9,503 research outputs found
Immunotherapy of lung cancer: An update
Full text linkIn Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine
Serum concentrations and profiles of polychlorinated biphenyls in Taiwan Yucheng victims twenty years after the incident.
No full textLocal lung responses following endobronchial elastase and lipopolysaccharide instillation in sheep
No full textChronic lipopolysaccharide (LPS) exposure may contribute to the pathogenesis of a number of lung diseases including COPD and emphysema. We sought to develop a large-animal model of emphysema using repeated LPS administration into sheep lung segments. An experimental protocol was designed to facilitate comparisons with elastase-treated and control segments within the same lung of individual sheep. Histopathologic evaluation of segments treated with LPS demonstrated low-grade inflammation characterized by an increase in the number of intra-alveolar macrophages and lymphocytes. Treated segments demonstrated a significant reduction in airspace surface area (ASA), an increase in percent disrupted alveolar attachments and the distance between normal alveolar attachments, and a reduction in the number of normal alveolar attachments surrounding nonrespiratory bronchioles. Coefficient of variation of individual ASA measurements in elastase-treated segments was indicative of a heterogeneous parenchymal response, in contrast to that associated with chronic LPS treatment. Our results demonstrate that chronic LPS treatment of individual lung segments in sheep induces microscopic emphysema qualitatively and quantitatively consistent with both accepted pathologic definitions of this condition and with that produced by airway instillation of elastolytic enzymes. Development of this phenotype is associated with evidence of downregulated activation of transforming growth factor beta
Early life origins of lung ageing : early life exposures and lung function decline in adulthood in two European cohorts aged 28-73 years
Full text linkEarly life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied.; Spirometry data from two time points (follow-up time 9-11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28-73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV1) decline were analysed using mixed-effects linear regression.; Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age.; Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further
Blueprint Of Services For Lung Cancer
Full text linkPrimary lung cancer is the commonest malignant disease in the developed world, and is the
most prevalent form of cancer among men over 65 years. It continues to rise in those aged
over 75 years. Mortality from lung cancer is increasing in women. The condition still has a
short clinical course and a poor prognosis. The literature is in agreement about the effectiveness
of preventing lung cancer incidence by targeting smoking behaviour, particularly in preventing
young people taking up smoking. There is further consensus about the lack of a population
screening method which can be recommended, and the desirability of detecting non-small cell
lung cancer early enough for surgical intervention. The effectiveness of treatment for advanced
disease is less marked, and it is of concern that many people who present with lung cancer are
unsuitable for surgical intervention. The role of palliative care is critical in this condition and
this care should be introduced early in the interaction between the patient and the services
Molecular mechanisms regulating Schwann cell development and injury response in the PNS
No full textThe work within examined different aspects of the Schwann cell (SC) development and injury response: the initial demyelination, de-differentiation, and the proliferation that follows. Previous studies have shown that demyelination in the PNS often results from hijacking of these pathways, leading to SC demyelination and proliferation. Therefore, understanding of the mechanism is important as it provides insight into developing therapeutic strategies for various demyelinating neuropathies. The work described in the first chapter focuses on the mechanism of demyelination and identified p38 MAPK as an important regulator of SC demyelination. Using both in vivo and in vitro methods for nerve injury, I showed that p38 MAPK inhibition strongly reduced demyelination whereas its ectopic activation resulted in spontaneous demyelination. After SCs de-differentiate and demyelinate, the distal SCs become highly proliferative, participating in the injury response to promote functional recovery. The proliferation of SCs is thought to be an important component of the injury repair processes. Further understanding of these processes may help in promoting functional recovery after nerve injury. The second part of the thesis examined the role of SC proliferation that occurs during this period. Using a transgenic animal model in which SCs do not proliferate after injury, I showed that SC proliferation is not required for functional recovery, but rather the excess SCs generated during this proliferative period are removed by apoptosis. Finally, in the third chapter the function of a transcription factor Dlx1 during SC development was examined. Results showed that Dlx1 specifically regulates development of the non-myelinating SC lineage. In the absence of Dlx1, radial sorting of the axons by non-myelinating SCs is impaired; axons in the Remak bundles remain clustered and unsegregated. Biochemical analysis showed alteration in the activation state of several regulators of cytoskeletal dynamics and cell morphology. Correspondingly, Dlx1-deficient SCs exhibit defects in radial lamellae formation, which may account for the axon sorting defect observed in vivo. Overall, these studies further our understanding of SC biology and provide additional insights into molecular regulators of SC development and injury response.Ph. D.Includes bibliographical referencesIncludes vitaby Po-Lung Yan
Environmental toxicity, redox signaling and lung inflammation:the role of glutathione
Full text linkGlutathione (gamma-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H(2)O(2) as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox-sensitive transcription factors such as Nrf2, NF-kappaB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation of GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-l-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease
Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease
Full text linkChronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD
Influence of long-range transported dust particles on local air quality: A case study on the Asian dust episodes in Taipei during the spring of 2002
No full textMRI of the lung (3/3)-current applications and future perspectives
Full text linkBackgroundMRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women.MethodsProvided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value.ResultsIn interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a “buffet” of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice.ConclusionNew developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed
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