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1.
BMJ Open ; 11(9): e051820, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475187

RESUMO

INTRODUCTION: Accurate diagnosis and staging of lung cancer is crucial because it directs treatment and prognosis. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound with bronchoscope fine-needle aspiration (EUS-B-FNA) are important in this process by sampling hilar/mediastinal lymph nodes and centrally located lung tumours. With the upcoming of immunotherapy and targeted therapies, assessment of programmed death ligand 1 (PD-L1) expression and molecular profiling has become important but is often impossible in cytological samples obtained through standard 22G TBNA needles. Recently, a three-pronged cutting edge 22G needle was developed that allows for transbronchial needle biopsy (TBNB). Our objective is to determine if EBUS/EUS-B-guided nodal/lung tumour sampling with Acquire 22G TBNB needles results in an improved suitability rate for the assessment of PD-L1 expression in comparison to standard 22G TBNA needles in patients with a final diagnosis of lung cancer. METHODS AND ANALYSIS: This is an investigator-initiated, parallel group randomised clinical trial. Patients are recruited at respiratory medicine outpatient clinics of participating university and general hospitals in the Netherlands, Poland and Italy. In total 158 adult patients with (suspected) lung cancer are included if they have an indication for mediastinal/hilar lymph node or lung tumour sampling by EBUS-TBNA and/or EUS-B-FNA based on current clinical guidelines. Web-based randomisation between the two needles will be performed. Samples obtained from mediastinal/hilar lymph nodes and/or primary tumour will be processed for cytology smears and cell block analysis and reviewed by blinded reference pathologists. An intention-to-treat analysis will be applied. Patients with missing data will be excluded from analysis for that specific variable but included in the analysis of other variables. This study is financially supported by Boston Scientific. ETHICS AND DISSEMINATION: The study was approved by the local Ethics Committee (Medisch Ethische Toetsingscommissie Amsterdam Medical Center (AMC)). Dissemination will involve publication in a peer-reviewed biomedical journal. TRIAL REGISTRATION NUMBER: NL7701; Pre-results.


Assuntos
Neoplasias Pulmonares , Agulhas , Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Medicine (Baltimore) ; 100(35): e27058, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477137

RESUMO

ABSTRACT: The treatment for squamous cell lung cancer (SqCLC) is limited, and the prognosis of SqCLC is poor. In this article, we aimed to analyze and identify immune-related cells and competition endogenous RNA (ceRNA) that influence the prognosis of SqCLC. SqCLC and lung adenocarcinoma data were downloaded from TCGA-GDC. A total of 22 types of immune cell fractions were estimated using CIBERSORT. R software was used to identify any significantly different transcriptome data, including mRNA, LncRNA, and miRNA. The univariate cox regression method was applied to screen for prognosis-related lncRNA, miRNA, mRNA and tumor-infiltrating immune cells. There were 504 patients included in this study. There was a higher proportion of memory activated CD4+ T cells and CD8+ T cells in younger women. Follicular helper T (Tfh) cells were predictive of a good prognosis and reflected immune activation in SqCLC. The SFTA1P/NKX2-1-AS1, hsa-mir-503, GREM2 ceRNA axes and NKX2-1-AS1, hsa-mir-96, PROK2 ceRNA axes were found to be important for the immune function, pathogenesis, and prognosis of SqCLC. Collectively, the immune-related ceRNA and tumor-infiltrating immune cells in SqCLC are likely important determinants of SqCLC pathogenesis, prognosis, and immune status.


Assuntos
Neoplasias Pulmonares/imunologia , Neoplasias de Células Escamosas/imunologia , Adolescente , Idoso , Criança , Células Epiteliais/patologia , Feminino , Ontologia Genética , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
3.
Medicine (Baltimore) ; 100(35): e27162, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477172

RESUMO

ABSTRACT: Cancer-associated fibroblasts (CAFs) have been attracting attention in recent years, but their nature has not been fully elucidated. Although CAFs have been recognized as an important therapeutic target, therapeutic agents have not been developed to date. CAFs are characterized by their high migration rate and involvement in epithelial-to-mesenchymal transition with some displaying a dendritic morphology that is reminiscent of fascin expression.The present study was designed to immunohistochemically investigate fascin expression in lung adenocarcinoma including CAFs and compare the results with existing CAF markers.We immunohistochemically investigated fascin expression in not only cancer tissue but also CAFs from 26 autopsy cases of lung adenocarcinoma. Immunohistochemistry of α-smooth muscle actin and fibroblast activation protein was also performed.Fascin-positive staining in CAFs was observed in all cases, with a strong correlation observed with existing CAF markers α-smooth muscle actin and fibroblast activation protein (P < .001). In addition, the proportion of tumor cells showing fascin-positive staining was found to correlate with its expression in CAFs (P < .05).We propose that CAFs express fascin, and that fascin may mediate crosstalk between cancer tissue and CAFs. Fascin might be a novel therapeutic target for treatments that target the cancer stroma.


Assuntos
Adenocarcinoma/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas dos Microfilamentos/metabolismo , Actinas/metabolismo , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Endopeptidases/metabolismo , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade
4.
Anticancer Res ; 41(9): 4479-4482, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475072

RESUMO

BACKGROUND/AIM: This study determined whether computed tomography (CT) is an appropriate means by which to differentiate non-invasive and minimally invasive forms of pulmonary adenocarcinoma from the invasive variant. PATIENTS AND METHODS: A total of 64 patients (38 men and 26 women, aged 42-76, mean age 64), who underwent surgery for pulmonary adenocarcinoma and a chest CT no less than 1 month before surgery, were included in the study. Lesions exhibiting ground glass opacity or ground glass opacity with a solid component of 5 mm or smaller, were defined as minimally invasive or non-invasive adenocarcinomas. CT findings were correlated with histopathological examination. RESULTS: Distinguishing minimally invasive and non-invasive adenocarcinoma from invasive adenocarcinoma using CT was achieved with a sensitivity of 77.7%, a specificity of 97.8%, a positive predictive value of 93.3%, and a negative predictive value of 91.8%. CONCLUSION: CT can be useful in assessing the degree of invasiveness of pulmonary adenocarcinoma and is a potential tool for the individualization of treatment.


Assuntos
Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
5.
Anticancer Res ; 41(9): 4571-4575, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475085

RESUMO

BACKGROUND/AIM: The purpose of this study was to compare the dose distribution between scanning carbon-ion radiotherapy (sCIRT) and volumetric-modulated arc therapy with stereotactic body radiation therapy (VMAT-SBRT) for stage I non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifteen patients with early-stage NSCLC who underwent sCIRT at Kanagawa Cancer Center between 2018-2020 were enrolled. Dose-volume histogram parameters of the planned target volume and normal organs for sCIRT and VMAT-SBRT were evaluated. RESULTS: The homogeneity index of the target volume of sCIRT was significantly lower than that of VMAT-SBRT. The dose of sCIRT was significantly lower than that of VMAT-SBRT at low volumes in the lung, heart, spinal cord, and esophagus. CONCLUSION: The dose distribution of sCIRT for early-stage NSCLC was better than that of VMAT-SBRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Radioterapia com Íons Pesados/métodos , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
7.
Ann Palliat Med ; 10(8): 8818-8826, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488370

RESUMO

BACKGROUND: Roughly 30-40% of lung cancer (LC) patients develop bone metastasis during the course of disease. The genetic differences between primary LC and matched bone metastasis are not yet fully understood. METHODS: A total of 40 LC patients with bone metastasis were collected and 450 targeted cancer-related genes were sequenced for genomic-alteration (GA) identification. RESULTS: Among the 40 LC patients, 33 had adenocarcinomas and 7 had squamous cell carcinomas. The metastatic sites of the 33 lung adenocarcinomas (LUADs) were the pelvis (6 patients), spine (16 patients), and limbs (11 patients). A total of 425 and 422 GAs were detected in the primary and metastatic lesions, respectively. The most common GAs were epidermal growth factor receptor (EGFR) mutations, which had mutation rates of 85.0% and 72.5% in the primary and metastatic lesions, respectively, and tumor protein 53 (TP53) mutations, which had mutation rates of 52.5% and 67.5% in the primary and metastatic lesions, respectively. Metastases to the pelvis and spine were most commonly accompanied by factor receptor substrate 2 (FRS2), cyclin-dependent kinase 4 (CDK4), and murine double minute 2 (MDM2) amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletion. The concordance between primary lung squamous cell carcinoma (LUSC) and corresponding metastasis was significantly higher than that of primary LUAD and corresponding metastasis (P=0.033). Compared to limb and pelvis metastases, the shared mutation in spine metastasis was significantly lower (P=0.016 and P=0.023, respectively). In matched primary LUSCs and bone metastasis lesions, there was no significant difference in the distribution of the tumor mutational burden (TMB) (P=0.9). Conversely, a significant difference of the TMB distribution was detected in pairs of primary LUAD and corresponding bone metastasis lesions (P=0.021). CONCLUSIONS: The consistency of mutation patterns between primary LC lesions and matched bone metastases may vary in terms of metastatic sites, but is very high in general. There was a significant difference in the TMB between primary LUAD and matched bone metastatic lesions. Our findings contribute to molecular understandings of primary LC and matched bone metastatic lesions.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Metástase Neoplásica/genética
8.
Medicine (Baltimore) ; 100(36): e27029, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516493

RESUMO

ABSTRACT: There has been no effective biomarker for small cell lung cancer (SCLC) patients with first-line immune checkpoint inhibitors (ICIs) treatment. The predictive value of neuron-specific enolase (NSE) in this cohort remains unclear.The medical records of 254 consecutive SCLC patients receiving programmed cell death receptor-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors were compiled from January 2015 to October 2020 in Chinese PLA General Hospital. Survival analysis was performed to explore the prognostic role of NSE at baseline and 3 weeks post treatment.One hundred two advanced SCLC patients treated with first-line PD-1/PD-L1 inhibitors were enrolled in this study. Normal baseline NSE levels were correlated with significantly prolonged progression-free survival (PFS, median: 8.7 vs 4.7 months, P = .006) and overall survival (OS, median: 23.8 vs 15.2 months, P = .014) compared with elevated baseline NSE levels, so as for normal NSE levels at 3 weeks with prolonged PFS (median PFS: 8.4 vs 4.5 months, P = .0002) and OS (median OS: 23.3 vs 7.4 months, P < .0001). Intriguingly, elevated NSE levels at 3 weeks were associated with shorter PFS (median PFS: 4.5 vs 5.8 months, P = .04) and OS (median OS: 5.5 vs 14.7 months, P < .0001) compared with normal NSE levels in the elevated baseline NSE subgroup. Most subgroup analyses stratified by clinical characteristics confirmed the prognostic value of baseline NSE level.Elevated NSE levels at baseline and 3 weeks were associated with worse prognosis in advanced SCLC patients receiving first-line ICIs treatment. NSE level might be applied as a useful prognostic tool for SCLC patients with immunotherapy.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fosfopiruvato Hidratase/sangue , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , China , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Registros Médicos , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida
9.
Medicine (Baltimore) ; 100(36): e27161, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516509

RESUMO

BACKGROUND: Huachansu injection (HCS) is a widely used traditional Chinese medicine for advanced non-small cell lung cancer (NSCLC) to alleviate the adverse drug reactions (ADRs) and enhance the clinical efficacy of chemotherapy. OBJECTIVE: To evaluate the efficacy and safety of HCS as an adjunctive treatment to platinum-based chemotherapy (PBC) for advanced NSCLC. METHODS: A systematic review and meta-analysis were conducted according to PRISMA guidelines. A total of nine databases were searched to select randomized controlled trials (RCTs) of HCS plus PBC to treat NSCLC from inception to October 10, 2020. RCTs on HCS plus PBC vs PBC alone for advanced NSCLC were included. Dichotomous data were pooled as risk ratio (RR) with 95% confidence intervals. RCTs compared to HCS plus PBC vs PBC alone were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), and secondary outcomes were survival rate, quality of life (QOL), and adverse drug reactions (ADRs). GRADE software was used to access the quality of evidence. RESULTS: A total of 32 RCTs, including 2753 patients, were included. Compared to PBC alone, HCS plus PBC improved the ORR, DCR, 1- and 2-year survival rates, and QOL and alleviated neutropenia, thrombocytopenia, nausea, vomiting, anemia, liver injury, renal injury, and alopecia. CONCLUSIONS: Compared to PBC alone, HCS plus PBC improved the clinical efficacy and alleviated the ADRs in advanced NSCLC patients. Considering the limitations of the included RCTs, high-quality trials with longer follow-ups are needed to further confirm the results.


Assuntos
Venenos de Anfíbios/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Platina/uso terapêutico , Venenos de Anfíbios/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Fitoterapia , Compostos de Platina/administração & dosagem , Resultado do Tratamento
10.
Isr Med Assoc J ; 23(9): 550-555, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34472229

RESUMO

BACKGROUND: Medical imaging and the resultant ionizing radiation exposure is a public concern due to the possible risk of cancer induction. OBJECTIVES: To assess the accuracy of ultra-low-dose (ULD) chest computed tomography (CT) with denoising versus normal dose (ND) chest CT using the Lung CT Screening Reporting and Data System (Lung-RADS). METHODS: This prospective single-arm study comprised 52 patients who underwent both ND and ULD scans. Subsequently AI-based denoising methods were applied to produce a denoised ULD scan. Two chest radiologists independently and blindly assessed all scans. Each scan was assigned a Lung-RADS score and grouped as 1 + 2 and 3 + 4. RESULTS: The study included 30 men (58%) and 22 women (42%); mean age 69.9 ± 9 years (range 54-88). ULD scan radiation exposure was comparable on average to 3.6-4.8% of the radiation depending on patient BMI. Denoising increased signal-to-noise ratio by 27.7%. We found substantial inter-observer agreement in all scans for Lung-RADS grouping. Denoised scans performed better than ULD scans when negative likelihood ratio (LR-) was calculated (0.04--0.08 vs. 0.08-0.12). Other than radiation changes, diameter measurement differences and part-solid nodules misclassification as a ground-glass nodule caused most Lung-RADS miscategorization. CONCLUSIONS: When assessing asymptomatic patients for pulmonary nodules, finding a negative screen using ULD CT with denoising makes it highly unlikely for a patient to have a pulmonary nodule that requires aggressive investigation. Future studies of this technique should include larger cohorts and be considered for lung cancer screening as radiation exposure is radically reduced.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Exposição à Radiação
11.
Zentralbl Chir ; 146(S 01): S33-S47, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34488231

RESUMO

Thorough mediastinal staging is pivotal for prognostic assessment and treatment planning in patients with non-small-cell lung cancer (NSCLC) without distant metastasis. It aims to answer the question of whether a technically and functionally feasible operation also makes sense from an oncological point of view. In case of a nodal-free mediastinum, primary surgical therapy can be considered. If the ipsilateral mediastinal lymph nodes are affected, multimodal therapy should be sought. Operating is usually no longer the first step, especially with extensive lymph node infestation. Surgery is recommended, if neoadjuvant (radio-)chemotherapy has achieved downstaging or major response. If the contralateral mediastinal lymph nodes are involved, curative surgery is no longer part of the therapeutic concept. The therapy of choice in this situation is definitive chemo-radiotherapy.Guidelines for mediastinal staging consistently require to combine radiological, nuclear medicine and minimally invasive methods. Imaging with CT and PET allows an initial assessment of the mediastinal status. In most cases it has to be complemented with tissue confirmation. Echoendoscopic assessment of the mediastinum with needle biopsy is the minimally invasive method of first choice ("needle first"). Surgical staging methods are reserved for situations, that cannot be satisfactorily clarified by echoendoscopy.Technique and outcome of the different methods are described and algorithms are presented for different oncological situations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Linfonodos/patologia , Mediastino/diagnóstico por imagem , Mediastino/patologia , Estadiamento de Neoplasias
12.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502019

RESUMO

The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people's health. Nerve growth factor (NGF) is a polypeptide which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Pulmão/patologia , Fator de Crescimento Neural/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/patologia , COVID-19/tratamento farmacológico , COVID-19/patologia , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/patologia , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular/métodos , Fator de Crescimento Neural/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia
13.
J Int Med Res ; 49(9): 3000605211044204, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34521244

RESUMO

OBJECTIVE: Segmentectomy is widely performed for early-stage lung cancer. However, the effects of segmentectomy versus lobectomy on pulmonary function remain unclear. We performed a meta-analysis with the aim of comparing segmentectomy and lobectomy in terms of preservation of pulmonary function in patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: We conducted a literature search of PubMed using the terms 'pulmonary function' AND 'segmentectomy' AND 'lobectomy'. The primary outcomes of interest were the forced expiratory volume in 1 second (FEV1), FEV1 as percent of predicted (%FEV1), change in FEV1 (Δ%FEV1), and the ratio of postoperative to preoperative FEV1. RESULTS: Thirteen studies comprising 2027 patients met the inclusion and exclusion criteria and were included for analysis, including 787 patients in the segmentectomy group and 1240 patients in the lobectomy group. Patients in the segmentectomy group showed significantly better preservation of FEV1 and %FEV1 compared with the lobectomy group. The reduction in FEV1 after surgery was significantly less in the segmentectomy group compared with the lobectomy group, and Δ%FEV1 was significantly higher in the segmentectomy group than in the lobectomy group. CONCLUSION: Segmentectomy results in better preservation of pulmonary function compared with lobectomy in patients with early-stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia , Estudos Retrospectivos
14.
BMJ Open ; 11(8): e043820, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373288

RESUMO

INTRODUCTION: Bronchoscopy is the main method in the diagnosis of various lung diseases. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the most modern bronchoscopic technique useful in diagnosis and staging of lung cancer (LC). OBJECTIVE: The aim of the study was to assess the yield of bronchoscopy in patients with suspected various respiratory diseases including LC. In particular, we examined the efficiency of different biopsy techniques in the diagnosis of LC in correlation with its localisation and pathomorphological type. PATIENTS AND METHODS: The results of pathomorphological examinations from 5279 bronchoscopies performed in 2016-2018 were analysed. The material was collected with EBUS-TBNA, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endobronchial forceps biopsy. Clinical and demographic factors were analysed using the Fisher χ2 test. RESULTS: 5279 patients were diagnosed due to various respiratory symptoms. LC was confirmed in 36.42% of patients. 40.81% of patients had no definitive pathomorphological diagnosis. Among patients with LC, the most frequent diagnosis was non-small cell LC: squamous cell lung cancer (SCC)-32.07% and adenocarcinoma (AC)-30.61%, then small cell LC-25.83% and not otherwise specified non-small cell lung cancer (NSCLC-NOS)-11.49%. Diagnosis of SCC was obtained significantly more often (χ2=43.143, p<0.000001) by forceps biopsy (41.09%) than by EBUS-TBNA/EUS-FNA (26.62%). On the contrary, diagnosis of AC or NSCLC-NOS was significantly more often (χ2=20.394, p<0.000007, and χ2=3.902, p<0.05, respectively) observed in EBUS-TBNA/EUS-FNA (34.31% and 12.6%) than in endobronchial biopsies (24.52% and 9.64%). CONCLUSIONS: The use of bronchoscopy in the diagnosis of various lung diseases is vital but also has many limitations. Effectiveness of EBUS-TBNA and endobronchial forceps biopsy in the diagnosis of lung cancer is strongly affected by tumour localisation and type of cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Transversais , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mediastino/patologia , Estadiamento de Neoplasias
15.
Molecules ; 26(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34361543

RESUMO

Lung cancer is one of the most common malignancies with the highest mortality rate and the second-highest incidence rate after breast cancer, posing a serious threat to human health. The accidental discovery of the antitumor properties of cisplatin in the early 1960s aroused a growing interest in metal-based compounds for cancer treatment. However, the clinical application of cisplatin is limited by serious side effects and drug resistance. Therefore, other transition metal complexes have been developed for the treatment of different malignant cancers. Among them, Ru(II/III)-based complexes have emerged as promising anticancer drug candidates due to their potential anticancer properties and selective cytotoxic activity. In this review, we summarized the latest developments of Ru(II/III) complexes against lung cancer, focusing mainly on the mechanisms of their biological activities, including induction of apoptosis, necroptosis, autophagy, cell cycle arrest, inhibition of cell proliferation, and invasion and metastasis of lung cancer cells.


Assuntos
Antineoplásicos , Complexos de Coordenação , Citotoxinas , Neoplasias Pulmonares/tratamento farmacológico , Rutênio , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Citotoxinas/química , Citotoxinas/uso terapêutico , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Rutênio/química , Rutênio/uso terapêutico
16.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445588

RESUMO

Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Microambiente Tumoral
18.
BMJ Case Rep ; 14(8)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340989

RESUMO

A 72-year-old female patient underwent endobronchial ultrasound and transbronchial needle aspirate sampling of mediastinal lymph nodes to investigate a middle lobe abnormality following an urgent referral. CT imaging completed the following day demonstrated a pneumomediastinum. At clinical review, the patient remained clinically stable and no intervention was required.


Assuntos
Neoplasias Pulmonares , Enfisema Mediastínico , Idoso , Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Mediastínico/etiologia , Mediastino/diagnóstico por imagem , Mediastino/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
19.
FASEB J ; 35(9): e21853, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34416038

RESUMO

We highlight the ability of the tuberculosis (TB) causing bacterial pathogen, Mycobacterium tuberculosis (Mtb), to induce key characteristics that are associated with established IARC classified Group 1 and Group 2A carcinogenic agents. There is sufficient evidence from epidemiological case-control, cohort and meta-analysis studies of increased lung cancer (LC) risk in pre-existing/active/old TB cases. Similar to carcinogens and other pathogenic infectious agents, exposure to aerosol-containing Mtb sprays in mice produce malignant transformation of cells that result in squamous cell carcinoma. Convincing, mechanistic data show several characteristics shared between TB and LC which include chronic inflammation, genomic instability and replicative immortality, just to name a few cancer hallmarks. These hallmarks of cancer may serve as precursors to malignant transformation. Together, these findings form the basis of our postulate that Mtb is a complete human pulmonary carcinogen. We also discuss how Mtb may act as both an initiating agent and promoter of tumor growth. Forthcoming experimental studies will not only serve as proof-of-concept but will also pivot our understanding of how to manage/treat TB cases as well as offer solutions to clinical conundrums of TB lesions masquerading as tumors. Clinical validation of our concept may also help pave the way for next generation personalized medicine for the management of pulmonary TB/cancer particularly for cases that are not responding well to conventional chemotherapy or TB drugs.


Assuntos
Transformação Celular Neoplásica , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/microbiologia , Pulmão/microbiologia , Pulmão/patologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/microbiologia , Adolescente , Adulto , Idoso , Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Carcinógenos , Transformação Celular Neoplásica/genética , Criança , Estudos de Coortes , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Biológicos , Mycobacterium tuberculosis/genética , Metástase Neoplásica/genética , Células-Tronco Neoplásicas/patologia , Fatores de Risco , Tuberculose Pulmonar/patologia , Adulto Jovem
20.
Nat Commun ; 12(1): 5060, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417454

RESUMO

Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.


Assuntos
DNA Tumoral Circulante/metabolismo , Fragmentação do DNA , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Diagnóstico Diferencial , Detecção Precoce de Câncer , Feminino , Genoma Humano , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Metástase Neoplásica , Estadiamento de Neoplasias , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto Jovem
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