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1.
Asian J Endosc Surg ; 15(3): 705-708, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35322560

RESUMEN

A 60-year-old woman with an abnormality discovered during a chest X-ray was referred to the authors' hospital for diagnosis and treatment. Upon enhanced computed tomography (CT), endoscopic ultrasonography, and magnetic resonance imaging, a tumor on the left side of the lower thoracic esophagus was detected. We diagnosed mediastinum cyst. One year after the first visit, a CT examination confirmed an increase in lesion size. Therefore, surgery was performed using a left thoracoscopic approach in the prone position. Before surgery, 3D models were used for simulation. Excision was performed without leakage of the contents. The histopathological diagnosis was a bronchogenic cyst. The left thoracoscopic surgery in the prone position is an uncommon approach but is useful for resecting tumors in the left side of the lower mediastinum. The authors were well-prepared and able to perform safe and reliable surgery.


Asunto(s)
Quiste Broncogénico , Quiste Broncogénico/diagnóstico por imagen , Quiste Broncogénico/cirugía , Esófago/cirugía , Femenino , Humanos , Mediastino/cirugía , Persona de Mediana Edad , Posición Prona , Toracoscopía
2.
Kyobu Geka ; 72(4): 321-323, 2019 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-31266919

RESUMEN

Pulmonary epithelioid hemangioendthelioma(PEH) is rare malignant disease known to originate from hemangioendthelial cells. We report a case of PEH that is difficult to differential diagnosis on image. A 55-year-old woman was diagnosed with malignant lymphoma 15 years ago and had been followed-up. She referred to our hospital due to abnormal shadow on chest X-ray. Multiple nodules of 0.2~1.0 cm in size with clear but irregular margin were found in bilateral lungs on chest computed tomography(CT) scan. Nodules were found to be increased both in size and in number compared to those of 10 years ago. Pulmonary metastases of lymphoma, lung cancer or granulomatous disease were suspected and a thoracoscopic lung biopsy was performed, which led to a diagnosis of PEH pathologically.


Asunto(s)
Hemangioendotelioma Epitelioide , Hemangioendotelioma , Neoplasias Pulmonares , Femenino , Humanos , Pulmón , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
3.
Gen Thorac Cardiovasc Surg ; 67(4): 370-371, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30610473

RESUMEN

Bronchial anastomosis is an important part of successful bronchoplasty, but it takes time to achieve stable results because of few opportunities to do it. To ensure a stable outcome, we have applied some tips for bronchial anastomosis. One of the tips is the use of a suture holder to obtain appropriate suture pitches, adjusting the discrepancy of the bronchial diameter, and another one is the use of a tourniquet to obtain an adequate tension upon tying the knots, ensuring good operative view.


Asunto(s)
Bronquios/cirugía , Enfermedades Pulmonares/cirugía , Técnicas de Sutura , Torniquetes , Anastomosis Quirúrgica/métodos , Humanos , Procedimientos de Cirugía Plástica , Procedimientos Quirúrgicos Torácicos
4.
Kyobu Geka ; 69(3): 245-7, 2016 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-27075295

RESUMEN

A case of pericardial cavernous hemangioma is presented. A 62-year-old man had a chest pain and was referred to our hospital because of an abnormal shadow in the mediastinum. Chest computed tomography showed a hypervascular tumor of 2.0 cm in size at the left side of pulmonary artery. Magnetic resonance imaging findings suggested the mucinous part of the tumor, suggesting liposarcoma, thymoma, and neurinoma etc. At surgery, the tumor was found to be in the pericardial cavity. After pericardotomy, the tumor was resected. The diagnosis of the tumor was cavernous hemangioma. There was no evidence of recurrence 2 years after the operation.


Asunto(s)
Neoplasias Cardíacas/cirugía , Hemangioma Cavernoso/cirugía , Pericardio , Neoplasias Cardíacas/diagnóstico , Hemangioma Cavernoso/diagnóstico , Humanos , Masculino , Persona de Mediana Edad
5.
Eur J Cardiothorac Surg ; 49(4): 1063-7, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26324682

RESUMEN

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) lobectomy is classified into hybrid VATS (direct and video vision) and thoracoscopic VATS (video vision only). In this study, the outcomes of hybrid VATS and thoracoscopic VATS for clinical stage I lung cancer were compared using a propensity score-matching analysis. METHODS: Hybrid and thoracoscopic VATS were performed in 178 and 76 patients, respectively. Propensity scores were calculated using logistic regression analysis and matched within a score of ±0.03 for age, sex, size of tumour, Charlson comorbidity index, preoperative therapy, percent vital capacity, forced expiratory volume in 1 s, clinical stage, pathological stage and histology. RESULTS: In the non-matched analysis, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean age, 69 ± 9 and 66 ± 10 years (P = 0.04); tumour size, 24 ± 10 and 20 ± 7 mm (P < 0.01); 2-deoxy-2 [F-18]fluorodeoxyglucose positron emission tomography SUV, 5.6 ± 4.4 and 3.6 ± 3.2 (P < 0.01); clinical stage (IA/IB), 130/48 and 69/7 (P < 0.01); pathological stage (IA/IB/IIA and IIB/IIIA and IIIB), 89/56/15/18 and 57/14/2/3 (P < 0.01); postoperative complications, 66 (37.1%) and 16 (21.1%; P = 0.01); respiratory complications, 32 (18.0%) and 6 (7.9%; P = 0.04); 5-year overall survival (OS), 77.0 and 88.8% (log-rank P = 0.045); and 5-year disease-free survival (DFS), 67.2 and 81.1% (log-rank P = 0.02). In 66 matched cases, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean operative time, 245 ± 96 and 285 ± 85 min (P = 0.01); blood loss, 95 ± 100 and 86 ± 123 ml (P = 0.67); mean duration of drainage, 3.6 ± 2.7 and 3.2 ± 2.2 days (P = 0.37); postoperative complications, 21 (31.8%) and 14 (21.2%; P = 0.17); respiratory complications, 11 (16.7%) and 5 (7.6%; P = 0.11); 5-year OS, 72.5 and 86.0% (log-rank P = 0.25); and 5-year DFS, 68.4 and 77.2% (log-rank P = 0.17). CONCLUSIONS: In this single-institution, propensity score-matched study, hybrid VATS showed a shorter operative time and similar outcomes compared with thoracoscopic lobectomy for clinical stage IA lung cancer.


Asunto(s)
Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Neumonectomía/estadística & datos numéricos , Cirugía Torácica Asistida por Video/métodos , Cirugía Torácica Asistida por Video/estadística & datos numéricos , Anciano , Estudios de Cohortes , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Neumonectomía/mortalidad , Puntaje de Propensión , Análisis de Supervivencia , Cirugía Torácica Asistida por Video/mortalidad
6.
Intern Med ; 54(16): 1977-80, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26278287

RESUMEN

OBJECTIVE: Analyses of tumor biopsy samples from non-small cell lung cancer patients with acquired epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance are expected to reveal the molecular mechanisms of resistance. However, due to limited tissue availability, performing such analyses can be challenging. We herein investigated the feasibility of tumor rebiopsy in this patient population. METHODS: From April 2004 to March 2013, 53 consecutive patients were treated with EGFR-TKIs at our department. A retrospective medical chart review was conducted among patients with progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors criteria, as assessed radiographically. Sites of progression were evaluated at the time of PD. RESULTS: Forty patients experienced PD at the following sites: isolated central nervous system (CNS) in 10 patients; isolated bone in five patients; isolated lymph nodes in two patients; the primary lesion in 10 patients; and systemic disease in 11 patients. Concerning the site of progression, 20 of the 40 patients had a lesion that could be accessed using endobronchial, transbronchial or percutaneous biopsy procedures. Among the 19 patients with oligoprogressive disease or CNS failure, the median overall survival was 24.1 months in eight patients who had received continuing treatment with EGFR-TKIs following radiotherapy and 16.8 months in 11 patients who received other therapies after PD. CONCLUSION: In this study, few patients had a site of progression capable of being accessed using relatively noninvasive biopsy procedures. Further investigations are warranted to develop more optimal treatment strategies after PD in patients with oligoprogressive disease or CNS failure.


Asunto(s)
Antineoplásicos/uso terapéutico , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Análisis Mutacional de ADN , Progresión de la Enfermedad , Receptores ErbB/efectos de los fármacos , Receptores ErbB/metabolismo , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Mutación , Estudios Retrospectivos
7.
Gan To Kagaku Ryoho ; 40(12): 2327-9, 2013 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-24394101

RESUMEN

Long-term survival in patients with non-small cell lung cancer( NSCLC) can be achieved more frequently with combined modality therapy. However, an increased risk of late treatment-related toxicities has been reported for this treatment strategy. We retrospectively evaluated NSCLC patients treated with chemoradiation therapy from January 1988 to January 2007. Patients who had survived for more than 5 years after treatment were included in an analysis of late adverse events (excluding radiation pneumonitis and pulmonary fibrosis). A total of 188 NSCLC patients treated with chemoradiation therapy were evaluated, with 25 patients having survived for more than 5 years. Of these patients, 4 had stage I disease, 4 had stage IIB disease, 1 had stage IIIA disease, 14 had stage IIIB disease, 1 had stage IV disease, and 1 had disease of unknown stage. The following grade 3 late adverse events were noted: skin ulceration( n=1), skin induration( n=1), brachial plexopathy( n=1), malignant neoplasm( n=1). Adequate management of late adverse events due to chemoradiation therapy is needed for long-term NSCLC survivors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/efectos adversos , Neoplasias Pulmonares/terapia , Adulto , Anciano , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Sobrevivientes , Factores de Tiempo
8.
Gan To Kagaku Ryoho ; 39(12): 2390-2, 2012 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-23268087

RESUMEN

Chemoradiotherapy is recommended for locally advanced non-small-cell lung cancer(NSCLC). However, the overall median survival time remains poor(<20 months). We evaluated the outcome and complications of chemoradiotherapy, followed by surgical resection, in locally advanced NSCLC. Eight patients(7 men and 1 woman; median age, 59.5 years (range, 47-68 years) who underwent chemoradiotherapy followed by surgical resection for locally advanced NSCLC from 2002 to 2011 were retrospectively analyzed. In all cases, chemotherapy consisted of platinum-based combination therapy. Postoperatively, bronchopleural fistula occurred in 1 patient and Horner syndrome was observed in 1 patient. No treatment -related deaths were observed. The median of progression-free survival was 34.2 months. In conclusion, chemoradiotherapy should be the standard of care for locally advanced NSCLC. Trimodality therapy is still experimental but seems to be promising for certain subgroups of patients with locally advanced NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos
9.
Gan To Kagaku Ryoho ; 38(12): 2191-3, 2011 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-22202326

RESUMEN

It has been expected that stereotactic radiotherapy (SRT) is one of the useful treatments for non-resectable early lung cancer. In the case radiotherapy was thought to be difficult due to the wideness of irradiation area, it is probable to undergo chemo-radiotherapy safely using SRT for a primary lesion. We report two cases of Stage III non-small-cell lung cancer, which underwent SRT for primary tumors following chemo-radiotherapy for the lymph node metastasis. In both two cases, a reduction of V20 (the normal pulmonary volume to receive radiation exposure: more than 20 Gy) was a possibility, and symptomatic radiation pneumonitis was not observed.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Técnicas Estereotáxicas , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Dosis de Radiación , Tomografía Computarizada por Rayos X
10.
Gan To Kagaku Ryoho ; 37(12): 2744-6, 2010 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-21224699

RESUMEN

Stereotactic radiotherapy (SRT) has recently been used for the treatment of small lung tumors. We retrospectively evaluated the efficacy and safety of SRT for non-small cell lung cancer (NSCLC) treated in our hospital. Between October 2007 and December 2009, 31 tumors of 29 patients were treated by SRT (mean age, 75 years: stage IA, n=13; stage IB, n=5; stage IIIA, n=1; stage IIIB, n=1; recurrence, n=11). All of the patients completed the treatment. In one patient who had radiation pneumonitis before SRT, a progression of pulmonary fibrosis was observed, and treated with steroid therapy. In evaluable 29 tumors of 27 patients, the recurrence rates are 11/29 (37.9%). Median progression free survival time was 8 months. The recurrence rate and median progression free survival time of stage IA and IB subgroups were 4/17 (23.5%) and 12 months, respectively. SRT is thought to be a safe and effective treatment for stage I NSCLC. For patients with stage I NSCLC, SRT can be a complemental therapy for surgical resection.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Radiocirugia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
11.
J Surg Res ; 162(2): 153-9, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19457496

RESUMEN

BACKGROUND: The objective of the present study was to investigate the effects of granulocyte colony-stimulating factor (G-CSF) on right ventricular hypertrophy following extensive pulmonary resection in rats. MATERIALS AND METHODS: Adult rats were divided into four groups: (1) Group S (right thoracotomy only); (2) Group L (right three lobectomy); (3) Group LG10 (Group L+G-CSF [10microg/kg/d]); and (4) Group LG100 (Group L+G-CSF [100microg/kg/d]). At postoperative day 21, weight ratio of the right ventricular to the left ventricle plus septum (RV/LV+S, indicator of right ventricular hypertrophy) were measured, and a histopathological study was conducted to determine percentage wall thickness of peripheral pulmonary arteries and proliferating cell nuclear antigen labeling index (indicator of oxidative DNA damage) of right ventricles. RESULTS: Mean RV/LV+S for Group S was 0.27+/-0.02, significantly smaller than that for the lobectomy groups (Group L, LG10, LG100; 0.47+/-0.05, 0.35+/-0.02, 0.38+/-0.05). G-CSF significantly suppressed right ventricular hypertrophy. Mean medial wall thickness of peripheral pulmonary arteries for Group S was 13.6% +/- 4.9%, significantly smaller than that for Group L (22.9% +/- 9.6%). Compared with Group L, G-CSF reduced medial wall thickness (LG10, 17.6% +/- 9.5%; LG100, 18.0% +/- 11.2%). Incidence of proliferating cell nuclear antigen positive nuclei for Group S was 1.07% +/- 0.49%, significantly smaller than that for Group L (13.77% +/- 5.87%). G-CSF significantly reduced the incidence of proliferating cell nuclear antigen positive nuclei (LG10, 4.04% +/- 2.14%; LG100, 3.18% +/- 1.66%). CONCLUSIONS: G-CSF administration not only reduce medial wall thickness of peripheral pulmonary arteries but also directly protect cardiomyocytes of the right ventricle, thus suppressing right ventricular hypertrophy. These results suggest that low-dose G-CSF administration can prevent right heart failure following extensive pulmonary resection.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Hipertrofia Ventricular Derecha/cirugía , Pulmón/cirugía , Animales , Lobectomía Temporal Anterior/mortalidad , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Hemoglobinas/efectos de los fármacos , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/cirugía , Hipertrofia Ventricular Derecha/tratamiento farmacológico , Hipertrofia Ventricular Derecha/etiología , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Pulmón/crecimiento & desarrollo , Pulmón/patología , Masculino , Células Musculares/fisiología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Arteria Pulmonar/patología , Ratas , Ratas Sprague-Dawley , Toracotomía
12.
J Heart Lung Transplant ; 27(6): 642-8, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18503964

RESUMEN

BACKGROUND: Graft damage due to acute rejection has been reported as one of the risk factors in the chronic stage of cardiac and renal allografts. This study was designed to elucidate the histologic changes of grafts after ongoing acute allograft rejection was discontinued in models of lung re-isotransplantation. METHODS: WKAH rat lungs were orthotopically transplanted into F344 recipients. Three days (3A group) and 5 days (5A group) after the first allotransplantation, the grafts were re-isotransplanted back into the WKAH rats (3RA and 5RA groups, respectively). Five days (5I group) after the first isotransplantation, the grafts were re-isotransplanted back into the WKAH rats (5RI group). The grafts were removed 30 and 60 days after re-isotransplantation and assessed histologically. RESULTS: Typical acute allograft rejection developed in the 3A and 5A groups, and the changes were reduced after re-isotransplantation, although they remained significantly greater in the 5RA group than in the 3RA and 5RI groups. For intimal hyperplasia, the graft score 60 days after re-isotransplantation in the 5RA group was significantly higher than in the 5RI and 3RA groups. The changes in airway inflammation were significantly greater in the 5RA group than in the 3RA and 5RI groups at 60 days. Peribronchiolar fibrosis was significantly more frequent in the 5RA and 3RA groups than in the 5RI group. CONCLUSIONS: Acute rejection and airway inflammation corresponded to the magnitude of rejection before retransplantation. Significant intimal hyperplasia developed in severe acute rejection, and peribronchiolar fibrosis occurred after the first acute rejection.


Asunto(s)
Rechazo de Injerto/patología , Trasplante de Pulmón/patología , Trasplante Homólogo/patología , Túnica Íntima/patología , Animales , Modelos Animales de Enfermedad , Fibrosis/etiología , Hiperplasia , Ratas , Ratas Endogámicas F344 , Reoperación , Factores de Riesgo , Factores de Tiempo
13.
J Hepatobiliary Pancreat Surg ; 14(6): 582-5, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18040625

RESUMEN

We describe a patient who underwent pulmonary resection three times for metastatic lung cancer from hepatocellular carcinoma (HCC). A 56-year-old man, who had a past history of right hepatic lobectomy for HCC, was referred to our department with an abnormal finding on chest computed tomography (CT). Chest CT showed three abnormal shadows, in the right upper lobe (S3b), right middle lobe (S5), and right lower lobe (S10), respectively, and there was no evidence of intrahepatic recurrence. He underwent surgical resections (right upper lobectomy and partial resections) for the metastatic lung cancer from HCC. Subsequently, 12 and 16 months after the first pulmonary resection, metastatic lung cancer recurred, in right S6 and S9, respectively. Because there was no evidence of intrahepatic recurrence and because of the feasibility of curative resection, we performed partial pulmonary resections. He had no postoperative morbidity, and is alive with no evidence of disease 60 months after the first pulmonary resection. Twelve cases of repeat pulmonary resections for metastatic lung cancer from HCC have been reported in the literature, and the authors of these reports described that repeated pulmonary resections for metastatic lung cancer from HCC resulted in long-term survival. Repeat pulmonary resections for metastatic lung cancer from HCC can be an effective treatment for patients with such metastases.


Asunto(s)
Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Reoperación , Tomografía Computarizada por Rayos X
14.
Surg Today ; 37(8): 704-7, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17643220

RESUMEN

We herein report a rare case of ectopic pancreatic acinar cell carcinoma (ACC) which presented as a submucosal tumor of the pylorus. A 73-year-old man came to our hospital presenting with epigastralgia. Esophago-gastroduodenal endoscopy showed no mucosal lesions, but a submucosal tumor was observed around the pylorus. Abdominal computed tomography revealed two round masses. One was located in the pylorus, while the other was found between the portal vein and the inferior vena cava. An examination of a biopsy specimen was inconclusive. We diagnosed a gastrointestinal stromal tumor or malignant lymphoma preoperatively, and decided to perform an operation in order to confirm the diagnosis and select the optimal treatment. Intraoperatively, the mass in the pylorus invaded the pancreatic head, and the lymph node in the hepatoduodenal ligament was swollen. We performed a pancreaticoduodenectomy as a radical excision. The resected specimen showed the 7.6 x 4.9-cm size tumor to mainly originate from the pylorus. Histopathologically, the tumor was identified as pancreatic ACC with lymph node metastasis. The tumor cells were labeled by immunohistochemical staining for alpha1-antitrypsin. Because of the tumor location, we considered the tumor to have originated from the ectopic pancreatic tissue in the stomach. This is only the second case of ACC originating from an ectopic pancreas reported in the literature.


Asunto(s)
Carcinoma de Células Acinares/patología , Neoplasias Pancreáticas/patología , Píloro/patología , Neoplasias Gástricas/secundario , Anciano , Carcinoma de Células Acinares/etiología , Carcinoma de Células Acinares/cirugía , Humanos , Masculino , Neoplasias Pancreáticas/cirugía , Píloro/cirugía , Neoplasias Gástricas/patología
15.
Lab Invest ; 84(7): 836-44, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15197407

RESUMEN

Lung fibrosis is a common feature of interstitial lung diseases, and apoptosis and fibrinogenesis play critical roles in its formation and progression. Hepatocyte growth factor (HGF) is one of the ideal therapeutic agents for prevention of lung fibrosis because of its antiapoptotic and fibrinolytic effects. The aim of this study is to establish nonviral HGF gene therapy of bleomycin-induced lung fibrosis avoiding the viral vector-related side effects. C57BL/6 mice were injected with 3.0 mg/kg body weight of bleomycin intratracheally. Following bleomycin injection, 50 microl of pUC-HGF (1 mg/ml) was injected into each of the quadriceps muscle. Immediately after plasmid injection, in vivo electroporation was performed with pulse generator. Skeletal muscle-targeting electroporation induced transgene expression on day 1 and persisted for 4 weeks, and human HGF was also detected in the lung. In mice transferred with HGF, pathological score (1.0+/-0.3 vs 3.2+/-0.6), TUNEL-positive cell index (4.5+/-1.1 vs 14.2+/-3.1), and hydroxyproline content (9.0+/-1.3 vs 14.4+/-5.1 micromol/g) were significantly reduced compared with the control. Furthermore, survival rate of HGF mice was significantly improved compared with the control. Our data indicate that HGF gene therapy with a single skeletal muscle-targeting electroporation has a therapeutic potential for bleomycin-induced lung fibrosis and this strategy can be applied as a practical gene therapy protocol for various organs.


Asunto(s)
Bleomicina/toxicidad , Electroporación , Terapia Genética/métodos , Factor de Crecimiento de Hepatocito/genética , Músculo Esquelético/metabolismo , Fibrosis Pulmonar/terapia , Animales , Apoptosis , Hidroxiprolina/análisis , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/patología , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología
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