胰腺癌GST—π耐药基因表达及意义

目的 检测胰腺癌组织中GST－π耐药基因的表达及其临床意义。方法 采用S－P免疫组织化学方法对150例异常和正常胰腺石蜡切片组织标本（包括原发性胰腺癌97例，胰腺炎32例和正常胰腺组织21例）进行GST－π耐药基因蛋白表达检测。结果 GST－π耐药基因在胰腺癌、胰腺炎和正常胰腺组织中阳性率分别为67％、15．6％和14．3％；胰腺癌组织中GST－π阳性率明显高于其他组织（P＜0．05）。胰腺癌高分化组织中GST－π耐药基因表达也明显高于低分化组织（P＜0．05）。GST－π耐药基因表达与胰腺癌病人的性别、年龄、肿瘤的部位、大小、侵袭性及临床分期等指标无关（P＞0．05），GST－π耐药基因表达阳性病人平均术后生存时间长于GST－π阴性病人。结论 GST－π可能参与胰腺癌的早期癌变过程，并在维护肿瘤的特性中起到一定的作用，GST-π 基因有可能成为胰腺癌的早期肿瘤酶标记物；GST－π耐药基因与胰腺癌的“天然性多药耐药”和肿瘤生物学特性有关，它是指导肿瘤化疗和预后的一个重要指标。     

肝癌差异表达基因研究进展

目前发现大量的癌基因、抑癌基因，或相关基因参与肝癌的发生，发展，在肝癌组织，癌旁肝组织，正常肝组织之间，在RNA，蛋白水平都存在众多的差异表达基因。认识这些基因及其转录，调控的分子机制，对于揭示肝癌的发病机制具有重要意义。本文就该领域的研究进展进行综述。     

绝经后Luminal B型乳腺癌的内分泌治疗

目的 探讨芳香化酶抑制剂和三苯氧胺对绝经后Luminal B型乳腺癌患者的疗效.方法 收集天津市肿瘤医院2002年7月至2005年3月间733例术后接受辅助内分泌治疗的原发性乳腺癌患者资料,肿瘤性质均经手术切除病理组织学证实.患者均为绝经后且ER阳性,其中501例接受三苯氧胺治疗,232例接受芳香化酶抑制剂治疗.采用免疫组化SP法进行ER、PR、HER2检测.随访时间36～90个月,中位随访时间46个月.结果 芳香化酶抑制剂治疗组Luminal B型乳腺癌患者三年无瘤生存率高于三苯氧胺组(90.6% vs.88.6%,P=0.038).三苯氧胺组亚组分析显示:LN+/HER2+患者三年无瘤生存率低于LN+/HER2-患者(88.2% vs 90.4%,P=0.037);HER2+/PR+患者高于HER2+/PR-患者(90.8% vs.89.5%,P=0.032).芳香化酶抑制剂组内LN(+)和LN(-)亚组中,HER2(+)患者与HER2(-)患者的三年无瘤生存率差异均无统计学意义(P>0.05);而HER2+/PR+组高于HER2+/PR-组(91.9% vs.90.5%,P=0.029).芳香化酶抑制剂组潮热、阴道出血、静脉血栓形成的发生率低,肌肉骨骼疼痛、骨折的发生率则高于三苯氧胺组(P<0.05).结论 芳香化酶抑制剂对绝经后Luminal B型患者疗效好于三苯氧胺,此效果不受患者腋窝淋巴结状态的影响,且耐受性和安全性较好.     

抗HLA和抗MICA抗体的表达对移植肾功能和急性排斥反应的预示作用

Objective To investigate the prediction of anti-human leukocyte antigen antibodies (HLA) and anti-major histocompatibility complex class I-related chain A antibodies (MICA) to the development of acute rejection (AR) and kidney allograft function. Methods Forty-one kidney transplant patients were prospectively tested for anti-HLA and anti-MICA. Thirty-seven patients were screened using Luminex/single-antigen beads to determine the HLA and MICA-specific antibody levels at 0,30,90, 180,360,720 and 1080 days post-transplantation. The patients and donors of HLA and MICA allele typing were determined by PCR-SSOP, and donor specific antibody (DSA) and non-donor specific antibody (NDSA) were identified.Simultaneously,their serum creatinine (SCr) levels and clinical data were analyzed. Results Nine patients (21.95 % ,9/41 ) had pre-existing anti-HLA and(or) anti-MICA, including 6 cases of anti-MICA,2 cases of anti-HLA, and one case of anti-MICA and anti-HLA. Nine patients had pre-existing DSA and NDSA. In the 37 patients, 6 patients (16.2% ) developed de novo anti-HLA, and 3 (8.1%) developed de novo antiMICA. In patients positive for de novo anti-HLA, the titer of antibody was gradually increased during the follow-up of three years. Four patients out of 9 patients with pre-existing antibodies were suffered from AR (44.4%); In 6 patients positive for de novo anti-HLA,three cases (50.0%) were suffered from AR; In three patients positive for de novo anti-MICA,no AR occurred (P＜0.05). In two patients positive for DSA of HLAⅡ antibody detected at the third and seventh day after transplantation, the renal grafts were renovecd due to rejection. The Scr levels in patients positive for pre-existing MICA with AR were higher than in those positive for pre-existing MICA without AR at each scheduled time point during the follow-up period (P＜0.05). The Scr levels in patients negative for antibodies pre-transplantation and having AR were higher than in those having no AR at each scheduled time point during the follow-up period (P＜0. 01 ). The Scr levels in patients positive for de novo HLA and MICA and having AR one month following transplantation were higher than in those negative for antibodies and having no AR (P＜0.01 ). Conclusion Pre-existing and de novo anti-HLA were the irnportant factors for the development of AR, but the mismatch of HLA and MICA alleles in donors and patients was primary causes for generation of de novo antibodies.     

伊马替尼治疗慢性移植物抗宿主病2例临床分析

目的探讨伊马替尼治疗异基因造血干细胞移植(allo-HSCT)后慢性移植物抗宿主病(GVHD)伴嗜酸性粒细胞增多的疗效及嗜酸性粒细胞增多与慢性GVHD的关系。方法回顾性分析2例白血病患者allo-HSCT术后慢性GVHD的诊治经过并结合文献复习讨论。结果 2例患者分别于移植后5个月和76d出现口腔溃疡、皮肤瘙痒、皮疹、胆红素水平增高和转氨酶水平增高,伴有嗜酸性粒细胞增多,诊断为局限型慢性GVHD,激素治疗不佳,加用伊马替尼后症状缓解,嗜酸性粒细胞数降至正常,无不良反应。结论伊马替尼治疗慢性移植物抗宿主病安全、有效,嗜酸性粒细胞增多可能与GVHD有一定的关系。     

造血干细胞移植相关早期并发症的防治

目的总结造血干细胞移植(HSCT)相关早期并发症的预防和治疗经验。方法 50例恶性血液病患者接受不同方法治疗,其中自体HSCT20例、异基因HSCT19例、混合HSCT10例和脐血HSCT1例。预处理方案包括白消安+环磷酰胺,卡莫司汀+依托泊苷+阿糖胞苷+马法兰,大剂量马法兰等。异基因HSCT患者采用环孢素+甲氨蝶呤为主的移植物抗宿主病(GVHD)预防方案,其中非亲缘异基因HSCT患者则采用环孢素+甲氨蝶呤+吗替麦考酚酯+抗胸腺细胞免疫球蛋白为主的GVHD强化预防方案。所有患者均采用小剂量肝素及复方丹参,部分联合前列腺素E1脂质体微球预防肝静脉闭塞病。所有献血员进行CMV特异性抗体筛查和分次全身照射。结果 50例患者中发生肝静脉闭塞病1例(2.0%),该患者合并Ⅳ度GVHD,症状持续加重且治疗无效,于+26d死亡。CMV血症4例(8.0%),1例发生CMV间质性肺炎,经过抗病毒治疗后痊愈。30例异基因及混合HSCT患者中16例(53.3%)发生急性GVHD,其中Ⅰ度3例、Ⅱ度6例和Ⅲ～Ⅳ度7例,经过治疗后,4例重度患者死亡,其余12例病情控制;6例(20.0%)发生慢性GVHD。发生出血性膀胱炎2例(4%),经对症治疗后痊愈。结论通过筛查献血员CMV-IgM和CMV-IgA抗体,输注经照射及白细胞滤除的血制品,监测CMV-pp65及抗CMV抗体,预防性使用抗病毒药物及分次全身照射等综合措施可以有效地防治CMV感染。对不同移植种类的受者采用不同强度的GVHD预防方案十分必要。     

干细胞移植治疗重症肌无力的机制及应用现状

干细胞移植能重建免疫平衡、诱导免疫耐受,已作为自身免疫病的重要治疗手段在临床上广泛应用。重症肌无力作为典型的自身免疫病,其移植治疗目前以自体造血干细胞移植为主,亦有异基因造血干细胞移植的案例,均取得了较好的疗效。间充质干细胞移植作为新的手段,大量的基础研究已显示了其潜在价值,正逐步向临床应用过渡。     

腺病毒介导反义细胞外信号调节蛋白激酶2基因转染可延缓移植肾慢性纤维化进程

严重制约肾移植受者长期存活的重要因素是慢性移植。肾纤维化。慢性移植肾纤维化由免疫学和非免疫学因素引起,临床上一般通过调整免疫抑制方案和其他辅助方法予以治疗,目前还没有直接对移植肾纤维化起作用的药物或治疗方案。我们的研究试图寻找可以保护移植物,阻止或延缓移植肾纤维化的方法和相应的治疗靶点。