Neuregulin-1对血管生成的影响

Neuregulin-1(NRG1)简称神经调节因子1,属于NRG家族的一员,广泛存在于人体各组织之中。NRG是一个由4种基因编码的多肽家族,其包含4种异构体NRG1、2、3和4。NRG的功能性受体由erb B酪氨酸激酶受体所组成。Erb B蛋白属于跨膜酪氨酸激酶的表皮生长因子受体(EGFR)家族成员。NRG通过与特异性Erb B受体结合,并活化后者而发挥其相应的生物学效应。本文总结归纳NRG1对血管方面的影响和作用。     

新型白蛋白微泡经超声介导破裂促进EGFP基因在Cos-7细胞的表达

目的：根据超声介导白蛋白微泡破裂空化效应可以增加真核细胞膜对大分子(如DNA)通透性的原理，探讨一种新的转基因方法，以便安全有效和定向地转移目的基因。方法：实验中选择绿色荧光蛋白基因EGFP为标记基因，以自制的白蛋白微泡为载体，用超声介导微泡破裂的方法在体外进行Cos—7细胞的基因转化，同时以脂质体为对照，激光共聚焦显微镜和流式细胞计数仪分别定性和定量观察细胞转化效率。锥虫蓝染色观察细胞的活性。结果：体外试验发现0．8MHz、1．0W／cm^2、10％占空比(dutycycle)、60s超声介导10％白蛋白微泡破裂可以有效稳定地转化EGFP基因在Cos—7细胞表达，且对细胞无毒副作用。结论：自制白蛋白微泡是一种安全、有效的新型基因载体，在一定超声条件控制下，能增强基因的转导与表达，有良好的靶向性，提示该技术有应用于临床基因治疗的广阔前景。     

结直肠癌c-erbB-2和nm23癌基因蛋白的免疫组织化学研究

目的　根据结直肠癌的生物学行为 ,探讨结直肠癌手术标本中c erbB 2和nm2 3蛋白表达的临床意义及其术前检测c erbB 2和nm2 3蛋白对结直肠癌的诊断价值。方法　收集结直肠癌手术标本96例 ,其中 5 6例经肠镜活检标本病理证实 ,应用免疫组化技术检测c erbB 2和nm2 3蛋白在手术标本及活检标本中的表达。结果　c erbB 2阳性率为 2 1.4%～ 2 8.6 % ,nm2 3为 6 9.6 %～ 76 .1%。c erbB 2的表达与组织学类型有关 ,c erbB 2表达阳性组 5年生存率低于阴性组 ;nm2 3的表达与肿瘤的浸润深度Dukes′分期及组织学类型有关 ,且nm2 3表达阳性组 5年生存率高于阴性组。c erbB 2和nm2 3蛋白的阳性率在结直肠癌的肠镜活检标本和手术标本中无显著差异。结论　对结直肠癌组织进行c erbB 2和nm2 3蛋白的检测 ,有助于结直肠癌的诊断及非手术临床分期的判断 ,以及进一步了解结直肠癌生物学行为和评估结直肠癌患者的预后     

A meta‐analysis on the association of HER‐2 overexpression with prognosis in human osteosarcoma

LI Y.G. & GENG X. (2010) European Journal of Cancer Care 19, 313–316
A meta‐analysis on the association of HER‐2 overexpression with prognosis in human osteosarcoma Various studies examining the relationship between HER‐2 overexpression and clinical outcome in patients with osteosarcoma have yielded inconclusive results. The purpose of the current study was to evaluate the relation of HER‐2 status with clinical outcome in osteosarcoma. We conducted a meta‐analysis of five studies that evaluated the relation between HER‐2 status and 2‐year survival. DerSimonian‐Laird random effects analysis was used to estimate the effects of HER‐2 overexpression on 2‐year survival. The combined relative risk in patients with osteosarcoma for 2‐year survival was 1.26 (95% confidence interval, 0.50–3.14; P = 0.63). HER‐2‐positive status tended to be associated with a worse 2‐year survival, but the overall results were not formally statistically significant. An unfavourable prognostic effect of HER‐2 overexpression in osteosarcoma was evident from the meta‐analysis. However, because several studies were excluded by the current eligibility criteria, caution is needed in interpreting the results.     

Quantitative HER2 protein levels predict outcome in fluorescence in situ hybridization‐positive patients with metastatic breast cancer treated with trastuzumab

BACKGROUND:

Only a portion of breast cancer patients currently selected for trastuzumab therapy respond.

METHODS:

Using a novel assay (HERmark) to quantify total human epidermal growth factor receptor 2 (HER2) expression, the authors examined outcomes in 102 trastuzumab‐treated metastatic breast cancer patients previously assessed as immunohistochemistry (IHC) 3+ by local but not central IHC, or fluorescence in situ hybridization (FISH) positive, and then retested by central FISH.

RESULTS:

Of 102 MBC patients previously scored as IHC 3+ or 2+/FISH‐positive and treated with trastuzumab‐containing regimens, 98 had both central FISH and HER2 total expression values. Sixty‐six of 76 central FISH‐positive patients (87%) had high HER2 total expression levels (concordant positive), and 19 of 22 central FISH‐negative patients (86%) were HER2 total expression low (concordant negative). Fourteen percent (3 of 22) of central FISH‐negative patients were HER2 total expression high (discordant HER2 total expression high), and 13% (10 of 76) of central FISH‐positive patients were HER2 total expression low (discordant HER2 total expression low). The concordant positive group had a significantly longer time to progression (TTP, median = 11.3 months) compared with the concordant negative group (median TTP, 4.5 months; hazard ratio [HR] = 0.42, P < .001), and also compared with the discordant HER2 total expression low group (median TTP, 3.7 months; HR = 0.43, P = .01). The discordant HER2 total expression low group behaved similarly compared with concordant negatives (HR = 1, P = .99). In analyses restricted to central FISH‐positive patients only (n = 77), Cox proportional hazards multivariate regression identified HER2 total expression as an independent predictor of TTP (HR = 0.29, P = .0015) and overall survival (HR = 0.19, P < .001).

CONCLUSIONS:

A subset of patients with HER2 gene amplification by FISH express low levels of HER2 protein and have reduced response to trastuzumab‐containing therapy, similar to FISH‐negative patients. This cohort represents a training dataset, and the observed relationships and derived cutoffs require validation in an independent cohort of trastuzumab‐treated metastatic breast cancer patients. Cancer 2010. © 2010 American Cancer Society.     

Characterization of the Individual and Cross-reactive Antigens Involved in the Anti-tumor Immunity Induced by Use of an H-2K-erbB Recombinant Gene Transfectant

The specificities of the antisera raised in the CDF4 mice that had been immunized with the Pl. HTR tumor cells xenogenized by transfection with recombinant H-2Kb-erbB gene were studied. The antisera cross-reacted with a broad range of tumor cell lines maintained either in vitro or in vivo in an immunofluorescence assay. However, they did not react at all with syngeneic normal tissue cells from thynms, spleen, bone marrow and fetal liver. Even though antigens related to the murine leukemia virus and murine mammary tumor virus (MuMTV) were demonstrated in many of the tumor cell lines tested with specific antibodies, these antigens did not seem to be primarily involved in the anti-Pl. HTR antibody activity. The 74 kDa molecule, which was precipitated by the anti-Pl. HTR anti-serum from the surface radiolabeled cell extract of Pl. HTR tumor and was discriminated from the 70 kDa molecule precipitated by the anti-MuMTV serum, was widely distributed among various tumor cell lines tested, but was absent in normal tissue cells. In contrast to the extensive cross-reaction by the antibody, the cytotoxic T lymphocyte generated in the Pl. HTR immune mice were shown to be specific to the Pl. HTR tumor, and the 98 kDa molecule was precipitated by the anti-Pl. HTR serum from the Pl. HTR tumor but not from other tumors tested. It is suggested from these results that the 98 kDa molecule is a candidate for an individual tumor-specific transplantation antigen, and is immunodominant for inducing cytotoxic T lymphocytes to coexisting intrinsic retroviral antigens and other serologically cross-reactive tumor antigens.     

erbB4／HER4在原发性肝癌的表达研究

目的：检测第四人体表史生长因子受体HER4在原发性肝癌组织中的表达,探讨HER4过度表达与肝癌临床病理的关系。方法：采用免疫组化的方法,检测有随访资料的56例肝癌组织中HER4的表达。结果：肝癌组织中HER4的过度表达率达82．93％,肝癌中HER4的过度表达仅与淋巴结转移、门静脉癌栓及TNM分期相关。结论：erbB4是晚期肝癌生长的一个调控基因,干预HER4的过度表达可能是治疗晚期肝癌的有效方法。     

骨髓增生异常综合征染色体异常与白血病发展

目的：探讨在骨髓增生异常基础上白血病发展。方法：骨髓细胞Brdu-SCD细胞周期检测法和R-带染色体核型分析法,在1989年-1998年间对361例MDS(按FAB分类)、11例回顾性诊断白血病前期(PL)和73例MDS-RCMD(按WHO分类)以及140例AA和PNH骨髓细胞进行分析。并对18例MDS-RCMD进行V-erbB基因诊断。还对30例MDS和AA进行动态观察。与此同时,有25例MDS转变为急性白血病,它们几乎都是骨髓细胞SCD阴性患者,与回顾性诊断白前的结果相同。结果：1)361例MDS中MDS-RA占91.3％,核型异常检出率为66.2％,SCD阴性病例占50．9％,与以往报道的结果相似。染色体异常检出率高于文献报道。MDS中两项均不正常的病例占31．5％。2)从和PNH核型异常检出率为13．5％,SCD阴性病例占19．2％。两项指标均明显低于MDS,且两项均不正常患者仅为1．4％。3)MDS,RCMD,AA和回顾性白前有相同染色体异常,但有不同的克隆性异常检出率。4)MDS从SCD阳性转变为阴性,从保持阳性或阴性转变为阳性。结论：1)白前和MDS发展为白血病,或白前转变为MDS而后发展为白血病的共同机制在于骨髓细胞SCD阴性。它可能与胸苷酸代谢异常和胸苷酸合成酶基因扩增并长期积累有关。2)白前、MDS和AA可能有共同的细胞克隆起源。这一点已为AA／AML家系研究所证实。