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OBJECTIVES: Smoking remains the leading cause of preventable disease. However, smokers have shown poor compliance with smoking cessation clinics. Smartphone applications present a promising opportunity to improve this compliance. This study aimed to explore the relationship between nicotine dependence, smartphone usage patterns, and anticipated compliance with a smoking cessation application among smokers, with the goal of informing future development of such applications. METHODS: A total of 53 current smokers were surveyed using a questionnaire. Nicotine dependence was assessed using the Fagerstrom Test for Nicotine Dependence (FTND). Variables included the number of hours spent using a phone, willingness to quit smoking, number of previous quit attempts, desired number of text messages about smoking cessation, expected duration of application usage, and FTND scores. Kendall's partial correlation, adjusted for age, was employed for the analysis. RESULTS: The amount of time smokers spent on their mobile devices was negatively correlated with the number of smoking cessation text messages they wanted to receive (τ coefficient = -0.210, p = 0.026) and the duration they intended to use the cessation application (τ coefficient = -0.260, p = 0.006). Conversely, the number of desired text messages was positively correlated with the intended duration of application usage (τ coefficient = 0.366, p = 0.00012). CONCLUSIONS: Smokers who spent more time on their mobile devices tended to prefer using the cessation application for shorter periods, whereas those who desired more text messages about smoking cessation were more inclined to use the application for longer durations.
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Smoking remains a primary cause of cancers, cardiovascular and respiratory diseases and death. Globally, efforts have been made to reduce smoking rates, but the addictive nature of nicotine, a key component of tobacco, makes cessation challenging for smokers. Medical interventions including medical advice and pharmacotherapies are effective methods for smoking cessation. The frequency of medical interventions correlates with success in smoking cessation. This study aims to compare the characteristics of the patients who visited the smoking cessation clinic once with those who visited more than once, in order to identify factors that are associated with repeat clinic visits. A total of 81 patients who have visited the smoking cessation clinic in Kangwon National University Hospital were included. Patients answered the questionnaire at their first visit. If the patient visited only once, the outcome was defined as negative and if the patient visited more than once, the outcome was defined as positive. The proportion of patients who answered "within 5 min" to the Fagerstrom Test for Nicotine Dependence's (FTND) 1st question and answered "yes" to the FTND's 6th question was higher in the negative outcome group. In the logistic regression, patients who had withdrawal symptoms previously were associated with positive outcomes (adjusted OR 3.466, 95% CI 1.088-11.034 and p value = 0.0354). Withdrawal symptoms during previous attempts were positively related to visiting the clinic more than once.
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Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential anti-tumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathione-dependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.
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Antineoplásicos , Lactoilglutationa Liase , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Estresse Oxidativo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Lactoilglutationa Liase/metabolismoRESUMO
Pulmonary fibrosis (PF) is a fatal chronic disease characterized by accumulation of extracellular matrix and thickening of the alveolar wall, ultimately leading to respiratory failure. PF is thought to be initiated by the dysfunction and aberrant activation of a variety of cell types in the lung. In particular, several studies have demonstrated that macrophages play a pivotal role in the development and progression of PF through secretion of inflammatory cytokines, growth factors, and chemokines, suggesting that they could be an alternative therapeutic source as well as therapeutic target for PF. In this review, we describe the characteristics, functions, and origins of subsets of macrophages involved in PF and summarize current data on the generation and therapeutic application of macrophages derived from pluripotent stem cells for the treatment of fibrotic diseases. Additionally, we discuss the use of macrophage-derived exosomes to repair fibrotic lung tissue.
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Exossomos , Células-Tronco Pluripotentes , Fibrose Pulmonar , Exossomos/metabolismo , Humanos , Pulmão/patologia , Macrófagos/metabolismo , Células-Tronco Pluripotentes/metabolismo , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/terapiaRESUMO
Using traditional statistical methods, we previously analyzed the risk factors and treatment outcomes of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation. Within the same cohort, we applied machine learning to create prediction and recommendation models. We analyzed 2572 transplants using eXtreme Gradient Boosting (XGBoost) to predict post-transplant VOD/SOS and early death. Using the XGBoost and SHapley Additive exPlanations (SHAP), we found influential factors and devised recommendation models, which were internally verified by repetitive ten-fold cross-validation. SHAP values suggested that gender, busulfan dosage, age, forced expiratory volume, and Disease Risk Index were significant factors for VOD/SOS. The areas under the receiver operating characteristic curves and the areas under the precision-recall curve of the models were 0.740, 0.144 for all VOD/SOS, 0.793, 0.793 for severe to very severe VOD/SOS, and 0.746, 0.304 for early death. According to our single feature recommendation, following the busulfan dosage was the most effective for preventing VOD/SOS. The recommendation method for six adjustable feature sets was also validated, and a subgroup corresponding to five to six features showed significant preventive power for VOD/SOS and early death. Our personalized treatment set recommendation showed reproducibility in repetitive internal validation, but large external cohorts should prospectively validate our model.
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Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Doenças Vasculares , Bussulfano/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/induzido quimicamente , Humanos , Aprendizado de Máquina , Reprodutibilidade dos Testes , Doenças Vasculares/induzido quimicamenteRESUMO
Human pluripotent stem cells (hPSCs) can give rise to a vast array of differentiated derivatives, which have gained great attention in the field of in vitro toxicity evaluation. We have previously demonstrated that hPSC-derived alveolar epithelial cells (AECs) are phenotypically and functionally similar to primary AECs and could be more biologically relevant alternatives for assessing the potential toxic materials including in fine dust and cigarette smoking. Therefore, in this study, we employed hPSC-AECs to evaluate their responses to exposure of various concentrations of diesel particulate matter (dPM), cigarette smoke extract (CSE) and nicotine for 48 hrs in terms of cell death, inflammation, and oxidative stress. We found that all of these toxic materials significantly upregulated the transcription of pro-inflammatory cytokines such as IL-1α, IL-ß, IL-6, and TNF-α. Furthermore, the exposure of dPM (100 µg/mL) strongly induced upregulation of genes related with cell death, inflammation, and oxidative stress compared with other concentrations of CSE and nicotine. These results suggest that hPSC-AECs could be a robust in vitro platform to evaluate pulmotoxicity of various air pollutants and harmful chemicals.
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The development of adsorbents with molecular precision offers a promising strategy to enhance storage of hydrogen and methaneâconsidered the fuel of the future and a transitional fuel, respectivelyâand to realize a carbon-neutral energy cycle. Herein we employ a postsynthetic modification strategy on a robust metal-organic framework (MOF), MFU-4l, to boost its storage capacity toward these clean energy gases. MFU-4l-Li displays one of the best volumetric deliverable hydrogen capacities of 50.2 g L-1 under combined temperature and pressure swing conditions (77 K/100 bar â 160 K/5 bar) while maintaining a moderately high gravimetric capacity of 9.4 wt %. Moreover, MFU-4l-Li demonstrates impressive methane storage performance with a 5-100 bar usable capacity of 251 cm3 (STP) cm-3 (0.38 g g-1) and 220 cm3 (STP) cm-3 (0.30 g g-1) at 270 and 296 K, respectively. Notably, these hydrogen and methane storage capacities are significantly improved compared to those of its isoreticular analogue, MFU-4l, and place MFU-4l-Li among the best MOF-based materials for this application.
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Increased mTOR activity has been shown to enhance regeneration of injured axons by increasing neuronal protein synthesis, while PTEN signaling can block mTOR activity to attenuate protein synthesis. MicroRNAs (miRs) have been implicated in regulation of PTEN and mTOR expression, and previous work in spinal cord showed an increase in miR-199a-3p after spinal cord injury (SCI) and increase in miR-21 in SCI animals that had undergone exercise. Pten mRNA is a target for miR-21 and miR-199a-3p is predicted to target mTor mRNA. Here, we show that miR-21 and miR-199a-3p are expressed in adult dorsal root ganglion (DRG) neurons, and we used culture preparations to test functions of the rat miRs in adult DRG and embryonic cortical neurons. miR-21 increases and miR-199a-3p decreases in DRG neurons after in vivo axotomy. In both the adult DRG and embryonic cortical neurons, miR-21 promotes and miR-199a-3p attenuates neurite growth. miR-21 directly bound to Pten mRNA and miR-21 overexpression decreased Pten mRNA levels. Conversely, miR-199a-3p directly bound to mTor mRNA and miR-199a-3p overexpression decreased mTor mRNA levels. Overexpressing miR-21 increased both overall and intra-axonal protein synthesis in cultured DRGs, while miR-199a-3p overexpression decreased this protein synthesis. The axon growth phenotypes seen with miR-21 and miR-199a-3p overexpression were reversed by co-transfecting PTEN and mTOR cDNA expression constructs with the predicted 3' untranslated region (UTR) miR target sequences deleted. Taken together, these studies indicate that injury-induced alterations in miR-21 and miR-199a-3p expression can alter axon growth capacity by changing overall and intra-axonal protein synthesis through regulation of the PTEN/mTOR pathway.
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Axônios , MicroRNAs , PTEN Fosfo-Hidrolase , Serina-Treonina Quinases TOR , Animais , Axônios/metabolismo , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , RNA Mensageiro , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
In statistical modelling with Gaussian process regression, it has been shown that combining (few) high-fidelity data with (many) low-fidelity data can enhance prediction accuracy, compared to prediction based on the few high-fidelity data only. Such information fusion techniques for multi-fidelity data commonly approach the high-fidelity model f h(t) as a function of two variables (t, s), and then use f l(t) as the s data. More generally, the high-fidelity model can be written as a function of several variables (t, s 1, s 2 .); the low-fidelity model f l and, say, some of its derivatives can then be substituted for these variables. In this paper, we will explore mathematical algorithms for multi-fidelity information fusion that use such an approach towards improving the representation of the high-fidelity function with only a few training data points. Given that f h may not be a simple function-and sometimes not even a function-of f l, we demonstrate that using additional functions of t, such as derivatives or shifts of f l, can drastically improve the approximation of f h through Gaussian processes. We also point out a connection with 'embedology' techniques from topology and dynamical systems. Our illustrative examples range from instructive caricatures to computational biology models, such as Hodgkin-Huxley neural oscillations.
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BACKGROUND: Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC). METHODS: Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0-150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014). CONCLUSION: Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptores do Ácido Retinoico/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia , Taxa de SobrevidaRESUMO
The original PDF version of this Article omitted to state that "Jeongho Han and Seok-Hyeon Kang contributed equally to this work" in the affiliations section. This has now been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.
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INTRODUCTION AND OBJECTIVES: Although tobacco smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), more than one-fourth of COPD patients are non-smokers. In this cross-sectional study, the differences in COPD phenotypes between non-smokers and smokers in male subjects were investigated and were focused on structural lung changes using a quantitative assessment of computed tomography (CT) images. METHODS: They divided male participants with COPD, from a Korean cohort near a cement plant, into non-smokers and smokers by a cutoff of a 5 pack-year smoking history. Clinical characteristics, including age, body mass index (BMI), spirometry results, history of biomass smoke exposure, and CT measurements, were compared between the two groups. Emphysema index (EI) and mean wall area percentage (MWA %) were used to evaluate the structural lung changes on volumetric CT scans. RESULTS: The non-smoker group (n = 49) had younger patients and had a greater BMI than the smoker group (n = 113) (P < .05). Spirometry results, including post-bronchodilator forced expiratory volume in 1 s, were comparable between the two groups. More smokers had emphysema than non-smokers (EI 10.0 vs. 6.5, P < .001), but after accounting the potential confounders in model analysis, the difference was borderline significance (P = .051). In the subgroup of biomass smoke-exposed subjects, MWA% was significantly greater in smokers than in non-smokers (MWA 69.1 vs. 65.3, P = .03), while EI was not statistically different (EI 7.1 vs. 10.4, P = .52). CONCLUSIONS: Non-smoker males with COPD were younger and had a greater BMI than the smokers. Tobacco smoke exposure seemed to be associated with an emphysema-predominant phenotype, while biomass smoke exposure exhibited a significant interaction with tobacco smoking in an airway-predominant phenotype.
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Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Fatores Etários , Idoso , Estudos Transversais , Estudos de Avaliação como Assunto , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Prevalência , Doença Pulmonar Obstrutiva Crônica/genética , Valores de Referência , República da Coreia/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Espirometria/métodos , Estatísticas não Paramétricas , Taxa de SobrevidaRESUMO
Superplastic alloys exhibit extremely high ductility (>300%) without cracks when tensile-strained at temperatures above half of their melting point. Superplasticity, which resembles the flow behavior of honey, is caused by grain boundary sliding in metals. Although several non-ferrous and ferrous superplastic alloys are reported, their practical applications are limited due to high material cost, low strength after forming, high deformation temperature, and complicated fabrication process. Here we introduce a new compositionally lean (Fe-6.6Mn-2.3Al, wt.%) superplastic medium Mn steel that resolves these limitations. The medium Mn steel is characterized by ultrafine grains, low material costs, simple fabrication, i.e., conventional hot and cold rolling, low deformation temperature (ca. 650 °C) and superior ductility above 1300% at 850 °C. We suggest that this ultrafine-grained medium Mn steel may accelerate the commercialization of superplastic ferrous alloys.Research in new alloy compositions and treatments may allow the increased strength of mass-produced, intricately shaped parts. Here authors introduce a superplastic medium manganese steel which has an inexpensive lean chemical composition and which is suited for conventional manufacturing processes.
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Cadmium (Cd), a major component of cigarette smoke, disrupts the normal functions of airway cells and can lead to the development of various pulmonary diseases such as chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms involved in Cd-induced pulmonary diseases are poorly understood. Here, we identified a cluster of genes that are altered in response to Cd exposure in human bronchial epithelial cells (BEAS-2B) and demonstrated that Cd-induced ER stress and inflammation are mediated via CCAAT-enhancer-binding proteins (C/EBP)-DNA-damaged-inducible transcript 3 (DDIT3) signaling in BEAS-2B cells. Cd treatment led to marked upregulation and downregulation of genes associated with the cell cycle, apoptosis, oxidative stress and inflammation as well as various signal transduction pathways. Gene set enrichment analysis revealed that Cd treatment stimulated the C/EBP signaling pathway and induced transcriptional activation of its downstream target genes, including DDIT3. Suppression of DDIT3 expression using specific small interfering RNA effectively alleviated Cd-induced ER stress and inflammatory responses in both BEAS-2B and normal primary normal human bronchial epithelial cells. Taken together, these data suggest that C/EBP signaling may have a pivotal role in the early induction of ER stress and inflammatory responses by Cd exposure and could be a molecular target for Cd-induced pulmonary disease.
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Cádmio/efeitos adversos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Inflamação/etiologia , Inflamação/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Análise por Conglomerados , Citocinas/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Homeostase/efeitos dos fármacos , Humanos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Mucosa Respiratória/patologia , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismoRESUMO
BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.
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Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-1α and K562) in vitro using Transwell® co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-1α and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.
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BACKGROUND: There is growing evidence about sex-related phenotypes of COPD. However, the sex differences in COPD mainly result from smokers. This study evaluated the sex differences in nonsmoking patients with COPD, focusing on structural changes in the lungs in airway diseases and emphysema. METHODS: Ninety-seven nonsmoking patients, defined as having <1 pack-year of lifetime cigarette smoking, diagnosed with COPD were selected from a Korean COPD cohort. Emphysema extent and mean wall area percentage (WA%) on computed tomography were compared between the male and female groups. RESULTS: The 97 patients with COPD included 62 females and 35 males. Emphysema index was significantly lower (3.5±4.2 vs 6.2±5.7, P<0.01) and mean WA% on computed tomography was significantly higher (71.8%±5% vs 69.4%±5%, P<0.01) in females than in males, after adjusting for age, body mass index, history of biomass exposure, and postbronchodilator forced expiratory volume in 1 second (% of predicted). CONCLUSION: WA% was higher and emphysema extent was lower in nonsmoking females with COPD than in nonsmoking males with COPD. These findings suggest that males may be predisposed to an emphysema phenotype and females may be predisposed to an airway phenotype of COPD.
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Tomografia Computadorizada de Feixe Cônico , Disparidades nos Níveis de Saúde , Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Remodelação das Vias Aéreas , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/fisiopatologia , República da Coreia , Índice de Gravidade de Doença , Fatores Sexuais , Capacidade VitalRESUMO
INTRODUCTION: The development of reliable gene expression profiling technology increasingly impacts our understanding of lung cancer biology. Here, we used RNA sequencing (RNA-Seq) to compare the transcriptomes of non-small cell lung cancer (NSCLC) and normal lung tissues and to investigate expression in lung cancer tissues. METHODS: We enrolled 88 male patients (mean age, 61.2 years) with NSCLC. RNA-Seq was performed on 88 pairs of NSCLC tumor tissue and non-tumor tissue from 54 patients with adenocarcinoma and 34 patients with squamous cell carcinoma. Immunohistochemistry was performed to validate differential candidate gene expression in a different NSCLC group. RESULTS: RNA-Seq produced 25.41 × 10(6) (± 8.90 × 10(6)) reads in NSCLC tissues and 24.70×10(6) (± 4.70 × 10(6)) reads in normal lung tissues [mean (± standard deviation)]. Among the genes expressed in both tissues, 335 were upregulated and 728 were downregulated ≥ 2-fold (p < 0.001). Four upregulated genes - CBX3, GJB2, CRABP2, and DSP - not previously reported in lung cancer were studied further. Their altered expression was verified by immunohistochemistry in a different set of NSCLC tissues (n = 154). CBX3 was positive in 90.3% (139 cases) of the samples; GJB2, in 22.7% (35 cases); CRABP2, in 72.1% (111 cases); and DSP, in 17.5% (27 cases). The positive rate of CRABP2 was higher in adenocarcinoma than squamous cell carcinoma (p < 0.01). CONCLUSIONS: CBX3 and CRABP2 expression was markedly increased in lung cancer tissues and especially CRABP2 may be promising candidate genes in lung adenocarcinoma.
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Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas Cromossômicas não Histona/biossíntese , Neoplasias Pulmonares/genética , Receptores do Ácido Retinoico/biossíntese , Idoso , Biomarcadores Tumorais/genética , Proteínas Cromossômicas não Histona/genética , Conexina 26 , Conexinas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Receptores do Ácido Retinoico/genética , Análise de Sequência de RNA , Análise Serial de Tecidos , Transcriptoma , Regulação para CimaRESUMO
Small proline-rich protein 2a (Sprr2a) is one of the structural components of the cornified keratinocyte cell envelope that contributes to form a protective barrier in the skin against dehydration and environmental stress. Interestingly, Sprr2a mRNA is detected in the mouse uterus and is regulated by 17ß-oestradiol (E2). In the present study, we investigated the effects of E2 and oestrogenic compounds on the regulation and localisation of Sprr2a protein in the mouse uterus. Immunohistochemical staining revealed that Sprr2a protein is detected only in the adult uterus, and not in the ovary, oviduct or testis. We also demonstrated that Sprr2a protein is tightly regulated by E2 in the mouse uterus and exclusively detected in luminal and glandular epithelial cells. Furthermore, Sprr2a is dose-dependently induced by oestrogenic compounds such as bisphenol A and 4-tert-octylphenol. Collectively, our studies suggest that Sprr2a protein may have a unique function in physiological events in the mouse uterus and can be used as an indicator to detect compounds with oestrogenic activity in the mouse uterus.
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Proteínas Ricas em Prolina do Estrato Córneo/metabolismo , Estradiol/análogos & derivados , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Útero/metabolismo , Animais , Compostos Benzidrílicos/farmacologia , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Estrogênios não Esteroides/farmacologia , Feminino , Fulvestranto , Masculino , Camundongos , Fenóis/farmacologia , Testículo/metabolismo , Útero/efeitos dos fármacosRESUMO
This paper describes the development of a hand-held gamma camera for intraoperative surgical guidance that is based on silicon photomultiplier (SiPM) technology. The camera incorporates a cerium doped lanthanum bromide (LaBr3:Ce) plate scintillator, an array of 80 SiPM photodetectors and a two-layer parallel-hole collimator. The field of view is circular with a 60 mm diameter. The disk-shaped camera housing is 75 mm in diameter, approximately 40.5 mm thick and has a mass of only 1.4 kg, permitting either hand-held or arm-mounted use. All camera components are integrated on a mobile cart that allows easy transport. The camera was developed for use in surgical procedures including determination of the location and extent of primary carcinomas, detection of secondary lesions and sentinel lymph node biopsy (SLNB). Here we describe the camera design and its principal operating characteristics, including spatial resolution, energy resolution, sensitivity uniformity, and geometric linearity. The gamma camera has an intrinsic spatial resolution of 4.2 mm FWHM, an energy resolution of 21.1 % FWHM at 140 keV, and a sensitivity of 481 and 73 cps/MBq when using the single- and double-layer collimators, respectively.