Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
1.
Transl Cancer Res ; 11(3): 475-487, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35402179

RESUMO

Background: A significant correlation has been identified between lncRNA and tumor cell resistance, diagnosis, and prognosis. Although mRNA studies have dominated the field of non-coding RNA biology in tumorigenesis in recent years, long-chain non-coding RNA (the biological function) has also attracted increasing attention. However, the lncRNA associated with lung adenocarcinoma (LUAD) remains unexplored. This study used bioinformatics analysis to screen and identify LncRNA01977 as a key oncogenic driver of LUAD. Methods: The experiment was divided into blank serum group (normal serum medium) and lung compound low, medium and high dose groups (5%, 10%, 15% and 15% lung compound drug serum medium, respectively). Transwell invasion ability of A549 cells was detected, and Western blot tested A549 cells SDF-1 specific receptor CXCR4, and CXCR4 gene expression in A549 cells were determined by reverse transcription-polymerase chain reaction (RT-PCR). In addition, western blotting, MTT proliferation test, colony formation test and apoptosis detection techniques were used to explore the mechanism of LncRNA01977's effects on LUAD. Results: In vitro assays demonstrated that LncRNA01977 can significantly promote the progression of LUAD and that stromal cells in tumor microenvironment secrete chemokine CXCL12, also known as stromal derived factor-1 (SDF-1), and its receptor CXCR4 is low expressed in normal tissues and high expressed in LUAD tissues. Lung cancer patients with high expression of CXCR4 are more prone to metastasis. Conclusions: LncRNA01977 can be used as a new prognostic indicator of LUAD, and can help patients to find more effective target treatment options for LUAD.

2.
JTO Clin Res Rep ; 3(1): 100257, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34977823

RESUMO

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

3.
Thorac Cancer ; 12(9): 1469-1488, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33787090

RESUMO

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Período Perioperatório
4.
Cancer Sci ; 112(6): 2349-2360, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33565687

RESUMO

Reliable and noninvasive biomarkers for the early diagnosis of non-small-cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver-operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.


Assuntos
Biomarcadores Tumorais/urina , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Malato Desidrogenase/urina , Regulação para Cima , Células A549 , Animais , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/urina , Estudos de Casos e Controles , Linhagem Celular Tumoral , Detecção Precoce de Câncer , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Espectrometria de Massas , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos
5.
Front Oncol ; 10: 1568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042801

RESUMO

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

6.
Thorac Cancer ; 11(11): 3234-3242, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32989915

RESUMO

BACKGROUND: Circulating genetically abnormal cells (CACs) with specific chromosome variations have been confirmed to be present in non-small cell lung cancer (NSCLC). However, the diagnostic performance of CAC detection remains unclear. This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC. METHODS: In this prospective study, a total of 339 participants (261 lung cancer patients and 78 healthy volunteers) were enrolled. An antigen-independent fluorescence in situ hybridization was used to enumerate the number of CACs in peripheral blood. RESULTS: Patients with early-stage NSCLC were found to have a significantly higher number of CACs than those of healthy participants (1.34 vs. 0.19; P < 0.001). The CAC test displayed an area under the receiver operating characteristic (ROC) curve of 0.76139 for discriminating stage I NSCLC from healthy participants with 67.2% sensitivity and 80.8% specificity, respectively. Compared with serum tumor markers, the sensitivity of CAC assays for distinguishing early-stage NSCLC was higher (67.2% vs. 48.7%, P < 0.001), especially in NSCLC patients with small nodules (65.4% vs. 36.5%, P = 0.003) and ground-glass nodules (pure GGNs: 66.7% vs. 40.9%, P = 0.003; mixed GGNs: 73.0% vs. 43.2%, P < 0.001). CONCLUSIONS: CAC detection in early stage NSCLC was feasible. Our study showed that CACs could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC. KEY POINTS: What this study adds: This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC. Significant findings of the study: CAC detection in early stage NSCLC was feasible. Our study showed that CACs could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Thorac Cancer ; 11(10): 2887-2895, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32856417

RESUMO

BACKGROUND: This study aimed to identify an efficient, simple, and specific method of detecting mutations in the epidermal growth factor receptor (EGFR) gene in isolated lung cancer circulating tumor cells (CTCs) and to improve the ability to obtain tumor tissue clinically. METHODS: EGFR peptide lipid magnetic spheres (EG-P-LMB) were prepared by reverse evaporation, and characterization and cell capture efficiency assessed. The peripheral blood samples of 30 lung cancer patients were isolated and identified with the EG-P-LMB using 20 healthy volunteers as controls. Finally, the isolated CTCs were tested for EGFR gene mutations, and the tissue samples selected for comparison. RESULTS: The prepared magnetic spheres had a smaller particle size and higher stability according to the particle size potential test. Their morphology was homogeneous by atomic force observation, and the UV test showed that there were peptides on the surface. The separation efficiency of EG-P-LMB was greater than 90% in PBS and greater than 80% in the blood simulation system. Compared with the tissue sample results, the positive rate of EGFR gene mutations was 94%. The CTC test results of 27 patients were consistent with the tissue test results of the corresponding patients, and the consistency with the tissue comparison test results was 90% (27/30). CONCLUSIONS: EG-P-LMB can effectively capture CTCs in the peripheral blood of patients with lung cancer. CTC detection can accurately identify mutations in the EGFR gene and improve the ability to obtain tumor tissue in clinical practice. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: EG-P-LMB can effectively capture CTCs in the peripheral blood of patients with lung cancer. CTC detection can accurately identify mutations in the EGFR gene and improve the ability to obtain tumor tissue in clinical practice. WHAT THIS STUDY ADDS: This study added EGFR peptide lipid magnetic spheres to capture CTCs in the blood. Genetic testing was performed and compared with tissues. It solves the problem of clinically difficult tumor tissue sampling.


Assuntos
Receptores ErbB/metabolismo , Neoplasias Pulmonares/genética , Peptídeos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Células Neoplásicas Circulantes/patologia
8.
Cancer Lett ; 486: 58-70, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32439420

RESUMO

First-generation EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib have significant activity in NSCLC patients with activating EGFR mutations. However, EGFR-TKI resistance inevitably occurs after approximately 12 months of treatment. Acquired mechanisms of resistance, other than secondary mutations in EGFR (T790 M) which account for 50-60%, are less well understood. Here, we identified lncRNA H19 as a significantly downregulated lncRNA in vitro models and clinical specimens with acquired EGFR-TKI resistance, H19 knockdown or overexpression conferred resistance or sensitivity, respectively, both in vitro and in vivo models. H19 downregulation contributed to erlotinib resistance through interaction and upregulation of PKM2, which enhanced the phosphorylation of AKT. AKT inhibitors restored the sensitivity of erlotinib-resistant cells to erlotinib. In EGFR-mutant patients treated with EGFR-TKIs, low H19 levels were associated with a shorter progression-free survival (PFS) (P = 0.021). These findings revealed a novel mechanism of low-level H19 in the regulation of erlotinib resistance in EGFR-mutant lung cancers. Combination of AKT inhibitors and EGFR-TKIs could be a rational therapeutic approach for some subgroups of EGFR-mutant lung cancer patients.


Assuntos
Proteínas de Transporte/fisiologia , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana/fisiologia , Mutação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/fisiologia , Hormônios Tireóideos/fisiologia , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Fosforilação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Regulação para Cima
9.
Comb Chem High Throughput Screen ; 23(5): 419-432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32233997

RESUMO

AIMS AND OBJECTIVE: The common disease of insomnia has complex and diverse clinical manifestations. Lavender represents an effective treatment of insomnia, but the molecular mechanism underlying the effectiveness of this treatment is not clear. The purpose of this study is to investigate the active components, target proteins and molecular pathways of lavender in the treatment of insomnia, thus explaining its possible mechanism. MATERIALS AND METHODS: Firstly, 54 active components of lavender were identified by gas chromatography-mass spectrometry (GC-MS). The target protein of lavender was predicted by the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform and the SwissTargetPredicating tool, and the target protein of insomnia was predicted by the DisGeNET and DrugBank databases. Then, the "component-target-disease" network diagram was constructed using the Cytoscape 3.7.1 software. KEGG and GO enrichments were analyzed using the R statistical language. Finally, the key target proteins were verified by collecting and verifying the target protein GEO data using the Discovery Studio 3.5 molecular docking verification software. RESULTS: 906 target proteins of lavender were predicted by the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform and the SwissTargetPredicating tool, and 182 insomnia target proteins were predicted by the DisGeNET and DrugBank databases. The results of GO enrichment analysis showed that it included the reaction process of ammonium ion, the regulation of the membrane potential and the secretion of catecholamine, while the results of KEGG enrichment included the calcium signaling pathway, serotonin synapse, morphine addiction and many more. Finally, using the Discovery Studio3.5 molecular docking verification software, it was verified that the key target proteins are ADRB1 and HLA-DRB1. CONCLUSION: The components in the lavender essential oil include the Ethyl 2-(5-methyl-5-vinyltetrahydrofuran- 2-yl)propan-2-ylcarbonate (0.774); 5-Oxatricyclo[8.2.0.04,6]dodecane, 4,12,12-trimethyl- 9-methylene-, (1R,4R,6R,10S)-(0.147); P-Cymen-7-ol (0.063); .alpha-Humulenem (0.317); Acetic acid, hexyl ester (1.374); etc. The role lavender plays in the treatment of insomnia might be accomplished through the regulation of the key targets ADRB1 and HLA-DRB1.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Lavandula/química , Óleos Voláteis/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/química , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Óleos Voláteis/química , Software
10.
EBioMedicine ; 53: 102689, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32114396

RESUMO

BACKGROUND: How the oncoprotein epidermal growth factor receptor (EGFR) evades proteolytic degradation and accumulates in non-small cell lung cancer (NSCLC) remains unclear, and ubiquitin pathway genes (UPGs) that are critical to NSCLC needs to be systematically identified. METHODS: A total of 696 UPGs (including E1, E2, E3, and deubiquitinases) were silenced by small interfering RNA (siRNA) library in NSCLC cells, the candidates were verified, and their significance was evaluated in patients with NSCLC. The effects of a candidate gene on EGFR were investigated in vitro and in vivo. FINDINGS: We report 31 candidates that are required for cell proliferation, with the E2 ubiquitin conjugase CDC34 as the most significant one. CDC34 is elevated in tumor tissues in 76 of 114 (66.7%) NSCLCs and inversely associated with prognosis, is higher in smoker patients than nonsmoker patients, and is induced by tobacco carcinogens in normal human lung epithelial cells. Forced expression of CDC34 promotes, whereas knockdown of CDC34 inhibits, NSCLC cell proliferation in vitro and in vivo. CDC34 competes with c-Cbl to bind Y1045 to inhibit polyubiquitination and degradation of EGFR. In EGFR-L858R and EGFR-T790M/Del (exon 19)-driven lung tumor growth in mouse models, knockdown of CDC34 significantly inhibits tumor formation. INTERPRETATION: These results demonstrate that an E2 enzyme is capable of competing with E3 ligase to stabilize substrates, and CDC34 represents an attractive therapeutic target for NSCLCs. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, and the CAMS Innovation Fund for Medical Sciences.


Assuntos
Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/metabolismo , Neoplasias Pulmonares/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Animais , Carcinogênese/efeitos dos fármacos , Carcinógenos/toxicidade , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos SCID , Poluição por Fumaça de Tabaco/efeitos adversos , Transcriptoma , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
11.
J Clin Oncol ; 37(25): 2235-2245, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31194613

RESUMO

PURPOSE: To assess the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as neoadjuvant/adjuvant therapies in locally advanced EGFR mutation-positive non-small-cell lung cancer. PATIENTS AND METHODS: This was a multicenter (17 centers in China), open-label, phase II, randomized controlled trial of erlotinib versus gemcitabine plus cisplatin (GC chemotherapy) as neoadjuvant/adjuvant therapy in patients with stage IIIA-N2 non-small-cell lung cancer with EGFR mutations in exon 19 or 21 (EMERGING). Patients received erlotinib 150 mg/d (neoadjuvant therapy, 42 days; adjuvant therapy, up to 12 months) or gemcitabine 1,250 mg/m2 plus cisplatin 75 mg/m2 (neoadjuvant therapy, two cycles; adjuvant therapy, up to two cycles). Assessments were performed at 6 weeks and every 3 months postsurgery. The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; secondary end points were pathologic complete response, progression-free survival (PFS), overall survival, safety, and tolerability. RESULTS: Of 386 patients screened, 72 were randomly assigned to treatment (intention-to-treat population), and 71 were included in the safety analysis (one patient withdrew before treatment). The ORR for neoadjuvant erlotinib versus GC chemotherapy was 54.1% versus 34.3% (odds ratio, 2.26; 95% CI, 0.87 to 5.84; P = .092). No pathologic complete response was identified in either arm. Three (9.7%) of 31 patients and zero of 23 patients in the erlotinib and GC chemotherapy arms, respectively, had a major pathologic response. Median PFS was significantly longer with erlotinib (21.5 months) versus GC chemotherapy (11.4 months; hazard ratio, 0.39; 95% CI, 0.23 to 0.67; P < .001). Observed adverse events reflected those most commonly seen with the two treatments. CONCLUSION: The primary end point of ORR with 42 days of neoadjuvant erlotinib was not met, but the secondary end point PFS was significantly improved.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Terapia Neoadjuvante , Estadiamento de Neoplasias
12.
Thorac Cancer ; 10(5): 1129-1135, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30932350

RESUMO

BACKGROUND: This study was conducted to investigate the gene expression profiles associated with thymoma to better understand the molecular mechanism underlying the pathogenesis of thymoma. METHODS: Eight patients with thymomas (type A, AB, B1, and B2) and four controls with thymic cysts were analyzed using microarray profiling to identify changes in gene expression. RESULTS: Across all of our samples, 2319 messenger RNAs were upregulated and 2776 were downregulated in thymomas relative to thymic cysts. Gene ontology and pathway analyses revealed that a large number of genes participate in cellular functions, among which MHC class II protein complex assembly, assembly with peptide antigen, calcium activated phosphatidylcholine scrambling, and release of cytoplasmic sequestered NF-κB were dysregulated, whereas intestinal immune network for immunoglobulin A production, cytokine-cytokine receptor interaction, the calcium signaling pathway, and pathways related to autoimmune diseases were downregulated. CONCLUSIONS: Our results revealed gene expression differences between thymomas and thymic cysts, and identified key candidate genes/pathways that might be used as diagnostic markers and potential therapeutic targets to treat cancer metastasis.


Assuntos
Regulação Neoplásica da Expressão Gênica , Timoma/genética , Transcriptoma , Biomarcadores Tumorais , Estudos de Casos e Controles , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Masculino , Cisto Mediastínico/genética , Timoma/patologia
13.
J Clin Oncol ; 36(29): 2935-2942, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30148659

RESUMO

PURPOSE: To investigate the prognostic impact of 4L lymph node (LN) dissection in left lung cancer and to analyze the relative risk factors for 4L LN metastasis. PATIENTS AND METHODS: We retrospectively collected data from 657 patients with primary left lung cancer who underwent surgical pulmonary resection from January 2005 to December 2009. One hundred thirty-nine patients underwent 4L LN dissection (4LD+ group); the other 518 patients did not receive 4L LN dissection (4LD- group). Propensity score weighting was applied to reduce the effects of observed confounding between the two groups. Study end points were disease-free survival (DFS) and overall survival (OS). RESULTS: The metastasis rate of station 4L was 20.9%, which was significantly higher than those of station 7 (14.0%; P = .048) and station 9 (9.8%; P < .001). Station 4L metastasis was associated with most other LN station metastases in univariate analysis, but only station 10 LN metastasis was an independent risk factor for 4L LN metastasis (odds ratio, 0.253; 95% CI, 0.109 to 0.588; P = .001) in multivariate logistic analysis. The 4LD+ group had a significantly better survival than the 4LD- group (5-year DFS, 54.8% v 42.7%; P = .0376; 5-year OS, 58.9% v 47.2%; P = .0200). After allowing potential confounders in multivariate survival analysis, dissection of 4L LN retained its independent favorable effect on DFS (hazard ratio, 1.502; 95% CI, 1.159 to 1.947; P = .002) and OS (hazard ratio, 1.585; 95% CI, 1.222 to 2.057; P = .001). Propensity score weighting further confirmed that the 4LD+ group had a more favorable DFS ( P = .0014) and OS ( P < .001) than the 4LD- group. CONCLUSION: Station 4L LN involvement is not rare in left lung cancer, and dissection of the 4L LN station seems to be associated with a more favorable prognosis as compared with those who did not undergo this dissection.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Excisão de Linfonodo/métodos , Metástase Linfática/diagnóstico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
14.
Transl Lung Cancer Res ; 7(3): 428-436, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30050780

RESUMO

The notable clinical success of cancer immunotherapy using checkpoint blockade suggests that it is likely to form the foundation of curative therapy for many malignancies. However, checkpoint blockades do not achieve sustained clinical response in most patients and thus amounts of problems needed to be figured out. Regarding these challenges, the 2017 Chinese Lung Cancer Summit expert panel organized a forum on the 14th Chinese Lung Cancer Summit to formally discuss these controversies. Five consensuses finally were reached to guide the application of checkpoint blockades.

15.
Zhongguo Zhong Yao Za Zhi ; 42(1): 157-161, 2017 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28945042

RESUMO

To study the effects of compound Longmaining(FFLMN) with different combinations on the intestinal absorption of puerarin. The rat single pass intestinal perfusion model was adopted, and the concentration of puerarin in intestinal samples was determined by HPLC. The effects of different combination groups on the absorption of puerarin in duodenum, jejunum, ileum and colon were investigated. The combined drugs were GG(Puerariae Lobatae Radix), GG-CSL (Puerariae Lobatae Radix compared with Dioscoreae Nipponicae Rhizoma), GG-CX(Puerariae Lobatae Radix compared with Chuanxiong Rhizoma) and FFLMN (compound Longmaining). We found that the absorption rate constant(Ka) and the apparent coefficient(Papp) of puerarin had no significant difference between GG-CSL and FFLMN groups, but significantly higher in GG and GG-CX groups(P<0.05) in the duodenum and ileum. In jejunum and colon, Ka and Papp of puerarin showed significant differences between GG and other groups(P<0.05). At the same time, FFLMN also had significant differences with GG-CSL and GG-CX groups(P<0.05). The results showed that in the whole intestine of rats, FFLMN could significantly promote the absorption of puerarin. In the duodenum and ileum, Dioscoreae Nipponicae Rhizoma played a significant role in promoting absorption of puerarin. In jejunum and colon, Dioscoreae Nipponicae Rhizoma and Chuanxiong Rhizoma have a synergistic effect in promoting absorption of puerarin.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Absorção Intestinal , Isoflavonas/farmacocinética , Animais , Ratos
16.
ESMO Open ; 2(Suppl 1): e000174, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28848676

RESUMO

The diagnosis and treatment of lung cancer have evolved into the era of precision medicine. Liquid biopsy, a minimally invasive approach, has emerged as a promising practice in genetic profiling and monitoring of lung cancer. Translating liquid biopsy from bench to bedside has encountered various challenges, including technique selection, protocol standardisation, data analysis and cost management. Regarding these challenges, the 2016 Chinese Lung Cancer Summit expert panel organised a trilateral forum involving oncologists, clinicians, clinical researchers, and industrial expertise on the 13th Chinese Lung Cancer Summit to formally discuss these controversies. Six consensuses were reached to guide the use of liquid biopsy and perform precision medicine in both clinic and research.

17.
Pharmacol Res ; 124: 105-115, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28754458

RESUMO

The acquired resistance of non-small cell lung cancer (NSCLC) to taxanes eventually leads to the recurrence and metastasis of tumours. Thus, the development of therapeutic strategies based on the mechanisms by which cells acquire resistance to prolong their survival rate in chemotherapy drug treatment failure patients are warranted. In this study, we found that the resistant cells acquired increased migratory and invasive capabilities, and this transformation was correlated with epithelial-mesenchymal transition (EMT) and Notch pathway deregulation in the resistant cells. Finally, we reported for the first time that terfenadine augmented the effect of epirubicin (EPI) better than Taxol and cisplatin (DDP) by inhibiting migration, invasion, and the EMT phenotype, and the combination therapy also reversed Notch signalling pathway and enhanced the accumulation of fluorescent P-gp substrate rhodamine 123 (Rh123). Similar activities of terfenadine on EPI were observed in xenografts. All of our results confirmed that terfenadine combined with EPI synergistically inhibits the growth and metastatic processes of resistant cells both in vitro and in vivo. Therefore, terfenadine or its derivatives are a promising approach for the clinical challenge of resistance in patients with advanced NSCLC.


Assuntos
Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Epirubicina , Neoplasias Pulmonares/tratamento farmacológico , Terfenadina , Células A549 , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Receptores Notch/metabolismo , Terfenadina/farmacologia , Terfenadina/uso terapêutico , Carga Tumoral/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
18.
Thorac Cancer ; 7(5): 556-563, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27766775

RESUMO

BACKGROUND: This study was conducted to investigate the clinical significance of claudin-1 (CLDN1) expression in patients with lung adenocarcinoma. METHODS: We examined CLDN1 protein expression by immunohistochemistry in a tissue microarray from 258 patients with lung adenocarcinoma. We investigated messenger ribonucleic acid (mRNA) expression in H358 (formerly bronchioloalveolar carcinoma) and lung adenocarcinoma cell lines (A549) by real-time reverse transcriptase-polymerase chain reaction. RESULTS: Multivariate analysis showed that prognostic factors for lung adenocarcinoma were histologic type, CLDN1, T stage and N stage. Patients with positive CLDN1 expression had a poorer prognosis than patients with negative CLDN1 expression. CLDN1 expression was correlated with Ras and epidermal growth factor receptor (EGFR) expression. Patients with positive expressions of both CLDN1 and Ras/EGFR had a poorer prognosis than patients with CLDN1 (+) Ras/EGFR(-) or CLDN1 (-) Ras/EGFR(+) and patients with negative expressions of both CLDN1 and Ras/EGFR. CLDN1 mRNA expression was lower in the H358 compared with the lung adenocarcinoma cell line (A549). CONCLUSION: The combination of CLDN1 and Ras/EGFR is a valuable independent prognostic predictor for lung adenocarcinoma.


Assuntos
Adenocarcinoma/patologia , Claudina-1/genética , Claudina-1/metabolismo , Neoplasias Pulmonares/patologia , Análise Serial de Tecidos/métodos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Linhagem Celular Tumoral , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Estadiamento de Neoplasias , Prognóstico , Regulação para Cima , Proteínas ras/genética
19.
Zhongguo Zhong Yao Za Zhi ; 41(8): 1535-1540, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28884552

RESUMO

To study the pharmacokinetics of puerarin in compound Longmaining(FFLMN) in normal rats and myocardial ischemia rats, and investigate its correlation with anti-myocardial ischemia effect of FFLMN. Models of myocardial ischemia rats were produced by subcutaneous injection of isoproterenol(ISO), then FFLMN extract solution was administered by gavage. Orbital sinus blood sampling was collected at different time points after gavage. HPLC-UV method was applied to determine the concentration of puerarin in plasma, and compare the difference in pharmacokinetics between normal rats and model rats after application of same dose of FFLMN. Meanwhile, microplate reader was used to determine IL-6 and SOD activities in plasma of different time points, and draw dose-effect curve. The results indicated that the pharmacokinetics of puerarin conformed to the two-compartment model in both normal group and myocardial ischemia model group. In the comparison of main pharmacokinetic parameters between two groups: AUC0-∞=(11.451±3.228) mg•h•L⁻¹,AUC0-t=(14.047±3.765) mg•h•L⁻¹, Cmax=(5.623±1.40) mg•L⁻¹ in normal group; AUC0-∞=(68.849±50.396 9) mg•h•L⁻¹, AUC0-t= (58.312±45.802) mg•h•L⁻¹,Cmax=(18.456±7.517) mg•L⁻¹ in treatment group. The SOD level was significantly increased and IL-6 concentration was significantly decreased in plasma, indicating that as compared with the normal group, puerarin in FFLMN had a higher plasma concentration, slower elimination rate and higher bioavailability. Therefore, puerarin concentration in plasma has correlation with the anti-myocardial ischemia effect of FFLMN, which could increase SOD level and inhibit the release of IL-6.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Isoflavonas/farmacocinética , Isquemia Miocárdica/tratamento farmacológico , Animais , Interleucina-6/sangue , Ratos , Superóxido Dismutase/sangue
20.
Zhong Yao Cai ; 39(1): 160-3, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30080019

RESUMO

Objective: To study the pharmacokinetic and tissue distribution of quercetin injection and submicron emulsion after intravenous administration in mice. Methods: The concentration of quercetin in mice plasma and tissues were determined by RPHPLC. Results: Liver had the highest tissue concentration of quercetin submicron emulsion, followed by plasma, kidney, spleen, lung, heart and brain. And their had significantly increased compared with the AUC0→tof plasma, liver, spleen, kidney and brain after administration of quercetin injection( P < 0. 05). The Rte and Re of liver, brain and spleen were all larger than 1. Conclusion: Quercetin submicron emulsion significantly alters the plasma pharmacokinetic characteristics of quercetin after intravenous administration in mice. And it has good targeting location features in liver, brain, spleen and kidney.


Assuntos
Fígado , Distribuição Tecidual , Animais , Encéfalo , Emulsões , Rim , Pulmão , Camundongos , Especificidade de Órgãos , Quercetina , Baço
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...