Skip directly to content

PubMed Lung Transplant

Subscribe to PubMed Lung Transplant feed PubMed Lung Transplant
NCBI: db=pubmed; Term=lung transplant
Updated: 1 hour 12 min ago

Innovation in pediatric clinical trials: The need to rethink the end-point.

Sun, 06/04/2017 - 10:06
Related Articles

Innovation in pediatric clinical trials: The need to rethink the end-point.

J Heart Lung Transplant. 2017 May 15;:

Authors: Glass L, Conway J

PMID: 28576400 [PubMed - as supplied by publisher]

Characterization of circadian COPD symptoms by phenotype: Methodology of the STORICO observational study.

Sun, 06/04/2017 - 10:06
Related Articles

Characterization of circadian COPD symptoms by phenotype: Methodology of the STORICO observational study.

Eur J Intern Med. 2017 May 30;:

Authors: Canonica GW, Blasi F, Scichilone N, Simoni L, Zullo A, Giovannetti C, Briguglio C, Barsanti S, Antonelli Incalzi R, STORICO study group

Abstract
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. The symptoms of COPD are troublesome, variable, can occur during all parts of the 24-h day and have a substantial impact on patients' health status, quality of life and healthcare resource utilization. Reducing symptoms, improving health status and increasing physical activity are major goals in the management of stable COPD. In order to provide effective, patient-oriented care, patients should be evaluated on the basis of lung function, frequency of symptoms and patient-perceived impact of symptoms on their lives and treatment decisions made on a case-by-case basis. The identification of COPD phenotypes is an evolving debate and literature data about the circadian variation of COPD symptoms according to phenotypes are nowadays lacking. The ongoing STORICO (STudio Osservazionale sulla caratteRizzazione dei sIntomi delle 24 ore nei pazienti con BPCO) study (NCT03105999) is aimed to describe by clinically defined phenotypes the frequency and 12-month evolution of early-morning, day- and night-time COPD symptoms in a cohort of 600 Italian patients with stable COPD. Secondary objectives include the description of the 12-month variation of outcomes of interest according to phenotypes and of the healthcare resources utilization (overall and by phenotype) during 12-month observation. An exploratory analysis will be conducted aimed to phenotype COPD patients in an alternative researcher-independent way based on circadian pattern of symptoms combined with measures of respiratory function, health-related quality of life and comorbidity. The present paper describes the methodology of the STORICO study.

PMID: 28576398 [PubMed - as supplied by publisher]

Diffuse myocardial fibrosis among healthy pediatric heart transplant recipients: Correlation of histology, cardiovascular magnetic resonance, and clinical phenotype.

Sat, 06/03/2017 - 12:45
Related Articles

Diffuse myocardial fibrosis among healthy pediatric heart transplant recipients: Correlation of histology, cardiovascular magnetic resonance, and clinical phenotype.

Pediatr Transplant. 2017 Jun 02;:

Authors: Feingold B, Salgado CM, Reyes-Múgica M, Drant SE, Miller SA, Kennedy M, Kellman P, Schelbert EB, Wong TC

Abstract
Fibrosis is commonly described in heart allografts lost late after transplantation. CMR-derived ECV is a validated measure of DMF in native adult hearts that may predict heart failure and mortality. We explored associations of ECV with histologic myocardial fibrosis and clinical features after pediatric heart transplantation. Twenty-five recipients (7.0±6.3 years at transplant and 10.7±6.5 years post-transplant) were prospectively recruited for CMR and BNP measurement at the time of surveillance biopsy. All had normal ejection fractions and lacked heart failure symptoms. Fibrosis was quantified on biopsy after picrosirius red staining as CVF. ECV was quantified using contemporaneous hematocrit on basal and mid-short-axis slices. ECV was moderately correlated with CVF (r=.47; P=.019). We found no associations of ECV with hemodynamics, ischemic time, time since transplantation, or number of prior biopsies or acute rejections. Compared to healthy non-transplant controls, there was no significant difference in ECV (25.1±3.0 vs 23.7±2.0%, P=.09). Log-transformed BNP was correlated with ECV (recipients: r=.46, P=.02; recipients and controls: r=.45, P=.006). These findings suggest ECV quantifies DMF and relates to biological indicators of cardiac function after pediatric heart transplantation.

PMID: 28574157 [PubMed - as supplied by publisher]

Modeling the Effect of the Aryl Hydrocarbon Receptor on Transplant Immunity.

Sat, 06/03/2017 - 12:45
Related Articles

Modeling the Effect of the Aryl Hydrocarbon Receptor on Transplant Immunity.

Transplant Direct. 2017 May;3(5):e157

Authors: Julliard W, Fechner JH, Owens L, O'Driscoll CA, Zhou L, Sullivan JA, Frydrych L, Mueller A, Mezrich JD

Abstract
BACKGROUND: Exposure to pollutants through inhalation is a risk factor for lung diseases including cancer, asthma, and lung transplant rejection, but knowledge of the effects of inhaled pollutants on pathologies outside of the lung is limited.
METHODS: Using the minor-mismatched model of male C57BL/6J (B6) to female B6 skin grafts, recipient mice were treated with an inhaled urban dust particle sample every 3 days before and after grafting. Graft survival time was determined, and analysis of the resulting immune response was performed at time before rejection.
RESULTS: Significant prolongation of male skin grafts occurred in recipient female mice treated with urban dust particles compared with controls and was found to be dependent on aryl hydrocarbon receptor (AHR) expression in the recipient mouse. T cell responses to the male histocompatibility antigen (H-Y) Dby were not altered by exposure to pollutants. A reduction in the frequency of IFNγ-producing CD4 T cells infiltrating the graft on day 7 posttransplant was observed. Flow cytometry analysis revealed that AHR expression is upregulated in IFNγ-producing CD4 T cells during immune responses in vitro and in vivo.
CONCLUSIONS: Surprisingly, inhalation of a pollutant standard was found to prolong graft survival in a minor-mismatched skin graft model in an AHR-dependent manner. One possible mechanism may be an effect on IFNγ-producing CD4 T cells responding to donor antigen. The increased expression of AHR in this CD4 T cell subset suggests that AHR ligands within the particulate matter may be directly affecting the type 1 T helper cell response in this model.

PMID: 28573192 [PubMed - in process]

Standard operating procedures for tuberculosis care.

Sat, 06/03/2017 - 12:45
Related Articles

Standard operating procedures for tuberculosis care.

Eur Respir J. 2017 Jun;49(6):

Authors: Solovic I, Abubakar I, Sotgiu G, Dara M, Goletti D, Duarte R, Aliberti S, de Benedictis FM, Ward B, Teixeira V, Gratziou C, Migliori GB

PMID: 28572129 [PubMed - in process]

Longitudinal Outcomes of Patients With Single Ventricle After the Fontan Procedure.

Sat, 06/03/2017 - 12:45
Related Articles

Longitudinal Outcomes of Patients With Single Ventricle After the Fontan Procedure.

J Am Coll Cardiol. 2017 Jun 06;69(22):2735-2744

Authors: Atz AM, Zak V, Mahony L, Uzark K, D'agincourt N, Goldberg DJ, Williams RV, Breitbart RE, Colan SD, Burns KM, Margossian R, Henderson HT, Korsin R, Marino BS, Daniels K, McCrindle BW, Pediatric Heart Network Investigators

Abstract
BACKGROUND: Multicenter longitudinal objective data for survival into adulthood of patients who have undergone Fontan procedures are lacking.
OBJECTIVES: This study sought to describe transplant-free survival and explore relationships between laboratory measures of ventricular performance and functional status over time.
METHODS: Exercise testing, echocardiography, B-type natriuretic peptide, functional health assessment, and medical history abstraction were repeated 9.4 ± 0.4 years after the Fontan Cross-Sectional Study (Fontan 1) and compared with previous values. Cox regression analysis explored risk factors for interim death or cardiac transplantation.
RESULTS: From the original cohort of 546 subjects, 466 were contacted again, and 373 (80%) were enrolled at 21.2 ± 3.5 years of age. Among subjects with paired testing, the percent predicted maximum oxygen uptake decreased (69 ± 14% vs. 61 ± 16%; p < 0.001; n = 95), ejection fraction decreased (58 ± 11% vs. 55 ± 10%; p < 0.001; n = 259), and B-type natriuretic peptide increased (median [interquartile range] 13 [7 to 25] pg/mol vs. 18 [9 to 36] pg/mol; p < 0.001; n = 340). At latest follow-up, a lower Pediatric Quality of Life Inventory physical summary score was associated with poorer exercise performance (R(2) adjusted = 0.20; p < 0.001; n = 274). Cumulative complications since the Fontan procedure included additional cardiac surgery (32%), catheter intervention (62%), arrhythmia treatment (32%), thrombosis (12%), and protein-losing enteropathy (8%). Since Fontan 1, 54 subjects (10%) have received a heart transplant (n = 23) or died without transplantation (n = 31). The interval risk of death or/cardiac transplantation was associated with poorer ventricular performance and functional health status assessed at Fontan 1, but it was not associated with ventricular morphology, the subject's age, or the type of Fontan connection.
CONCLUSIONS: Interim transplant-free survival over 12 years in this Fontan cohort was 90% and was independent of ventricular morphology. Exercise performance decreased and was associated with worse functional health status. Future interventions might focus on preserving exercise capacity. (Relationship Between Functional Health Status and Ventricular Performance After Fontan-Pediatric Heart Network; NCT00132782).

PMID: 28571639 [PubMed - in process]

Role of mesothelin in carbon nanotube-induced carcinogenic transformation of human bronchial epithelial cells.

Sat, 06/03/2017 - 12:45
Related Articles

Role of mesothelin in carbon nanotube-induced carcinogenic transformation of human bronchial epithelial cells.

Am J Physiol Lung Cell Mol Physiol. 2016 Sep 01;311(3):L538-49

Authors: He X, Despeaux E, Stueckle TA, Chi A, Castranova V, Dinu CZ, Wang L, Rojanasakul Y

Abstract
Carbon nanotubes (CNTs) have been likened to asbestos in terms of morphology and toxicity. CNT exposure can lead to pulmonary fibrosis and promotion of tumorigenesis. However, the mechanisms underlying CNT-induced carcinogenesis are not well defined. Mesothelin (MSLN) is overexpressed in many human tumors, including mesotheliomas and pancreatic and ovarian carcinomas. In this study, the role of MSLN in the carcinogenic transformation of human bronchial epithelial cells chronically exposed to single-walled CNT (BSW) was investigated. MSLN overexpression was found in human lung tumors, lung cancer cell lines, and BSW cells. The functional role of MSLN in the BSW cells was then investigated by using stably transfected MSLN knockdown (BSW shMSLN) cells. MSLN knockdown resulted in significantly decreased invasion, migration, colonies on soft agar, and tumor sphere formation. In vivo, BSW shMSLN cells formed smaller primary tumors and less metastases. The mechanism by which MSLN contributes to these more aggressive behaviors was investigated by using ingenuity pathway analysis, which predicted that increased MSLN could induce cyclin E expression. We found that BSW shMSLN cells had decreased cyclin E, and their proliferation rate was reverted to nearly that of untransformed cells. Cell cycle analysis showed that the BSW shMSLN cells had an increased G2 population and a decreased S phase population, which is consistent with the decreased rate of proliferation. Together, our results indicate a novel role of MSLN in the malignant transformation of bronchial epithelial cells following CNT exposure, suggesting its utility as a potential biomarker and drug target for CNT-induced malignancies.

PMID: 27422997 [PubMed - indexed for MEDLINE]

Effects of two different decellularization routes on the mechanical properties of decellularized lungs.

Fri, 06/02/2017 - 12:45
Related Articles

Effects of two different decellularization routes on the mechanical properties of decellularized lungs.

PLoS One. 2017;12(6):e0178696

Authors: Urbano JJ, da Palma RK, de Lima FM, Fratini P, Guimaraes LL, Uriarte JJ, Alvarenga LH, Miglino MA, Vieira RP, Prates RA, Navajas D, Farrè R, Oliveira LVF

Abstract
Considering the limited number of available lung donors, lung bioengineering using whole lung scaffolds has been proposed as an alternative approach to obtain lungs suitable for transplantation. However, some decellularization protocols can cause alterations on the structure, composition, or mechanical properties of the lung extracellular matrix. Therefore, the aim of this study was to compare the acellular lung mechanical properties when using two different routes through the trachea and pulmonary artery for the decellularization process. This study was performed by using the lungs excised from 30 healthy male C57BL/6 mice, which were divided into 3 groups: tracheal decellularization (TDG), perfusion decellularization (PDG), and control groups (CG). Both decellularized groups were subjected to decellularization protocol with a solution of 1% sodium dodecyl sulfate. The behaviour of mechanical properties of the acellular lungs was measured after decellularization process. Static (Est) and dynamic (Edyn) elastances were obtained by the end-inspiratory occlusion method. TDG and PDG showed reduced Est and Edyn elastances after lung decellularization. Scanning electron microscopy showed no structural changes after lung decellularization of the TDG and PDG. In conclusion, was demonstrated that there is no significant difference in the behaviour of mechanical properties and extracellular matrix of the decellularized lungs by using two different routes through the trachea and pulmonary artery.

PMID: 28570606 [PubMed - in process]

Spiradenocarcinoma: A Comprehensive Data Review.

Fri, 06/02/2017 - 12:45
Related Articles

Spiradenocarcinoma: A Comprehensive Data Review.

Am J Dermatopathol. 2017 May 16;:

Authors: Staiger RD, Helmchen B, Papet C, Mattiello D, Zingg U

Abstract
INTRODUCTION: Spiradenocarcinomas (SCs) are rare and potentially aggressive skin adnexal tumors. Optimal treatment has not yet been established. Experiences with this carcinoma are mostly presented in case reports and few case series.
OBJECTIVE: To generate to a synopsis of published data on SC with regard to diagnostic procedures, treatment, and outcome.
RESULTS: Median patient age was 60 years and sex distribution was balanced. Tumor manifestations were evenly distributed within the sweat gland carrying skin. The most commonly reported symptom was accelerated growth of a longstanding indolent lesion, typically present for more than 2 years. Metastatic spread to the lung, bone, lymph nodes, liver, kidney, and breast has been documented. For staging computed tomography (CT) and positron emission tomography-CT are recommended, especially for detection of hematogenic metastases and lymph node involvement. Clear resection margins and tumor free regional lymph nodes reduce recurrence and carcinoma related death. Although low-grade SCs were reported over 3 times more often, high-grade carcinomas show a greater likelihood for recurrence and lethal outcome.
CONCLUSION: Suspicion of an SC should lead to performance of a magnetic resonance imaging for defining tumor extent, and a fludeoxyglucose positron emission tomography-CT for detection of metastases. Radical tumor excision and resection of tumor involved regional lymph nodes are essential for a curative approach. Histopathological evaluation should involve determination of tumor differentiation grade, because high-grade carcinomas seem to have a much more aggressive behavior. Excision of distant metastases has no therapeutic value. Follow-up needs to be carried out in short intervals with frequent imaging.

PMID: 28570391 [PubMed - as supplied by publisher]

A New Step in the Marathon of Understanding Chronic Rejection after Lung Transplantation.

Fri, 06/02/2017 - 12:45
Related Articles

A New Step in the Marathon of Understanding Chronic Rejection after Lung Transplantation.

Am J Respir Cell Mol Biol. 2017 Jun;56(6):683-684

Authors: Vanaudenaerde B, Verleden S, Neyrinck A, Verleden G, Vos R

PMID: 28569594 [PubMed - in process]

Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis.

Fri, 06/02/2017 - 12:45
Related Articles

Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis.

J Immunol. 2017 May 31;:

Authors: Amarsaikhan N, Sands EM, Shah A, Abdolrasouli A, Reed A, Slaven JE, Armstrong-James D, Templeton SP

Abstract
The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γδ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA.

PMID: 28566368 [PubMed - as supplied by publisher]

Heme Oxygenase-1 Modulates Human Respiratory Syncytial Virus Replication and Lung Pathogenesis during Infection.

Fri, 06/02/2017 - 12:45
Related Articles

Heme Oxygenase-1 Modulates Human Respiratory Syncytial Virus Replication and Lung Pathogenesis during Infection.

J Immunol. 2017 May 31;:

Authors: Espinoza JA, León MA, Céspedes PF, Gómez RS, Canedo-Marroquín G, Riquelme SA, Salazar-Echegarai FJ, Blancou P, Simon T, Anegon I, Lay MK, González PA, Riedel CA, Bueno SM, Kalergis AM

Abstract
Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/β mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II(+) cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection.

PMID: 28566367 [PubMed - as supplied by publisher]

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study.

Fri, 06/02/2017 - 12:45
Related Articles

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study.

Lancet Diabetes Endocrinol. 2017 May 26;:

Authors: Zewinger S, Kleber ME, Tragante V, McCubrey RO, Schmidt AF, Direk K, Laufs U, Werner C, Koenig W, Rothenbacher D, Mons U, Breitling LP, Brenner H, Jennings RT, Petrakis I, Triem S, Klug M, Filips A, Blankenberg S, Waldeyer C, Sinning C, Schnabel RB, Lackner KJ, Vlachopoulou E, Nygård O, Svingen GFT, Pedersen ER, Tell GS, Sinisalo J, Nieminen MS, Laaksonen R, Trompet S, Smit RAJ, Sattar N, Jukema JW, Groesdonk HV, Delgado G, Stojakovic T, Pilbrow AP, Cameron VA, Richards AM, Doughty RN, Gong Y, Cooper-DeHoff R, Johnson J, Scholz M, Beutner F, Thiery J, Smith JG, Vilmundarson RO, McPherson R, Stewart AFR, Cresci S, Lenzini PA, Spertus JA, Olivieri O, Girelli D, Martinelli NI, Leiherer A, Saely CH, Drexel H, Mündlein A, Braund PS, Nelson CP, Samani NJ, Kofink D, Hoefer IE, Pasterkamp G, Quyyumi AA, Ko YA, Hartiala JA, Allayee H, Tang WHW, Hazen SL, Eriksson N, Held C, Hagström E, Wallentin L, Åkerblom A, Siegbahn A, Karp I, Labos C, Pilote L, Engert JC, Brophy JM, Thanassoulis G, Bogaty P, Szczeklik W, Kaczor M, Sanak M, Virani SS, Ballantyne CM, Lee VV, Boerwinkle E, Holmes MV, Horne BD, Hingorani A, Asselbergs FW, Patel RS, GENIUS-CHD consortium, Krämer BK, Scharnagl H, Fliser D, März W, Speer T

Abstract
BACKGROUND: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.
METHODS: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.
FINDINGS: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies.
INTERPRETATION: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
FUNDING: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.

PMID: 28566218 [PubMed - as supplied by publisher]

Anti-fibrotic effects of bone morphogenetic protein-7-modified bone marrow mesenchymal stem cells on silica-induced pulmonary fibrosis.

Fri, 06/02/2017 - 12:45
Related Articles

Anti-fibrotic effects of bone morphogenetic protein-7-modified bone marrow mesenchymal stem cells on silica-induced pulmonary fibrosis.

Exp Mol Pathol. 2017 Feb;102(1):70-77

Authors: Li X, An G, Wang Y, Liang D, Zhu Z, Lian X, Niu P, Guo C, Tian L

Abstract
Silicosis is an occupational lung disease caused by exposure to small particles of crystalline silica, which ultimately results in diffuse pulmonary fibrosis. Evidence indicates an anti-fibrotic role of bone morphogenetic protein-7 (BMP-7) and bone marrow mesenchymal stem cells (BMSCs) in lung diseases. Therefore, strategies incorporating genetic engineering and stem cell biology might have a tremendous potential to treat critical injuries and diseases. Therefore, we modified BMSCs to overexpress the BMP-7 gene (BMP-7-BMSCs) by lentivirus transduction, and then evaluated whether fibrotic processes were inhibited by these cells in vivo. Wistar rats were divided into four groups: control, silica, BMSCs, and BMP-7-BMSCs. The control group received saline, the silica group received silica and saline, the BMSCs group received silica and BMSCs, and the BMP-7-BMSCs group received silica and BMP-7-BMSCs. Rats were sacrificed on days 15 or 30 after silica instillation. Hematoxylin and eosin, and Masson's trichrome staining were performed for histological examination. The severity of fibrosis was evaluated by the levels of hydroxyproline, fibronectin (FN), and transforming growth factor (TGF)-β1. Restoration of the alveolar epithelium was detected by the epithelial marker surfactant protein (SP)-C and aquaporin (AQP)-5. Histopathological results showed that BMP-7-BMSCs could remarkably block the progression of silica-induced fibrosis. Hydroxyproline, FN, and TGF-β1 contents in the BMP-7-BMSCs-treated group were significantly lower than those in the BMSCs group (P<0.05). Furthermore, the expression of SP-C and AQP-5 in the BMP-7-BMSCs-treated group was significantly higher than those in the BMSCs group (P<0.05). In conclusion, the pulmonary fibrosis induced by silica in rats was significantly reduced by treatment with BMP-7-BMSCs and BMSCs. The anti-fibrotic effect of BMSCs can be strengthened by BMP-7. Treatment with BMP-7-BMSCs might be a potential therapeutic intervention for silicosis.

PMID: 28062213 [PubMed - indexed for MEDLINE]

Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment.

Fri, 06/02/2017 - 12:45
Related Articles

Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment.

Cancer Cell. 2016 Dec 12;30(6):953-967

Authors: Park JS, Kim IK, Han S, Park I, Kim C, Bae J, Oh SJ, Lee S, Kim JH, Woo DC, He Y, Augustin HG, Kim I, Lee D, Koh GY

Abstract
A destabilized tumor vasculature leads to limited drug delivery, hypoxia, detrimental tumor microenvironment, and even metastasis. We performed a side-by-side comparison of ABTAA (Ang2-Binding and Tie2-Activating Antibody) and ABA (Ang2-Blocking Antibody) in mice with orthotopically implanted glioma, with subcutaneously implanted Lewis lung carcinoma, and with spontaneous mammary cancer. We found that Tie2 activation induced tumor vascular normalization, leading to enhanced blood perfusion and chemotherapeutic drug delivery, markedly lessened lactate acidosis, and reduced tumor growth and metastasis. Moreover, ABTAA favorably altered the immune cell profile within tumors. Together, our findings establish that simultaneous Tie2 activation and Ang2 inhibition form a powerful therapeutic strategy to elicit a favorable tumor microenvironment and enhanced delivery of a chemotherapeutic agent into tumors.

PMID: 27960088 [PubMed - indexed for MEDLINE]

Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells.

Fri, 06/02/2017 - 12:45
Related Articles

Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells.

J Biol Chem. 2017 Jan 13;292(2):435-445

Authors: Roy S, Lu K, Nayak MK, Bhuniya A, Ghosh T, Kundu S, Ghosh S, Baral R, Dasgupta PS, Basu S

Abstract
Lung carcinoma is the leading cause of cancer-related death worldwide, and among this cancer, non-small cell lung carcinoma (NSCLC) comprises the majority of cases. Furthermore, recurrence and metastasis of NSCLC correlate well with CD133+ve tumor cells, a small population of tumor cells that have been designated as cancer stem cells (CSC). We have demonstrated for the first time high expression of D2 dopamine (DA) receptors in CD133+ve adenocarcinoma NSCLC cells. Also, activation of D2 DA receptors in these cells significantly inhibited their proliferation, clonogenic ability, and invasiveness by suppressing extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT, as well as down-regulation of octamer-binding transcription factor 4 (Oct-4) expression and matrix metalloproteinase-9 (MMP-9) secretion by these cells. These results are of significance as D2 DA agonists that are already in clinical use for treatment of other diseases may be useful in combination with conventional chemotherapy and radiotherapy for better management of NSCLC patients by targeting both tumor cells and stem cell compartments in the tumor mass.

PMID: 27920206 [PubMed - indexed for MEDLINE]

Biodistribution and Clearance of Human Mesenchymal Stem Cells by Quantitative Three-Dimensional Cryo-Imaging After Intravenous Infusion in a Rat Lung Injury Model.

Fri, 06/02/2017 - 12:45
Related Articles

Biodistribution and Clearance of Human Mesenchymal Stem Cells by Quantitative Three-Dimensional Cryo-Imaging After Intravenous Infusion in a Rat Lung Injury Model.

Stem Cells Transl Med. 2016 12;5(12):1668-1675

Authors: Schmuck EG, Koch JM, Centanni JM, Hacker TA, Braun RK, Eldridge M, Hei DJ, Hematti P, Raval AN

Abstract
: Cell tracking is a critical component of the safety and efficacy evaluation of therapeutic cell products. To date, cell-tracking modalities have been hampered by poor resolution, low sensitivity, and inability to track cells beyond the shortterm. Three-dimensional (3D) cryo-imaging coregisters fluorescent and bright-field microcopy images and allows for single-cell quantification within a 3D organ volume. We hypothesized that 3D cryo-imaging could be used to measure cell biodistribution and clearance after intravenous infusion in a rat lung injury model compared with normal rats. A bleomycin lung injury model was established in Sprague-Dawley rats (n = 12). Human mesenchymal stem cells (hMSCs) labeled with QTracker655 were infused via jugular vein. After 2, 4, or 8 days, a second dose of hMSCs labeled with QTracker605 was infused, and animals were euthanized after 60, 120, or 240 minutes. Lungs, liver, spleen, heart, kidney, testis, and intestine were cryopreserved, followed by 3D cryo-imaging of each organ. At 60 minutes, 82% ± 9.7% of cells were detected; detection decreased to 60% ± 17% and 66% ± 22% at 120 and 240 minutes, respectively. At day 2, 0.06% of cells were detected, and this level remained constant at days 4 and 8 postinfusion. At 60, 120, and 240 minutes, 99.7% of detected cells were found in the liver, lungs, and spleen, with cells primarily retained in the liver. This is the first study using 3D cryo-imaging to track hMSCs in a rat lung injury model. hMSCs were retained primarily in the liver, with fewer detected in lungs and spleen.
SIGNIFICANCE: Effective bench-to-bedside clinical translation of cellular therapies requires careful understanding of cell fate through tracking. Tracking cells is important to measure cell retention so that delivery methods and cell dose can be optimized and so that biodistribution and clearance can be defined to better understand potential off-target toxicity and redosing strategies. This article demonstrates, for the first time, the use of three-dimensional cryo-imaging for single-cell quantitative tracking of intravenous infused clinical-grade mesenchymal stem cells in a clinically relevant model of lung injury. The important information learned in this study will help guide future clinical and translational stem cell therapies for lung injuries.

PMID: 27460855 [PubMed - indexed for MEDLINE]

Bosutinib induced pleural effusions: Case report and review of tyrosine kinase inhibitors induced pulmonary toxicity.

Thu, 06/01/2017 - 12:45
Related Articles

Bosutinib induced pleural effusions: Case report and review of tyrosine kinase inhibitors induced pulmonary toxicity.

Respir Med Case Rep. 2017;21:154-157

Authors: Moguillansky NI, Fakih HAM, Wingard JR

Abstract
Tyrosine kinase inhibitors are known to cause pulmonary complications. We report a case of bosutinib related bilateral pleural effusions in a patient with chronic myeloid leukemia. Characteristics of the pleural fluid are presented. We also discuss other tyrosine kinase inhibitors induced pulmonary toxicities, including pulmonary hypertension and interstitial lung disease.

PMID: 28560147 [PubMed - in process]

Fatal invasive aspergillosis caused by Aspergillus niger after bilateral lung transplantation.

Thu, 06/01/2017 - 12:45
Related Articles

Fatal invasive aspergillosis caused by Aspergillus niger after bilateral lung transplantation.

Med Mycol Case Rep. 2017 Sep;17:4-7

Authors: Atchade E, Jean-Baptiste S, Houzé S, Chabut C, Massias L, Castier Y, Brugière O, Mal H, Montravers P

Abstract
Aspergillus niger is usually considered to be a low virulence fungus, not commonly reported to cause invasive infections. Invasive pulmonary aspergillosis due to Aspergillus niger was diagnosed in a 43-year-old woman following bilateral lung transplantation. Intravenous voriconazole failed to control progression of the disease. Despite salvage therapy with a combination of voriconazole and caspofungin for 23 days, the patient developed massive hemoptysis leading to death. The authors report the clinical features and treatment of this case.

PMID: 28560131 [PubMed - in process]

Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality.

Thu, 06/01/2017 - 12:45
Related Articles

Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality.

J Occup Med Toxicol. 2017;12:13

Authors: Neuhaus V, Schaudien D, Golovina T, Temann UA, Thompson C, Lippmann T, Bersch C, Pfennig O, Jonigk D, Braubach P, Fieguth HG, Warnecke G, Yusibov V, Sewald K, Braun A

Abstract
BACKGROUND: Investigation of basic chronic inflammatory mechanisms and development of new therapeutics targeting the respiratory tract requires appropriate testing systems, including those to monitor long- persistence. Human precision-cut lung slices (PCLS) have been demonstrated to mimic the human respiratory tract and have potential of an alternative, ex-vivo system to replace or augment in-vitro testing and animal models. So far, most research on PCLS has been conducted for short cultivation periods (≤72 h), while analyses of slowly metabolized therapeutics require long-term survival of PCLS in culture. In the present study, we evaluated viability, physiology and structural integrity of PCLS cultured for up to 15 days.
METHODS: PCLS were cultured for 15 days and various parameters were assessed at different time points.
RESULTS: Structural integrity and viability of cultured PCLS remained constant for 15 days. Moreover, bronchoconstriction was inducible over the whole period of cultivation, though with decreased sensitivity (EC501d = 4 × 10(-8) M vs. EC5015d = 4 × 10(-6) M) and reduced maximum of initial airway area (1d = 0.5% vs. 15d = 18.7%). In contrast, even though still clearly inducible compared to medium control, LPS-induced TNF-α secretion decreased significantly from day 1 to day 15 of culture.
CONCLUSIONS: Overall, though long-term cultivation of PCLS need further investigation for cytokine secretion, possibly on a cellular level, PCLS are feasible for bronchoconstriction studies and toxicity assays.

PMID: 28559920 [PubMed - in process]

Pages