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1.
Front Immunol ; 12: 745769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867972

RESUMO

Tumor necrosis factor (TNF) family members participate in the body's antitumor immunity response and influence tumor prognosis and treatment response. However, little is known about the roles of TNF family members in small cell lung cancer (SCLC). Therefore, we conducted the first comprehensive investigation of TNF family members in patients with SCLC, with the goal of using them to predict prognosis and chemotherapy benefit. Abnormal genetic alterations and expression of TNF family members were found to be widespread in SCLC patients. Using LASSO Cox regression analysis, we constructed a TNF family-based signature that separated SCLC patients in the training set (n=77) into high- and low-risk groups with distinct survival and chemotherapy benefit, and the signature was well-validated in the validation set (n=137) by RT-qPCR. Importantly, the signature exhibited superior predictive performance and was identified as a novel independent prognostic factor. Additionally, different immune phenotypes were found between the low-risk and high-risk groups, and high-risk patients had higher CMTM6 expression, suggesting that these patients could benefit from therapeutic methods targeting CMTM6. We constructed the first clinically applicable TNF family-based signature for predicting prognosis and chemotherapy benefit for patients with SCLC. The findings reported here provide a new method for predicting the prognosis of SCLC patients and optimizing clinical management.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Fatores de Necrose Tumoral/genética , Idoso , Área Sob a Curva , Quimioterapia Adjuvante , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/fisiopatologia , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , Curva ROC , Receptores do Fator de Necrose Tumoral/biossíntese , Receptores do Fator de Necrose Tumoral/genética , Estudos Retrospectivos , Risco , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Microambiente Tumoral/imunologia , Fatores de Necrose Tumoral/biossíntese
3.
Thorac Cancer ; 12(18): 2478-2486, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34337879

RESUMO

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is a common spirometric pattern that is associated with respiratory symptoms and higher mortality rates. However, the relationship between lung cancer and PRISm remains unclear. This study investigated the clinical characteristics of lung cancer patients with PRISm and the potential role of PRISm as a prognostic factor. METHODS: We retrospectively reviewed data collected from 2014 to 2015 in the Korean Association for Lung Cancer Registry. We classified all patients into three subgroups according to lung function as follows: normal lung function; PRISm (forced expiratory volume in 1 s [FEV1 ] < 80% predicted and FEV1 /forced vital capacity [FVC] ≥ 0.7); and chronic obstructive pulmonary disease (COPD; FEV1/FVC < 0.7). In non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the overall survival period was compared among the three subgroups. The prognostic factors were investigated using Cox regression analysis. RESULTS: Of the 3763 patients, 38.6%, 40.1%, and 21.3% had normal lung function, COPD, and PRISm, respectively. Patients with PRISm had poorer overall survival than those with COPD or normal lung function in NSCLC and SCLC (Mantel-Cox log-rank test, p < 0.05). In the risk-adjusted analysis, overall survival was independently associated with COPD (hazard ratio [HR] 1.209, p = 0.027) and PRISm (HR 1.628, p < 0.001) in NSCLC, but was only associated with PRISm (HR 1.629, p = 0.004) in SCLC. CONCLUSIONS: PRISm is a significant pattern of lung function in patients with lung cancer. At the time of lung cancer diagnosis, pre-existing PRISm should be considered a predictive factor of poor prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Espirometria/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia , Estudos Retrospectivos , Taxa de Sobrevida
4.
Genes Dev ; 35(11-12): 847-869, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34016693

RESUMO

ASCL1 is a neuroendocrine lineage-specific oncogenic driver of small cell lung cancer (SCLC), highly expressed in a significant fraction of tumors. However, ∼25% of human SCLC are ASCL1-low and associated with low neuroendocrine fate and high MYC expression. Using genetically engineered mouse models (GEMMs), we show that alterations in Rb1/Trp53/Myc in the mouse lung induce an ASCL1+ state of SCLC in multiple cells of origin. Genetic depletion of ASCL1 in MYC-driven SCLC dramatically inhibits tumor initiation and progression to the NEUROD1+ subtype of SCLC. Surprisingly, ASCL1 loss promotes a SOX9+ mesenchymal/neural crest stem-like state and the emergence of osteosarcoma and chondroid tumors, whose propensity is impacted by cell of origin. ASCL1 is critical for expression of key lineage-related transcription factors NKX2-1, FOXA2, and INSM1 and represses genes involved in the Hippo/Wnt/Notch developmental pathways in vivo. Importantly, ASCL1 represses a SOX9/RUNX1/RUNX2 program in vivo and SOX9 expression in human SCLC cells, suggesting a conserved function for ASCL1. Together, in a MYC-driven SCLC model, ASCL1 promotes neuroendocrine fate and represses the emergence of a SOX9+ nonendodermal stem-like fate that resembles neural crest.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição SOX9/genética , Carcinoma de Pequenas Células do Pulmão/genética , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Crista Neural/citologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Células-Tronco/citologia
5.
Thorac Cancer ; 12(5): 699-702, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33458956

RESUMO

Immune-checkpoint inhibitors (ICIs) provide a promising treatment option for advanced tumors including small cell lung cancer (SCLC). Nevertheless, in addition to immune-related adverse events (irAEs), an increased risk of infection including tuberculosis has been previously described. Here, we report a case of long-term remission of a patient with SCLC after reactivation of lung tuberculosis following ICI therapy. Our case illustrates the complexity of ICI-associated immune modulation in tuberculosis. Since new lesions in lung cancer patients are commonly associated with tumor progression, infections with mycobacterial tuberculosis may be underdiagnosed in lung cancer.


Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Tuberculose/induzido quimicamente , Adulto , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Indução de Remissão , Tuberculose/fisiopatologia
6.
Physiol Res ; 70(S3): S381-S386, 2021 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35099256

RESUMO

Sarcopenia is an independent risk factor for morbidity and mortality in patients suffering from small cell lung cancer (SCLC), however, a universal indicator of sarcopenia usable in clinical practice is still missing. A novel indicator for describing the severity of cancer could be helpful in tailoring the anti-tumor therapy. The aim of this study was to evaluate the computed tomography (CT) scans of total muscle area and radiation attenuation in patients suffering from small cell lung cancer. We used staging CT scans performed at the time of diagnosis to measure total muscle area (TMA) and average psoas density (PD) at level of the 3rd lumbar vertebra. TMA and PD were statistically evaluated in association with overall survival and disease staging. We used Mann-Whitney test and Spearman´s correlation coefficient for statistical testing and p-value under 0.05 was considered statistically significant. Retrospectively we examined 47 patients suffering from SCLC (mean age 65.05+/-7.3 years, BMI 23.97+/-4.4 kg/m2, BSA 1.77+/-0.2 m2, 30-day mortality was 4.3 % with 10 months median survival). As sarcopenia was pointed TMA under 55 and 39 cm2/m2 for men and women respectively. The sarcopenic patients had significantly shorter median survival (7 vs. 11 months, p=0.05). We observed a significant relationship between survival and performance status (Spearman´s correlation, R=-0.39, p=0.05). The patients were divided into two groups according to the extensive (ED, n=34) or limited (LD, n=13) form of the disease. We observed significant difference in PD (42.49+/-6.1 vs. 47.67+/-4.5 HU, p=0.006) between ED vs. LD groups.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Músculos Psoas/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Composição Corporal , Feminino , Nível de Saúde , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Músculos Psoas/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/mortalidade , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Fatores de Tempo
7.
Int J Radiat Oncol Biol Phys ; 107(2): 279-287, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142869

RESUMO

PURPOSE: Our purpose was to evaluate neurocognitive function (NCF) and clinical outcomes after early hippocampal avoidance (HA) prophylactic cranial irradiation (PCI) in limited disease (LD) small cell lung cancer (SCLC). METHODS AND MATERIALS: In a phase 2 trial, patients with LD SCLC received HA-PCI concomitant with the second cycle of chemotherapy and thoracic radiation therapy. All patients underwent objective NCF testing at baseline, 6 weeks, and 6 and 12 months after HA-PCI. NCF tests included Hopkins Verbal Learning Test Revised, Controlled Oral Word Association, and Trail Making Tests A and B. The primary endpoint was NCF decline at 6 months after HA-PCI. We assumed ≤30% of patients with no NCF decline to be unpromising. Secondary endpoints included brain metastases-free survival (BMFS), overall survival (OS), and safety of the concomitant treatment. RESULTS: Among the 44 patients enrolled in the trial, 38 had evaluable NCF assessment at 6 months after HA-PCI. The proportion of evaluable patients showing no NCF decline at 6 and 12 months was 34.2% (90% confidence interval [CI], 21.6-48.8) and 48.5% (95% CI, 30.8-66.5), respectively. Median follow-up was 13.2 months (95% CI, 12.6-14.1). At 12 months, BMFS was 84.2% and OS was 87.7% (95% CI, 73.0-94.7). Four patients died of SCLC, 1 of respiratory failure, 1 of hemorrhage, and 1 for unknown reason. The most frequently reported grade ≥3 acute adverse events were anemia (21.4%), febrile neutropenia (19.1%), and fatigue (14.3%). CONCLUSIONS: The proportion of patients showing no NCF decline 6 and 12 months after early HA-PCI does not appear to be better than, but rather similar to, that observed in patients receiving sequential PCI without HA. Early HA-PCI in LD SCLC is feasible, with observation of promising BMFS and OS in this selected population.


Assuntos
Irradiação Craniana , Hipocampo/efeitos da radiação , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/radioterapia , Órgãos em Risco/efeitos da radiação , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Adulto , Idoso , Irradiação Craniana/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/psicologia , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Qualidade de Vida , Carcinoma de Pequenas Células do Pulmão/psicologia , Estresse Psicológico/complicações , Fatores de Tempo
8.
Clin Interv Aging ; 15: 171-175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103919

RESUMO

Anti-γ-aminobutyric acid B receptor (anti-GABABR) encephalitis is a rare type of autoimmune encephalitis (AE). Although it responds well to immunomodulating therapy and has favorable prognosis, anti-GABABR AE has often been misdiagnosed as infectious encephalitis. Herein, we present a case of a 59-year-old female with anti-GABABR AE associated with small cell lung cancer (SCLC) that was once misdiagnosed as infectious encephalitis. Our findings increase the awareness that patients presenting with a clinical trial of cognitive impairment, seizures and SCLC may harbor AE. Our case also highlights the importance of anti-SOX1 antibody in the detection of SCLC.


Assuntos
Autoanticorpos/sangue , Encéfalo/diagnóstico por imagem , Encefalite , Doença de Hashimoto , Neoplasias Pulmonares , Pulmão , Receptores de GABA-B/imunologia , Fatores de Transcrição SOXB1/imunologia , Carcinoma de Pequenas Células do Pulmão , Erros de Diagnóstico/prevenção & controle , Eletroencefalografia/métodos , Encefalite/diagnóstico , Encefalite/imunologia , Feminino , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Resultado do Tratamento
9.
Elife ; 82019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31833833

RESUMO

Metastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic cancer types. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that these cancer cells become relatively more neuronal and less neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human SCLC cells in culture and in vivo can grow cellular protrusions that resemble axons. The formation of these protrusions is controlled by multiple neuronal factors implicated in axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like protrusions impairs cell migration in culture and inhibits metastatic ability in vivo. The co-option of developmental neuronal programs is a novel molecular and cellular mechanism that contributes to the high metastatic ability of SCLC.


Assuntos
Movimento Celular , Extensões da Superfície Celular/metabolismo , Neoplasias Pulmonares/fisiopatologia , Metástase Neoplásica/fisiopatologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Animais , Humanos , Camundongos , Células Tumorais Cultivadas
10.
Genes Dev ; 33(23-24): 1718-1738, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31727771

RESUMO

More than 90% of small cell lung cancers (SCLCs) harbor loss-of-function mutations in the tumor suppressor gene RB1 The canonical function of the RB1 gene product, pRB, is to repress the E2F transcription factor family, but pRB also functions to regulate cellular differentiation in part through its binding to the histone demethylase KDM5A (also known as RBP2 or JARID1A). We show that KDM5A promotes SCLC proliferation and SCLC's neuroendocrine differentiation phenotype in part by sustaining expression of the neuroendocrine transcription factor ASCL1. Mechanistically, we found that KDM5A sustains ASCL1 levels and neuroendocrine differentiation by repressing NOTCH2 and NOTCH target genes. To test the role of KDM5A in SCLC tumorigenesis in vivo, we developed a CRISPR/Cas9-based mouse model of SCLC by delivering an adenovirus (or an adeno-associated virus [AAV]) that expresses Cre recombinase and sgRNAs targeting Rb1, Tp53, and Rbl2 into the lungs of Lox-Stop-Lox Cas9 mice. Coinclusion of a KDM5A sgRNA decreased SCLC tumorigenesis and metastasis, and the SCLCs that formed despite the absence of KDM5A had higher NOTCH activity compared to KDM5A+/+ SCLCs. This work establishes a role for KDM5A in SCLC tumorigenesis and suggests that KDM5 inhibitors should be explored as treatments for SCLC.


Assuntos
Diferenciação Celular/genética , Células Neuroendócrinas/citologia , Receptores Notch/fisiologia , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Transdução de Sinais/genética , Carcinoma de Pequenas Células do Pulmão/enzimologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Linhagem Celular , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/genética , Histona Desmetilases/metabolismo , Humanos , Técnicas In Vitro , Camundongos , Células Neuroendócrinas/patologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia
11.
Medicina (Kaunas) ; 55(10)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561410

RESUMO

Introduction: Antrodia cinnamomea (AC) is an extremely rare medicinal fungus native to forested regions of Taiwan. It possesses numerous biological activities, especially anti-tumor effects shown in various in vitro cancer cells and in vivo animal models. However, there are few clinical reports about AC as a treatment for cancer patients. This report attempts to demonstrate the therapeutic effect of dish-cultured AC (DAC) on a small cell lung cancer (SCLC) patient taken orally for an extended duration. Patient concerns: An 88-year-old male with a history of diabetes mellitus and hypertension visited the outpatient department with the symptoms of dyspnea and a cough for two weeks. After a diagnosis of SCLC, the patient declined both chemotherapy and radiotherapy because of the side effects and only accepted supportive care without additional therapy. Diagnosis: Limited-stage SCLC (T4N2M1a, stage IV) after the chest radiograph, computed tomography-guided biopsy, and pathological diagnosis. Interventions: The patient was prescribed DAC with an increasing dosage, from 5 g/d up to 10 g/d DAC, for six months, without radiation or chemotherapy treatment. Outcomes: DAC caused the tumor to shrink substantially. Surprisingly, the patient survived for 32 months without relapse after six months of DAC treatment. Laboratory examinations indicated that the patient's health had improved significantly, reverting to near normal levels. Notably, he had a good quality of life with a high Barthel index score. Unfortunately, this patient died of septic shock caused by acute cholangitis. Conclusion: DAC may exert an anti-cancer effect, which can lead to tumor regression. This is supposed to be achieved by the combined DAC's immunomodulatory, anti-angiogenic, anti-metastatic, anti-proliferative, and pro-apoptotic effects mediated through multiple signaling pathways. We propose that DAC can be used as a complementary medicine to prolong the life expectancy and improve the life quality of SCLC patients.


Assuntos
Antrodia/química , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso de 80 Anos ou mais , Humanos , Masculino , Cooperação do Paciente , Qualidade de Vida , Transdução de Sinais , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Análise de Sobrevida , Resultado do Tratamento
12.
Med Sci Monit ; 25: 5630-5639, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31356586

RESUMO

BACKGROUND The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic factor in patients who have some types of malignant tumors. The aim of this study was to investigate the prognostic significance of the HALP score in patients with small cell lung cancer (SCLC) before first-line treatment with etoposide. MATERIAL AND METHODS A retrospective study included 178 patients with SCLC who received first-line chemotherapy with etoposide between September 2015 and May 2019. The baseline clinical characteristics and blood parameters were recorded. Univariate and multivariate analysis and Kaplan-Meier plots were used to identify the factors associated with progression-free survival (PFS). RESULTS The optimal cut-off values of the HALP score was determined by X-tile software to be 25.8. Univariate and multivariate analysis showed that in 178 patients, the HALP score, body mass index (BMI), and serum albumin levels had no prognostic significance. In the patient age group <65 years, a BMI ≥24 kg/m² was an independent prognostic factor (HR, 1.943; 95% CI, 1.251-3.018) (P=0.003). In the patient age group ≥65 years, a HALP score >25.8 was an independent positive prognostic factor for outcome following first-line treatment with etoposide (HR, 0.483; 95% CI, 0.270-0.865) (P=0.014). CONCLUSIONS In patients <65 years with SCLC who underwent first-line treatment with etoposide, a BMI ≥24 kg/m² an independent prognostic factor, and in patients ≥65 years, a HALP score >25.8 was an independent predictor of improved outcome, associated with increased PFS.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/sangue , Plaquetas/metabolismo , Índice de Massa Corporal , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Feminino , Hemoglobinas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Albumina Sérica Humana/metabolismo , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Resultado do Tratamento
13.
J Thorac Oncol ; 14(9): 1594-1607, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31163278

RESUMO

INTRODUCTION: The relationships between morbid obesity, changes in body mass index (BMI) before cancer diagnosis, and lung cancer outcomes by histology (SCLC and NSCLC) have not been well studied. METHODS: Individual level data analysis was performed on 25,430 patients with NSCLC and 2787 patients with SCLC from 16 studies of the International Lung Cancer Consortium evaluating the association between various BMI variables and lung cancer overall survival, reported as adjusted hazard ratios (aHRs) from Cox proportional hazards models and adjusted penalized smoothing spline plots. RESULTS: Overall survival of NSCLC had putative U-shaped hazard ratio relationships with BMI based on spline plots: being underweight (BMI < 18.5 kg/m2; aHR = 1.56; 95% confidence interval [CI]:1.43-1.70) or morbidly overweight (BMI > 40 kg/m2; aHR = 1.09; 95% CI: 0.95-1.26) at the time of diagnosis was associated with worse stage-specific prognosis, whereas being overweight (25 kg/m2 ≤ BMI < 30 kg/m2; aHR = 0.89; 95% CI: 0.85-0.95) or obese (30 kg/m2 ≤ BMI ≤ 40 kg/m2; aHR = 0.86; 95% CI: 0.82-0.91) was associated with improved survival. Although not significant, a similar pattern was seen with SCLC. Compared with an increased or stable BMI from the period between young adulthood until date of diagnosis, a decreased BMI was associated with worse outcomes in NSCLC (aHR = 1.24; 95% CI: 1.2-1.3) and SCLC patients (aHR=1.26 (95% CI: 1.0-1.6). Decreased BMI was consistently associated with worse outcome, across clinicodemographic subsets. CONCLUSIONS: Both being underweight or morbidly obese at time of diagnosis is associated with lower stage-specific survival in independent assessments of NSCLC and SCLC patients. In addition, a decrease in BMI at lung cancer diagnosis relative to early adulthood is a consistent marker of poor survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/mortalidade , Análise de Sobrevida , Adulto Jovem
14.
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 , Angústia Psicológica , 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
15.
J Neurol ; 266(1): 195-206, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30460450

RESUMO

OBJECTIVE: To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplastic patients with GABAB receptor antibodies (GABABR-Abs). METHODS: Retrospective clinical study of CSF-confirmed cases of GABABR-Abs encephalitis. RESULTS: We identified 22 patients (4 female) with GABABR-Abs, with a median age of 64 years (range 55-85). All were paraneoplastic: 20 small-cell lung cancer, one malignant thymoma, and one uncharacterized lung mass. The most frequent first symptom was the isolated recurrent seizures without cognitive inter-ictal impairment in 17 patients (77%). In the other, three presented the first behavioral disorders and two presented de novo status epilepticus (SE). After a median delay of 10 days (range 1-30), the recurrent seizures' phase was followed by an encephalitic phase characterized by confusion in 100% of cases and SE in 81% (n = 17), with 53% (n = 9) non-convulsive SE. Dysautonomic episodes were frequent (36%, n = 8, bradycardia and central apnea) and killed three patients. CSF study was abnormal in 95% of the cases (n = 21). At the encephalitic phase, MRI showed a temporal FLAIR hypersignal in 73% (n = 16) of the cases. First-line immunotherapy was initiated after a median delay of 26 days (range 6-65) from disease onset, and a partial response was observed in 10 out of 20 patients (50%). There was no complete response. Two years after onset, a massive anterograde amnesia affected all still alive patients. Nine patients died from cancer progression (median survival: 1.2 years). CONCLUSION: Paraneoplastic GABABR-Abs encephalitis is characterized by a stereotype presentation with an epilepsy phase before an encephalitic phase with dysautonomia. The functional prognosis is poor.


Assuntos
Encefalite/fisiopatologia , Síndromes Paraneoplásicas do Sistema Nervoso/fisiopatologia , Receptores de GABA-B/imunologia , Convulsões/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Amnésia Anterógrada/etiologia , Amnésia Anterógrada/fisiopatologia , Autoanticorpos/líquido cefalorraquidiano , Encefalite/diagnóstico , Encefalite/terapia , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/terapia , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/fisiopatologia
16.
J Nucl Med Technol ; 46(4): 355-358, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30076247

RESUMO

Chemotherapy followed by prophylactic cranial irradiation (PCI) is associated with increased survival in patients with small cell lung cancer but is associated with fatigue and cognitive impairment. This retrospective study evaluated regional differences in 18F-FDG uptake by the brain before and after PCI. The null hypothesis was that direct toxic effects on the brain from PCI and chemotherapy are symmetric; thus, asymmetric deviations may reflect functional changes due to therapy. Methods: Electronic medical records from 2013 to 2016 were reviewed for patients with small cell lung cancer, MRI of brain negative for metastasis, and 18F-FDG PET/CT scans before and after PCI. As the standard of care, patients received first-line chemotherapy or chemoradiation to the thorax followed by PCI. The 18F-FDG PET/CT scans nearest the PCI were selected. Sixteen patients met these initial criteria. Commercially available PET software was used to register and subtract the PET scans before and after PCI to obtain difference maps. Occipital and cerebellar regions were excluded from the final statistical analysis given the known high variability and misregistration. The χ2 test was used to analyze the data. Results: Two patients had 18F-FDG uptake differences only in the occipital and cerebellar regions. The software registration failed on 1 patient's scans. Therefore, 13 patients were included in the final analysis. Nine of 13 patients demonstrated significant unilateral changes in only 1 region of the brain, and 3 of 13 showed significant changes unilaterally in 2 regions. The χ2 test revealed a significant unilateral regional difference on a patient level (χ2 = 6.24, P = 0.025). The most commonly affected brain region was the frontal lobe. Conclusion: Significantly more patients had unilateral than bilateral regional differences (both increases and decreases) in 18F-FDG uptake in the brain before and after PCI. This finding suggests that differences in unilateral distribution are related to functional changes, since direct toxicity alone from PCI and chemotherapy would be symmetric. The frontal region was the most commonly affected, suggesting a potential contributing etiology for cognitive impairment and decreased executive function after therapy.


Assuntos
Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Irradiação Craniana , Fluordesoxiglucose F18/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Transporte Biológico/efeitos da radiação , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/fisiopatologia
17.
Genes Dev ; 32(13-14): 865-867, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29967289

RESUMO

Tumor heterogeneity of a primary histologic cancer type has major implications for cancer research and therapeutics. An important and understudied aspect of this heterogeneity is the role of transcription factors that serve as "lineage oncogenes" in a tumor type. A demonstration that different subgroups have distinct dependencies on lineage-specific transcription factors is highlighted in a relatively homogenous cancer type: the pulmonary neuroendocrine cancer small cell lung carcinoma (SCLC). Identification of these factors is providing new insights into the origin of the heterogeneity and subtype-specific vulnerabilities in SCLC and provides a template for studying heterogeneity in other cancer types.


Assuntos
Carcinoma Neuroendócrino/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Linhagem da Célula , Heterogeneidade Genética , Humanos , Mutação
18.
Genes Dev ; 32(13-14): 915-928, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945888

RESUMO

Small cell lung cancer (SCLC) is widely considered to be a tumor of pulmonary neuroendocrine cells; however, a variant form of this disease has been described that lacks neuroendocrine features. Here, we applied domain-focused CRISPR screening to human cancer cell lines to identify the transcription factor (TF) POU2F3 (POU class 2 homeobox 3; also known as SKN-1a/OCT-11) as a powerful dependency in a subset of SCLC lines. An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Using chromatin- and RNA-profiling experiments, we provide evidence that POU2F3 is a master regulator of tuft cell identity in a variant form of SCLC. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Our CRISPR screens exposed other unique dependencies in POU2F3-expressing SCLC lines, including the lineage TFs SOX9 and ASCL2 and the receptor tyrosine kinase IGF1R (insulin-like growth factor 1 receptor). These data reveal POU2F3 as a cell identity determinant and a dependency in a tuft cell-like variant of SCLC, which may reflect a previously unrecognized cell of origin or a trans-differentiation event in this disease.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/fisiopatologia , Fatores de Transcrição de Octâmero/genética , Fatores de Transcrição de Octâmero/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular , Linhagem Celular Tumoral , Linhagem da Célula , Humanos , Pulmão/patologia , Camundongos , Receptor IGF Tipo 1/metabolismo
19.
Thorac Cancer ; 9(8): 1069-1073, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29932301

RESUMO

The scientific evidence supporting pulmonary rehabilitation (PR) for lung cancer patients undergoing cytotoxic chemotherapy is accumulating; however, the feasibility of outpatient-based PR in these patients has not yet been evaluated in Korea. We conducted an eight-week outpatient-based PR feasibility study in a tertiary referral hospital setting. Patients with advanced lung cancer (non-small cell lung cancer IIIB-IV and small-cell lung cancer extensive disease) scheduled to undergo first-line cytotoxic chemotherapy underwent PR consisting of 60-minute sessions twice a week under the guidance and supervision of a physical therapist, for a total of eight weeks. Feasibility was assessed based on completion of the PR program. In total, 12 patients (median age 68 years) were enrolled; 11 (91.7%) were male with a history of smoking. Among these 12 patients, 9 (75%) completed the eight-week outpatient-based PR program. Three patients could not complete the PR program: two were unwilling and one died from complications of lung cancer. This study showed a 75% completion rate of an eight-week outpatient-based PR program for advanced lung cancer patients undergoing cytotoxic chemotherapy, which supports its feasibility.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/reabilitação , Neoplasias Pulmonares/reabilitação , Carcinoma de Pequenas Células do Pulmão/reabilitação , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Testes de Função Respiratória , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento
20.
Medicine (Baltimore) ; 97(25): e11159, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924023

RESUMO

RATIONALE: Small cell lung cancer accounts for 15-20% of all lung cancers and is the most common pulmonary neuroendocrine neoplasm. Most small cell lung cancers arise from lobar or main bronchi, the most common manifestations of small cell lung cancer is a large mass centrally located within the lung parenchyma or a mediastinal mass involving the hilus. Small cell lung cancer is easily ignored by clinicians without lung parenchyma and hilus involvement. Here, we report a case of small cell lung cancer, which was misdiagnosed as the lymphoma in contrast enhanced CT and Ga-DOTA-NOC PET/CT imagings. PATIENT CONCERNS: A 49-year-old male with chief complaint of discontinuous cough for 1 month. DIAGNOSES: Small cell lung cancer. INTERVENTIONS: Radiotherapy and chemotherapy were given thereafter. OUTCOMES: The case had multiple enlarged lymph nodes due to tumor progression. LESSONS: Small cell lung cancer is a malignant and progressive disease, and easy to be ignored in clinical. The case of small cell lung cancer without parenchyma and hilus involvement has never been reported before. Here, we report it and hope it provides a differential diagnosis for clinicians in the following similar cases.


Assuntos
Erros de Diagnóstico/prevenção & controle , Neoplasias Pulmonares , Linfoma/diagnóstico , Neoplasias do Mediastino , Carcinoma de Pequenas Células do Pulmão , Diagnóstico Diferencial , Radioisótopos de Gálio/farmacologia , Humanos , Biópsia Guiada por Imagem/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/fisiopatologia , Neoplasias do Mediastino/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organometálicos/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Intensificação de Imagem Radiográfica/métodos , Compostos Radiofarmacêuticos/farmacologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Carcinoma de Pequenas Células do Pulmão/terapia , Tomografia Computadorizada por Raios X/métodos
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