Efficacy of additional dexamethasone administration for the attenuation of paclitaxel-associated acute pain syndrome.
- 作者列表："Saito Y","Kobayashi M","Yamada T","Sakakibara-Konishi J","Shinagawa N","Kinoshita I","Dosaka-Akita H","Iseki K
PURPOSE:Paclitaxel-associated acute pain syndrome (P-APS) affects 80% of patients undergoing therapy. Although it has been shown that prednisone administration for 5 days relieves P-APS, detailed results have not been reported thus far. Therefore, in this study, we evaluated the preventive effect of dexamethasone (DEX) administration against P-APS. METHODS:A total of 60 patients who received carboplatin (area under the curve; AUC = 5-6) plus paclitaxel (200 mg/m2) (plus bevacizumab 15 mg/kg, if non-squamous carcinoma of lung) were enrolled. Eight milligrams of DEX was orally administered on days 2 and 3 to the DEX group patients, and the frequency, severity, duration of P-APS, and other adverse effects in the first cycle were retrospectively evaluated and compared to those observed in control group patients, who were not administered DEX on days 2 and 3. RESULTS:No difference in terms of patient characteristics, except for type of cancer, was observed between groups. The results showed that the frequency of all grade P-APS was approximately 70% and there was no difference between groups. Frequency of ≥ G2 P-APS was 40% in the control group and 14% in the DEX group, demonstrating a significant reduction. Duration of P-APS was 5.8 days in the control group and 4.3 days in the DEX group, which tended to become shorter following additional DEX administration, although this was not significant. Adverse effects other than P-APS induced by chemotherapy were similar between the two groups. CONCLUSION:Additional DEX administration is safe and useful for the attenuation of the severity of P-APS.
目的: 紫杉醇相关的急性疼痛综合征 (p-aps) 影响 80% 接受治疗的患者。尽管已经表明泼尼松给药 5 天缓解了p-aps，但迄今为止还没有详细的结果报道。因此，在本研究中，我们评估了地塞米松 (DEX) 给药对p-aps的预防作用。 方法: 共 60 例接受卡铂 (曲线下面积; Auc = 5-6) 加紫杉醇 (200 mg/m2) (加贝伐单抗 15 mg/kg，如果非鳞状细胞癌) 入组。DEX组患者在第 2 天和第 3 天口服DEX 8 毫克，p-aps的频率，严重程度，持续时间，回顾性评估第一周期中的其他不良反应，并与在第 2 天和第 3 天未施用DEX的对照组患者中观察到的不良反应进行比较。 结果: 除癌症类型外，两组患者特征无差异。结果显示，所有等级p-aps的频率约为 70%，并且组间没有差异。对照组和DEX组中 ≥ G2 P-APS的频率分别为 40% 和 14%，表明显著降低。P-aps的持续时间在对照组中为 5.8 天，在DEX组中为 4.3 天，其在额外的DEX施用后趋于变短，尽管这并不显著。除化疗诱导的P-APS外，两组的不良反应相似。 结论: 额外的DEX给药对于减轻p-aps的严重程度是安全和有用的。
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.