PTEN对髓系白血病细胞VEGF及MMP表达的影响简

 目的 探讨在慢性髓系白血病中与张力蛋白同源的10号染色体缺失的磷酸酶基因(PTEN)对血管内皮生长因子(VEGF)及金属基质蛋白酶(MMP)相互影响及其作用机制。方法 1)研究10例慢性髓系白血病慢性期CML-CP、10例急变期CML-BC及10例正常人骨髓单个核细胞内PTEN、VEGF、MMP-2和MMP-9 mRNA表达水平变化。2)将携带有野生型PTEN和绿色荧光蛋白的腺病毒（Ad-PTEN-GFP）及对照载体腺病毒（Ad-GFP）转染人慢性髓系白血病细胞系K562。MTT检测细胞增殖;荧光定量PCR（FQ-PCR）检测PTEN、VEGF、MMP-2和MMP-9 mRNA水平变化,Western blot及明胶酶谱检测PTEN、p-Akt、VEGF、MMP-2和MMP-9蛋白表达。结果 CML-BC患者中PTEN mRNA表达水平低于CML-CP及正常对照组(P<0.05),而VEGF、MMP-2、MMP-9 mRNA在CML-BC患者中均高于CML-CP及正常对照组(P<0.05)。以MOI=200转染K562细胞3d后Ad-PTEN-GFP组K562细胞内VEGF、MMP-2、MMP-9 mRNA表达水平均明显低于Ad-GPF组和未转染组(P<0.05),PTEN与VEGF、MMP-2、MMP-9 mRNA表达水平负相关,转染Ad-PTEN-GFP组与转染Ad-GFP组比较VEGF、MMP-2、MMP-9 mRNA表达水平分别降低4.80、5.88、5.72倍,p-Akt及VEGF、MMP-2、MMP-9蛋白表达水平分别降低26.0、5.23、2.86、4.76倍。结论 PTEN基因可能通过抑制VEGF、MMP-2、MMP-9表达,抑制髓系白血病细胞血管新生及侵袭。     

去分化用于细胞治疗的前景与展望简

 去分化是一种重要的细胞生物学现象,在体和离体环境下均可发生。去分化后得到的细胞具有未分化细胞的特征。去分化的过程较为复杂,涉及细胞自噬、细胞结构再循环等一系列生物学行为。越来越多的研究证实细胞去分化与细胞更新、组织再生和肿瘤发生等有着密切联系。     

互联网在外科临床教学中的意义简

 分析在互联网时代,互联网给外科教学带来的影响,通过分析其在外科教学过程中的应用,以便充分合理地利用互联网资源,更好地提高外科教学效果。     

YAP蛋白与肿瘤简

 Hippo-YAP 信号通路是新发现的生长控制信号通路, 能够限制调结细胞的生长增殖, 细胞凋亡, 信号通路异常有利于肿瘤的发生。YAP蛋白还参与调控AKT-mTORC、WNT和MAPK等信号通路,进而影响肿瘤细胞的生长和侵润转移。YAP蛋白在多种类型的人类肿瘤中表达异常增加,或许成为肿瘤新的治疗靶点。     

调整紫杉醇化疗预处理方案的临床观察简

 目的 观察不同紫杉醇预处理方案化疗的用药安全性和不良反应,探索新的紫杉醇化疗预处理方案 方法 紫杉醇 135~175mg/m2,联合铂类药物,21d/周期,输注紫杉醇前用2种预处理方案,比较应用2种预处理方案化疗的不良反应 结果 77例应用调整预处理方案的患者与78例标准预处理方案患者的急性过敏反应、神经毒性、胃肠道反应发生率比较均无差异 结论 调整后的紫杉醇预处理方案安全、有效,与标准预处理方案比较无差异。     

分支DNA技术检测血浆游离DNA方法的建立及在急性心肌梗死患者中的初步应用简

 目的 采用分支DNA（bDNA）信号放大定量技术建立检测血中游离DNA（cf-DNA）—ALU基因表达的方法并分析其在急性心肌梗死（AMI）患者血浆中的含量。方法 根据ALU基因序列特点设计探针,建立检测血ALU的bDNA信号放大定量方法,并对其线性、灵敏度及精密度进行评价;根据标准曲线计算出AMI患者血浆中ALU的含量,并与肌钙蛋白I（cTnI）、肌酸激酶同功酶MB（CK-MB）和肌红蛋白（MYO）进行相关性分析。结果 线性范围为0~400 ng/mL,相关系数为0.99,批内变异系数（CV）为7.85%~11.75%,批间CV为10.05%~14.32%。AMI患者和健康对照组血浆ALU的含量分别是中位数4223 ng/mL和118 ng/mL,四分位数区间2285~7864 ng/mL和81~218 ng/mL（P＜0.001）,提示AMI患者血浆ALU含量上调,但与cTnI、CK-MB和MYO浓度无相关性。ALU的ROC曲线下面积为0.99,敏感度98.8%,特异性100.0%。结论 本研究建立的检测方法具有灵敏、重复性好等优点,升高的ALU含量与AMI存在一定相关性。     

HSP90抑制剂在急性髓细胞白血病治疗中的最新研究进展

热休克蛋白90(HSP90)是许多癌基因下游蛋白的分子伴侣,参与多重致癌途径,涉及急性髓细胞白血病(AML)的发生和不良预后。HSP90抑制剂是当前AML分子靶向治疗研究药物之一,通过抑制HSP90同时实现对多重致癌信号通路的调控发挥抗白血病作用。     

蛋白酶体抑制剂MG132减轻糖尿病大鼠肾小管间质纤维化简

 目的 探讨蛋白酶体抑制剂MG132是否减轻或延缓糖尿病肾病(DN)大鼠肾小管间质纤维化及其可能机制。方法 用链脲菌素复制糖尿病大鼠模型(DM),实验分为对照组(NC) 及DM组,每组n = 10。24周处死大鼠,检测相应生化指标,观察肾组织病理改变;体外培养NRK-52E细胞,予以不同剂量MG132预处理后高糖培养。免疫组化、免疫荧光染色、Western blot检测肾组织和NRK-52E细胞中Smad7、Smurf2、E钙黏蛋白(E-cadherin)和α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)及胶原蛋白(Col-Ⅰ)的表达。结果 与NC组相比,DM组大鼠肾组织E-cadherin减少(P<0.05)、α-SMA增多(P<0.05),FN及Col-Ⅰ蛋白在间质沉积增多(P<0.05),而Smad7蛋白减少(P<0.05), Smurf2表达增加(P<0.05)。MG132 抑制了高糖诱导的NRK-52E细胞α-SMA和Col-Ⅰ蛋白的表达(P<0.05),并呈量效依赖性,但对Smurf2的蛋白表达无影响;相反,MG132上调了Smad7蛋白及E-cadherin的表达(P<0.05)。结论MG132减缓糖尿病大鼠肾小管间质纤维化。     

胆胰转流术改善2型糖尿病的研究进展简

 胆胰转流术（BPD）将胆胰液转流至回肠,减少胆胰液与食物的混合时间,进而减弱消化吸收。临床观察上发现,BPD可以长期稳定地改善2型糖尿病并减少糖尿病各并发症,与胃旁路术有相似的效果,其确切机制不明,目前研究提示与胃肠激素、血脂、胰岛细胞功能的改变和胆胰液转流等有关。     

对泰兴麻风村康复模式的探讨简

 麻风村是特殊历史时期的产物,它为麻风病防治做出了突出贡献。因防治得力,新发麻风患者减少,麻风村工作的重点也开始转向康复者的康复工作。2012年夏,北京协和医学院临床医学2008级28名同学赴江苏省泰兴市麻风村进行社会实践。调研发现目前麻风村隔离式的康复模式存在一定弊端,不利于驻村康复者的身心健康。因此,建议改进康复模式、增进社会人文关怀。     

Polychemotherapy of acute myelogenous leukemia in a patient with acute intermittent porphyria

Summary The safety of drugs in hepatic porphyrias has largely been established by clinical experience, which is very limited in the case of antineoplastic agents. We administered three cycles of polychemotherapy consisting of daunorubicin, cytarabine and 6-thioguanine, and modified supportive care to a 33-year-old Turkish woman suffering from acute myelogenous leukemia. The urinary excretion of total porphyrins, porphobilinogen, and aminolevulinic acid was continuously monitored. Excreation of these metabolites was permanently elevated, but the values were comparatively low during cytotoxic therapy while peak values were recorded at the onset of fever during bone marrow aplasia; yet there were no clinical signs of porphyritic attacks at that time. A few potentially unsafe drugs were tolerated without an increase in porphyrin excretion. Although the susceptibility to drugs is highly variable in patients with hepatic porphyrias, the treatment of malignancy in these patients seems justified as long as porphyrin excretion under therapy is not grossly elevated over baseline values and appropriately modified supportive care is administered.Abbreviations AIP Acute intermittent porphyria - ALA Aminolevulinic acid - CR Complete remission - DAT Daunorubicin, cytarabine (Ara-C), 6-thioguanine - FAB French, American, British classification - PBG Porphobilinogen - Po Porphyrin - RBC Red blood cells     

The potential for antitumor vaccination in acute myelogenous leukemia

 While many advances have been made in the treatment of patients with cancer, significant challenges that remain include tumor cell resistance and the toxicity associated with currently used intensive chemotherapeutic regimens. This is particularly true for patients with acute myelogenous leukemia (AML). Most patients with AML usually are able to achieve complete remission, but only a minority obtain long-term survival. In addition, much of the success achieved has been due to escalation of chemotherapeutic dosing and hematopoietic stem cell transplantation. There is thus a great need for improved therapies which would ideally be able to circumvent drug resistance and more specifically target leukemic cells. Advances in immunobiology over the past century have led to new hope for the development of immune-mediated vaccine therapies for patients with cancer. This review focuses on the development of vaccine approaches for treatment of AML and some of the potential advantages and problems. Received: 10 December 1996 / Accepted: 12 May 1997     

HLA-DRB1基因多态性与急性淋巴细胞白血病和慢性髓性白血病易感性关联的研究

目的探讨急性淋巴细胞白血病（ALL）和慢性髓性白血病（CML）易感性与HLA-DRB1基因多态性之间的关联性,找出急性淋巴细胞白血病和慢性髓性白血病的易感基因。方法采用序列特异性引物聚合酶链反应（PCR-SSP）DNA分型技术对56例ALL患者、48例CML患者和105例健康对照进行了HLA-DRB1基因分型。结果ALL患者组与HLA-DR7基因关联,基因频率为24.1%,RR=2.56,χ     

酪氨酸激酶抑制剂治疗后慢性髓细胞白血病患者Ph阴性细胞中染色体异常的遗传学特征和转归

目的 观察酪氨酸激酶抑制剂治疗后慢性髓细胞白血病(chronic myelogenous leukemia,CML)Ph阴性细胞中染色体异常(chromosomal abnormalities in Ph negative cells,Ph- CAs)的遗传学特征和转归.方法 对15例接受酪氨酸激酶抑制剂治疗后出现Ph- CAs的CML患者进行遗传学和分子学动态观察.结果 出现Ph- CAs患者中,依马替尼治疗12例,达沙替尼治疗2例,伯舒替尼治疗1例,染色体异常以+8最为多见,占46.7％.Ph- CAs出现在ph+克隆减少或消失时,出现的平均时间为11.1个月(1～28个月);7例Ph- CAs已经消失,Ph- CAs持续的平均时间为10.9个月(3～24个月).Ph- CAs出现时,所有病例均未见骨髓病态造血或急性白血病;Ph- CAs出现后,除1例患者演变为ph+急性单核细胞白血病外,其余均获得骨髓缓解,11例获完全细胞遗传学反应,4例获完全分子学反应.结论 依马替尼、达沙替尼和伯舒替尼治疗CML患者均可能出现Ph- CAs;Ph- CAs多数为一过性,对酪氨酸激酶抑制剂治疗效果无影响.     

Ovarian granulocytic sarcoma as the primary manifestation of acute myelogenous leukemia

Granulocytic sarcoma (GS) usually occurs concomitantly with or after the onset of acute myeloid leukemia (AML) or other myeloproliferative disorders, however, GS of the ovary as the primary manifestation of AML is exceedingly rare. To the best of our knowledge, eight cases of ovarian GS as the first sign of AML have been reported in the literature. Here, we report the ninth case: a 27-year-old female who presented with an ovarian mass without any underlying hematologic disorder. A high index of suspicion aided by immunohistochemistry established the correct diagnosis of undifferentiated GS that involved the ovary. Simultaneously, laboratory findings indicated that the blood counts continually increased after surgery. Five days after the surgery, bone marrow biopsy confirmed the presence of AML. After establishing the diagnosis, the patient was sent to the hematology department to receive cytosine arabinoside and idarubicin chemotherapy. This report outlines an exceedingly rare case of AML that initially manifested as an ovarian GS. Awareness of this entity will enable earlier diagnosis and appropriate treatment.     

泛素蛋白酶系统通过稳定PPARγ调节脂肪细胞分化

目的:探讨泛素蛋白酶系统(ubiquitin-proteasome system,UPS)在体外脂肪细胞分化中的作用。方法:常规方法诱导前脂肪细胞分化为脂肪细胞,Western blot检测蛋白质表达,免疫共沉淀检查蛋白质间结合,油红O染色检测脂肪细胞中的脂质,RT-PCR检测mRNA表达。结果:UPS抑制剂硼替佐米可抑制3T3-L1前脂肪细胞分化为脂肪细胞,表现为细胞内脂质含量降低以及脂肪细胞标志蛋白mRNA表达的降低。蛋白激酶G激动剂西地那非可激活UPS,并增强脂肪细胞的分化。抑制UPS可降低热休克蛋白90(HSP90)和过氧化物酶体增殖物活化受体γ(PPARγ)间的结合;同时降低细胞可溶性组分中HSP90和PPARγ的表达,增强其在不可溶性组分中的表达。HSP90特异性的N末端抑制剂格尔德霉素可抑制西地那非促进的PPARγ表达和脂肪细胞的分化。结论:泛素蛋白酶系统通过HSP90调节PPARγ的表达,从而影响脂肪细胞的分化。     

Molecular variation of human HSP90alpha and HSP90beta genes in Caucasians

Understanding DNA variation within the human genome is fundamental to the identification and interpretation of genetic components underlying complex traits and diseases. Despite their role in many crucial cellular pathways and their reported involvement in many complex diseases no data are available on the molecular variability of the genes coding for Heat Shock Proteins 90Kda (HSP90). Towards this purpose we have used DHPLC methodology to survey, a sample of Caucasians for genetic polymorphisms in the exons and exon-flanking regions of the expressed genes of human HSP90 gene families, HSP90alpha (HSPCAL4, 14q31.3) and HSP90beta (HSPCB, 6p12). A total of 18 and 11 variants were found in the HSP90-alpha and -beta genes respectively, providing an initial view of human genetic variation in these important genes. Only three of the observed mutations altered the genic product. Interestingly, one of the variations observed was a missense mutation leading to the impairment of the hsp90alpha protein.     

Expression of minichromosome maintenance 8 in chronic myelogenous leukemia

Objectives: Minichromosome maintenance 8 (MCM8) is identified as an initiating helicase involved in DNA elongation and involved in cancer. However, little information is available for the role of MCM8 on chronic myelogenous leukemia (CML). We aimed to explore the expression and effect of MCM8 on CML. Methods: Peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) were prepared from six patients with CML and three healthy individuals. The mRNA levels of MCM8 were determined and compared. The expression of MCM8 was silenced by small interfering RNA (siRNA) approach in human CML cell line K562. After transfection with MCM8 siRNA, cell viability and apoptotic rate were analyzed, as well as the protein expression levels of Caspase-3 and B-cell lymphoma (Bcl)-xL. Results: Relative mRNA levels of MCM8 were both significantly higher in PBMC and BMMC from CML patients than those in healthy individuals (P < 0.05). The cell viability was significantly reduced while the apoptotic rate was statistically increased by knockdown of MCM8 compared to control group or the scramble siRNA group (both P < 0.05). Moreover, the protein expression levels of Caspase-3 were significantly increased (P < 0.05), and while the levels of Bcl-xL were statistically reduced (P < 0.05) compared to the control group or the scramble siRNA group. Conclusion: MCM8 plays a significant role in CML, and knockdown of MCM8 might be a potentially targeted therapy for CML.     

Esophageal aspergillosis in cytologic brushings: report of two cases associated with acute myelogenous leukemia

Aspergillus, which commonly involves the sinonasal region and upper respiratory tract, is reported for the first time in esophageal brushings in two immunocompromised patients with a history of acute myelogenous leukemia (AML). Aspergillus species was identified in both cases in smears as scattered three-dimensional groups of fungi with 45 degrees angle branching. One case had a local esophageal noninvasive form, while the other, in addition to the esophagus, had disseminated to the spleen. Although Aspergillus is an uncommon cause of esophagitis in immunocompromised patients, its presence may be associated with an extremely poor prognosis as both expired shortly after detecting this fungus on esophageal brushings.