specificity, 81.7% accuracy). CONCLUSION: We found that the diagnostic capability of STIR MRI was not significantly different from that of 18F-FDG PET/CT. However, when those methods were combined, the diagnostic capability for N-staging was significantly improved.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/patologia , Metástase Linfática/diagnóstico por imagem , Radiografia Torácica , Tórax/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática/patologia , Imageamento por Ressonância Magnética , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/secundário , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons , Sensibilidade e Especificidade , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X
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