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1.
J Int Med Res ; 49(2): 300060520982687, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527860

RESUMO

OBJECTIVE: To evaluate the efficacy of rapid on-site cytological evaluation (ROSE) in determining specimen adequacy and diagnostic accuracy in the interventional diagnosis of lung lesions. METHODS: This retrospective study included 127 consecutive cases of lung lesions, which were sampled by bronchoscopy or transthoracic fine needle aspiration, and diagnosed on ROSE followed by histopathology. ROSE was performed by a trained pulmonologist and the diagnosis of ROSE was compared with the final diagnosis. RESULTS: The sensitivity of ROSE in determining adequacy of specimens was 97.5% and specificity in determining inadequacy was 85.7%. The diagnostic efficacy of ROSE for assessing malignancy (sensitivity of 94.5% and specificity of 100%) and non-malignancy (sensitivity of 97.8% and specificity of 100%) was excellent. The sensitivity of ROSE for diagnosing small cell carcinoma (100%) was highest, followed by adenocarcinoma (89.2%) and squamous cell carcinoma (75.0%). Performance of ROSE by a trained pulmonologist also determined tuberculosis with a high diagnostic sensitivity (83.3%) and specificity (100%). CONCLUSIONS: A trained pulmonologist can reliably carry out ROSE to ensure the adequacy of the sample, distinguish between malignancy and non-malignancy, and make a preliminary diagnosis in a large number of cases.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Técnicas Histológicas/métodos , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Biópsia por Agulha Fina , Broncoscopia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Pneumologistas , Estudos Retrospectivos , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/cirurgia
3.
Anticancer Res ; 41(1): 91-99, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419802

RESUMO

BACKGROUND/AIM: Small-cell lung cancer (SCLC) is aggressive and confers poor prognosis. Although SCLC shows more response to chemotherapy than other types of lung cancer, it is difficult to cure because of its frequent recurrence. New drugs and molecular targets need to be identified. MATERIALS AND METHODS: We investigated the effect of nelfinavir, an HIV protease inhibitor, on SCLC cells and in preclinical treatment studies using SCLC patient-derived xenograft (PDX) mouse models. RESULTS: Nelfinavir inhibited SCLC cell proliferation and induced cell death in vitro, which was caused by induction of the unfolded protein response (UPR), inhibition of mammalian/mechanistic target of rapamycin (mTOR) activation, and reduction in the expression of SCLC-related molecules such as achaete-scute homolog 1 (ASCL1). In vivo, nelfinavir inhibited the growth of SCLC PDX tumors, which correlated with the induction of UPR and reduced expression of ASCL1. CONCLUSION: Nelfinavir is highly effective in SCLC in vitro and in vivo, suggesting possible incorporation of nelfinavir into clinical trials for patients with SCLC.


Assuntos
Antineoplásicos/farmacologia , Reposicionamento de Medicamentos , Nelfinavir/farmacologia , Animais , Antineoplásicos/uso terapêutico , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Nelfinavir/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Serina-Treonina Quinases TOR/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Medicine (Baltimore) ; 99(51): e22559, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371055

RESUMO

RATIONALE: Lung cancer is a leading cause of cancer-related deaths. Smoking is major risk factor for initial and subsequent lung cancer especially in active smokers. Treatment of subsequent lung cancer depends on whether it is synchronous or metachronous. We report a rare case of triple metachronous lung cancer and review of literature of patients with triple metachronous cancers. This will be the second case reported of triple metachronous lung cancer. PATIENT CONCERNS: A 60-year-old male, active smoker with diabetes mellitus, chronic obstructive pulmonary disease (COPD) and peripheral arterial disease presented with cough and hemoptysis. Initial computed tomography (CT) scan showed right upper lobe spiculated mass. DIAGNOSIS: He underwent transthoracic needle biopsy for right upper lobe mass, showing primary lung adenocarcinoma (ADC)-Stage-IIIA. He continued to smoke and 9-years later had new left upper lobe spiculated nodule, which on surgical resection showed squamous cell carcinoma (SCC)-Stage-IA1. Despite counselling on smoking cessation, he was unable to quit. Six months later, he presented with shortness of breath and CT chest showing right hilar adenopathy in right upper and lower lobes. He underwent transbronchial biopsies of lesion which showed small cell lung carcinoma (SCLC). INTERVENTIONS: His initial lung ADC-Stage-IIIA, was treated with chemotherapy, weekly thoracic radiation and additional chemotherapy cycles. Nine years later, his left upper lobe mass showing SCC-Stage-IA1 was deemed curative after apical resection and he was kept on surveillance. Six months later, after diagnosis of SCLC in right upper and lower lobe, patient was not a candidate for systemic chemotherapy due to poor performance status and opted for hospice care. OUTCOMES: His initial lung ADC-Stage-IIIA showed complete radiological response with chemotherapy and radiation. Subsequent SCC-Stage-IA1 was deemed curative after resection. Due to his poor performance status, he was not a candidate for chemotherapy for SCLC and patient opted for hospice care. LESSONS: Smoking is a major risk factor for developing lung cancer and with continued smoking, patients are at higher risk for developing subsequent primary lung cancers. We recommend, patients with lung cancer must quit smoking, and those who do not, should remain on long-term surveillance.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Uso de Tabaco/patologia , Humanos , Masculino , Pessoa de Meia-Idade
5.
BMC Cancer ; 20(1): 1040, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121456

RESUMO

BACKGROUND: The COVID-19 pandemic is predicted to significantly affect patients with lung cancer, owing to its rapid progression and high mortality. Studies on lung cancer diagnosis and treatment during an epidemic are lacking. We analyzed the impact of COVID-19 on lung cancer diagnosis in Korea, where lung cancer incidence continues to rise. METHODS: The number of newly diagnosed lung cancer cases in three university-affiliated hospitals during the pandemic and their clinical features were compared with lung cancer cases diagnosed during the same period in the past 3 years. The effectiveness of measures taken by the study hospitals to prevent nosocomial transmission was reviewed. RESULTS: A total of 612 patients were diagnosed with lung cancer from February through June, 2017-2020. During the pandemic, the number of patients who sought consultation at the division of pulmonology of study hospitals dropped by 16% from the previous year. Responding to the pandemic, the involved hospitals created physically isolated triage areas for patients with acute respiratory infection symptoms. Wide-range screening and preventive measures were implemented, thus minimizing the delay in lung cancer diagnosis. No patient acquired COVID-19 due to hospital exposure. The proportion of patients with stage III-IV non-small-cell lung cancer (NSCLC) significantly increased (2020: 74.7% vs. 2017: 57.9%, 2018: 66.7%, 2019: 62.7%, p = 0.011). The number of lung cancers diagnosed during this period and the previous year remained the same. CONCLUSIONS: The proportion of patients with advanced NSCLC increased during the COVID-19 pandemic.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Infecções por Coronavirus , Neoplasias Pulmonares/diagnóstico , Pandemias , Pneumonia Viral , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Controle de Infecções/métodos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , República da Coreia/epidemiologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Triagem
6.
Zhonghua Zhong Liu Za Zhi ; 42(8): 624-628, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867452

RESUMO

Small cell lung cancer (SCLC), a special type of lung cancer, is a highly malignant neuroendocrine tumor with strong invasiveness and rapid progression. SCLC is sensitive to radiotherapy and chemotherapy, so radiotherapy and chemotherapy have been the main first-line treatment of SCLC. However, it is easy to develop drug resistance after treatment. Therefore, the study of anti-angiogenic therapy has attracted more and more attention. At present, anti-angiogenic drugs mainly focus on four categories: monoclonal antibodies (such as bevacizumab), endogenous angiogenesis inhibitors (such as endostar), anti-angiogenic fusion protein (such as aflibercept) and small molecular tyrosine kinase inhibitors (such as anlotinib). There are still some bottlenecks in the research and clinical application of antiangiogenic drugs. It is the right direction to explore better combination therapy and effective dual-field and multi-target drugs.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Neovascularização Patológica/patologia , Medicina de Precisão , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
7.
Asian Cardiovasc Thorac Ann ; 28(9): 583-591, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32878450

RESUMO

BACKGROUND: According to practice guidelines, patients with clinical stage T1-2 node-negative small-cell lung cancer are candidates for surgical resection. However, the role of pneumonectomy in small-cell lung cancer patients is not well understood. The objective of this study was to assess the extent to which pneumonectomy is used and to evaluate the survival implications for small-cell lung cancer patients who underwent pneumonectomy. METHODS: A total of 106 small-cell lung cancer patients who underwent pneumonectomy between 2006 and 2016 and met the study criteria were identified in the National Cancer Database. Demographics and treatment regimens are described, and overall survival was assessed using Kaplan-Meier and log-rank tests. RESULTS: The most common treatment was surgery with adjuvant chemotherapy, followed by surgery only and surgery with neoadjuvant therapy. The 5-year overall survival for the entire cohort after pneumonectomy was 23%. In subgroup analysis, the 5-year overall survival was 30% for guideline-concordant clinical stage I patients and 28% for clinical stage II/III patients who underwent pneumonectomy. There was no statistical difference in survival according to pathologic N disease. Patients with a right-sided pneumonectomy had higher mortality than patients with a left-sided pneumonectomy. CONCLUSIONS: This study suggests a role for pneumonectomy in clinical stage I and potentially some clinical stage II and III small-cell lung cancer patients. Right-sided pneumonectomy is associated with higher mortality and should be approached with caution. Despite declining trends over the past decades, pneumonectomy is still an effective treatment that is able to achieve acceptable survival outcomes.


Assuntos
Neoplasias Pulmonares/cirurgia , Pneumonectomia/tendências , Carcinoma de Pequenas Células do Pulmão/cirurgia , Idoso , Quimioterapia Adjuvante , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
8.
Anticancer Res ; 40(9): 4947-4960, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878783

RESUMO

BACKGROUND/AIM: This study aimed to investigate the anticancer effects and potential mechanisms of sclareol in a human small cell lung carcinoma (SCLC) cell line. MATERIALS AND METHODS: Cell viability was determined by the MTT assay. Cell cycle, apoptosis and caspase activity were evaluated by flow cytometry. Cell cycle and DNA damage related protein expression was determined by western blotting. In vivo evaluation of sclareol was carried out in xenografted tumor mice models. RESULTS: Sclareol significantly reduced cell viability, induced G1 phase arrest and subsequently triggered apoptosis in H1688 cells. In addition, this sclareol-induced growth arrest was associated with DNA damage as indicated by phosphorylation of H2AX, activation of ATR and Chk1. Moreover, in vivo evaluation of sclareol showed that it could inhibit tumor weight and volume in a H1688 xenograft model. CONCLUSION: Sclareol might be a novel and effective therapeutic agent for the treatment of SCLC patients.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Diterpenos/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Lancet Oncol ; 21(9): 1224-1233, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888454

RESUMO

BACKGROUND: Topotecan is currently the only drug approved in Europe in a second-line setting for the treatment of small-cell lung cancer. This study investigated whether the doublet of carboplatin plus etoposide was superior to topotecan as a second-line treatment in patients with sensitive relapsed small-cell lung cancer. METHODS: In this open-label, randomised, phase 3 trial done in 38 hospitals in France, we enrolled patients with histologically or cytologically confirmed advanced stage IV or locally relapsed small-cell lung cancer, who responded to first-line platinum plus etoposide treatment, but who had disease relapse or progression at least 90 days after completion of first-line treatment. Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group performance status 0-2. Enrolled patients were randomly assigned (1:1) to receive combination carboplatin plus etoposide (six cycles of intravenous carboplatin [area under the curve 5 mg/mL per min] on day 1 plus intravenous etoposide [100 mg/m2 from day 1 to day 3]) or oral topotecan (2·3 mg/m2 from day 1 to day 5, for six cycles). Randomisation was done using the minimisation method with biased-coin balancing for ECOG performance status, response to the first-line chemotherapy, and treatment centre. The primary endpoint was progression-free survival, which was centrally reviewed and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02738346. FINDINGS: Between July 18, 2013, and July 2, 2018, we enrolled and randomly assigned 164 patients (82 in each study group). One patient from each group withdrew consent, therefore 162 patients (81 in each group) were included in the intention-to-treat population. With a median follow-up of 22·7 months (IQR 20·0-37·3), median progression-free survival was significantly longer in the combination chemotherapy group than in the topotecan group (4·7 months, 90% CI 3·9-5·5 vs 2·7 months, 2·3-3·2; stratified hazard ratio 0·57, 90% CI 0·41-0·73; p=0·0041). The most frequent grade 3-4 adverse events were neutropenia (18 [22%] of 81 patients in the topotecan group vs 11 [14%] of 81 patients in the combination chemotherapy group), thrombocytopenia (29 [36%] vs 25 [31%]), anaemia (17 [21%] vs 20 [25%]), febrile neutropenia (nine [11%] vs five [6%]), and asthenia (eight [10%] vs seven [9%]). Two treatment-related deaths occurred in the topotecan group (both were febrile neutropenia with sepsis) and no treatment-related deaths occurred in the combination group. INTERPRETATION: Our results suggest that carboplatin plus etoposide rechallenge can be considered as a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer. FUNDING: Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie).


Assuntos
Carboplatina/administração & dosagem , Etoposídeo/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Etoposídeo/efeitos adversos , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Topotecan/efeitos adversos
10.
Am J Clin Oncol ; 43(9): 670-675, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889839

RESUMO

During the course of therapy, patients with small cell lung cancer have been noted to develop transformation to non-small cell lung cancer and conversely, patients with non-small cell lung cancer have had transformation to small cell lung cancer or other non-small cell histologies. Transformation may occur after prior tyrosine kinase inhibitors, chemotherapy, immunotherapy or radiation therapy. These changes reflect on the overlapping biology of these cell types and the clinical need for re-biopsy at times of disease progression. The optimum therapy after transformation will depend upon prior therapies received, the functional capacity of the patient, and further research to define the best therapy options.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Transformação Celular Neoplásica , Receptores ErbB/genética , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Mutação , Nivolumabe/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/terapia
11.
J Cancer Res Ther ; 16(4): 752-756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930114

RESUMO

Background: In extensive-disease-small cell lung cancer (ED-SCLC), the median survival is 8-10 months and 2-year survival is <5%. Primary tumor progression occurs in 90% of patients approximately within 1 year. The role of consolidative thoracic radiotherapy (C-TRT) for the postchemotherapy residue with the aim of improving local control (LC) and survival is currently of great interest. The objective of this study is to determine the effectiveness of C-TRT on LC, progression-free survival (PFS), and overall survival (OS) in ED-SCLC. Materials and Methods: Medical records of patients diagnosed as SCLC between January 2010 and December 2015 were evaluated retrospectively. Patients who received C-TRT were identified. Pre- and post-chemotherapy radiological evaluations, radiotherapy schedules, relapse patterns, toxicity incidence, LC, PFS, and OS were analyzed. Results: Among 552 SCLC patients, 26 ED-SCLC patients who underwent C-TRT were analyzed. Median follow-up was 7.5 months (range, 6.5-8.5 months). Nearly 50% of the patients had >4 metastatic lesions. Restaging was performed mostly by positron emission tomography/computed tomography and cranial magnetic resonance imaging. All patients had complete or near-complete response distantly. C-TRT was 10 × 300 cGy (n = 1), 23 × 200 cGy (n = 2), 25 × 200 cGy (n = 7), 30 × 200 cGy (n = 12), and 33 × 200 cGy (n = 4). There was no toxicity ≥ Grade 3. LC rate was 77%; there was no isolated local relapse. PFS was 3 months. Median survival was 13 months. The 1- and 2-year OS rates were 62% and 8%, respectively. Conclusion: In ED-SCLC patients, C-TRT may prevent isolated local recurrence and may improve 1-year survival. This survival improvement might be the reflection of high intrathoracic control achieved in 77% of patients.


Assuntos
Neoplasias Pulmonares/radioterapia , Recidiva Local de Neoplasia/radioterapia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Indução de Remissão , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Resultado do Tratamento
12.
J Cancer Res Ther ; 16(4): 764-770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930116

RESUMO

Background: The benefits of second-line chemotherapy on the overall survival (OS) of small-cell lung cancer (SCLC) patients might be confounded by subsequent therapies. In this study, we aimed to determine the influence of progression-free survival (PFS) and postprogression survival (PPS) on OS after second-line chemotherapy in patients with refractory SCLC treated with amrubicin monotherapy. Materials and Methods: We analyzed the data of 35 patients with refractory SCLC who were treated with amrubicin monotherapy as second-line chemotherapy between July 2005 and December 2015. The correlations of PFS and PPS with OS were statistically analyzed at the individual level using Spearman's rank correlation and linear regression analyses. Results: The correlation between PPS and OS was strong (r = 0.88, P < 0.05, R2 = 0.87), while that between PFS and OS was weak (r = 0.60, P < 0.05, R2 = 0.15). The number of regimens administered after disease progression postsecond-line chemotherapy was significantly associated with PPS (P = 0.003). Conclusions: OS is more strongly linked to PPS than to PFS in refractory SCLC patients who undergo amrubicin monotherapy as a second-line treatment. These results suggest that treatments administered after second-line chemotherapy affect the OS of refractory SCLC patients treated with amrubicin monotherapy.


Assuntos
Antraciclinas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Antineoplásicos/uso terapêutico , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida
14.
J Cancer Res Clin Oncol ; 146(10): 2519-2534, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32648226

RESUMO

PURPOSE: Metastasis is an unavoidable event happened among almost all small cell lung cancer (SCLC) patients. However, the molecular driven factors have not been elucidated. Recently, a novel hydrolase called cell migration inducing hyaluronidase (CEMIP) triggered both migration and invasion in many tumors but not SCLC. Therefore, in this study, we verified that CEMIP promoted migration and invasion in SCLC and applied proteomics analysis to screen out potential target profiles and the signaling pathway related to CEMIP regulation. METHOD: Immunofluorescence was conducted to exam the expression of CEMIP on SCLC and paired adjacent normal tissues among enrollment. RT-qPCR and Western blot (WB) assays were conducted to valuate cellular protein and mRNA expression of CEMIP and EMT markers. Lentivirus-CEMIP-shRNAs and CEMIP plasmid were used for expression manipulating. Changes of cellular migration and invasion were tested through transwell assays. Tandem Mass Tag (TMT) peptide labeling coupled with LC-MS/MS was used for quantifying proteins affected by reducing expression of CEMIP on H446 cells. RESULTS: The expression of CEMIP showed 1.64 ± 0.16-fold higher in SCLC tissues than their normal counterpart. Decreasing the expression of CEMIP on SCLC cells H446 regressed both cellular migration and invasion ability, whereas the promoting cellular migration and invasion was investigated through over-expressing CEMIP on H1688. Proteomic and bioinformatics analysis revealed that total 215 differentially expressed proteins (DEPs) that either their increasing or decreasing relative expression met threshold of 1.2-fold changes with p value ≤ 0.05. The dramatic up-regulated DEPs included an unidentified peptide sequence (encoded by cDNA FLJ52096) SPICE1 and CRYAB, while the expression of S100A6 was largely down-regulated. DEPs mainly enriched on caveolae of cellular component, calcium ion binding of biological process and epithelial cell migration of molecular function. KEGG enrichment indicated that DEPs mainly exerted their function on TGF-ß, GABAergic synapse and MAPK signaling pathway. CONCLUSION: It is the first report illustrating that CEMIP might be one of the metastatic triggers in SCLC. And also, it provided possible molecular mechanism cue and potential downstream target on CEMIP-induced cellular migration and invasion on SCLC.


Assuntos
Hialuronoglucosaminidase/metabolismo , Neoplasias Pulmonares/metabolismo , Proteoma/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Idoso , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Feminino , Imunofluorescência , Humanos , Hialuronoglucosaminidase/biossíntese , Hialuronoglucosaminidase/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Transdução de Sinais , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia
15.
Oncology ; 98(11): 749-754, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32663833

RESUMO

Lung cancer is a leading cause of cancer death in the United States and around the world. Approximately 13% of lung cancers are small cell lung cancer (SCLC). SCLC is generally classified as a limited-stage and extensive-stage disease depending on the extent of involvement. For patients with the extensive-stage disease, until recently, chemotherapy alone has been the recommended treatment, although radiotherapy could be used in select patients for palliation of symptoms. The standard of care for extensive-stage SCLC is platinum doublet chemotherapy with either cisplatin or carboplatin in combination with etoposide. Even though first-line therapy has an initial response rate of 60-80%, the prognosis is poor, with overall survival of 10-12 months. The only FDA-approved second line of therapy is topotecan, approved both as an intravenous formulation as well as an oral formulation, with response rates of 6-12% in chemorefractory disease and 15-37% in chemosensitive disease. Immunotherapy has recently been approved as a first-line agent in metastatic SCLC in combination with chemotherapy. It is also approved as a third-line agent in metastatic SCLC after the failure of two chemotherapy regimens. The FDA approved four drugs, two of them being PD-1 inhibitors (pembrolizumab, nivolumab), and two of them being PD-L1 inhibitors (atezolizumab and durvalumab) in SCLC. This review article summarizes the significance of immunotherapy in the treatment of extensive-stage SCLC, its side effects, and limitations.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia
16.
ESMO Open ; 5(Suppl 3)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32581069

RESUMO

The COVID-19 pandemic, characterised by a fast and global spread during the first months of 2020, has prompted the development of a structured set of recommendations for cancer care management, to maintain the highest possible standards. Within this framework, it is crucial to ensure no disruption to essential oncological services and guarantee the optimal care.This is a structured proposal for the management of lung cancer, comprising three levels of priorities, namely: tier 1 (high priority), tier 2 (medium priority) and tier 3 (low priority)-defined according to the criteria of the Cancer Care Ontario, Huntsman Cancer Institute and Magnitude of Clinical Benefit Scale.The manuscript emphasises the impact of the COVID-19 pandemic on lung cancer care and reconsiders all steps from diagnosis, staging and treatment.These recommendations should, therefore, serve as guidance for prioritising the different aspects of cancer care to mitigate the possible negative impact of the COVID-19 pandemic on the management of our patients.As the situation is rapidly evolving, practical actions are required to guarantee the best patients' treatment while protecting and respecting their rights, safety and well-being. In this environment, cancer practitioners have great responsibilities: provide timely, appropriate, compassionate and justified cancer care, while protecting themselves and their patients from being infected with COVID-19. In case of shortages, resources must be distributed fairly. Consequently, the following recommendations can be applied with significant nuances, depending on the time and location for their use, considering variable constraints imposed to the health systems. An exceptional flexibility is required from cancer caregivers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Infecções por Coronavirus/epidemiologia , Assistência à Saúde/métodos , Neoplasias Pulmonares/terapia , Pneumonia Viral/epidemiologia , Carcinoma de Pequenas Células do Pulmão/terapia , Assistência Ambulatorial , Betacoronavirus , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Humanos , Neoplasias Pulmonares/patologia , Oncologia , Estadiamento de Neoplasias , Pandemias , Pneumonectomia , Guias de Prática Clínica como Assunto , Radioterapia (Especialidade) , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão/patologia , Oncologia Cirúrgica , Telemedicina , Tempo para o Tratamento , Tomografia Computadorizada por Raios X , Triagem
17.
Clin Chest Med ; 41(2): 269-280, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32402362

RESUMO

Small cell lung cancer (SCLC) is an aggressive malignancy and carries a poor prognosis with limited effective treatments in the advanced setting. SCLC is characterized by a high tumor mutation burden and alterations in Notch signaling and DNA damage repair pathways, providing rationale for the use of immunotherapy and targeted therapies. Immunotherapies have led to the most significant advances in treating SCLC in decades, and several promising targeted approaches have emerged from the increased understanding of the biology of SCLC. However, responses to these novel approaches are far from universal, and efforts to refine these therapies are ongoing.


Assuntos
Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Humanos , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia
18.
Mol Carcinog ; 59(8): 967-979, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32424979

RESUMO

Drug resistance is the leading cause for rapid progression and relapse in small-cell lung cancer (SCLC) patients. Thus overcoming drug resistance still remains to be urgently resolved during SCLC treatment. Here, we found p62/SQSTM1 was enriched in SCLC spheroids, a subpopulation possessing cancer stem-like properties, which is responsible for cancer relapse and metastasis. Subsequent functional assays in vitro showed that short hairpin RNA (shRNA)-mediated p62 knockdown increased sensitivity of SCLC cell lines to cisplatin (DDP), whereas lentivirus-mediated p62 ectopic overexpression diminished DDP-induced cytotoxicity in both NCI-H446 and NCI-H1688 cell lines. Moreover, ectopic p62 overexpression promoted DDP resistance of NCI-H446 cells-derived tumor xenografts in immunodeficient mice in vivo, as indicated by accelerated tumor growth rate and reduced fluorescent activity of cleaved caspase-3. Gene expression profiling analysis revealed that p62 was positively correlated with neuronal precursor cell-expressed, developmentally downregulated gene 9 (NEDD9) expression level. Consistently, NEDD9 messenger RNA (mRNA) level was decreased upon p62 suppression by small interfering RNA (siRNA) and increased with p62 transient overexpression in SCLC cell lines, suggesting that p62 positively regulated NEDD9 mRNA. Depletion of NEDD9 by siRNA, to a large extent, reversed p62-overexpressed SCLC cells to DDP-induced cytotoxicity, implying NEDD9 might act as a downstream target which was in charge of p62-mediated DDP resistance. Taken together, our findings uncovered a previously unknown role of p62 in the regulation of SCLC drug resistance, assigning p62 as an attractive target for SCLC treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteína Sequestossoma-1/antagonistas & inibidores , Carcinoma de Pequenas Células do Pulmão/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , RNA Interferente Pequeno/genética , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Tunis Med ; 98(1): 85-89, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32395782

RESUMO

The metastases of bronchopulmonary cancer in the submandibular gland are infrequent. We report a case of metastasis in the submandibular gland in a patient with small cell lung cancer who had chemotherapy with disease stability.


Assuntos
Neoplasias Pulmonares/patologia , Neoplasias das Glândulas Salivares/secundário , Carcinoma de Pequenas Células do Pulmão/patologia , Glândula Submandibular/patologia , Antineoplásicos/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Recidiva , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Falha de Tratamento
20.
Zhonghua Zhong Liu Za Zhi ; 42(4): 336-339, 2020 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-32375451

RESUMO

Objective: To investigate the outcomes of limited stage small cell lung cancer (L-SCLC) undergoing surgical therapy and to explore the value of adjuvant therapy for those patients. Methods: A retrospective analysis was initialed for the L-SCLC patients who underwent the surgical treatment in the Zhongnan Hospital of Wuhan University from January 2012 to December 2018. The median disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method. Cox regression was used to explore the prognostic factors. Results: A total of 44 patients were included in our study. The median DFS was 25 months, 1- and 2-year DFS rate were 70.2% and 51.9%, respectively. The median OS was 41 months, 1- and 2- year OS rate were 88.4% and 69.9%, respectively. Multivariate analysis showed male (RR=6.56, P=0.03), T3-4 (RR=6.23, P=0.01), pathological lymph node metastasis (RR=6.52, P=0.03) and adjuvant radiotherapy (RR=0.13, P=0.002) were associated with disease relapse significantly. Moreover, pathological lymph node metastasis (RR=3.62, P=0.01) coupled with sufficient adjuvant chemotherapy (≥4 cycles) (RR=0.12, P=0.01) were independent prognostic factors of OS. Conclusions: Surgical therapy may be an alternative primary treatment for L-SCLC. Additional adjuvant radiotherapy can reduce the risk of recurrence. Giving sufficient course of adjuvant chemotherapy can improve OS.


Assuntos
Quimioterapia Adjuvante/métodos , Neoplasias Pulmonares/terapia , Pneumonectomia/métodos , Radioterapia Adjuvante/métodos , Carcinoma de Pequenas Células do Pulmão/terapia , Adulto , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
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