阿特珠单抗联合化疗治疗 1 例双原发癌患者。
- 作者列表："Okauchi S","Sasatani Y","Ohara G","Kagohashi K","Satoh H
BACKGROUND:Immune checkpoint inhibitors are indicated for non-small cell lung cancer (NSCLC) and head and neck cancer, and combined treatment of immune checkpoint inhibitor and chemotherapy has recently been carried out in patients with NSCLC. However, there is no established standard therapy for synchronous locally advanced or metastatic cancers of lung and nasopharynx. CASE REPORT:We report a case of a metastatic lung adenocarcinoma and locally advanced epipharyngeal carcinoma successfully treated with chemotherapy and immune checkpoint inhibitor, paclitaxel, carboplatin, bevacizumab and atezolizumab. The tumor proportion score of programmed death ligand 1 was 5-10% and 70-80% for metastatic lung adenocarcinoma and locally advanced epipharyngeal carcinoma, respectively. Shrinkage of both carcinomas was confirmed, and the treatment effect was judged to be a partial response. CONCLUSION:This was the first patient who was treated with this combination treatment. Our clinical experience suggests that this treatment could be one of the options for patients with these advanced cancers and an overall good clinical condition.
背景: 免疫检查点抑制剂适用于非小细胞肺癌 (NSCLC) 和头颈癌，免疫检查点抑制剂和化疗的联合治疗已在NSCLC患者中开展。然而，对于肺和鼻咽的同步局部晚期或转移性癌症，还没有确定的标准疗法。 病例报告: 我们报告 1 例转移性肺腺癌和局部晚期咽周癌，用化疗和免疫检查点抑制剂、紫杉醇、卡铂、贝伐单抗和阿特珠单抗成功治疗。对于转移性肺腺癌和局部晚期咽旁癌，程序性死亡配体 1 的肿瘤比例评分分别为 5-10% 和 70-80%。证实了两种癌的缩小，并且判断治疗效果是部分反应。 结论: 这是第一例接受这种联合治疗的患者。我们的临床经验表明，这种治疗可能是这些晚期癌症患者和总体良好临床状况的选择之一。
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.