香烟提取物和腺病毒E1A基因对肺泡上皮细胞ICAM-1表达的影响

目的:探讨香烟提取物(CSE)致肺泡上皮细胞细胞间粘附分子-1(ICAM-1)表达的作用及腺病毒E1A基因的影响.方法:通过脂质体转染的方法将腺病毒E1A基因转染A549细胞,获取E1A阳性表达A549细胞,不同浓度的CSE活化,测定细胞ICAM-1的表达.结果:CSE显著增加A549细胞ICAM-1表达,且呈浓度依赖性;与未转染和对照质粒转染A549细胞相比较,CSE活化后E1A阳性表达A549细胞ICAM-1表达显著增加.结论:CSE能够诱导肺泡上皮细胞ICAM-1表达,而腺病毒E1A基因显著增加CSE所致的肺泡上皮细胞ICAM-1表达,提示腺病毒潜伏感染放大吸烟所致的气道炎症反应.     

沉默Bax基因对TNF-α诱导人肺泡Ⅱ型上皮细胞凋亡的影响

目的:运用RNA干扰(RNAi)技术沉默人肺泡Ⅱ型上皮细胞株A549的B细胞淋巴瘤-2相关基因(Bax),探讨Bax在肿瘤坏死因子-α(TNF-α)诱导A549细胞凋亡中的作用。方法:体外培养A549细胞,利用脂质体LipofectamineTM2000将化学合成的Bax小干扰RNA(siRNA)转染入A549细胞,给予10μg/LTNF-α刺激24h,RT-PCR检测bax mRNA的表达,Western blotting和免疫组化检测Bax蛋白的表达,流式细胞术检测细胞凋亡率的变化。结果:化学合成的Bax siRNA抑制了A549细胞Bax mRNA和蛋白的表达(P0.05),流式细胞术显示BaxsiRNA组的细胞凋亡率明显低于TNF-α组和阴性对照siRNA组(P0.05)。结论:体外实验证明Bax的高表达在TNF-α诱导A549细胞凋亡中发挥了重要的促凋亡作用,利用RNAi技术沉默Bax基因可以有效抑制由TNF-α介导的A549细胞凋亡。     

FOXO1真核表达载体构建及其对TNF-α介导的A549细胞凋亡的影响

目的构建FOXO1真核表达质粒,明确FOXO1对TNF-α介导的Ⅱ型肺泡上皮细胞凋亡的影响及其可能存在的调控机制。方法根据Gen Bank中人FOXO1 CDS序列设计并合成引物,提取A549细胞总RNA,通过RT-PCR获得FOXO1目的基因片段;通过酶切、连接,构建GV230-FOXO1真核表达质粒并进行测序分析鉴定;经鉴定后的表达载体瞬时转染入A549细胞,荧光显微镜及Western blot法检验FOXO1蛋白表达。体外培养A549细胞,利用脂质体Lipofectamine~(TM) 2000将本次合成的GV230-FOXO1质粒转染入A549细胞,给予10 ng/ml TNF-α刺激24 h,流式细胞术检测细胞凋亡率,Western blot检测凋亡相关蛋白Bim的表达。结果成功构建GV230-FOXO1荧光真核表达质粒;FOXO1组细胞凋亡率明显高于TNF-α组和阴性对照组(P0.05),FOXO1组蛋白Bim的表达明显高于TNF-α组和阴性对照组(P0.05)。结论 FOXO1在TNF-α介导的A549细胞损伤中起促进细胞凋亡的作用,其作用机制可能为通过上调促凋亡蛋白Bim的表达,从而促进细胞凋亡。     

CXCR4启动子的条件复制型腺病毒对肺癌细胞的靶向杀伤作用

目的:构建CXCR4启动子的条件复制型腺病毒载体CRAd-CXCR4-GFP,探究CRAd-CXCR4-GFP对肺癌细胞的靶向杀伤效应。方法:PCR法扩增人CXCR4-E1A基因并克隆至穿梭质粒p DC316-GFP,将骨架质粒p BHG-lox-E1,3Cre和重组质粒p DC316-CXCR4-GFP共转染293细胞,产生重组腺病毒CRAd-CXCR4-GFP并扩增,扩增后进行PCR鉴定和腺病毒滴度测定;real-time PCR检测5种肺癌细胞株CXCR4的mRNA表达,筛选出表达最高的A549细胞;将CRAd-CXCR4-GFP和Ad-NULL分别转染A549细胞,检测两者转染后CXCR4启动子活性和腺病毒复制数;将CRAd-CXCR4-GFP和Ad-NULL分别转染A549细胞和16HBE细胞,流式细胞术检测各组细胞凋亡情况,CCK-8检测各组细胞活性。结果:成功构建重组质粒p DC316-CXCR4-GFP,与骨架质粒p BHG-lox-E1,3Cre共转染293细胞后第11天可见片状绿色荧光;PCR表明目的基因CXCR4-E1A已成功整合在重组腺病毒基因组中;测定重组腺病毒滴度为1×1013PFU/L;CRAd-CXCR4-GFP转染A549细胞后E1A的mRNA和E4表达较Ad-NULL组明显上升;与Ad-NULL组和空白对照组相比,CRAd-CXCR4-GFP组前4 d A549细胞凋亡率和活性无明显差异,第5天细胞凋亡率明显增加,细胞活性明显降低,各组间5 d内16HBE细胞的细胞凋亡率和细胞活性均无明显变化。结论:成功构建条件复制型腺病毒表达载体CRAd-CXCR4-GFP,该载体对肺癌细胞具有靶向杀伤作用。     

反义Bmi-1 RNA转染对人肺癌细胞株A549体外增殖的影响

目的 研究转染反义Bmi-1 RNA对人肺腺癌细胞A549的体外增殖及细胞周期和凋亡的影响.方法 将表达反义Bmi-1 RNA的真核表达载体稳定转染A549细胞株,GA18筛选挑取阳性克隆.应用即时荧光定量RT-PCR及Western blot检测转染后Bmi-1基因在mRNA水平及蛋白水平的表达;应用MTT比色法及平板克隆形成实验检测A549细胞体外生长能力;用PI单染及Annexin-V-PI双染技术在流式细胞仪上检测细胞周期及凋亡情况.结果 Western blot结果显示转染反义Bmi-1RNA使A549细胞中Bmi-1蛋白表达量减少了95%;MTT检测细胞生长曲线表明反义Bmi-1 RNA使A549细胞生长速度明显减慢;平板克隆形成实验结果显示转染反义Bmi-1 RNA的A549细胞在平板中形成集落的数目(0.67±0.50)明显低于未转染组(73.0±4.1)及转染空质粒组(67.0±4.0,P<0.01);流式细胞仪结果显示反义Bmi-1使A549细胞阻滞在G_0/G_1期,但对细胞凋亡没有影响.结论 反义Bmi-1 RNA在体外对A549细胞增殖有明显的抑制作用,其抑制作用是通过使A549细胞阻滞在G0/G1期实现的.     

靶向髓样细胞表达的激发受体1基因短发夹RNA真核质粒表达载体的构建及筛选

目的 构建编码髓样细胞表达的激发受体1(TREM-1)基因短发夹RNA(shRNA)真核质粒表达载体,并筛选出基因沉默效果最明显的shRNA质粒表达载体.方法 针对TREM-1的靶位点设计含shRNA的靶序列,分别构建pGCsi-TREM-1 shRNA1和pGCsi-TREM-1 shRNA2的质粒表达载体和pGCsi-NegshRNA阴性质粒表达载体,通过酶切及测序进行鉴定.鉴定后以脂质体包裹转染肺泡上皮A549细胞,分为未转染对照组(A组)、转染空质粒载体pGCsi对照组(B组)、转染阴性shRNA质粒表达载体pGCsi-NegshRNA对照组(C组)、转染TREM-1 shRNA1质粒表达载体组(D组)和转染TREM-1shRNA2质粒表达载体组(E组),48 h后观察转染细胞绿色荧光蛋白表达效果.转染24、48、72 h后,以A组为对照采用MTT法测定B、C、D、E组细胞的存活率.转染48 h后,通过荧光定量PCR检测各组TREM-1 mRNA的表达水平并与转染前相比较.结果 经酶切和测序鉴定证实,目的 TREM-1基因shRNA1和shRNA2片段已被克隆到pGCsi载体中.荧光显微镜下,B、C、D、E组A549细胞有明显的绿色荧光蛋白表达.各时间点B、C、D、E组细胞存活率均达90%以上.A、B、C 3组转染前后TREM-1mRNA的表达水平差异无统计学意义,D、E组转染的重组质粒均能有效抑制A549细胞的TREM-1mRNA的表达([(1.945±0.252)×105比(1.010±0.194)×105,(1.933±0.216)×105比(1.202±0.171)×105,均P＜0.05],抑制率分别为48.07%和37.82%.结论 成功构建了靶向TREM-1基因的shRNA质粒表达载体,可有效抑制细胞中TREM-1目的 基因的表达,为后续脓毒症的基因治疗提供了依据.     

放射敏感性启动子调控Apoptin基因表达对肺腺癌细胞的杀伤作用研究

目的构建放射敏感性启动子调控的凋亡素(Apoptin)基因的真核表达质粒pE6-Apoptin-EGFP,探讨其在X线调控下对肺腺癌细胞A549的杀伤作用。方法分别以限制性内切酶EcoRⅠ/NotⅠ双酶切质粒pE6-p53-EGFP及pApoptin-EGFP,电泳分离,回收目的线性DNA片段,T4连接酶连接,构建重组质粒pE6-Apoptin-EGFP,测序、鉴定。脂质体介导瞬时转染肺腺癌细胞A549,RT-PCR、荧光显微镜等检测照射前后融合蛋白表达,流式细胞仪检测放射诱导前后转染细胞的凋亡变化。结果成功构建重组质粒pE6-Apoptin-EGFP,并在被转染A549细胞中检测到Apoptin基因表达;经放射诱导的pE6-Apoptin-EGFP/A549细胞及对照组pE6-EGFP/A549细胞的凋亡率分别为(32.48±3.56)%和(10.67±2.42)%,未经放射诱导的pE6-Apoptin-EGFP/A549细胞及对照pE6-EGFP/A549细胞的凋亡率分别为(6.33±1.21)%、(4.25±0.87)%;与其它3组相比,放射诱导的pE6-Apoptin-EGFP/A549细胞凋亡率明显增高,具有非常显著统计学差异(P<0.01)。结论放射敏感性启动子调控的Apoptin基因表达可在放射线调控下在A549细胞中有效表达并诱导凋亡,为进一步研究非小细胞肺癌的放射-基因联合治疗奠定了基础。     

Ad-ING4-IRES-IL-24双基因共表达载体的构建及表达

目的:构建IRES介导的携带人肿瘤生长抑制因子4(ING4)和人白介素24(IL-24)双基因的重组腺病毒共表达载体(简称为Ad-ING4-IRES-IL-24),研究其表达产物对A549肺癌细胞生长的影响。方法:将PCR扩增的IRES、ING4和IL-24基因片段分别插入pAdTrack-CMV载体中构建pAdTrack-CMV-ING4-IRES-IL-24双基因共表达重组转移载体。按腺病毒载体常规构建方法获得同源重组腺病毒质粒pAdEasy-1-pAdTrack-CMV-ING4-IRES-IL-24,并在QBI-293A包装细胞中进行包装和病毒扩增。将扩增后的Ad-ING4-IRES-IL-24腺病毒感染A549肺癌细胞,并用RT-PCR和Western blot法鉴定ING4和IL-24基因在QBI-293A细胞或A549肺癌细胞中的表达,MTT法和流式细胞仪检测其对A549肺癌细胞生长抑制和诱导凋亡的功能和抑癌增效作用。结果:DNA测序结果显示pAdTrack-CMV转移载体中插入的ING4、IRES和IL-24片段的序列与GenBank报道的完全一致,Ad-ING4-IRES-IL-24能成功介导ING4和IL-24基因在QBI-293A和A549细胞中表达,不仅能明显抑制A549肺癌细胞生长和诱导其凋亡(72小时生长抑制率为62.82%±0.65%,凋亡率为19.40%±1.29%),而且与Ad-ING4-IRES(72小时生长抑制率为42.31%±0.43%,凋亡率为13.30%±1.85%)和Ad-IRES-IL-24单基因组(72小时生长抑制率为47.44%±0.39%,凋亡率为12.40%±1.05%)相比具有显著性差异(P<0.05)。结论:成功构建了IRES介导的Ad-ING4-IL-24双基因共表达重组腺病毒载体,Ad-ING4-IL-24不仅能明显抑制A549肺癌细胞生长和诱导其凋亡,而且与Ad-ING4和AdIL-24单基因组相比具有抑癌增效作用。     

RNA干扰抑制乙酰肝素酶对肺腺癌细胞A549增殖、侵袭和凋亡的影响

目的 探讨抑制乙酰肝素酶表达对人肺腺癌细胞A549增殖、侵袭和凋亡的影响.方法 构建靶向人乙酰肝素酶基因短发夹状双链RNA(shRNA)真核表达质粒(pshRNA-Hpa),用脂质体将其转入A549细胞,建立稳定转染细胞株系,经逆转录.PCR和Western blot法检测转染效率后,分别用四甲基偶氮唑蓝(MTT)、Transwell侵袭实验和流式细胞术(AnnexinV-FITC/PI双染法)检测其对A549细胞增殖、侵袭和凋亡的影响.采用Western blot法检测转染后磷酸化蛋白激酶B(PKB/Akt-Ser473)的表达.结果 转染pshRNA-Hpa的A549细胞乙酰肝素酶mRNA及蛋白表达明显低于未处理A549细胞,抑制率分别为54.09%和48.26%,细胞增殖速度减缓,侵袭能力降低,流式细胞术显示早期细胞凋亡率达(12.53±0.34)%,较空白对照组、空载体转染细胞组和阴性对照组明显增加(P＜0.01).同阴性对照质粒相比,转染pshRNA-Hpa的A549细胞Akt-Ser473的磷酸化水平降低52.15%.结论 靶向乙酰肝素酶重组shRNA质粒pshRNA-Hpa能有效抑制A549细胞乙酰肝素酶的表达,并可能通过下调磷酸化蛋白激酶B途径抑制细胞的增殖侵袭、促进细胞的凋亡.     

LKB1基因转染对人肺腺癌细胞生物学行为的影响

目的:探讨外源性LKB1基因表达对人肺腺癌细胞生物学行为的影响。方法:应用巢式PCR方法扩增LKB1基因编码区,利用脂质体转染技术将真核表达重组体pcDNA-LKB1质粒和空载体pcDNA3.1质粒分别导入A549细胞,经G418筛选后获得稳定转染细胞克隆,Western blot检测LKB1和STAT3在A549细胞中的表达变化。通过绘制生长曲线和克隆形成试验检测获得性表达LKB1基因后肺癌细胞的增殖变化,流式细胞术(FCM)分析其细胞周期及其凋亡的变化。结果:成功获得了稳定表达外源性LKB1基因的A549细胞系,与转染空白载体组比较,转染LKB1基因的细胞生长速度明显减慢,细胞周期中G1/G0期比例明显增加,S期比例减少,细胞凋亡率升高;同时STAT3蛋白的磷酸化水平明显降低。结论:LKB1可能通过下调STAT3蛋白磷酸化水平的表达从而抑制A549细胞的恶性生物学行为。     

Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity

The cellular origin, in vivo function and fate of donor bone marrow‐derived cells residing in the recipient intestinal epithelial cells, pericryptal myofibroblasts or endothelial cells remain obscure. Although ‘immunoprivileged’ mesenchymal stem cells (MSCs) are prime candidates for cell‐ and gene‐based therapy, their precise role in colitis remains largely undetermined. Using a dextran sulphate sodium (DSS) colitis with busulphan (BU)‐induced hypoplastic marrow model, we examined the therapeutic effects of MSC transplantation, focusing on the role of MSCs as both cell providers and immunomodulators. Donor‐derived MSCs were detected by eGFP immunofluorescence and fluorescence in situ hybridization for Y‐chromosome (Y‐FISH) analysis. Western blot analysis of apical‐most tight junction proteins was performed with antibodies against claudin‐2, ‐7, ‐8, ‐12, ‐13, ‐15 and ZO‐1. Cytokine and cell cycle profiles were analysed by semi‐quantitative RT‐PCR and flow cytometry. Susceptibility to DSS colitis was significantly increased by co‐existing BU‐induced bone marrow hypoplasia and this increase was significantly reduced by enhancing epithelial engraftment of MSCs, an effect depending on restoring epithelial barrier integrity rather than inhibiting host immune responses. We provide evidence that implicates MSCs in maintaining epithelial barrier function by reassembling apical‐most tight junction proteins, claudins. The therapeutic efficacy of extrinsic MSCs depends on enhancing epithelial engraftment in damaged crypts by busulphan conditioning. Such a role for the MSC‐derived intestinal cells in colitis therapy merits further examination and may offer a promising new treatment for inflammatory bowel disease (IBD). Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Thyroid epithelial tumours

The traditional classification of thyroid tumours is derived from follicular and ‘C’ cells and based on morphology and clinical features, but molecular studies have shown the involvement of distinct genes in each of these tumours. The high prevalence of papillary microcarcinoma in thyroid glands removed for other reasons underpinned the alteration of the TNM classification of thyroid tumors. Molecular studies showed that the high prevalence of BRAF mutations in papillary carcinomas, reaching ≤70% in some series, contrasts with lower levels of this mutation in cases of follicular variants. Follicular variants of papillary carcinoma share oncogene changes with follicular tumours, making the differential diagnosis of follicular lesions a challenge. Hyalinizing trabecular tumour has the same RET oncogene rearrangement encountered in many papillary carcinomas, raising the possibilty that it is a variant of papillary carcinoma. The ‘mixed medullary-follicular cell carcinoma’ is of uncertain histogenesis and merits separate classification.     

Organization of thymic medullary epithelial heterogeneity: implications for mechanisms of epithelial differentiation

Summary: There are accumulating data to show that thymic epithelium expresses a remarkable array of molecules previously considered to be tissue‐specific antigens, such as parathyroid hormone, thyroglobulin, insulin, and C‐reactive protein. From an immunological perspective, this property of thymic epithelium would provide an ideal mechanism to effect central tolerance of epithelial‐restricted antigens. However, from a mechanistic perspective, this phenomenon remains mysterious. Two explanations have been proposed. One invokes promiscuous gene expression by medullary thymic epithelial cells that would allow transient derepression of selected gene expression. The other proposes that the expression of tissue‐restricted genes by thymic epithelium reflects alternate pathways of epithelial development by small numbers of cells to form a mosaic of different epithelial types within the thymus. Here we show thymic expression of lung‐associated gene products by an organized epithelial ‘organoid’ with ultrastructural features of respiratory epithelium and present data suggesting that the thymus also contains structures that ultrastructurally and phenotypically resemble solitary thyroid follicles. Based on these data, it is proposed that some thymic epithelial progenitor cells resemble pharyngeal endoderm in terms of their developmental potential and that alternative differentiation fates taken by these cells serve to maintain the spectrum of epithelial ‘self’ in the thymus.     

Gastric epithelial dysplasia

Gastric dysplasia is considered to be the penultimate stage of the gastric carcinogenesis sequence. Its clinical importance has been underscored since its association with gastric adenocarcinoma was established. High-grade dysplasia and to a lesser degree low-grade dysplasia are markers of increased cancer risk, although their natural histories are difficult to determine. There are many pitfalls in the diagnosis of gastric dysplasia. Its recognition and grading are subject to interobserver variability, particularly at the lower end of the histologic spectrum (negative v indefinite for dysplasia v low-grade dysplasia) when inflammation is present. Also, diagnostic criteria and grading schemes have evolved differently worldwide resulting in disagreement between pathologists. Against this background, the authors review contemporary issues related to gastric dysplasia, its definition, classification, grading, and natural history. We also discuss new classifications of gastric epithelial dysplasia designed to develop equivalence between grading schemes worldwide.     

Benign epithelial nephroblastoma

Summary The occurence of a malignant Wilms'tumor in the right kidney and of a benign epithelial nephroblastoma in the left kidney of a 5-year-old girl is reported. Both kidneys contained foci of persistent well differentiated blastema. In the left kidney a direct transformation of the primitive metanephric epithelium into a benign nephroblastoma is shown. This finding suggests an origin of epithelial nephroblastoma from persistent nephrogenic tissue and indicates that the former represents the benign counterpart of the malignant Wilms'tumor.Dedicated to Prof. Dr. Max Marcus on his 85th birthday     

Sensory epithelial cells acquire features of prosensory cells via epithelial to mesenchymal transition

Epithelial to mesenchymal transition (EMT) plays a critical role during normal development and in adult tissue repair. It is known that immortalized epithelial cells can undergo an EMT and become cancer stem cells, and that epithelial cells from mouse pancreatic islet and avian inner ear can acquire mesenchymal traits in vitro via EMT. However, it is unclear whether epithelial cells from mammalian sensory system can undergo an EMT and obtain features of stem/progenitor cells. In this study, we used mouse utricle sensory epithelial cells (MUCs) as a mammalian cell model to address this issue. When cultured on 2-dimensional substrates, dissociated MUCs gradually lost their columnar shape and started to expand on the substrate with downregulation of expression of epithelial junction markers and upregulation of genes and proteins that are widely shown in mesenchymal cells. Moreover, MUCs expressed genes and proteins that are usually presented in prosensory epithelial cells and stem cells. These MUCs showed potential to differentiate into epithelial cells via a reverse EMT when they were forced to suspend in culture medium. Our findings reveal that sensory epithelial cells from mammalian tissue can undergo an EMT to become cells expressing features of stem cells that can be induced to become epithelial cells via a reverse EMT. The outcomes of this study may provide a novel approach to generate epithelial progenitors for use in cell replacement therapy to treat a number of human diseases, such as hearing loss and vision loss.     

Secretion of IL-13 by airway epithelial cells enhances epithelial repair via HB-EGF

Inappropriate repair after injury to the epithelium generates persistent activation, which may contribute to airway remodeling. In the present study we hypothesized that IL-13 is a normal mediator of airway epithelial repair. Mechanical injury of confluent airway epithelial cell (AEC) monolayers induced expression and release of IL-13 in a time-dependent manner coordinate with repair. Neutralizing of IL-13 secreted from injured epithelial cells by shIL-13Ralpha2.FC significantly reduced epithelial repair. Moreover, exogenous IL-13 enhanced epithelial repair and induced epidermal growth factor receptor (EGFR) phosphorylation. We examined secretion of two EGFR ligands, epidermal growth factor (EGF) and heparin-binding EGF (HB-EGF), after mechanical injury. Our data showed a sequential release of the EGF and HB-EGF by AEC after injury. Interestingly, we found that IL-13 induces HB-EGF, but not EGF, synthesis and release from AEC. IL-13-induced EGFR phosphorylation and the IL-13-reparative effect on AEC are mediated via HB-EGF. Finally, we demonstrated that inhibition of EGFR tyrosine kinase activity by tyrphostin AG1478 increases IL-13 release after injury, suggesting negative feedback between EGFR and IL-13 during repair. Our data, for the first time, showed that IL-13 plays an important role in epithelial repair, and that its effect is mediated through the autocrine release of HB-EGF and activation of EGFR. Dysregulation of EGFR phosphorylation may contribute to a persistent repair phenotype and chronically increased IL-13 release, and in turn result in airway remodeling.     

Purinergic regulation of epithelial transport

Purinergic receptors are a family of ubiquitous transmembrane receptors comprising two classes, P1 and P2 receptors, which are activated by adenosine and extracellular nucleotides (i.e. ATP, ADP, UTP and UDP), respectively. These receptors play a significant role in regulating ion transport in epithelial tissues through a variety of intracellular signalling pathways. Activation of these receptors is partially dependent on ATP (or UTP) release from cells and its subsequent metabolism, and this release can be triggered by a number of stimuli, often in the setting of cellular damage. The function of P2Y receptor stimulation is primarily via signalling through the G_q/PLC-β pathway and subsequent activation of Ca²⁺-dependent ion channels. P1 signalling is complex, with each of the four P1 receptors A₁, A_2A, A_2B, and A₃ having a unique role in different epithelial tissue types. In colonic epithelium the A_2B receptor plays a prominent role in regulating Cl⁻ and water secretion. In airway epithelium, A_2B and A₁ receptors are implicated in the control of Cl⁻ and other currents. In the renal tubular epithelium, A₁, A_2A, and A₃ receptors have all been identified as playing a role in controlling the ionic composition of the lumenal fluid. Here we discuss the intracellular signalling pathways for each of these receptors in various epithelial tissues and their roles in pathophysiological conditions such as cystic fibrosis.     

Desmosomes of epithelial malignant mesothelioma

Morphometric examination of desmosomes by electron microscopy may help distinguish epithelial malignant mesotheliomas (EMM) from adenocarcinomas (AC). The lengths of 225 desmosomes from 10 AC and 296 desmosomes from 12 EMM were measured. The mean desmosome length was not significantly different in the two groups. However, only one desmosome greater than 1-micron length was found among the 225 AC desmosomes, whereas seven such "giant" desmosomes were found among 296 EMM desmosomes (p less than 0.001). These long desmosomes ranged up to 4.2 micron in length and involved 4 of 12 cases of EMM. The longest AC desmosome was 1.34 micron. Thus, it is suggested that giant desmosomes be defined as measuring greater than 1 micron in length and that such desmosomes are found much more commonly in EMM than AC and tend to attain greater lengths in EMM.