Related Articles

Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study.

PLoS One. 2013;8(8):e69299

Authors: Moodley Y, Vaghjiani V, Chan J, Baltic S, Ryan M, Tchongue J, Samuel CS, Murthi P, Parolini O, Manuelpillai U

Abstract
Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.

PMID: 23936322 [PubMed - in process]

Dual-function theranostic nanoparticles for drug delivery and medical imaging contrast: perspectives and challenges for use in lung diseases.

Drug Deliv Transl Res. 2013 Aug 1;3(4):352-363

Authors: Howell M, Wang C, Mahmoud A, Hellermann G, Mohapatra SS, Mohapatra S

Abstract
Theranostic nanoparticles with both therapeutic and imaging abilities have the promise to revolutionize diagnosis, therapy, and prognosis. Early and accurate detection along with swift treatment are the most important steps in the successful treatment of any disease. Over the last decade, a variety of nanotechnology-based platforms have been created in the hope of improving the treatment and diagnosis of a wide variety of diseases. However, significant hurdles still remain before theranostic nanoparticles can bring clinical solutions to the fight against chronic respiratory diseases. Some fundamental issues such as long-term toxicity, a precise understanding of the accumulation, degradation and clearance of these particles, and the correlation between basic physicochemical properties of these nanoparticles and their in vivo behavior have to be fully understood before they can be used clinically. To date, very little theranostic nanoparticle research has focused on the treatment and diagnosis of chronic respiratory illnesses. Nanomedicine approaches incorporating these theranostic nanoparticles could potentially be translated into clinical advances to improve diagnosis and treatment of these chronic respiratory diseases and enhance quality of life for the patients.

PMID: 23936754 [PubMed - as supplied by publisher]

The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers.

Ann Thorac Surg. 2013 Aug 7;

Authors: Izar B, Sequist L, Lee M, Muzikansky A, Heist R, Iafrate J, Dias-Santagata D, Mathisen D, Lanuti M

Abstract
BACKGROUND: Mutations of the epidermal growth factor hormone receptor (EGFR) gene have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identify the pure prognostic role of EGFR mutation in patients with completely resected stage I NSCLC who received no adjuvant therapy.
METHODS: Mutation status was tested in treatment-naïve patients who had complete resection of stage I (T1-2aN0) NSCLC (from 2004 to 2011) using direct sequencing or multiplex polymerase chain reaction-based assay. Recurrence rates, disease-free survival, and overall survival were compared between EGFR-mutant and wild-type patients using Kaplan-Meier methods and Cox regression models.
RESULTS: Three hundred seven patients were included in this study; 62 harbored tumors with EGFR mutations and 245 had wild-type EGFR. Tumors in patients with EGFR mutations were associated with a significantly lower recurrence rate (9.7% versus 21.6%; p = 0.03), greater median disease-free survival (8.8 versus 7.0 years; p = 0.0085), and improved overall 5-year survival (98% versus 73%; p = 0.003) compared with wild-type tumors. Lobectomy was the most frequently performed procedure, accounting for 209 of 307 operations. Among these patients, EGFR mutation was associated with superior overall survival (hazard ratio, 0.45; 95% confidence interval, 0.13 to 0.83; p = 0.017), with an estimated 5-year survival of 98% versus 70%. The presence of EGFR mutation (p = 0.026) and tumor size less than 2 cm (p = 0.04) were identified as independent prognostic markers for disease-free survival, whereas age, sex, and smoking status were not.
CONCLUSIONS: Completely resected stage I EGFR mutation-positive NSCLC patients have a significant survival advantage compared with EGFR wild-type patients. Mutation of the EGFR gene is a positive prognostic marker in completely resected stage I NSCLC.

PMID: 23932319 [PubMed - as supplied by publisher]

Assessment of palliative care for advanced non-small-cell lung cancer in France: A prospective observational multicenter study (GFPC 0804 study).

Lung Cancer. 2013 Aug 6;

Authors: Vergnenègre A, Hominal S, Edem Tchalla A, Bérard H, Monnet I, Fraboulet G, Baize N, Audigier-Valette C, Robinet G, Oliviero G, Le Caer H, Thomas P, Gérinière L, Mastroianni B, Chouaïd C, the GFPC 0804 team

Abstract
INTRODUCTION: Few studies assessed, in real life, symptoms, specific interventions and factors influencing palliative care (PC) initiation for patients with advanced non-small-cell lung cancer (NSCLC). The objective of this study was to examine, in a prospective cohort of advanced NSCLC patients, PC use and factors associated with early (≤3 months after diagnosis) PC initiation.
METHODS: It was an observational multicenter study. Each center included 10 consecutive patients with PC initiation.
RESULTS: 514 patients were enrolled by 39 centers (age: 62.3±10.7 years, performance status: 0/1; 68.6% cases). At baseline, the most frequent symptoms concerned pain (43.6%), malnutrition (37%) and psychological disorders (25.3%). Specific interventions were infrequent for pain control and malnutrition, but were more numerous for psychological and social problems and terminal care. Median time between diagnosis and PC initiation was 35 [13-84] days, median PC duration was 4.2 [0.6-9.3] months. Median overall survival was 8.6 [6.6-10.7] months; median survival after PC initiation was 3.6 [3.2-4.5] months. In multivariate analysis, only PS ≥2 was linked to early PC.
CONCLUSION: This study showed that early PC initiation is not a standard for patients with advanced NSCLC.

PMID: 23932456 [PubMed - as supplied by publisher]