凋亡抑制蛋白Bcl—2在两种皮肤肿瘤中的表达

为进一步了解Ｂｃｌ－２在基底细胞癌和鳞状细胞癌发生中的作用，作者应用免疫组织化学方法观察了４例ＢＣＣ和４例ＳＣＣ冰冻组织内Ｂｃｌ－２的表达。在４例ＳＣＣ中２例组织内肿瘤细胞见有明显的阳性染色，而ＢＣＣ阳性染色主要在间质的炎细胞中，瘤细胞末见确切的阳性染色。作者认为这些瘤组织内Ｂｃｌ－２阳性表达不同，可能是不同瘤组织自身抑制肿瘤细胞凋亡的一种自动平衡反应。     

凋亡抑制蛋白Bcl—2在皮肤基底细胞癌中的表达

用免疫组化方法检测了凋亡抑制基因蛋白Ｂｃｌ－２蛋白在基底细胞癌中的表达，同时分析比较了ｐ５３蛋白、Ｐａｎ－ｒａｓ蛋白和增殖细胞核抗原（ＰＣＮＡ）的表达。结果ＢＣＣ中２１／２１例Ｂｃｌ－２蛋白阳性，且几乎所有肿瘤细胞均呈阳性胞浆反应；５／１０例ｐ５３蛋白阳性，阳性细胞率小于５０％；Ｐａｎ－ｒａｓ蛋白在１０／１０例中均阴性；ＰＣＮＡ在９／１０例中阳性，但阳性细胞率小于１０％，这些表明，ＢＣＣ是一种低增     

皮肤鳞状细胞癌细胞凋亡和Bcl—2,Bax基因的表达

用特异性ＤＮＡ片断标记法（ＴＵＮＥＬ）研究了２５例皮肤鳞状细胞癌（ＳＣＣ）,同时观察了Ｂａｘ和Ｂｃｌ－２基因的表达。结果１９例发现凋亡细胞,６例Ｂｃｌ－２弱阳性以,全部病例Ｂａｘ染色阳性,凋亡均数与Ｂａｘ强度显著正相关,推测ＳＣＣ发生的原因不同由于细胞凋亡受到抑制。     

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。     

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。     

皮肤基底细胞癌p53,Bcl—2和Ki—67表达的研究

目的：研究和探讨p53,Bcl-2及Ki-67在皮肤基底细胞癌（BCC）中的表达情况,为临床诊断及治疗提供帮助。方法：采用免疫组化方法检测BCC石蜡切片中p53,Bcl-2和Ki-67蛋白表达,结果：33例BCC中p53,Bcl-2和Ki-67蛋白的表达率分别为45．45％,54．55％,36．36％,结论：突变的p53可能参与BCC的发生,发展过程。     

抗凋亡基因Bcl-2在皮肤良恶性肿瘤中的表达

为探讨Ｂｃｌ－２蛋白与皮肤肿瘤的关系,作者用流式细胞免疫荧光技术,检测了３３例皮肤良恶性病变。结果显示：Ｂｃｌ－２蛋白的相对含量ＦＩ（ｆｌｕｏｒｅｓｃｅｎｃｅ ｉｎｄｅｘ）在恶性肿瘤蝇的表达明显高于良性肿瘤,Ｐ〈０．００１。提示细胞恨抑止作用在肿瘤的发生、发展中也起着重要的作用,同时研究下调Ｂｃｌ－２的机制,可能成为Ｂｃｌ－蛋白过度表达肿瘤治疗的一种途径。     

Bcl-2、Bcl-xl在皮肤增生性疾病中的表达及意义

bcl-2、bcl-xl是细胞凋亡调控基因，它们的异常表达与肿瘤的发生、耐药关系密切。着重介绍bcl-2、bcl-xl在皮肤良恶性增生性疾病中的表达及意义。虽然在恶性角质形成细胞疾病中多以Bcl-2的高表达为主，而在良性增生性疾病中主要表现为Bcl-xl的表达增强，但并不能以此区别细胞的良恶性增生。     

突变型P53基因产物在皮肤鳞状细胞癌和基因细胞癌中的表达

应用免疫组化技术检测皮肤鳞状细胞（SCC）和基底细胞癌（BCC）中P53基因突变产物。结果显示，正常皮肤粘膜组织中无P53蛋白表达，而在肿瘤标本中，36例SCC中55．6％（20／36），33例BCC45．5％（15／33）P53蛋白过度表达，两换显性差异（X^2=0.33,P>0.05)，源于肛门－生殖器周围的SCC中的67％（8／12）P53免疫组化阳性，P53基因产物可以在肿瘤组织和／或其表皮中表达。结果提示P53基因突变在皮肝恶履性肿瘤发生、发展过程中起重要作用，P53免疫组化对皮肤恶性肿瘤有一定诊断价值，但不断鉴别BCC和SCC。SCC组织学分化程度可能与P53基因突变无关。     

中波紫外线诱导小鼠表皮细胞Bax和Bcl-2的表达

目的:探讨中波紫外线(UVB)对正常小鼠表皮细胞凋亡及凋亡相关基因Bax和Bcl-2的调控.方法:将正常ICR小鼠随机分为对照组(假照射组)、不同剂量紫外线照射后2 h组.1500 J/m2紫外线照射不同时间组.采用SP法染色检测凋亡相关基因Bax和Bcl-2的蛋白表达.结果:小鼠皮肤用不同剂量紫外线照射2 h后,Bax的表达随紫外线剂量增大而变大,Bcl-2表达减少,呈剂量依赖性.用1500 J/m2紫外线照射小鼠后,Bax和Bcl-2的表达与紫外线照射后时间有关.结论:中波紫外线照射小鼠皮肤后,Bax表达上调,Bcl-2表达下调,促进小鼠紫外线损伤的表皮细胞凋亡.     

Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene

Abstract The bcl-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide varity of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nevus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescencc staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivtiy in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first time, that normal human Merkel cells and Merkel cell carcinomas express bcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.     

Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene

Abstract The bcl-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide varity of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nevus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescence staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20. CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first lime, that normal human Merkel cells and Merkel cell carcinomas express hcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma     

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）和侵袭组（ 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-xl、 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、 Bcl-xl、 Bax蛋白可能参与了基底细胞癌的发生、发展。     

A case of basal cell carcinoma treated with photodynamic therapy – changes in histological features and bcl-2 expression

Photodynamic therapy (PDT) is based on the phototoxicity of photosensitizers, mostly porphyrins. Since systemic photodynamic therapy with δ-aminolevulinic acid (δ-ALA) causes prolonged whole-skin photosensitivity, topical photodynamic therapy was developed. We describe the histological findings and the results of immunohistochemical staining for bcl-2 protein in the basal cell carcinoma of a 71-year-old patient treated by photodynamic therapy with δ-ALA. After histological confirmation of the diagnosis, 20%δ-ALA in an aqueous cream base was applied to one lesion for 3 h. After 3 h the tumor was exposed to light emitted by a Kodak carousel light projector. Biopsies were taken before exposure and at days 3 and 21 after exposure. The specimens were stained with hematoxylin-eosin and with monoclonal antibody to bcl-2 protein. The intermediate histological response 3 days after exposure was characterized by "squamoid" transformation of the tumor cells along with signs of necrosis, loss of bcl-2 expression and an inflammatory cell reaction. Clinical and histological examinations 3 weeks after treatment showed no sign of residual tumor.     

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.     

银屑病患者表皮及真皮中Bcl-X、Bcl-2、Bax表达的免疫组化研究

目的 探讨银屑病患者细胞增殖与凋亡的调节。方法 用免疫组化ＳＰ法检测银屑病皮损及非皮损中Ｂｃｌ－Ｘ、Ｂｃｌ－２、Ｂａｘ的表达情况。结果 银屑病皮损中,Ｂｃｌ－Ｘ在表皮各层、真皮炎症细胞及血管内皮的表达均较正常明显增高;Ｂａｘ在颗粒层与棘层的表达轻度增高。上述异常在非皮损中已经部分存在,且隍未完全恢复正常。而Ｂｃｌ－２表达与正常相似,局限于基底层黑素细胞,角质形成细胞未是性。结论 银屑病中角质形成细     

Survivin和Bcl-2在尖锐湿疣中的表达

目的:测定survivin和Bcl-2在尖锐湿疣(CA)组织中的表达并探讨两者表达的关系。方法:应用免疫组织化学链霉菌抗生物素蛋白过氧化物酶方法(SP法)分别检测60例CA组织及10例正常包皮组织中survivin、Bcl-2基因的表达。在镜下观察切片并计算阳性细胞百分比。结果:CA组织中survivin的表达率为86.67%,显著高于正常包皮的表达率20%(P<0.01)。其中棘层的表达率85.00%显著高于基底层的表达率70.00%和颗粒层的表达率66.67%(P<0.05),基底层与颗粒层的表达率之间无显著性差异(P>0.05)。Bcl-2在CA的表达率为66.67%,正常包皮组织中未见Bcl-2蛋白表达。survivin在CA中的表达与Bcl-2呈正相关(P<0.01)。结论:本实验检测出survivin基因在CA组织中有异常表达,提示survivin蛋白引起的细胞凋亡抑制在CA的发生中起到重要的作用。survivin与Bcl-2在CA的发生发展过程中起到协同作用。     

Bcl-2／Bax及Caspase-3在大鼠脑缺血后处理中的表达及作用

目的观察Bcl-2,Bax半胱氨酸蛋白水解酶,（Caspase-3）在大鼠脑缺血后处理中的表达情况,并探讨其在脑缺血后处理中的作用。方法30只雄性Wistar大鼠,随机分为3组（n=10）：假手术组（S）、缺血再灌注组（I／R）和缺血后处N2H（IPost）。采用4-VO法建立大鼠全脑缺血再灌注模型。IPost组分离双侧颈总动脉,夹闭10min,开放30S,夹闭10s,反复三次。术后2d处死大鼠取出脑组织,采用SABC法测定Bcl-2,Bax,Caspase-3含量,采用TUNEL法检测大鼠皮质神经元凋亡情况。结果与s组比较,I／R组Bax,Caspase-3表达明显升高,而Bcl-2表达明显降低（P〈0．01）,皮质神经元凋亡增加（P〈0．01）;与I／R组相比,IPost组Bcl-2表达水平显著升高（P〈0．01）,Bax,Caspase-3表达均明显降低fP〈0．01）,皮质神经元凋亡减少。结论缺血后处理能诱导Bcl-2表达增强,Bax和Casepase-3表达降低,可能是缺血后处理抗凋亡产生脑保护的机制之一。     

Expression of lamins depends on epidermal differentiation and transformation

BACKGROUND: It has been suggested that A- and B-type lamins, proteins of the nuclear lamina, play important roles in the morphogenesis of the nucleus and cellular differentiation. OBJECTIVE: To investigate the expression of these nuclear proteins in normal skin and some keratinocytic tumours of the skin. METHODS: We examined by means of immunohistochemistry the expression of lamins in normal skin and some keratinocytic tumours of the skin, such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease, solar keratosis, keratoacanthoma and seborrhoeic keratosis. RESULTS: In normal skin, A-type lamin was expressed in all epidermal cells, but the expression level of B-type lamins diminished from basal cells to granular cells. In keratinocytic tumours, the expression of A-type lamin was reduced, especially in BCCs, Bowen's disease and poorly differentiated SCCs. B-type lamins were reduced and exhibited heterogeneous expression patterns in most well-differentiated SCCs and keratoacanthomas. Antibodies against B-type lamins stained only peripheral cells of the lobules in keratoacanthomas, while no regular staining patterns were seen in well-differentiated SCCs. CONCLUSIONS: Lamin expression depends on the differentiation and transformation of the human skin. This finding should be useful for the diagnosis of keratinocytic tumours.