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1.
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
2.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
J Nucl Med ; 49(10): 1606-12, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18794269

RESUMO

UNLABELLED: (18)F-FDG PET is increasingly used for lung cancer; however, some insufficient results have been reported. The purpose of this study was to evaluate the efficacy of dual-time-point (18)F-FDG PET for staging lung cancer and for differentiating metastatic from nonmetastatic lung cancer lesions. METHODS: One hundred fifty-five lung cancer patients with known or suspected mediastinal and hilar lymph node involvement or distant metastases underwent whole-body (18)F-FDG PET at 2 time points: scan 1 at 60 min (early imaging) and scan 2 at 180 min (delayed imaging) after (18)F-FDG injection. (18)F-FDG PET findings of nodal and distant metastases were evaluated using conventional imaging, clinical follow-up findings, and the results of autopsy or biopsy. RESULTS: A total of 580 lesions (155 primary lesions, 315 metastatic lesions, and 110 nonmetastatic lesions) were used for analysis. A closer correlation between the primary lesions and metastases was observed for the retention index (RI) standardized uptake value (SUV) than for early and delayed SUV. There was no relationship between the RI SUV results of primary lesions and those of nonmetastatic lesions. The RI SUV of metastatic lesions was approximately 0.5-2 times the RI SUV of primary tumors. We found that the accuracy of (18)F-FDG PET was improved when RI SUV was used for detecting lymph node and distant metastases, because of the significant improvement in specificity relative to early and delayed SUV. CONCLUSION: RI SUV raised the accuracy for diagnosis of metastases and was superior to early and delayed imaging in terms of differentiating malignancy from nonmetastatic uptake.


Assuntos
Diagnóstico por Imagem/métodos , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico , Estadiamento de Neoplasias/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Idoso , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias/métodos , Estudos Prospectivos , Resultado do Tratamento
11.
Lung Cancer ; 61(2): 227-34, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18243405

RESUMO

The present study examines the significance of defining feeding arteries to arterial infusion chemotherapy for patients with non-small cell lung carcinoma. We retrospectively studied feeding arteries and findings from 32 patients treated by arterial infusion chemotherapy. We graded tumor staining by angiography and compared grade in the bronchial artery with that of total staining in all detected feeding arteries, and investigated the relationship between grade and treatment response. One patient achieved a complete response and 16 achieved a partial response with no serious adverse effects. Many feeding arteries were detected and the grade of total tumor staining in these patients was significantly higher than that of tumor staining in the bronchial artery. The number of lesions that responded was significantly increased among those with a higher grade of total tumor staining. Precise definition of feeding arteries and sufficient tumor staining are vital to ensure a successful outcome of arterial infusion chemotherapy for patients with NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Artérias Brônquicas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Infusões Intra-Arteriais , Neoplasias Pulmonares/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artérias Brônquicas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica , Radiografia , Estudos Retrospectivos , Análise de Sobrevida
12.
Ann Nucl Med ; 22(4): 335-8, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18535887

RESUMO

Several studies have reported the findings of fluorine-18-labeled fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) in benign lung disease with diffuse pulmonary injury; however, the characteristics and effectiveness of FDG-PET imaging for interstitial pneumonitis have not been substantiated. We report two cases of drug-induced pneumonitis in two patients treated for breast cancer who were diagnosed by FDG-PET examination. Both the cases showed diffuse interstitial infiltration in the bilateral lungs on computed tomography, but the degree of FDG accumulation was different. It is probable that the degree of FDG accumulation reflected the activity of the drug-induced pneumonitis. The present cases show very interesting FDG-PET imaging findings of diffuse lung disease.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Pneumonia/diagnóstico por imagem , Idoso , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/etiologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Dibenzotiazepinas/efeitos adversos , Dibenzotiazepinas/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Pneumonia/induzido quimicamente , Pneumonia/fisiopatologia , Tomografia por Emissão de Pósitrons , Fumarato de Quetiapina , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Imagem Corporal Total
13.
Nihon Rinsho ; 66(11): 2077-82, 2008 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-19051723

RESUMO

PPARgamma is a member of a family of nuclear receptors/ligand-dependent transcription factors, which bind to hormone response elements on target gene promoters. An antiproliferative and proapoptotic action profile of PPARgamma has been described, but little is known about the role of PPARgamma in vascular remodeling. We reported a reduced PPARgamma gene and protein expression in the lungs from patients with severe pulmonary hypertension and loss of PPARgamma expression in their complex vascular lesion. We showed that fluid shear stress reduces PPARgamma expression in ECV304 endothelial cells and that ECV304 cells that stably express dominant-negative PPARgamma form lumen-obliterating lung vascular lesion in the artificial capillaries under fluid shear stress and in the intrapulmonary arteries after tail vein injection in nude mice. Recently, there are some evidences that PPARgamma may represent a novel therapeutic target in pulmonary hypertension.


Assuntos
Células Endoteliais/citologia , PPAR gama/fisiologia , Artéria Pulmonar/citologia , Animais , Proliferação de Células , Hipertensão Pulmonar/patologia , Camundongos , Camundongos Nus
14.
Lung Cancer ; 55(2): 241-7, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17098326

RESUMO

Arterial infusion chemotherapy is considered to be a treatment option for lung cancer patients who are intolerant of systemic chemotherapy because of an increased risk of severe toxicity. However, a number of major studies regarding arterial infusion chemotherapy for lung cancer have reported disappointing results. We performed arterial infusion chemotherapy for four patients with advanced NSCLC who were unable to receive systemic chemotherapy or radiotherapy. After detecting the feeding arteries precisely by angiography, low-dose chemotherapeutic agents were administrated into the corresponding arteries. In each case, multiple feeding arteries including main feeding arteries other than the bronchial artery were detected and a partial response (PR) was obtained without severe toxicity in all. We consider that the present method is an effective treatment option for lung cancer patients who are restricted from undergoing standard systemic chemotherapy or radiotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Angiografia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Taxoides/administração & dosagem , Tomografia Computadorizada por Raios X , Gencitabina
15.
Respir Res ; 8: 77, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17974037

RESUMO

BACKGROUND: Hypoxia induces the proliferation of pulmonary arterial smooth muscle cell (PASMC) in vivo and in vitro, and prostacyclin analogues are thought to inhibit the growth of PASMC. Previous studies suggest that p27kip1, a kind of cyclin-dependent kinase inhibitor, play an important role in the smooth muscle cell proliferation. However, the mechanism of hypoxia and the subcellular interactions between p27kip1 and prostacyclin analogues in human pulmonary arterial smooth muscle cell (HPASMC) are not fully understood. METHODS: We investigated the role of p27kip1 in the ability of Beraprost sodium (BPS; a stable prostacyclin analogue) to inhibit the proliferation of HPASMC during hypoxia. To clarify the biological effects of hypoxic air exposure and BPS on HPASMC, the cells were cultured in a hypoxic chamber under various oxygen concentrations (0.1-21%). Thereafter, DNA synthesis was measured as bromodeoxyuridine (BrdU) incorporation, the cell cycle was analyzed by flow cytometry with propidium iodide staining. The p27kip1 mRNA and protein expression and it's stability was measured by real-time RT-PCR and Western blotting. Further, we assessed the role of p27kip1 in HPASMC proliferation using p27kip1 gene knockdown using small interfering RNA (siRNA) transfection. RESULTS: Although severe hypoxia (0.1% oxygen) suppressed the proliferation of serum-stimulated HPASMC, moderate hypoxia (2% oxygen) enhanced proliferation in accordance with enhanced p27kip1 protein degradation, whereas BPS suppressed HPASMC proliferation under both hypoxic and normoxic conditions by suppressing p27kip1 degradation with intracellular cAMP-elevation. The 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP), a cAMP analogue, had similar action as BPS in the regulation of p27kip1. Moderate hypoxia did not affect the stability of p27kip1 protein expression, but PDGF, known as major hypoxia-induced growth factors, significantly decreased p27kip1 protein stability. We also demonstrated that BPS and 8-Br-cAMP suppressed HPASMC proliferation under both hypoxic and normoxic conditions by blocking p27kip1 mRNA degradation. Furthermore, p27kip1 gene silencing partially attenuated the effects of BPS and partially restored hypoxia-induced proliferation. CONCLUSION: Our study suggests that moderate hypoxia induces HPASMC proliferation, which is partially dependent of p27kip1 down-regulation probably via the induction of growth factors such as PDGF, and BPS inhibits both the cell proliferation and p27kip1 mRNA degradation through cAMP pathway.


Assuntos
Epoprostenol/análogos & derivados , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/fisiologia , Oxigênio/metabolismo , Artéria Pulmonar/citologia , Artéria Pulmonar/fisiologia , Hipóxia Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p27 , Relação Dose-Resposta a Droga , Epoprostenol/administração & dosagem , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Vasodilatadores/administração & dosagem
16.
Nihon Kokyuki Gakkai Zasshi ; 45(5): 424-9, 2007 May.
Artigo em Japonês | MEDLINE | ID: mdl-17554988

RESUMO

A 60-year-old woman was referred to our hospital because of an abnormal chest radiograph in May, 2000. She was found to have rheumatoid arthritis in March, 1998, and pharmacologic therapy with anti-rheumatic drug was started. The chest CT scan revealed bilateral multiple lung nodular lesions of various sizes up to 30 mm. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated a lesion with intense FDG activity in the right lung with a standardized uptake value (SUV) of 10.1. Fiberoptic bronchoscopy revealed no endobronchial lesions. Video-assisted thoracoscopic surgery was done to ascertain the pathological diagnosis. Histological examination showed that the pulmonary nodules were composed of amyloid A (AA) protein. Secondary Sjögren syndrome was subsequently diagnosed. A diagnosis of localized nodular pulmonary amyloidosis with AA type amyloid protein was made, and therapy with anti-rheumatic drugs was continued. After six years of therapy, the size of pulmonary amyloidoma was reduced, and the accumulation of FDG returned to normal. We reported this interesting case in which FDG-PET apparently reflected the disease activity of pulmonary amyloidosis.


Assuntos
Amiloidose/diagnóstico por imagem , Fluordesoxiglucose F18 , Pneumopatias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade
17.
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
18.
Circ Res ; 92(10): 1162-9, 2003 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-12714563

RESUMO

PPARgamma is a member of a family of nuclear receptors/ligand-dependent transcription factors, which bind to hormone response elements on target gene promoters. An antiproliferative and proapoptotic action profile of PPARgamma has been described and PPARgamma may function as a tumor suppressor gene, but little is known about the role of PPARgamma in vascular remodeling. One group of human diseases that shows impressive vascular remodeling exclusively in the lungs is the group of severe pulmonary hypertensive disorders, which is characterized by complex, endothelial cell-proliferative lesions of lung precapillary arterioles composed of clusters of phenotypically altered endothelial cells that occlude the vessel lumen and contribute to the elevation of the pulmonary arterial pressure and reduce local lung tissue blood flow. In the present study, we report the ubiquitous PPARgamma expression in normal lungs, and in contrast, a reduced lung tissue PPARgamma gene and protein expression in the lungs from patients with severe PH and loss of PPARgamma expression in their complex vascular lesions. We show that fluid shear stress reduces PPARgamma expression in ECV304 endothelial cells, that ECV304 cells that stably express dominant-negative PPARgamma (DN-PPARgamma ECV304) form sprouts when placed in matrigel and that DN-PPARgamma ECV304 cells, after tail vein injection in nude mice, form lumen-obliterating lung vascular lesions. We conclude that fluid shear stress decreases the expression of PPARgamma in endothelial cells and that loss of PPARgamma expression characterizes an abnormal, proliferating, apoptosis-resistant endothelial cell phenotype.


Assuntos
Endotélio Vascular/metabolismo , Hipertensão Pulmonar/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose , Divisão Celular , Linhagem Celular , Modelos Animais de Doenças , Endotélio Vascular/citologia , Endotélio Vascular/transplante , Feminino , Expressão Gênica , Genes Dominantes , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/patologia , Imuno-Histoquímica , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica/genética , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/patologia , Ratos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/genética , Estresse Mecânico , Fatores de Transcrição/genética , Transfecção
19.
Nihon Kokyuki Gakkai Zasshi ; 44(12): 899-905, 2006 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-17233385

RESUMO

This study evaluated 18F-FDG-PET imaging for the detection of gastrointestinal tract cancer in patients with suspected lung cancer. A total of 351 patients who had abnormal lung shadows and who underwent whole-body FDG-PET between June 1998 and January 2006 were retrospectively entered for analysis. Gastrointestinal tract cancers were subsequently found in 15 patients (4.3%) who had been found to have lung diseases consisting of 7 inflammatory changes, 6 lung cancers, and 2 metastatic lung carcinomas, 9 colon cancers, 4 gastric cancers, and 2 esophageal cancers. Five patients (2 colon cancers, 2 gastric cancers, and 1 esophageal cancer) had early stage carcinoma. In this study, FDG-PET was useful not only for the diagnosis and staging of lung cancer, but also for the detection of unexpected gastrointestinal tract cancers. FDG-PET may be most suitable for cancer screening.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Chest ; 127(4): 1276-82, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15821205

RESUMO

BACKGROUND: As the number of elderly people has increased in Japan, the occurrence of aspiration pneumonia has also increased. Guidelines for the treatment of pneumonia have been proposed, in which the use of antibiotics, such as beta-lactam plus beta-lactamase inhibitor, clindamycin, and carbapenem, has been recommended as effective against anaerobic bacteria in the treatment of aspiration pneumonia. However, to our knowledge, a prospective comparison of these antibiotics regarding their clinical efficacy in aspiration pneumonia has not been performed. STUDY OBJECTIVES: We compared the effects of IV administration of a half dose of ampicillin/sulbactam (SBT/ABPC), normal dose of SBT/ABPC, IV clindamycin, and IV panipenem/betamiprom (PAPM/BP) for treatment of mild-to-moderate aspiration pneumonia in elderly patients. DESIGN: Randomized prospective study. PATIENTS: One hundred adult patients with compatible signs and symptoms of aspiration pneumonia. ASSESSMENTS: Patients were assessed before, during, and after treatment regarding symptoms, as well as results of laboratory values, chest radiograph examinations, and sputum bacterial cultures. RESULTS: We found few differences between the groups regarding cure rate, duration of IV medication, and occurrence of adverse effects with the tested therapies. However, clindamycin therapy was less expensive and was associated with a lower rate of posttreatment occurrence of methicillin-resistant Staphylococcus aureus. CONCLUSIONS: Clindamycin therapy for mild-to-moderate aspiration pneumonia is clinically effective, and provides economic advantages as compared to SBT/ABPC or PAPM/BP therapy.


Assuntos
Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Clindamicina/administração & dosagem , Pneumonia Aspirativa/tratamento farmacológico , Sulbactam/administração & dosagem , Tienamicinas/administração & dosagem , beta-Alanina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intravenosas , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , beta-Alanina/análogos & derivados
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