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Acute lung injury (ALI) is a severe condition that can progress to acute respiratory distress syndrome (ARDS), with a high mortality rate. Currently, no specific and compelling drug treatment plan exists. Mesenchymal stem cells (MSCs) have shown promising results in preclinical and clinical studies as a potential treatment for ALI and other lung-related conditions due to their immunomodulatory properties and ability to regenerate various cell types. The present study focuses on analyzing the role of umbilical cord MSC (UC-MSC))-derived exosomes in reducing lipopolysaccharide-induced ALI and investigating the mechanism involved. The study demonstrates that UC-MSC-derived exosomes effectively improved the metabolic function of alveolar macrophages and promoted their shift to an anti-inflammatory phenotype, leading to a reduction in ALI. The findings also suggest that creating three-dimensional microspheres from the MSCs first can enhance the effectiveness of the exosomes. Further research is needed to fully understand the mechanism of action and optimize the therapeutic potential of MSCs and their secretome in ALI and other lung-related conditions.
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Lesão Pulmonar Aguda , Exossomos , Transplante de Células-Tronco Mesenquimais , Humanos , Lipopolissacarídeos/efeitos adversos , Exossomos/metabolismo , Macrófagos Alveolares/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/terapia , Lesão Pulmonar Aguda/metabolismo , Cordão Umbilical/metabolismoRESUMO
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases in critically ill patients. Although pathophysiology of ALI/ARDS has been investigated in many studies, effective therapeutic strategies are still limited. Mesenchymal stem cell (MSC)-based therapy is emerging as a promising therapeutic intervention for patients with ALI. During the last two decades, researchers have focused on the efficacy and mechanism of MSC application in ALI animal models. MSC derived from variant resources exhibited therapeutic effects in preclinical studies of ALI with different mechanisms. Based on this, clinical studies on MSC treatment in ALI/ARDS has been tried recently, especially in COVID-19 caused lung injury. Emerging clinical trials of MSCs in treating COVID-19-related conditions have been registered in past two years. The advantages and potential of MSCs in the defense against COVID-19-related ALI or ARDS have been confirmed. This review provides a brief overview of recent research progress in MSC-based therapies in preclinical study and clinical trials in ALI treatment, as well as the underlying mechanisms.
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Lesão Pulmonar Aguda , COVID-19 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Síndrome do Desconforto Respiratório , SARS-CoV-2 , Humanos , Lesão Pulmonar Aguda/terapia , COVID-19/terapia , Células-Tronco Mesenquimais/citologia , Animais , Síndrome do Desconforto Respiratório/terapia , Ensaios Clínicos como AssuntoRESUMO
Acute lung injury (ALI) is a severe medical condition that causes inflammation and fluid buildup in the lung, resulting in respiratory distress. Moreover, ALI often occurs as a complication of other medical conditions or injuries, including the coronavirus disease of 2019. Mesenchymal stem/stromal cells (MSCs) are being studied extensively for their therapeutic potential in various diseases, including ALI. The results of recent studies suggest that the beneficial effects of MSCs may not be primarily due to the replacement of damaged cells but rather the release of extracellular vesicles (EVs) and other soluble factors through a paracrine mechanism. Furthermore, EVs derived from MSCs preserve the therapeutic action of the parent MSCs and this approach avoids the safety issues associated with live cell therapy. Thus, MSC-based cell-free therapy may be the focus of future clinical treatments.
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Lesão Pulmonar Aguda , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Lesão Pulmonar Aguda/terapia , Terapia Baseada em Transplante de Células e Tecidos , InflamaçãoRESUMO
This study aims to investigate the effect of placenta-derived mesenchymal stem cells (PMSCs) administration on tissue repair following acute lung injury (ALI). PMSCs were transplanted intravenously to a mouse model of lipopolysaccharide-induced ALI. The therapeutic effects were determined by evaluating several indicators, including pathology; the wet/dry ratio of the lungs; blood gas analysis; the total protein content, cell numbers, and the activity of myeloperoxidase (MPO) in bronchial alveolar lavage fluid (BALF); and the levels of anti-inflammatory and proinflammatory cytokines in serum and BALF. To investigate the underlying mechanism, PMSC-derived exosomes were used for ALI treatment. Administration of PMSCs improved the degree of lung injury, reduced inflammation, increased the expression levels of anti-inflammatory cytokines, and protected lung function. As expected, the effects of PMSC-derived exosomes in the ALI model were similar to those of PMSCs, both in terms of improved lung function and reduced inflammation. These findings suggest that PMSCs have ameliorating effects on ALI that are potentially mediated via their secreted exosomes.
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Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Camundongos , Animais , Humanos , Células-Tronco Mesenquimais/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/terapia , Lesão Pulmonar Aguda/metabolismo , Pulmão/metabolismo , Citocinas/metabolismo , Lipopolissacarídeos/efeitos adversos , Fatores Imunológicos , Inflamação/metabolismoRESUMO
Mesenchymal stromal/stem cells (MSCs) possess the ability to self-renew and differentiate into other cell types. Because of their anti-inflammatory and immunomodulatory abilities, as well as their more ready availability compared to other stem cell sources, MSCs hold great promise for the treatment of many diseases, such as haematological defects, acute respiratory distress syndrome, autoimmunity, cardiovascular diseases, etc. However, immune rejection remains an important problem. MSCs are considered to have low immunogenicity, but they do not have full immunological privilege. This review analyzes and discusses the safety of MSCs from the perspective of their immunogenicity, with the aim of providing a reference for future research and clinical application.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Diferenciação Celular/imunologia , ImunomodulaçãoRESUMO
Osimertinib, the third generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the standard treatment for nonsmall cell lung cancer with EGFR mutation. However, osimertinib-induced interstitial lung disease (OsiILD) is considered to be a serious adverse event, so some patients will have to discontinue the use of osimertinib due to OsiILD. Almonertinib is a novel third-generation EGFR-TKI. We herein report a patient who developed OsiILD after the use of osimertinib and then switched to almonertinib for further treatment with success. This is the first report of a successfull rechallenge with low-dose almonertinib after OsiILD. We also reviewed the literature to explore the possible risk factors and the subsequent treatment of OsiILD, suggesting that low-dose almonertinib may be an option for follow-up treatment of OsiILD.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Receptores ErbB/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Compostos de Anilina/uso terapêutico , Mutação , Doenças Pulmonares Intersticiais/induzido quimicamenteRESUMO
To explore the effect of lycorine in inducing apoptosis of pulmonary carcinoma cell A549 and its mechanism. In the study, pulmonary carcinoma cell A549 were taken as the experimental subject and processed with different concentrations of lycorine (0, 0.5, 1.0, 2.0, 4.0 and 8.0 µmol x L(-1)). The MTT method was used to observe the cell proliferation. The apoptosis rate of A549 cells was determined by Annexin FITC/PI double staining. The microplate reader was used to detect the activities of Bcl-2, Bax and p53. The changes in mitochondrial membrane potential were measured by the flow cytometry. The expressions of apoptosis-related factors Bcl-2, Bax, p53 and Survivin were determined by Real-time PCR. The results showed that lycorine significantly inhibited the proliferation of A549 cells (P < 0.05), induced the apoptosis on A549 cells (P < 0.05), increased the activities of Bax and p53, reduced Bcl-2 activity and mitochondrial membrane potential, and notably changed the gene expressions of Bcl-2, Bax, p53 and Survivin (P < 0.05). In conclusion, lycorine can induce the apoptosis of A549 cells and be applied to treat pulmonary carcinoma. Its mechanism may be related to the activation of relevant factors in Bcl-2 signaling pathway.
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Alcaloides de Amaryllidaceae/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma/fisiopatologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/fisiopatologia , Fenantridinas/farmacologia , Carcinoma/tratamento farmacológico , Carcinoma/genética , Carcinoma/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Background: Community-acquired pneumonia (CAP) is a global health concern due to its high rates of morbidity and mortality. Bacterial pathogens are common causes of CAP. It is one of the most common causes of acute respiratory distress syndrome (ARDS), a common severe respiratory system manifestation threatening human health. This study aimed to establish a predictive model for ARDS in patients with bacterial pneumonia, which was conducive to early identification of the occurrence and effective prevention of ARDS. Methods: We collected the clinical data of hospitalized patients with bacterial pneumonia in Affiliated Huzhou Hospital of Zhejiang University School of Medicine from January 2022 to November 2022. The independent risk factors for ARDS in patients with bacterial pneumonia were determined by univariate and multivariate binary logistic regression analyses. The nomogram was constructed to display the predictive model, and the receiver-operating characteristic curve was plotted to evaluate the predictive value of ARDS. Results: This study included 254 patients with bacterial pneumonia, of which 114 developed ARDS. The multivariate logistic regression analysis revealed age [odds ratio (OR) = 1.041, P = 0.003], heart rate (OR = 1.020, P = 0.028), lymphocyte count (OR = 0.555, P = 0.033), white blood cell count (OR = 1.062, P = 0.033), bilateral lung lesions (OR = 7.352, P = 0.011) and pleural effusion (OR = 2.512, P = 0.002) as the independent risk factors for ARDS. The predictive model was constructed based on the six independent factors, which was valuable in predicting ARDS with area under the curve of 0.794. Conclusion: The predictive model was beneficial to evaluate the disease progression in patients with bacterial pneumonia and identify ARDS. Further, our nomogram might help doctors predict the incidence of ARDS and conduct treatment as early as possible.
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AIM: To investigate the expression profile of microRNAs in inoperable advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and the potential relevance of microRNAs to clinicopathological characteristics and prognosis. METHODS: Serum samples were taken from 260 inoperable advanced NSCLC patients and 260 healthy individuals. All the patients received cisplatin-based chemotherapy, including NP/NC regimens, GP/GC regimens, and TP/TC regimens. The serum levels of microRNAs (miR-125b, miR-10b, miR-34a and miR-155) were determined by quantitative real-time PCR. RESULTS: Serum levels of the 4 microRNAs examined in NSCLC patients were significantly increased as compared with healthy individuals. The levels of miR-125b and miR-155 were changed in a similar pattern: the patients with stage IV disease had the highest one, while the patients with stage III A and stage III B disease showed similar increased levels. The levels of miR-10b and miR-34a in the patients with different stages were increased to similar extent. The level of miR-125b in poorly differentiated cancer was significantly higher than those in well and moderately differentiated cancers, while the levels of miR-10b, miR-34a, and miR-155 did not significantly differ with cancer differentiation. Among the 4 microRNAs examined, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression levels in non-responsive patients. Furthermore, the high level of miR-125b was significantly correlated with poor patient survival. A multivariate Cox regression analysis showed that the expression level of miR-125b was an independent prognostic marker in NSCLC patients. CONCLUSION: Our results suggest that miR-125b is a potential diagnostic or prognostic biomarker for NSCLC. This finding has important implications for development of targeted therapeutics to overcome chemotherapeutic resistance in NSCLC.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Diagnóstico , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , PrognósticoRESUMO
Background and Objective: Lung cancer is the second most prevalent malignancy and has the highest death rate. The main approaches for lung cancer treatment include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, the treatments of the disease need to be further improved. An increasing number of scientific investigations indicated cell therapy to be a successful new treatment for lung cancer. Cell therapy can improve the host's immunity to disease and can compensate for the shortcomings in the therapeutic effects of traditional treatments, particularly in the case of cancer treatment. However, due to its recent development, its clinical efficacy still needs to be further examined. In order to provide an updated source on cell therapy for lung cancer, this paper summarizes the clinical use of chimeric antigen receptor T cells (CAR-Ts), stem cells, cytokine-induced killer cells (CIKs), and tumor-infiltrating lymphocytes (TILs) and discusses recent clinical advancements. Methods: We performed a search of the PubMed database on March 28, 2023, and again on June 10, 2023. A review of retrieved literature related to cell therapy and treatments for lung cancer was completed. Key Content and Findings: Cell therapy has been applied in clinical studies on the treatment of disorders of the hematologic system, digestive system, respiratory system, and other systems. CAR-T therapy has been successfully used in the treatment of B-cell malignancies, which suggests that cell therapy has broad prospects in the treatment of malignant tumors. CAR-T, stem cells, CIKs, and TILs exert antitumor activity and can recognize and could be used to treat lung cancer. Conclusions: Cell therapy represents a novel solution in the treatment of lung cancer. Cell therapy, when combined with traditional therapies, can compensate for the shortcomings of these methods. Further research is needed to reduce the occurrence of adverse reactions and provide a more effective approach in treating lung cancer.
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Introduction: Acute lung injury (ALI) is a severe respiratory tract disorder facilitated by dysregulated inflammation, oxidative stress and intestinal ecosystem. Fecal microbiota transplantation (FMT) is a rapid method for gut microbiota (GM) reconstruction. Furthermore, our previous studies have confirmed that human umbilical cord mesenchymal stromal cells (HUC-MSCs) can alleviate ALI by improving GM composition. Therefore, we aimed to explore the efficacy and mechanism of FMT from HUC-MSCs-treated mice on ALI. Methods: In brief, fresh feces from HUC-MSCs-treated mice were collected for FMT, and the mice were randomly assigned into NC, FMT, LPS, ABX-LPS, and ABX-LPS-FMT groups (n = 12/group). Subsequently, the mice were administrated with antibiotic mixtures to deplete GM, and given lipopolysaccharide and FMT to induce ALI and rebuild GM. Next, the therapeutic effect was evaluated by bronchoalveolar lavage fluid (BALF) and histopathology. Immune cells in peripheral blood and apoptosis in lung tissues were measured. Furthermore, oxidative stress- and inflammation-related parameter levels were tested in BALF, serum, lung and ileal tissues. The expressions of apoptosis-associated, TLR4/NF-κB pathway-associated, Nrf2/HO-1 pathway related and tightly linked proteins in the lung and ileal tissues were assessed. Moreover, 16S rRNA was conducted to assess GM composition and distribution. Results: Our results revealed that FMT obviously improved the pathological damage of lung and ileum, recovered the immune system of peripheral blood, decreased the cell apoptosis of lung, and inhibited inflammation and oxidative stress in BALF, serum, lung and ileum tissues. Moreover, FMT also elevated ZO-1, claudin-1, and occludin protein expressions, activating the Nrf2/HO-1 pathway but hindering the TLR4/NF-κB pathway. Of note, the relative abundances of Bacteroides, Christensenella, Coprococcus, and Roseburia were decreased, while the relative abundances of Xenorhabdus, Sutterella, and Acinetobacter were increased in the ABX-LPS-FMT group. Conclusion: FMT from HUC-MSCs-treated mice may alleviate ALI by inhibiting inflammation and reconstructing GM, additionally, we also found that the TLR4/NF-κB and Nrf2/HO-1 pathways may involve in the improvement of FMT on ALI, which offers novel insights for the functions and mechanisms of FMT from HUC-MSCs-treated mice on ALI.
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BACKGROUND: Acute lung injury (ALI) and its final severe stage, acute respiratory distress syndrome, are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments. Gut microbiota homeostasis, including that in ALI, is important for human health. Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis. Human umbilical cord mesenchymal cells (HUC-MSCs) have attractive prospects for ALI treatment. This study hypothesized that HUC-MSCs improve ALI via the lung-gut microflora. AIM: To explore the effects of HUC-MSCs on lipopolysaccharide (LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process. METHODS: C57BL/6 mice were randomly divided into four groups (18 rats per group): Sham, sham + HUC-MSCs, LPS, and LPS + HUC-MSCs. ALI was induced in mice by intraperitoneal injections of LPS (10 mg/kg). After 6 h, mice were intervened with 0.5 mL phosphate buffered saline (PBS) containing 1 × 106 HUC-MSCs by intraperitoneal injections. For the negative control, 100 mL 0.9% NaCl and 0.5 mL PBS were used. Bronchoalveolar lavage fluid (BALF) was obtained from anesthetized mice, and their blood, lungs, ileum, and feces were obtained by an aseptic technique following CO2 euthanasia. Wright's staining, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, Evans blue dye leakage assay, immunohistochemistry, fluorescence in situ hybridization, western blot, 16S rDNA sequencing, and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice, and the involvement of the lung-gut axis in this process was explored. One-way analysis of variance with post-hoc Tukey's test, independent-sample Student's t-test, Wilcoxon rank-sum test, and Pearson correlation analysis were used for statistical analyses. RESULTS: HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury, and decrease mononuclear cell and neutrophil counts, protein concentrations in BALF and inflammatory cytokine levels in the serum, lung, and ileum of ALI mice. Especially, HUC-MSCs decreased Evans blue concentration and Toll-like receptor 4, myeloid differentiation factor 88, p-nuclear factor kappa-B (NF-κB)/NF-κB, and p-inhibitor α of NF-κB (p-IκBα)/IκBα expression levels in the lung, and raised the pulmonary vascular endothelial-cadherin, zonula occludens-1 (ZO-1), and occludin levels and ileal ZO-1, claudin-1, and occludin expression levels. HUC-MSCs improved gut and BALF microbial homeostases. The number of pathogenic bacteria decreased in the BALF of ALI mice treated with HUC-MSCs. Concurrently, the abundances of Oscillospira and Coprococcus in the feces of HUS-MSC-treated ALI mice were significantly increased. In addition, Lactobacillus, Bacteroides, and unidentified_Rikenellaceae genera appeared in both feces and BALF. Moreover, this study performed metabolomic analysis on the lung tissue and identified five upregulated metabolites and 11 downregulated metabolites in the LPS + MSC group compared to the LPS group, which were related to the purine metabolism and the taste transduction signaling pathways. Therefore, an intrinsic link between lung metabolite levels and BALF flora homeostasis was established. CONCLUSION: This study suggests that HUM-MSCs attenuate ALI by redefining the gut and lung microbiota.
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Acute lung injury (ALI) is significantly associated with morbidity and mortality in patients with critical diseases. In recent years, studies have identified that mesenchymal stem/stromal cells (MSCs) ameliorate ALI and pulmonary fibrosis. However, the mechanism underlying this outcome in ALI has not yet been investigated. In this study, RNA sequencing technology was used to analyze the gene expression profile of lung tissue in lipopolysaccharide (LPS)-induced ALI rats following treatment with human umbilical cord MSC (HUCMSC). Differential expression analyses, gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes enrichment, protein-protein interaction network identification, and hub gene analysis were also performed. HUCMSC treatment decreased inflammatory factor production and alveolar exudates, and attenuated lung damage in LPS-induced ALI rats. The RNA-Seq data indicated that HUCMSC treatment activated the IL-17, JAK-STAT, NF-κB, and TNF-α signaling pathways, increased oxygen transport, and decreased extracellular matrix organization. HUCMSC exert beneficial effects on ALI via these signaling pathways by reducing inflammation, inhibiting pulmonary fibrosis, and improving lung ventilation. Moreover, our study further revealed the hub genes (Tbx2, Nkx2-1, and Atf5) and signaling pathways involved in HUCMSC treatment, thus providing novel perspectives for future research into the molecular mechanisms underlying cell treatment of ALI. HUCMSC can regulate multiple genes and signaling pathways, which can prevent LPS-induced lung damage in an ALI rat model.
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Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Fibrose Pulmonar , Humanos , Ratos , Animais , Lipopolissacarídeos/efeitos adversos , Fibrose Pulmonar/metabolismo , Cordão Umbilical , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/terapia , Células-Tronco Mesenquimais/metabolismo , Análise de Sequência de RNA , RNA/metabolismoRESUMO
To study the role of the adiponectin (ADIPOQ) gene single-nucleotide polymorphism (SNP) in the susceptibility and prognosis for non-small cell lung cancer (NSCLC), we recruited 344 patients with NSCLC, of which 141 had undergone surgical resection and post-surgery follow up. For controls, there were 264 healthy volunteers for the control group, matched in age and sex with the NSCLC patients. Genotyping of SNPs in the ADIPOQ gene, namely, rs266729 (11365C>G); rs822395 (4034A>C); rs822396 (3964A>G); rs2241766 (+45T>G) were performed. Of all SNPs in the ADIPOQ gene, only the TT genotype and T allele frequency of the rs2241766 were more prevalent in NSCLC subjects than in controls. The TT genotype of rs2241766 was significantly associated with susceptibility to NSCLC before and after adjustment for age, sex, body mass index, and smoking status. In the survival analyses of subjects receiving surgical resection, only the SNPs of rs2241766 were significantly related to overall survival of NSCLC. Our results suggest that the SNP rs2241766 of the ADIPOQ gene may determine both susceptibility to NSCLC, and the prognosis for those who underwent surgical treatment.
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Biomarcadores/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos de Associação Genética , Polimorfismo de Nucleotídeo Único , Adiponectina/sangue , Adiponectina/genética , Fatores Etários , Índice de Massa Corporal , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos de Casos e Controles , Impressões Digitais de DNA , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo Genético , Prognóstico , Fatores de Risco , Fatores Sexuais , Fumar , Análise de SobrevidaRESUMO
[This corrects the article on p. 3921 in vol. 8, PMID: 27725871.].
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Adiponectin is the most abundant adipokine in the tumor microenvironment. The role of this protein in tumor progression, however, remains controversial. In the present study, we aimed to investigate the effects of adiponectin on the abilities of migration and invasion in nonsmall cell lung carcinoma (NSCLC). Using NSCLC cell lines, we examined the effects of adiponectin on cell migration and invasion using Transwell assays. Expression of epithelialmesenchymal transition markers was examined via microscopy and western blotting. We also performed a knockdown of Twist, AdipoR1 and AdipoR2 in NSCLC cells with siRNAs. The addition of adiponectin to NSCLC cells inhibited both the migration and invasion abilities. Furthermore, we found that NSCLC cells displayed increased epithelial marker expression and downregulation of mesenchymal marker expression following adiponectin administration. Twist AdipoR1 and AdipoR2 knockdown reversed the inhibitory effects of adiponectin on migration and invasion in NSCLC and epithelialmesenchymal transition. Exogenous adiponectin significantly impaired the migratory and invasive capacities of NSCLC cells through reversal of EMT, suggesting that adiponectin may be a novel promising therapeutic approach against NSCLC.
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Adiponectina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Apoptose , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células , Humanos , Neoplasias Pulmonares/metabolismo , Invasividade Neoplásica , RNA Interferente Pequeno/genética , Células Tumorais CultivadasRESUMO
OBJECTIVE: The aim of this article is to study the superiority and safety of laparoscopic surgery for colorectal carcinoma. SUMMARY BACKGROUND DATA: Laparoscopy in rectal cancer is still not recommended as the treatment of choice by National Comprehensive Cancer Network guidelines. Laparoscopic rectal surgery is more complex and technically demanding, especially for mid and low rectal cancer. METHODS: A computer-based online research of retrospective or prospective studies addressing laparoscopic surgery versus conventional open surgery for colorectal carcinoma published in the last 11 years was performed in electronic database (Wangfang Database, China National Knowledge Infrastructure, Chinese Medical Current Contents, Pubmed, Medline, Ovid, Elsevier, ISI Web of Knowledge, Cohrane Database of Systematic Reviews). Selective trials were analyzed by the Review Manager 5.2 software. RESULTS: A total of 9 clinical trials, involving a total of 4747 patients, were identified. A meta-analysis showed that operating time was not significantly different between the 2 groups [WMDâ=â0.46, 95% confidence interval (95% CI): -55.68 to 56.60, Pâ=â.99], intraoperative blood loss in laparoscopic surgery group was less than conventional open surgery group (WMDâ=â-64.66, 95% CI: -87.31 to 42.01, Pâ<â.01); No significant difference in the number of lymph node retrieved from postoperative pathologic specimens was found between the 2 groups (WMDâ=â-0.75, 95% CI: -1.72 to 0.23, Pâ=â.14); Postoperative time to flatus in laparoscopic surgery group was earlier than that in open surgery significantly (WMDâ=â-1.22, 95% CI: -1.53 to -0.91, Pâ<â.01). The cases of postoperative complications were significantly different between the 2 groups, which showed that the cases of laparoscopic surgery group were less than those of open surgery group [odds ratio (OR)â=â0.62, 95% CI: 0.52â¼0.72, Pâ<â.01]; Moreover, hospital stay of laparoscopic surgery group was shorter than that of open surgery that showed significant difference (WMDâ=â-2.38, 95% CI:-3.30 to -1.46, Pâ<â.01). CONCLUSION: Short-term outcomes of laparoscopic surgery are superior than conventional open surgery that include more safety and feasibility, and is expected to be a standardization operation method for colorectal carcinoma.
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Neoplasias Colorretais/cirurgia , Laparoscopia , HumanosRESUMO
Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) promotes progression of a variety of tumors. The study was designed to explore the role of COUP-TFII in colorectal carcinoma (CRC) resistance to doxorubicin. The sensitivity of CRC cell lines to doxorubicin was calculated by different proliferation rate measured with cell count kit-8 and EdU (5-Ethynyl-2'-deoxyuridine) assay. The expression of COUP-TFII, Vimentin and E-cadherin were verified using western blot. After doxorubicin administration, CRC cell lines presented apparently down-regulated COUP-TFII, E-cadherin expression and increased Vimentin expression. Besides, COUP-TFII knock-down resulted in significantly increased sensitivity to doxorubicin in all of CRC cell lines, but Twist knock-down presented totally reversed this effect. Furthermore, COUP-TFII knock-down promoted mesenchymal-epithelial transition (MET) in CRC cell lines. After doxorubicin treatment, immediately decreased COUP-TFII expression significantly suppresses CRC cells survival outcomes by suppressing EMT [corrected].
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BACKGROUND AND OBJECTIVES: Midkine (MK) mRNA was highly expressed in various human cancer tissues and cells. The present study aimed to investigate whether MK mRNA level in peripheral blood mononuclear cells (PBMC) could serve as a diagnostic biomarker for patients having primary non-small cell lung cancer (NSCLC). METHODS: MK mRNA level in PBMC from 87 patients with primary NSCLC, 35 patients with lung benign lesion (LEL), and 30 healthy volunteers was analyzed by real-time quantitative RT-PCR. The levels of serum carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase were detected by chemiluminescent microparticle enzyme immunoassay. RESULTS: PBMC MK mRNA level was significantly higher in patients with primary NSCLC than that in other groups (P < 0.001), while there was no significant difference between LEL patients and healthy volunteers (P > 0.05). Higher MK mRNA level was correlated with clinical stages (P = 0.026), differentiation (P = 0.025), and lymph node metastasis (P = 0.022) of NSCLC. Using a cutoff of 0.0063, the sensitivity and specificity of MK mRNA levels to differentiate between patients with NSCLC and patients with LEL were 57.47 and 93.33 %,and it were 56.32 and 93.33 % for patients with NSCLC and healthy volunteers, respectively. Furthermore, multivariate analysis indicated that PBMC MK mRNA level above the cutoff value presented a chance of 11-fold higher for NSCLC occurrence. CONCLUSIONS: MK mRNA level in PBMC may be a potential non-invasive molecular marker for the diagnosis of primary NSCLC.
Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Fatores de Crescimento Neural/genética , Derrame Pleural Maligno/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Midkina , Fatores de Crescimento Neural/metabolismo , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/metabolismo , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE) and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC). METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.