- 作者列表："Feliciano J","Chang A","Venkatraman D","Brooks S","Zagaja C","Ettinger D","Hann C","Naidoo J","Voong R","Hales R","Turner M","Peterson V","Bodurtha J
BACKGROUND:Genetic and environmental interactions predispose certain groups to lung cancer, including families. Families or caregiving units experience the disease interdependently. We have previously evaluated the concerns and preferences of patients in addressing the lung cancer experience and cancer risks in their families. This qualitative study evaluates the concerns and preferences of family members and caregivers of patients with lung cancer in the lung cancer experience and familial cancer risks. METHODS:We held focus groups to discuss the format and timing of addressing these preferences and concerns. Qualitative data generated was analyzed using a grounded theory approach. RESULTS:Five focus groups totaling 19 participants were conducted. Seven themes were identified: (1) journey to lung cancer diagnosis has core dimensions for patient and family, (2) importance of communication between patients, families, and providers, (3) challenges for caregivers and family, (4) mixed perceptions of lung cancer causation among relatives, (5) discussion of cancer risk with relatives has complex dynamics, (6) impact of diagnosis on family health behaviors and screening, (7) role of genetic counseling. CONCLUSIONS:Family members of patients with lung cancer are interested in discussing risk factors, prevention, and diagnoses and also would like access to other supportive services do learn about and cope with some of the stresses and barriers they experience in the family lung cancer journey. The diagnosis represents a potential teachable moment with the opportunity to reduce the risk of LC development or improve early detection in LC patient's family members.
背景: 遗传和环境相互作用使某些群体易患肺癌，包括家族。家庭或护理单位相互依赖地经历疾病。我们之前已经评估了患者在解决肺癌经历和家庭癌症风险方面的担忧和偏好。这项定性研究评估了肺癌患者的家庭成员和照顾者在肺癌经历和家族性癌症风险方面的担忧和偏好。 方法: 我们召开了焦点小组讨论解决这些偏好和问题的形式和时间。使用基础理论方法分析生成的定性数据。 结果: 进行了五个焦点小组共 19 名参与者。确定了七个主题 :( 1) 肺癌诊断之旅具有患者和家庭的核心维度，(2) 患者，家庭和提供者之间沟通的重要性，(3) 照顾者和家庭的挑战，(4) 亲属对肺癌因果关系的混合看法，(5)与亲属讨论癌症风险具有复杂的动态，(6) 诊断对家庭健康行为和筛查的影响，(7) 遗传咨询的作用。 结论: 肺癌患者家属对探讨危险因素、预防、和诊断，也希望获得其他支持服务，了解和应对他们在家庭肺癌之旅中经历的一些压力和障碍。诊断代表了一个潜在的可教时刻，有机会降低LC发展的风险或改善LC患者家庭成员的早期检测。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.