Clinical study on bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer

Objective:To investigate the effect of bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer on tumor markers, angiogenesis molecules and invasive growth molecules.Methods:A total of 68 patients who were diagnosed with non-small cell lung cancer complicated by pleural effusion in the Affiliated T.C.M Hospital of Southwest Medical University between June 2013 and August 2016 were selected and randomly divided into two groups, the combined group received bevacizumab combined with carboplatin chemotherapy, and the carboplatin group received carboplatin chemotherapy. Before treatment as well as 3 cycles and 6 cycles after treatment, the contents of tumor markers, angiogenesis molecules and invasive growth molecules in pleural effusion were examined.Results:3 cycles and 6 cycles after treatment, CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of both groups of patients were significantly lower than those before treatment while TIMP1 and TIMP2 contents were significantly higher than those before treatment, and CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of combined group were significantly lower than those of carboplatin group while TIMP1 and TIMP2 contents were significantly higher than those of carboplatin group.Conclusion:Bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer can effectively kill cancer cells, and inhibit angiogenesis and cell invasion.

Evaluation of serum and pleural levels of endostatin and vascular epithelial growth factor in lung cancer patients with pleural effusion

Objective:To evaluate the diagnostic value of endostatin(ES),vascular endothelial growth factor (VEGF) and careinoembryonie antigen(CEA) in both serum and pleural effusion of lung cancer patients.Methods:Levels of ES,VEGF and CEA in 52 malignant pleural effusion due to lung cancer and 50 patients with non-malignant disease were measured by using sandwich enzymelinked immunosorbent assay and microparticle enzyme immunoassay.Results:The ES.VEGF and CEA levels in pleural effusion and serum,and their ratio(F/S) were higher in lung cancer group than that in benign group,and the differences were statistically significant(P【0.05).The diagnostic efficiency of ES+VEGF for lung cancer was superior to either single detection.The diagnostic efficiency of ES+VEGK+CEA was superior to either ES+VEGF or ES+CEA.Conclusions: The results suggest that ES,VEGF and CEA might be useful in the differentiation between benign and malignant pleural effusion due to lung cancer.In comparison with either single determination of concentration in serum or pleural fluid,the couiljined detection of two or three markers is of important clinical significance in the diagnosis of lung cancer.

Comparison of intra-pleural injection efficacy between Endostar and Bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor-/anaplastic lymphoma kinase-lung adenocarci

Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor(EGFR)-/anaplastic lymphoma kinase(ALK)-lung adenocarcinoma. Methods Sixty-four pCVatients with EGFR-/ALK-lung adenocarcinoma with malignant pleural effusion(MPE) were admitted to the authors' hospital between January 2016 and June 2017. Patients were randomly divided into two groups: Endostar combined with pemetrexed/cisplatin(Endostar group); and bevacizumab plus pemetrexed/cisplatin(Bevacizumab group). They underwent thoracic puncture and catheterization, and MPE was drained as much as possible. Both groups were treated with pemetrexed 500 mg/m^2, intravenous drip(d1), cisplatin 37.5 mg/m^2 per time, intra-pleural injection(d1, d3). Patients in the Endostar group were treated with Endostar 30 mg per time, intra-pleural injection(d1, 3), and patients in the Bevacizumab group were treated with bevacizumab 5 mg/kg per time, intra-pleural injection(d1). Only one cycle of treatment was applied. MPE was extracted before treatment and on day 7 after treatment. The levels of vascular endothelial growth factor(VEGF) were determined using ELISA. Efficacy and side effects were evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1, and National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) version 3.0 criteria. Results The objective response rates in the Endostar and Bevacizumab groups were 50.0% and 56.3%, respectively; there was no statistical difference between the groups(P > 0.05). After one cycle of treatment, the mean VEGF levels in MPE in both groups decreased significantly, and there was no significant difference in the degree of decline between the two groups(P > 0.05). In both groups, pre-treatment VEGF levels for patients achieving complete response were significantly higher than those for patients achieving stable disease + progressive disease(P < 0.05). No specific side effects were recorded. Conclusion Endostar and Bevacizumab demonstrated similar efficacy in controlling MPE in patients with EGFR-/ALK-lung adenocarcinoma through an anti-angiogenesis pathway, with tolerable side effects. The levels of VEGF in MPE could predict the efficacy of intra-pleural injection of anti-angiogenesis drugs.

Effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion

Objective:To study the effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion.Methods:Patients with lung cancer and malignant pleural effusion treated in our hospital between April 2013 and December 2015 were selected and randomly divided into two groups, the observation group received intrapleural endostatin and mannatide infusion treatment and control group accepted routine intrapleural infusion treatment. 4 weeks after treatment, the pleural fluid samples were collected to determine the levels of tumor markers, invasion-related molecules, VEGF-related molecules and anti-tumor cytokines.Results:4 weeks after treatment, CEA, CYFRA21-1, NSE, SCC-Ag, CXCL12, CXCR4, MMP2, MMP9, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2 and VEGF-R3 levels in pleural fluid of observation group were significantly lower than those of control group while LASS2/TMSG-1, IFN-γ, IL-2, TNF-α, IL-17 and IL-23 levels were significantly higher than those of control group.Conclusion:Intrapleural endostatin and mannatide infusion treatment of malignant pleural effusion can more effectively kill cancer cells, inhibit cell invasion, angiogenesis and lymphangiogenesis, and enhance antitumor immune response.

The Observation of Clinical Efficacy and Safety of De-Platinum-Based Pleural Perfusion in the Treatment of Malignant Pleural Effusion and Its Correlation with the Expression of VEGF in Pleural Fluid

Background: Malignant pleural effusion (MPE) is the most common complication of advanced NSCLC. Infusion chemotherapy is currently one of the most common intracavitary treatments for MPE. Unfortunately, there is no definitive consensus on which intracavitary infusion drug has the best effect on the treatment. The use of de-platinum-based thoracic perfusion therapy can offer several advantages, such as reducing drug toxicity and contributing to an improvement in patients’ physical condition. Therefore, this study was to investigate the clinical efficacy and safety of de-platinum-based pleural perfusion bevacizumab combined with Brucea Javanica Oil Emulsion Injection (BJOEI) in the treatment of malignant pleural effusion in advanced lung adenocarcinoma. Methods: A total of 60 patients diagnosed with lung adenocarcinoma and malignant pleural effusion were selected from Binzhou People’s Hospital, Shandong Provincial Cancer Hospital, and Binzhou Central Hospital between June 2022 and May 2024, with 30 cases treated in each group. The study was divided into two groups: the treatment group received bevacizumab injection perfusion in combination with intravenous infusion of Brucea Javanica Oil Emulsion Injection (BJOEI), while the control group received bevacizumab injection combined with cisplatin perfusion. To analyze the data and evaluate their efficacy and adverse reactions, such as disease control rate (DCR), overall response rate (ORR), Karnofsky Performance Status (KPS), vascular endothelial growth factor (VEGF), and so forth. Results: Following the treatment, the quality of life scores in both groups exhibited an increase compared to pre-treatment levels. Moreover, the enhancement observed in the treatment group was deemed statistically significant (P = 0.007). Following treatment, The expression of VEGF in the pleural effusion of both groups of patients was significantly decreased, and the disparity within the same group was found to be statistically significant (P P χ2 = 0.317, P = 0.573;χ2 = 0.218, P = 0.640). A stratified analysis of factors influencing the ORR revealed that the ORR in both groups exhibited statistical significance when the previous KPS score was below 70 (χ2 = 5.850, P = 0.016). The main adverse reactions in both groups included nausea, vomiting, gastrointestinal reactions, fatigue, and hematological toxicity. Among them, there was a statistically significant difference in the occurrence of gastrointestinal reactions and fatigue between the two groups (χ2 = 8.148, P = 0.004;χ2 = 6.696, P = 0.010). Conclusion: Bevacizumab, when combined with Brucea Javanica Oil Emulsion Injection (BJOEI), demonstrates noteworthy efficacy in treating malignant pleural effusion. This combination therapy reduces VEGF expression, in which the reduction supports the efficacy of thoracic perfusion and is associated with minimal adverse reactions, contributing to an improvement in patients’ physical condition and overall clinical tolerability, especially for the poor physique, especially in the elderly and KPS score is less than 70. Therefore, it can be considered a recommended approach for managing malignant pleural effusion, offering significant clinical value.

Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance

Background:Non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations or anaplastic lymphoma kinase(ALK)fusions show dramatic responses to specific tyrosine kinase inhibitors(TKIs);however,after 10-12 months,secondary mutations arise that confer resistance.We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK-and EGFR-targeted TKIs crizotinib and osimertinib,respectively.Methods:Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing(WES),and patients and xenograft-bearing mice received targeted treatment(crizotinib or osimertinib)accordingly.Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size.Finally,the pathology of patients biopsies and xenograft tumors were compared histologically.Results:The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients.WES showed that the genotypes of the xenograft and patient tumors were similar(an echinoderm microtu-bule-associated protein-like 4-ALK(EML4-ALK)gene fusion(patient/xenograft:CTC15035EML4-ALK)and EGFR L858R and T790M mutations(patient/xenograft:CTC15063EGFR L858R,T790M)).After continuous crizotinib or osimertinib treatment,WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4-ALK xenograft,while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B(BRAF)G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha(PIK3C2A)A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R,T790M xenografts.Conclusions:We successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology,which might be a useful tool to investigate the mechanisms of drug resist-ance in NSCLC.

Immune Regulation of Interleukin-27 in Malignant Pleural Effusion

Background： lnterlcukin （IL）-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion （MPE） remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon （IFN）-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE. Methods： The distribution ofl L-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions otcytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription （STAT） signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored. Results： The expression of IL-27 was increased in M PE when compared with blood （ 147.3 ± 25. 1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04）. IL-27 was noted to suppress both proliferation （18.33 ±0.21 vs. 27.77 ±0.88, P = 0.0005） and migration （1.82 ±0.44 vs. 3.13 ±0.07, P = 0.04） of A549 cells, but obviously prornoted apoptosis of A549 cells （9.47 ±1.14 vs. 4.96 ±0.17, P = 0.02） by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities ofA549 cells to pleural mesothelial cell monolayer by activating different STAT signalings. Conelusions： IL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.

Downregulation of miR-4772-3p promotes enhanced regulatory T cell capacity in malignant pleural effusion by elevating Helios levels

Background:Malignant pleural effusion(MPE)is a complicated condition of patients with advanced tumors.Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression.Methods:The possible involvement of microRNAs(miRNAs)in malignant pleural fluid was investigated using small RNA sequencing.Regulatory T cell(Treg)markers(CD4,CD25,forkhead box P3),and Helios(also known as IKAROS Family Zinc Finger 2[IKZF2])were detected using flow cytometry.The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction.The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays.The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system.Correlation assays between miR-4772-3p and functional molecules of Tregs were performed.Results:Compared with non-malignant controls,patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells.The verified downregulation of miR-4772-3p was inversely related to the Helios*Tregs frequency and Helios expression in the MPE.Overexpression of miR-4772-3p could inhib让Helios expression in in vitro experiments.However,ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression.Additionally,miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA.Conclusion:Downregulation of miR-4772-3p,by targeting Helios,contributes to enhanced Tregs activities in the MPE microenvironment.

非小细胞肺癌不同胸腔积液严重程度及预后患者lncRNA MEG3表达及其与Th17/CD4^(+)T细胞的关系

目的:研究非小细胞肺癌(NSCLC)不同胸腔积液严重程度及预后患者lncRNA MEG3表达及其与Th17/CD4^(+)T细胞的关系。方法:选取2020年1月至2022年12月福建医科大学附属泉州第一医院收治的104例NSCLC恶性胸腔积液患者作为研究对象,根据胸腔积液量分为3组:少量胸腔积液组(35例)、中量胸腔积液组(42例)、大量胸腔积液组(27例)。根据患者疾病实际发展转归分为预后良好组(29例未出现复发和转移)和预后不良组(75例出现复发和转移)。另选取同期于福建医科大学附属泉州第一医院治疗的60例肺炎良性胸腔积液患者作为对照组。实时荧光定量PCR检测两组胸腔积液中MEG3表达。收集受试者外周静脉血,流式细胞术检测外周血Th17细胞、CD4^(+)T细胞比例,并计算Th17/CD4^(+)T。对比各组患者lncRNA MEG3及外周血Th17、CD4^(+)T细胞水平。Logistic回归分析NSCLC胸腔积液及预后的影响因素。结果:NSCLC组胸腔积液lncRNA MEG3表达及CD4^(+)T细胞百分比低于对照组,Th17细胞百分比、Th17/CD4^(+)T高于对照组(P<0.05)。大量胸腔积液组lncRNA MEG3表达及CD4^(+)T细胞百分比低于少量胸腔积液组、中量胸腔积液组,中量胸腔积液组lncRNA MEG3表达及CD4^(+)T细胞百分比低于少量胸腔积液组,大量胸腔积液组Th17细胞百分比、Th17/CD4^(+)T高于少量胸腔积液组、中量胸腔积液组,中量胸腔积液组Th17细胞百分比、Th17/CD4^(+)T高于少量胸腔积液组(P<0.05)。预后不良组lncRNA MEG3表达及CD4^(+)T百分比低于预后良好组,而Th17细胞百分比、Th17/CD4^(+)T高于预后良好组(P<0.05)。Logistic回归分析结果显示,lncRNA MEG3为NSCLC胸腔积液的保护因素,Th17/CD4^(+)T为危险因素(P<0.05);lncRNA MEG3为NSCLC预后的保护因素,Th17/CD4^(+)T为危险因素(P<0.05)。结论:NSCLC不同胸腔积液严重程度及预后患者lncRNA MEG3表达及Th17/CD4^(+)T不同,且lncRNA MEG3为NSCLC胸腔积液及预后的保护因素,Th17/CD4^(+)T为危险因素,可作为胸腔积液严重程度及预后诊断的有效生物标志物。

斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液的疗效和安全性

目的观察斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液的疗效和安全性。方法选取2018—2022年扬中市人民医院收治的肺癌合并恶性胸腔积液患者130例,按照随机抽签法分为A组与B组,各65例。所有患者将胸腔积液完全排出后,A组经导管注入注射用顺铂、地塞米松磷酸钠注射液、注射用人白介素-2胸腔内热灌注,B组在A组基础上加用斑蝥酸钠维生素B_(6)注射液胸腔内热灌注。比较2组临床疗效,KPS评分改善分级,治疗前后肿瘤标志物[癌胚抗原(CEA)、细胞角蛋白19片段抗原21-1(CYFRA21-1)和神经元特异性烯醇化酶(NSE)],不良反应。结果B组客观缓解率高于A组(82.67%vs.50.67%,χ^(2)=17.280,P<0.001)。B组KPS评分改善分级优于A组(u=2.053,P=0.040)。治疗后,2组血清CEA、CYFRA21-1、NSE水平低于治疗前,且B组低于A组(P<0.01)。B组与A组不良反应总发生率比较,差异无统计学意义(34.67%vs.29.33%,χ^(2)=0.490,P=0.484)。结论斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液可提高疗效、改善患者功能状态,抑制肿瘤标志物表达,延缓病情进展,且未提高不良反应发生率。

金水葶苓汤对肺癌移植瘤恶性胸腔积液模型小鼠的治疗作用及机制研究

目的:通过复制Lewis肺癌移植瘤胸腔积液小鼠模型,考察金水葶苓汤对模型小鼠胸腔积液的抑制作用。方法:通过胸腔注射Lewis细胞复制C57小鼠胸腔积液肺癌模型,观察金水葶苓汤及金水葶苓汤协同顺铂注射液对模型小鼠胸腔积液体积、胸壁转移瘤数量和转移瘤质量、生存时间的影响;采用Western blotting法检测壁层胸膜AQP1和胸腔积液中VEGF蛋白表达的水平,评价金水葶苓汤对肺癌移植瘤胸腔积液小鼠的治疗作用和机制。结果:与模型组比较,各给药组小鼠体质量增长明显升高,胸腔积液体积、胸壁转移瘤数量、转移瘤质量明显降低,小鼠胸腔积液中VEGF及胸膜中AQP1蛋白表达明显低于模型组,差异均有统计学意义(P<0.05或P<0.01),且金水葶苓汤+顺铂组比单用金水葶苓汤或顺铂注射液效果更好,差异有统计学意义(P<0.05)。结论:金水葶苓汤可以抑制恶性胸腔积液模型小鼠胸腔积液生成,改善小鼠体质量,延长小鼠生存时间,降低胸壁肿瘤转移数量和抑制肿瘤生长,降低胸腔积液中VEGF及胸膜中AQP1蛋白表达水平,且金水葶苓汤协同顺铂注射液优于金水葶苓汤或顺铂注射液单用效果。

贝伐珠单抗联合顺铂治疗非小细胞肺癌合并恶性胸腔积液疗效及安全性的Meta分析

目的系统评价贝伐珠单抗联合顺铂胸腔灌注治疗非小细胞肺癌(NSCLC)合并恶性胸腔积液(MPE)的疗效及安全性。方法检索PubMed、Embase、The Cochrane Library、Web of Science、ProQuest、中国生物医学文献数据库、中国知网、维普、万方数据库中收录的关于贝伐珠单抗联合顺铂对比顺铂胸腔灌注治疗NSCLC合并MPE的随机对照试验,检索时间均从建库至2022年4月18日。依照Cochrane系统评价方法对纳入的随机对照试验进行质量评价,采用RevMan5.3和Stata15软件进行Meta分析。结果本研究最终纳入14项随机对照试验,共计932例患者。Meta分析结果显示,试验组患者总有效率(RR=1.42,95%CI:1.30~1.54,P﹤0.01)和生活质量改善率(RR=1.57,95%CI:1.27~1.94,P﹤0.01)均明显高于对照组,胸腔积液中血管内皮生长因子(VEGF)水平明显低于对照组(MD=-56.50,95%CI:-67.79~-45.21,P﹤0.01)。试验组和对照组患者胃肠道反应、骨髓抑制、肝肾功能异常、高血压、出血事件发生率比较,差异均无统计学意义(P﹥0.05)。结论贝伐珠单抗联合顺铂胸腔灌注治疗NSCLC合并MPE可提高疗效,抑制MPE生成,同时不增加不良反应发生率。

重组人血管内皮抑制素胸腔灌注治疗对非小细胞肺癌恶性胸腔积液患者的效果

目的分析不同剂量重组人血管内皮抑制素(恩度)胸腔灌注治疗对非小细胞肺癌(non-small cell lung cancer,NSCLC)恶性胸腔积液患者的疗效与安全性。方法选取150例NSCLC恶性胸腔积液患者作为研究对象,分为3组,各50例。3组均给予恩度胸腔灌注治疗:低剂量组30 mg,中剂量组60 mg,高剂量组90 mg。对比3组的疗效、肿瘤标志物[细胞角蛋白片段21-1(cytokeratin fragment 21-1,CYFRA21-1)、癌胚抗原(carcinoembryonic antige,CEA)、癌抗原125(cancer antigen 125,CA125)、癌抗原19-9(cancer antigen 19-9,CA19-9)]变化以及安全性。结果治疗后,中、高剂量组的总有效率高于低剂量组(P<0.05),中、高剂量组总有效率比较差异无统计学意义(P>0.05);3组CYFRA21-1、CEA、CA19-9水平均降低(P<0.05),低剂量组CEA、CA125、CA19-9水平高于中、高剂量组(P<0.05);3组并发症总发生率比较差异无统计学意义(P>0.05)。结论恩度60 mg与90 mg进行胸腔灌注治疗均可提高NSCLC恶性胸腔积液患者的疗效,还有助于积极控制肿瘤标志物水平,且随恩度用药剂量的增加其用药风险并未升高。

榄香烯联合恩度及顺铂治疗非小细胞肺癌恶性胸腔积液的疗效观察

目的分析榄香烯联合恩度(重组人血管内皮抑制素)、顺铂治疗非小细胞肺癌恶性胸腔积液的效果。方法纳入2020年10月至2023年10月于聊城市第二人民医院就诊的非小细胞肺癌恶性胸腔积液患者98例,电脑随机数字法分组,研究组、对照组各49例,均行恩度及顺铂治疗,研究组则再加用榄香烯,完成近期疗效评估,治疗前/后测量患者血清肿瘤标志物、T淋巴细胞亚群,评估其体力状态及生活质量,统计患者胸痛、发热、白细胞减少等不良反应。结果缓解率比较,研究组为73.47%,显著高于对照组的51.02%,差异有统计学意义(P<0.05);治疗后研究组血清鳞状上皮细胞癌抗原(squamous cell carcinoma antigen,SCC)及癌胚抗原(carcinoembryonic antigen,CEA)为(6.98±0.71)mg/L、(7.05±0.73)mg/L,显著低于对照组的(8.06±0.88)mg/L、(8.45±0.91)mg/L,差异有统计学意义(P<0.05);治疗后研究组CD4^(+)及CD4^(+)/CD8^(+)T细胞为(44.97±4.87)%、(2.24±0.22),高于对照组的(41.63±4.69)%、(1.80±0.19),CD8^(+)T细胞为(20.05±2.17)%,低于对照组的(23.12±2.69)%,差异有统计学意义(P<0.05);治疗后研究组美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分为(1.47±0.15)分,低于对照组的(1.83±0.19)分,卡氏功能状态量表(Karnofsky Function Status Score,KPS)评分为(80.93±8.14)分,高于对照组的(76.14±7.91)分,差异均有统计学意义(P<0.05);研究组胸痛、白细胞减少、血小板减少等不良反应总发生率为32.65%,与对照组(26.53%)相比,差异无统计学意义(P>0.05)。结论榄香烯联合恩度、顺铂治疗非小细胞肺癌恶性胸腔积液效果良好,可下调患者肿瘤标志物水平,恢复其T淋巴细胞亚群平衡,有利于患者生活质量的改善。

非小细胞肺癌合并胸腔积液患者留置导管时间及其相关因素分析

目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)合并胸腔积液患者留置导管时间及相关因素。方法 选取2020年1月至2022年10月我院NSCLC合并胸腔积液患者240例为研究对象。记录成功移除胸腔导管患者胸腔导管留置时间,并根据胸腔导管留置中位时间分为A组和B组,对比两组一般资料、治疗前胸腔积液情况及实验室资料,同时采用多元线性回归分析模型分析影响NSCLC合并胸腔积液患者留置导管时间的相关因素。结果 植入胸腔导管后的240例NSCLC合并胸腔积液患者中,30例由于不明原因或患者随访而丢失,46例因继发性胸膜炎而终止,最终164例患者成功拔除胸腔导管,管道留置时间18(15,21)d,将导管留置时间<18d为A组(n=77),导管留置时间≥18d为B组(n=87)。A组吸烟史占比、治疗前胸腔积液量、胸腔积液乳酸脱氢酶(Lactate Dehydrogenase,LDH)水平低于B组,放化疗、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分≤2分占比高于B组(P<0.05);多因素线性回归分析显示,吸烟史、胸腔积液量、LDH正向影响NSCLC合并胸腔积液患者留置导管时间(B=3.320,B=0.003,B=0.011,P<0.05),ECOG评分≤2分、放化疗负向影响NSCLC合并胸腔积液患者留置导管时间(B=-1.559,B=-0.971,P<0.05)。结论 NSCLC合并胸腔积液患者留置导管时间与ECOG评分、吸烟、放化疗、胸腔积液量、胸腔积液LDH水平有关。临床医生在判断留置胸腔导管是否是治疗NSCLC合并胸腔积液的理想方法时,应考虑影响胸腔导管留置时间的影响因素。

肺癌患者外周血和胸腔积液T细胞受体组库特征分析

目的 比较肺癌患者外周血和胸腔积液的T细胞受体(TCR)组库的免疫学特征。方法 收集2020年7月至2021年1月在复旦大学附属中山医院就诊的5例合并恶性胸腔积液肺癌患者的外周血和胸腔积液,分离外周血单个核细胞(PBMC)和胸腔积液单个核细胞(PEMC),提取基因组DNA,采用Illumina MiSeq平台对TCR进行高通量测序,分析TCR组库的多样性等特征。结果 PBMC和PEMC中的TCR克隆型、VJ pairs和互补决定区3(CDR3)序列的多样性和相关性差异均无统计学意义。PBMC中检测到的TCR克隆数量高于PEMC(P<0.05),VJ pairs和CDR3数量与PEMC差异无统计学意义。PBMC和PEMC配对样本的共有VJ pairs数量占总VJ pairs的比例高于共有克隆型和CDR3序列的数量比例(P<0.05),后两者差异无统计学意义。PEMC中高扩增克隆(HEC)数量和占比均高于PBMC。同时鉴定了36个在PBMC和PEMC中差异表达的VJ pairs,其中25个在PEMC中表达升高、9个在PEMC中表达降低。结论 肺癌患者外周血和胸腔积液的TCR组库表现出不同的特征性变化,可能为肺癌重要的免疫病理学特征。

重组人血管内皮抑制素不同给药方式治疗非小细胞肺癌恶性胸腔积液的有效性和安全性的网状Meta分析

目的 系统评价重组人血管内皮抑制素(Endostatin)不同给药方式治疗非小细胞肺癌(NSCLC)恶性胸腔积液的有效性和安全性,为临床上规范Endostatin超药品说明书用药提供更多循证依据。方法 计算机检索PubMed、The Cochrane Library、Web of Science、Embase、ChiCTR、VIP、CNKI、WanFang和SinoMed数据库,搜索有关Endostatin单用或联合化疗治疗NSCLC恶性胸腔积液的随机对照试验。运用Stata 14.0软件进行网状Meta分析。结果 共纳入50篇RCT,合计3 429例患者,涉及5种干预措施。网状Meta结果显示,在临床有效率方面,Endostatin(胸腔灌注)+化疗(胸腔灌注或静脉滴注)与Endostatin(静脉滴注)+化疗(胸腔灌注或静脉滴注)、Endostatin(胸腔灌注)与化疗(胸腔灌注)比较差异均无统计学意义(P> 0.05);Endostatin(胸腔灌注)+化疗(胸腔灌注或静脉滴注)与Endostatin(胸腔灌注)[OR=3.44,95%CI(2.29,5.16),P <0.05]、Endostatin(胸腔灌注)+化疗(胸腔灌注或静脉滴注)与化疗(胸腔灌注)[OR=3.78,95%CI(3.16,4.51),P <0.05]比较,差异有统计学意义;累积排序概率曲线下面积显示Endostatin(胸腔灌注)+化疗(胸腔灌注或静脉滴注)> Endostatin(静脉滴注)+化疗(胸腔灌注或静脉滴注)> Endostatin(胸腔灌注)>化疗(胸腔灌注)>化疗(静脉滴注)。不同干预措施胃肠道反应、白细胞及血小板减少发生率的组间比较差异均无统计学意义(P> 0.05)。结论 Endostatin胸腔灌注或静脉滴注联合一线化疗药物均可显著提高NSCLC恶性胸腔积液的临床有效率,但其胸腔灌注疗效更佳且安全性较好。

肺腺癌恶性胸水细胞学标本PD-L1的表达及与临床和分子特征关系

目的:分析PD-L1(细胞程序性死亡-配体1)在肺腺癌患者恶性胸水脱落细胞中的表达,分析PD-L1与肺腺癌患者临床病理参数的关系。方法:采用免疫组化方法检测54例肺腺癌患者恶性胸水中的脱落细胞标本中PD-L1的表达,同时检测73例肺腺癌组织标本中PD-L1的表达,分析两者之间表达一致性。结果:在54例细胞标本中PD-L1阳性率68.5%,而73例组织标本中仅为53.4%(P>0.05);其中31例肺腺癌患者既有恶性胸水细胞标本,也有组织标本,恶性胸水中肿瘤细胞PD-L1阳性比例TPS 1%-49%为26%,TPS≥50%为39%,PD-L1在同一患者的组织学和细胞学标本中的表达阳性率一致性尚可(Kappa=0.49,P<0.05)。恶性胸水细胞中PD-L1表达与淋巴结转移状态相关(P<0.05),而与患者性别、年龄、远处转移等均无相关性(P>0.05)。结论:在肺腺癌恶性胸水细胞学标本中检测PD-L1的结果可靠,在组织学标本无法获得的情况下,可用恶性胸水细胞学标本进行PD-L1检测。

肺癌恶性胸腔积液来源肿瘤细胞的小鼠PDX模型构建及实验验证

目的·构建肺癌患者恶性胸腔积液(malignant pleural effusion,MPE)肿瘤细胞来源的肿瘤异种移植(patientderived tumor xenograft,PDX)模型,并进行实验验证。方法·从基因表达综合数据集(Gene Expression Omnibus,GEO)下载人肺癌伴MPE单细胞转录组测序公共数据GSE131907和人肺癌实体瘤单细胞转录组测序公共数据GSE203360,对数据进行聚类、差异基因本体功能富集分析,明确应用MPE建模的可行性。同时收集肺癌患者的MPE样本,经离心、裂解红细胞等富集细胞操作后,将其植入非肥胖型糖尿病重症联合免疫缺陷(non-obese diabetic/severe combined immunodeficient,NOD/SCID)小鼠皮下,待移植瘤生长至1000 mm³时进行瘤体传代及保存。对稳定传代移植瘤进行组织病理学检测,通过苏木精-伊红染色(hematoxylin-eosin staining,H-E染色)观察细胞组织形态,免疫组织化学法(immunohistochemistry,IHC)检测肺癌标志物表达情况。结果·经单细胞数据分析发现MPE中肿瘤细胞的增殖功能更强,提示MPE中肿瘤细胞PDX建模或具备更佳成瘤效果;共收集35例肺癌MPE样本,成功构建13例PDX模型,成功率达37.14%;在组织病理学检测中,H-E染色可见移植瘤组织细胞异型性明显,IHC检测显示细胞角蛋白7(cytokeratin 7,CK7)、甲状腺转录因子1(thyroid transcription factor-1,TTF1)和天冬氨酸蛋白酶A(Napsin A)等肺癌标志物均呈阳性表达。结论·通过富集肺癌患者MPE中的肿瘤细胞,成功构建了更为简便高效、可实时动态建模的PDX模型。该模型保留了肺癌患者肿瘤细胞的恶性特征及蛋白表达特性,为肺癌伴MPE患者的基础研究和临床用药指导提供了重要的实验模型工具。

液基细胞学联合免疫细胞化学对肺腺癌胸腔积液的诊断价值

目的研究液基细胞学联合免疫细胞化学染色对肺腺癌胸腔积液的诊断价值。方法收集中山大学附属第三医院病理科2022年6月至2023年2月送检的50例胸腔积液样本,以细胞蜡块免疫组化作为诊断标准,其中30例确诊为肺腺癌,20例为非腺癌积液(包括17例非肿瘤积液、2例小细胞肺癌和1例肺鳞癌),均采用液基薄层制片技术中的沉降式液基薄层细胞制片技术(liquid-based cytology technology,LCT)和膜式薄层细胞制作技术(thinprep cytologic test,TCT)制片,行免疫细胞化学染色,比较分析液基细胞学免疫细胞化学染色的可行性。结果液基细胞学联合免疫细胞化学诊断结果与细胞蜡块免疫组织化学诊断结果一致,但TCT制片法明显优于LCT制片法,样本间细胞数量一致,分布均匀,阳性染色定位准确,细胞质和细胞核呈色清晰。TTF-1、napsin A、CK7在TCT联合免疫细胞化学检测肺腺癌的灵敏度分别100%、91.66%、93.10%,特异性为100%、100%、83.33%;而P40在1例肺鳞癌中弥漫表达。结论液基细胞学联合免疫细胞化学在胸腔积液肺腺癌的诊断中表现出较高的敏感性和特异性,在临床工作尤其是晚期患者原发灶难以获取的患者具有重要价值;因其操作时间短,在缩短报告时长方面更显示出巨大优势。