RESUMO
Small cell lung cancer (SCLC) continues to cause poor clinical outcomes due to limited advances in sustained treatments for rapid cancer cell proliferation and progression. The transcriptional factor Forkhead Box M1 (FOXM1) regulates cell proliferation, tumor initiation, and progression in multiple cancer types. However, its biological function and clinical significance in SCLC remain unestablished. Analysis of the Cancer Cell Line Encyclopedia and SCLC datasets in the present study disclosed significant upregulation of FOXM1 mRNA in SCLC cell lines and tissues. Gene set enrichment analysis (GSEA) revealed that FOXM1 is positively correlated with pathways regulating cell proliferation and DNA damage repair, as evident from sensitization of FOXM1-depleted SCLC cells to chemotherapy. Furthermore, Foxm1 knockout inhibited SCLC formation in the Rb1fl/flTrp53fl/flMycLSL/LSL (RPM) mouse model associated with increased levels of neuroendocrine markers, Ascl1 and Cgrp, and decrease in Yap1. Consistently, FOXM1 depletion in NCI-H1688 SCLC cells reduced migration and enhanced apoptosis and sensitivity to cisplatin and etoposide. SCLC with high FOXM1 expression (N = 30, 57.7%) was significantly correlated with advanced clinical stage, extrathoracic metastases, and decrease in overall survival (OS), compared with the low-FOXM1 group (7.90 vs. 12.46 months). Moreover, the high-FOXM1 group showed shorter progression-free survival after standard chemotherapy, compared with the low-FOXM1 group (3.90 vs. 8.69 months). Our collective findings support the utility of FOXM1 as a prognostic biomarker and potential molecular target for SCLC.
Assuntos
Biomarcadores Tumorais , Proteína Forkhead Box M1/genética , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/etiologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Feminino , Proteína Forkhead Box M1/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Microtomografia por Raio-X , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
(1) Background: Lung cancer is silent in its early stages and fatal in its advanced stages. The current examinations for lung cancer are usually based on imaging. Conventional chest X-rays lack accuracy, and chest computed tomography (CT) is associated with radiation exposure and cost, limiting screening effectiveness. Breathomics, a noninvasive strategy, has recently been studied extensively. Volatile organic compounds (VOCs) derived from human breath can reflect metabolic changes caused by diseases and possibly serve as biomarkers of lung cancer. (2) Methods: The selected ion flow tube mass spectrometry (SIFT-MS) technique was used to quantitatively analyze 116 VOCs in breath samples from 148 patients with histologically confirmed lung cancers and 168 healthy volunteers. We used eXtreme Gradient Boosting (XGBoost), a machine learning method, to build a model for predicting lung cancer occurrence based on quantitative VOC measurements. (3) Results: The proposed prediction model achieved better performance than other previous approaches, with an accuracy, sensitivity, specificity, and area under the curve (AUC) of 0.89, 0.82, 0.94, and 0.95, respectively. When we further adjusted the confounding effect of environmental VOCs on the relationship between participants' exhaled VOCs and lung cancer occurrence, our model was improved to reach 0.92 accuracy, 0.96 sensitivity, 0.88 specificity, and 0.98 AUC. (4) Conclusion: A quantitative VOCs databank integrated with the application of an XGBoost classifier provides a persuasive platform for lung cancer prediction.
RESUMO
Lung cancer is one of the leading causes of death worldwide. Fifteen percent of lung cancer patients will present with malignant pleural effusion initially, and up to 50% will have malignant pleural effusion throughout the course of the disease. In this study, we developed a spiral microfluidic device that can rapidly isolate cancer cells and improve their purity through fluid dynamics. This label-free, high-throughput device continuously isolates cancer cells and other unrelated molecules from pleural effusion. Most of the background cells that affect interpretation are flushed to outlets 1 to 3, and cancer cells are hydrodynamically concentrated to outlet 4, with 90% of lung cancer cells flowing to this outlet. After processing, the purity of cancer cells identified in pleural effusion by CD45 and epithelial cell adhesion molecule (EpCAM) antibodies in flow cytometry will be increased by 6 to 24 times. The microfluidic device presented here has the advantages of rapid processing and low cost, which are conducive to rapid and accurate clinical diagnosis.
Assuntos
Neoplasias Pulmonares , Derrame Pleural Maligno , Derrame Pleural , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/diagnóstico , Microfluídica , Derrame Pleural/diagnóstico , Derrame Pleural Maligno/diagnósticoRESUMO
The purpose of this study was to explore the behavioral responses to tocolysis of an older woman who has experienced two failed pregnancies. As a participant observer the primary researcher simultaneously provided care and recorded the woman's verbal and nonverbal behaviors. After repeated data analysis, it was found that the woman's stress mainly resulted from her un certainty about a safe passage through pregnancy and about the health of her fetus. In her effort to ensure a successful pregnancy and good fetal health, she exhibited the following behaviors: worrying about the status of her pregnancy, adopting effective strategies to ensure the success of the tocolysis, complying with medical procedures and nursing instructions, establishing the time marks of the pregnancy for the purpose of self-encouragement, and attaching importance to oral intake for the sake of good fetal health. The article concludes that medical personnel should actively identify the needs of pregnant women and provide family-centered nursing care to diminish the impact of preterm premature rupture of membrane and maximize the positive results of tocolysis.