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1.
Recent Results Cancer Res ; 215: 299-318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605236

RESUMO

Lung cancer is the number one cause of cancer-related mortality worldwide. To improve disease outcome, it is crucial to implement biomarkers into the clinics which assist physicians in their decisions regarding diagnosis, prognosis, as well as prediction of treatment response. Liquid biopsy offers an opportunity to obtain such biomarkers in a minimal invasive manner by retrieving tumor-derived material from body fluids of the patient. The abundance of circulating microRNAs is known to be altered in disease and has therefore been studied extensively as a cancer biomarker. Circulating microRNAs present a variety of favorable characteristics for application as liquid biopsy-based biomarkers, including their high stability, relatively high abundance, and presence is nearly all body fluids. Although the application of circulating microRNAs for the management of lung cancer has not entered the clinics yet, several studies showed their utility for diagnosis, prognosis, and efficacy prediction of various treatment strategies, including surgery, radio-/chemotherapy, as well as targeted therapy. To compensate for their limited tumor specificity, several microRNAs are frequently combined into microRNA panels. Moreover, the possibility to combine single microRNAs or microRNA panels with tumor imaging or other cancer-specific biomarkers has the potential to increase specificity and sensitivity and could lead to the clinical application of novel multi-marker combinations.


Assuntos
Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , RNA Neoplásico/sangue , Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Prognóstico , RNA Neoplásico/genética
2.
Rev Med Suisse ; 15(671): 2092-2097, 2019 Nov 13.
Artigo em Francês | MEDLINE | ID: mdl-31742940

RESUMO

Lung cancer remains the most common cause of cancer deaths in the world, but its mortality can be significantly reduced by diagnosis and early detection. Computerized resources were developed to assist radiologists in their management of the large volume of thoracic images to be analyzed. Their objective is the detection of pulmonary nodules with high sensitivity and a low rate of false-positives and the ability to differentiate benign and malignant nodules. The volume of a pulmonary nodule and its volume doubling time are essential to nodule management. Computer aided detection or diagnosis (CAD) software are not currently used in clinically settings on a routine basis . Significant advances are expected due to the implementation of the artificial intelligence systems who will probably be integrated into the multidisciplinary management of any pulmonary nodule.


Assuntos
Inteligência Artificial , Diagnóstico por Computador , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Humanos , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/patologia , Nódulos Pulmonares Múltiplos/terapia , Sensibilidade e Especificidade
3.
Anticancer Res ; 39(11): 6231-6240, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704852

RESUMO

BACKGROUND/AIM: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFN-γ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx). PATIENTS AND METHODS: IGR was measured using enzyme-linked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx. RESULTS: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes. CONCLUSION: IFN-γ levels could be a biomarker for ICI-Tx.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Interferon gama/metabolismo , Neoplasias Pulmonares/metabolismo , Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Interferon gama/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/etiologia , Tuberculose Latente/metabolismo , Doenças Pulmonares Intersticiais/etiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Estudos Prospectivos , Linfócitos T/imunologia , Fatores de Tempo
4.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704853

RESUMO

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/enzimologia , Mesotelioma/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/análise , Neoplasias Pleurais/enzimologia , Serina-Treonina Quinases TOR/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidade , Mesotelioma/terapia , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Terapia de Alvo Molecular , Pemetrexede/administração & dosagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Pneumonectomia , Prognóstico , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo
5.
Medicine (Baltimore) ; 98(40): e17214, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577711

RESUMO

The role of surgery in small cell lung cancer (SCLC) is controversial. This study explored whether surgery offered a survival benefits for patients with SCLC.Patients diagnosed with SCLC between 2010 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The tumor, node, and metastasis (TNM) stage of SCLC in these patients was reclassified according to the 8th edition of the TNM classification for lung cancer. Overall survival (OS) was separately compared according to TNM stage between patients who underwent surgery and those who did not using Kaplan-Meier method. A Cox regression model was used to identify relevant variables affecting survival. Additional Kaplan-Meier curves were created to compare different types of surgery. Cox regression models and Forest plots were used to identify the predictors of survival in the surgery cohort.A total of 26,659 patients with SCLC were included, among which 627 (2.4%) patients underwent surgery. Surgery was associated with longer survival in patients with stage IA (45.0 vs 20.0 months, P < .001), stage IB (47.0 vs 19.0 months, P = .001), stage IIA (16.0 m vs NR, P = .007), stage III (18.0 vs 12.0 months, P < .001), and stage IV (9.0 vs 5.0 months, P < .001) disease, although the difference was not statistically significant for patients with stage IIB disease. Multivariate analysis identified surgery as an independent predictor of improved survival for all cohorts divided by stages except for stage IIB. Lobectomy was the most commonly performed procedure. Multivariate analysis in patients who underwent surgery identified lobectomy (hazard ratio [HR], 0.544; 95% confidence interval [CI], 0.341-0.869; P = .011) and chemotherapy (HR, 0.634; 95% CI, 0.487-0.827; P < .001) as independent predictors of improved survival in the surgery cohort.In a national analysis, surgery was performed in some patients for both early and advanced-stage SCLC. Surgery for SCLC was associated with improved survival except for patients with stage IIB disease. These results support an increased role of surgery in multimodal therapy for SCLC.


Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/cirurgia , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Regressão , Programa de SEER , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Análise de Sobrevida , Carga Tumoral
6.
Khirurgiia (Mosk) ; (10): 88-90, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31626245

RESUMO

Cardiovascular diseases and malignancies are leading causes of mortality in the world. Two categories of advanced age patients with cancer are observed in clinical practice. These are patients with cardiovascular diseases as comorbidities and patients with cardiovascular diseases as a complications of targeted therapy for cancer. Cardiac toxicity of chemotherapeutic drugs results myocardial dysfunction, occurrence or progression of heart valve disease, coronary artery disease, arterial hypertension and thromboembolism. A patient who underwent aortic valve replacement and coronary artery bypass surgery is discussed in the article. Aortic valve disease and coronary artery disease were complications of targeted radio- and chemotherapy for sigmoid colon cancer followed by lung and liver metastases. Questions of timely diagnosis and treatment of advanced age patients in multi-field surgical clinic are also analyzed.


Assuntos
Antineoplásicos/efeitos adversos , Cardiopatias/etiologia , Radioterapia/efeitos adversos , Neoplasias do Colo Sigmoide/terapia , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/efeitos da radiação , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/cirurgia , Ponte de Artéria Coronária , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/cirurgia , Cardiopatias/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Neoplasias do Colo Sigmoide/patologia
7.
Anticancer Res ; 39(9): 5077-5081, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519618

RESUMO

BACKGROUND/AIM: Patient performance scores are used widely in clinical practice to assess a patient's general condition. The aim of this study was to evaluate the prognostic role of Eastern Cooperative Oncology Group performance score (ECOG PS) before, after and its changes during chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Records of 99 patients with stage III NSCLC were evaluated. ECOG PS before, during and after chemoradiotherapy was analyzed for prognostic impact on overall (OS) and event-free (EFS) survival. RESULTS: Median OS considering the entire cohort was 20.8 months (range=15.3-26.2 months). Median OS, and 1- and 2-year survival rates were 26.4 months, 85% and 53% in patients with ECOG PS 0 versus 18.9 months, 69% and 37% in patients with ECOG PS 1 (p=0.1, log-rank test), respectively. After the first follow-up, 35% of patients presented worsening ECOG PS, while in 65% it was stable or improved. Median EFS according to ECOG PS 0, 1, 2 and 3 was 9.6, 9.0, 7.9 and 3.5 months, respectively, at the first follow-up (p=0.018, log-rank test). Deterioration of ECOG PS after chemoradiotherapy resulted in reduced OS in the subgroups with initial ECOG PS 0 and 1 (p=0.005 and p=0.001, log-rank test). CONCLUSION: ECOG PS and its changes have a strong impact on patient outcome. Deterioration of performance status was a strong negative prognostic factor for EFS and OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimiorradioterapia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Tomografia Computadorizada por Raios X
8.
Anticancer Res ; 39(9): 5219-5223, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519636

RESUMO

AIM: This study evaluated the prognostic value of soluble mesothelin-related protein (SMRP) levels in pleural effusions (PE) from patients with pleural mesothelioma (MPM). PATIENTS AND METHODS: SMRP level in PE was tested using an enzyme-linked immunosorbent assay (ELISA) in 109 patients with MPM at diagnosis before any treatment. The Kaplan-Meier method and the Cox regression were applied to compare overall survival probabilities across tertile categories of SMRP level. RESULTS: No significant differences in Kaplan-Meier overall survival probabilities among the SMRP categories were found. A statistically non-significant trend for increased death rate ratio (RR) was computed (p=0.327) when the higher (>46.5 nM, RR=1.38) and intermediate (8.5-46.5 nM, RR=1.18) SMRP categories were compared to the lower category (<8.5 nM, RR=1.00). Cox regression modelling including a restricted cubic spline showed a moderately rising non-linear trend in death rate. CONCLUSION: The SMRP level in PE does not appear to have prognostic significance and its detection is not recommended in routine clinical management of patients with MPM.


Assuntos
Proteínas Ligadas por GPI/metabolismo , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Mesotelioma/complicações , Mesotelioma/mortalidade , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurais/complicações , Neoplasias Pleurais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/diagnóstico , Mesotelioma/terapia , Pessoa de Meia-Idade , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Prognóstico , Curva ROC , Resultado do Tratamento
9.
J Cancer Res Clin Oncol ; 145(10): 2495-2506, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494736

RESUMO

PURPOSE: Histology samples are important for the appropriate administration of tumor type-specific cytotoxic and molecular-targeted therapies for the treatment of non-small cell lung cancer (NSCLC). When biopsy samples lack a definite morphology, a diagnosis can be selected from three subtypes based on immunohistochemistry (IHC) results, as follows: favor adenocarcinoma (ADC), favor squamous cell carcinoma (SQC), or not otherwise specified (NOS)-null. In terms of patient outcome, however, the validity of IHC-based classifications remains unknown. METHODS: A large series of 152 patients with advanced NSCLC whose diagnoses had been made based on morphological findings and who had been homogeneously treated were enrolled. We used IHC staining (TTF-1, SP-A, p40, and CK5/6) to examine tumor samples and refined the diagnoses. We then analyzed the pathological subgroups according to the IHC staining results. RESULTS: IHC profiling resulted in 50% of the cases being classified as favor ADC, 31% being classified as favor SQC, and 19% being classified as NOS-null groups. Compared with the favor ADC and favor SQC groups, the NOS-null group had a significantly poorer outcome. Pemetrexed-containing platinum regimens produced a response rate similar to that of other platinum doublet regimens in the favor ADC group (44% vs. 46%), whereas it produced a poorer response in the favor SQC group (0% vs. 52%) and the NOS-null group (0% vs. 24%). The favor ADC group tended to have a higher percentage of EGFR positivity and ALK positivity than the favor SQC group (25% vs. 11% and 7% vs. 0%, respectively). CONCLUSIONS: These findings support the use of immunohistological subtyping of NSCLC biopsy specimens to select patient-appropriate treatments.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Biópsia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento , Adulto Jovem
10.
Cancer Treat Rev ; 79: 101887, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491661

RESUMO

Small cell lung cancer (SCLC) was defined as a "recalcitrant cancer" because of its dismal prognosis and lack of outcome improvements in the last 30 years. Immunotherapy with checkpoint inhibitors revolutionized treatment in many cancer types and results from the IMpower133 study, a double-blind placebo-controlled phase III trial, showed overall survival benefit for atezolizumab when added to standard platinum-etoposide chemotherapy in first-line SCLC setting for the first time since years. Trials with other checkpoint inhibitors, e.g. pembrolizumab, durvalumab, nivolumab and ipilimumab, are ongoing in various settings, but, to date, there are no defined factors to identify patients who are more likely to benefit from such treatments. This review summarizes results of immunotherapy trials in SCLC for first-line, maintenance and further-line therapies for single-agents and combinations with checkpoint inhibitors. Predictive factors from these trials are reviewed in order to identify their clinical value, with particular emphasis on PD-L1 expression on both tumor cells and in stroma, especially in pembrolizumab-treated patients, and tumor mutational burden, for patients treated with the ipilimumab and nivolumab combination.


Assuntos
Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
11.
Cancer Invest ; 37(8): 376-386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474153

RESUMO

This meta-analysis aims to evaluate the effectiveness of chemotherapy before (I-CRT) or after (CRT-C) chemoradiotherapy (CRT) for inoperable locally advanced non-small cell lung cancer (LA-NSCLC). According to the object response rate (ORR) and disease control rate (DCR), there were no differences among I-CRT, CRT, and CRT-C treatments. I-CRT did not have significant survival benefits compared with CRT alone. Similar results comparing CRT-C with CRT were observed. Furthermore, I-CRT was not associated with improved survival compared to CRT-C with respect to OS and PFS. Our meta-analysis suggests the effects of additional chemotherapy added to CRT were limited for unselected LA-NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
12.
Cancer Treat Rev ; 80: 101892, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522079

RESUMO

BACKGROUND: The concept of oligometastatic disease (OMD) has expanded the scope of potentially curative therapy for metastatic NSCLC. However, large uncertainties remain regarding its definition and optimal management strategies. We therefore conducted a systematic review to investigate the value of various multimodality treatment concepts. METHODS: We searched the available literature in Pubmed, Medline and EMBASE using the terms "oligomet*", "synchron*", "oligorec*", "metachr*" "NSCLC", "lung cancer" and "stage IV" and included studies reporting treatment regimens and outcomes on radically treated patients with either "synchronous", "metachronous" or "mixed" OMD. Only de-novo diagnosis of OMD was considered. The impact of patient and treatment characteristics on overall survival (OS) and time trends in patterns of care were investigated. RESULTS: 54 studies published between 1987 and 2018 were included. Despite a wide range of OMD definitions, 90.1% of patients were treated for a single metastasis. Systemic therapy was used as backbone treatment for most patients. Although surgery was the preferred local treatment in earlier studies, the use of stereotactic radiotherapy increased rapidly after 2011. No OS difference was observed between surgery or radiotherapy as the treatment of primary tumor or metastases, respectively. A time trend towards improved OS after 2011 could be detected. CONCLUSIONS: While evidence in favor of radical treatment is emerging, most studies remain retrospective and mainly evaluate patients with singular metastases. While surgery, stereotactic radiotherapy and chemotherapy are the cornerstones of current treatment strategies, future clinical trials need to address the high risk of distant metastases by integrating targeted or immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Humanos , Metástase Neoplásica
13.
Int J Clin Pharmacol Ther ; 57(12): 607-611, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31488241

RESUMO

The anti-programmed cell death-ligand 1 (PD-L1) antibody atezolizumab is a promising agent for various cancers. Although immune-related adverse events (irAEs) induced by atezolizumab are rare, they can be severe. Clinical experience in irAE management is presently insufficient. Herein, we present a case of a patient with non-small cell lung cancer (NSCLC) who developed life-threatening irAEs including pneumonitis, thrombocytopenia, and cardiac dysfunction under immunotherapy with atezolizumab. Under expectant treatment and corticosteroid regimen, pneumonitis was totally resolved. However, thrombocytopenia and cardiac dysfunction did not improve. The patient sadly passed away 28 days after a single dose of atezolizumab. This case alarmed us once more to the importance of irAE management under cancer immunotherapy.
.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Cardiopatias/complicações , Neoplasias Pulmonares/terapia , Pneumonia/complicações , Trombocitopenia/complicações , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Evolução Fatal , Humanos , Imunoterapia , Neoplasias Pulmonares/complicações
14.
Cancer Sci ; 110(11): 3595-3602, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31512325

RESUMO

Coxsackievirus and adenovirus receptor (CAR) is a single-pass transmembrane protein that is associated with adenoviral infection. CAR is involved in the formation of epithelial tight junctions and promotes tumor growth in some cancers. Previously, we developed mouse monoclonal antibodies against human CAR and found that one, mu6G10A, significantly inhibited tumor growth in xenografts of human cancer cells. Herein, we generated and characterized a mouse-human chimeric anti-CAR antibody (ch6G10A) from mu6G10A. ch6G10A had binding activity, inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, and in vivo anti-tumor activity against CAR-expressing prostate cancer DU-145 cells. In addition, cancer tissue array analysis confirmed that CAR is highly expressed in neuroendocrine lung cancers including small cell lung cancer, and treatment with ch6G10A effectively inhibited in vivo subcutaneous tumor growth of NCI-H69 small cell lung cancer cells in nude mice. Moreover, treatment with mu6G10A effectively inhibited both in vivo orthotopic tumor growth and distant metastatic formation in mouse xenograft models of a highly metastatic subline of human small cell lung cancer DMS273 cells. These results suggest that targeting therapy to CAR with a therapeutic antibody might be effective against several cancer types including small cell lung cancer.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/antagonistas & inibidores , Neoplasias Pulmonares/terapia , Neoplasias da Próstata/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Animais , Citotoxicidade Celular Dependente de Anticorpos , Proteínas do Sistema Complemento/imunologia , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/imunologia , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/metabolismo , Neoplasias das Glândulas Endócrinas/metabolismo , Neoplasias das Glândulas Endócrinas/terapia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular , Neoplasias da Próstata/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Medicine (Baltimore) ; 98(37): e17179, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517874

RESUMO

We investigated oxidative stress parameters in the sera of patients with lung cancer and healthy individuals to evaluate their correlations with lung cancer.Ninety-four lung cancer patients and 64 healthy controls were enrolled after obtaining informed consent. Their sera oxidative stress parameters were measured.Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were significantly different between patients and healthy groups (all P < .001). TAS gradually decreased and TOS and OSI gradually increased from stage I to III, but it did not reach statistical significance (all P > .05). TAS and OSI were significantly different between the nonsmoking and smoking groups, radiotherapy and without radiotherapy groups, chemotherapy and without chemotherapy groups (P < .05), but not TOS (P > .05). In a receiver operating characteristic curve analysis comparing patients with lung cancer with healthy controls, the Youden indices of TOS, TAS, and OSI were 0.541, 0.532, and 1, respectively.The oxidative stress may be correlation with lung cancer staging. Smoking, surgery, radiotherapy, and chemotherapy showed correlation with parts oxidative stress parameters.


Assuntos
Antioxidantes/metabolismo , Neoplasias Pulmonares/sangue , Oxidantes/sangue , Biomarcadores Tumorais/sangue , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Curva ROC , Fumar/sangue
18.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(8): 596-601, 2019 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-31378021

RESUMO

Objective: To evaluate the feasibility of cell-free tumor DNA in pleural effusion supernatant for assessing the tumor mutational burden (TMB) of advanced lung cancers. Methods: From December 2016 to August 2018, 34 lung cancer patients (19 males and 15 females) with pleural effusion were enrolled at Zhongshan Hospital, Fudan University. The median age of the patients was 65 (range, 34-85) years. Before systemic or local antitumor therapy, tumor specific mutations in tumor tissue, pleural effusion supernatant, pleural effusion sediment, and plasma samples from these patients were examined using targeted next-generation sequencing, and TMB levels were calculated respectively. Subgroup analysis was based on smoking history and driver mutation status. Statistical differences were determined using SPSS 16.0 software, and individual groups were compared using the one-way analysis of variance (ANOVA) and LSD-t test. Results: The median TMB level of pleural effusion supernatant was 6.23 mutations/Mb, similar to that of tumor tissue (6.23 vs 6.86 mutations/Mb, t=1.174, P=0.245), but significantly higher than that of pleural effusion sediment (2.49 mutations/Mb, t=3.044, P=0.003) and plasma (2.49 mutations/Mb, t=2.464, P=0.016). Compared with tumor tissue in TMB assessment, pleural effusion supernatant had a positive percentage agreement of 52% (9/17), and a negative percentage agreement of 65% (11/17). Subgroup analysis showed that the TMB level was higher in smokers (n=11) than that in non-smokers (n=23, 14.4 vs 5.4 mutations/Mb, t=3.238, P=0.003). Conclusion: For advanced lung cancer patients with pleural effusion, pleural effusion supernatant is a promising substitute to tumor tissue for TMB assessment, which is a potential biomarker for immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , DNA Tumoral Circulante , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Derrame Pleural , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Resultado do Tratamento
19.
Anticancer Res ; 39(8): 4517-4523, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366554

RESUMO

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have dramatically changed the clinical outcomes of advanced tumours. However, biomarkers for monitoring immunological features during immunotherapy remain unclear, especially those in the peripheral blood, which are easily available. This study evaluated the usefulness of nCounter Analysis System in identifying immunological biomarkers in peripheral blood mononuclear cells (PBMCs) during ICI therapy. PATIENTS AND METHODS: PBMCs from two patients who responded well to ICI therapy were used, and the expression levels of immune-related mRNA and extracellular proteins were analyzed. RESULTS: Changes in the expression levels of 55 genes from pre-treatment to on-treatment were bioinformatically similar between the two cases. The expression levels of PD-1 were consistent with those by flow cytometry analysis, a reliable tool for monitoring various markers. CONCLUSION: The nCounter Analysis System may be a potent tool to simultaneously investigate genes and proteins on PBMCs as biomarkers during immunotherapy using a small amount of sample.


Assuntos
Biomarcadores Tumorais/sangue , Imunoterapia , Neoplasias Pulmonares/sangue , Proteínas de Neoplasias/genética , Idoso , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue
20.
Cancer Immunol Immunother ; 68(9): 1429-1441, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31428800

RESUMO

MHC class I-related chain A (MICA) is one of the major ligands for natural killer group 2 member D (NKG2D), which is an activating NK receptor. MICA is expressed on the surface of human epithelial tumor cells, and its shedding from tumor cells leads to immunosuppression. To activate immune response in the tumor microenvironment, we designed an anti-VEGFR2-MICA bispecific antibody (JZC01), consisting of MICA and an anti-VEGFR2 single chain antibody fragment (JZC00) and explored its potential anti-tumor activity. JZC01 targeted vascular endothelial growth factor receptor 2 (VEGFR2) and inhibited tumorigenesis by blocking the VEGFR2 signaling pathway. Additionally, JZC01 promoted NK and CD8+ T cells to release IFN-γ and engaged activated lymphocytes to lysis of VEGFR2-expressing tumor cells. The in vivo anti-tumor activity of JZC01 was investigated by establishing a Lewis lung cancer cell-transplanted mouse model. It effectively reduced the tumor vascular density and increased the infiltration and activation of NK and CD8+ T cells in the tumor microenvironment. Thus, JZC01 functions in anti-tumor angiogenesis and anti-tumor immune activation, and showed improved anti-tumor efficacy combined with docetaxel, which provides a new insight into anti-tumor therapy.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/terapia , Linfócitos do Interstício Tumoral/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia , Animais , Anticorpos Biespecíficos/genética , Apoptose , Carcinoma Pulmonar de Lewis , Citotoxicidade Imunológica , Modelos Animais de Doenças , Humanos , Tolerância Imunológica , Interferon gama/metabolismo , Neoplasias Pulmonares/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral
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