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1.
Ann Transl Med ; 10(8): 462, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571392

RESUMO

Background: Comprehensive genomic profiling has become standard clinical practice in the management of advanced lung cancer. In addition to tissue and plasma, other body fluids are also being actively explored as alternative sources of tumor DNA. This study investigated the utility of induced sputum obtained from patients with non-small-cell lung cancer (NSCLC) for somatic variation profiling. Methods: Our study included 41 treatment-naïve patients diagnosed with locally advanced to advanced NSCLC between October 2018 and June 2019. Capture-based targeted sequencing was performed on matched tumor, plasma, and induced sputum samples of 41 patients using a 168-gene panel. We analyzed the somatic variations detected from each sample type and the concordance of variations detected between matched samples. The concordance rate was defined as the proportion of the total number of variations detected from one sample type relative to the reference sample type. Results: Comparative analysis on the somatic variation detection using matched tumor samples as a reference revealed detection rates of 76.9% for plasma, 72.4% for sputum-supernatant, and 65.7% for sputum-sediment samples. Plasma, sputum-supernatant, and sputum-sediment achieved positive predictive values of 73.3%, 80.4%, and 55.6% and sensitivities of 50.0%, 36.9%, 31.3%, respectively, relative to tumor samples for 168 genes. Sputum-supernatants had significantly higher concordance rates relative to matched tumor samples (69.2% vs. 37.8%; P=0.031) and maximum allelic fraction (P<0.001) than their matched sputum-sediments. Sputum-supernatants had comparable detection rates (71.4% vs. 67.9%; P=1.00) but with significantly higher maximum allelic fraction than their matched plasma samples (P=0.003). Furthermore, sputum-supernatant from smokers had a significantly higher maximum allelic fraction than sputum-supernatant from non-smokers (P=0.021). Conclusions: Our study demonstrated that supernatant fraction from induced sputum is a better sampling source than its sediment and performs comparably to plasma samples. Induced sputum from NSCLC patients could serve as an alternative media for next-generation sequencing (NGS)-based somatic variation profiling.

2.
Cancer Med ; 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35526266

RESUMO

BACKGROUND: Anlotinib as a third-line or beyond therapy for extensive-stage small-cell lung cancer (ES-SCLC) was studied. This single-arm phase II trial was to investigate the value of anlotinib plus platinum-etoposide as first-line treatment in ES SCLC. METHODS: The primary endpoint was progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints included overall survival (OS), disease control rate (DCR), time to progression (TTP), duration of remission (DoR), and safety. The subgroups of preset liver metastasis and brain metastasis were analyzed. RESULTS: In 35 ES-SCLC patients, the median PFS, ORR, DCR, and OS were 8.02 months [95% confidence interval (CI): 6.90-9.66], 85.71% (95% CI: 69.74-95.19), 94.29% (95% CI: 80.84-99.30), and 15.87 months (95% CI: 10.38-18.89), respectively. The median PFS in the liver metastasis and brain metastasis subgroups was 7.33 months (95% CI: 4.76-9.69) and 7.34 months (95% CI: 5.68-9.20), respectively. The most common AEs with grade 3-4 were hand-foot syndrome (17%), granulocytosis (17%), stomatitis (14%), hypertriglyceridemia (11%), hypercholesterolemia (11%), as well as nausea and vomiting (11%), and no grade 5 AEs were recorded. CONCLUSIONS: Anlotinib combined with platinum-etoposide provided an effective and safe therapy for patients with ES-SCLC.

3.
Front Oncol ; 11: 646577, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513661

RESUMO

INTRODUCTION: Epidermal growth factor receptor (EGFR) 19del and L858R mutation are known as "common mutations" in non-small cell lung cancer (NSCLC) and predict sensitivities to EGFR tyrosine kinase inhibitors (TKIs), whereas 20ins and T790M mutations confer drug-resistance to EGFR-TKIs. The role of the remaining uncommon EGFR mutations remains elusive. METHODS: We retrospectively screened a group of NSCLC patients with uncommon EGFR mutations other than 20ins and T790M. The mutation patterns, use of different generations of EGFR-TKIs, and concurrent genetic alterations were analyzed. Meanwhile, a cohort of patients with single 19del or L858R were included for comparison. RESULTS: A total of 180/1,300 (13.8%) patients were identified. There were 102 patients with advanced or recurrent NSCLC that received first-line therapy of gefitinib/erlotinib/icotinib and afatinib and were eligible for analysis. The therapeutic outcomes among patients with common mutations (EGFRcm, n = 97), uncommon mutation plus common mutations (EGFRum+EGFRcm, n = 52), complex uncommon mutations (complex EGFRum, n = 22), and single uncommon mutations (single EGFRum, n = 28) were significantly different (ORRs: 76.3%, 61.5%, 54.5%, and 50.0%, respectively, p = 0.023; and mPFS: 13.3, 14.7, 8.1, and 6.0 months, respectively, p = 0.004). Afatinib showed superior efficacy over gefitinib/erlotinib/icotinib in EGFRcm (ORR: 81.0% vs. 75.0%, p = 0.773; mPFS: 19.1 vs. 12.0m, p = 0.036), EGFRum+EGFRcm (ORR: 100% vs. 54.5%, p = 0.017; mPFS: NE vs. 13.6m, p = 0.032), and single EGFRum (ORR: 78.6% vs. 21.4%, p = 0.007; mPFS: 10.1 vs. 3.0m, p = 0.025) groups. Comprehensive genomic profiling by Next Generation Sequencing encompassing multiple cancer-related genes was performed on 51/102 patients; the mPFS of patients without co-mutation (n = 16) and with co-mutations of tumor-suppressor genes (n = 31) and driver oncogenes (n = 4) were 31.1, 9.2, and 12.4 months, respectively (p = 0.046). TP53 mutation was the most common co-alteration and showed significantly shorter mPFS than TP53 wild-type patients (7.0 vs. 31.1m, p < 0.001). Multivariate analysis revealed that concurrent 19del/L858R and tumor-suppressor gene alterations independently predicted better and worse prognosis in patients with uncommon mutations, respectively. CONCLUSIONS: Uncommon EGFR mutations constitute a highly heterogeneous subgroup of NSCLC that confer different sensitivities to EGFR-TKIs with regard to the mutation patterns. Afatinib may be a better choice for most uncommon EGFR mutations. Concurrent 19del/L858R and tumor-suppressor gene alterations, especially TP53, can be established as prognostic biomarkers.

5.
Ann Palliat Med ; 10(1): 202-209, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545757

RESUMO

BACKGROUND: Recent clinical studies have reported that some cytokines are associated with lung cancer prognosis and mortality. However, the relationship between cytokines and clinical outcomes in severe lung cancer patients was unclear. IL-6 as an important cytokine in inflammation, expression level in severe lung cancer patients was unknown. METHODS: A cohort of 55 severe lung cancer patients were enrolled retrospectively in this study. The clinical characteristics, including performance status (PS), therapeutic effect, and patients' adverse effects, were recorded. The association of cytokines and the concerned clinical outcomes were assessed by logistic regression analysis. The area under the curve (AUC) was assessed to evaluate the strength of prediction. RESULTS: The mean age of the patients was 59.8, and 42 patents were males. Increased IL-6 levels were associated with worse PS. Logistic regression analysis demonstrated that higher IL-6 was associated with an increased risk of progressive disease (PD) (OR =1.03, 95% CI: 1.0-1.06). The area under the ROC curve (AUC) of the model used for predicting PD was 0.821. CONCLUSIONS: Increased IL-6 levels are correlated with worse PS and are an essential predictor for PD in severe lung cancer patients. Monitoring the IL-6 level may represent an essential strategy in improving the prognosis of patients with severe lung cancer.


Assuntos
Neoplasias Pulmonares , Citocinas , Feminino , Humanos , Interleucina-6 , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
6.
Ann Transl Med ; 9(22): 1645, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34988154

RESUMO

BACKGROUND: Transbronchial cryobiopsy (TBCB) has been widely used to diagnose interstitial lung disease (ILD). Existing reports on TBCB in ILD are mostly single-center prospective or retrospective studies but rarely multicenter prospective real-world studies. We explored the diagnostic efficiency and safety of TBCB in ILD in a real world setting. METHODS: A prospective, multicenter, real-world study was conducted to analyze the data of patients with unclarified ILD who underwent TBCB in 20 hospitals in China from October 2018 to October 2019. The results of the pathological and multidisciplinary discussion (MDD) diagnosis and complications related to TBCB were then analyzed. RESULTS: A total of 373 patients were enrolled in this study, including 194 males and 179 females, with an average age of 52.6±12.4 years. None of the patients had severe hemorrhaging, and the incidence of pneumothorax was 4.8%. The proportions of definitive, possible, and unclassified pathological diagnoses were 62.5%, 5.6%, and 31.9%, respectively. The overall diagnostic yield of MDD was 63.5%. There were 237 patients with a definitive diagnosis of MDD and 136 patients with an unclarified MDD diagnosis. The cooling gas pressure, freezing durations, number of specimens, maximum lengths of specimens, and specimen sizes varied significantly between the definitive and unclarified MDD diagnoses. CONCLUSIONS: In China, the application of TBCB in ILD is generally safe, and its diagnostic efficiency is acceptable. Using a 1.9-mm cryoprobe to collect five samples would achieve a better positive diagnostic rate for TBCB in ILD, without a significant increase in complication risk. TRIAL REGISTRATION: ClinicalTrials.gov; date of registration: 09/25/2018; registration number: NCT03704233; URL: clinicaltrials.gov.

7.
Cell Cycle ; 19(20): 2701-2719, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33017562

RESUMO

Fibrotic microenvironment has been reported to have a pro-metastasis effect on tumor cells, but the mechanism remains unclear. The current study aimed to explore the underlying mechanism by which the fibrotic microenvironment affects tumor cells. A tumor metastasis model was established by injecting tumor cells containing GFP into mice with pulmonary fibrosis. Lung tissues and fibroblasts were harvested, and conditioned medium (CM) were collected from fibrotic lungs and fibroblasts. Hematoxylin & eosin staining and immunohistochemistry were used to detect pulmonary metastasis and FSP1 expression, respectively. Bioinformatics and dual-luciferase reporter assay proved that the target genes of ZEB1-AS1 and miR-200b-3p were miR-200b-3p and ZEB1, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of GFP, ZEB1-AS1, and miR-200b-3p. Transwell assay, Annexin V/PI assay, and colorimetry were performed to examine the effects of CM, ZEB1-AS1, miR-200b-3p, and ZEB1 on cell invasion, apoptosis, and the activity level of caspase-3/-9. Pulmonary metastasis was promoted and the expressions of FSP1 and GFP were increased in mice with pulmonary fibrosis. CM enhanced the invasion and inhibited the apoptosis of tumor cells. SiZEB1-AS1 and siZEB1 inhibited the invasion and apoptosis of tumor cells, while miR-200b-3p inhibitor had the opposite effect of SiZEB1-AS1 and siZEB1, and further reversed the effect of siZEB1 on tumor cell invasion and apoptosis. SiZEB1-AS1 reversed the effects of both miR-200b-3p inhibitor and miR-200b-3p inhibitor+siZEB1 on tumor cell invasion and apoptosis. Fibrotic microenvironment promoted the metastatic seeding of tumor cells into the lungs via mediating the ZEB1-AS1/miR-200b-3p/ZEB1 signaling.


Assuntos
Pulmão/patologia , MicroRNAs/genética , Transdução de Sinais/genética , Microambiente Tumoral/genética , Microambiente Tumoral/fisiologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Células HeLa , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos
8.
Zhongguo Fei Ai Za Zhi ; 23(10): 858-865, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32987493

RESUMO

BACKGROUND: Anlotinib is a newly developed small molecule multiple receptor tyrosine kinase (RTK) inhibitor that was approved for the treatment of patients with lung cancer in China. We aim to report 3 cases of rare complication of anlotinib-bronchial fistula (BF) during the treatment of lung cancer patients and summarize the possible causes. METHODS: We collected three patients who developed BF due to anlotinib treatment, and conducted a search of Medline and PubMed for medical literature published between 2018 and 2020 using the following search terms: "anlotinib," "lung cancer," and "fistula." RESULTS: Our literature search produced two case reports (three patients) which, in addition to our three patients. We collated the patients' clinical characteristics including demographic information, cancer type, imaging features, treatment received, risk factors for anlotinib related BF, and treatment-related outcomes. The six patients shared some common characteristics: advanced age, male, concurrent infection symptoms, diabetes mellitus (DM), advanced squamous cell and small cell lung cancers, centrally located tumors, tumor measuring ≥5 cm in longest diameter, and newly formed tumor cavitation after multi-line treatment especially after receiving radiotherapy. Fistula types included broncho-pericardial fistula, broncho-pleural fistula, and esophago-tracheobronchial fistula. Six patients all died within 6 months. CONCLUSIONS: Although anlotinib is relatively safe, it is still necessary to pay attention to the occurrence of BF, a rare treatment side effect that threatens the quality of life and overall survival of patients. Anlotinib, therefore, requires selective use and close observation of high-risk patients.


Assuntos
Antineoplásicos/efeitos adversos , Fístula Brônquica/etiologia , Indóis/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Quinolinas/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Fístula Brônquica/diagnóstico por imagem , China , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico
10.
J Photochem Photobiol B ; 197: 111510, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31163288

RESUMO

Treatment of chronic lung infection becomes a great challenge due to the drug resistant bacteria. In this scenario, evolving a new drug based on lipid metal conjugation loaded with potential antibiotic provides better drug delivery. In this study, ciprofloxacin loaded selenium-lipid nanoparticle (CxLSENPs) is produced in a novel route and its antimicrobial properties were tested against clinically important Gram-negative P. aeruginosa. The synthesized CxLSENPs was characterized by biophysical techniques (UV, Fluorescence spectroscopy, Raman spectroscopy, FTIR, FESEM, HRTEM and Zeta potential). Raman spectra coupled with FTIR spectra confirmed the possible interaction of lipid components in the NPs. HRTEM analysis confirmed the spherical shape of NPs. CxLSENPs recorded greater antibacterial effects on P. aeruginosa. A drastic reduction in the count of P. aeruginosa was observed after treatment with CxLSENPs. In order to further confirm the antibacterial efficiency, the live/dead cell assay was carried out. Live/dead analysis helps us to investigate the viability of bacterial cells. The number of dead bacterial cells was significantly higher in CxLSENPs treated groups when compare to the control. Furthermore, CxLSENPs increased the antioxidant enzyme activities (SOD, GPx, CAT and LPO) in mouse and protected the liver damage from bacterial infection. This study concludes that the developed CxLSENPs might be employed as strong antimicrobial and antioxidant agents for treating lung infection or interstitial lung diseases.


Assuntos
Antibacterianos/química , Ciprofloxacina/química , Portadores de Fármacos/síntese química , Lipídeos/química , Nanopartículas/química , Selênio/química , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antioxidantes/metabolismo , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Catalase/metabolismo , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Portadores de Fármacos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/microbiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Camundongos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Superóxido Dismutase/metabolismo
11.
Cancer Manag Res ; 11: 2425-2439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988640

RESUMO

Purpose: Large-scale studies have revealed that appropriate antiangiogenic treatment enables the recovery of the normal structure and function of solid tumor vessels. Epigallocatechin-3-gallate (EGCG), a natural extract of green tea, has multiple effects on angiogenesis. However, normalization of blood vessels due to natural ingredients has not yet been reported. Therefore, we examined the microvasculature, microenvironment, and efficacy of EGCG combined with chemotherapy in a xenograft model. Methods: We treated A549 cell (human lung adenocarcinoma cell line) xenograft-bearing nude mice with EGCG in vivo. CD31, αSMA, and collagen IV were labeled and detected using quantum-dot double-labeled immunofluorescence to measure microvessel density, microvessel pericyte-coverage index, and collagen IV expression. Vessel-perfusion function was determined by lectin injection, permeability by Evans blue extravasation, interstitial fluid pressure using the wick-in-needle technique, and hypoxia levels using a polarographic electrode and immunohistochemical pimonidazole labeling. Cisplatin concentration in tumor tissue was detected using graphite-furnace atomic absorption spectrophotometry. Xenograft mice were randomized into five groups: treated with saline, cisplatin, EGCG, EGCG + cisplatin on day 1, or EGCG + cisplatin during the vascular normalization window. Tumor-growth delay and tumor-suppression rate were measured to evaluate tumor growth. Results: EGCG treatment in vivo caused temporary changes, including transient depression of microvessel density, microvessel pericyte-coverage index, and collagen IV expression, transient elevation of vessel perfusion and permeability, and decreased interstitial fluid pressure and hypoxia. During vascular normalization, pretreatment with EGCG increased cisplatin concentration in tumor tissue compared with treatment with cisplatin only. Tumor-growth delay after treatment in the five groups during the vascular normalization window was 6.3±1.51, 7.5±1.57, 8.3±1.79, 12.1±1.35, and 15.4±1.99 days, indicating synergistic EGCG-cisplatin effects, especially during the vascular normalization window (P<0.01). Conclusion: EGCG-induced vascular normalization in human lung adenocarcinoma may be a novel modality for enhancing chemotherapy effects.

12.
Respiration ; 97(5): 416-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30554211

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a leading cause of morbidity and mortality in China, with tobacco smoke, air pollution, and occupational biohazards being the major risk factors. OBJECTIVES: The REACH trial is a multicenter, prospective, randomized controlled trial undertaken in China to assess the safety and effectiveness of the Spiration® Valve System (SVS) compared to standard medical care in COPD patients with severe emphysema. METHODS: Patients with severe airflow obstruction, hyperinflation, and severe dyspnea with interlobar fissure integrity were evaluated for enrollment. A total of 107 subjects were randomized in a 2: 1 allocation ratio to either the treatment group (SVS valves and medical management) or the control group (medical management alone). RESULTS: The 3-month primary endpoint showed statistically significant improvement in forced expiratory volume in 1 s in the treatment group compared to the control group (0.104 ± 0.18 vs. 0.003 ± 0.15 L, p = 0.001), with the difference being durable through 6 months. Statistically significant target lobe volume reduction was achieved at 3 months (mean change 684.4 ± 686.7 mL) and through 6 months (757.0 ± 665.3 mL). Exercise function and quality of life measures improved in the treatment group, but showed a deterioration in the control group. The serious adverse event (SAE) rate was 33% in the treatment group and 24.2% in the control group. The predominance of SAEs were acute exacerbations of COPD in both groups. There was 1 death in the control group and no deaths in the treatment group. CONCLUSION: The SVS represents a novel approach for the treatment of severe emphysema with a clinically acceptable risk-benefit profile.


Assuntos
Broncoscopia/métodos , Dispneia , Pneumonectomia , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar , Qualidade de Vida , Progressão da Doença , Dispneia/etiologia , Dispneia/psicologia , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/instrumentação , Pneumonectomia/métodos , Desenho de Prótese , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/prevenção & controle , Enfisema Pulmonar/terapia , Testes de Função Respiratória/métodos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Am J Med Sci ; 356(1): 79-83, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30049332

RESUMO

Solitary laryngeal neurofibromas are exceedingly rare with only 14 cases reported in the previous literature. Herein, we reported a case of solitary laryngeal neurofibroma and reviewed all the published cases of this disease on the clinical manifestations and management options. Patients with solitary laryngeal neurofibromas can present with a variety of respiratory symptoms. Immunohistochemical examination of tumor specimen is critical for pathologic diagnosis and complete surgical resection is the optimal therapy. Endoscopic microsurgeries followed by CO2 laser management of the surgical border may be effective on preventing recurrence. Depending on the location, size and invasiveness of the lesions, the management and prognosis vary among patients. Long-term follow-up is highlighted owing to the possibility of recurrence during a long period of time after surgery.


Assuntos
Neoplasias Laríngeas , Laringoscopia , Terapia a Laser , Recidiva Local de Neoplasia , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Neurofibroma/diagnóstico , Neurofibroma/metabolismo , Neurofibroma/cirurgia
14.
Onco Targets Ther ; 11: 2637-2646, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29780256

RESUMO

Purpose: The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients. Materials and methods: We performed NGS on either liquid or tissue tumor biopsies obtained from 53 NSCLC patients. The sequences were analyzed for oncogenic mutations, which were then correlated to clinical prognosis and smoking history. Results: NGS of tumor biopsies detected both well-known driver mutations as well as rare or novel mutations. EGFR was the most frequently mutated gene, accounting for 32.4% (33/102) of the somatic mutations in this study. The EGFR mutations detected included rare variants such as EGFR exon 19 insertion (K745_E746insIPVAIK) and in cis H835L+L833V. Additionally, novel RET fusion mutations PCM1-RET and ADD3-RET were detected in two adenocarcinoma patients. To demonstrate the functional applications of NGS, we correlated mutations with patient characteristics, outcomes of matched targeted therapy, and outcomes based on allelic frequency of the EGFR-T790M mutation. Finally, we demonstrated that circulating tumor DNA can be used both to measure response to targeted therapy and as a predictor of clinical outcome, by presenting a case study of a single patient. Conclusion: We demonstrated that NGS can be used in multiple applications to effectively identify potential oncogenic driver mutations, guide mutation-targeted therapy decisions, and predict clinical outcomes in Chinese NSCLC patients.

15.
Clin Respir J ; 12(4): 1651-1660, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29028140

RESUMO

OBJECTIVES: Tracheobronchial mucormycosis is a rare and invasive pulmonary mucormycosis involving the tracheobronchial tree. DATA SOURCE: At a 3500-bed tertiary care center. STUDY SELECTION: This was a retroactive study of 12 cases of tracheobronchial mucormycosis diagnosed in our hospital, and 48 cases that were previously reported in the English literature. RESULTS: Rhizopus was the predominant species of pathogen (66.7%). Primary bronchus was the most frequently involved location (38.2%), and upper lobes (51% of cases) were a predilection. Obstructive necrosis and mucosal necrosis were the most common pathological forms (40% and 34.5%, respectively). Fever (59.3%), cough (59.3%), dyspnea (40.7%) and hemoptysis (30.5%) were the most common symptoms. 51.4% patients had rales, 40% had moist rales and 28.6% had negative physical findings. Ninety-five percent patients had immunosuppressive diseases. Diabetes mellitus (66.7%), diabetes ketoacidosis (21.7%), corticosteroid therapy (20%) and kidney insufficiency (18.3%) were the most common predisposing factors. 13.2% had neutropenia which was mostly among the non-diabetic patients (P = .006). Endobronchial lesion of 23.2% had imaging reports with 33.9% exhibiting single mass. Pathological diagnosis of 76.7% used the transbronchial biopsy. The most frequent antifungal therapies were intravenous amphotericin B (79.7%), surgery (33.3%) and surgery combined with amphotericin B therapy (28.3%). Overall in-hospital mortality was 52.5%, with hemoptysis (P = .017), dyspnea at presentation (P = .022) and angioinvasion (P = .03) as independent risk prognostic factors. In contrast, surgery (P = .003) was an independent protection prognostic factor. CONCLUSIONS: Tracheobronchial mucormycosis is a rare but severe disease with high mortality because of its nonspecific clinical presentations and variable predisposing factors.


Assuntos
Anfotericina B/uso terapêutico , Broncopatias/diagnóstico , Pulmão/diagnóstico por imagem , Mucormicose/diagnóstico , Doenças da Traqueia/diagnóstico , Antifúngicos/uso terapêutico , Broncopatias/tratamento farmacológico , Broncopatias/microbiologia , Broncoscopia , Feminino , Humanos , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Mucorales/isolamento & purificação , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Tomografia Computadorizada por Raios X , Doenças da Traqueia/tratamento farmacológico , Doenças da Traqueia/microbiologia
16.
DNA Cell Biol ; 36(4): 264-272, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28151013

RESUMO

Sex-determining region Y-box 2 (SOX2) is an oncogene known to be amplified and overexpressed in various human malignancies, including lung squamous cell carcinoma (SCC). However, the role played by SOX2 in lung SCC development remains to be elucidated. We measured the levels of SOX2 and cyclin D1 mRNA and protein expression in lung SCC tissues and a lung SCC cell line, and found that both levels were dramatically upregulated in specimens of lung SCC tissue when compared with their expression levels in samples of adjacent nonneoplastic tissue. The lung SCC cell line also showed higher levels of SOX2 and cyclin D1 expression than a normal human bronchial epithelium cell line. After using RNA interference to knock down SOX2 expression in NCI-H520 lung SCC cells, their proliferation was reduced. Furthermore, overexpression of SOX2 promoted the proliferation of normal human bronchial epithelium cells. To further determine whether cyclin D1 was downstream target gene of SOX2, we measured the levels of cyclin D1 expression that occurred when SOX2 was knocked down or overexpressed. SOX2 knockdown significantly decreased the levels of cyclin D1 mRNA and protein expression, while SOX2 overexpression upregulated the levels of cyclin D1. We used bioinformatics data to identify potential cyclin D1 promoter binding sites for SOX2. Results of luciferase reporter assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays confirmed that cyclin D1 was a direct target of transcription factor SOX2 in human lung SCC cells.


Assuntos
Carcinoma de Células Escamosas/genética , Ciclina D1/genética , Neoplasias Pulmonares/genética , Fatores de Transcrição SOXB1/metabolismo , Brônquios/citologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Células Epiteliais/citologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/fisiologia
17.
Oncotarget ; 8(70): 114769-114786, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29383119

RESUMO

Lung cancer has a high propensity for metastasis. Cancer-associated fibroblasts (CAFs) are the main type of stromal cells in cancer tissue, are activated by tumor cells, and play a significant role in tumor development. However, whether CAFs induce lung cancer cell metastasis, as well as pathway involved in CAF-induced lung cancer cell metastasis, is uncertain. Snail1 is a transcriptional factor whose expression in the stroma is associated with lower survival rates in patients with cancer. However, how Snail1 regulates the crosstalk between stromal cells and tumor cells when it is expressed in the stroma has not been determined. Altered microRNA (miRNA) expression is correlated with lung cancer metastasis. Our previous study of microRNAs showed that miR-33b levels were clearly reduced in lung cancer cell lines and lung cancer tissues, and miR-33b suppressed tumor cell epithelial-mesenchymal transition (EMT) when its expression was elevated. In this study, we found that co-culturing CAFs with lung cancer cells induced miR-33b downregulation and promoted epithelial cells EMT. Moreover, we found that miR-33b overexpression in lung cancer cells counteracted CAF-induced EMT. Interestingly, Snail1 expression in fibroblasts activate the inductive effects of CAFs on lung cancer cell EMT. Hence, understanding the molecular mechanism underlying the communication between stromal cells and tumor cells mediated by miR-33b may lead to the identification of novel targets for the treatment of lung cancer. Additionally, understanding the role of Snail1 driving CAFs to induce lung cancer cell EMT may provide with a new perspective on the treatment of lung cancer.

18.
Clin Respir J ; 11(4): 440-447, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26260022

RESUMO

BACKGROUND AND AIMS: Bronchoscopy is an important method for diagnosing respiratory disease. Multiple tracheobronchial nodules are rarely reported and their causes remain unclear. OBJECTIVES: The aim of this study was to describe the clinical characteristics of multiple nodule tracheobronchial abnormalities found under bronchoscopy caused by different diseases. METHODS: Eighty-seven patients with multiple tracheobronchial nodules were enrolled in this study. The characteristics of the multinodule lesions and the patient were diagnosed based on the pathology findings in our hospital. Chest computed tomography images were retrospectively reviewed by pulmonologists and radiologist. RESULTS: In 55 patients with definite pathological diagnosis, 16 (29%) patients were diagnosed as tuberculosis (TB) granuloma; 23 (41.8%) cases were diagnosed as malignant disease; 12 (21.8%) cases were diagnosed as tracheobronchopathia osteochondroplastica; 2 (3.6%) cases were diagnosed as sarcoidosis; and one case (1.8%) was diagnosed as lymphoma and one case (1.8%) as fungal infection. There were 32 cases of chronic inflammation. There was no relationship between nodule distribution and the pathological diagnosis. Malignant nodules usually smaller with a pale outlook, while nodules with larger size and smooth and intact mucosa usually turn out to be granuloma of unknown reason. CONCLUSION: The major causes of mutinodule lesions observed using bronchoscopy are tumor and TB. The presence of multiple endotracheobronchial nodules suggest that pulmonary lesion is present, and biopsy should be performed. Malignant nodules can be diagnosed by appearance and biopsy. Pathology results of TB, sarcoidosis and fungal infection can turn out to be granuloma of unknown reason. Further diagnosis needs other clinical materials.


Assuntos
Brônquios/patologia , Broncoscopia/instrumentação , Pulmão/patologia , Traqueia/patologia , Adulto , Idoso , Broncoscopia/métodos , Feminino , Granuloma/diagnóstico , Granuloma/patologia , Humanos , Inflamação/patologia , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/patologia , Estudos Retrospectivos , Sarcoidose/diagnóstico , Sarcoidose/patologia , Fumar/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Doenças da Traqueia/diagnóstico , Doenças da Traqueia/patologia , Tuberculose/diagnóstico , Tuberculose/patologia
19.
J Thorac Dis ; 8(5): E369-73, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27162702

RESUMO

Intermediate hemangioendothelioma is a group of rare tumors of vascular origin that show a borderline biological behavior and commonly arise in extremities, trunk, head or neck. Intermediate hemangioendothelioma originating in pleura is extremely rare. Herein we describe a case of primary pleural intermediate hemangioendothelioma in a 48-year-old man presenting with pleural effusion only. The patient was diagnosed by pleura biopsy and immunohistochemistry in our hospital. Even though neither systemic chemotherapy nor surgery was applied, he got relieved gradually and sustained asymptomatic during follow-up for 10 months.

20.
Zhonghua Yi Xue Za Zhi ; 96(4): 306-10, 2016 Jan 26.
Artigo em Chinês | MEDLINE | ID: mdl-26879795

RESUMO

OBJECTIVE: To quantitatively evaluate the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. METHODS: To establish the preclinical transplantation model of lung adenocarcinoma, 60 BALB/c nu/nu mice was inoculated with A549 cell lines via axilla. Sixty mice were randomly divided into 2 groups. The treatment group was treated with intravenous Bevacizumab (10 mg/kg weight, in a single injection), and the control group received saline only in the same dose. Five times of volume perfusion CT (VPCT) scan was performed before treatment, and on the second, forth, sixth and tenth days of treatment, respectively. The values of blood flow (BF) in the A549 tumors were measured after scanning. The microvessel density (MVD), vessel maturity index (VMI) in the tumors were determined using multiplexed QDs-based immunohistochemical staining. RESULTS: Comparing the values of BF, VMI and MVD between the two groups on the same day before treatment, the values of BF, VMI and MVD of the treatment group were (13.5±1.5) ml·(100 ml)(-1)·min(-1,) 0.14±0.04, (45.7±16.5)/HPF, respectively, and those in the control group were (13.4±1.6) ml·(100 ml)(-1)·min(-1) , 0.14±0.05, (48.0±7.0) /HPF , respectively. There was no significant difference between the two groups (all P>0.05). And on the second, forth, sixth, tenth days of treatment, the values of BF of the treatment group were (17.9±7.3), (32.2±6.9), (18.5±2.4) and (13.8±1.8) ml·(100 ml)(-1)·min(-1,) respectively, and those in the control group were (10.5±0.6), (9.6±0.8), (5.7±1.2) and (1.9±1.0) ml·(100 ml)(-1)·min(-1,) respectively. The values of VMI of the treatment group were 1.17±0.22, 3.25±0.23, 2.94±0.31 and 1.07±0.18, respectively, and those in the control group were 0.12±0.03, 0.13±0.03, 0.15±0.03, and 0.13±0.03, respectively. The values of MVD of the treatment group were (38.0±6.3), (24.3±5.4), (15.2±3.4) and (13.5±4.7)/HPF, respectively, and those in the control group were (44.8±5.9), (48.0±12.8), (41.8±5.7) and (45.7±20.3)/HPF, respectively. In treated mice, BF and VMI were significantly higher than those in the control group (all P<0.01). BF and VMI increased from day2, and reached the peak at day4 (P<0.01), then decreased at day6, however the value of BF at day6 was still higher than that in the baseline (P<0.01) and decreased to the baseline level at day10; while the value of VMI was still higher than that in the baseline at day10. And on the forth, sixth, tenth days of treatment, in treated mice, the values of MVD were significantly lower than those in the control group and the baseline level before treatment (all P<0.01). In control mice, BF decreased (all P<0.01) with the time, while MVD and VMI had no changes. CONCLUSIONS: The tumor perfusion and vessel maturity are transiently increased in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. VPCT is helpful to quantify the evolution of the tumor perfusion and then evaluate the functional changes of tumor vessel maturity.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Transplante de Pulmão , Adenocarcinoma de Pulmão , Animais , Bevacizumab , Linhagem Celular Tumoral , Tomografia Computadorizada de Feixe Cônico , Humanos , Camundongos , Camundongos Nus , Neovascularização Patológica , Ensaios Antitumorais Modelo de Xenoenxerto
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