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1.
Respir Res ; 25(1): 206, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745285

RESUMO

BACKGROUND: Previous studies have largely neglected the role of sulfur metabolism in LUAD, and no study has combine iron, copper, and sulfur-metabolism associated genes together to create prognostic signatures. METHODS: This study encompasses 1564 LUAD patients, 1249 NSCLC patients, and over 10,000 patients with various cancer types from diverse cohorts. We employed the R package ConsensusClusterPlus to separate patients into different ICSM (Iron, Copper, and Sulfur-Metabolism) subtypes. Various machine-learning methods were utilized to develop the ICSMI. Enrichment analyses were conducted using ClusterProfiler and GSVA, while IOBR quantified immune cell infiltration. GISTIC2.0 and maftools were utilized for CNV and SNV data analysis. The Oncopredict package predicted drug information based on GDSC1. TIDE algorithm and cohorts GSE91061 and IMvigor210 evaluated patient response to immunotherapy. Single-cell data was processed using the Seurat package, AUCell package calculated cells geneset activity scores, and the Scissor algorithm identified ICSMI-associated cells. In vitro experiments was conducted to explore the role of ICSMRGs in LUAD. RESULTS: Unsupervised clustering identified two distinct ICSM subtypes of LUAD, each with unique clinical characteristics. The ICSMI, comprising 10 genes, was constructed using integrated machine-learning methods. Its prognostic power was validated in 10 independent datasets, revealing that LUAD patients with higher ICSMI levels had poorer prognoses. Furthermore, ICSMI demonstrated superior predictive abilities compared to 102 previously published signatures. A nomogram incorporating ICSMI and clinical features exhibited high predictive performance. ICSMI positively correlated with patients gene mutations, and integrated analysis of bulk and single-cell transcriptome data revealed its association with TME modulators. Cells representing the high-ICSMI phenotype exhibited more malignant features. LUAD patients with high ICSMI levels exhibited sensitivity to chemotherapy and targeted therapy but displayed resistance to immunotherapy. In a comprehensive analysis across various cancers, ICSMI retained significant prognostic value and emerged as a risk factor for the majority of cancer patients. CONCLUSIONS: ICSMI provides critical prognostic insights for LUAD patients, offering valuable insights into the tumor microenvironment and predicting treatment responsiveness.


Assuntos
Adenocarcinoma de Pulmão , Cobre , Ferro , Neoplasias Pulmonares , Aprendizado de Máquina , Enxofre , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Enxofre/metabolismo , Cobre/metabolismo , Prognóstico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Ferro/metabolismo , Resultado do Tratamento , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Valor Preditivo dos Testes , Masculino , Feminino
2.
Inflamm Res ; 73(5): 841-866, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38507067

RESUMO

BACKGROUND: Previous studies have largely neglected the role of ADCC in LUAD, and no study has systematically compiled ADCC-associated genes to create prognostic signatures. METHODS: In this study, 1564 LUAD patients, 2057 NSCLC patients, and more than 5000 patients with various cancer types from diverse cohorts were included. R package ConsensusClusterPlus was utilized to classify patients into different subtypes. A number of machine-learning algorithms were used to construct the ADCCRS. GSVA and ClusterProfiler were used for enrichment analyses, and IOBR was used to quantify immune cell infiltration level. GISTIC2.0 and maftools were used to analyze the CNV and SNV data. The Oncopredict package was used to predict drug information based on the GDSC1. Three immunotherapy cohorts were used to evaluate patient response to immunotherapy. The Seurat package was used to process single-cell data, the AUCell package was used to calculate cells' geneset activity scores, and the Scissor algorithm was used to identify ADCCRS-associated cells. RESULTS: Through unsupervised clustering, two distinct subtypes of LUAD were identified, each exhibiting distinct clinical characteristics. The ADCCRS, consisted of 16 genes, was constructed by integrated machine-learning methods. The prognostic power of ADCCRS was validated in 28 independent datasets. Further, ADCCRS shows better predictive abilities than 102 previously published signatures in predicting LUAD patients' survival. A nomogram incorporating ADCCRS and clinical features was constructed, demonstrating high predictive performance. ADCCRS positively correlates with patients' gene mutation, and integrated analysis of bulk and single-cell transcriptome data revealed the association of ADCCRS with TME modulators. Cells representing high-ADCCRS phenotype exhibited more malignant features. LUAD patients with high ADCCRS levels exhibited sensitivity to chemotherapy and targeted therapy, while displaying resistance to immunotherapy. In pan-cancer analysis, ADCCRS still exhibited significant prognostic value and was found to be a risk factor for most cancer patients. CONCLUSIONS: ADCCRS offers a critical prognostic insight for patients with LUAD, shedding light on the tumor microenvironment and forecasting treatment responsiveness.


Assuntos
Adenocarcinoma de Pulmão , Citotoxicidade Celular Dependente de Anticorpos , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/terapia , Adenocarcinoma de Pulmão/imunologia , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Aprendizado de Máquina , Prognóstico , Transcriptoma
3.
Biotechnol J ; 19(2): e2300296, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38403456

RESUMO

Doxorubicin (DOX) could be utilized to treat lung adenocarcinoma (LUAD), while dose-limiting cardiotoxicity limits its clinical utilization. MDA-MB-231 cell-derived exosomes show lung-specific organotropism features. In this study, we aimed to explore the potential of MDA-MB-231 cell-derived exosomes in DOX specific delivery to the lung. MDA-MB-231 cell-derived exosomes were coincubated with to construct for the doxorubicin delivery system (D-EXO). Exosomes labeled with fluorescein isothiocyanate were incubated with A549 cells or 293T cells, and the engulf and the mean intensity of the fluorescence were detected with immunofluorescence and flow cytometry assay. Cell viability was detected with cell counting kit-8 (CCK-8), and cell migration was determined by scratch test. The protein expression was detected by Western blot assay. A549 cell line-derived xenograft mouse model was constructed to examine the treatment effect of D-EXO. MDA-MB-231 cell-derived exosomes could be specially taken up by A549 cells with diminished cell viability but not engulfed by 293T cells. D-EXO inhibited A549 cell migration, and upregulated the protein expression of caspase 3 and cleaved caspase 3 expression, while did not show any inhibition on 293T cells. In vivo orthotopic xenotransplantation model indicated that D-EXO inhibited tumor growth characterized by diminished tumor weight and improved survival rate. No significant change in body weight was observed after the D-EXO treatment. In conclusion, D-EXO proposed in this study could be utilized to treat LUAD with lung-specific delivery effects to improve the survival rate.


Assuntos
Adenocarcinoma de Pulmão , Exossomos , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Caspase 3/metabolismo , Exossomos/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Pulmão , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Linhagem Celular Tumoral
4.
BMC Pulm Med ; 24(1): 36, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233781

RESUMO

BACKGROUND: Chlamydia pneumoniae (Cpn) IgG and IgA has been strongly linked to lung cancer, but its impact on patients' quality of life remains unclear. Our objective was to investigate the relationship between pre-treatment Cpn IgG and IgA and time to deterioration (TTD) of the HRQoL in patients with primary lung cancer. METHODS: A prospective hospital-based study was conducted from June 2017 to December 2018, enrolling 82 patients with primary lung cancer admitted to the First Affiliated Hospital of Fujian Medical University for questionnaire surveys. Cpn IgG and IgA was detected by microimmunofluorescence method. HRQoL was assessed at baseline and during follow-up using the EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13). HRQoL scores were calculated using the QoLR package, and TTD events were determined (minimum clinically significant difference = 5 points). Cox regression analysis was used to evaluate the effect of Cpn IgG and IgA on HRQoL. RESULTS: We investigated the relationship between Cpn IgG and IgA and quality of life in patients with primary lung cancer. The study was found that 75.61% of cases were Cpn IgG + and 45.12% were Cpn IgA + . Cpn IgA + IgG + was 41.46%. For EORTC QLQ-C30, Physical function (PF) and Pain (PA) TTD events on the functional scale and Symptom scale were the most common during follow-up. After adjusting for gender and smoking status, Pre-treatment Cpn IgA + was found to signifcantly delay TTD of Physical functioning(HR = 0.539, 95% CI: 0.291-0.996, P = 0.048). In addition, Cpn IgG + before treatment significantly delayed TTD in Emotional functioning (HR = 0.310, 95% CI: 0.115-0.836, P = 0.021). For EORTC QLQ-LC13, deterioration of dyspnea (LC-DY) was the most common event. However, Cpn IgG and IgA before treatment had no effect on the TTD of EORTC QLQ-LC13 items. CONCLUSIONS: According to EORTC QLQ-C30 and EORTC QLQ-LC13, Cpn IgA delayed TTD in Physical functioning and Cpn IgG delayed TTD in Emotional functioning.


Assuntos
Infecções por Chlamydophila , Neoplasias Pulmonares , Humanos , Qualidade de Vida/psicologia , Neoplasias Pulmonares/terapia , Estudos Prospectivos , Infecções por Chlamydophila/complicações , Imunoglobulina A , Imunoglobulina G , Inquéritos e Questionários
5.
J Pathol ; 262(3): 320-333, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38108121

RESUMO

Bone morphogenetic protein (BMP)-Smad1/5/8 signaling plays a crucial regulatory role in lung development and adult lung homeostasis. However, it remains elusive whether BMP-Smad1/5/8 signaling is involved in the pathogenesis of emphysema. In this study, we downregulated BMP-Smad1/5/8 signaling by overexpressing its antagonist Noggin in adult mouse alveolar type II epithelial cells (AT2s), resulting in an emphysematous phenotype mimicking the typical pathological features of human emphysema, including distal airspace enlargement, pulmonary inflammation, extracellular matrix remodeling, and impaired lung function. Dysregulation of BMP-Smad1/5/8 signaling in AT2s leads to inflammatory destruction dominated by macrophage infiltration, associated with reduced secretion of surfactant proteins and inhibition of AT2 proliferation and differentiation. Reactivation of BMP-Smad1/5/8 signaling by genetics or chemotherapy significantly attenuated the morphology and pathophysiology of emphysema and improved the lung function in Noggin-overexpressing lungs. We also found that BMP-Smad1/5/8 signaling was downregulated in cigarette smoke-induced emphysema, and that enhancing its activity in AT2s prevented or even reversed emphysema in the mouse model. Our data suggest that BMP-Smad1/5/8 signaling, located at the top of the signaling cascade that regulates lung homeostasis, represents a key molecular regulator of alveolar stem cell secretory and regenerative function, and could serve as a potential target for future prevention and treatment of pulmonary emphysema. © 2023 The Pathological Society of Great Britain and Ireland.


Assuntos
Enfisema , Enfisema Pulmonar , Transdução de Sinais , Animais , Humanos , Camundongos , Células Epiteliais Alveolares/metabolismo , Enfisema/metabolismo , Pulmão/metabolismo , Enfisema Pulmonar/genética , Transdução de Sinais/fisiologia , Proteína Smad1/genética , Proteína Smad1/metabolismo
6.
Front Oncol ; 13: 1282335, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37927467

RESUMO

Background: Cell death caused by neutrophil extracellular traps (NETs) is known as NETosis. Despite the increasing importance of NETosis in cancer diagnosis and treatment, its role in Non-Small-Cell Lung Cancer (NSCLC) remains unclear. Methods: A total of 3298 NSCLC patients from different cohorts were included. The AUCell method was used to compute cells' NETosis scores from single-cell RNA-sequencing data. DEGs in sc-RNA dataset were obtained by the Seurat's "FindAllMarkers" function, and DEGs in bulk-RNA dataset were acquired by the DESeq2 package. ConsensusClusterPlus package was used to group patients into different NETosis subtypes, and the Enet algorithm was used to construct the NETosis-Related Riskscore (NETRS). Enrichment analyses were conducted using the GSVA and ClusterProfiler packages. Six distinct algorithms were utilized to evaluate patients' immune cell infiltration level. Patients' SNV and CNV data were analyzed by maftools and GISTIC2.0, respectively. Drug information was obtained from the GDSC1, and predicted by the Oncopredict package. Patient response to immunotherapy was evaluated by the TIDE algorithm in conjunction with the phs000452 immunotherapy cohort. Six NRGs' differential expression was verified using qRT-PCR and immunohistochemistry. Results: Among all cell types, neutrophils had the highest AUCell score. By Intersecting the DEGs between high and low NETosis classes, DEGs between normal and LUAD tissues, and prognostic related genes, 61 prognostic related NRGs were identified. Based on the 61 NRGs, all LUAD patients can be divided into two clusters, showing different prognostic and TME characteristics. Enet regression identified the NETRS composed of 18 NRGs. NETRS significantly associated with LUAD patients' clinical characteristics, and patients at different NETRS groups showed significant differences on prognosis, TME characteristics, immune-related molecules' expression levels, gene mutation frequencies, response to immunotherapy, and drug sensitivity. Besides, NETRS was more powerful than 20 published gene signatures in predicting LUAD patients' survival. Nine independent cohorts confirmed that NETRS is also valuable in predicting the prognosis of all NSCLC patients. Finally, six NRGs' expression was confirmed using three independent datasets, qRT-PCR and immunohistochemistry. Conclusion: NETRS can serves as a valuable prognostic indicator for patients with NSCLC, providing insights into the tumor microenvironment and predicting the response to cancer therapy.

7.
J Cancer Res Clin Oncol ; 149(15): 13553-13574, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37507593

RESUMO

BACKGROUND: Innate immune effectors, dendritic cells (DCs), influence cancer prognosis and immunotherapy significantly. As such, dendritic cells are important in killing tumors and influencing tumor microenvironment, whereas their roles in lung adenocarcinoma (LUAD) are largely unknown. METHODS: In this study, 1658 LUAD patients from different cohorts were included. In addition, 724 cancer patients who received immunotherapy were also included. To identify DC marker genes in LUAD, we used single-cell RNAsequencing data for analysis and determined 83 genes as DC marker genes. Following that, integrative machine learning procedure was developed to construct a signature for DC marker genes. RESULTS: Using TCGA bulk-RNA sequencing data as the training set, we developed a signature consisting of seven genes and classified patients by their risk status. Another six independent cohorts demonstrated the signature' s prognostic power, and multivariate analysis demonstrated it was an independent prognostic factor. LUAD patients in the high-risk group displayed more advanced features, discriminatory immune-cell infiltrations and immunosuppressive states. Cell-cell communication analysis indicates that tumor cells with lower risk scores communicate more actively with the tumor microenvironment. Eight independent immunotherapy cohorts revealed that patients with low-risk had better immunotherapy responses. Drug sensitivity analysis indicated that targeted therapy agents exhibited greater sensitivity to low-risk patients, while chemotherapy agents displayed greater sensitivity to high-risk patients. In vitro experiments confirmed that CTSH is a novel protective factor for LUAD. CONCLUSIONS: An unique signature based on DC marker genes that is highly predictive of LUAD patients' prognosis and response to immunotherapy. CTSH is a new biomarker for LUAD.

8.
Biomater Sci ; 11(12): 4346-4358, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37140070

RESUMO

Monotherapy of lung cancer shows limited therapeutic effects due to its poorly targeted enrichment and low bioavailability. Using nanomaterials as carriers to form drug delivery systems has become a popular method to improve the targeting of anticancer drug therapy and patients' safety. However, the uniformity of the loaded drugs and the unsatisfactory effects are still the bottleneck in this field up to now. This study aims to construct a novel nanocomposite carrying 3 different types of anticancer drugs to enhance treatment efficacy. Herein, mesoporous silica (MSN) with high loading rate was constructed by dilute sulfuric acid thermal etching as the framework. Hyaluronic acid (HA) was loaded with CaO2, p53 and DOX to construct nanoparticle complexes-SiO2@CaO2@DOX@P53-HA. First, MSN was proved to be a porous sorbent with a mesoporous structure through BET analysis. The images obtained from the uptake experiment clearly show the gradual enrichment of the DOX and Ca2+ within the target cell. For in vitro experiments, the pro-apoptotic effects of SiO2@CaO2@DOX@P53-HA significantly increased compared to that of the single-agent group at different time points. Furthermore, in the tumor-bearing mouse experiment, the tumor volume was remarkably inhibited in the SiO2@CaO2@DOX@P53-HA group compared to that in the single-agent group. By observing the pathological sections of the euthanized mice, it is obvious that the tissues of the mice treated with the nanoparticles were more intact. Based on these beneficial results, it is believed that multimodal therapy is a meaningful treatment strategy for lung cancer.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Camundongos , Animais , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Ácido Hialurônico/química , Dióxido de Silício/química , Proteína Supressora de Tumor p53/genética , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Portadores de Fármacos/química
9.
Physiol Genomics ; 55(5): 213-221, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939206

RESUMO

Current research has shown that inhibiting deoxythymidylate kinase (DTYMK) can significantly reduce development of lung cancer without liver kinase B1. However, its underlying regulatory mechanism is still unclear. We therefore aimed to investigate whether DTYMK inhibitors could suppress lung adenocarcinoma (LUAD) progression. In this study, human tissues, A549 cells, and xenograft tumors were used to explore the regulation and mechanism of DTYMK on LUAD cell proliferation and migration. Meanwhile, YMU1 (a DTYMK inhibitor) was applied to A549 cells and xenograft tumors to investigate its potential as a drug for LUAD. DTYMK was overexpressed in LUAD tissues and correlated with tumor stage. Knockdown of DTYMK suppressed cell viability, migration, and invasion. In addition, the activation of signal transducers and activators of transcription 3 (STAT3) was repressed upon DTYMK inhibition. YMU1 showed the same effect as DTYMK knockdown in vivo and in vitro. DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may have the potential to inhibit the development of LUAD.NEW & NOTEWORTHY DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may serve as a novel drug to suppress the development of LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Timidina Monofosfato/farmacologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Transdução de Sinais , Pulmão/patologia , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologia
10.
Front Surg ; 9: 914677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36303858

RESUMO

Background: Transareolar uniportal thoracoscopic extended thymectomy (TUTET) has not been previously reported. We attempted to assess the feasibility and safety of TUTET for male myasthenia gravis (MG) patients. Patients and methods: From February 2013 to February 2020, 46 men with MG underwent TUTET. All patients were followed up for 12-84 months postoperatively by clinic visits or telephone/e-mail interviews. Results: All surgeries were completed successfully, with an average operation time of 72.6 min. The mean length of transareolar uniportal incision was 3.0 ± 0.4 cm, and the mean postoperative cosmetic score was 3.1 ± 0.5 at discharge. Three months postoperatively, no patients had an apparent surgical scar on the chest wall or complained of postoperative pain. Substantial amelioration of the disease was achieved in a short period, and several benefits were clear. At the 1-year follow-up, all patients showed a good cosmetic effect and high satisfaction. Conclusions: TUTET is an effective and safe way for men with MG. The uniportal incision is hidden in the areola with sound cosmetic effects. We believe that TUTET is an acceptable procedure for extended thymectomy.

11.
Front Genet ; 12: 756493, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777476

RESUMO

Background: Approximately 50% of thymoma patients also show myasthenia gravis (MG), which is an autoimmune disease; however, the pathogenesis of MG-associated thymoma remains elusive. Our aim was to investigate immune-related lncRNA profiles of a set of candidate genes for better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without MG. Methods: Molecular profiles of thymoma with or without MG were downloaded from The Cancer Genome Atlas, and Pearson's correlation analysis was performed to identify immune-related lncRNAs. T test was used to examine the differential expression and differential methylation between thymoma patients with or without MG. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of target genes of immune-related lncRNAs. Results: Analyses of the 87 thymoma samples with complete MG information revealed that 205 mRNAs and 56 lncRNAs showed up-regulated expression in thymoma with MG patients, while 458 mRNAs and 84 lncRNAs showed down-regulated expression. The methylation level of three immune-related lncRNAs (AP000787.1, AC004943.1, WT1-AS, FOXG1-AS1) was significantly decreased in thymoma tissues, and the methylation level of these immune-related lncRNAs (WT1-AS: Cor = 0.368, p < 0.001; FOXG1-AS1: Cor = 0.288, p < 0.01; AC004943.1: Cor = -0.236, p < 0.05) correlated with their expression. GO and KEGG pathway analysis revealed that targets of the immune-related lncRNA FOXG1-AS1 were enriched in small GTPase binding and herpes simplex virus 1 infection. Transcription coregulator activity and cell cycle were the most enriched pathways for targets of lncRNA AC004943.1. LncRNA WT1-AS targets were most enriched in actin binding and axon guidance. Conclusion: Our results revealed the immune-related molecular profiling of thymoma with MG and without MG and identified key pathways involved in the underlying molecular mechanism of thymoma-related MG. These findings provide insights for further research of potential markers for thymoma-related MG.

12.
Updates Surg ; 73(4): 1541-1548, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33394357

RESUMO

In this study, we report the use of transareolar uniportal video-assisted thoracoscopic surgery (VATS) in thoracic surgery for the treatment of male patients with peripheral pulmonary nodules. From February 2014 to September 2018, 46 male patients with small PPNs underwent VATS, of whom 41 underwent unilateral VATS, and five underwent bilateral VATS. All procedures were successfully performed. Patients received 1 year of outpatient follow-up postoperatively. The data indicated that the average operation times were 32.7 min (unilateral) and 58.6 min (bilateral). The mean length of the incision was 2.7 ± 0.3 cm, with a mean cosmetic score of 3.2 ± 0.7 at the time of discharge. All patients rapidly recovered consciousness postoperatively. The length of postoperative hospitalization (LOH) was 3.4 ± 1.4 days. There was no obvious surgical scarring on the chest wall, and no patients complained of postoperative pain at 6 months postoperatively. No recurrence or metastasis was found during the 1-year follow-up. Transareolar uniportal VATS for peripheral pulmonary nodules resulted in good cosmetic outcomes and high patient satisfaction. Transareolar uniportal VATS is a safe and effective therapeutic procedure for male patients with small PPNs and especially produces good cosmetic outcomes.


Assuntos
Neoplasias Pulmonares , Cirurgia Torácica , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida
13.
Mol Cell Biochem ; 476(2): 853-861, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33128214

RESUMO

Rab-interacting lysosomal protein (RILP) has been suggested to perform as a tumor suppressor in breast and prostate cancer cell lines. However, its expression profile and functional role in lung cancer have never been investigated. We applied the well-established cancer genomic database-The Cancer Genome Atlas to compare the RILP expression and methylation between lung cancer tissues and normal tissues. The potential correlation of RILP with clinical characteristics of lung cancer patients (e.g., stages, smoking, TP53, and methylation) was also be explored. Our results showed that the downregulation of RILP and upregulation of RILP methylation were identified in lung cancer tissues compared to normal healthy tissues. Downregulation of RILP was positively associated with lung cancer later stage (N3), smoking history, TP53 mutation, and poor prognosis, as well as inversely correlated with DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression. Demethylation treatment enhanced RILP expression in lung cancer cells, suggesting hypermethylation is responsible for RILP silencing in lung cancer. We further found that RILP depletion promoted lung cancer cell proliferation, migration, and invasion. We concluded that RILP acts as a tumor suppressor in lung cancer cells. Our results provided the theoretical basis for developing RILP-targeting or demethylating agents for lung cancer treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células Escamosas/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Metilação de DNA , Neoplasias Pulmonares/genética , Proteínas Supressoras de Tumor/metabolismo , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Biologia Computacional/métodos , DNA (Citosina-5-)-Metiltransferase 1/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Taxa de Sobrevida , Proteínas Supressoras de Tumor/genética
14.
Exp Cell Res ; 392(1): 112002, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32277958

RESUMO

AarF domain containing kinase 5 (ADCK5) is a member of an atypical kinase family and overexpressed in many carcinomas including lung cancer, while the function of this protein has not been elucidated. Here we investigated the mechanism of ADCK5 involved in regulating invasion and migration of lung cancer cells, and showed that ADCK5 might regulate the expression of tumor oncogene human pituitary tumor transforming gene-1 (PTTG1) by phosphorylating transcription factor SOX9, therefore enhancing the migration and invasion capabilities of lung cancer cells. Mutagenesis of potential serine phosphorylation sites on SOX9 indicated that serine 181 might be required to maintain transcription activation of SOX9 as well as increase PTTG1 levels. The serine 181 site of SOX9 is in a motif that is targeted by ADCK5. The ADCK5-SOX9-PTTG1 pathway might be a potential therapeutic target for lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/genética , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/fisiologia , Fatores de Transcrição SOX9/genética , Securina/genética , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Adesão Celular/genética , Proliferação de Células/genética , Células Cultivadas , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Invasividade Neoplásica/genética , Metástase Neoplásica , Proteínas Serina-Treonina Quinases/genética , Fatores de Transcrição SOX9/metabolismo , Securina/metabolismo , Transdução de Sinais/genética
15.
Ann Transl Med ; 8(24): 1659, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33490171

RESUMO

BACKGROUND: Transareolar single-port endoscopic thoracic sympathectomy (ETS) with a flexible endoscope has rarely been reported. This study assessed the performance of this novel minimally invasive technique for primary palmar hyperhidrosis (PPH). METHODS: From January 2019 to September 2019, 118 males with severe PPH requiring single-port and bilateral ETS were randomly allocated to undergo transareolar ETS using a flexible endoscope (group A, n=58) or transaxillary ETS using a 5 mm thoracoscope (group B, n=60). RESULTS: Both groups had similar patient characteristics. All procedures were performed successfully, with no mortality or conversion to open surgery. All patients had dry and warm palms immediately after surgery. Compared with group B, group A had a significantly shorter median incision length [5.1 (5.0-5.2) vs. 10.9 (10.8-11.9) mm; P<0.001], and significantly lower median postoperative pain score [1 (1.0-2.0) vs. 3 (3.0-4.0); P<0.001]. There were no differences between the two groups in operative time, palmar temperature increase, and transient postoperative sweating. After complete follow-up, group A had a significantly higher median cosmetic score than group B [4.0 (3.0-4.0) vs. 3.0 (3.0-3.0); P<0.001]. There were no differences between the two groups regarding symptom resolution, compensatory hyperhidrosis, and satisfaction score. No patient reported residual pain or symptom recurrence. CONCLUSIONS: Transareolar single-port ETS with a flexible endoscope is safe, effective, and minimally invasive with a small incision, minimal pain, and excellent cosmetic results. This novel procedure is suitable for routine treatment of PPH in males.

16.
Mitochondrial DNA B Resour ; 5(3): 2688-2690, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-33457906

RESUMO

Lung cancer is one of the most common malignant tumors. It is clinically divided into two types: small cell lung cancer and non-small cell lung cancer. Populus simonii distributed in East Asia region including China used as traditional medicine, which is an important medicinal plant for anti-lung cancer activity. The complete chloroplast genome sequence of P. simonii was characterized from Illumina pair-end sequencing. The chloroplast genome of P. simonii was 156,559 bp in length, containing a large single-copy region (LSC) of 84,825 bp, a small single-copy region (SSC) of 47,561 bp, and two inverted repeat (IR) regions of 16,494 bp. The overall GC content is 36.70%, while the corresponding values of the LSC, SSC, and IR regions are 34.5%, 30.0%, and 42.0%, respectively. The genome contains 131 complete genes, including 86 protein-coding genes (68 protein-coding gene species), 37 tRNA genes (29 tRNA species), and 8 rRNA genes (4 rRNA species). The neighbour-joining phylogenetic analysis showed that P. simonii and P. qamdoensis clustered together as sisters to other Populus species.

17.
Surg Endosc ; 33(6): 2015-2023, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30617423

RESUMO

BACKGROUND: Video-assisted thoracoscopic lobectomy with lymphadenectomy is considered one of the most effective treatments for early non-small cell lung cancer. We developed a novel approach for lobectomy in patients with right upper lung cancer through simplified synchronous disconnection of pulmonary arteries and veins. This study aimed to evaluate the feasibility, efficacy, safety, and cost-effectiveness of this minimally invasive technique in managing right upper lobectomy. PATIENTS AND METHODS: From March 2016 to September 2017, 62 patients with right upper lung cancer underwent lobectomy via simplified synchronous disconnection of pulmonary arteriovenous by video-assisted thoracoscopic surgery. All patients were followed up for 6-12 months after the procedure through clinic visits or telephone/e-mail interviews. RESULTS: Of the 62 patients (mean age, 57.2 ± 8.7 years), 28 were men (45.2%) and 34 (54.8%) were women. All procedures were successfully performed by thoracoscopy, with a mean operating time of 66.2 ± 9.0 min. The mean blood loss was 40.3 ± 19.5 mL. Only 1 (1.61%) patient required blood transfusion. The mean number of endoscopic linear stapling devices used was 2.6 ± 0.7. The mean number of lymph nodes harvested was 16.0 ± 1.6. Postoperative pneumonia was encountered in 4 (6.45%) patients. There was no postoperative mortality. The mean length of hospital stay was 5.3 ± 1.3 days. Six-month follow-up revealed an excellent clinical result and degree of satisfaction. CONCLUSIONS: Simplified synchronous disconnection of pulmonary arteries and veins is a feasible, economical, safe, and effective therapeutic procedure for right upper lung carcinoma. This novel procedure shows promise as a viable surgical approach for right upper lobectomy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Artéria Pulmonar/patologia , Cirurgia Torácica Vídeoassistida , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Resultado do Tratamento
18.
J Drug Target ; 25(2): 119-124, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27282915

RESUMO

With the advent of molecularly targeted therapy, it is necessary to reconsider the strategy for malignant pleural effusion in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The aim of this study was to evaluate the efficacy of a two-line sequential treatment strategy in this patient subgroup. First-line treatment was gefitinib (250 mg/day) until disease progression. Second-line treatment was thoracoscopic talc pleurodesis followed by chemotherapy. Primary endpoints were the overall response and progression-free survival rates after first-line treatment, and the overall survival rate after first- and second-line treatment. Secondary endpoints were the success rate of thoracoscopic talc pleurodesis and gefitinib toxicity. Among the 76 patients enrolled, 61 (80%) were female and the median age was 62 years. The overall response rate after first-line treatment was 92.1% and median progression-free survival was 15 months. The success rate for thoracoscopic talc pleurodesis in 33 patients was 94%. Median follow-up was 35 months. Median overall survival was 39 months. The 1- and 3-year overall survival rates were 86.4% and 46.1%, respectively. The two-line sequential treatment strategy enhanced survival. These preliminary findings provide an insight into novel therapeutic models for malignant pleural effusion in NSCLC harbouring EGFR mutations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Receptores ErbB/genética , Derrame Pleural Maligno/tratamento farmacológico , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Gefitinibe , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Derrame Pleural Maligno/etiologia
19.
J Laparoendosc Adv Surg Tech A ; 26(12): 958-964, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27556596

RESUMO

OBJECTIVES: Transareolar single-port needlescopic thoracic sympathectomy under intravenous anesthesia without intubation has rarely been attempted in managing primary palmar hyperhidrosis (PPH). The objective of this study is to evaluate the feasibility and safety of this minimally invasive technique. MATERIALS AND METHODS: From May 2012 to May 2015, 168 male patients with severe PPH underwent single-port endoscopic thoracic sympathectomy (ETS) and were randomly allocated to groups A or B. Patients in group A underwent nonintubated transareolar ETS with a 2-mm needle endoscope, while those in group B underwent intubated transaxillary ETS with a 5-mm thoracoscope. RESULTS: All procedures were performed successfully. The palms of all patients became dry and warm immediately after surgery. The mean resuscitation time was significantly shorter in nonintubated patients than in intubated patients. Postoperative sore throat occurred in 4 patients in group A and in 32 patients in group B (P < .01). The mean incision length was significantly shorter in group A than in group B. The mean postoperative pain scores were markedly higher in group B than in group A. The mean cost of anesthesia was considerably lower in nonintubated patients than in intubated patients. The mean cosmetic scores were higher in group A than in group B (P < .01). CONCLUSIONS: Nonintubated transareolar single-port ETS with a needle endoscope is a safe, effective, and minimally invasive therapeutic procedure, which allows a smaller incision with less pain and excellent cosmetic results. This novel procedure can be performed in a routine clinical practice for male patients with severe PPH.


Assuntos
Anestesia Intravenosa/métodos , Hiperidrose/cirurgia , Intubação Intratraqueal/estatística & dados numéricos , Agulhas , Ventilação não Invasiva/métodos , Simpatectomia/métodos , Toracoscopia/métodos , Adolescente , Adulto , Analgésicos/uso terapêutico , Axila , Humanos , Máscaras Laríngeas , Masculino , Mamilos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Respiração Artificial , Resultado do Tratamento , Adulto Jovem
20.
J Thorac Cardiovasc Surg ; 152(4): 999-1005, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27496616

RESUMO

BACKGROUND: Conventional 3-port video-assisted thoracoscopic surgery is the classic approach for the diagnosis and treatment of primary spontaneous pneumothorax. Transareolar pulmonary bullectomy rarely has been attempted. This study aimed to evaluate the feasibility and safety of this novel minimally invasive technique in managing primary spontaneous pneumothorax. METHODS: From January 2013 to December 2014, a total of 112 male patients with primary spontaneous pneumothorax underwent transareolar pulmonary bullectomy by use of a 5-mm thoracoscope. RESULTS: All procedures were performed successfully, with a mean operating time of 26.5 minutes. The mean length of transareolar incision for the main operation was 2.0 ± 0.2 cm, the mean length of incision for the camera port was 0.6 ± 0.1 cm, and the mean postoperative cosmetic score was 3.0 ± 0.8. All patients regained consciousness rapidly after surgery. One hundred seven patients (95.5%) were discharged on postoperative day 2 or 3, with the remainder discharged on postoperative day 4 or 5. Postoperative complications were minor. At 6 months postoperatively, there was no obvious surgical scar on the chest wall, and no patient complained of postoperative pain. No recurrent symptoms were observed. One-year follow-up revealed an excellent cosmetic result and degree of satisfaction. CONCLUSIONS: Transareolar pulmonary bullectomy is a safe and effective therapeutic procedure for primary spontaneous pneumothorax caused by pulmonary bullae. The incision is hidden in the areola with excellent cosmetic effects. This novel procedure shows promise as a treatment of primary spontaneous pneumothorax.


Assuntos
Pneumotórax/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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