皮肤鳞状细胞癌研究进展

鳞状细胞癌在皮肤非黑色素细胞性恶性肿瘤中发病率居第二位,近年来发病率呈增高趋势。鳞状细胞癌病因复杂且临床表现无特异性,有时易导致误诊。虽然鳞状细胞癌通常生长较慢,但一些特殊类型可较早发生侵袭、转移。近年来,人们对鳞状细胞癌的认识逐渐深入,在其诊断、治疗、预防等方面研究成果显著。本文就鳞状细胞癌流行病学、病因、临床表现及病理、临床分期、治疗及预后等方面进行综述。     

慢病毒介导的RNA干扰FOXC2表达对皮肤鳞状细胞癌A431细胞功能影响

目的:探讨慢病毒介导的RNA干扰叉头框C2(FOXC2)表达对皮肤鳞状细胞癌A431细胞增殖、侵袭和凋亡的影响及其机制.方法:采用实时荧光定量聚合酶链反应(PCR)和免疫印迹法检测人正常永生化上皮Hecate细胞和皮肤鳞状细胞癌A431细胞中FOXC2 mRNA和蛋白的表达水平.将体外培养的A431细胞分为对照组(正常...     

多发性皮肤鳞状细胞癌1例

 皮肤恶性肿瘤中 ,鳞状细胞癌的发病率较高 ,而同时或相继发生两个或两个以上彼此无关联的鳞癌 ,在国内尚未见报道。我科于 2 0 0 1年 9月收治了 1例胸部先后发生三处皮肤鳞状细胞癌的患者。报告如下。1　病例报告　　男性 ,6 1岁 ,因胸部皮肤肿瘤于 2 0 0 1年 9月收住入院。 3年前胸骨前皮肤无明显诱因出现绿豆大小的红斑样皮损 ,伴鳞样脱屑和痂皮形成 ,高出皮肤表面 ,因局部瘙痒而先后自涂“皮炎平霜”、中药糊剂等 ,于入院前 4个月病灶开始糜烂 ,伴有渗血、渗液 ;后糜烂面自行愈合结痂 ,但不久痂皮脱落而再现糜烂面 ,如此反复使糜烂面逐渐扩大 ,至入院前增至6 .0ｃｍ× 11.0ｃｍ ,外观呈菜花状 ,基底高低不平 ,边缘有略隆起的溃疡 ,质脆。于入院前 6月 (即胸部皮损糜烂、出血前 2月 )双季肋部 (距胸部肿瘤约 18ｃｍ ,2 0ｃｍ)几乎同时重现上述病变 ,形态与前胸部初起时病变相似 ,大小分别为 3.0ｃｍ× 2 .0ｃｍ ,2 .0ｃｍ× 1.0ｃｍ ,病灶增大不明显。耳前、耳后、颈部淋巴结未触及肿大。入院诊断 :皮肤肿瘤。治疗 :经术前准备 ,于前胸部距病灶边缘 4 .0ｃｍ作切...     

皮肤鳞状细胞癌的外科治疗

目的 探讨皮肤鳞状细胞癌的外科治疗方法及效果。方法 收集1981年12月至2011年12月鳞状细胞癌105例,其中手术治疗101例。切除病灶后,根据创面不同部位、大小、深度,选择任意皮瓣、肌皮瓣或皮片修复创面;创面位于面部及关节部位采用分区植皮方法。结果病灶切除后,移植皮片48例,任意皮瓣或肌皮瓣修复53例;随诊6个月以上85例,随诊5年以上52例,16例发生局部复发或远处转移,其中8例死亡,其余患者术区外形良好,局部无复发。结论 皮肤鳞状细胞癌早期发现行完整手术切除仍然是最佳的治疗手段,对手术缺损可以采用整形美容方法修复,实现患者的生存时间和生活质量的提高。     

circ_0001821靶向miR-203调控皮肤鳞状细胞癌A431细胞的增殖、凋 亡、迁移和侵袭

目的：探讨circ_0001821通过靶向miR-203调控皮肤鳞状细胞癌（cutaneous squamous cell carcinoma,CSCC）A431细胞 增殖、凋亡、迁移及侵袭的分子机制。方法：选取2018年2月至2019年8月海南医学院第二附属医院收治的39例CSCC患者的癌 及配对癌旁组织,以及人CSCC细胞系A431,用qPCR法检测CSCC癌和癌旁组织中circ_0001821的表达水平。利用脂质体转染技 术,分别将si-circ_0001821、si-NC、miR-203 mimic、miR-NC、si-circ_0001821与anti-miR-NC、si-circ_0001821与anti-miR-203转染至 A431细胞,用qPCR法检测转染细胞中circ_0001821和miR-203的表达水平,MTT法、流式细胞术和Transwell实验分别检测A431 细胞的增殖、凋亡、迁移及侵袭能力,WB法检测细胞中增殖、凋亡、迁移及侵袭相关蛋白的表达水平。通过Circinteractome数据库 预测circ_0001821与miR-203存在结合位点,双荧光素酶报告基因实验验证circ_0001821与miR-203的靶向关系。结果：CSCC组 织中circ_0001821的表达水平显著高于癌旁组织（P<0.01）。转染 si-circ_0001821 可显著降低细胞中circ_0001821的表达水平（P<0.01）,降低细胞增殖、迁移和侵袭能力（均P<0.01）,提高细胞凋亡率（P<0.01）。双荧光素酶报告基因实验证实,circ_0001821可 靶向结合miR-203。转染miR-203 mimic可显著降低A431细胞的增殖、迁移和侵袭能力（均P<0.01）,提高细胞凋亡率（P<0.01）。共转染si-circ_0001821与anti-miR-203 可明显逆转下调circ_0001821 表达对 A431 细胞增殖、迁移、侵袭及凋亡的调控作用。结论： circ_0001821通过靶向miR-203调控CSCC细胞A431的增殖、迁移、侵袭能力及细胞凋亡。     

跨膜接头蛋白CBP对皮肤鳞癌细胞A431生长增殖的负调控作用研究

背景与目的：跨膜接头蛋白(Csk-binding protein,CBP)是新发现的Src家族成员,与多种肿瘤的发生有关。该研究旨在观察CBP基因过表达对皮肤鳞癌细胞系A431增殖及细胞凋亡的影响,探讨其相关的分子机制。方法：构建CBP-增强型绿色荧光蛋白(enhanced green fluorescent protein,EGFP)融合蛋白的慢病毒过表达载体,采用反转录病毒转染的方法建立CBP过表达的A431细胞株。实验分为亲本细胞组(未进行基因转染的A431细胞)、对照组(A431细胞转染仅含EGFP阴性对照病毒)和实验组(A431细胞转染CBP-EGFP病毒)。在激光共聚焦显微镜下观察细胞转染率,验证转染成功与否;CCK-8法检测CBP过表达对A431细胞增殖能力的影响,并采用流式细胞术(flow cytometry,FCM)检测对细胞凋亡的影响;实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)和蛋白［质］印迹法(Western blot)检测Lck、Csk和Fyn三种上游信号转导分子分别在mRNA和蛋白中的表达水平变化。结果：建立了稳定过表达CBP的A431细胞株;CCK-8法结果提示,CBP过表达明显抑制细胞生长,第2~6天的组间差异有统计学意义(P<0.05);FCM检测显示,实验组细胞凋亡率显著增加,与亲本细胞组及对照组相比差异有统计学意义(P<0.001);RTFQ-PCR结果显示,实验组A431细胞Lck mRNA的相对表达水平显著下调(P<0.001),实验组细胞Csk和Fyn mRNA的表达分别约为亲本细胞组的1.6倍和3.8倍,表达显著上调(P<0.001);Western blot结果表明,实验组Lck蛋白的相对表达水平明显下降(P<0.001),实验组细胞Csk和Fyn蛋白与亲本细胞组和对照组相比表达明显增加(P<0.001)。结论：CBP过表达可抑制皮肤鳞癌细胞增殖,诱导细胞凋亡及坏死。CBP通过调节上游信号转导通路中的蛋白酪氨酸激酶Lck、Csk和Fyn来调控细胞的增殖活性。     

TIPE1在皮肤鳞状细胞癌中的表达及意义

目的:研究TIPE1在皮肤鳞状细胞癌中的表达变化情况。方法:采用免疫组化方法检测31例皮肤鳞状细胞癌组织和31例正常皮肤组织中TIPE1的表达情况。结果:在正常皮肤组织中,TIPE1弱表达于表皮基底层及棘层下部,在表皮全层表达的阳性率为23.20%。在皮肤鳞状细胞癌中,可见TIPE1高表达于大部分的癌细胞中,阳性率为77.41%。TIPE1在皮肤鳞状细胞癌中的表达显著高于正常皮肤组织(P＜0.05)。结论:TIPE1可能参与皮肤鳞状细胞癌的发生和发展。     

mTOR siRNA对喉鳞状细胞癌Hep-2细胞生物学行为的影响

目的观察mTOR siRNA对喉鳞状细胞癌Hep-2细胞增殖能力的影响。方法选取45例喉鳞状细胞癌组织和45例正常喉黏膜组织,采用免疫组织化学法检测mTOR蛋白的表达;将喉鳞状细胞癌Hep-2细胞分为空白对照组、空载体组和mTOR siRNA组,及正常对照组、溶剂对照组和雷帕霉素组,分别利用mTOR siRNA和雷帕霉素进行治疗,采用Western bloting法检测不同浓度的mTOR siRNA和雷帕霉素分别处理细胞后对mTOR蛋白表达的影响,并采用CCK-8试剂盒分析mTOR蛋白表达下调对喉鳞状细胞癌Hep-2细胞增殖能力的影响。结果 mTOR蛋白在喉鳞状细胞癌组织中表达的阳性率显著高于正常喉黏膜组织(P<0.05)。3种不同浓度mTOR siRNA分别转染Hep-2细胞24、48、72 h,各组与空白对照组、空载体组相比,mTOR蛋白表达均有所降低(P<0.05),且mTOR蛋白表达随mTOR siRNA浓度的增加、作用时间的延长而降低(P<0.05)。3种不同浓度雷帕霉素处理Hep-2细胞24、48、72 h,各组与溶剂对照组及正常对照组相比,mTOR蛋白表达量均有所降低(P<0.05);且mTOR蛋白表达随雷帕霉素浓度的增加、处理时间的延长而降低(P<0.05)。与空白对照组、空载体组相比,各mTOR siRNA组的Hep-2细胞增殖在转染后24、48、72 h均受到明显抑制(P<0.05)。结论 mTOR siRNA均能降低喉鳞状细胞癌Hep-2细胞中mTOR蛋白的表达,有效抑制细胞的生长,为喉鳞状细胞癌的分子治疗提供了理论依据。     

微小RNA在皮肤鳞状细胞癌中的研究进展

皮肤鳞状细胞癌(cSCC)是角质形成细胞来源的恶性肿瘤之一。转录组是特定条件下细胞内全部转录产物的总和,包括编码mRNA和非编码RNA。研究发现,与正常细胞相比,鳞癌细胞在基因转录水平和模式上存在很大差异,具有不同转录表达谱。微小RNA(miRNA)可通过抑制转录产物的翻译,从而调控靶基因的表达,影响cSCC细胞的增殖、分化和凋亡等病理过程。越来越多的研究表明,miRNAs作为cSCC诊断、预测预后和治疗靶点的生物标志物,在临床上具有广阔的应用前景。本文通过回顾分析cSCC的miRNA表达谱,主要对其中经实验证实表达上调和下调的miRNAs在cSCC中的研究进展作一综述。     

皮肤鳞状细胞癌FHIT基因的异常改变及意义

目的检测脆性组氨酸三联体基因在皮肤SCC中外显子5和8的缺失和突变情况,分析该异常在皮肤SCC发生中的作用机制。方法PCR-SSCP方法检测皮肤SCC患者皮损FHIT基因外显子5和8的缺失和突变状况。结果10例CSCC组织中,E5有3例缺失,E8有8例缺失,其中有2例同时缺失E5和E8,对扩出的外显子进行SSCP分析没有检测到其突变。结论皮肤SCC中存在外显子5和8的缺失异常,没有发现其突变,这种异常与该肿瘤的发生可能有关,其具体的发生机制需做更进一步的探讨。     

Identification of potential immune-related circRNA-miRNA-mRNA regulatory network in cutaneous squamous cell carcinoma

Circulating RNAs (circRNAs) are involved in tumor development and progression by participating in immune regulation. Nevertheless, the circRNAs expression profiles and their roles on the immunomodulatory effects in cutaneous squamous cell carcinoma (cSCC) have rarely been studied. In our study, we identified the differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), mRNAs (DEmRNAs) in cSCC and established the circRNA competing endogenous RNAs (ceRNAs) network. Subsequently, the hub differentially expressed immune-related genes were identified and validated by immunochemistry as well as the GO and KEGG pathway analysis were performed. 54 differentially expressed circRNAs were identified and hub differentially expressed immune-related genes were identified and they were mostly associated with immune response in the progression of cSCC. Our results indicated that the potential immune-related circRNA-miRNA-mRNA network may assist in understanding the molecular mechanisms underlying the carcinogenesis and progression in cSCC. Moreover, the immune-related genes may provide an insight into the pathogenesis, molecular biomarkers, and potential therapeutic targets for cSCC patients.     

Treatment of unresectable and metastatic cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is an already common disorder with a rapidly increasing incidence. Treatment of early disease depends primarily on surgery or destructive techniques. In contrast to the frequency of early SCC, unresectable or metastatic SCC is relatively rare, but potentially life-threatening without clearly proven treatment options. Few rigorous studies of the treatment of advanced SCC have been undertaken. In the past, various agents have been explored in a limited fashion, including chemotherapy (cisplatin, fluoropyrimidines, bleomycin, doxorubicin), 13-cis-retinoic acid, and interferon-α2a. Clinical activity has been suggested by these trials, but their small sizes, heterogeneous patient populations, and lack of randomization have hindered the use of their results in defining treatment paradigms. Only one rigorous randomized trial has focused on cutaneous SCC. Enrolling 66 patients, that trial randomized patients at high recurrence risk to either observation or postoperative interferon-α2a and 13-cis-retinoic acid. This treatment did not improve time to recurrence or prevent secondary cutaneous SCC from developing. Though not in the metastatic setting, this study casts doubt on the ability of this regimen to control metastatic disease. Recently, agents targeting the human epidermal growth factor receptor (erlotinib, gefitinib, cetuximab) have displayed preliminary evidence of activity in phase II clinical trials and case series reports. Expression of this receptor is frequent in cutaneous SCC and appears to be prognostically adverse. Only the conduct of rigorous trials, with well-defined endpoints, adequate patient numbers, and preferably randomization, can prove the clinical efficacy of this promising treatment approach and define better therapy for this vexing clinical problem.     

PSMD7基因在人食管鳞癌组织中的表达及影响癌细胞增殖、凋亡的机制研究

背景与目的：26S蛋白酶体非ATP酶调节亚基7（26S proteasome non-ATPase regulatory subunit 7,PSMD7）作为组成19S蛋白酶体盖子结构的核心成员是否参与肿瘤的发生、发展,以及具体的分子机制尚不清楚。本实验将研究PSMD7基因在人食管鳞癌组织中的表达,以及对癌细胞增殖及凋亡的影响。方法：采用实时荧光定量聚合酶链反应（real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR）和蛋白质印迹法（Western blot）检测食管鳞癌及其癌旁正常组织标本中PSMD7的mRNA及蛋白表达情况。在人食管鳞癌细胞系TE-1中,用慢病毒介导的RNA干扰技术下调PSMD7的表达,观察细胞增殖及凋亡的变化,检测线粒体膜电位的变化、细胞质中Cyt C的表达以及凋亡相关因子的表达。结果：PSMD7基因的mRNA和蛋白在食管鳞癌组织中的表达显著高于癌旁正常组织（P<0.05）,PSMD7蛋白的高表达与淋巴结转移阳性呈正相关（P<0.05）。抑制PSMD7蛋白的表达可使细胞的增殖能力降低（P<0.05）,并促进细胞的凋亡（P<0.05）,同时线粒体膜电位降低,促进Cyt C释放进入细胞质,激活caspase级联反应,说明抑制PSMD7的表达诱导细胞凋亡是通过线粒体信号通路进行的。结论：PSMD7在食管鳞癌中呈高表达,并通过线粒体依赖的方式促进TE-1细胞凋亡。     

Laser immunotherapy for cutaneous squamous cell carcinoma with optimal thermal effects to enhance tumour immunogenicity

Background: Laser immunotherapy is a new anti-cancer therapy combining photothermal therapy and immunostimulation. It can eliminate the tumours by damaging tumour cells directly and promoting the release of damage-associated molecular patterns (DAMPs) to enhance tumour immunogenicity. The aim of this study was to investigate the thermal effects of laser immunotherapy and to evaluate the effectiveness and safety of laser immunotherapy for cutaneous squamous cell carcinoma (cSCC).

Methods: The cell viability and the DAMPs productions of heat-treated cSCC A431 cells in different temperatures were investigated. Laser immunotherapy with the optimal thermal effect for DAMPs production was performed on SKH-1 mice bearing ultraviolet-induced cSCC and a patient suffering from a large refractory cSCC.

Results: The temperature in the range of 45–50?°C killing half of A431 cells had an optimal thermal effect for the productions of DAMPs. The thermal effect could be further enhanced by local application of imiquimod, an immunoadjuvant. Laser immunotherapy eliminated most tumours and improved the survival rate of the ultraviolet-induced cSCC-bearing SKH-1 mice (p?Conclusions: Our results strongly indicate that laser immunotherapy with optimal thermal effects is an effective and safe treatment modality for cSCC.     

和厚朴酚对人皮肤鳞癌细胞A431增殖凋亡作用及可能的机制分析

目的:研究和厚朴酚（Honokial,HNK）对人皮肤鳞癌细胞A431增殖凋亡作用及可能的机制分析。方法:采用CCK8实验方法检测和厚朴酚对A431细胞增殖的影响;Western blot定量分析和厚朴酚对Bcl-2和Bad蛋白表达的影响;Western blot定分析和厚朴酚对A431细胞中p53蛋白表达的影响;利用p53过表达腺病毒,并联合应用药物,通过CCK8和Western blot方法分析和厚朴酚对细胞增殖和凋亡的影响。结果:和厚朴酚以浓度和时间依赖性地抑制A431细胞增殖,并诱导其凋亡,上升Bad蛋白水平,下调Bcl-2蛋白水平;和厚朴酚可上调A431细胞中p53蛋白表达水平;加入p53过表达腺病毒可增强和厚朴酚的作用,抑制细胞增殖,促进细胞凋亡。结论:和厚朴酚能够抑制人皮肤鳞癌细胞A431的增殖并诱导凋亡,其机制可能与p53信号通路有关。     

Thioredoxin domain-containing protein 9 protects cells against UV-B-provoked apoptosis via NF-κB/p65 activation in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC), a type of non-melanoma skin cancer (NMSC), is the mostcommon malignancy worldwide. Thioredoxin (TXN) domain-containing protein 9 (TXNDC9) is a member of theTXN family that is important in cell differentiation. However, the biological function of this protein in cancer,particularly cSCC, is still unknown. In the present study, our experiments revealed the protective effects of TXNDC9on UV-B-irritated cSCC cells. The initial findings showed that TXNDC9 is significantly upregulated in cSCC tissueand cells compared to normal skin tissue and keratinocytes. UV-B radiation robustly induces the expression ofTXNDC9, and UV-B-induced cSCC cell death is boosted by TXNDC9 deficiency. Moreover, cSCC cells lackingTXNDC9 displayed attenuated activation of the NF-κB pathway. Additional studies by inhibiting TXNDC9 confirmedthis finding, as TXNDC9 deficiency attenuated UV-B radiation-induced translocation of NF-κB p65 from thecytoplasm to the nucleus of cSCC. In conclusion, our work demonstrates the biological roles of TXNDC9 in cSCCprogression and may provide a novel therapeutic target to treat cSCC in the future.     

KMT2D loss drives aggressive tumor phenotypes in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most lethal skin cancer. Due to ultraviolet light-induced damage, cSCCs have a high mutation rate, but some genes are more frequently mutated in aggressive cSCCs. Lysine-specific histone methyltransferase 2D (KMT2D) has a two-fold higher mutation frequency in metastatic cSCCs relative to primary non-metastatic associated cSCCs. The role of KMT2D in more aggressive phenotypes in cSCC is uncharacterized. Studies of other tumor types suggest that KMT2D acts to suppress tumor development. To determine whether KMT2D loss has an impact on tumor characteristics, we disrupted KMT2D in a cSCC cell line using CRISPR-cas9 and performed phenotypic analyses. KMT2D loss modestly increased cell proliferation and colony formation (1.4- and 1.6-fold respectively). Cells lacking KMT2D showed increased rates of migration and faster cell cycle progression. In xenograft models, tumors with KMT2D loss showed slight increases in mitotic indices. Collectively, these findings suggest that KMT2D loss-of-function mutations may promote more aggressive and invasive behaviors in cSCC, suggesting that KMT2D-related pathways could be targets for cancer therapies. Future studies to determine the downstream genes and mechanism of phenotypic effect are needed.