Effects of antifibrotic agents on TGF-beta1, CTGF and IFN-gamma expression in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-gamma-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-beta, CTGF) and immunomodulatory/antimicrobial activity (IFN-gamma), in the lungs of patients with IPF. Fourteen (14) patients with an established diagnosis of IPF received either 200 microg of IFN-gamma-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor beta1 (TGF-beta1), connective-tissue growth factor (CTGF), and interferon-gamma (IFN-gamma) genes in lung tissue before and after treatment with IFN-gamma-1b or colchicine. Marked mRNA expression of TGF-beta1 and CTGF, but complete lack of interferon-gamma was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-gamma gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-beta1 remained almost stable before and after treatment, in the IFN-gamma-1b group, while TGF-beta1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-gamma-1b group (p=0.04). In addition, the IFN-gamma-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02). In conclusion, we report the effect of antifibrotic agents (IFN-gamma-1b and colchicine) in TGF-beta, CTGF, and endogenous IFN-gamma gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings.

Bronchial artery embolization for management of massive cryptogenic hemoptysis: a case series.

INTRODUCTION: Hemoptysis constitutes a common and urgent medical problem. Swift and effective management is of crucial importance, especially in severe, life-threatening cases. In cases of idiopathic hemoptysis, in which no underlying pulmonary pathology can be identified, treatment is challenging. We report our experience with bronchial artery embolization in the treatment of massive idiopathic hemoptysis. CASES PRESENTATION: We report three consecutive cases of acute severe idiopathic hemoptysis. Our patients (two men aged 51 and 56 years and one woman aged 46 years), were of Caucasian ethnicity. We discuss the results and management of the patients, and review the literature. All three patients were treated safely and successfully with transcatheter embolization of the bronchial arteries using tris-acryl gelatin microspheres. Hemoptysis was controlled. All cases were followed up for 12 months, and there was no recurrence of bleeding. CONCLUSION: Bronchial artery embolization is an effective tool for the evaluation and treatment of massive idiopathic hemoptysis.

A multicenter phase II study of the combination of irinotecan and gemcitabine in previously treated patients with small-cell lung cancer.

OBJECTIVE: To evaluate efficacy and toxicity of the combination of irinotecan and gemcitabine in pretreated patients having small-cell lung cancer. PATIENTS AND METHODS: Thirty-one patients (median age 60 years, performance status 0-1 in 87% and 2 in 13% of the patients) with limited or extensive-stage disease, refractory or relapsing after at least one prior chemotherapy regimen, received gemcitabine 1,000 mg/m(2) on days 1 and 8 and irinotecan 300 mg/m(2) on day 8, every 21 days. Sixteen (52%) patients had sensitive and 15 (48%) refractory disease. Fifteen patients (48%) had received > or =2 prior regimens. RESULTS: All patients were evaluable for toxicity and 26 for response analysis. A median of three (range 1-6) cycles per patient was administered. Three partial responses were documented for an overall response rate of 10% (95% CI 0.73-20.09), and disease stabilization was obtained in 7 patients (22%; intention-to-treat analysis). Two of the responders had refractory, and 1 had sensitive disease. The median time to progression was 4.5 months, the median duration of responses was 2.5 months, and the median survival time was 6 months. Grade 3-4 (WHO) neutropenia was observed in 9 patients (29%), grade 3-4 thrombocytopenia in 4 (13%), and grade 3-4 diahrrea in 3 patients (10%). Three patients experienced febrile neutropenia. No toxic deaths occurred. CONCLUSIONS: The combination showed modest activity in this patient group with a poor prognosis. Thus we believe it merits further investigation in the treatment of patients with small-cell lung cancer who have failed one prior chemotherapy regimen.