5-Aza-CdR对人结肠癌Lovo细胞增殖凋亡及抑癌基因RUNX3表达的影响

目的:研究抑癌基因RUNX3在人结肠癌细胞中的表达情况,探讨5-氮-2′-脱氧胞苷 (5-Aza-CdR)对人结肠癌Lovo细胞增殖凋亡及 RUNX3表达的影响．方法:用特异性甲基转移酶抑制剂5-Aza-CdR 0．4,4,40μmol/L处理人结肠癌细胞株Lovo 3 d,继续常规培养5d后,采用四唑盐(MTT) 比色观察细胞经药物处理前后的生长活性．以半定量RT-PCR检测细胞处理前后抑癌基因 RUNX3 mRNA的表达,应用流式细胞仪进行细胞凋亡率的检测结果:人结肠癌细胞Lovo经处理后,与对照组比较,5-Aza-CdR 0．4,4,40 μmol/L均能明显抑制肿瘤细胞生长,随5-Aza-CdR浓度增加,细胞生长速率下降;对照组Lovo细胞未见 RUNX3 mRNA表达．经药物处理后的细胞均检出该种mRNA的重新表达,其mRNA的表达相对量分别为0．46±0．06,0．71±0．06,0．84 ±0．07,与药物存在剂量依赖性(F=168．4, P<0．01):对照组细胞凋亡率为2．92％±0．93％, 5-Aza-CdR 0．4,4,40 μmol／L处理后Lovo细胞凋亡率分别为10．95％±2．09％,17．61％± 1．51％,26．60％±1．89％,与对照组相比较均有统计学意义(P<0．01),且凋亡率与5-Aza-CdR 剂量呈正相关(F=145．7,P<0．01)．结论:在人结肠癌细胞株Lovo中,基因 RUNX3可能因过甲基化而导致转录失活, RUNX3基因重新表达能抑制细胞生长,并能诱导部分细胞凋亡．     

5-氮杂-2'-脱氧胞苷对人胃癌SGC-7901细胞株生长及EDNRB基因启动子异常甲基化的影响

目的:探讨去甲基化药物5-氮杂-2'-脱氧胞苷(5-Aza-CdR)对人胃癌细胞系SGC-7901细胞株的生长及EDNRB基因启动子异常甲基化的影响.方法:使用1、2、5、10μmol/L5-Aza-CdR干预胃癌SGC-7901细胞,甲基化特异性PCR(MSP)和逆转录聚合酶链反应(RT-PCR)分别检测药物干预前后EDNRB基因的甲基化状态和EDNRB mRNA的表达,MTT法检测细胞增殖活性,流式细胞术分析细胞周期及细胞凋亡的改变.结果:未经5-Aza-CdR处理的SGC-7901细胞中EDNRB基因启动子区域CpG岛高甲基化,且EDNRB mRNA不表达,经1、2、5、10μmol/L5-Aza-CdR处理4d后,EDNRB基因启动子区域高甲基化状态得到逆转,细胞中EDNRB mRNA表达恢复.4种浓度5-Aza-CdR处理的SGC-7901细胞后,细胞增殖受到抑制,且呈时间和剂量依赖性;并抑制SGC-7901细胞生长周期,其细胞周期阻滞于S期,5、10μmol/L5-Aza-CdR实验组细胞凋亡率显著高于对照组,且差异有统计学意义(7.13%±0.87%,13.34%±1.12% vs 3.69%±...     

5-氮杂-2′-脱氧胞苷对结肠腺癌细胞株Caco-2细胞生物学行为的影响

[目的]研究去甲基化5-氮杂-2′-脱氧胞苷(5-Aza-CdR)对人结肠腺癌细胞株Caco-2细胞生长周期及凋亡的影响,探讨其临床治疗的可能性。[方法]分别使用0.4、1.6、6.4、25.6、102.4μmol/L浓度的5-Aza-CdR处理Caco-2细胞;通过MTT检测5-Aza-CdR对Caco-2细胞存活率的影响;应用流式细胞检测5-Aza-CdR对Caco-2细胞生长周期及凋亡的影响;RT-PCR检测处理前后抑癌基因RASSF1A mRNA表达的改变。[结果]1.6μmol/L浓度的5-Aza-CdR可以明显的抑制Caco-2细胞的增殖,细胞周期中处于G0/G1期的细胞明显的增多,阻滞于G1期,凋亡率增高;5-Aza-CdR的作用与其浓度、时间在一定范围内呈正相关。5-Aza-CdR处理后,无RASSF1A表达的Caco-2细胞可检测出基因RASSF1A的重新表达。[结论]5-Aza-CdR可消除某些抑癌基因启动子甲基化状态,使其重新表达而抑制Caco-2细胞的生长,并促进其凋亡。     

5′-氮杂-2′-脱氧胞苷对T47D乳腺癌细胞生物学行为的影响

目的探讨去甲基化5′-氮杂-2′-脱氧胞苷（5-Aza-CdR）对T47D乳腺癌细胞株生长周期及凋亡的影响。方法分别使用浓度为0．5、1．0、2．0．5．0、25．0、100．0μmol／L 5-Aza-CdR处理T47D细胞株。MTT法检测T47D细胞存活率。流式细胞仪检测T47D细胞生长周期,观察细胞凋亡情况。RT—PCR法检测处理前后抑癌基因p16 mR—NA表达。结果5-Aza-CdR作用后T47D细胞明显受抑,G0／G1期细胞明显增多,细胞阻滞于G1期,凋亡率明显增高;5-Aza—CdR处理后无p16表达的T47D细胞检测出p16基因的重新表达。结论5-Aza—CdR可抑制T47D细胞的生长,并促进其凋亡;其机制可能为消除某些抑癌基因启动子甲基化。     

5-氮杂-2′-脱氧胞苷对胃癌AGS细胞CHFR基因去甲基化作用及意义

目的观察5-氮杂-2′-脱氧胞苷（5-Aza-CdR）对胃癌AGS细胞CHFR基因去甲基化的作用,并探讨其临床意义。方法分别采用BSP和RT-PCR技术检测5-Aza-CdR处理前后胃癌AGS细胞CHFR基因启动子甲基化状态及其mRNA。结果 AGS细胞CHFR基因启动子在5-Aza-CdR处理前呈现高甲基化状态（甲基化率≥60%）,其mRNA表达完全缺失;5-Aza-CdR处理后则表现为低或无甲基化状态（甲基化率≤20%）,其mRNA表达恢复正常。结论 CHFR基因启动子在AGS细胞中呈高甲基化状态,5-Aza-CdR能显著逆转其CHFR基因异常甲基化,诱导CHFR基因表达,为胃癌的治疗提供新思路。     

5-Aza-CdR体外诱导胃癌细胞系p16基因去甲基化及表达增强

目的: 观察去甲基化制剂--5-Aza-CdR对体外培养的胃癌细胞SGC7901 p16基因启动子区甲基化状态及表达的影响, 探讨胃癌细胞p16基因失活的机制及去甲基化制剂对p16基因表达的调控.方法:应用不同浓度的5-Aza-CdR(1×10-7, 5×10-7, 1×10-6, 5×10-6 mol/L)处理体外培养的胃癌细胞SGC7901后, MSP法检测用药前后细胞中p16基因的甲基化状态, RT-PCR及 Western-blot法检测用药前后细胞中p16基因mRNA及蛋白表达的变化.结果: p16基因在胃癌细胞系SGC7901中启动子区呈异常甲基化状态, 在mRNA及蛋白水平低表达. 经过1×10-7, 5×10-7, 1×10-6, 5×10-6 mol/L 5-Aza-CdR处理后, p16基因启动子区呈去甲基化状态, 各组mRNA及蛋白表达相应的比值分别与处理前的比例为2.21±0.36, 2.01±0.31;2.82±0.39, 2.22±0.33;2.98±0.42, 3.15±0.43及3.35±0.55, 3.75±0.61.结论:5-Aza-CdR能逆转胃癌细胞p16基因甲基化状态, 调控p16基因表达.     

5-氮杂-2′-脱氧胞苷通过上调法尼酯X受体启动子甲基化水平抑制HepG2细胞载脂蛋白A表达

目的 探索5-氮杂-2′-脱氧胞苷（5-Aza-CdR）的DNA去甲基化作用对HepG2细胞载脂蛋白A（ApoA）表达的影响,并探讨其作用机制。方法 选取ApoA高表达细胞株HepG2细胞为研究对象。噻唑蓝法测定HepG2经不同浓度（0、10、20、40、80 μmol/L）的5-Aza-CdR处理不同时间（12、24、48、72、96 h）后细胞相对存活率;Western blot检测5-Aza-CdR不同浓度组HepG2细胞ApoA、法尼酯X受体（FXR）的表达水平;逆转录聚合酶链反应检测ApoA、FXR的mRNA水平;亚硫酸氢盐测序PCR检测FXR基因启动子在5-Aza-CR不同浓度组的甲基化水平。结果 与对照组相比,5-Aza-CR 10、20、40 μmol/L组在12、24、48、72 h各组间细胞存活率无统计学差异（P>0.05）,而在20 μmol/L 96 h组、40 μmol/L 96 h组、80 μmol/L 24 h组、80 μmol/L 48 h组、80 μmol/L 72 h组以及80 μmol/L 96 h组HepG2细胞存活率存在统计学差异（P<0.05）,选取0～40 μmol/L为5-Aza-CdR的安全浓度范围,0～72 h为合适作用时间。与对照组相比,5-Aza-CdR呈剂量和时间依赖性上调FXR蛋白、下调ApoA蛋白表达,其中以40 μmol/L组最为明显（P<0.05）;与对照组相比,5-Aza-CdR呈剂量依赖性上调FXR mRNA、下调ApoA mRNA表达,其中以40 μmol/L组最为明显（P<0.05）。随着5-Aza-CdR浓度的递增,FXR基因启动子甲基化水平呈下降趋势,其中对照组FXR基因启动子甲基化率为58.3%,而40 μmol/L组FXR基因启动子甲基化率仅为8.3%。结论 5-Aza-CdR通过DNA去甲基化作用促进FXR表达,从而下调ApoA的表达。     

5-Aza-CdR 对人卵巢癌3AO、SKOV3细胞增殖凋亡及抑癌基因RUNX3表达的影响

目的探讨5-氮-2’脱氧胞苷（5-Aza—CdR）对人卵巢癌3AO及SKOV3细胞增殖凋亡及抑癌基因RUNX3表达的影响。方法以浓度为0．5、5、50μmol／L的5-Aza—CdR处理人卵巢癌细胞株3AO及SKOV33d，常规培养5d后采用四唑盐（MTT）比色法观察细胞的生长活性，以半定量RT—PCR法检测抑癌基因RUNX3mRNA的表达，并用流式细胞仪检测细胞凋亡率。结果5-Aza—CdR能明显抑制肿瘤细胞生长，随5-Aza—CdR浓度增加，细胞生长速率下降；药物处理后RUNX3mRNA的表达明显高于处理前（P〈0．05），且存在明显剂量依赖性。5-Aza—CdR处理后3AO及SKOV3细胞凋亡率均高于处理前（P均〈0．05），细胞凋亡率与5-Aza—CdR剂量均呈正相关。结论5-Aza—CdR能使RUNX3基因去甲基化，增强其抑癌功能。     

肼屈嗪对人胃癌细胞株RUNX3基因甲基化及其表达的调节作用

背景:甲基化所致的抑癌基因RUNX3表达沉默是胃癌发生的重要机制,以脱甲基化制剂恢复其表达可起到抗肿瘤作用。目的:研究脱甲基化制剂肼屈嗪对人胃癌细胞株RUNX3基因甲基化及其表达的调节作用,观察肼屈嗪对胃癌细胞生长和凋亡的影响。方法:分别以RT-PCR和甲基化特异性PCR(MSP)检测肼屈嗪和5-Aza-dC处理前后SGC7901、MKN28和MGC803细胞的RUNX3 mRNA表达及其甲基化状态。以MTT法检测MKN28细胞增殖活性,以流式细胞术检测细胞周期和细胞凋亡。结果:MKN28细胞存在甲基化所致的RUNX3基因表达沉默。40μmol/L肼屈嗪作用72 h后,MKN28细胞可扩增出 RUNX3非甲基化条带,呈部分脱甲基化,RUNX3 mRNA恢复表达,但相对表达量低于5-Aza-dC组(P0.05)。10μmol/L以上浓度的肼屈嗪对MKN28细胞生长具有抑制作用,可使细胞周期阻滞于G0/G1期,并诱导细胞凋亡(P0.05)。结论:肼屈嗪可通过脱甲基化恢复RUNX3基因表达并能抑制MKN28细胞生长,诱导细胞凋亡。有必要对肼屈嗪在胃癌治疗中的作用作进一步研究。     

5-Aza-CdR对胃癌细胞系生长及Apaf-1基因异常甲基化的影响

目的:观察5-氮杂-2′-脱氧胞苷(5-aza-2′-deoxycitydine,5-Aza-CdR)对体外培养的胃癌SGC7901细胞和BGC823细胞增生、细胞周期和凋亡的影响及其对此两株细胞中Apaf-1基因的甲基化状态的影响.方法:不同浓度5-Aza-CdR处理体外培养的SGC7901细胞和BGC823细胞后,用MTT法检测处理24,48和72 h的细胞增殖活性;PI染色和流式细胞仪检测药物处理后72 h细胞周期分布和细胞凋亡率;MSP法检测用药前后细胞中Apaf-1基因的甲基化状态;RT-PCR法及Western blot法检测用药前后细胞中Apaf-1的mRNA及蛋白表达的变化.结果:1×10-7,5×10-7,1×10-6和5×10-6 mol/L5-Aza-CdR处理SGC7901和BGC823细胞24,48,72 h后,细胞增生受到抑制,有时间和剂量的依赖性.流式细胞仪分析表明,各药物浓度处理72 h后凋亡率增加明显:SGC7901细胞5×10-7,1×10-6和5×10-6 mol/L组分别为2.53%±1.19%,5.93%±0.86%,10.14%±1.51%,与对照组(0.12%±0.03%)相比差异显著(P＜0.05);BGC823细胞5×10-7,1×10-6和5×10-6 mol/L组分别为1.57%±0.26%,4.64%±1.05%,8.21%±1.46%,与对照组(0.57%±0.03%)相比差异显著(P＜0.05).在5-Aza-CdR处理前未检测到SGC7901细胞系及BGC823细胞系的Apaf-1基因的mRNA及蛋白表达,经过5-Aza-CdR处理后,Apaf-1基因在SGC7901细胞系及BGC823细胞系中甲基化状态得到了逆转,Apaf-1基因的mRNA及蛋白重新表达.结论:5-Aza-CdR对SGC7901细胞和BGC823细胞具有增生抑制作用;Apaf-1基因的表达情况与其甲基化状态的改变有关.     

Liver cell adenoma and liver cell adenomatosis

During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection.     

Smooth muscle cell and endothelial cell growth factors

Blood vessels are composed basically of two cell types, vascular endothelial cells (ECs) and vascular smooth muscle cells (SMCs), whose proliferation in vivo is tightly regulated. A number of growth regulatory polypeptides have been identified that stimulate the proliferation of vascular cells. This article reviews briefly the structural properties and biologic activities of the best-characterized vascular cell growth factors. A fuller understanding of the properties of vascular cell growth modulators is an important element in delineating the proliferative events that are associated with vascular injury; with SMC hyperplasia such as occurs in restenosis following angioplasty, in atherosclerosis, and in hypertension; and with angiogenesis, both physiologic and pathologic.     

Mixed small cell and non-small cell lung cancer

Seventeen (10 percent) of 176 patients with small-cell carcinoma of the lung seen at this hospital since 1976 proved to have mixed small-cell and non-small-cell tumors. The presence of a mixed lung cancer was established prior to chemotherapy or irradiation in nine patients. Eight were initially diagnosed as pure small-cell carcinoma but proved to have a mixed tumor at either surgery or autopsy. Of the 17 patients, eight received chemotherapy, and four had a partial response. Six of the 40 autopsies performed on patients with small-cell lung cancer demonstrated intrathoracic tumor which was histologically mixed. Extrathoracic metastases in these patients were heterogeneous and included pure small-cell, pure non-small-cell, and mixed histologic type. We conclude that mixed small-cell and non-small-cell lung cancers are relatively frequent and carry important prognostic and therapeutic implications. Clinical management of patients with small-cell lung cancer should therefore be flexible and tailored to the potential for histologic diversity. Mixed lung cancer in previously untreated patients suggests a common endodermal origin for small-cell and non-small-cell pulmonary tumors.     

Actin filament debranching regulates cell polarity during cell migration and asymmetric cell division

The formation of the branched actin networks is essential for cell polarity, but it remains unclear how the debranching activity of actin filaments contributes to this process. Here, we showed that an evolutionarily conserved coronin family protein, the Caenorhabditis elegans POD-1, debranched the Arp2/3-nucleated actin filaments in vitro. By fluorescence live imaging analysis of the endogenous POD-1 protein, we found that POD-1 colocalized with Arp2/3 at the leading edge of the migrating C. elegans neuroblasts. Conditional mutations of POD-1 in neuroblasts caused aberrant actin assembly, disrupted cell polarity, and impaired cell migration. In C. elegans one-cell−stage embryos, POD-1 and Arp2/3, moved together during cell polarity establishment, and inhibition of POD-1 blocked Arp2/3 motility and affected the polarized cortical flow, leading to symmetric segregation of cell fate determinants. Together, these results indicate that F-actin debranching organizes actin network and cell polarity in migrating neuroblasts and asymmetrically dividing embryos.

Cell polarity is a fundamental feature of virtually all eukaryotic cells and plays crucial roles in a wide range of cellular processes, including cell motility, asymmetric cell division, and cell signaling (1). The establishment of cell polarity involves the asymmetric assembly of distinct cellular components to perform specialized functions. The actin-related protein (Arp) 2/3 complex-dependent branched actin networks and the pushing force they produce provide the principal means for cells to remodel the plasma membrane during cellular polarization (2). For example, in the leading edge of a migrating cell, the local Arp2/3-nucleated actin polymerization powers asymmetric projections of the plasma membrane (3). During asymmetric cell division of the Caenorhabditis elegans zygote, an actomyosin flow is central to the transport of the polarity PAR proteins into defined subcellular domains (4).Actin filaments'' continuous assembly must be balanced by actin depolymerization to ensure a constant supply of actin monomers for new growth. The Arp2/3 complex potency in actin nucleation empowers this complex as an essential regulator to organize the actin cytoskeleton. While Arp2/3 by itself is biochemically inactive, interactions with nucleation-promoting factors (NPFs) such as the Wiskott Aldrich syndrome protein (WASP)/WASP family verproline-homologous (WASP/WAVE) family proteins shift the Arp2/3 complex from its open, inactive conformation to a closed, active conformation (5, 6). The conformationally activated Arp2/3 complex then binds to the side of preexisting actin filaments to nucleate a branch from the mother filament (7–12). Conversely, nucleation by Arp2/3 can be inhibited by several binding partners, including glia maturation factor (GMF), Gadkin, Arpin, and Coronin, whose activities replenish available pools of actin monomers and Arp2/3 complexes for sustained actin assembly (13–18).The coronin family proteins are conserved actin regulators (19). The phylogenetic analysis grouped coronin genes into three types (19, 20). The best-characterized coronin is the Type I coronin (e.g., Coronin 1B) that binds to actin filaments through the β-propeller structure and to the Arp2/3 complex via its N terminus. These interactions block the docking of Arp2/3 onto actin filaments or facilitate debranching the existing actin network (20). Coronin 1B simultaneously interacts with the Slingshot phosphatase to dephosphorylate and activate ADF/Cofilin proteins that sever actin filaments, thereby promoting the actin network disassembly (13). Despite significant progress on Type I coronin, the activity and function of other coronins remain unclear. In particular, Type III coronins, known as POD-1 in C. elegans and Drosophila or Coronin7 in Dictyostelium and humans, contain two tandem coronin repeats, making them distinct from other coronins (19–21). POD-1 was biochemically isolated from C. elegans oocytes (22), and its mutations disrupted the polarity and architecture in early C. elegans embryos and impaired midlife touch sensitivity of the nematode (21, 23). However, it remains unclear how the Type III coronin functions. The Drosophila homolog of POD-1 is required for correct axon guidance, and the purified Dpod-1 cross-links the actin and microtubule cytoskeletons (24), whereas the mammalian Coronin7 was implicated in the Golgi morphology and function (25, 26), demonstrating the functional divergence of this family of coronin. Here, we show that the C. elegans POD-1 debranches Arp2/3-nucleated actin filaments in vitro and that POD-1 regulates cell polarity by remodeling the actin cytoskeleton during cell migration and asymmetric cell division.     

Red cell transfusion and alloimmunization in sickle cell disease

Red cell transfusion remains a critical component of care for acute and chronic complications of sickle cell disease. Randomized clinical trials demonstrated the benefits of transfusion therapy for prevention of primary and secondary strokes and postoperative acute chest syndrome. Transfusion for splenic sequestration, acute chest syndrome, and acute stroke are guided by expert consensus recommendations. Despite overall improvements in blood inventory safety, adverse effects of transfusion are prevalent among patients with sickle cell disease and include alloimmunization, acute and delayed hemolytic transfusion reactions, and iron overload. Judicious use of red cell transfusions, optimization of red cell antigen matching, and the use of erythrocytapheresis and iron chelation can minimize adverse effects. Early recognition and management of hemolytic transfusion reactions can avert poor clinical outcomes. In this review, we discuss transfusion methods, indications, and complications in sickle cell disease with an emphasis on alloimmunization.     

Mechanism of red blood cell aging: Relationship of cell density and cell age

The human red cell has a life span of 120 days. The mechanism that determines cell removal from the circulation with such precision remains unknown. Most studies of red cell aging have been based on analysis of cells of progressively increasing age separated by density. The relationship between red cell age and density has been recently challenged, and the hypothesis has been put forward that cell death is not the result of a progressive deterioration of essential cell constituents. This theory was based on preliminary observations in transient erythroblastopenia of childhood, which could not later be confirmed. When the relationship between cell aging and increasing density is critically reviewed, it appears to be based on firm experimental evidence, confirmed by in vivo demonstration of decreasing survival of cells of increasing age. Analysis of studies using buoyant density gradients reveals that this technique can easily distinguish the single exponential slope of decline for those cell components that change progressively throughout the red cell life span from the biphasic decline of those that decrease drastically at the reticulocyte-mature red cell transition. The view that the aging of the red cell and its removal from the circulation result from a progressive series of events during the 120 days of its life span appears to be the most consistent with the available data. Density separation, validated by much experimental evidence, remains a most useful technique for the study of the mechanism of aging of the red cell. © 1993 Wiley-Liss, Inc.     

Red cell rheology in stomatocyte-echinocyte transformation: roles of cell geometry and cell shape

The influence of the shape of the red blood cell during stomatocyte- echinocyte transformation on its deformability was studied by microsieving through pores with diameters of 2.6, 4.5, and 6.9 micron. A stomatocytic transformation was produced by chlorpromazine (0.02, 0.1, and 0.5 mmol/L) and an echinocytic transformation by sodium salicylate (7.5, 30, and 120 mmol/L). For spherostomatocytes, an increase in filtration resistance through 2.6 and 4.5 micron pores was observed, whereas for spheroechinocytes, a decrease in filtration resistance through 2.6 micron pores was found. Larger pores (6.9 micron) were not sensitive to those shape changes. The changes in deformability can be explained by the fact that the surface area of (sphero)-stomatocytes decreased, whereas that of (sphero)-echinocytes increased; the cell volume remained essentially constant. Echinocytes produced by 24-hour adenosine triphosphate depletion differed from drug- induced echinocytes: they had an increased cell volume at constant surface area and consequently an increased filtration resistance through 2.6- and 4.5-micron filter pores. Shape changes with spicule formation are therefore not a homogeneous entity, and cell geometric factors (eg, surface area and volume) must be assessed with care. The viscosity of red cell suspensions at a hematocrit level of 45% was higher for drug-induced echinocytes than discocytes or stomatocytes at all shear rates tested. We conclude that the normal discocyte represents an optimum shape for the flow in vivo since a stomatocytic transformation could impair the passage through the microcirculation (decrease in cell filterability) and an echinocytic transformation could impair the flow in larger vessels (increase in blood viscosity).     

细胞自噬与结肠癌Lovo细胞迁移和侵袭的相关性研究

目的探讨不同自噬状态对结直肠癌Lovo细胞迁移和侵袭能力的影响。 方法将Lovo细胞分为自噬增强组、正常细胞组和3-甲基嘌呤自噬抑制组。用激光共聚焦显微镜观察绿色荧光颗粒,用Q-PCR检测Beclin1 mRNA表达水平,透射电镜观察自噬溶酶体,Transwell实验评价Lovo细胞迁移与侵袭能力。 结果绿色荧光颗粒数以自噬增强组最多,其次为正常细胞组,而自噬抑制组最少。Beclin1 mRNA表达量自噬增强组为(1.23±0.12)个,正常细胞组为(1±0.13)个,自噬抑制组为(0.98±0.1)个。自噬增强组可见大量的自噬溶酶体,明显多于正常细胞组和自噬抑制组。迁移实验细胞计数：自噬增强组高于正常细胞组(138.0±16.7与90.7±12.9,P＝0.026)和自噬抑制组(138.0±16.7与92.7±26.7,P＝0.030)。侵袭实验细胞计数：自噬增强组高于正常细胞组(147.0±13.0与99.0±20.5,P＝0.028)和自噬抑制组(147.0±13.0与95.7±25.6,P＝0.021)。 结论结肠癌Lovo细胞自噬增强促进肿瘤细胞迁移和浸润,可能是局部浸润和远处转移的机制之一。     

Plasma cell leukaemia and other aggressive plasma cell malignancies

Extramedullary plasma cell cancers, such as plasma cell leukaemia (PCL) and multiple extramedullary plasmacytomas (MEP) are very aggressive malignancies. These can be primary (de‐novo) or secondary due to progressive prior multiple myeloma (MM). Recent reports suggest an increase in incidence of these disorders. Compared to MM, organ invasion is common in PCL, while soft tissue tumors involving the head, neck or paraspinal area are common sites for MEP. Markers of poor prognosis are frequently observed in these extramedullary forms of plasma cell cancers, and survival is significantly inferior compared to patients with MM. Conventional chemotherapeutic and radiotherapy approaches have been employed with variable results. Even high dose chemotherapy with autologous stem cell rescue has not been able to demonstrate consistent improvement in survival outcome. Although not specifically evaluated, novel anti‐plasma cell agents, such as the proteasome inhibitor bortezomib, and immunomodulatory drugs, such as lenalidomide, appear to be active against these aggressive cancers. Clinical and translational research directed at improved understanding of disease biology and development of novel therapeutics is urgently needed.