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1.
Zhonghua Zhong Liu Za Zhi ; 41(10): 783-791, 2019 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-31648503

RESUMO

Objective: To investigate the clinical effects of first generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) compared with platinum-based chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations. Methods: Clinical data of 4 276 patients diagnosed as advanced lung adenocarcinoma (ⅢB/Ⅳ) underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University from January 2012 to February 2018 were collected and 99 cases with uncommon EGFR mutations were selected. The clinical pathological features, treatment outcomes, treatment options and prognosis after first-line treatment of the 99 cases were analysed and compared with other patients with common EGFR mutations. Results: The objective response rates of patients with uncommon EGFR mutations receiving EGFR-TKIs or platinum-based chemotherapy were 33.0% and 27.1%, respectively. The disease control rates were 76.5% and 87.5%, respectively. The progression-free survival (PFS) of patients treated with EGFR-TKIs was 7.2 months, significantly superior than 4.9 months of patients receiving chemotherapy (P=0.009). The overall survival of patients treated with EGFR-TKIs was 14.3 months, significantly worse than 20.7 months of patients receiving chemotherapy (P=0.034). Multivariate analysis showed that distant metastases (P=0.001) and smoking history (P=0.013) were independent prognostic factors for OS of lung adenocarcinoma patients with EGFR uncommon mutations. Conclusions: Compared with chemotherapy, the usage of first generation of EGFR-TKIs as first-line therapy can improve the short-term efficacy of advanced lung adenocarcinoma patients with EGFR uncommon mutations. However, platinum-based chemotherapy shows a longer overall survival.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Receptores ErbB/uso terapêutico , Genes erbB-1/efeitos dos fármacos , Genes erbB-1/genética , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma de Pulmão/patologia , Humanos , Neoplasias Pulmonares/patologia , Mutação , Resultado do Tratamento
2.
Magy Seb ; 72(3): 98-102, 2019 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-31544482

RESUMO

Introduction: Authors present their 7-year experience since the introduction of minimal-invasive (VATS) lobectomies for lung cancer in regard to their surgical technique, results and oncological follow-up. Method: 173 VATS lobectomies were performed between June 2011 and December 2017, 105 men and 68 women. The mean age of patients was 64.1 years. Duration of surgery was 130 minutes on average. Results: Conversion to thoracotomy was required in 8 cases (3 bleedings, 3 pulmonary vessel lymph node infiltrations, 2 bronchial suture insufficiencies). Twenty persistent air leaks developed postoperatively, requiring 10 re-drainages and 10 re-operations: 7 re-VATS and 3 thoracotomies. Two hematomas were evacuated by re-VATS, 1 postoperative atrial fibrillation required cardioversion. There were no perioperative deaths. The 164 malignant cases were: 110 adenocarcinomas, 32 squamous cell carcinomas, 6 small cell neuroendocrine carcinomas, 4 undifferentiated carcinomas, 4 carcinoid tumours, 1 synchronous adenocarcinoma and squamous cell carcinoma, 1 synchronous adenocarcinoma and small cell carcinoma, 1 carcinosarcoma and 5 metastasis from other primary tumours. 118 patients received adjuvant chemotherapy. Tumour staging distribution was: IA 40, IB 53, IIA 29, IIB 16 and IIIA 21 cases. During an average follow-up time of 19.5 months, 9 local tumour recurrence and 27 distant metastasis evaluated, of which 11 were pulmonary (3 multiplex), 10 bone, 6 cerebral, 3 hepatic (1 multiplex), and 3 suprarenal gland. Conclusion: Our results correlate with published literature. During the period of this review, VATS lobectomies became a routine surgical technique in our department. Our experience proved that axillary thoracotomy is an advantage to learn the anterior VATS lobectomy technique.


Assuntos
Tumor Carcinoide/cirurgia , Carcinoma de Células Pequenas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/estatística & dados numéricos , Toracotomia/métodos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Analgesia Controlada pelo Paciente , Tumor Carcinoide/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Recidiva Local de Neoplasia , Duração da Cirurgia , Reoperação/estatística & dados numéricos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
3.
Med Oncol ; 36(11): 91, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31560089

RESUMO

The vasoactive intestinal peptide receptor-1(VIPR1) has prominent growth effects on a number of common neoplasms. However, there were contradictions in the effect cross different cancers. We aimed to explore the effect of VIPR1 overexpression on a human lung adenocarcinoma cell line H1299. GEO dataset was used to screen differentially expressed genes in lung adenocarcinoma tissues. The expression of VIPR1 mRNA was determined in the cancer Genome Atlas (TCGA). Immunohistochemical analysis was performed to determine VIPR1 protein expression in lung adenocarcinoma and corresponding adjacent tissues (n = 22). Fluorescence real-time quantitative PCR detected the expression of VIPR1 in human normal lung epithelial cell line BEAS-2B and lung adenocarcinoma cell line H1299. Overexpression strategies were employed to assess functions of VIPR1 expression on several malignant phenotypes in H1299. The expression of VIPR1 was lower in lung adenocarcinoma tissues than that in adjacent tissues. Compared with the normal lung epithelial cells BEAS-2B, VIPR1 was down-regulated in lung cancer cells H1299 (P < 0.05). After the overexpression of VIPR1, we found that VIPR1 significantly inhibited growth, migration, and invasion of H1299 cells (P < 0.05). Our findings point out the tumor suppressor roles of VIPR1 in human LUAD pathogenesis.


Assuntos
Adenocarcinoma de Pulmão/genética , Regulação Neoplásica da Expressão Gênica , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/genética , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/biossíntese , Regulação para Cima
4.
J Cancer Res Clin Oncol ; 145(9): 2273-2283, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31428934

RESUMO

OBJECTIVES: Recent research has classified lung adenocarcinoma patients with KRAS mutation into three subtypes by co-occurring genetic events in TP53 (KP subgroup), STK11/LKB1 (KL subgroup) and CDKN2A/B inactivation plus TTF-1 low expression (KC subgroup). The aim of this study was to identify valuable biomarkers by searching the candidate molecules that contribute to lung adenocarcinoma pathogenesis, especially KC subtype. MATERIALS AND METHODS: We analyzed the publicly available database and identified the candidate REG4 using the E-GEOD-31210 dataset, and then confirmed by TCGA dataset. In addition, an independent cohort of 55 clinical samples was analyzed by quantitative real-time PCR analysis. Functional studies and RNA sequencing were performed after silencing the REG4 expression. RESULTS: REG4, an important regulator of gastro-intestinal carcinogenesis, was highly expressed in KRAS mutant lung adenocarcinoma with low expression of TTF-1 (KC subtype). The results were validated both by gene expression analysis and immunohistochemistry study in an independent 55 clinical samples from Fudan University Shanghai Cancer Center. Further in vitro and in vivo functional assays revealed silencing REG4 expression significantly reduces cancer cell proliferation and tumorigenesis. Moreover, RNA sequencing and GSEA analysis displayed that REG4 knockdown might induce cell cycle arrest by regulating G2/M checkpoint and E2F targets. CONCLUSION: Our results indicate that REG4 plays an important role in KRAS-driven lung cancer pathogenesis and is a novel biomarker of lung adenocarcinoma subtype. Future studies are required to clarify the underlying mechanisms of REG4 in the division and proliferation of KC tumors and its potential therapeutic value.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/genética , Transformação Celular Neoplásica/genética , Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/diagnóstico , Proteínas Associadas a Pancreatite/genética , Proteínas Proto-Oncogênicas p21(ras)/fisiologia , Fatores de Transcrição/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/patologia , Estudos de Coortes , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Mutantes/genética , Proteínas Mutantes/fisiologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Transcrição/metabolismo
5.
Anticancer Res ; 39(8): 4117-4128, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366496

RESUMO

BACKGROUND/AIM: Carbonic anhydrase 12 (CA12) is a membrane-associated enzyme that is highly expressed on many human cancers. It is a poor prognostic marker and hence an attractive target for cancer therapy. This study aimed to develop a humanized CA12-antibody with anti-cancer activity. MATERIALS AND METHODS: Antibody libraries were constructed and screened by the Retrocyte display®. Antibody binding and blocking properties were determined by ELISA, flow cytometry and enzymatic activity assays. Spheroid viability was determined by Cell-Titer-Fluor assay. RESULTS: We developed a novel humanized CA12-specific antibody, 4AG4, which recognized CA12 as an antigen and blocked CA12 enzymatic activity. Our humanized CA12-antibody significantly inhibited spheroid growth of lung adenocarcinoma A549-cells in vitro by blocking CA12 enzymatic activity. Similar anti-tumor effects were recapitulated with CA12-gene knockout of A549-cells. CONCLUSION: Our newly identified humanized CA12-antibody with anti-cancer activity, represents a new tool for the treatment of CA12-positive tumors.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Anidrases Carbônicas/genética , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Anticorpos Monoclonais Humanizados/imunologia , Anidrases Carbônicas/imunologia , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Esferoides Celulares/efeitos dos fármacos
6.
Cancer Invest ; 37(8): 367-375, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31462083

RESUMO

The aryl hydrocarbon receptor (AhR) is activated by the ligand, benzo[a]pyrene (B[a]P), a component of smoke that is implicated in lung carcinogenesis in humans. However, the role of B[a]P and AhR in lung cancer malignancy is not well known. In this study, we analyzed the effects of B[a]P and AhR in the 3 D spheroids of human lung cancer cells in vitro. In these spheroids, B[a]P and AhR enhanced cancer cell proliferation. These results suggest that the AhR-dependent effects of B[a]P on cell proliferation may contribute to the adverse effects of continuous smoking with respect to lung cancer malignancy.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Benzo(a)pireno/toxicidade , Proliferação de Células/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Receptores de Hidrocarboneto Arílico/agonistas , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Esferoides Celulares
7.
Cancer Sci ; 110(10): 3215-3224, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432603

RESUMO

Patient-derived xenograft (PDX) models are a useful tool in cancer biology research. However, the number of lung cancer PDX is limited. In the present study, we successfully established 10 PDX, including three adenocarcinoma (AD), six squamous cell carcinoma (SQ) and one large cell carcinoma (LA), from 30 patients with non-small cell lung cancer (NSCLC) (18 AD, 10 SQ, and 2 LA), mainly in SCID hairless outbred (SHO) mice (Crlj:SHO-Prkdcscid Hrhr ). Histology of SQ, advanced clinical stage (III-IV), status of lymph node metastasis (N2-3), and maximum standardized uptake value ≥10 when evaluated using a delayed 18 F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scan was associated with successful PDX establishment. Histological analyses showed that PDX had histology similar to that of patients' surgically resected tumors (SRT), whereas components of the microenvironment were replaced with murine cells after several passages. Next-generation sequencing analyses showed that after two to six passages, PDX preserved the majority of the somatic mutations and mRNA expressions of the corresponding SRT. Two out of three PDX with AD histology had epidermal growth factor receptor (EGFR) mutations (L858R or exon 19 deletion) and were sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib and osimertinib. Furthermore, in one of the two PDX with an EGFR mutation, osimertinib resistance was induced that was associated with epithelial-to-mesenchymal transition. This study presented 10 serially transplantable PDX of NSCLC in SHO mice and showed the use of PDX with an EGFR mutation for analyses of EGFR-TKI resistance.


Assuntos
Adenocarcinoma de Pulmão/patologia , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Camundongos , Camundongos Pelados , Camundongos SCID , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Cancer Sci ; 110(9): 3006-3011, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301084

RESUMO

Decreased cell adhesion has been reported as a significant negative prognostic factor of lung cancer. However, the molecular mechanisms responsible for the cell incohesiveness in lung cancer have not yet been elucidated in detail. We herein describe a rare histological variant of lung adenocarcinoma consisting almost entirely of individual cancer cells spreading in alveolar spaces in an incohesive pattern. A whole exome analysis of this case showed no genomic abnormalities in CDH1 or other genes encoding cell adhesion molecules. However, whole mRNA sequencing revealed that this case had an extremely high expression level of mucin 21 (MUC21), a mucin molecule that was previously shown to inhibit cell-cell and cell-matrix adhesion. The strong membranous expression of MUC21 was found on cancer cells using mAbs recognizing different O-glycosylated forms of MUC21. An immunohistochemical analysis of an unselected series of lung adenocarcinoma confirmed that the strong membranous expression of MUC21 correlated with incohesiveness. Thus, MUC21 could be a promising biomarker with potential diagnostic and therapeutic applications for lung adenocarcinoma showing cell incohesiveness.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Glicoproteínas de Membrana/metabolismo , Mucinas/metabolismo , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Idoso , Antígenos CD/genética , Caderinas/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Tomografia Computadorizada por Raios X , Sequenciamento Completo do Exoma
9.
Cancer Sci ; 110(9): 2960-2972, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301086

RESUMO

In recent years, circular RNAs (circRNAs) have been revealed to have important roles in carcinogenesis. Metastasis is the leading cause of lung adenocarcinoma (LUAC) death. However, the contributions of circRNA to the metastasis of LUAC remain largely unknown. Based on circBase data and our biobank tissues, we identified circCRIM1 (a circRNA derived from exons 2, 3 and 4 of the CRIM1 gene, hsa_circ_0002346) as having a significantly decreased expression in LUAC samples compared with matched normal control samples. Both in vivo and in vitro experiments revealed that circCRIM1 suppresses the invasion and metastasis of LUAC. In vitro precipitation of circRNAs, luciferase reporter assay, and biotin-coupled microRNA capture were carried out to investigate the Ago2-dependent interaction of circCRIM1 and microRNA (miR)-93/miR-182. Mechanistically, we found that circCRIM1 could promote the expression of leukemia inhibitory factor receptor, a well-known tumor suppressor, by sponging miR-93 and miR-182. In the clinical and pathological analyses, the downregulation of circCRIM1 in LUAC was significantly correlated with lymphatic metastasis and TNM stage, which served as an independent risk factor for the overall survival of patients with LUAC. Our study showed that circCRIM1 inhibits the invasion and metastasis of lung adenocarcinoma cancer cells, which makes it a potential therapeutic target.


Assuntos
Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , RNA/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Proteínas de Membrana/genética , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , RNA/genética , RNA Interferente Pequeno/metabolismo , Análise de Sobrevida , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Cancer Imaging ; 19(1): 47, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292000

RESUMO

OBJECTIVE: To evaluate the relationship between clinicopathologic characteristics and prognosis in patients with invasive mucinous adenocarcinoma (IMA) of the lung. METHODS: A total of 68 patients who underwent surgical resection for primary lung IMA were reviewed during the period of 2009 and 2017. Tumors were classified as solitary-type or pneumonic-type according to the computed tomography (CT) findings. Cox proportional hazards model was used to assess the effects of clinicopathological characteristics on univariate and multivariable analyses of disease-free survival (DFS). RESULTS: Solitary-type was found in 54 patients, while pneumonic-type was found in 14 patients. The patients' age varied between 56 and 68 years (patients' median age was 61 years). Besides, 50 patients had T1/T2 tumor stage (73.5%). Compared with solitary-type, higher T stage, N stage, and pathological stage (P < 0.001) were found in pneumonic-type. Moreover, the survival analysis showed that the pneumonic-type had a significantly poorer DFS compared with solitary-type (P = 0.004). Univariate analysis showed that pneumonic pattern on CT scan, T stage, pathologic stage, and thyroid transcription factor-1 (TTF-1) were significant predictive factors of survival (P = 0.011, 0.014, 0.013, 0.029, respectively). Multivariate analysis further indicated that pneumonic-type was the only independent prognostic factor for poor survival [hazard ratio (HR) = 6.764, 95% confidence interval (CI): 1.563-29.269, P = 0.011]. CONCLUSIONS: Based on CT findings, the solitary-type IMA is associated with a lower stage and better prognosis compared with the pneumonic-type IMA.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma Mucinoso/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X/normas
11.
Life Sci ; 232: 116630, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279783

RESUMO

AIMS: Lung adenocarcinoma consists of multiple therapeutic targets, however, patients will inevitably progress to later stage diagnosis with Tyrosine Kinase Inhibitor treatment resistance. We aim to investigate the roles of non-coding TUSC7 in ordering the cell division tendency, helping to sensitize the resistance in a miRNA incorporating way. MATERIALS AND METHODS: Online study of bioinformatics analysis, molecular experiments of luciferase test, immunofluorescence staining and qRT-PCR were applied to dig out the mechanistic regulations. KEY FINDINGS: TUSC-7 inhibited the renewal ability of adenocarcinoma stem cells, yielding to asymmetric cell splitting. Informatics analysis and the luciferase testing confirmed the 3'UTR binding site, and revealed the post-transcriptional regulation of NUMB referring to miR-146. TUSC-7 sponged miR-146 and abolished its degradation toward to NUMB, and this integrated cascade made several genes become tangled to full functionality. SIGNIFICANCE: TUSC-7 was proved to be one strong suppressive lnc-RNA in lung adenocarcinoma stem cells, functioning through inactivating NOTCH signaling, and the turbulence on division modes precisely pointed to the key mechanisms of stem cells' renewal. The decreasing of tumor suppressive miR-146 was necessary in TUSC-7 conducted renewal repression, despite it alone could also reduce the renewal efficiency, indicating that more complicated non-coding genes may be involved in its regulation.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/metabolismo , RNA Longo não Codificante/fisiologia , Regiões 3' não Traduzidas , Adenocarcinoma de Pulmão/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo
12.
DNA Cell Biol ; 38(8): 814-823, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31314552

RESUMO

Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026-1.723, p = 0.031 and adjusted OR = 1.450, 95% CI = 1.112-1.890, p = 0.006, respectively). The results of crossover analysis revealed that rs3733845 and rs3733846 risk genotypes along with cooking oil exposure increased lung cancer risk by 1.862-fold and 2.260-fold, respectively (adjusted OR = 1.862, 95% CI = 1.105-3.138, p = 0.020 for rs3733845; adjusted OR = 2.260, 95% CI = 1.354-3.769, p = 0.002 for rs3733846). There was positive multiplicative interaction between the two SNPs and cooking oil fume exposure (adjusted OR = 1.362, 95% CI = 1.078-1.719, p = 0.009 for oil × rs3733845; adjusted OR = 1.399, 95% CI = 1.122-1.745, p = 0.003 for oil × rs3733846). In nonsmoking females, rs3733845 and rs3733846 polymorphisms might be associated with lung adenocarcinoma risk. Moreover, the interactions between the two SNPs and cooking oil fume exposure were statistically significant on a multiplicative scale rather than an addictive scale.


Assuntos
Neoplasias Pulmonares/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Estudos de Casos e Controles , Culinária , Estudos Cross-Over , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Fumar
13.
J Cancer Res Clin Oncol ; 145(9): 2375-2382, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31292713

RESUMO

OBJECTIVES: Spread through air spaces (STAS) as a pattern of invasion in lung adenocarcinomas had been recognized by WHO in 2015. Moreover, STAS was associated significantly with aggressive micropapillary or solid components when presented predominant pattern in lung adenocarcinomas, which had a poor prognostic significance. Small amounts of micropapillary or solid with components could also reduce overall survival and recurrence-free survival but its impact on STAS is unknown now. Some studies have demonstrated manipulations of surgeons and pathologists could affect STAS but the degree of these impacts is not clear. MATERIALS AND METHODS: We reviewed resected small (≤ 2 cm) stage I invasive lung adenocarcinomas by thoracoscopic surgery at our institution from January 2017 to October 2018 (n = 277). Micropapillary or solid pattern was considered to be present when the subtype occupied at least 1% of the entire tumor. Lobectomy and segmentectomy were performed using three portals thoracoscopic surgery. Statistical analysis was performed to analyze the correlations of STAS and clinicopathological characteristics. Moreover, we also analyzed the correlated factors of STAS in solid nodules. RESULTS: STAS was found in 59 of 163 (36.2%) lobectomy cases and 27 of 114 (23.7%) limited resection cases. Lobectomy group showed a higher incidence of STAS compared with limited resection group (p = 0.027), but the difference was disappeared in multivariate analysis, which showed that STAS was significantly correlated to solid nodules and presence of high grade histologic subtype (mircopapillary or solid). However, both lobectomy and presence of high grade histologic subtype were significantly correlated with STAS in solid nodules. CONCLUSIONS: The small amounts of high grade histologic subtypes were also associated with STAS. Thoracoscopic surgery could affect STAS to some degree.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Sistema Respiratório/patologia , Sistema Respiratório/cirurgia , Cirurgia Torácica Vídeoassistida , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Sistema Respiratório/diagnóstico por imagem , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Adulto Jovem
14.
J Cancer Res Clin Oncol ; 145(9): 2325-2333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317326

RESUMO

PURPOSE: Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated. METHODS: Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1-2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence. RESULTS: About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1-2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244-4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449-9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy. CONCLUSIONS: Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/metabolismo , Linfonodos/metabolismo , Mutação , Transcriptoma/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
15.
J Cardiothorac Surg ; 14(1): 143, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340823

RESUMO

BACKGROUNDS: The pulmonary ciliated muconodular papillary tumor (CMPT) is a very rare tumor with only several case reports in published literatures, and its clinicopathological features, standard treatment methods and prognosis has not been well defined. METHODS: Two cases of CMPT diagnosed and treated in our hospital and 39 cases reported in the published literature were analyzed retrospectively. RESULTS: The cohort of 41 CMPT patients comprised of 20 males and 21 females, aged 9-84 years. The diameter of the primary tumor was 0.3-4.5 cm. Most of these lesions were subsolid nodules, as observed on computed tomography and easily misdiagnosed as early lung adenocarcinoma. Tumors of 26 patients were stained by immunohistochemistry method, which revealed that CK7, CEA, and TTF-1 were positive and CK20 was negative in most patients. The results of gene alternation demonstrated mutations in EGFR, KRAS, and BRAF and ALK rearrangements in CMPT. All the patients underwent surgical treatment and did not receive postoperative adjuvant therapy. The follow-up duration was 0-120 months, and no case of tumor recurrence was found until the final follow-up. CONCLUSIONS: The incidence of CMPT was low and rate of image misdiagnosis high. Immunohistochemistry is helpful for accurate diagnosis of CMPT. Sub-lobectomy may be proper and adjuvant treatment should be avoided since the disease is now prone to benign lesions. Furthermore, since the biological behavior of this tumor is not yet fully elucidated, additional case data are essential for accurate conclusions.


Assuntos
Adenocarcinoma de Pulmão/patologia , Adenocarcinoma Mucinoso/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cílios/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
16.
Medicine (Baltimore) ; 98(29): e16262, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335674

RESUMO

RATIONALE: The thoracic epidural block and thoracic paravertebral block are widely used techniques for multimodal analgesia after thoracic surgery. However, they have several adverse effects, and are not technically easy. Recently, the erector spinae plane block (ESPB), an injected local anesthetic deep to the erector spinae muscle, is a relatively simple and safe technique. PATIENT CONCERNS: Three patients were scheduled for video assisted thoracoscopic lobectomy with mediastinal lymph node dissection. All the patients denied any past medical history to be noted. DIAGNOSES: They were diagnosed with primary adenocarcinoma requiring lobectomy of lung. INTERVENTIONS: The continuous ESPB was performed at the level of the T5 transverse process. The patient was received the multimodal analgesia consisted of oral celecoxib 200 mg twice daily, intravenous patient-controlled analgesia (Fentanyl 700 mcg, ketorolac 180 mg, total volume 100 ml), and local anesthetic (0.375% ropivacaine 30 ml with epinephrine 1:200000) injection via indwelling catheter every 12 hours for 5 days. Additionally, we injected a mixture of ropivacaine and contrast through the indwelling catheter for verifying effect of ESPB and performed Computed tomography 30 minutes later. OUTCOMES: The pain score was maintained below 3 points for postoperative 5 days, and no additional rescue analgesics were administered during this period. In the computed tomography, the contrast spread laterally from T2-T12 deep to the erector spinae muscle. On coronal view, the contrast spread to the costotransverse ligament connecting the rib and the transverse process. In the 3D reconstruction, the contrast spread from T6-T10 to the costotransverse foramen. LESSONS: Our contrast imaging data provides valuable information about mechanism of ESPB from a living patient, and our report shows that ESPB can be a good option as a multimodal analgesia after lung lobectomy.


Assuntos
Adenocarcinoma de Pulmão , Adjuvantes Anestésicos , Neoplasias Pulmonares , Bloqueio Nervoso/métodos , Dor Pós-Operatória/terapia , Músculos Paraespinais/fisiopatologia , Pneumonectomia , Ropivacaina/administração & dosagem , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Adjuvantes Anestésicos/administração & dosagem , Adjuvantes Anestésicos/classificação , Idoso , Analgesia Controlada pelo Paciente/métodos , Anestésicos Locais/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Manejo da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Toracoscopia/efeitos adversos , Toracoscopia/métodos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
17.
Medicine (Baltimore) ; 98(29): e16313, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335678

RESUMO

We evaluated the relationships among functional imaging modality such as PET-CT and DW-MRI and lung adenocarcinoma pathologic heterogeneity, extent of invasion depth, and tumor cellularity as a marker of tumor microenvironment.In total, 74 lung adenocarcinomas were prospectively included. All patients underwent 18F-fluorodeoxyglucose (FDG) PET-CT and MRI before curative surgery. Pathology revealed 68 stage I tumors, 3 stage II tumors, and 3 stage IIIA tumors. Comprehensive histologic subtyping was performed for all surgically resected tumors. Maximum standardized uptake value (SUVmax) and ADC values were correlated with pathologic grade, extent of invasion, solid tumor size, and tumor cellularity.Mean solid tumor size (low: 1.7 ±â€Š3.0 mm, indeterminate: 13.9 ±â€Š14.2 mm, and high grade: 30.3 ±â€Š13.5 mm) and SUVmax (low: 1.5 ±â€Š0.2, indeterminate: 3.5 ±â€Š2.5, and high grade: 15.3 ±â€Š0) had a significant relationship with pathologic grade based on 95% confidence intervals (P = .01 and P < .01, respectively). SUVmax showed a strong correlation with tumor cellularity (R = 0.713, P < .001), but was not correlated with extent of invasion (R = 0.387, P = .148). A significant and strong positive correlation was observed among SUVmax values and higher cellularity and pathologic grade. ADC did not exhibit a significant relationship with tumor cellularity.Intratumor heterogeneity quantification using a multimodal-multiparametric approach might be effective when tumor volume consists of a real tumor component as well as a non-tumorous stromal component.


Assuntos
Adenocarcinoma de Pulmão , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Pulmonares , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Microambiente Tumoral , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Correlação de Dados , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , República da Coreia , Carga Tumoral
18.
Medicina (B Aires) ; 79(3): 208-211, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31284257

RESUMO

The lymphomas of mucosa-associated lymphoid tissue (MALT), are uncommon entities, of low grade of malignancy with very infrequent or no lymph node involvement. They represent about 80% of the primary pulmonary lymphomas. The synchronous appearance with lung adenocarcinoma is an extremely rare finding. We present the case of an ex-smoker 68-year-old man, in whom, in the follow-up of a pulmonary nodule, a second pulmonary nodule was found. The surgical biopsy confirmed the diagnosis of both neoplasms.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Idoso , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Tomografia Computadorizada por Raios X
19.
Chem Biol Interact ; 310: 108731, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265827

RESUMO

Lung cancer is one of the most common and lethal types of oncological diseases. Despite the advanced therapeutic approaches, the prognosis for lung cancer still remains poor. Apparently, there is an imperative need for more efficient therapeutic strategies. In this work we report that concurrent treatment of human adenocarcinoma A549 cells with specific concentrations of two antitumor agents, the sphingosine kinase 1 inhibitor N, N dimethylsphingosine (DMS) and the alkylphosphocholine miltefosine, induced synergistic cytotoxic effect, which was confirmed by calculation of the combination index. The simultaneous action of these agents, induced significant decrease of A549 cell number, as well as pronounced morphological alterations. Combined drugs caused substantial apoptotic events, and significant reduction of the pro-survival marker sphingosine- 1-phosphate (S1P), when compared to the individual treatments with each of the anticancer drugs alone. Miltefosine is known to affect the synthesis of choline-containing phospholipids, including sphingomyelin, but we report for the first time that it also reduces S1P. Here we suggest a putative mechanism underlying the effect of miltefosine on sphingosine kinase 1, involving miltefosine-induced inhibition of protein kinase C. In conclusion, our findings provide a possibility for treatment of lung cancer cells with lower concentrations of the two antitumor drugs, DMS and miltefosine, which is favorable, regarding their potential cytotoxicity to normal cells.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Apoptose/efeitos dos fármacos , Fosforilcolina/análogos & derivados , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Células A549 , Adenocarcinoma de Pulmão/patologia , Protocolos de Quimioterapia Combinada Antineoplásica , Sinergismo Farmacológico , Humanos , Lisofosfolipídeos/análise , Fosforilcolina/farmacologia , Fosforilcolina/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Esfingosina/análogos & derivados , Esfingosina/análise
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