肺癌患者血清PGE2水平及其对IL-2/sIL-2R的影响

目的 :探讨肺癌患者围手术期血清PGE2 水平的变化及其对IL 2 /sIL 2R的影响。方法 :采用放射免疫检测法 ( 12 5I RIA以及ELISA试剂盒 )分别检测 43例肺癌患者手术前、后的外周静脉血清PGE2 水平和IL 2 /sIL 2R ,术中抽取肿瘤回流静脉血用于检测PGE2 水平。结果 :肺癌患者外周静脉血存在较高的PGE2 ( 78 81± 3 2 15 )pg/mL ,与肿瘤回流静脉血中的PGE2 ( 13 1 0 7± 3 6 41)pg/mL呈显著相关 ,r =-0 3 15 ,P <0 0 1,术后其PGE2 显著下降 ;手术前后其IL 2 /sIL 2R处于相对较低水平 ,IL 2与PGE2 呈相关关系 ,而与sIL 2R无明显相关。术后IL 2有所上升 ( 15 3 83± 5 3 3 9)pg/mL ,但仍低于正常对照组 ( 2 3 0 2 9± 5 3 3 9)pg/mL ,P <0 0 5。结论 :肺癌患者存在着高水平的PGE2 ,是由肺部肿瘤引起的 ,对IL 2有一定的抑制作用。     

Prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) 8473T>C polymorphism associated with prognosis for patients with colorectal cancer treated with capecitabine and oxaliplatin

Purpose  The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer. Patients and methods  A total of 76 patients with recurrent or metastatic colorectal cancer treated with capecitabine and oxaliplatin (XELOX) combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 15 apoptosis-related genes (TP53, BCL2L, TNFRSF10B, AKT1, PTGS2/COX2, BID, RIPK1, FAS, FASL, caspase 3, and caspase 6-10) were determined using a PCR-RFLP assay. Results  No significant association between the polymorphisms and the response was found for any of the genes analyzed. However, the T/T genotype of PTGS2 8473T>C (rs5275) was significantly correlated with a better progression-free survival (PFS) and overall survival (OS) when compared to the combined T/C and C/C genotype (Hazard ratio [HR] = 0.47; P value = 0.046 and HR = 0.16; P = 0.013, respectively) in a multivariate analysis adjusted for age, sex, performance status, disease status and curative resection. No association was noted between the other polymorphisms and survival. Conclusion  The PTGS2 8473T>C polymorphism was found to be correlated with PFS and OS in patients with advanced colorectal cancer treated with XELOX chemotherapy.     

结肠癌合并2型糖尿病患者血清IGF-2、IGFBP-2升高与肿瘤复发的关系

摘 要：［目的］ 观察结肠癌合并2型糖尿病患者血清胰岛素样生长因子-2(IGF-2)及胰岛素样生长因子结合蛋白-2(IGFBP-2)升高与结肠癌复发的关系。［方法］ 选择结肠癌合并2型糖尿病患者90例为观察对象,以同期在院治疗合并2型糖尿病的良性结肠疾病患者90例为对照,在结肠癌术后1周时检测其血清IGF-2、IGFBP-2水平,与对照组进行比较,记录结肠癌患者在1年中复发的数据,按复发与否,描绘IGF-2、IGFBP-2水平与复发关系的ROC曲线图,观察IGF-2、IGFBP-2水平与复发的关系,统计IGF-2、IGFBP-2水平预测复发的灵敏度、特异性。［结果］ 结肠癌患者血清IGF-2、IGFBP-2水平明显高于对照组,具有统计学差异;IGF-2、IGFBP-2水平升高与结肠癌复发存在相关性,具有统计学差异（P<0.05）。［结论］ 结肠癌合并2型糖尿病患者血清IGF-2、IGFBP-2升高,并与结肠癌术后的复发相关。     

Thyroiditis after treatment with interleukin-2 and interferon alpha-2a

Serial thyroid functions studies were carried out in patients with melanoma and renal cell carcinoma treated with interleukin-2 (3 MU m-2 by continuous infusion days 1-4) and interferon alpha-2a (6 MU m-2 subcutaneously on days 1 and 4), both given on alternate weeks. The results on eight patients who completed at least three cycles of treatment are described. Four patients developed thyroid dysfunction with a hyperthyroid phase of 2 weeks followed by a hypothyroid phase ranging from 12 to 24 weeks. Two patients became clinically symptomatic and required treatment. Fine-needle aspirates of the thyroid were obtained in three patients with thyroid dysfunction. The cytology revealed a mixed cellular infiltrate with lymphocytes and histiocytes, and immunocytochemical staining showed strong HLA-DR expression of all thyrocytes, both suggestive of an autoimmune thyroiditis. One patient with thyroiditis developed anti-thyroglobulin antibodies, the serology of all other patients was normal. Patients with thyroid dysfunction tended to have higher in vivo stimulated lytic activity of peripheral mononuclear blood cells and had significantly higher levels of CD16 positive blood cells as compared to euthyroid patients. The possibility of autoimmune thyroiditis should be anticipated in future trails combining interleukin-2 and interferon alpha-2a.     

Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort

BackgroundHER2 mutations have been identified as oncogenic drivers in lung cancers and are found in 1–2% of lung adenocarcinomas. There is, to date, no standard of care for these patients. We thus aim to study the therapeutic outcomes of patients harboring HER2 mutations and establish the efficacy of various drug regimens.Patients and methodsThis retrospective cohort study in European centers assessed patients with advanced non-small-cell lung cancer (NSCLC), a known HER2 exon-20 insertion, treated with chemotherapy and/or HER2-targeted drugs.ResultsWe identified 101 eligible patients from 38 centers: median age 61 years (range: 30–87), 62.4% women, 60.4% never-smokers. All tumors were adenocarcinomas. Concomitant EGFR mutations, ALK translocations, and ROS translocations were observed in 5, 1, and 1 patients, respectively. The median number of treatment lines was 3 (range: 1–11). The median overall survival was 24 months. Overall response rate (ORR) and the median progression-free survival (PFS) with conventional chemotherapy (excluding targeted therapies) were 43.5% and 6 months in first-line (n = 93), and 10% and 4.3 months in second-line (n = 52) therapies. Sixty-five patients received HER2-targeted therapies: trastuzumab = 57, neratinib = 14, afatinib = 9, lapatinib = 5, T-DM1 = 1. ORR was 50.9% and PFS was 4.8 months with trastuzumab or T-DM1.ConclusionThis series shows the chemosensitivity of HER2-driven NSCLC, and the potential interest of HER2-targeted agents. Our results should help to define the best therapeutic strategy for these patients and to orient future clinical trials.     

反义核酸抑制胃癌细胞Bcl-2表达

本文采用分子克隆技术成功地构建了反义核酸表达载体pDOR-Bcl-2 cDNA.以脂质体介导法将重组反义核酸表达载体转染受体细胞SGC7901,并经C418筛选,从2×10~5细胞中筛选出大约150个抗性克隆,转导率大于1‰,随机挑选2个克隆继续筛选与扩增培养,获得了1株稳定的抗性细胞,从而建立了Bcl-2表达阻断的胃癌细胞株,我们命名为7901anBcl-2 cells.通过Southern印迹法、Northern印迹法、Western印迹法检测显示,转导株与非转导株均有Bcl-2 cDNA的表达,但转导株Bcl-2 mRNA及蛋白的表达明显低于非转导株.说明在胃癌细胞中Bcl-2基因处于高表达状态,通过真核表达载体介导的转染,反义Bcl-2可成功地导入胃癌细胞,并有效地阻断Bcl-2表达.     

鼻咽癌患者白细胞介素—2活性变化的研究

选出鼻咽癌病例及正常人对照各32例。测定放疗前后外周血IL-2活性。结果表明:病例组放疗前IL-2活性显著低下,放疗后明显回升,但仍低于对照组(P<0.01)。4例肿瘤残存者IL-2活性回升不良。讨论认为:肿瘤负荷可能是抑制IL-2活性的主要因素,IL-2活性检测可能作为监测肿瘤负荷及估计肿瘤患者预后的指标。     

Interleukin-2 (IL-2) production and interleukin-2 receptor expression in patients with aplastic anemia

IL-2 production and IL-2 receptor (Tac antigen) of the peripheral blood mononuclear cells in 30 patients with aplastic anemic (AA) were studied. We found that mononuclear cells from patients produce spontaneously IL-2 in the absence of exogenous lectin stimulation, the proportion of Tac⁺ cells in mononuclear cells increased. The release of IL-2 and/or Tac antigen expression were elevated in almost every patient with AA. The plasma from patients stimulate mitogen-induced blastogenesis and Tac antigen expression of normal human lymphocytes. Immunological 1 abnormalities of patients with AA possibly might represents secondary response to bone marrow depression.     

Adoptive immunotherapy with interleukin 2 in oncology

Forty-seven patients with renal carcinoma were included in first line or rescue protocols of immunotherapy including IL2 alone or in association with LAK cells, INF alpha or TNF. The toxicity was mild and the mortality was 2% (1 patient). The response rate was 26%. Nineteen children with neuroblastoma received IL2 either alone or in combination with LAK cells. The morbidity and mortality were higher in patients with end stage disease who had previously received high dose and prolonged chemotherapy. In contrast, the toxicity was mild and transient in patients treated in the months following autologous bone marrow transplantation. The only complete response observed was in 1 child treated with IL2, 4 months after high dose chemotherapy and ABMT. Immunological analysis showed that the immunomodulatory effect of IL2 is very different depending on whether IL2 is used alone or in combination with other cytokines; moreover, the biological effect of IL2 is dependent on the immunological status of the patients prior to IL2 therapy.     

Ⅱ型糖尿病与结直肠癌的相关性研究

目的:探讨结直肠癌与Ⅱ型糖尿病的相关性,了解Ⅱ型糖尿病对结直肠癌的发病、围手术期并发症以及预后的影响。方法:选取2002年-2010年间经病理确诊的结直肠癌手术后患者256例,同时期的非肿瘤手术后患者372例作对照,比较两组年龄、性别、体重指数(body mass index,BMI)、病程、糖尿病病史、糖尿病家族史、并发症、肿瘤系列生化检查及环境因素如吸烟和饮酒等因素,同时还分析了结直肠癌的发生率,以及各组对手术后并发症和预后的影响。结果:结直肠癌患者中Ⅱ型糖尿病的患者发生率为30.1%;较非肿瘤患者高;其并发感染占6.6%。结论:多因素分析结果显示,结直肠癌与Ⅱ型糖尿病存在某种相关性,Ⅱ型糖尿病增加了感染机会,并且增加了结直肠癌的风险和结直肠癌根治手术后感染的风险。     

INT2 and ERBB2 amplification and ERBB2 expression in breast tumors from patients with different outcomes

Summary The relationships of INT2 and ERBB2 amplification and of ERBB2 overexpression in primary breast tumors to prognostic factors, recurrence, and survival have generated considerable controversy. The rationale for this study is that long-term, recurrence-free survival is a more direct criterion for testing the validity of a tumor marker than correlation either with prognostic factors or with short-term recurrence and survival. We examined the association of recurrence with INT2 and ERBB2 amplification and ERBB2 expression by comparing primary breast tumors from patients surviving without recurrence for 8.5 years after diagnosis. the LTS group, to tumors from patients recurring within two years, the RR group. The RR (N = 63) and LTS (N = 61) samples were coded and examined for amplification by Southern blotting and for expression by immunohistochemistry. Comparison between the RR and LTS groups demonstrated that INT2 amplification was associated with a significantly (P = 0.018) higher (5.6-fold) risk of recurrence, an association that remained significant after controlling for lymph node (LN), tumor size (TS), and histograde (HG) status. ERBB2 amplification and expression were not associated with a higher recurrence risk. Survival analyses within the RR group, however, demonstrated significantly shorter survival time among cases with than without ERBB2 amplification (P = 0.018, median survival 16 vs 25 months), or ERBB2 expression (P = 0.019, median survival 15 vs 25 months), but not INT2 amplification. Univariate Cox proportional hazards regression models also demonstrated significantly shorter survival among cases with ERBB2 amplification (P = 0.016) or expression (P = 0.049), that remained significant in multivariate analyses (P = 0.022) for ERBB2 amplification. These results indicate a significant positive association between INT2 amplification and risk for tumor recurrence in the RR as compared to the LTS group. The relationship of ERBB2 amplification or overexpression to patient outcome is more complex. ERBB2 amplification and expression have a significant relationship with shorter survival among patients recurrent within two years, but their occurrence in tumors from women surviving without recurrence for 8.5 years suggests that ERBB2 status is not predictive of shorter survival for all breast cancers.