Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.163
Filtrar
1.
J Cancer Res Clin Oncol ; 146(2): 401-406, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31691871

RESUMO

PURPOSE: Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) for tumor angiogenesis and tumor cell proliferation. The efficacy of anlotinib as a third-line or beyond therapy for SCLC was confirmed in the ALTER1202 trial. For lung cancer patients treated with antiangiogenesis agents, the phenomenon of cavitation is commonly seen in the lung target lesions. The impact of tumor cavitation on survival in lung cancer patients treated with vascular-targeted therapy remains controversial. Our retrospective study was to investigate the prognostic value of tumor cavitation in extensive-stage SCLC patients treated with anlotinib. METHODS: A total of 73 extensive-stage SCLC patients confirmed by histopathology from January 2018 to January 2019 were retrospectively analyzed. All patients received anlotinib therapy at Shanghai Chest Hospital. We defined tumor cavitation of the lung target lesions as that part of solid component was changed to air-filled area according to chest CT. Progression-free survival (PFS) was calculated from the beginning of anlotinib therapy to the disease progression or the last follow-up visit. RESULTS: Eleven (15.0%) patients had tumor cavitation during anlotinib therapy. The ORR of the 73 patients was 15.1%. Multivariate logistic regression analysis showed that tumor cavitation during anlotinib therapy was not associated with gender (P = 0.630), age (P = 0.190), smoking status (P = 0.165), anatomy type (P = 0.641), and the line of anlotinib therapy (P = 0.302). The median PFS of all patients was 2.6 months (95%CI 2.1-3.2). According to the univariate analysis, the median PFS in patients with and without tumor cavitation was 5.0 months and 2.2 months, respectively, and the difference was statistically significant (P = 0.041). According to the multivariate analysis, tumor cavitation was an independent factor for PFS after adjusting gender, age, smoking status, anatomy type, the line of anlotinib therapy, tumor cavitation, and response to anlotinib (adjusted HR 0.316, 95%CI 0.142-0.702; P = 0.005). CONCLUSIONS: In 73 extensive-stage SCLC patients treated with anlotinib, no demographic/clinical characteristic was related to tumor cavitation, and tumor cavitation was an independent factor in predicting better PFS.


Assuntos
Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Quinolinas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Idoso , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Prognóstico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
2.
J Oncol Pharm Pract ; 26(1): 256-258, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31566114

RESUMO

INTRODUCTION: The immune checkpoint inhibitors recently entered to small cell lung cancer (SCLC) stage, firstly in the third and recently in the first lines of therapy. This efficacy comes at the expense of many toxicities including skin toxicity. This toxicity is usually in the form of rash and pruritis; however, rare reactions like psoriasis can also be seen. CASE REPORT: Herein, we report an SCLC case who developed de novo psoriasis while treated with nivolumab as the third-line treatment for SCLC. MANAGEMENT AND OUTCOME: The psoriatic plaques were regressed with the topical highly potent steroid therapy, and immunotherapy was continued without further complications. DISCUSSION: We think that rare adverse events like de novo psoriasis are important considering the expanding role of these agents; their timely recognition and treatment are important in the management of cancer patients.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Psoríase/induzido quimicamente , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores
3.
Cancer Sci ; 111(2): 610-620, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31845438

RESUMO

High-grade neuroendocrine lung cancer (HGNEC), which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is a rapidly proliferating, aggressive form of lung cancer. The initial standard chemotherapeutic regimens of platinum doublets are recommended for SCLC and have been frequently used for LCNEC. However, there are currently no molecularly targeted agents with proven clinical benefit for this disease. The deubiquitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCHL1) is a neuroendocrine cell-specific product that is known as a potential oncogene in several types of cancer, but little is known about the biological function of UCHL1 and its therapeutic potential in HGNEC. In this study, we found that preclinical efficacy evoked by targeting UCHL1 was relevant to prognosis in HGNEC. UCHL1 was found to be expressed in HGNEC, particularly in cell lines and patient samples of SCLC, and the combined use of platinum doublets with selective UCHL1 inhibitors improved its therapeutic response in vitro. Immunohistochemical expression of UCHL1 was significantly associated with postoperative survival in patients with HGNEC and contributed towards distinguishing SCLC from LCNEC. Circulating extracellular vesicles (EV), including exosomes isolated from lung cancer cell lines and serum from early-stage HGNEC, were verified by electron microscopy and nanoparticle tracking analysis. Higher levels of UCHL1 mRNA in EV were found in the samples of patients with early-stage HGNEC than those with early-stage NSCLC and healthy donors' EV. Taken together, UCHL1 may be a potential prognostic marker and a promising druggable target for HGNEC.


Assuntos
Carcinoma Neuroendócrino/patologia , Vesículas Extracelulares/genética , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Células A549 , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Vesículas Extracelulares/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Platina/farmacologia , Platina/uso terapêutico , Prognóstico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Ubiquitina Tiolesterase/antagonistas & inibidores , Regulação para Cima
4.
Crit Rev Oncol Hematol ; 143: 148-152, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31675543

RESUMO

Soluble PD-1 and PD-L1 are detected in the serum and plasma of lung cancer patients. The significance of these soluble proteins as prognostic or predictive markers in lung cancer is uncertain. The testing methods used to detect soluble PD1/PD-L1 are variable with no agreement on a common definition of a positive test. The advantages of validating soluble PD1/PD-L1 relevance in lung cancer include easiness of obtaining blood samples for testing, serial measurements to assess response to treatments such as immunotherapy, and potentially early identification of cancer relapse in cases treated with curative intent. In this review, we present the available data published on soluble PD1 and PD-L1 in lung cancer.


Assuntos
Antígeno B7-H1/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Receptor de Morte Celular Programada 1/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Prognóstico , Receptor de Morte Celular Programada 1/imunologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/imunologia
5.
Lancet ; 394(10212): 1929-1939, 2019 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-31590988

RESUMO

BACKGROUND: Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC. METHODS: This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum-etoposide; durvalumab plus tremelimumab plus platinum-etoposide; or platinum-etoposide alone. All drugs were administered intravenously. Platinum-etoposide consisted of etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum-etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum-etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum-etoposide group versus the platinum-etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. FINDINGS: Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum-etoposide group and 269 to the platinum-etoposide group. Durvalumab plus platinum-etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59-0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5-14·8) in the durvalumab plus platinum-etoposide group versus 10·3 months (9·3-11·2) in the platinum-etoposide group, with 34% (26·9-41·0) versus 25% (18·4-31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum-etoposide group and 166 (62%) of 266 in the platinum-etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. INTERPRETATION: First-line durvalumab plus platinum-etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. FUNDING: AstraZeneca.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Etoposídeo/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Esquema de Medicação , Etoposídeo/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Carcinoma de Pequenas Células do Pulmão/mortalidade
6.
Anticancer Res ; 39(10): 5725-5731, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570474

RESUMO

BACKGROUND/AIM: In lung cancer (LC) patients, pre-existing interstitial lung disease (ILD) is a risk of chemotherapy-associated acute exacerbation of ILD (AE-ILD). AE-ILD shows a diverse clinical course varying from fatal respiratory failure to asymptomatic event, and the prognostic impact is still unclear. MATERIALS AND METHODS: We retrospectively evaluated the association between the prognosis and AE-ILD in 86 LC patients with pre-existing ILD who were treated with cytotoxic chemotherapy, especially focusing on histological types of LC. RESULTS: Thirty (34.9%) patients had AE-ILD, that was significantly associated with a poor prognosis in LC patients with ILD. When analyzed by histological types, a significant association of AE-ILD with shorter survival was observed only in the small cell LC (SCLC) group, but not in the non-small cell LC group. CONCLUSION: The development of AE-ILD by cytotoxic chemotherapy is associated with poor prognosis in LC patients with ILD, especially in patients with SCLC.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
7.
Medicine (Baltimore) ; 98(42): e17335, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626089

RESUMO

BACKGROUND: Previous studies have shown that microRNA-32 (miRNA-32) is an exosome microRNA that affects the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells. In this study, our goal was to assess the expression of plasma microRNA-32 and its potential as a biomarker to predict the tumor response and survival of patients with NSCLC undergoing platinum-based chemotherapy. METHODS: Plasma microRNA-32 levels before and after 1 cycle of platinum-based chemotherapy in 43 patients with NSCLC were measured using a quantitative real-time polymerase chain reaction assay (qPCR). In addition, the demographic and survival data of the patients were collected for analysis. RESULTS: A significant correlation was observed between the changes in microRNA-32 levels before and after 1 chemotherapy cycle and the treatment response (P = .035). In addition, Kaplan-Meier analysis showed that the level of microRNA-32 after 1 chemotherapy cycle was significantly correlated with the prognosis of patients. The median progression-free survival (P = .025) and overall survival (P = .015) of patients with high microRNA-32 levels (≥7.73) after 1 chemotherapy cycle was 9 and 21 months, respectively. In contrast, the median survival of patients with low microRNA-32 levels (<7.73) was 5 and 10 months, respectively. CONCLUSIONS: The plasma levels of microRNA-32 correlated with the efficacy of platinum-based chemotherapy and survival, indicating that microRNA-32 may be useful for predicting the effectiveness of platinum-based chemotherapy and prognosis in NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Carcinoma de Pequenas Células do Pulmão/genética , Idoso , Biomarcadores Tumorais/genética , Estudos Controlados Antes e Depois , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Resultado do Tratamento
8.
Chemotherapy ; 64(3): 129-137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622969

RESUMO

INTRODUCTION: Small-cell lung cancer (SCLC) is a very chemosensitive solid tumor but is characterized by rapid progression. The modified Glasgow prognostic score (mGPS) has been shown to be an independent prognostic factor in various tumors. However, there have been few reports regarding the prognostic value of mGPS in extensive disease (ED)-SCLC. OBJECTIVE: This study was designed to clarify the clinical significance of mGPS focusing on its usefulness as a prognostic indicator for the survival and serial administrations of chemotherapies in patients with ED-SCLC. METHODS: We retrospectively analyzed the clinical records of ED-SCLC patients diagnosed and treated at Shinshu University School of Medicine between January 2005 and December 2018. Overall survival (OS) was compared according to mGPS and we examined whether mGPS could be a prognostic factor in ED-SCLC using the Kaplan-Meier method and univariate and multivariate Cox hazard analyses. RESULTS: Eighty-three patients were enrolled in this study. The median OS of mGPS 0, mGPS 1, and mGPS 2 groups were 13.6, 9.2, and 5.7 months, respectively. The OS of the mGPS 0 group was significantly longer than those of mGPS 1 and mGPS 2 groups (log-rank, p = 0.025 and 0.008, respectively). The rates of second-line chemotherapy administration in mGPS 0, mGPS 1, and mGPS 2 groups were 79.4, 61.9, and 33.3%, respectively. The rate in the mGPS 0 group was significantly higher than that in the mGPS 2 group (p = 0.003). Multivariate analyses indicated that mGPS 2 was an independent unfavorable prognostic factor in addition to old age (≥75 years), poor performance status (2-3), and elevated serum lactate dehydrogenase level (≥223 IU/L). CONCLUSION: In ED-SCLC patients, mGPS was useful as a prognostic indicator for OS.


Assuntos
Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade
9.
J Cancer Res Ther ; 15(4): 876-881, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436246

RESUMO

Aims: Lung cancer is one of the leading causes of cancer-related mortality. Tobacco usage is considered as associated with the carcinogenesis, progression, and prognosis of lung cancer. Previous studies have demonstrated that the smoking inhibited medical therapy results from K-Ras gene mutation through suppressing the epidermal growth factor receptor (EGFR) pathway. However, recent clinical trials have revealed that few smoked lung cancer patients present K-Ras gene mutation; yet, the majority of smoked lung cancer patients remain K-Ras nonmutation. The chemo-resistant mechanism remains unclear. Recently, microRNA (miRNA) interaction has been found to play an important role in drug resistance process. We hypothesized that miRNA may exert medicine resistance during the processes of lung cancer therapy. Methods: Here, we analyzed miRNA array data from the GEO database. Results: Our results showed that the interaction network among hsa-miR-30d-3p, hsa-miR-184, hsa-miR-500a, hsa-miR-542-3p, among others, inhibited EGFR-targeted medicine therapy. Conclusion: The research will provide evidence that promotes novel therapy of lung cancers.


Assuntos
Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Inibidores de Proteínas Quinases/farmacologia , Carcinoma de Pequenas Células do Pulmão/genética , Receptores ErbB/antagonistas & inibidores , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Prognóstico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia
10.
BMC Pulm Med ; 19(1): 156, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438923

RESUMO

BACKGROUND: Nintedanib is a tyrosine kinase inhibitor that efficiently slows the progression of idiopathic pulmonary fibrosis (IPF) and has an acceptable tolerability profile. In contrast, immune checkpoint inhibitors (ICIs) such as programmed death 1 and programmed death ligand 1 inhibitors have shown clinical activity and marked efficacy in the treatment of non-small cell lung cancer. However, it is unclear whether nintedanib reduces the risk of ICI-induced pneumonitis in IPF. CASE PRESENTATION: A 78-year-old man with squamous cell lung carcinoma in IPF underwent second-line treatment with pembrolizumab. He was diagnosed as having pembrolizumab-induced pneumonitis after two cycles. He was administered prednisolone (PSL) and then improved immediately. Thereafter, his lung cancer lesion enlarged despite treatment with TS-1. Atezolizumab was then administered as 4th-line chemotherapy, but he immediately developed atezolizumab-induced pneumonitis after 1 cycle. The re-escalated dosage of PSL improved the pneumonitis, and then nintedanib was started as additional therapy. Under careful observation with nintedanib, atezolizumab was re-administered on day 1 of an every-21-day cycle. After three cycles, it remained stable without exacerbation of drug-induced pneumonitis. CONCLUSION: This case indicates the possibility that the addition of nintedanib to ICI therapy might prevent drug-induced pneumonitis or acute exacerbation of IPF. However, whether anti-fibrotic agents such as nintedanib are actually effective in preventing ICI-induced pneumonitis in ILD remains unknown and additional research is greatly needed to identify effective therapies for ILD combined with lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/complicações , Progressão da Doença , Humanos , Fibrose Pulmonar Idiopática/complicações , Neoplasias Pulmonares/complicações , Masculino , Pneumonia/induzido quimicamente , Retratamento , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X
11.
Medicine (Baltimore) ; 98(35): e16593, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464894

RESUMO

RATIONALE: Limbic encephalitis is one of the most common paraneoplastic neurological disorders (PND). The role of brain Fluorine-18-fluorodeoxyglucose position emission tomography/computed tomography (CT) in paraneoplastic limbic encephalitis (PLE) and of the whole body 18F-FDG PET/CT in this setting, remains still not well defined. PATIENT CONCERNS: We report a case of a patient with chronic inflammatory rheumatism, psoriasis and Hashimoto thyroiditis and subsequent appearance of static and dynamic ataxia and episodic memory deficit who was diagnosed as PLE combined with small cell lung cancer (SCLC). DIAGNOSES: The diagnosis of SCLC was made with EBUS-TBNA of a mediastinal lymph node. INTERVENTIONS: Whole-body 18F-FDG PET/CT was performed for the initial staging of SCLC, in the planning of radiotherapy treatment, to evaluate therapeutic response and in the follow-up. A dedicated brain scan was included to the same PET session. Whole-body contrast enhanced computed tomography (CT) and contrast enhanced whole-brain MRI were also performed. OUTCOMES: She was administered neoadjuvant chemioterapy with Cisplatin and Etoposide with concomitant radiotherapy treatment. Whole body 18F-FDG PET/CT showed a complete metabolic response already after 3 cycles of chemioterapy. Brain functional study showed a metabolic pattern characterized by the migration of hypermetabolism in the bilateral hippocampal areas during the therapeutic treatment, which correlated with the persistence of clinical symptoms. LESSONS: In the era of personalized medicine and targeted therapy, this case highlights the importance of the 18F-FDG PET/CT study as an accurate tool to identify PLE and to guide the diagnostic work-up of the underlying tumor. Considering that most of these are 18F-FDG avid tumors and that the 18F-FDG PET/CT scan is often added to the diagnostic work-up when screening patients for malignancy, this functional imaging can play a decisive role.


Assuntos
Fluordesoxiglucose F18/administração & dosagem , Encefalite Límbica/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Encéfalo/diagnóstico por imagem , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Encefalite Límbica/tratamento farmacológico , Encefalite Límbica/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Imagem Corporal Total
12.
Asian Pac J Cancer Prev ; 20(8): 2391-2396, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450911

RESUMO

Objectives: Numerous studies addressed the effect of statin on cancer patients. The aim of this study is to define the effect of statin administration with chemotherapy on the patients' outcomes. Methods: We retrospectively researched the database of the University of Cincinnati cancer to identify lung cancer patients who received statins (S+, n=41) during their treatment in our institute. We also, retrieved data for contemporaneously treated patients who did not receive statins (S-, n=159) as a control arm. Clinico-demographical data and overall survival (OS) were analyzed using Pearson's Chi-square (χ2) test and Kaplan-Meier survival curves with Log-rank test. Adjustment using Cox proportional hazard ratios (HR) were done based on (age, gender, race and stage) to identify effect of statins on their outcomes. Results: The median age for S+ was 64y (IQR; 55-69) and 71.2% of the patients were white. Histopathology was 55.4% and 31.7% for adenocarcinoma and squamous cell carcinoma, respectively. Fifty-six percent were stage IV in each study arm and the median OS was14.9 m. Median OS was insignificantly lower in S­ve arm (13.7 vs 15.6 months; P=0.652, HR=0.91, 95%CI 0.52-1.57). Our results show that after different types of adjustments, S+ did not show survival advantage (P>0.05) compared to the control arm. Conclusion: While showing an increase in overall survival in patients with advanced lung cancer, the results of this study did not reach statistical significance. This could be due for the small sample size of this retrospective study.


Assuntos
Adenocarcinoma de Pulmão/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Resultado do Tratamento
13.
Nat Commun ; 10(1): 3485, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375684

RESUMO

MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients.


Assuntos
Apoptose/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Terapia de Alvo Molecular/métodos , Proteínas Proto-Oncogênicas c-myc/genética , RNA Interferente Pequeno/metabolismo , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
14.
Intern Med ; 58(22): 3261-3265, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31292388

RESUMO

Small cell lung cancer (SCLC) transformation of epidermal growth factor receptor (EGFR) mutant adenocarcinoma (ADC) during EGFR tyrosine kinase inhibitor (TKI) treatment is an example of a rare subset of acquired drug resistance. We herein report the case of a 75-year-old man treated with afatinib who was then diagnosed with SCLC transformation. After two years of successful treatment with afatinib, the tumor relapsed, and a re-biopsy revealed SCLC harboring EGFR exon 19 deletion. We encountered a case of transcriptional alteration, potentially important for SCLC transformation of EGFR mutant lung ADC, that was recognized via the expression of NOTCH, ASCL1 and RB1 on immunohistochemical staining.


Assuntos
Adenocarcinoma de Pulmão/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Afatinib , Idoso , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
15.
Anticancer Res ; 39(7): 3711-3718, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262897

RESUMO

BACKGROUND/AIM: Small cell lung cancer (SCLC) originates from neuroendocrine branchial cells (15-20%). It is regarded as distinct from other lung cancers due to its biological and clinical features. In most cases of SCLC, surgery or radiotherapy alone is not an effective cure. The aim of our study was to examine the cytotoxic effects of chemotherapy supported by electroporation (EP) on a resistant SCLC model, in vitro. MATERIAL AND METHODS: The multidrug resistant small lung cell line H69AR was used to evaluate the cytotoxic effects of cisplatin (CPPD) and vinorelbine (Navirel®; NAV) at lower doses when used with EP. Cells were treated with different concentrations of CPPD and NAV, alone or in combination with the following EP parameters: 400-1200 V/cm, 8 pulses of 100 µs duration, at 1Hz. The cell viability was estimated by MTT assay after 24 and 48 h. Apoptotic cells were detected by neutral comet assay and immunofluorescence assay with PARP-6. RESULTS: CPPD and NAV alone showed a dose-dependent effect on cell viability. Cytostatic drugs combined with EP revealed increased anticancer activity. Lower doses of CPPD or NAV delivered by EP were as effective as higher doses of these drugs without EP. The electrochemotherapeutic protocols increased the number of apoptotic cells and increased immunoreactivity of PARP-6. Our results indicated higher sensitivity of H69AR cells to NAV supported by EP. CONCLUSION: In SCLC cells, an increased anticancer activity was potentiated by exposure of cells to high intensity electric pulses and low drug doses. It is suggested that this method could be effectively applied in the treatment of lung cancer.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Eletroquimioterapia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Vinorelbina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos
16.
BMJ Case Rep ; 12(7)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315840

RESUMO

Paraneoplastic syndromes (PS) are a rare presentation of cancer, most commonly associated with small cell lung cancer (SCLC), breast cancer and haematologic malignancies. The diagnosis of PS is challenging because it could affect multiple organ systems and it may present before the tumour is visible by imaging. We report a malignant tumour diagnosed in a male patient who referred long-term paraesthesia and proximal muscle strength loss. After ruling out common causes of polyneuropathy, the anti-SOX1 antibody gave light to the diagnosis. A pulmonary opacity in the upper right lobe was observed in the chest X-ray and a pulmonary tumour was later confirmed by CT scan. The biopsy of the cervical lymphadenopathy determined an SCLC, which caused a PS called Lambert-Eaton myasthenic syndrome (LEMS). Our case raises awareness of a rare PS presentation, which can be diagnosed by specific antibodies, allowing early diagnosis and treatment of lung cancer.


Assuntos
Síndrome Miastênica de Lambert-Eaton/sangue , Síndromes Paraneoplásicas/diagnóstico , Parestesia/etiologia , Fatores de Transcrição SOXB1/antagonistas & inibidores , Carcinoma de Pequenas Células do Pulmão/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoanticorpos/sangue , Diagnóstico Diferencial , Eletromiografia/métodos , Humanos , Síndrome Miastênica de Lambert-Eaton/complicações , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Masculino , Síndromes Paraneoplásicas/fisiopatologia , Fatores de Transcrição SOXB1/sangue , Biópsia de Linfonodo Sentinela/métodos , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
17.
Gene ; 713: 143964, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279707

RESUMO

This study aimed to investigate single-nucleotide polymorphisms (SNPs) associated with lobaplatin-induced thrombocytopenia in patients with advanced lung cancer in China. Thirty-nine patients who received lobaplatin-based chemotherapy in the 307 Hospitals of Chinese People's Liberation Army from April 2017 to March 2018 were enrolled as study subjects. Peripheral blood DNA was extracted, and 79 candidate SNP positions were selected. A Sanger sequencing platform was employed to measure genotypes for locating the SNP positions associated with lobaplatin-induced thrombocytopenia. Of the 79 candidate genes, SNPs rs342275 and rs7694379 were significantly associated with lobaplatin-induced decrease in platelet (PLT) count (P < 0.05). SNPs rs342275, rs342293, rs11789898, and rs17824620 showed significant association with lobaplatin-induced lowest PLT counts (P < 0.05). SNPs rs342275, rs342293, rs11789898, rs17824620, and rs7694379 can be used as predictors of thrombocytopenia induced by lobaplatin-based chemotherapy in patients with advanced lung cancer in China.


Assuntos
Adenocarcinoma/tratamento farmacológico , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Ciclobutanos/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Polimorfismo de Nucleotídeo Único , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Trombocitopenia/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , China , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/genética
18.
BMC Cancer ; 19(1): 602, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215481

RESUMO

BACKGROUND: Chemo-resistance is one of the major challenges in the therapy of small cell lung cancer (SCLC). Multiple mechanisms are thought to be involved in chemo-resistance during SCLC treatment, but unfortunately, these mechanisms have not been well elucidated. Herein, we investigated the role of miRNA in the resistance of SCLC cells to doxorubicin (Dox). METHODS: MiRNA microarray analysis revealed that several miRNAs, including miR-7-5p, were specifically decreased in Dox-resistant SCLC cells (H69AR) compared to parental cells (H69). The expression level of miR-7-5p was confirmed by qRT-PCR in Dox-resistant cells (H69AR and H446AR cells) and their parental cells. Bioinformatic analysis indicated that poly ADP-ribose polymerase 1 (PARP1) is a direct target of miR-7-5p. The binding sites of miR-7-5p in the PARP1 3' UTR were verified by luciferase reporter and Western blot assays. To investigate the role of miR-7-5p in the chemo-resistance of SCLC cells to doxorubicin, mimic or inhibitor of miR-7-5p was transfected into SCLC cells, and the effect of miR-7-5p on homologous recombination (HR) repair was analyzed by HR reporter assays. Furthermore, the expression of HR repair factors (Rad51 and BRCA1) induced by doxorubicin was detected by Western blot and immunofluorescent staining in H446AR cells transfected with miR-7-5p mimic. RESULTS: The expression level of miR-7-5p was remarkably reduced (4-fold) in Dox-resistant SCLC cells (H69AR and H446AR cells) compared with that in parental cells (H69 and H446 cells). Poly ADP-ribose polymerase 1 (PARP1) is a direct target of miR-7-5p, and PARP1 expression was downregulated by miR-7-5p. MiR-7-5p impeded Dox-induced HR repair by inhibiting the expression of HR repair factors (Rad51 and BRCA1) that resulted in resensitizing SCLC cells to doxorubicin. CONCLUSIONS: Our findings provide evidence that miR-7-5p targets PARP1 to exert its suppressive effects on HR repair, indicating that the alteration of the expression of miR-7-5p may be a promising strategy for overcoming chemo-resistance in SCLC therapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Neoplasias Pulmonares/genética , MicroRNAs/farmacologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Reparo do DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Reparo de DNA por Recombinação/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Ubiquitina-Proteína Ligases/metabolismo
19.
Zhongguo Fei Ai Za Zhi ; 22(6): 355-362, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31196369

RESUMO

Small cell lung cancer (SCLC) is a refractory cancer with high degree of malignancy, rapid disease progression, poor prognosis and easy recurrence. In the past 30 years, the traditional treatment of SCLC, mainly chemotherapy and radiotherapy, has not changed significantly, and the effective treatment method for clinical needs is extremely urgent. The rapid development of precision medicine has revealed the molecular biological characteristics of SCLC, so its diagnosis and treatment will into a new era. At present, some studies have shown that anti-angiogenic drugs, immunotherapy and so on have improved the efficacy of SCLC treatment to some extent, and there are more studies on the diagnosis and treatment of SCLC, so a new field of SCLC treatment are coming and bringing more survival benefits to patients. New studies on targeted therapy, anti-angiogenesis drugs and immunotherapy of molecular pathology of SCLC are emerging. This paper reviews the new diagnosis and treatment methods of SCLC to provide new guidance for its clinical treatment.
.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Fatores Imunológicos/administração & dosagem , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Animais , Humanos , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico
20.
Eur J Cancer Care (Engl) ; 28(5): e13120, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31184792

RESUMO

AIM: A randomised controlled trial (RCT) was implemented to verify the feasibility and acceptability of cognitive education in the format of mind maps for increasing perceived control and decreasing the symptom distress of lung cancer patients who were receiving chemotherapy. METHODS: A total of 136 lung cancer patients who were receiving chemotherapy were randomised using stratified blocks (1:1 ratio, from March 2016 to April 2017). The intervention group was given cognitive education in the format of mind maps. The control group was provided conventional education. The primary outcomes were perceived control, including cancer experience and cancer efficacy; the secondary outcomes included symptom distress (arising from fatigue, distress, sleep disturbance, poor appetite, drowsiness, shortness of breath, etc.). The Mann-Whitney U test, chi-squared test, two-sample t test and repeated measurement analysis of variance were used. RESULTS: Ninety-four patients completed the final study. The results of the repeated measurement analysis of variance indicated that at the 8th or 12th week following cognitive education intervention in the format of mind maps, the cancer experience, cancer efficacy (except personal efficacy) and symptom distress (arising from fatigue, distress, sleep disturbance, and sadness and its total scores) of the patients in the intervention group were considerably improved compared with those of the control group (p < 0.05). The longer the intervention was, the higher the level of the patients' perceived control was and the lower the degree of patient symptom distress was (p < 0.05). CONCLUSIONS: Our findings suggest that cognitive education in the format of mind maps could improve perceived control and decrease the symptom distress of lung cancer patients who were receiving chemotherapy and that it was feasible and acceptable. Cognitive education in the format of mind maps was found to be an effective teaching tool for lung cancer patients who were receiving chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/psicologia , Controle Interno-Externo , Neoplasias Pulmonares/psicologia , Educação de Pacientes como Assunto/métodos , Carcinoma de Pequenas Células do Pulmão/psicologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Cognição , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/fisiopatologia , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Autoeficácia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA