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1.
Medicine (Baltimore) ; 99(9): e19346, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118771

RESUMO

RATIONALE: Available literature states that the histological subtype of the gastrointestinal stromal tumor (GIST) with pulmonary metastasis is often spindle cell type. To our knowledge, this is the first report of the GIST with pulmonary metastasis of very uncommon epithelioid subtype. PATIENT CONCERNS: We report a 63-year-old male presenting with the symptom of bloodstained sputum without obvious inducement. The patient had no chest pain, low back pain, fatigue, fever or night sweats symptoms. DIAGNOSES: Combined chest digital radiography and the history of the patient who presented with the colon GIST of the epithelioid subtype two years ago that the mass may be a metastasis tumor. Combined with morphological and immunohistochemical staining results, a pathological diagnosis of the GIST with pulmonary metastasis was considered. INTERVENTIONS: Right lobectomy and partial upper lobectomy were performed. OUTCOMES: The patient had not experienced any noticeable symptom and recurrent tumors at 6 months follow-up. LESSONS: We report a rare case of the GIST with pulmonary metastasis of epithelioid subtype. This case is of great significance to the pathologist's clinical work. For pathologists, if an epithelioid tumor in the lung is found, it is necessary to check whether the gastrointestinal tract also has the tumor, which may be an epithelioid GIST with pulmonary metastasis.


Assuntos
Tumores do Estroma Gastrointestinal/complicações , Neoplasias Pulmonares/etiologia , Biomarcadores Tumorais/análise , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/fisiopatologia , Humanos , Pulmão/anormalidades , Pulmão/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Metástase Neoplásica/fisiopatologia
2.
Nat Commun ; 11(1): 74, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900393

RESUMO

Despite the promising clinical efficacy of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with ALK-rearranged lung cancer, some tumor cells survive and eventually relapse, which may be an obstacle to achieving a cure. Limited information is currently available on the mechanisms underlying the initial survival of tumor cells against alectinib. Using patient-derived cell line models, we herein demonstrate that cancer cells survive a treatment with alectinib by activating Yes-associated protein 1 (YAP1), which mediates the expression of the anti-apoptosis factors Mcl-1 and Bcl-xL, and combinatorial inhibition against both YAP1 and ALK provides a longer tumor remission in ALK-rearranged xenografts when compared with alectinib monotherapy. These results suggest that the inhibition of YAP1 is a candidate for combinatorial therapy with ALK inhibitors to achieve complete remission in patients with ALK-rearranged lung cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Quinase do Linfoma Anaplásico/genética , Apoptose/efeitos dos fármacos , Carbazóis/administração & dosagem , Rearranjo Gênico/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Piperidinas/administração & dosagem , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Quinase do Linfoma Anaplásico/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Fatores de Transcrição/genética
3.
Khirurgiia (Mosk) ; (1): 61-66, 2020.
Artigo em Russo | MEDLINE | ID: mdl-31994501

RESUMO

OBJECTIVE: To develop a method for analysis of lymphatic drainage pathways from the lobe of the lung affected by non-small cell lung cancer (NSCLC) using infrared fluorescence. MATERIAL AND METHODS: A study enrolled patients with NSCLC who underwent anatomic resection of the lung with systematic lymph node dissection and preliminary intraoperative peritumoral injection of indocyanine green conjugate with human albumin. Registration of fluorescence in regional lymph nodes (LN) was carried out immediately after excision of specimen using the FLUM-808 instrumental system. RESULTS: Infrared fluorescence was observed in 117 hilar and mediastinal lymph nodes from 43 patients (2.7 nodes per a patient). Comparison of localization of fluorescent LN with localization of tumor in various lobes established significant variability of lymphatic drainage pathways. CONCLUSION: The developed method of infrared fluorescent evaluation of lymphatic drainage in patients with NSCLC confirms the necessity of systematic lymph node dissection for adequate staging.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática/diagnóstico por imagem , Estadiamento de Neoplasias/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Corantes , Fluorescência , Humanos , Verde de Indocianina , Raios Infravermelhos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/fisiopatologia , Linfonodos/cirurgia , Metástase Linfática/fisiopatologia
4.
Medicine (Baltimore) ; 98(51): e17532, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860945

RESUMO

BACKGROUND: Discordant results about the causal relationship between hormone replacement therapy use (HRT) and lung cancer risk in women had been reported. We therefore conducted a meta-analysis of cohort studies to evaluate this association. METHODS: The PubMed and Embase databases were searched. Fixed- or random-effects model was used to pool the study-specific relative risks (RRs) with corresponding 95% confidence intervals (CIs). Sensitivity analysis, publication bias, and subgroup analysis were performed. RESULTS: A total of 13 cohort studies met the inclusion criteria. Combined results indicated that compared with nonusers, women with HRT use were at a decreased risk (RR: 0.95, 95% CI: 0.91-0.99, I = 30.8%, P for heterogeneity = .137). In subgroup analysis by geographic area, smoking statue, type of hormones, and histology type of lung cancer, no significant association between HRT use and lung cancer was observed in most subgroups except in those studies which reported risk estimates adjusted for age, body mass index, smoking, and other confounders (RR: 0.95, 95 CI: 0.91-0.99, I = 33.0%, P for heterogeneity = .214). Both Begg funnel plot and Egger test (P = .243) suggested no evidence for publication bias. CONCLUSION: Our meta-analysis suggests ever use of HRT is associated with a decreased risk of lung cancer in women.


Assuntos
Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/métodos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Feminino , Humanos , Neoplasias Pulmonares/fisiopatologia , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Prevalência , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Análise de Sobrevida
6.
BMC Complement Altern Med ; 19(1): 281, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651320

RESUMO

BACKGROUND: Cedrus deodara (Roxb.) Loud (normally called as deodar), one out of four species in the genus Cedrus, exhibits widely biological activities. The Cedrus deodara total lignans from the pine needles (CTL) were extracted. The aim of the study was to investigate the anticancer potential of the CTL on A549 cell line. METHODS: We extracted the CTL by ethanol and assessed the cytotoxicity by CCK-8 method. Cell cycle and apoptosis were detected by a FACS Verse Calibur flow cytometry. RESULTS: The CTL were extracted by means of ethanol hot refluxing and the content of total lignans in CTL was about 55.77%. By the CCK-8 assays, CTL inhibited the growth of A549 cells in a dose-dependent fashion, with the IC50 values of 39.82 ± 1.74 µg/mL. CTL also inhibited the growth to a less extent in HeLa, HepG2, MKN28 and HT-29 cells. CONCLUSION: At low doses, the CTL effectively inhibited the growth of A549 cells. By comparison of IC50 values, we found that A549 cells might be more sensitive to the treatment with CTL. In addition, CTL were also able to increase the population of A549 cells in G2/M phase and the percentage of apoptotic A549 cells. CTL may have therapeutic potential in lung adenocarcinoma cancer by regulating cell cycle and apoptosis.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cedrus/química , Lignanas/farmacologia , Neoplasias Pulmonares/fisiopatologia , Extratos Vegetais/farmacologia , Células A549 , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Lignanas/isolamento & purificação , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Sincalida/genética , Sincalida/metabolismo
7.
J Bras Pneumol ; 45(6): e20180132, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31618297

RESUMO

OBJECTIVE: Preoperative functional evaluation is central to optimizing the identification of patients with non-small cell lung cancer (NSCLC) who are candidates for surgery. The minute ventilation/carbon dioxide output (VE/VCO2) slope has proven to be a predictor of surgical complications and mortality. Pulmonary rehabilitation programs (PRPs) could influence short-term outcomes in patients with COPD undergoing lung resection. Our objective was to evaluate the effects of a PRP on the VE/VCO2 slope in a cohort of patients with COPD undergoing lung resection for NSCLC. METHODS: We retrospectively evaluated 25 consecutive patients with COPD participating in a three-week high-intensity PRP prior to undergoing lung surgery for NSCLC, between December of 2015 and January of 2017. Patients underwent complete functional assessment, including spirometry, DLCO measurement, and cardiopulmonary exercise testing. RESULTS: There were no significant differences between the mean pre- and post-PRP values (% of predicted) for FEV1 (61.5 ± 22.0% vs. 62.0 ± 21.1%) and DLCO (67.2 ± 18.1% vs. 67.5 ± 13.2%). Conversely, there were significant improvements in the mean peak oxygen uptake (from 14.7 ± 2.5 to 18.2 ± 2.7 mL/kg per min; p < 0.001) and VE/VCO2 slope (from 32.0 ± 2.8 to 30.1 ± 4.0; p < 0.01). CONCLUSIONS: Our results indicate that a high-intensity PRP can improve ventilatory efficiency in patients with COPD undergoing lung resection for NSCLC. Further comprehensive prospective studies are required to corroborate these preliminary results.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/reabilitação , Terapia por Exercício/métodos , Neoplasias Pulmonares/reabilitação , Doença Pulmonar Obstrutiva Crônica/reabilitação , Idoso , Dióxido de Carbono/metabolismo , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Teste de Esforço , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Valores de Referência , Estudos Retrospectivos , Espirometria , Fatores de Tempo , Resultado do Tratamento , Capacidade Vital/fisiologia
8.
Phys Med ; 64: 33-39, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31515033

RESUMO

Proton radiotherapy has a potential to provide an effective cancer treatment while sparing greater volume of healthy tissue than the conventional X-ray based radiotherapy. However, in lungs this potential is hindered by motion due to breathing. An important quantity in treatment verification is the correlation between the respiratory phases (RP) and the timing of pencil beam scanning (PBS). In this note, we demonstrate how the RP can be estimated using Prompt gamma (PG) detection profiles collected during a treatment. We utilized a 4D-CT of a patient with lung cancer, a treatment plan and a PG simulator. The treatment plan consisted of ten layers corresponding to ten proton energies. The RPs of the 4D-CT were interpolated using a deformable registration algorithm, so as to have fifty RPs in total. Deviations from regular breathing were introduced via time dependent frequency modulation. Fifty unique breathing patterns were generated, for which PG profiles were simulated for each pencil beam. Poisson noise was added to each PG profile to account for photon statistics. The RPs were estimated by comparing the PG profiles with and without Poisson noise via three different methods: the RP associated with each layer was estimated 1) independently of the other layers, 2) using a linear correlation between the layers, and 3) using a quadratic correlation between the layers. The best model, the quadratic model, yielded an average error in RP estimation relative to the breathing period of 5% of the breathing period or less with a 90% confidence interval.


Assuntos
Tomografia Computadorizada Quadridimensional , Raios gama , Terapia com Prótons/métodos , Respiração , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/radioterapia , Método de Monte Carlo , Planejamento da Radioterapia Assistida por Computador , Fatores de Tempo
9.
Adv Exp Med Biol ; 1222: 43-53, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31529288

RESUMO

Behavioral cognitive therapy is recommended for lung cancer-related pain. The aim of the study was to analyze the strategies of coping with pain in relation to the histological type of lung cancer. The study included 257 lung cancer patients, divided into small cell lung carcinoma (SCLC) group (n = 72) and non-small cell lung carcinoma (NSCLC) group (n = 185). Pain was evaluated on a visual analog scale (VAS), while pain-coping strategies with the Coping Strategies Questionnaire. The two groups differed concerning the perception of pain - VAS score of 4.8 ± 2.0 in SCLC vs. 4.2 ± 2.0 in NSCLC group (p = 0.003). SCLC patients were less likely to use the active coping strategies, such as increasing behavioral activity (13.6 ± 7.0 vs. 16.9 ± 6.9; p = 0.001), and pain control (2.5 ± 1.2 vs. 3.4 ± 1.2; p < 0.001), and were lees able to decrease pain (2.4 ± 1.3 vs. 3.5 ± 1.3; p < 0.001). The most common pain-coping strategy in SCLC was praying or hoping, while it consisted of increased behavioral activity and active coping in NSCLC. Correlation analysis for coping strategies and pain intensity showed a negative influence (increased pain) for the following domains: diverting attention (r = 0.264, ß = 0.93); reinterpreting of pain sensations (r = 0.327, ß = 0.97); catastrophizing (r = 0.383, ß = 1.11); ignoring pain sensations (r = 0.306, ß = 0.93), praying or hoping (r = 0.220, ß = 0.76), coping self-statements (r = 0.358, ß = 1.10), and increased behavioral activity (r = 0.159, ß = 0.57). For pain control (r = -0.423, ß = -0.27) and the ability to decrease pain (r = -0.359, ß = -0.27), a positive influence (decreased pain) was found. The significant independent determinants of pain perception in the NSCLC group were: pain control strategy (ß = -0.39) and coping self-statement (ß = 0.72). We conclude that in NSCLC patients both pain control and the ability to decrease pain are the strategies which decrease the intensity of perceived pain. In contrast, SCLC patients have no clear strategy for pain-coping.


Assuntos
Adaptação Psicológica , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Manejo da Dor/psicologia , Dor/psicologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/psicologia , Terapia Cognitivo-Comportamental , Feminino , Humanos , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/psicologia , Masculino , Pessoa de Meia-Idade , Polônia , Carcinoma de Pequenas Células do Pulmão/psicologia , Fatores Socioeconômicos , Inquéritos e Questionários , Escala Visual Analógica
10.
EBioMedicine ; 47: 58-64, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31495719

RESUMO

BACKGROUND: Impaired lung health represents a significant burden on global health, including chronic obstructive pulmonary disease (COPD) and lung cancer. Given its global health impact, it is important to understand the determinants of impaired lung function and its relation to lung cancer risk independent of smoking. However, to date, no study has evaluated determinants of impaired lung function in a cohort exclusively of never-smokers, who also represent a growing proportion of all lung cancers. METHODS: A total of 222,274 never-smokers with reproducible spirograms were identified in the UK Biobank population-based cohort and included in the analysis. Baseline volumetric measures of lung function, including forced expiratory volume in 1-s (FEV1) and forced vital capacity (FVC), were used to define lung function impairment. Determinants of impaired lung function were evaluated using Poisson regression with robust variance estimation. The added value of lung function in lung cancer prediction was evaluated using Fine and Gray regression accounting for the competing risk of all-cause mortality. FINDINGS: Lung function impairment was associated with low birthweight, ambient air pollution (PM2·5 µg/mm3), and overweight, after adjustment for other important risk factors. We observed modest improvement in discrimination by adding lung function to our lung cancer prediction model for never-smokers. The highest optimism-corrected AUC at 3 (0·700, 95% CI: 0·654-0·734) and 5 years (0·694, 95% CI: 0·658-0·736) included FEV1 (% of GLI predicted FEV1), while the highest AUC at 7 years was based on the inclusion of FEV1/FVC (0·722, 95% CI: 0·687-0·762). INTERPRETATION: We identified several modifiable risk factors associated with increased risk of lung function impairment among lifetime never-smokers in UKB. We achieved moderate discrimination for lung cancer risk-prediction for never-smokers, and found modest improvement with the inclusion of lung function. FUND: This study was supported by a Canada Research Chair to RJH.


Assuntos
Neoplasias Pulmonares/epidemiologia , Testes de Função Respiratória , Fumantes , Adulto , Idoso , Bancos de Espécimes Biológicos , Biomarcadores , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Testes de Função Respiratória/métodos , Testes de Função Respiratória/estatística & dados numéricos , Tomografia Computadorizada por Raios X
11.
BMC Pulm Med ; 19(1): 149, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412851

RESUMO

BACKGROUND: Lung cancer is a common comorbidity of idiopathic pulmonary fibrosis (IPF) and has poor outcomes. The incidence and clinical factors related to development of lung cancer in idiopathic pulmonary fibrosis (IPF) are unclear. The aim of this study was to elucidate the cumulative incidence, risk factors, and clinical characteristics of lung cancer in IPF. METHODS: In this retrospective study, we analyzed clinical data for 938 patients who were diagnosed with IPF without lung cancer between 1998 and 2013. Demographic, physiologic, radiographic, and histologic characteristics were reviewed. Cumulative incidence of lung cancer and survival were estimated by the Kaplan-Meier method. Risk factors of lung cancer development were determined by Cox proportional hazard analysis. RESULTS: Among 938 IPF patients without lung cancer at initial diagnosis, lung cancer developed in 135 (14.5%) during the follow-up period. The cumulative incidences of lung cancer were 1.1% at 1 year, 8.7% at 3, 15.9% at 5, and 31.1% at 10 years. Risk factors of lung cancer were male gender, current smoking at IPF diagnosis, and rapid annual decline of 10% or more in forced vital capacity (FVC). Patients who developed lung cancer were mostly elderly men with smoking history. Squamous cell carcinoma followed by adenocarcinoma was the most common histologic type. Lung cancer was frequently located in areas abutting or within fibrosis. Survival was significantly worse in patients with lung cancer compared to patients with IPF alone. CONCLUSION: Lung cancer frequently developed in patients with IPF and was common in current-smoking men with rapid decline of FVC.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma de Células Escamosas/mortalidade , Fibrose Pulmonar Idiopática/complicações , Neoplasias Pulmonares/mortalidade , Adenocarcinoma/fisiopatologia , Idoso , Carcinoma de Células Escamosas/fisiopatologia , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Incidência , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Centros de Atenção Terciária , Tomografia Computadorizada por Raios X , Capacidade Vital
12.
Phys Med ; 65: 53-58, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430587

RESUMO

PURPOSE: It is still not conclusive which four-dimensional computed tomography (4DCT)-based ventilation imaging algorithm is most accurate and efficient. In this study, we proposed a simplified algorithm (VIAAVG) which only requires the average computed tomography (AVG CT) as input, and quantitatively compared its accuracy and efficiency with three other popular algorithms. MATERIAL AND METHODS: Fifty patients with lung or esophageal cancer who underwent radiotherapy were enrolled. Single photon emission computed tomography (SPECT) ventilation images (VI-SPECT) and 4DCT were acquired 1-3 days before the first treatment session. The end of exhalation and the end of inhalation CT were registered to derive deformable vector field (DVF) using MIMvista. 4DCT-based ventilation images (CTVI) were first calculated respectively by means of four algorithms (VIAJAC, VIAHU, VIAPRO and VIAAVG). The computation times were compared using paired t-test. The corresponding CTVIs (CTVIJAC, CTVIHU, CTVIPRO and CTVIAVG) and VI-SPECT were segmented into three equal sub-volumes (high, medium and low function lung, respectively) after smoothing and normalization. The Dice Similarity Coefficients (DSCs) were calculated for each sub-volume between each CTVI and VI-SPECT. The average DSCs for high, medium and low function lung in different CTVIs for each patient were compared using paired t-test. RESULTS: The mean DSCs for CTVIJAC, CTVIHU, CTVIPRO and CTVIAVG were 0.3255, 0.4465, 0.5865 and 0.5958, respectively. The average computation times for CTVIJAC, CTVIHU, CTVIPRO and CTVIAVG were 18.3 s, 24.2 s, 144.8 s and 15.0 s. CONCLUSION: VIAAVG is available for clinical use because of its high accuracy, improved efficiency and less input requirement compared to the other algorithms.


Assuntos
Algoritmos , Tomografia Computadorizada Quadridimensional/métodos , Ventilação Pulmonar , Adulto , Idoso , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/fisiopatologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton Único
13.
J Bras Pneumol ; 45(4): e20170458, 2019 Jul 29.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31365681

RESUMO

OBJECTIVE: To translate the European Organisation for Research and Treatment of Cancer (EORTC) 29-item Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC29, developed for the assessment of quality of life in patients with lung cancer) to Portuguese, conducting a pilot study of the Portuguese-language version and adapting it for use in Brazil. METHODS: For the translation, cultural adaptation, and pilot testing of the QLQ-LC29, we followed the guidelines established by the EORTC. The translation (English → Portuguese) and back-translation (Portuguese → English) were both carried out by translators, working independently, who were native speakers of one language and fluent in the other. After review, a draft version was created for pilot testing in lung cancer patients in Brazil. RESULTS: A total of 15 patients diagnosed with lung cancer completed the Portuguese-language version of the questionnaire. At the end of the process, we conducted a structured interview to identify any patient difficulty in understanding any of the questions. The final versions were sent to the EORTC and were approved. CONCLUSIONS: The Portuguese-language version of the EORTC QLQ-LC29 appears to be a useful, important, reliable questionnaire that is a valid tool for assessing quality of life in patients with lung cancer in Brazil.


Assuntos
Neoplasias Pulmonares/fisiopatologia , Qualidade de Vida , Inquéritos e Questionários/normas , Traduções , Idoso , Brasil , Comparação Transcultural , Feminino , Humanos , Linguagem , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valores de Referência , Reprodutibilidade dos Testes
14.
PLoS Comput Biol ; 15(8): e1007278, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31449515

RESUMO

Understanding intrinsic and acquired resistance is crucial to overcoming cancer chemotherapy failure. While it is well-established that intratumor, subclonal genetic and phenotypic heterogeneity significantly contribute to resistance, it is not fully understood how tumor sub-clones interact with each other to withstand therapy pressure. Here, we report a previously unrecognized behavior in heterogeneous tumors: cooperative adaptation to therapy (CAT), in which cancer cells induce co-resistant phenotypes in neighboring cancer cells when exposed to cancer therapy. Using a CRISPR/Cas9 toolkit we engineered phenotypically diverse non-small cell lung cancer (NSCLC) cells by conferring mutations in Dicer1, a type III cytoplasmic endoribonuclease involved in small non-coding RNA genesis. We monitored three-dimensional growth dynamics of fluorescently-labeled mutant and/or wild-type cells individually or in co-culture using a substrate-free NanoCulture system under unstimulated or drug pressure conditions. By integrating mathematical modeling with flow cytometry, we characterized the growth patterns of mono- and co-cultures using a mathematical model of intra- and interspecies competition. Leveraging the flow cytometry data, we estimated the model's parameters to reveal that the combination of WT and mutants in co-cultures allowed for beneficial growth in previously drug sensitive cells despite drug pressure via induction of cell state transitions described by a cooperative game theoretic change in the fitness values. Finally, we used an ex vivo human tumor model that predicts clinical response through drug sensitivity analyses and determined that cellular and morphologic heterogeneity correlates to prognostic failure of multiple clinically-approved and off-label drugs in individual NSCLC patient samples. Together, these findings present a new paradox in drug resistance implicating non-genetic cooperation among tumor cells to thwart drug pressure, suggesting that profiling for druggable targets (i.e. mutations) alone may be insufficient to assign effective therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/fisiopatologia , Adaptação Fisiológica/genética , Sistemas CRISPR-Cas , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Proliferação de Células/fisiologia , Técnicas de Cocultura , Biologia Computacional , Simulação por Computador , RNA Helicases DEAD-box/genética , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pulmonares/genética , Modelos Biológicos , Mutação , Ribonuclease III/genética
15.
Food Funct ; 10(9): 5816-5826, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31463494

RESUMO

Several studies have shown that mushroom polysaccharides enhance the ability of natural killer (NK) cells to recognize cancer cells as foreign and thereby enhance the effectiveness of host immune defence mechanisms. Nevertheless, the use of NK cells in cancer treatment requires finding selective stimulators of their cytotoxicity without disturbing organism homeostasis. Our studies revealed that Cantharellus cibarius polysaccharides present in the CC2a fraction, mainly composed of an O-2 and O-3 branched (1→6)-linked mannan, not only beneficially influenced the viability and proliferation of the human natural killer cells NK92 but also enhanced their anticancer properties against the human lung and colon cancer cells A549 and LS180, and at the same time did not affect the human lung and colon epithelial cells NL20 and CCD841 CoN. Furthermore, the CC2a fraction used alone was also nontoxic to the normal epithelium, while it inhibited the viability of these cancer cells. Nevertheless, the therapeutic potential of NK92 cells was greatly enhanced after coincubation with these polysaccharides and the observed effect was dependent on the CC2a concentrations. The beneficial effect of CC2a on NK92 cells was associated with stimulation of p38 and Erk expression as well as induction of the transcription factor CREB. The discovered beneficial impact of the CC2a fraction on NK92 cells suggested the therapeutic use of the investigated compound especially as an adjuvant. Furthermore, taking into account the abundance of these water soluble mannans in C. cibarius, the results also suggest that an increase in the intake of C. cibarius may promote innate immunity response against cancer through the enhancement of NK cell activity.


Assuntos
Agaricales/química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias Pulmonares/imunologia , Mananas/farmacologia , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/imunologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/fisiopatologia , Humanos , Imunidade Inata/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/fisiopatologia , Mananas/química , Extratos Vegetais/química
16.
Zhongguo Fei Ai Za Zhi ; 22(8): 537-540, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31451146

RESUMO

The National Comprehensive Cancer Network (NCCN) clinical practice guideline of non-small cell lung cancer (NSCLC) in 2018 points out that anatomic pulmonary resection is a preferred option for early stage NSCLC. With the development of video-assisted thoracoscopy, minimally invasive thoracic surgery represented by thoracoscopy has been widely used in clinical practice. Video-assisted thoracoscopic segmentectomy has become one of the treatment options for early stage NSCLC. Clinical studies have found that sublobar resection can achieve similar results and preserve more pulmonary function in the treatment of early stage NSCLC compared with lobectomy, but the changes of pulmonary function after segmentectomy are still controversial. This article focuses on the research progress of pulmonary function changes in NSCLC patients after video-assisted thoracoscopic segmentectomy.
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Assuntos
Neoplasias Pulmonares/cirurgia , Mastectomia Segmentar/tendências , Cirurgia Torácica Vídeoassistida/tendências , Humanos , Pulmão/fisiopatologia , Pulmão/cirurgia , Neoplasias Pulmonares/fisiopatologia
17.
BMJ Case Rep ; 12(8)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451457

RESUMO

Kaposi sarcoma (KS) is an angioproliferative disorder that is commonly associated with human herpes virus 8 as well as the HIV. In fact, KS is one of the most common AIDS-defining illnesses. KS typically presents with diffuse, violaceous cutaneous nodules, and may have concomitant visceral involvement. However, visceral involvement rarely occurs without skin manifestations. A rare case of localised bronchopulmonary KS without skin involvement is described in a patient with previously undiagnosed HIV. This atypical presentation represents a challenge for modern-day physicians in developed countries where the prevalence of AIDS-related diseases is decreasing.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Neoplasias Pulmonares , Oseltamivir/administração & dosagem , Sarcoma de Kaposi , Síndrome de Imunodeficiência Adquirida/diagnóstico , Síndrome de Imunodeficiência Adquirida/etiologia , Antivirais/administração & dosagem , Lavagem Broncoalveolar/métodos , Contagem de Linfócito CD4/métodos , Deterioração Clínica , Confusão/diagnóstico , Confusão/etiologia , Desidratação/complicações , Desidratação/diagnóstico , Desidratação/terapia , Diagnóstico Diferencial , Evolução Fatal , Hidratação/métodos , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/fisiopatologia , Infecções por HIV/terapia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Carga Viral/métodos
18.
Med Phys ; 46(9): 4087-4094, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31299097

RESUMO

PURPOSE: Motion management is critical for the efficacy of carbon ion therapy for moving targets such as lung tumors. We evaluated the feasibility of using four-dimensional cone beam computed tomography (4D-CBCT) reconstructed by Simultaneous Motion Estimation and Image Reconstruction (SMEIR) for dose calculation and accumulation in carbon ion treatment of lung cancer. METHODS: Motion-compensated 4D-CBCT images were reconstructed with the SMEIR algorithm to capture the most updated anatomy and motion with an updated interphase motion model on the treatment day. Projections of all CBCT phases were simulated from the planning 4D-CT by the ray tracing technique. Treatment planning and dose calculation were performed with a GPU-based Monte Carlo dose calculation software for carbon ion therapy. The treatment plan was optimized on the average computed tomography (CT) to obtain optimal intensity of the carbon ions. From the optimized plan, dose distributions on individual phases of 4D-CT and 4D-CBCT were calculated by the Monte Carlo-based dose engine. Dose accumulation was performed on 4D-CBCT images using deformable vector fields (DVF) generated by SMEIR. The accumulated planning target volume (PTV) dose based on 4D-CBCT was then compared to the accumulated dose calculated on 4D-CT, where the DVFs between different phases were obtained by the demons deformable registration algorithm. RESULTS: Dose value histograms (DVH) as well as absolute deviations of the maximum dose ( Δ D max ), mean dose ( Δ D mean ), and dose coverage metrics ( Δ V 95 % and Δ V 100 % ) for PTV were quantitatively evaluated for the two sets of plans. Good agreement was found between the 4D-CT and 4D-CBCT-based PTV-DVH curves. The average values of Δ D max , Δ D mean , Δ V 95 % , and Δ V 100 % calculated between the 4D-CT and SMEIR-4D-CBCT-based plans were 1.91 % , 3.55 % , 2.12%, and 1.15 % , respectively, for the PTVs of ten patient case studies. CONCLUSIONS: Based on these results, SMEIR-reconstructed 4D-CBCTs can potentially be used for motion estimation, dose evaluation, and adaptive treatment planning in lung cancer carbon ion therapy.


Assuntos
Tomografia Computadorizada Quadridimensional , Radioterapia com Íons Pesados , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Movimento , Estudos de Viabilidade , Humanos , Neoplasias Pulmonares/fisiopatologia , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Fatores de Tempo
19.
Eur J Radiol ; 117: 120-125, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31307636

RESUMO

PURPOSE: We compared image quality and volume of a moving simulated tumour and of lung tumours in patients who were treated with stereotactic body radiotherapy (SBRT) in a 16-row multi-detector CT (MDCT) versus a 320-row area-detector CT (ADCT). Tumour volumes in each respiratory phase were also evaluated. MATERIALS AND METHODS: We acquired static and four-dimensional CT (4DCT) images of a moving phantom with 10- and 30-mm amplitudes with three periods of patterns (2, 4, and 6 s). Breath-hold and 4DCT images were acquired for 12 lung tumour patients who underwent SBRT. Image data were acquired via MDCT and ADCT. The tumours were delineated in each respiratory phase and their volumes in end-expiratory/end-inspiratory phase and mid-respiratory phase were compared. RESULTS: In the phantom study, tumour volumes were smaller and closer to the static image when evaluated by ADCT than by MDCT. In the clinical study, average tumour volumes ± standard deviations were 9.58 ± 1.07 cm3 with MDCT (2.5-mm slice), and 7.12 ± 0.23 cm3 with ADCT (p < 0.01). Tumour volumes were closer to that of the breath hold CT in all patients evaluated by ADCT than by MDCT. Unlike MDCT, tumour volumes acquired by ADCT were smaller in end-expiratory or end-inspiratory phase than in the mid-respiratory phase. CONCLUSIONS: Tumour volumes in each of the respiratory phases in ADCT were significantly smaller and closer to the static image than the corresponding volumes in MDCT. This suggests that treated volume can be reduced if ADCT is used in treatment planning.


Assuntos
Tomografia Computadorizada Quadridimensional , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/radioterapia , Masculino , Imagens de Fantasmas , Radiocirurgia , Respiração
20.
Clin Interv Aging ; 14: 1187-1197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308642

RESUMO

Objectives: To assess the role of a pre-chemotherapy frailty index based on routine laboratory data in predicting mortality and chemotherapy adverse reactions among older patients with primary lung cancer. Design: Retrospective cohort study. Setting: West China Hospital, Chengdu, China. Participants: We included patients aged ≥60 years with primary lung cancer receiving the first course of chemotherapy. Measurements: Data were collected from medical records, local government death databases or telephone interviews. Outcomes included chemotherapy adverse reactions and all-cause mortality. We constructed a frailty index based on 44 laboratory variables (FI-LAB) before chemotherapy, and chose the following cutoff points: robust (0.0-0.2), pre-frail (0.2-0.35) and frail (≥0.35). Results: We included 1,020 patients (71.4% male; median age: 65 years old). Both pre-frailty and frailty was associated with any chemotherapy adverse reactions and infections during chemotherapy (OR=3.48, 95%CI: 1.77-6.87; OR=3.58, 95%CI: 1.55-8.26, respectively). Frail patients had a shorter median overall survival rate compared to robust patients (18.05 months vs 38.89 months, log-rank p<0.001). After adjusting for some potential confounding variables, the risk of all-cause mortality was dramatically increased in frail patients (HR:2.13, 95% CI:1.51-3.00) with an average follow-up of 3.9 years. Each 0.01 or per standard deviation (SD) increase in the FI-LAB value significantly increased the HR of death by 2.0% (HR:1.02, 95% CI: 1.01-1.03) and 23.0% (HR: 1.23, 95% CI: 1.13-1.34), respectively. Conclusions: Frailty assessed by routine laboratory data indicates increased risks of chemotherapy adverse reactions and death in older patients with primary lung cancer receiving the first course of chemotherapy.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Fragilidade/mortalidade , Avaliação Geriátrica/métodos , Neoplasias Pulmonares/mortalidade , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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