目的 探讨磷酸丙糖异构酶1（TPI1）在肺腺癌中的表达及其与患者临床预后的联系。方法 通过免疫组化法检测54例肺腺癌及其配对的癌旁肺组织中TPI1表达，分析肺腺癌中TPI1表达和肿瘤的临床病理特征及患者临床预后之间的相关性。结果 TPI1在肺腺癌中高表达（36/54,66.7%）与年龄（P=0.026）、N分期和肿瘤分期均相关（均P＜0.001）。单因素分析结果显示，TPI1高表达是肺腺癌患者预后的影响因素（log-rank test,P=0.02）。多因素分析结果显示，TPI1高表达（P=0.012）和N分期（P=0.008）是肺腺癌患者临床预后的独立危险因素。结论TPI1在肺腺癌中高表达与肿瘤的转移和临床预后密切相关，TPI1可能成为未来肺腺癌个体化精准治疗的靶点。

摘要：目的 探究系统性免疫炎症指数（SII）与晚期非小细胞肺癌免疫治疗疗效及预后的关系。方法 整理我院2018年1月至2021年1月初治的88例晚期非小细胞肺癌患者作为实验对象，依据系统性免疫炎症指数（SII）水平划分两组，即高SII组、低SII组，分析SII对总生存（OS）和无进展生存（PFS）的影响。结果 非小细胞肺癌患者SII水平与临床分期、KPS评分密切相关，P<0.05；高SII组的患者有效率（ORR）、无进展生存（PFS）较低SII组有降低，差异具有统计意义P<0.05；晚期非小细胞肺癌患者SII>660×109为总生存期的独立危险因素。结论 晚期非小细胞肺癌患者治疗期间，注意SII水平变化情况，实现对患者生存情况预测，可作为患者预后情况的评价指标。

目的 探讨小柴胡汤联合泼尼松对肺癌患者免疫性肺炎及T淋巴细胞的影响.方法 将80例免疫检查点抑制剂(ICI)所致免疫性肺炎的肺癌患者随机分为两组,对照组(n=40)采用泼尼松治疗,联合组(n=40)在此基础上加用小柴胡汤.连续治疗7天后,比较两组患者的临床-影像-生理(CRP)评分、T淋巴细胞水平、Karnofsky评分的变化.结果 治疗后,两组CRP评分均显著下降,且联合组显著低于对照组(P<0.05);治疗后,对照组CD4+、CD4+/CD8+T细胞亚群水平较治疗前显著下降,且显著低于联合组(P<0.05);两组治疗后Karnofsky评分均显著升高,且联合组明显高于对照组(P<0.05).结论 小柴胡汤联合泼尼松治疗肺癌患者免疫性肺炎的疗效优于单用泼尼松,有助于调节免疫抑制状态,增强免疫功能,改善生活质量.

Introduction : This study is aimed to evaluate the efficacy and safety of sintilimab combined with albumin-bound paclitaxel/ cisplatin as a second-line treatment in these patients with relapsed or refractory extensive-stage small cell lung cancer (ES-SCLC). Methods and Materials : ES-SCLC patients received a second-line regimen of sintilimab combined with albumin-bound paclitaxel/cisplatin. Albumin-bound paclitaxel/cisplatin can be used for up to 6 cycles. Sintilimab use was not stopped until the disease progressed or untolerable side effects occurred. After 2 cycles of chemotherapy or when the patient's condition progressed significantly, computed tomography was rechecked to observe the clinical curative effect and adverse reactions. Results : Totally 38 patients with recurrent SCLC were included for efficacy evaluation. The objective response rate and disease control rate were 26.3% and 84.2% respectively. The median PFS and OS were 6.5 months (95% CI: 3.8-7.8) and 10.8 months (95% CI: 8.5-16.2), respectively. The main adverse reactions are bone marrow suppression, alopecia, peripheral neurotoxicity, muscle and joint pain, gastrointestinal reactions, and fatigue. The severe adverse reactions (grade 3-4) are mainly leukopenia (21.1%), neutropenia (21.1%) and decreased hemoglobin (7.9%). No significant correlation was found between PD-L1 expression and efficacy. Conclusion : Sintilimab combined with albumin-bound paclitaxel/cisplatin has a positive effect on the treatment of ES-SCLC, and the adverse reactions are tolerable.

目的:探讨贝伐珠单抗联合XELOX化疗方案治疗老年晚期结、直肠癌肝转移患者的临床疗效及安全性.方法:选取自2018年2月至2019年2月收治的老年晚期结、直肠癌肝转移患者82例,按照随机数字表法分成两组.对照组患者41例,行XE-LOX方案治疗,观察组患者41例,采用贝伐珠单抗联合XELOX方案治疗.对比两组患者疗效及安全性.结果:观察组患者客观缓解率(ORR)为65.85％,高于对照组的46.34％(P<0.05);观察组患者KPS评分改善率为87.80％,对照组为78.05％(P>0.05);治疗后观察组患者躯体、角色和情绪功能评分显著高于对照组患者(P<0.05),而ALT、AST、指标均低于对照组(P<0.05);观察组患者的不良反应发生率为53.66％,高于对照组的39.02％,但差异无显著性意义(P>0.05).结论:贝伐珠单抗联合XELOX化疗方案治疗老年晚期结、直肠癌肝转移,可更好地改善患者肝脏功能状态,提高临床疗效.

目的 探讨晚期消化道肿瘤患者化疗前后外周血中CD14-CD11b+MDSC(粒系,G-MDSCs)与CD14+CD1 1b+MDSC(单核系,M-MDSCs)2个MDSCs亚群的含量变化.方法 收集2017年2月至2018年2月我院收治的晚期消化道肿瘤患者(n=58)化疗前后及来我院做健康体检的健康人(n=46)外周血标本6ml,采用流式细胞术(FCM)检测G-MDSCs与M-MDSCs的水平,然后将肿瘤患者与健康人的G-MDSCs与M-MDSCs分别提纯后与CD8+T细胞共培养,检测T细胞的增殖情况.比较患者化疗前后G-MDSCs与M-MDSCs的含量变化及不同疗效组患者G-MDSCs与M-MDSCs的含量差异.结果 晚期消化道肿瘤患者G-MDSCs明显高于健康人(P＜0.001),而2组间M-MDSCs的含量未见显著性差异(P＞0.05);肿瘤患者的G-MDSCs与M-MDSCs对CD8+T细胞增殖抑制作用显著高于健康人(P＜0.05).G-MDSCs含量在不同疗效组之间差异有统计学意义(P＜0.01),疗效越差者G-MDSCs含量越高(x2=4.182,P=0.043).结论 晚期消化道肿瘤患者外周血中MDSCs过量积聚,其中G-MDSCs含量变化与化疗疗效负相关.

目的:探讨贝伐珠单抗联合培美曲塞治疗老年晚期肺腺癌的临床疗效及对机体免疫功能的影响.方法:采用前瞻性队列研究设计,纳入2015年8月至2018年12月首都医科大学大兴教学医院收治的符合入组标准的晚期肺腺癌患者,根据治疗方案的不同分为对照组和研究组.对照组40例患者给予培美曲塞500 mg/m2,静脉滴注,仅第1日给药,每21 d为1个周期.研究组42例患者给予培美曲塞500 mg/m2,静脉滴注,仅第1日给药,每21 d为1个周期;贝伐珠单抗7.5 mg/kg,静脉滴注,仅第1日给药,每14 d为1个周期.两组患者均接受至少4个周期的化疗,4个周期后比较两组患者的临床疗效、不良反应及外周血免疫指标变化,并随访疾病无进展生存期(progression free survival,PFS).结果:研究组、对照组患者的客观有效率分别为52.4％(22/42)、37.5％(15/40),差异无统计学意义(P=0.176);疾病控制率分别为83.3％(35/42)、62.5％(25/40),差异有统计学意义(P=0.033).研究组患者的中位PFS为6.5个月(95％CI:5.82～7.29个月),对照组患者的PFS为5.2个月(95％CI:4.45～5.97个月),两组比较,差异有统计学意义(P=0.04).两组患者主要的3/4级不良反应包括中性粒细胞减少、血小板减少、贫血、恶心呕吐、乏力、高血压及蛋白尿,两组患者各不良反应发生率的差异均无统计学意义(P>0.05).对照组患者治疗后T细胞亚群、自然杀伤细胞(NK细胞)活性、免疫球蛋白A(IgA)和免疫球蛋白M(IgM)水平明显降低,与治疗前比较的差异均有统计学意义(P<0.05);研究组患者治疗后T细胞亚群、NK细胞活性、IgA和IgM水平较治疗前降低不明显,与对照组治疗后的差异均有统计学意义(P<0.05).治疗前后,两组患者IgG水平组内、组间比较,差异均无统计学意义(P>0.05).结论:贝伐珠单抗联合培美曲塞治疗老年晚期肺腺癌的疗效确切,疾病控制率优于培美曲赛单药治疗,不良反应可耐受,对外周血免疫指标水平的影响相对较小.

BACKGROUND:Patients with anaplastic lymphoma kinase (ALK) rearrangements are particularly prone to development of brain metastases (BMs). Newer anti-ALK treatments have demonstrated far greater intracranial efficacy. Here we performed a meta-analysis with the aim of assessing the efficacy of ALK inhibitors on BMs.METHODS:A search of published trials was conducted in PubMed, The Cochrane Library, Web of Science, and Embase. Data were pooled using the number of events/number of evaluable patients (non-small cell lung cancer patients with BMs) according to fixed or random effect models. Intracranial efficacy was assessed through overall response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS). Subgroup analyses for baseline BMs, previous treatment with ALK inhibitor, study type, and current ALK inhibitor were made.RESULTS:Twenty studies accounting for 2,715 patients were included. The pooled iORR was 48% (95% CI: 32-63%) in fifteen single-arm studies. The overall DCR was 65% (95% CI: 60-69%) from three studies include available data. The iORR was 79% (95% CI: 64-91%), 45% (24-67%), 48% (34-63%), 18% (13-24%) in patients receiving alectinib, ceritinib, brigatinib, and crizotinib, respectively. Five randomized studies assessed the intracranial efficacy of anti-ALK agents versus chemotherapy, the pooled RR for iORR was 3.54 (95% CI: 2.38-5.26), and the pooled HR for iPFS was 0.52 (95% CI: 0.36-0.75; P=0.71) estimated in 2 studies.CONCLUSIONS:Despite the limitation from lack of published clinical data, our results showed that ALK inhibitors are effective at the brain site regardless of previous anti-ALK treatments, systemic therapy with ALK inhibitors should be considered as a preferred approach over for controlling BMs from ALK-positive NSCLC.

目的 探讨传统教学法(LBL)、以病例为基础的教学法(CBL)和以问题为基础的教学法(PBL)相结合的"三轨教学模式"在肿瘤内科临床教学中的教学效果.方法 某院2016年9月至2018年8月实习的60名学生,随机分为实验组和对照组,实验组采用"LBL+CBL+PBL"的三轨教学模式,对照组采用传统LBL教学法.实习结束后,进行理论考核、五站式考核以及教学效果评价.结果 理论考核成绩实验组(85.6±3.57)和对照组(84.33±2.98)无显著差异(P=0.081),五站式考核总成绩实验组(86.70±1.66)优于对照组(83.88±1.47)(P<0.001),主要表现在问诊(P=0.003)、辅助检查判读(P<0.001)、病历书写(P<0.001)及口试(P<0.001)方面.教学效果评价方面,实验组在提高学习的积极性(P=0.002)、理论知识的掌握(P<0.001)、临床能力的培养(P<0.001)、培养思维能力(P<0.001)、培养自学能力(P<0.001)、提高文献查阅能力(P<0.001)、培养团队协作能力(P<0.001)、提高分析解决问题的能力(P<0.001)、提高学习效率(P=0.03)这9个方面均优于对照组,差异有统计学意义.结论 三轨教学模式在肿瘤内科临床教学中有一定的优势,值得进一步研究.

Background: Patients with anaplastic lymphoma kinase (ALK) rearrangements are particularly prone to development of brain metastases (BMs). Newer anti-ALK treatments have demonstrated far greater intracranial efficacy. Here we performed a meta-analysis with the aim of assessing the efficacy of ALK inhibitors on BMs. Methods: A search of published trials was conducted in Pubmed, The Cochrane Library, Web of Science, and Embase. Data were pooled using the number of events/number of evaluable patients (non-small cell lung cancer patients with BMs) according to fixed or random effect models. Intracranial efficacy was assessed through overall response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS). Subgroup analyses for baseline BMs, previous treatment with ALK inhibitor, study type, and current ALK inhibitor were made. Results: Twenty studies accounting for 2,715 patients were included. The pooled iORR was 48% (95% CI: 32–63%) in fifteen single-arm The overall DCR was 65% (95% CI: 60–69%) from three studies include available data. The iORR was 79% (95% CI: 64–91%), 45% (24–67%), 48% (34–63%), 18% (13–24%) in patients receiving alectinib, ceritinib, brigatinib, and crizotinib, respectively. Five randomized studies assessed the intracranial efficacy of anti-ALK agents versus chemotherapy, the pooled RR for iORR was 3.54 (95% CI: 2.38–5.26), and the pooled HR for iPFS was 0.52 (95% CI: 0.36–0.75; P=0.71) estimated in 2 studies. Conclusions: Despite the limitation from lack of published clinical data, our results showed that ALK inhibitors are effective at the brain site regardless of previous anti-ALK treatments, systemic therapy with ALK inhibitors should be considered as a preferred approach over for controlling BMs from ALK-positive NSCLC.

Objective To compare the clinical efficacy and safety of erlotinib and docetaxel in patients with advanced non-small cell lung cancer ( NSCLC) with the first-line chemotherapy failure, and assess quality of life. Methods 78 cases of NSCLC patients with first-line chemotherapy failure were enrolled, according to the random number table method, they were divided into 2 groups, using docetaxel (docetaxel group, n =39) 75 mg/m2 intravenous infusion of 2 h, every 21 days;erlo-tinib (erlotinib group, n =39) 150 mg orally, once daily. The objective relieve rate (ORR), disease control rate (DCR), Karnofsky score, progression free survival ( PFS) and adverse reactions were compared between the 2 groups. Results Erlo-tinib group’ s ORR and DCR were significantly higher than those in docetaxel group (28. 2% vs. 10. 3%, 61. 5% vs. 38. 5%, P <0. 05);compared with docetaxel group, erlotinib group rash degree increased significantly, platelet count were decreased and liver function abnormalities were ameliorated ( P <0. 05 ); after chemotherapy, Karnofsky scores of the 2 groups were significantly increased ( t =7. 16, t =5. 00, P <0. 05), and erlotinib group was significantly higher than that of the docetaxel group ( t =3. 81, P <0. 05). Erlotinib group had a median PFS of 7. 73 months (95% CI 7. 51-7. 90), do-cetaxel group had a median PFS of 7. 30 months (95% CI 7. 08-7. 52) and erlotinib group’ s median PFS was longer than docetaxel group (χ2 =5. 80, P <0. 05). Conclusion Erlotinib targeted treatment can improve clinical effects of advanced NSCLC, safety and tolerability are better, and it can improve the quality of life of patients and prolong survival time.

This study was designed to explore the genetic polymorphism of IL-10 (−1082A/G, −592A/C, −819T/C), TNF-α (−308G/A) with susceptibility to docetaxel-induced liver injury (DILI) in Chinese breast cancer patients.

OBJECTIVE:Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the resistance to anti-HER2 therapy is a growing clinical dilemma. We aim to determine whether HER2-specific T cells generated from dendritic cells (DCs) modified with HER2 gene could effectively kill the HER2-positive breast cancer cells, especially the trastuzumab-resistant cells.METHODS:The peripheral blood mononuclear cells (PBMCs) from healthy donors, whose HLA haplotypes were compatible with the tumor cell lines, were transfected with reconstructive human adeno-association virus (rhAAV/HER2) to obtain the specific killing activities of T cells, and were evaluated by lactate dehydrogenase (LDH) releasing assay.RESULTS:Trastuzumab produced a significant inhibiting effect on SK-BR-3, the IC50 was 100ng/ml. MDA-MB-453 was resistant to trastuzumab even at a concentration of 10,000 ng/ml in vitro. HER2-specific T lymphocytes killed effectively SK-BR-3 [(69.86±13.41)%] and MDA-MB-453 [(78.36±10.68)%] at 40:1 (effector:target ratio, E:T), but had no significant cytotoxicity against HER2-negative breast cancer cell lines MDA-MB-231 or MCF-7 (less than 10%).CONCLUSION:The study showed that HER2-specific T lymphocytes generated from DCs modified by rhAAV/HER2 could kill HER2-positive breast cancer cell lines in a HER2-dependent manner, and result in significantly high inhibition rates on the intrinsic trastuzumab-resistant cell line MDA-MB-453 and the tastuzumab-sensitive cell line SK-BR-3. These results imply that this immunotherapy might be a potential treatment to HER2-positive breast cancer.

Objective: To investigate the protective effect of hematopoietic stem cells for chemotherapeutic drug-induced acute liver injury.Methods: With the NCI CTC 3.0 adverse drug reactions as the standard version,clinical data of 115 cases with high-dose chemotherapy(HDC) supported by hematopoietic stem cells,from 2005 to 2009 in department of oncology of our hospital were surveyed.Results: There were 40 patients in all of 115 patients,whose liver function improved more or less in the second cycle of HDC with hematopoietic stem cells infusion,compared with that in the previous cycle(P = 0.000),which indicated that the incidence of abnormal liver function was significantly lower in group of HDC combined with hematopoietic stem cells infusion than in simple chemotherapy group.After the first cycle of chemotherapy,incidence of patients with severe hepatic toxicity of grade 2-4 was 13.9%(16 cases),while after the second cycle that was 6.1%(7 cases),and P = 0.048,indicating that the incidence of moderate-severe liver toxicity decreased significantly after the combination use with hematopoietic stem cells.Conclusion: The ALT difference between two cycles chemotherapy and the rate of moderate-severe acute drug-induced liver injury was significantly different in patients with or without hematopoietic stem cells support,and after hematopoietic stem cells infusion,the patients with abnormal liver function in the first cycle recovered significantly.So hematopoietic stem cells may have protective effect on chemotherapeutic drug-induced hepatotoxicity.

Chemotherapy plays an important role in the treatment of metastatic breast cancer. It is important to monitor chemotherapeutic efficacy, to find a simple and efficient tool to guide treatment, and to predict the efficacy of treatment in a timely and accurate manner. This study aimed to detect mucin-1 (MUC1)-positive circulating tumor cells and MUC1 protein in the peripheral blood of patients with metastatic breast cancer and to investigate their relationship to chemotherapeutic efficacy. MUC1 mRNA was detected in the peripheral blood of 34 patients with newly diagnosed metastatic breast cancer by reverse transcription-polymerase chain reaction. The positive rates of MUC1 mRNA were 88.2% before chemotherapy and 70.6% after chemotherapy, without a significant difference (P=0.564); MUC1 mRNA expression before chemotherapy had no correlation with treatment effectiveness (P=0.281). The response rate of MUC1 mRNA-negative patients after first-cycle chemotherapy was significantly higher (P=0.009) and the progression-free survival (PFS) was clearly longer than those of MUC1 mRNA-positive patients (P=0.095). MUC1 protein in peripheral blood plasma was detected by an ELISA competitive inhibition assay. The patients with decreased MUC1 protein after chemotherapy had a significantly longer PFS than those with elevated MUC1 protein (P=0.044). These results indicate that the outcomes of MUC1 mRNA-negative patients after chemotherapy are better than those of MUC1 mRNA-positive patients. In addition, patients with decreased expression of MUC1 protein have a better PFS.

Objective To investigate the relationship of BRCA1,CDH1,DKK1 and SFRP1 gene methylation with ER status,relapse and metastasis in patients of Metastatic breast cancer.Methods Explore the methylation status of four genes BRCA1,CDH1,DKK1 and SFRP1 in 115 metastasis breast cancer patients' peripheral blood.65 patients with healthy controls with comparison.Results Percent of BRCA1.CDH1 and SFRP1methylation in patients are significantly higher compared to healthy controls.About 27.5% of patients with ER positive tumor were CDH1 methylated in peripheral blood cells,while 47.8% with ER negative tumor were methylated.In contrast,ER positive patients had a higher rate of SFRP1 methylation compared to ER negative patients.CDH1 methylation was negatively related to distant metastasis.Conclusion The four candidate genes methylation in PBC were strongly associated with clinical progress for breast cancer patients.CDH1 and SFRP1 methylation were significantly related with ER status.They provide certain reference for disease assessment,treatment and prognostic analysis.

The purpose of this study is to explore RT-PCR method to set up the examination platform for detecting circulating tumor cells (CTC) in peripheral blood from metastatic breast cancer patients. The primary endpoint is to find out the correlation of existence of CTC with clinical responses and progression-free survival (PFS).