Translational respiratory medicine最新文献_第2页

The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update. 气溶胶在全身药物输送、基因治疗和疫苗接种中日益扩大的作用:最新进展。

Translational respiratory medicine Pub Date : 2014-01-13 eCollection Date: 2014-01-01 DOI: 10.1186/2213-0802-2-3

Beth L Laube

{"title":"The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update.","authors":"Beth L Laube","doi":"10.1186/2213-0802-2-3","DOIUrl":"https://doi.org/10.1186/2213-0802-2-3","url":null,"abstract":"Until the late 1990s, aerosol therapy consisted of beta2-adrenergic agonists, anti-cholinergics, steroidal and non-steroidal agents, mucolytics and antibiotics that were used to treat patients with asthma, COPD and cystic fibrosis. Since then, inhalation therapy has matured to include drugs that: (1) are designed to treat diseases outside the lung and whose target is the systemic circulation (systemic drug delivery); (2) deliver nucleic acids that lead to permanent expression of a gene construct, or protein coding sequence, in a population of cells (gene therapy); and (3) provide needle-free immunization against disease (aerosolized vaccination). During the evolution of these advanced applications, it was also necessary to develop new devices that provided increased dosing efficiency and less loss during delivery. This review will present an update on the success of each of these new applications and their devices. The early promise of aerosolized systemic drug delivery and its outlook for future success will be highlighted. In addition, the challenges to aerosolized gene therapy and the need for appropriate gene vectors will be discussed. Finally, progress in the development of aerosolized vaccination will be presented. The continued expansion of the role of aerosol therapy in the future will depend on: (1) improving the bioavailability of systemically delivered drugs; (2) developing gene therapy vectors that can efficiently penetrate the mucus barrier and cell membrane, navigate the cell cytoplasm and efficiently transfer DNA material to the cell nucleus; (3) improving delivery of gene vectors and vaccines to infants; and (4) developing formulations that are safe for acute and chronic administrations. ","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"2 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2014-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-2-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32905586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 54

Second generation tyrosine kinase inhibitors for the treatment of metastatic non-small-cell lung cancer. 第二代酪氨酸激酶抑制剂治疗转移性非小细胞肺癌。

Translational respiratory medicine Pub Date : 2014-01-06 eCollection Date: 2014-01-01 DOI: 10.1186/2213-0802-2-2

Irene Stasi, Federico Cappuzzo

{"title":"Second generation tyrosine kinase inhibitors for the treatment of metastatic non-small-cell lung cancer.","authors":"Irene Stasi, Federico Cappuzzo","doi":"10.1186/2213-0802-2-2","DOIUrl":"https://doi.org/10.1186/2213-0802-2-2","url":null,"abstract":"Backgruond: Since their first description, activating epidermal growth factor receptor (EGFR) mutations identify a distinct clinical entity of patients with non-small-cell lung cancer (NSCLC).Findings: New targeted therapies for molecularly selected NSCLC are changing the natural history of the disease, with results superior to standard chemotherapy as demonstrated in large phase III studies with first generation EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. However, after an initial response, all patients inevitably progress and several mechanisms including a secondary mutation in exon 20 of the EGFR gene (T790M) or MET or HER2 amplifications are responsible for acquired resistance (AR). In clinical practice few options are available for patients with AR, and several new agents or strategies are currently under investigation, including second generation TKIs.Conclusions: Aim of the present review is to present available data on new EGFR-TKIs and to discuss how these agents could overcome AR to erlotinib or gefitinib.","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"2 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2014-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-2-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32905585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Acute lung injury and the role of histones. 急性肺损伤及组蛋白的作用。

Translational respiratory medicine Pub Date : 2014-01-03 eCollection Date: 2014-01-01 DOI: 10.1186/2213-0802-2-1

Peter A Ward, Jamison J Grailer

{"title":"Acute lung injury and the role of histones.","authors":"Peter A Ward, Jamison J Grailer","doi":"10.1186/2213-0802-2-1","DOIUrl":"https://doi.org/10.1186/2213-0802-2-1","url":null,"abstract":"Acute respiratory distress syndrome (ARDS) in humans involves ≥ 200,000 individuals in the United States, and has a mortality rate (40%) for which no specific drug has been approved for use in humans. We have studied experimental acute lung injury (ALI) in mice following airway deposition of bacterial lipopolysaccharide (LPS) or the recombinant mouse complement anaphylatoxin, C5a. As ALI developed over 6 hr, extracellular histones appeared in bronchoalveolar lavage fluids (BALF). Extracellular histone appearance required both C5a receptors (C5aR, C5L2) as well as neutrophils (PMNs) and lung macrophages, as genetic loss of either C5a receptor or depletion of PMNs or macrophages reduced histone levels found in BALF during ALI. It is possible that extracellular histones were derived from formation of neutrophil extracellular traps (NETs) in lung after PMN contact with C5a. When purified histones were delivered to lung via the airways, intense inflammatory injury ensued and type II cells developed large blebs indicating cellular damage and apoptosis. Detailed physiological measurements revealed severe disruption of blood/alveolar gas exchange. These data suggest a key role for histones in development of experimental ALI. ","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"2 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2014-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-2-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33187611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 35

Respiratory diseases call for special attention from clinical and translational science. 呼吸系统疾病需要临床和转化科学的特别关注。

Translational respiratory medicine Pub Date : 2013-12-01 Epub Date: 2013-02-22 DOI: 10.1186/2213-0802-1-1

Chunxue Bai

{"title":"Respiratory diseases call for special attention from clinical and translational science.","authors":"Chunxue Bai","doi":"10.1186/2213-0802-1-1","DOIUrl":"https://doi.org/10.1186/2213-0802-1-1","url":null,"abstract":"Respiratory diseases will become one of the top 3 leading causes of estimated mortality in 2020 and become about one third of total causes of estimated mortality. The journal of Translational Respiratory Medicine is a truly international, peer-reviewed journal devoted to the publication of articles on outstanding work with translational potentials between basic research and clinical application to understanding respiratory disease. Translational respiratory medicine will more focus on biomarker identification and validation in pulmonary diseases in combination with clinical informatics, targeted proteomics, bioinformatics, systems medicine, or mathematical science; on different translational strategies of cell-based therapy to clinical application to treat lung diseases; on targeted therapies in combination with personalized medicine; and on distant electronic medicine to monitor a large population of people's health. Translational Respiratory Medicine is an additional but unique opportunity for scientists and clinicians who work on pulmonary diseases to publish their outstanding findings, initiative results, and critical and perceptive opinions in the journal. ","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34588947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

A linear polyethylenimine mediated siRNA-based therapy targeting human epidermal growth factor receptor in SPC-A1 xenograft mice. 线性聚乙烯亚胺介导的sirna靶向人表皮生长因子受体在SPC-A1异种移植小鼠中的治疗。

Translational respiratory medicine Pub Date : 2013-12-01 Epub Date: 2013-02-22 DOI: 10.1186/2213-0802-1-2

Pinghai Zhang, Nuo Xu, Lei Zhou, Xin Xu, Yuehong Wang, Ka Li, Zhaochong Zeng, Xiangdong Wang, Xin Zhang, Chunxue Bai

{"title":"A linear polyethylenimine mediated siRNA-based therapy targeting human epidermal growth factor receptor in SPC-A1 xenograft mice.","authors":"Pinghai Zhang, Nuo Xu, Lei Zhou, Xin Xu, Yuehong Wang, Ka Li, Zhaochong Zeng, Xiangdong Wang, Xin Zhang, Chunxue Bai","doi":"10.1186/2213-0802-1-2","DOIUrl":"https://doi.org/10.1186/2213-0802-1-2","url":null,"abstract":"Background: Linear polyethylenimine (LPEI) is considered as a desirable gene in vivo delivery system, but whether it could deliver the specific siRNA targeted EGFR to the tumor site to inhibit the growth of NSCLC xenograft in nude mice still needs to be examined.Methods: In this study, LPEI/siRNA was made into a complex and SPC-A1-xenografted mice model was established. Then, stable LPEI/siRNA-EGFR complexes were intraperitoneally administrated. Afterwards, tumor growth was measured every 3 days. At the end of the experiment, tumor volume was calculated, and tumors were weighed, and examined for EGFR expression, proliferation, and apoptosis evaluations. By using blood samples, toxicity tests including aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine (Cr) were measured for liver and renal function evaluation. Serum concentrations of TNF-α and IFN-γ were also examined.Results: Our results demonstrated that LPEI/siRNA-EGFR complexes could downregulate EGFR expression in SPC-A1 xenografted tumor upon single i.p. injection. LPEI/siRNA-EGFR complexes inhibited tumor growth and did not induce organ toxicity in SPC-A1-xenografted mice. At the end of the experiment no significant IFN-α increase was detected in LPEI/siRNA complexes or glucose-treated groups.Conclusions: The novel modality of siRNA-based therapy targeting EGFR may be of great potential in NSCLC treatment.","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34588949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

The need for translational research in respiratory medicine. 呼吸医学转化研究的必要性。

Translational respiratory medicine Pub Date : 2013-12-01 Epub Date: 2013-04-19 DOI: 10.1186/2213-0802-1-9

Y C Gary Lee, Grant W Waterer

引用次数: 2

Standardization developments for large scale biobanks in smoking related diseases - a model system for blood sample processing and storage. 大型吸烟相关疾病生物库的标准化发展——血液样本处理和储存的模型系统。

Translational respiratory medicine Pub Date : 2013-12-01 Epub Date: 2013-08-30 DOI: 10.1186/2213-0802-1-14

Johan Malm, Thomas E Fehniger, Pia Danmyr, Ákos Végvári, Charlotte Welinder, Henrik Lindberg, Paul Upton, Stephanie Carter, Roger Appelqvist, Karin Sjödin, Elisabet Wieslander, Magnus Dahlbäck, Melinda Rezeli, David Erlinge, György Marko-Varga

{"title":"Standardization developments for large scale biobanks in smoking related diseases - a model system for blood sample processing and storage.","authors":"Johan Malm, Thomas E Fehniger, Pia Danmyr, Ákos Végvári, Charlotte Welinder, Henrik Lindberg, Paul Upton, Stephanie Carter, Roger Appelqvist, Karin Sjödin, Elisabet Wieslander, Magnus Dahlbäck, Melinda Rezeli, David Erlinge, György Marko-Varga","doi":"10.1186/2213-0802-1-14","DOIUrl":"https://doi.org/10.1186/2213-0802-1-14","url":null,"abstract":"Background: Biobank samples stored in biobanks give researchers and respiratory healthcare institutions access to datasets of analytes valuable for both diagnostic and research practices. The usefulness of these samples in clinical decision-making is highly dependent on their quality and integrity. New procedures that better preserve sample integrity and reduce degradation are being developed to meet the needs of both present and future biobanking. Hereby we present an automatic sample workflow scheme that is designed to handle high numbers of blood samples.Methods: Blood fractions are aliquoted, heat sealed using novel technology, and stored in 384 tube high-density sample arrays.Results: The newly developed 384 biobank rack system is especially suited for preserving identical small aliquots. We provide data on robotic processing of clinical samples at -80°C, following initial processing, analysis and shipping between laboratories throughout Europe. Subsequent to unpacking, re-sorting, and storage at these sites, the samples have been returned for analysis. Biomarker analysis of 13 common tests in the clinical chemistry unit of the hospital provides evidence of qualitative and stable logistics using the 384-sample tube system.Conclusions: This technology development allows rapid access to a given sample in the frozen archive while maintaining individual sample integrity with sample tube confinement and quality management.","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34525582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Pulmonary vascular remodeling and right heart failure in pulmonary hypertension: future role of positron emission tomography in decoding the enigma. 肺动脉高压的肺血管重构和右心衰:正电子发射断层扫描在解码之谜中的未来作用。

Translational respiratory medicine Pub Date : 2013-12-01 Epub Date: 2013-12-11 DOI: 10.1186/2213-0802-1-16

Hendrik J Harms, Mariëlle C van de Veerdonk, Adriaan A Lammertsma, Anton Vonk Noordegraaf, Harm Jan Bogaard

引用次数: 1

Bacteria in COPD; their potential role and treatment. 慢性阻塞性肺病中的细菌；其潜在作用和治疗方法。

Translational respiratory medicine Pub Date : 2013-12-01 Epub Date: 2013-08-30 DOI: 10.1186/2213-0802-1-13

Paul T King, Martin MacDonald, Philip G Bardin

{"title":"Bacteria in COPD; their potential role and treatment.","authors":"Paul T King, Martin MacDonald, Philip G Bardin","doi":"10.1186/2213-0802-1-13","DOIUrl":"10.1186/2213-0802-1-13","url":null,"abstract":"The role of bacterial infection in chronic obstructive pulmonary disease (COPD) and how it should be treated has been an ongoing source of controversy. For many years bacterial infection has not been thought to have an important effect in the pathology of this condition. Recent advances in diagnostic techniques, particularly the use 16S sequencing has demonstrated that there are a large range of bacteria present in the lower respiratory tract, both in terms of exacerbations and chronic colonization. A proportion of the bacteria present in the lower respiratory have also been shown to produce inflammation and hence are likely to be relevant for the pathogenesis of COPD. The accurate diagnosis of bacterial infection in individual patients remains a major challenge. The trials that have assessed the effect of antibiotics in COPD have generally been of low quality and have not been placebo controlled. Recent studies of macrolides for long-term treatment in COPD have found significantly reduced rates of exacerbations. Major challenges remain in accurately defining the potential role of bacteria in the inflammatory process and how best to optimize the use of antibiotics without the overuse of this limited resource. Alternative strategies to treat infection in COPD remain very limited. ","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34525581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Self-aggregating TIAF1 in lung cancer progression. 自聚集TIAF1在肺癌进展中的作用。

Translational respiratory medicine Pub Date : 2013-12-01 Epub Date: 2013-02-28 DOI: 10.1186/2213-0802-1-5

Qunying Hong, Li-Jin Hsu, Pei-Yi Chou, Ying-Tsen Chou, Chen-Yu Lu, Yu-An Chen, Nan-Shan Chang

{"title":"Self-aggregating TIAF1 in lung cancer progression.","authors":"Qunying Hong, Li-Jin Hsu, Pei-Yi Chou, Ying-Tsen Chou, Chen-Yu Lu, Yu-An Chen, Nan-Shan Chang","doi":"10.1186/2213-0802-1-5","DOIUrl":"https://doi.org/10.1186/2213-0802-1-5","url":null,"abstract":"Recent studies have demonstrated that transforming growth factor beta (TGF-β1)-induced antiapoptotic factor (TIAF1) is able to form aggregates in the hippocampi of middle-aged normal individuals. The aggregating TIAF1 induces generation of amyloid beta (Aβ) for causing neurodegeneration. Intriguingly, TIAF1 aggregates are shown, together with Smad4 and Aβ, in the cancer stroma and peritumor capsules of many solid tumors. During lung cancer progression, for example, TIAF1 and amyloid fibrils are significantly upregulated in the cancer stroma. Aggregates of TIAF1 and Aβ are shown on the interface between metastatic lung cancer cells and the brain tissues. Conceivably, these peritumor materials are needed for cancer cells to survive. In vitro experiments revealed that TIAF1 is a crucial component for tumor suppressors p53 and WWOX-mediated tumor suppression and apoptosis. While metastatic lung cancer cells are frequently devoid of WWOX and p53, we provide new perspectives regarding the role of TIAF1 in the pathogenesis of lung cancer development, and propose a therapeutic approach for targeting TIAF1. ","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34524548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15