基底细胞癌Bcl—2、Bax、Bcl—xl蛋白免疫组化表达的定量研究

目的 通过对基底细胞癌Bcl-2、Bax、Bcl-xl蛋白表达的研究，探讨3种蛋白在基底细胞癌发生、发展中的作用。方法 按病理亚型将46例基底细胞癌分为非侵袭组（21例）侵袭组（25例），采用免疫组化SP法检测Bcl-2、Bax、Bcl-xl蛋白在石蜡切片上的表达，并对组化结果进行图像分析以获得平均光密度和Bcl-2／Bax的比值。结果 非侵袭性基底细胞癌组Bcl－2蛋白表达水平和Bcl-2/Bax的比值高于侵袭性基底细胞癌组，P值分别为0．005和0．044；两组间Bcl-2、Bax蛋白表达水平的差异无显著性，P值分别为0．097和0．979。结论 Bcl-2、Bax、Bcl-xl蛋白可能参与了基底细胞癌的发生、发展。     

CXCR7在常见皮肤恶性肿瘤及其细胞株中的表达及意义

目的 探讨趋化因子受体CXCR7在皮肤鳞状细胞癌、基底细胞癌、侵袭性皮肤黑素瘤及其细胞株中的表达及其意义。方法 收集30例皮肤鳞状细胞癌、25例基底细胞癌、30例皮肤黑素瘤的癌组织,采用免疫组织化学方法,检测CXCR7蛋白表达水平。采用RT-PCR、细胞免疫组化方法检测CXCR7在A375、M14、A431、HaCaT细胞株中mRNA及蛋白水平。结果 CXCR7在侵袭性皮肤黑素瘤中表达明显,高表达率为80%（24/30）,皮肤鳞状细胞癌及基底细胞癌分别为26.67%（8/30）、8%（2/25）;皮肤黑素瘤CXCR7高表达率与鳞状细胞癌、基底细胞癌比较,差异均有统计学意义（χ2值分别为17.16和28.36,P值均 < 0.05）。CXCR7 mRNA在A375、M14、A431细胞株中均可检出,其中A375表达最强,而HaCaT细胞不表达;细胞免疫组化显示,仅在A375细胞见棕黄色颗粒着色。结论 皮肤黑素瘤及其细胞株A375高表达CXCR7,其可能参与了其恶性侵袭与转移。     

β联蛋白对过氧化氢诱导人皮肤成纤维细胞增殖活性及凋亡相关基因Bcl-2、Bax表达的影响

目的 观察高表达的β联蛋白对过氧化氢（H2O2）诱导衰老人皮肤成纤维细胞（HSF）增殖活性以及凋亡相关基因Bcl-2、Bax表达的影响。 方法 实验分3组。HSF细胞分别转染pcDNA3.1-β联蛋白或空载体pcDNA3.1,然后150 μmol/L H2O2处理2 h。噻唑蓝检测细胞增殖活性,流式细胞仪检测细胞凋亡水平,RT-PCR和Western印迹分析凋亡相关基因Bcl-2、Bax的表达。 结果 HSF + 空载体组、HSF + 空载体 + H2O2组、HSF + β联蛋白 + H2O2组细胞增殖活性分别为0.792 ± 0.012、0.462 ± 0.012、0.521 ± 0.015,细胞凋亡率分别为（3.407 ± 0.217）%、（24.555 ± 1.793）%、（15.360 ± 0.755）%,各组比较,差异有统计学意义（均P ＜ 0.01）。HSF + 空载体 + H2O2组Bcl-2 mRNA和蛋白水平（与GAPDH mRNA和蛋白的比值分别为0.333 ± 0.003和0.336 ± 0.004）明显低于HSF + 空载体组（分别为0.507 ± 0.013和0.514 ± 0.021）,两组比较,均P ＜ 0.01。HSF + β联蛋白 + H2O2组Bcl-2 mRNA和蛋白水平分别为0.404 ± 0.006和0.411 ± 0.005明显高于HSF + 空载体 + H2O2组,两组比较,均P ＜ 0.01。HSF + 空载体 + H2O2组Bax mRNA和蛋白水平（与GAPDH mRNA和蛋白的比值分别为0.451 ± 0.002和0.460 ± 0.008）明显高于HSF + 空载体组,两组比较,均P ＜ 0.01。HSF + β联蛋白 + H2O2组Bax mRNA和蛋白水平（分别为0.339 ± 0.012和0.346 ± 0.013）明显低于HSF + 空载体 + H2O2组,两组比较,均P ＜ 0.01。 结论 高表达的β联蛋白能够提高衰老人皮肤成纤维细胞增殖活性。     

Bcl—2在非侵袭性和侵袭性皮肤基底细胞癌中的不同表达研究

采用免疫组化方法来研究和探讨Bcl-2在非侵袭性和侵袭性皮肤基底细胞癌（BCC）中的表达情况,为临床的预后判断提供帮助。我们的结果表明BCC中Bcl-2的阳性率大于80%,其中32例非侵袭性BCC的Bcl-2呈强阳性表达,达到84．4％,而26例侵袭性BCC的Bcl-2蛋白的表达则以弱阳性为主,到达80．8％,两者有显著差异,提示Bcl-2基因可作为判断BCC预后的参考指标之一。     

土贝母苷甲通过调控circ_0000376/miR-203轴影响皮肤鳞状细胞癌SCL-1细胞恶性表型

 目的:探讨土贝母苷甲对皮肤鳞状细胞癌SCL-1细胞恶性表型的影响及可能机制。方法：将体外SCL-1细胞分为对照组、不同剂量（5、10、20 μg/mL）土贝母苷甲组、si-NC组、si-circ_0000376组、土贝母苷甲+pcDNA组和土贝母苷甲+pcDNA-circ_0000376组,CCK-8法检测细胞增殖抑制率,Transwell检测细胞迁移和侵袭,流式细胞仪检测细胞凋亡,Western blot检测细胞中Ki-67、MMP-2、MMP-9、Bcl-2和Bax蛋白表达,RT-qPCR检测circ_0000376和miR-203表达。双荧光素酶报告基因实验验证circ_0000376和miR-203调控关系。对照组与不同剂量土贝母苷甲组各检测指标比较用单因素方差分析;si-NC组与si-circ_0000376及土贝母苷甲+pcDNA组与土贝母苷甲+pcDNA-circ_0000376组各检测指标比较行独立样本t检验。结果： 与对照组比较,土贝母苷甲组SCL-1细胞增殖抑制率、凋亡率及Bax蛋白表达升高（F值分别为772.61、352.20、277.56,P值均<0.01）,细胞迁移数、侵袭数及Ki-67、MMP-2、MMP-9和Bcl-2蛋白表达降低（F值分别为125.57、180.50、257.87、301.22、399.27、233.29,P值均<0.01）,circ_0000376表达降低（F=205.36,P<0.01）,miR-203表达升高（F=247.14,P<0.01）,且呈剂量依赖性。与si-NC组比较,si-circ_0000376组SCL-1细胞增殖抑制率、凋亡率及Bax蛋白表达升高（t值分别为36.78、21.56、25.20,P值均<0.01）,细胞迁移数、侵袭数及Ki-67、MMP-2、MMP-9和Bcl-2蛋白表达降低（t值分别为16.00、17.79、21.73、21.02、21.62、19.68,P值均<0.01）。双荧光素酶报告基因实验结果显示,circ_0000376靶向负调控miR-203。与土贝母苷甲+pcDNA组比较,土贝母苷甲+pcDNA-circ_0000376组SCL-1细胞增殖抑制率、凋亡率及Bax蛋白表达降低（t值分别为35.31、19.65、19.55,P值均<0.01）,细胞迁移数、侵袭数及Ki-67、MMP-2、MMP-9和Bcl-2蛋白表达升高（t值分别为12.27、21.37、24.15、23.40、23.48、22.28,P值均<0.01）。结论： 土贝母苷甲可能通过调控circ_0000376/miR-203轴抑制皮肤鳞状细胞癌细胞增殖、迁移和侵袭,并促进细胞凋亡。     

Mansonone F对前列腺癌细胞增殖、凋亡、侵袭和迁移的影响及其机制研究

目的研究Mansonone F在前列腺癌细胞增殖、凋亡、侵袭和迁移中的作用及其机制。方法噻唑蓝(MTT)检测0μmol/L、2μmol/L、4μmol/L、8μmol/L Mansonone F作用于前列腺癌DU145细胞48h后的细胞增殖。流式细胞术检测细胞凋亡,蛋白质印迹法(Western blot)检测B细胞淋巴瘤/白血病-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)、磷酸化蛋白激酶B(p-Akt)、蛋白激酶B(Akt)蛋白表达,Transwell小室法检测细胞侵袭和迁移。使用8μmol/L Mansonone F和激活剂IGF-1处理DU145细胞,观察激活PI3K/Akt信号通路对Mansonone F干预的DU145细胞增殖、凋亡、侵袭和迁移的影响。结果 Mansonone F明显抑制DU145细胞增殖(P0.05);8μmol/L Mansonone F显著提高细胞凋亡率、Bax蛋白表达(P0.05),降低细胞侵袭数、迁移数、Bcl-2、p-Akt蛋白水平(P0.05),对Akt蛋白表达无明显影响。激活PI3K/Akt信号通路逆转Mansonone F表现出对DU145细胞增殖、侵袭、迁移、Bcl-2蛋白表达的抑制作用,以及细胞凋亡、Bax蛋白表达的促进作用。结论 Mansonone F通过抑制PI3K/Akt信号通路,进而抑制前列腺癌细胞的增殖、侵袭和迁移并促进其凋亡。     

残疾基因同源物2相互作用蛋白在皮肤基底细胞癌中的表达及临床意义

【摘要】 目的 探讨残疾基因同源物2相互作用蛋白（DAB2IP）基因在皮肤基底细胞癌组织中的表达及临床意义。方法 采用回顾性分析方法,选择2012年1月至2017年11月在广东省第二人民医院皮肤科以及广州市皮肤病防治所门诊或住院接受皮肤肿物切除且资料完整的患者105例,其中病理证实为皮肤基底细胞癌患者79例作为病例组,除皮损外无其他明显临床症状、且病理证实为良性皮赘患者26例作为对照组。免疫组化法检测两组中DAB2IP的表达,分析DAB2IP表达水平与皮肤基底细胞癌临床表型及病理的相关性。采用SPSS21.0统计软件进行统计分析,计数资料比较采用χ2检验。结果 DAB2IP蛋白在对照组26例中阳性11例（42.3%）,病例组79例中阳性74例（93.7%）,两组比较,差异有统计学意义（χ2 = 33.50,P < 0.05）。DAB2IP表达与皮肤基底细胞癌患者性别、年龄、肿瘤大小无关（均P > 0.05）,浅表性组（5/7）浸润性组（95.8%）DAB2IP阳性表达率差异有统计学意义（χ2 = 6.47,P < 0.05）。79例皮肤基底细胞癌中,Ki?67蛋白阳性31例（39.2%）,且表达Ki?67的癌细胞都表达DAB2IP。结论 DAB2IP在皮肤基底细胞癌中表达增加,可能与皮肤基底细胞癌的发生和浸润有关。     

基底细胞癌中hTERT、Bcl-2的表达

目的:观察hTERT、Bcl-2在基底细胞癌中的表达,探讨其意义及关系。方法:运用免疫组织化学(SABC)方法检测41例基底细胞癌、21例正常皮肤组织中hTERT蛋白和Bcl-2蛋白的表达,并用图象分析系统加以定量分析。结果:hTERT蛋白和Bcl-2蛋白在基底细胞癌中的表达量均明显高于正常皮肤组织,差异有统计学意义(P<0.01),相关分析发现两者表达呈负相关(P<0.05)。结论:hTERT、Bcl-2与基底细胞癌的发生、发展密切相关,可作为基底细胞癌诊断的重要形态学指标,端粒酶有望成为恶性肿瘤治疗的新靶点。     

lncRNA LEF1-AS1通过靶向miR-612调控皮肤鳞状细胞癌细胞株增殖、凋亡、迁移侵袭的体外实验研究

【摘要】 目的 探讨长链非编码RNA（lncRNA）LEF1-AS1对皮肤鳞状细胞癌细胞增殖、凋亡、迁移、侵袭的影响及其机制。方法 通过干扰皮肤鳞状细胞癌SCC13细胞LEF1-AS1的表达和过表达、抑制miR-612的表达，将SCC13细胞分为转染LEF1-AS1干扰序列、无义序列的干扰LEF1-AS1组、干扰对照组，转染miR-612过表达序列、无义序列的miR-612过表达组、过表达对照组，以及转染LEF1-AS1干扰序列与miR-612抑制序列的干扰抑制组，和转染LEF1-AS1干扰序列与miR-612抑制无义序列的干扰抑制对照组。采用qRT-PCR法检测各组细胞miR-612的相对表达，CCK8法检测细胞增殖，流式细胞仪分析细胞的凋亡情况，Transwell试验检测细胞的迁移、侵袭能力，Western印迹检测细胞周期蛋白依赖激酶1（cyclinD1）、细胞周期蛋白依靠性激酶抑制剂（p21）、Bcl-2家族蛋白（Bcl-2）、Bcl-2相关X蛋白（Bax）、基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）的表达。用LncBase Predicted v.2 在线预测网站预测lncRNA LEF1-AS1与miR-612之间的互补序列，将互补/非互补序列用于构建荧光素酶报告基因质粒，分别与miR-612过表达及过表达对照基因共转染SCC13细胞，验证lncRNA LEF1-AS1与miR-612的结合能力。两组间比较采用t检验，多组间比较采用单因素方差分析，组间两两比较采用LSD-t检验。结果 miR-612过表达组细胞增殖能力、迁移及侵袭细胞数均低于过表达对照组（均P < 0.05），凋亡率高于过表达对照组（P < 0.05）。干扰LEF1-AS1组、干扰对照组、干扰抑制组、干扰抑制对照组miR-612的相对表达差异有统计学意义（F = 150.78，P < 0.001），24、48、72 h时的增殖能力差异有统计学意义（均P < 0.05），凋亡率、迁移及侵袭细胞数差异均有统计学意义（均P < 0.05）。干扰LEF1-AS1组细胞中miR-612表达、凋亡率高于干扰对照组，48、72 h细胞增殖能力、迁移细胞数和侵袭细胞数低于干扰对照组（均P < 0.05），而干扰抑制组细胞中miR-612表达、细胞凋亡率低于干扰抑制对照组，48、72 h细胞增殖能力、迁移细胞数和侵袭细胞数高于干扰抑制对照组（均P < 0.05）。Western印迹显示，4组细胞cyclinD1、p21、Bcl-2、Bax、MMP-2、MMP-9蛋白相对水平差异均有统计学意义（均P < 0.001），干扰LEF1-AS1组cyclinD1、Bcl-2、MMP-2、MMP-9蛋白相对水平均高于干扰对照组，p21、 Bax蛋白相对水平低于干扰对照组（均P < 0.05）；而干扰抑制组cyclinD1、Bcl-2、MMP-2、MMP-9蛋白相对水平均高于干扰抑制对照组，p21、 Bax蛋白相对水平低于干扰抑制对照组（均P < 0.05）。共转染互补序列后，miR-612过表达组细胞荧光活性低于过表达对照组（t = 21.19，P < 0.001）；而共转染非互补序列后，miR-612组细胞荧光活性与过表达对照组差异无统计学意义（t = 0.28，P = 0.78）。结论 lncRNA LEF1-AS1调控皮肤鳞状细胞癌细胞的增殖、凋亡、迁移和侵袭，机制与靶向miR-612相关。     

Fascin-1蛋白在基底细胞癌及鳞状细胞癌中的表达

目的 探讨fascin-1蛋白与基底细胞癌及鳞状细胞癌局部侵袭的相关性。方法 免疫组化方法对10例正常皮肤组织、13例皮肤基底细胞癌（8例结节型、5例浅表型）、24例皮肤鳞状细胞癌（11例原位鳞状细胞癌,13例侵袭性鳞状细胞癌均无转移）进行fascin-1染色,计算机图像分析系统进行观察及定量分析。结果 Fascin-1蛋白在原位鳞状细胞癌（平均光密度0.1152 ± 0.04574）、侵袭性鳞状细胞癌（平均光密度0.1257 ± 0.03096）中的表达明显高于正常上皮组织（平均光密度0.0293 ± 0.00981,P ＜ 0.05）。在结节型基底细胞癌（平均光密度0.0808 ± 0.05642）、浅表型基底细胞癌（平均光密度0.0806 ± 0.04346）中表达差异无统计学意义,但明显高于正常上皮组织（平均光密度0.0293 ± 0.00981,P ＜ 0.05）。结论 在基底细胞癌及鳞状细胞癌中,fascin-1蛋白表达上调可能与肿瘤的局部侵袭相关。     

Immunohistochemical evaluation of basal cell carcinoma and trichepithelioma using Bcl-2, Ki67, PCNA and P53

Most basal cell neoplasms with follicular differentiation represent a heterogenous group of tumors. Although may arise anywhere in the skin, these neoplasms commonly occur on the head and neck regions. The majority of these neoplasms are basal cell carcinomas (BCC) and trichoepitheliomas (TE). Overlapping histopathologic features between these benign and malignant tumors are occasionally seen which may create problems in rendering a definitive diagnosis. The intent of this investigation was two-fold: 1) to examine whether there are quantitative differences of the cellular expression of Bcl-2, Ki67, PCNA and P53 between BCC and TE; and 2) to examine the value of these immunostains in differentiating between BCC and TE. Twenty cases of BCC were stained with antibodies for Bcl-2, Ki67, PCNA and P53. The positive cell indices and staining characteristic of these immunostains were compared with those of 20 cases of TE. The cell indices for each group were analyzed statistically utilizing the analysis of variance (ANOVA) technique. Intensity and patterns of Bcl-2 and P53 expression were similar between BCC and TE. The ANOVA analysis showed no statistically significant differences between cell indices for cases stained with antibodies for Bcl-2 and P53 (p=0.49 and p=0.87 respectively) in the two neoplastic groups. There were intense labelling and generalized patterns of Ki67 and PCNA expression in BCC. Conversly, Ki67- and PCNA-labelled cells were much fewer in TEs than those noted in BCCs. Additionally, Ki67- and PCNA-positive cells were limited to the peripheral layers of the neoplastic islands of TEs. There were statistically significant differences between cell indices for cases stained with antibodies for Ki67 and PCNA (p=0.02 and p=0.05 respectively) in the two neoplastic groups. BCC and TE exhibited comparable expressions of Bcl-2 and P53 with similar intensity of labelling and patterns of distribution. This suggests possible similar mechanisms of growth regulation in both neoplasms. However, Ki67 and PCNA labelling was noted with significantly increased numbers and recognizably different patterns in BCCs compared to TEs. This may help explain the significant capabilities in tumor proliferation and the aggressive behavior of BCC compared to the limited growth potential of TE. Additionally, Ki67 and PCNA staining intensity and characteristics may have some value in differentiating between BCC and TE.     

Efficacy of imiquimod for the expression of Bcl-2, Ki67, p53 and basal cell carcinoma apoptosis

BACKGROUND: Imiquimod is a modifier of the immune response that has been proven to be an effective treatment for basal cell carcinoma (BCC). However, its mechanism of action is still unknown. OBJECTIVES: To determine whether imiquimod modifies the expression of proteins such as Bcl-2, Ki67, p53 and the BCC apoptotic index. PATIENTS AND METHODS: Thirty caucasian patients with primary BCCs larger than 8 mm in diameter were included in a double-blind randomized clinical and immunohistochemical study which was designed in a reference university hospital. The 30 BCCs were randomized in two treatment arms between September 2001 and February 2002. Twenty-four BCCs were treated with imiquimod 5% cream and six BCCs with Aldara (3M Pharmaceuticals) excipient. Histological samples were obtained before treatment and on days 8 and 15 during the course of treatment. The BCC expression of Bcl-2, Ki67 and p53 was determined in paraffin samples and the apoptotic index of the BCC was studied using the TUNEL technique (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labelling) in frozen samples. All variables were evaluated quantitatively in fields with a magnification x 400. RESULTS: The BCCs treated with imiquimod showed a decrease in the expression of Bcl-2 (88.7% before treatment, 61.4% day 15, P = 0.01) and an increase in the apoptotic index (0.53% before treatment, 1.66% day 15, P = 0.002), which were not observed in the BCCs treated with the excipient. Ki67 and p53 did not show significant changes in any group. CONCLUSIONS: Imiquimod reduces the expression of Bcl-2 in the BCC cells and increases the BCC apoptotic index.     

Expression of p53 in aggressive and non-aggressive histologic variants of basal cell carcinoma

Basal cell carcinoma (BCC) generally has an indolent course but a subgroup of BCCs tends to grow aggressively into deep tissues and even metastasize. Although studies have shown a positive correlation between mutations in the tumor suppressor gene p53 and aggressive behavior in epithelial tumors, the results for BCC are conflicting. We aimed to determine whether there is any relationship between p53 expression in BCC and histopathologic subtype of the tumor.Thirty-three formalin-fixed BCC tissue samples were examined at Hazrat-e Rasool University Hospital, Tehran, Iran, from March 2003 to April 2004. Tumors were categorized as aggressive (infiltrative or morpheic) and non-aggressive (nodular or superficial) based on histopathological examination of hematoxylin and eosin sections. p53 expression was demonstrated by immunohistochemical staining using the monoclonal anti-p53 antibody (PAb240) and results were reported using a semiquantitative score. Expression of p53 was compared between aggressive and non-aggressive tumors. All of the 11 aggressive tumors exhibited nuclear staining in more than 50% of the tumor cells. In the 22 non-aggressive tumors, less than 50% of cells showed positive staining. p53 immunoreactivity was significantly higher in aggressive BCCs than non-aggressive ones (x(2) test; p < 0.01). No correlation was found between p53 expression and the age of the patient or site of the tumor. History of childhood radiotherapy correlated positively with higher levels of p53 expression. We conclude that expression of p53 might be used as a marker to predict the aggressiveness of BCCs.     

苦参碱对HaCaT细胞Bcl-2/Bax和Fas/FasL的调控

目的:明确苦参碱对HaCaT细胞Bcl-2/Bax和Fas/FasL表达的影响。方法:体外培养HaCaT细胞,选择第二代细胞对数生长期HaCaT细胞作为研究对象,将细胞随机分为4组:苦参碱2mg/mL、10 mg/mL和50 mg/mL 3组及对照组(加入相同体积的0.9%盐水),孵育48 h后,MTT法测定各浓度下细胞增殖,RT-PCR检测Bcl-2/Bax和Fas/FasL的表达。结果:与对照组相比,当苦参碱浓度为2 mg/mL时,HaCaT细胞增殖活性无明显变化;Bcl-2、Bax、Fas、FasL表达也无明显变化(P0.05)。当苦参碱浓度为10 mg/mL时HaCaT细胞增殖活性较对照组明显下降(P0.001);Bcl-2表达明显下降,Bax表达上升(P0.001);Fas、FasL表达上升(P0.05)。当苦参碱浓度为50 mg/mL时,MTT法检测HaCaT细胞增殖明显抑制(P0.001);同时Bcl-2、Bax、Fas和FasL的变化与10 mg/mL时相似(P0.05)。结论:苦参碱能够调控上皮细胞致炎因子的表达,抑制细胞的增殖。     

Bcl-2-related proteins,alpha-smooth muscle actin and amyloid deposits in aggressive and non-aggressive basal cell carcinomas

Aberrant expression of bcl-gene products has been implicated in the development of non-melanoma skin cancers. Recently, altered expression of alpha-smooth muscle actin has been proposed as predictive of tumour behaviour in basal cell carcinomas. The purpose of this study was to compare the aggressive and non-aggressive basal cell carcinomas in terms of bcl-gene products and alpha-smooth muscle actin expression. Fifty excisional biopsy samples were studied by immunohistochemical technique for the differential expressions of bcl-2, bax, bcl-x and alpha-smooth muscle actin. Bcl-2, bcl-x and bax were expressed in 34 (68%), 38 (76%) and 41(82%) specimens, respectively. Immunoreactivity for alpha-smooth muscle actin was noted both in tumour nests (64%) and within the stroma (54%). There was a significant difference between aggressive and non-aggressive basal cell carcinomas in terms of bcl-2 and stromal alpha-smooth muscle actin immunoreactivity. Non-aggressive basal cell carcinomas display a concordant expression of bcl-family proteins, whereas aggressive tumours reveal a discordant pattern. An increased expression of stromal alpha-smooth muscle actin with a concomitant decrease or loss of bcl-2 expression may be highly suggestive of aggressiveness in basal cell carcinoma.     

Bax expression and growth behavior of basal cell carcinomas

BACKGROUND: To understand the typical growth behavior of basal cell carcinoma (BCC) we searched for the correlation between proliferation and apoptosis and progression of BCC. METHODS: Expression of Bcl-2, Bax, and Ki-67 was immunohistochemically investigated in both normal skin and BCC cells, as well as in the epidermis overlying BCC. RESULTS: The results showed that in normal epidermis, Bcl-2 was homogeneously expressed in the basal cell compartment, whereas Ki-67 expression was largely restricted to the parabasal layer, the layer just above the basal cell layer, and exhibited a more scattered staining pattern. Bax was occasionally expressed in the basal layer and widely in the suprabasal compartment. Strikingly, the apparently normal epidermis overlying BCC showed an increased Bd-2 staining. In BCC, cells stained homogeneously for Bcl-2, whereas Bax and Ki-67 showed scattered staining patterns. Simultaneous expression was seen for Bcl-2 and Bax in 80 +/- 7% of the tumor cells, and co-expression of Bcl-2 and Ki-67 in 20 +/- 7% of the tumor cells. The cells expressing Bcl-2 and Ki-67, but lacking expression of Bax, the progressive fraction, comprised on average 7 +/- 3% of the tumor cell population. CONCLUSION: These results suggest that this small progressive fraction of tumor cells, in combination with the relatively high percentage of cells still prone to apoptosis, can explain the indolent growth behavior of BCC.     

基底细胞癌瘤细胞增殖、凋亡和微血管密度的相关性研究

目的 :　探讨侵袭性基底细胞癌 (A -BCC)与非侵袭性基底细胞癌 (NA -BCC)的瘤细胞凋亡、增殖及瘤间质微血管密度之间的相关性。方法 :　应用免疫组化SP法检测 78例BCC石蜡标本组织 (36例A -BCC ,42例NA -BCC)中的Ki6 7、M30和vWF表达 ;并采用TMVLD测量法检测肿瘤间质中微血管密度。结果 :　A -BCC组的AI、PI和TMVLD的均值皆明显比NA -BCC组的高 (P <0 .0 5 ) ;其中A -BCC组的AI与PI在统计学上具有显著的相关性 (r=0 .45 9,P <0 .0 5 )。未发现BCC的AI和PI与TMVLD在统计学上有相关性。结论 :　不同性质BCC的凋亡与增殖特点不同 ;肿瘤微血管的形成与BCC瘤细胞的凋亡与增殖没有必然联系。     

Suberythemal ultraviolet B radiation alters the expression of cell cycle-related proteins in the epidermis of human subjects without leading to photoprotection

Background  Deregulation of the cell cycle proteins is one of the critical factors leading to cutaneous carcinogenesis.
Objectives  To monitor the expression of cell cycle proteins in the epidermis of subjects after repeated exposure to ultraviolet (UV) B radiation, and to test for the development of photoprotection by subsequent irradiation with a single erythemal UVB dose.
Methods  A total of 26 healthy volunteers were divided into four groups: group 1 ( n  =   9) were given whole-body UVB irradiation for 10 consecutive days with 0·7 minimal erythema dose (MED), group 2 ( n  =   9) were irradiated as in group 1 followed 24 h later by a single UVB dose of 3 MED on buttock skin, group 3 ( n  =   4) were irradiated with a UVB dose of 3 MED on buttock skin, and group 4 ( n  =   4) were not irradiated. Skin biopsies were collected 24 h after the final irradiation and stained for cyclins A, B1, D1, and p16, p18, p21, p27, p53, pRB, Bax and Bcl-2.
Results  The expression of cyclin D1, p18 and p21 was significantly higher in groups 1 and 2 compared with the nonirradiated group 4 controls and, in group 2, the expression of pRB, p53 and Bax was also increased. In group 3, only p53 and Bax proteins were significantly elevated compared with group 4. The expression of cyclin D1, p16, p18, p27, pRB and Bcl-2 was higher in group 2 compared with group 3.
Conclusions  Suberythemal UVB radiation was sufficient to cause changes in the expression of several epidermal cell cycle proteins. When tested by irradiation with a single erythemal UVB dose following the repeated exposures, no photoprotection against the UV-induced alteration in cell cycle protein expression was apparent.     

溶瘤腺病毒介导IL-24增强黑素瘤细胞MV3放疗敏感性的研究

目的:研究溶瘤腺病毒介导IL-24(ZD55-IL-24)对黑素瘤细胞MV3放疗敏感性的影响。方法:将对数生长的MV3细胞分为ZD55-IL-24联合放疗组、ZD55-IL-24组、放疗组、PBS对照组。应用免疫细胞化学法检测黑素瘤MV3细胞中Bax和Bcl-2凋亡相关蛋白的表达:应用Western blot法检测E1A蛋白及Bax、Bcl-2、Caspase-3凋亡相关蛋白的表达。结果:免疫细胞化学法检测联合治疗组Bax染色强度最大,Bcl-2染色强度最小。ZD55-IL-24联合放疗作用的MV3细胞高效表达E1A,较其它组Bax的表达量增加,Bcl-2的表达量降低,Caspase-3活化更明显。结论:ZD55-IL-24联合放疗有明显的协同杀伤黑素瘤细胞的作用。     

Usefulness of Dermatoscopy for the Preoperative Assessment of the Histopathologic Aggressiveness of Basal Cell Carcinoma

BackgroundLimited information is available regarding dermatoscopic differences between non-aggressive and aggressive types of basal cell carcinoma (BCC).ObjectiveTo investigate dermatoscopic differences between non-aggressive and aggressive types.MethodsWe evaluated 145 histopathologically confirmed BCCs from 141 patients. Histopathologic types and aggressiveness from 4 mm punch biopsy and their dermatoscopic findings were evaluated. We assessed the statistical significance of dermatoscopic differences between non-aggressive and aggressive types. To objectively predict aggressiveness, we created a "dermatoscopic index of BCC aggressiveness" in which 1 point was added and subtracted for each dermatoscopic finding significantly higher in aggressive and non-aggressive types, respectively.ResultsLarge blue-gray ovoid nests were found more frequently in non-aggressive type than aggressive one (85/105 [80.9%] vs. 21/40 [52.5%], p=0.001). Compared to non-aggressive type, aggressive type had more multiple blue-gray globules (29/40 [72.5%] vs. 57/105 [54.3%], p=0.046), arborizing telangiectasia (29/40 [72.5%] vs. 48/105 [45.7%], p=0.004), and concentric structure (11/40 [27.5%] vs. 12/105 [11.4%], p=0.018). Regarding dermatoscopic index, cases of aggressive type with a score of 1 were most common (n=18, 45.0%), followed by a score of 2 (n=14, 35.0%). Limited number of aggressive type of BCCs and the effect of width on the determination of histopathologic aggressiveness.ConclusionAggressive type BCCs more often exhibited multiple blue-gray globules, arborizing telangiectasia, and concentric structure, while the non-aggressive type exhibited large blue-gray ovoid nests more frequently. Score exceeding 2 on the dermoscopic index can be screening criteria for aggressiveness. These dermatoscopic features and dermoscopic index could be useful for assessing aggressiveness of BCCs before surgery.