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1.
Cell Death Dis ; 13(3): 285, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35354796

RESUMO

The incidence of lung cancer is increasing worldwide. Although great progress in lung cancer treatment has been made, the clinical outcome is still unsatisfactory. Tripartite motif (TRIM)-containing proteins has been shown to be closely related to tumor progression. However, the function of TRIM46 in lung cancer is largely unknown. Here, TRIM46 amplification was found in lung adenocarcinoma (LUAD) tissues and TRIM46 amplification was significantly associated with a poor survival rate. Overexpression of wild type TRIM46 increased the proliferation of LUAD cells and glycolysis, promoted xenografts growth, and enhanced cisplatin (DDP) resistance of LUAD cells via increased ubiquitination of pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) and upregulation of p-AKT. In contrast, overexpression of RING-mutant TRIM46 did not show any effects, suggesting the function of TRIM46 was dependent on the E3 ligase activity. Furthermore, we found that TRIM46 promoted LUAD cell proliferation and DDP resistance by enhancing glycolysis. PHLPP2 overexpression reversed the effects of TRIM46 overexpression. Amplification of TRIM46 also promoted LUAD growth and enhanced its DDP resistance in a patient-derived xenograft (PDX) model. In conclusion, our data highlight the importance of TRIM46/PHLPP2/AKT signaling in lung cancer and provide new insights into therapeutic strategies for lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Glicólise , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitinação
2.
Interact Cardiovasc Thorac Surg ; 31(6): 912-914, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33164072

RESUMO

A 71-year-old man had experienced an irritating cough for 3 months. A diagnosis of squamous cell carcinoma in the carina was made from the bronchoscopic examination. The patient underwent a robotic-assisted resection and reconstruction of the carina. The patient's postoperative course was uneventful. This is the first description of the feasibility of robotic-assisted carina resection and reconstruction.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Pulmonares/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Pneumonectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Toracoscopia/métodos , Traqueia/cirurgia , Idoso , Broncoscopia , Carcinoma de Células Escamosas/diagnóstico , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Tomografia Computadorizada por Raios X
3.
Drug Des Devel Ther ; 14: 4503-4510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122893

RESUMO

INTRODUCTION: This study aims to develop a novel co-delivery gefitinib and quercetin system loaded with PLGA-PEG nanoparticles and evaluate their antitumor activity in vitro and in vivo. METHODS: Gef/Qur NPs were prepared and characterized. The release of drugs, stability, cellular uptake and cytotoxicity were evaluated in vitro. The antitumor effects and systemic toxicity of different formulations were also investigated. RESULTS: Gef/Qur NPs displayed a smaller particle size and a PDI and zeta potential of 0.11 and -23.5 mV, respectively. The hydrophobic Gef and Qur content in NPs reached up to 65.2% and 56.4%, respectively, and their high entrapment efficiencies recorded 83.7% and 82.3%, respectively. The in vitro release of Gef/Qur from the NPs was sustained for 12 h. Compared with control groups, Gef/Qur NPs showed higher cellular uptake and cell inhibition rates. In vivo studies identified the lungs as the target tissue and the region of maximum drug release. Through pharmacodynamics analysis, we found that two drugs (Gef and Qur) were incorporated into one nanoparticle carrier, which played a good role in generating synergistic effect. DISCUSSION: It is concluded that PLGA-PEG is an ideal drug carrier for the co-delivery of Gef/Qur to treat lung cancer.


Assuntos
Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Gefitinibe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química , Quercetina/farmacologia , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Gefitinibe/química , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Estrutura Molecular , Tamanho da Partícula , Quercetina/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
4.
World J Surg Oncol ; 18(1): 157, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631334

RESUMO

BACKGROUND: This study aimed to assess the correlation of katanin P60 expression with clinical characteristics and survival profiles of surgical non-small cell lung cancer (NSCLC) patients. METHODS: Two hundred and sixty-five primary NSCLC patients treated by surgical resection were retrospectively viewed. The expression of katanin P60 in the tumor specimen was detected by the immunohistochemical (IHC) staining assay. Preoperative clinical data were collected from patients' medical records, and survival data were extracted from follow-up records. RESULTS: There were 127 (47.9%) and 138 (52.1%) patients with katanin P60-low expression and -high expression, respectively; in addition, patients presenting katanin P60-high+, -high++, and -high+++ expression were 62 (23.4%), 63 (23.8%), and 13 (4.9%), respectively. Katanin P60 expression was correlated with lymph node (LYN) metastasis and advanced TNM stage but not pathological grade, tumor size, carcinoembryonic antigen (CEA) level or other non-tumor features in NSCLC patients. Regarding survival profiles, disease-free survival (DFS) and overall survival (OS) were both the lowest in katanin P60-high+++ expression patients, followed with katanin P60-high++ patients, katanin P60-high+ patients, and the highest in katanin P60-low expression patients. Further analysis illustrated that katanin P60-high expression was an independent predictive factor for unfavorable DFS and OS in NSCLC patients. CONCLUSIONS: Katanin P60 presents potential as a biomarker for lymph node metastasis and prognosis in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Katanina , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
5.
Cell Death Dis ; 10(6): 429, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160576

RESUMO

Cisplatin resistance is the main cause of treatment failure in patients with non-small-cell lung cancer (NSCLC). Autophagy is a key mechanism of resistance to chemotherapy. Given that tripartite motif (TRIM)-containing proteins are involved in the regulation of autophagy and chemoresistance, we aimed to study the functions of TRIM protein members in autophagy-mediated chemoresistance of NSCLC. We found that TRIM65 was significantly increased in cisplatin-resistant NSCLC cell line (A549/DDP) as compared to the parental cell line (A549). Knockdown of TRIM65 can enhance cisplatin-induced apoptosis and inhibit autophagy in A549/DDP cells, as indicated by Annexin V/PI staining, caspase3 activity test, and LC3-II immunofluorescence staining. Additionally, knockdown of TRIM65 significantly decreased the expression of an important autophagy mediator, ATG7, which was a potential target of miR-138-5p. miR-138-5p inhibitor significantly abolished the effects of TRIM65 knockdown on autophagy and cisplatin-induced apoptosis. Moreover, TRIM65 induced the ubiquitination and degradation of TNRC6A, resulting in the suppressed expression of miR-138-5p. TRIM65 knockdown inhibited the growth of tumors derived from A549/DDP cells. Furthermore, cisplatin-resistant NSCLC tissues displayed higher expression of TRIM65 mRNA and lower expression of miR-138-5p as compared to cisplatin non-resistant ones. miR-138-5p expression was negatively correlated with TRIM65 mRNA in NSCLC tissues. Collectively, the present study indicates that TRIM65 knockdown attenuates autophagy and cisplatin resistance in A549/DDP cells via regulating miR-138-5p.


Assuntos
Antineoplásicos/farmacologia , Proteína 7 Relacionada à Autofagia/metabolismo , Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Cisplatino/farmacologia , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Células A549 , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Autoantígenos/genética , Autoantígenos/metabolismo , Autofagia/efeitos dos fármacos , Proteína 7 Relacionada à Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/genética
6.
Mol Med Rep ; 16(5): 6483-6488, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901459

RESUMO

Hyperoside (HY) is a major pharmacologically active component from Prunella vulgaris L. and Hypericum perforatum. The present study aimed to determine the anticancer effect of HY and determine the underlying mechanisms involved. Human A549 cells were treated with HY (10, 50 and 100 µM), and cell viability was detected by an MTT assay. Cell apoptosis and mitochondrial membrane potential were determined by flow cytometry. Western blot analysis was used to identify the expression of apoptosis­associated proteins and phosphorylation of MAPK. The present study demonstrated that HY significantly inhibited the viability of A549 cells in a time­ and dose­dependent manner, and enhanced the percentage of apoptotic cells. HY also significantly increased the protein phosphorylation of p38 mitogen­activated protein kinase (MAPK) and c­Jun N­terminal kinase (JNK), disrupted mitochondrial membrane penetrability, and triggered the release of mitochondrial cytochrome c and apoptosis­inducing factor into the cytosol. Treatment with HY also activated the expression of caspase­9 and caspase­3. These results suggested that HY­induced apoptosis was associated with activation of the p38 MAPK­ and JNK­induced mitochondrial death pathway. HY may offer potential for clinical applications in treating human non­small cell lung cancer and improving cancer chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Mitocôndrias/efeitos dos fármacos , Quercetina/análogos & derivados , Células A549 , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Fracionamento Celular , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Relação Dose-Resposta a Droga , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosforilação/efeitos dos fármacos , Quercetina/farmacologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Oncotarget ; 7(18): 26837-43, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27072586

RESUMO

N-Myc downstream-regulated gene 2 (NDRG2) protein is a tumor suppressor that inhibits cancer growth, metastasis and invasion. The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin through its selective recognition and ubiquitination of SUMO-modified proteins. We evaluated NDRG2 SUMOylation in lung adenocarcinoma cells and its underlying molecular mechanism. The results showed that NDRG2 is covalently modified by SUMO1 at K333, which suppressed anchorage independent adenocarcinoma cell proliferation and tumor growth. In human lung adenocarcinomas cells, RNF4 targeted NDRG2 to proteasomal degradation by stimulating its SUMOylation. Endogenous RNF4 expression was increased in human lung adenocarcinomas cells, and there was a concomitant upregulation of SUMO. These findings indicate that SUMOylation of NDRG2 is necessary for its tumor suppressor function in lung adenocarcinoma and that RNF4 increases the efficiency of this process.


Assuntos
Adenocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Pulmonares/patologia , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Sumoilação
8.
Ann Thorac Surg ; 101(1): 294-300, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26431923

RESUMO

BACKGROUND: Primary tracheal cancer comprises a heterogeneous and rare group of neoplasms. Management of patients with primary tracheal carcinoma at our institution has improved in recent years. METHODS: This retrospective review included patients with localized primary tracheal adenoid cystic carcinoma treated surgically at our institution between January 1995 and December 2014. Patients were classified according to the timing of first operation: "early years" operation was performed between January 1995 and December 2002, and subsequent "recent years" operation was associated with improved management and a focus on early diagnosis. RESULTS: The proportion of patients with tracheal malignancy who underwent operation for adenoid cystic carcinoma increased with time. Patients in the recent group were significantly younger than those in the early group at diagnosis (49.3 ± 7.8 years versus 45.7 ± 9.4 years; p = 0.042), and the resected tumor size and tracheal lengths tended to be smaller (28.2 ± 7.6 mm versus 30.3 ± 7.0 mm; p = 0.161) and shorter (32.1 ± 7.7 mm versus 34.4 ± 6.7 mm; p = 0.123). The use of postoperative radiotherapy in patients with R1 resection was also managed more effectively in the recent group compared with the early group (90.6% versus 65.0%; p = 0.009). Five- and 10-year overall survival rates in the early and recent groups were 86.4% and 90.8%, and 31.8% and 61.2%, respectively (p = 0.084), and the corresponding 5- and 10-year disease-free survival rates were 39.7% and 75.3%, and 9.9% and 21.2%, respectively (p = 0.025). CONCLUSIONS: There have been improved outcomes of adenoid cystic carcinomas. Early diagnosis, experienced surgical treatments, and postoperative adjuvant radiotherapy for patients with positive margins may contribute to the improved survival of patients with primary tracheal adenoid cystic carcinoma.


Assuntos
Carcinoma Adenoide Cístico/cirurgia , Diagnóstico Precoce , Procedimentos Cirúrgicos Torácicos/métodos , Neoplasias da Traqueia/cirurgia , Adulto , Idoso , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/mortalidade , China/epidemiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Neoplasias da Traqueia/diagnóstico , Neoplasias da Traqueia/mortalidade , Resultado do Tratamento , Adulto Jovem
9.
Mol Med Rep ; 13(2): 1097-104, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26647768

RESUMO

The present study aimed to measure the effect of heterophyllin B (HB) on the adhesion and invasion of ECA-109 human esophageal carcinoma cells, and examine the possible mechanism involved. A Cell Counting kit 8 assay was performed to determine the cell viability. Cell adhesion and invasion were determined following treatment of the ECA-109 cells with HB (0, 10, 25 and 50 µM) for 24 h. The levels of phosphorylated (p-)ATK and p-phosphoinositide 3-kinase (PI3K), and the protein levels of ß-catenin were measured using western blot analysis. The mRNA and protein expression levels of E-cadherin, vimentin, snail, matrix metalloproteinase (MMP)2 and MMP9 were detected using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. HB (10, 25 and 50 µM) significantly suppressed the adhesion and invasion of the ECA-109 human esophageal carcinoma cells in a dose-dependant manner. The expression levels of p-ATK, p-PI3K and ß-catenin were markedly decreased. The expression of E-cadherin was promoted, whereas the expression levels of snail, vimentin, MMP 2 and MMP 9 were decreased significantly in the ECA-109 cells treated with HB. In addition, HB inhibited the adhesion and invasion induced by PI3K activating peptide in the ECA-109 cells, and the protein expression levels were also adjusted. These results suggested that HB effectively suppressed the adhesion and invasion of the human esophageal carcinoma cells by mediating the PI3K/AKT/ß-catenin pathways and regulating the expression levels of adhesion- and invasion-associated genes.


Assuntos
Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Peptídeos Cíclicos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Vimentina/metabolismo
10.
J Thorac Dis ; 7(7): 1227-34, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26380739

RESUMO

OBJECTIVES: To present our experience of reconstructing wide defects with porously titanium mesh after radical resection of malignant chest wall tumors. METHODS: A retrospective review of surgical reconstruction for large chest wall resections with titanium mesh was conducted from January 2009 to August 2014 in Shanghai Chest Hospital. RESULTS: A total of 27 patients underwent major chest wall reconstructions with titanium mesh, following oncological resections. Chest wall sarcomas were the most frequent (63.0%). The mean tumor size was 72.4 (range, 36-140) cm(2). The average size of the applied porously titanium mesh was 140.9 (range, 80-225) cm(2). Mean postoperative length of stay was 7.1 (range, 4-14) days. There were no perioperative mortalities. Four (14.8%) patients experienced treatable complications. All had a resection of at least 3 ribs (median 3, mean 3.5 ribs). A total of 22 patients underwent ribs without sternal resections, and five patients underwent partial sternal resections with adjacent costal cartilage. Anterior chest wall resections were performed in 13 patients while lateral chest wall resections were performed in 9 patients. Three patients had extended resections beyond the chest wall in patients with primary chest wall malignancies, including two with wedge resections of lung and one with partial resection of pericardium. No patient was lost to follow-up. Mean follow-up was 30.7 months. Neither chest wall instability nor wound infection/necrosis was observed. Of these, 23 patients (85.2%) were alive at the last follow-up. Local recurrence was detected in three cases. The 5-year disease-free and overall survivals of primary chest tumors were 72.1% and 80.8%, respectively. CONCLUSIONS: Our results showed that chest wall reconstruction utilizing synthetic titanium meshes following extensive resections of the chest wall malignant tumors allowed adequate resection size, with acceptable complications and survival benefits.

11.
Int J Clin Exp Pathol ; 8(7): 7887-95, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26339353

RESUMO

OBJECTIVE: Long non-coding RNAs (lncRNAs) XIST and HIF1A-AS1 have been shown to play important regulatory roles in cancer biology, and lncRNA-XIST and HIF1A-AS1 are upregulated in several cancers such as glioblastoma, breast cancer and thoracoabdominal aorta aneurysm, however, its value in the diagnosis of non-small cell lung cancer (NSCLC) is unclear. The aim of this study is to evaluate the clinical significance of serum XIST and HIF1A-AS1 as a biomarker in the screening of NSCLC. METHODS: Expression levels of lncRNA-XIST and HIF1A-AS1 in tumor tissues and serum from NSCLC patients were evaluated by quantitative real-time PCR, and its association with overall survival of patients was analyzed by statistical analysis. Moreover, the XIST and lncRNA-XIST expression correlation between tumor tissues and plasma was demonstrated by linear regression analysis. RESULTS: The levels of XIST (P < 0.05) and HIF1A-AS1 (P < 0.05) were significantly increased in tumor tissues or serum from NSCLC patients as compared to those of control group. Correlation of lncRNA-XIST or HIF1A-AS1 expression between tumor tissues and serum from the same individuals was confirmed in NSCLC patients. Moreover, serum levels of XIST and HIF1A-AS1 were significantly decreased after surgical treatment as compared to pre-operative. The ROC curves illustrated strong separation between the NSCLC patients and control group, with an AUC of 0.834 (95% CI: 0.726-0.935; P < 0.001) for XIST and 0.876 (95% CI: 0.793-0.965; P < 0.001) for HIF1A-AS1, however, the combination of XIST and HIF1A-AS1 yielded an AUC of 0.931 (95% CI: 0.869-0.990; P < 0.001), which was significantly improved as compared to XIST or HIF1A-AS1 alone. CONCLUSION: Our results demonstrated that increased serum XIST and HIF1A-AS1 could be used as a predictive biomarker for NSCLC screening, and that combination of XIST and HIF1A-AS1 had a higher positive diagnostic efficiency of NSCLC than XIST or HIF1A-AS1 alone.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/sangue , RNA Longo não Codificante/sangue , Área Sob a Curva , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Valor Preditivo dos Testes , RNA Longo não Codificante/genética , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento , Regulação para Cima
12.
Eur J Med Res ; 19: 52, 2014 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-25358439

RESUMO

BACKGROUND: The aim of this study was to identify the candidate genes of esophageal squamous cell carcinoma (ESCC). METHODS: Gene expression profiling of 17 ESCC samples and 17 adjacent normal samples, GSE20347, was downloaded from Gene Expression Omnibus database. The raw data were preprocessed, and the differentially expressed genes (DEGs) between ESCC and normal samples were identified by using SAM software (false discovery rate <0.001). Then, the co-expression network of DEGs was constructed based on Pearson's correlation test (r-value ≥0.8). Furthermore, the topological properties of the co-expression network were analyzed through NetworkAnalyzer (default settings) of Cytoscape. The expression fold changes of DEGs and topological properties were utilized to identify the candidate genes of ESCC (Crin score >4), which were further analyzed based on DAVID functional enrichment analysis (P-value <0.05). RESULTS: A total of 1,063 DEGs were identified, including 490 up-regulated and 573 down-regulated DEGs. Then, the co-expression network of DEGs was constructed, containing 999 nodes and 46,323 edges. Based on the expression fold changes of DEGs and the topological properties of the co-expression network, DEGs were ranked, and the top 24 genes were candidate genes of ESCC, such as CRISP3, EREG, CXCR2, and CRNN. Furthermore, the 24 genes were significantly enriched in bio-functions regarding cell differentiation, glucan biosynthetic process and immune response. CONCLUSION: The present study suggested that CRISP3, EREG, CXCR2, and CRNN might be causative genes of ESCC, and play vital roles in the development of ESCC. However, further experimental studies are needed to confirm our results.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes , Estudos de Associação Genética/classificação , Carcinoma de Células Escamosas/patologia , Biologia Computacional , Bases de Dados Genéticas , Epirregulina/biossíntese , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Perfilação da Expressão Gênica , Humanos , Proteínas de Membrana/biossíntese , Proteínas de Neoplasias/biossíntese , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Interleucina-8B/biossíntese , Proteínas e Peptídeos Salivares/biossíntese , Proteínas de Plasma Seminal/biossíntese
13.
Tumour Biol ; 35(1): 689-94, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23959479

RESUMO

Genome-wide association studies have identified 6p21 as a new lung cancer susceptibility locus in populations of European descent. Since then, the relationship between common variations on 6p21 and lung cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 11 studies involving a total of 36,890 cases and 52,767 controls for three widely studies polymorphisms (rs4324798, rs3117582, and rs9295740) to evaluate its effect on genetic susceptibility for lung cancer. An overall random-effects per-allele odds ratio (OR) of 1.11 (95% confidence interval (CI) 1.04­1.19; P = 0.002) and 1.20 (95% CI 1.14­1.26; P < 10(−5)) was found for the rs4324798 and rs3117582 polymorphism, respectively. Marginal significant associations were also detected for rs9295740 with per-allele OR of 1.09 (95% CI 1.01­1.18; P = 0.03). In the subgroup analysis by ethnicity, significantly increased risks were found for the three polymorphisms among Caucasians. Similar results were also observed using dominant or recessive genetic models. This meta-analysis demonstrated that the three common variations (rs4324798, rs3117582, and rs9295740) on 6p21 are risk factors associated with increased lung cancer susceptibility, but these associations vary in different ethnic populations.


Assuntos
Cromossomos Humanos Par 6 , Variação Genética , Neoplasias Pulmonares/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/etnologia , Razão de Chances , Polimorfismo de Nucleotídeo Único , Viés de Publicação , Risco
14.
Surg Endosc ; 28(1): 122-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23963682

RESUMO

BACKGROUND: This study aimed to compare the perioperative outcomes for patients who underwent transsternal or robot-assisted thymectomy and to determine the feasibility of robot-assisted thymectomy for the treatment of Masaoka stages 1 and 2 thymomas. METHODS: The study evaluated the short-term outcomes for 74 patients undergoing surgery for Masaoka stages 1 and 2 thymomas without myasthenia gravis between January 2009 and December 2012. Of these 74 patients, 23 underwent thymoma resection using unilateral robot-assisted thoracoscopic surgery (RATS group), and 51 underwent transsternal thymectomy (TST group). Duration of surgery, amount of intraoperative blood loss, duration of chest drainage, duration of postoperative hospital stay, and postoperative complications were evaluated. RESULTS: The intraoperative blood loss was significantly less in the RATS groups (61.3 ml) than in the TST group (466.1 ml) (p < 0.01). The postoperative hospital stay was significantly shorter in the RATS group (3.7 vs 11.6 days; p < 0.01). No patients in the RATS group underwent conversion to open surgery. No severe surgical complications (e.g., bleeding caused by injury to the left brachiocephalic vein) and only one case of pulmonary atelectasis (appearing in a male patient 2 days after surgery) were detected in this series. CONCLUSION: Robot-assisted thoracoscopic thymectomy for early-stage thymomas is technically feasible, safe, and less invasive for the patient.


Assuntos
Robótica/métodos , Toracoscopia/métodos , Timectomia/métodos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida , Toracoscopia/efeitos adversos , Timectomia/efeitos adversos , Timoma/patologia , Neoplasias do Timo/patologia , Resultado do Tratamento
15.
J Thorac Cardiovasc Surg ; 147(5): 1599-603, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24290709

RESUMO

OBJECTIVE: The present study compared the outcomes between patients who had undergone video-assisted thoracoscopic surgery (VATS) thymectomy and transsternal (TS) thymectomy for Masaoka stage I and II thymoma. METHODS: The outcomes of 262 patients without myasthenia gravis who had undergone surgery for Masaoka stage I and II thymoma from January 2008 to December 2012 at our center were retrospectively evaluated. The study included 125 patients who had undergone unilateral VATS thymectomy (VATS group) and 137 patients who had undergone TS thymectomy (TS group). RESULTS: The VATS group had a shorter operative time than the TS group (170 vs 210 minutes, P < .001). The VATS group also had a smaller intraoperative blood loss (200 vs 450 mL, P < .001), smaller pleural drainage volume in the first 24 hours postoperatively (300 vs 500 mL, P < .0010), shorter postoperative pleural drainage duration (3 vs 5 days, P < .001), and shorter postoperative hospital stay (8 vs 10 days, P < .001). Four patients in the VATS group underwent conversion to open surgery because of injury to the innominate vein. The postoperative complication rate was similar between the 2 groups. One patient in the VATS group developed pleural recurrence, and one in the TS group developed local recurrence. CONCLUSIONS: Unilateral VATS thymectomy for Masaoka stage I and II thymoma is technically feasible and safe and is less invasive than TS thymectomy, with a shorter duration of surgery, less intraoperative blood loss, less postoperative pleural drainage, shorter postoperative pleural drainage duration, and shorter postoperative hospital stay. We have concluded that it is preferable to perform VATS thymectomy, although perhaps under certain circumstances sternotomy might be preferred. The oncologic outcomes were comparable between the 2 procedures. Additional follow-up is required to evaluate the long-term outcomes.


Assuntos
Cirurgia Torácica Vídeoassistida , Timectomia/métodos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Adulto , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Veias Braquiocefálicas/lesões , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Duração da Cirurgia , Neoplasias Pleurais/secundário , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Timectomia/efeitos adversos , Timoma/secundário , Neoplasias do Timo/patologia , Fatores de Tempo , Resultado do Tratamento , Lesões do Sistema Vascular/etiologia
16.
Thorac Cancer ; 5(4): 325-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26767020

RESUMO

BACKGROUND: The aim of this study was to report a single referral center experience in robotic extended thymectomy for clinical early stage thymomas, evaluating its safety, feasibility and efficacy, with special regard to oncological outcomes. METHODS: Between January 2009 and December 2012, we retrospectively selected patients who underwent robotic extended thymectomy for clinical early stage thymomas. Operative time, morbidity, mortality, duration of hospitalization, and overall and disease-free survival were analyzed. RESULTS: There were 23 patients (15 males, eight females) with a mean age of 49.3 years (range 20-66). There were no intra-operative complications, and no mortality. The mean operative time was 85.2 minutes (range 60-180). No patient underwent conversion to open surgery. All post-operative complications (4.3%) were conservatively treated. The mean post-operative stay was 3.6 days (range two to nine). The pathological analysis revealed Masaoka stage I (21 cases) and II (two cases). No disease recurrence occurred at a mean follow-up of 24.8 months. CONCLUSIONS: Robotic thymectomy is a safe and feasible technique, with a short operative time and low morbidity. Even on a small series with short follow-up, robotic extended thymectomy for thymoma appeared to be an effective treatment for early-stage thymomas.

17.
Thorac Cancer ; 5(6): 494-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26767043

RESUMO

BACKGROUND: The aim of this study was to compare the short and long-term results between sleeve resection (SR) and pneumonectomy (PN) in lung cancer patients over 70 years of age. METHODS: We retrospectively reviewed 105 lung cancer patients over 70 years of age who had undergone SR or PN at Shanghai Chest Hospital from January 2003 to December 2012. RESULTS: The SR group showed a higher frequency of airway clearance via bronchoscopy (48.6% vs. 25.7%, P = 0.04), longer surgical time (162.7 vs. 140.9 minutes, P = 0.01), and shorter postoperative stay (13.7 vs. 18.1 days, P = 0.02) than the PN group. There was no difference in hospital mortality (P = 1.00) or morbidity (P = 0.40) between the two groups. A logistic regression model showed that preoperative predicted forced expiratory volume in 1 second was the only independent risk factor for overall morbidity (P = 0.04). In survival analysis, SR showed better prognosis than PN (median 50.0 vs. 20.0 months, P < 0.01). In subgroup analysis, SR showed better survival in N0 (P = 0.03) and N1 (P < 0.01) cases, but not in N2 cases (P = 0.36). It also showed better survival in stage I + II patients (P = 0.03), but not in stage III patients (P = 0.10). CONCLUSIONS: Although PN could be carried out as safely as SR in patients over 70 years of age with a good pulmonary reservoir, SR is still recommended as a less traumatic procedure, sparing lung parenchyma with better long-term results.

19.
World J Surg Oncol ; 11: 157, 2013 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-23870330

RESUMO

BACKGROUND: The purpose of this study was to compare perioperative outcomes in patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracoscopic surgery and assess the feasibility of robotic-assisted thymectomy for the treatment of Masaoka stage I. METHODS: We evaluated the short-term outcomes of 46 patients who underwent surgery for Masaoka stage I thymoma without myasthenia gravis between January 2009 and June 2012. Of these patients, 25 received unilateral video-assisted thoracoscopic surgery (VATS group) and the rest 21 recieved unilateral robotic-assisted thoracoscopic surgery (RATS group). We evaluated the duration of surgery, amount of intraoperative blood loss, duration of chest drainage, duration of postoperative hospital stay, hospitalization costs, postoperative complications and oncological outcomes. RESULTS: The duration of surgery was not significantly different between the two groups. Intraoperative blood loss volumes did not differ significantly between the VATS and RATS groups (86.8 mL and 58.6 mL, respectively; P=0.168). The postoperative hospital stay was significantly shorter in the RATS group (3.7 days vs. 6.7 days; P <0.01), and the postoperative pleural drainage volume of the RATS group was significantly less than VATS group (1.1 days vs. 3.6 days; P <0.01). No patients in the RATS group needed conversion to open surgery. However, in the VATS series, one patient had conversion to an open procedure. No surgical complications were observed except that one case had pulmonary atelectasis in the RATS group and one case developed pneumonia after surgery. Use of robot is much more expensive than video. No early recurrence was observed in both groups. CONCLUSIONS: Robotic thymectomy is feasible and safe for Masaoka stage I thymoma. RATS is equally minimally invasive as VATS and results in a shorter drainage period and reduced hospital stay compared with the VATS approach.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias , Robótica , Cirurgia Torácica Vídeoassistida , Toracoscopia , Timectomia/mortalidade , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Timoma/mortalidade , Timoma/patologia , Neoplasias do Timo/mortalidade , Neoplasias do Timo/patologia
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