表皮肿瘤组织超氧化物歧化酶的表达及意义

目的：探讨铜锌超氧化物歧化酶(CuZnSOD)和锰超氯化物歧化酶(MnSOD)在表皮肿瘤中的表达及作用。方法：通过半定量逆转录聚合酶链式反应(RT—PCR)和蛋白免疫印记(Western Blot)方法．研究了26例基底细胞癌(Basal cell carcinoma)、23例鳞状细胞癌(Squamas cell carcinoma)、18例日光性角化(Actinic Keratosis)以及8例曝光部正常皮肤、8例非曝光部正常皮肤中CuZnSOD和MnSOD的mRNA和蛋白表达水平。结果：正常皮肤曝光部和非曝光部2种SOD的mRNA和蛋白表达无差别；表皮肿瘤中CuZnSOD mRNA表达与正常皮肤一致，MnSOD mRNA表达升高；表皮肿瘤中2种SOD蛋白的表达较正常皮肤低。结论：表皮肿瘤中SOD的mRNA与蛋白表达水平存在差异，低蛋白表达可能与表皮肿瘤发生有关。     

锰超氧化物歧化酶与肿瘤关系研究进展

目前对于锰超氧化物歧化酶（MnSOD）在肿瘤中的表达水平和所起的作用众说纷纭。MnSOD在许多肿瘤细胞中表达下调,但在其他甚至同样的肿瘤细胞中也有表达上调的报告。MnSOD高表达可增强肿瘤细胞清除活性氧的能力,促进肿瘤的分化与进展,但肿瘤细胞体外培养普遍发现MnSOD高表达却抑制肿瘤的生长及恶性表型。MnSOD与肿瘤之间的关系复杂,其影响机制在不同肿瘤中也不尽相同。     

锰超氧化物歧化酶和E-钙黏蛋白在鼻咽癌组织中的表达及意义

目的 观察锰超氧化物歧化酶(MnSOD)和E-钙黏蛋白(E-Cad)在鼻咽癌组织中的表达及其生物学意义.方法 应用免疫组织化学S-P法,对60例鼻咽癌组织中MnSOD及E-Cad的表达水平进行检测和评价.结果 MnSOD强阳性表达率全组的为47%(28例),淋巴结阳性者(51例)中的为49%(25例),淋巴结阴性者(9例)中的为33%(3例)(x2=0.76,P=0.382).E-Cad强阳性表达率全组的为47%(28例),淋巴结阳性者中的为43%(22例),淋巴结阴性者中的为78%(7例)(x2=3.69,P=0.047).随T、N分期增加MnSOD表达水平上升,且仅与转移淋巴结大小呈正相关(r=0.46,P=0.002),与淋巴结转移区域无关(r=0.22,P=0.116);MnSOD高表达时放射敏感性低、疗效差.E-Cad表达越低N分期越晚,其表达水平与淋巴结转移区域呈负相关(r=0.33,P=0.020),但与T分期、转移淋巴结大小及放射敏感性无关(r=-2.19,P=0.093;r=-0.07,P=0.623;r=-0.18,P=0.170).多因素分析显示MnSOD、E-Cad表达水平升高与预后生存有关(x2=4.45,P=0.035;x2=5.12,P=0.024).结论 MnSOD高表达可能促进肿瘤生长,降低鼻咽癌放射敏感性.ECad高表达可抑制癌细胞淋巴转移,但与肿瘤生长、浸润无关.MnSOD、E-Cad表达水平有可能影响鼻咽癌预后.     

锰超氧化物歧化酶在肿瘤治疗中的作用

锰超氧化物歧化酶（MnSOD)是生命所必须的，不同组织类型的肿瘤MnSOD活恬不同。MnSOD通过非细胞毒性机制抑制肿瘤生长。肿瘤细胞内MnSOD低表达增加了肿瘤放化疗的敏感性。通过脂质体或病毒载体转染正常组织使其高表达MnSOD可增加正常组织对放化疗的抵抗作用。     

涎腺炎及良恶性混合瘤中铜锌超氧化物歧化酶免疫组化定位…

本文报道首次采用ＡＢＣ免疫组化法和免疫荧光直接法（单克隆抗体），对正常涎腺，涎腺炎及良恶性混合瘤的ＣｕＺｎＳＯＤ进行了检测。发现ＣｕＺｎＳＯＤ富集于涎腺导管上皮细胞和肌上皮细胞；良恶性混合瘤呈现不同程度的阳性反应，恶性混合瘤ＣｕＺｎＳＯＤ的阳性率及阳性反哟度均高于良性混合瘤，二者间差异有显著性（Ｐ＜０．０５）。结果提示：ＡＢＣ免疫组化法是检涎腺组织及良恶性混合瘤的ＣｕＺｎＳＯＤ的组化指标，，对涎腺     

Fas,FasL在表皮肿瘤中的表达及其意义

目的：探讨由Fas,FasL介导的免疫调节作用与某些表皮肿瘤良、恶性分级间的关系。方法：应用免疫组化技术对Bowen氏病，鳞状细胞癌（SCC），基底细胞癌（BCC）皮损组织中Fas,FasL的表达情况进行检测。结果：Fas,FasL在Bowen氏病SCC上均有表达，且随着肿瘤恶性程度的升高，Fas表达逐渐减弱而FasL表达逐渐增强；同Bowen氏病和SCC相比，BCC表达Fas,FasL较弱。结论：Fas,FasL介导的免疫调节作用能参于某些表皮肿瘤的免疫逃避机制，并与肿瘤的良，恶性分级及预后有关。     

锰超氧化物歧化酶在食管鳞癌组织中的表达及其临床意义

目的 探讨锰超氧化物歧化酶(MnSOD)在食管鳞癌组织中的表达及其与食管鳞癌临床病理特征及生物学行为的关系.方法 采用免疫组织化学SP法和逆转录聚合酶链反应(RT-PCR),检测45例食管鳞癌组织及距肿瘤组织边缘＞5 cm的正常组织中MnSOD蛋白和mRNA的表达水平,并分析其与食管癌临床病理特征及生物学行为之间的关系.结果 MnSOD蛋白在45例食管鳞癌组织中的阳性表达率为31.1%,明显低于正常食管组织中的阳性表达率(86.7%,P＜0.05).MnSOD mRNA在45例食管鳞癌组织的相对表达量为0.310±0.036,亦明显低于其在正常食管组织中的相对表达量(0.482±0.053,P＜0.05).MnSOD蛋白和mRNA的表达与食管鳞癌的病变长度、浸润深度和组织学分级有关,即病变长度越长、浸润深度越深、组织学分级越高者,MnSOD表达水平越低(均P＜0.05).MnSOD蛋白和mRNA的表达与食管鳞癌的淋巴结转移状况、病变部位和病变类型均无关(均P＞0.05).结论 食管鳞癌组织中,MnSOD蛋白和mRNA的表达水平均明显降低,检测MnSOD的表达对食管癌的临床治疗和预后判断有一定的参考价值.     

铜锌-超氧化物歧化酶在肝癌组织中的异常表达及意义

目的：观察铜锌-超氧化物歧化酶（CuZn-SOD）mRNA和蛋白在黄曲霉毒素B1（AFB1）诱发树的肝细胞癌（HCC）形成过程中的表达变化，并对其在人肝癌组织中的表达情况进行验证和对比，探讨CuZn-SOD在肝癌形成中的作用。方法：应用逆转录多聚酶链反应（RT-PCR）和免疫组化方法检测35例AFB1诱发的树鼩肝癌、癌旁以及这些动物癌发生前自身的活检肝组织和相应对照组织中CuZn-SOD基因在mRNA水平和蛋白水平的表达情况，并且在35例人肝癌和癌旁组织进行验证。结果：CuZn-SOD mRNA和蛋白在树鼩肝癌组织的表达水平不仅明显低于癌旁及癌前组织，也明显低于实验组虽经AFB。处理但最终未发生肝癌的动物以及正常对照动物的同期活检肝组织。人肝癌组织的CuZn-SOD mRNA和蛋白表达情况与树鼩相似，癌组织的阳性表达率和表达水平均明显低于癌旁组织，并且分化较低的肝癌组织的蛋白表达水平下调更显著。结论：CuZn-SOD可能是肝癌发生的相关基因之一，它在mRNA水平和蛋白水平的表达下降与肝癌的发生发展可能互为因果。     

涎腺炎及良恶性混合瘤中铜锌超氧化物歧化酶免疫组化定位检测及意义

本文报道首次采用ＡＢＣ免疫组化法和免疫荧光直接法（单克隆抗体），对正常涎腺，涎腺炎及良恶性混合瘤的ＣｕＺｎＳＯＤ进行了检测。发现ＣｕＺｎＳＯＤ富集于涎腺导管上皮细胞和肌上皮细胞；良恶性混合瘤呈现不同程度的阳性反应，恶性混合瘤ＣｕＺｎＳＯＤ的阳性率及阳性反应强度均高于良性混合瘤，二者间差异有显著性（Ｐ＜０．０５）。结果提示：ＡＢＣ免疫组化法是检测涎腺组织及良恶性混合瘤的ＣｕＺｎＳＯＤ的组化指标，对涎腺混合瘤恶变的诊断及治疗有一定的应用价值。文中讨论了ＣｕＺｎＳＯＤ在不同病变中出现的意义。     

锰超氧化物歧化酶在肿瘤治疗中的作用

锰超氧化物歧化酶(MnSOD)是生命所必须的，不同组织类型的肿瘤MnSOD活性不同。MnSOD通过非细胞毒性机制抑制肿瘤生长。肿瘤细胞内MnsOD低表达增加了肿瘤放化疗的敏感性。通过脂质体或病毒载体转染正常组织使其高表达MnSOD可增加正常组织对放化疗的抵抗作用。     

胸腺瘤上皮生长因子受体的表达及其临床意义

目的　研究上皮生长因子受体 (EGFR)在胸腺瘤中的表达水平及其与临床病理关系。方法　应用SABC免疫细胞化学方法检测EGFR在 6 2例胸腺瘤组织和 8例正常胸腺组织中的表达程度。结果　EGFR在胸腺瘤中的表达率及染色强度均显著高于正常胸腺组织 (P <0 .0 1) ;EGFR随着胸腺瘤Masaoka分期进展而染色强度呈增高趋势 ;在合并严重的重症肌无力(MG)的胸腺瘤中EGFR的染色程度明显增强。结论　EGFR与胸腺瘤及重症肌无力的发生、发展有一定的内在联系 ,EGFR高表达者 ,肿瘤的侵袭性强 ,出现严重的MG的几率高 ,预后不理想 ,需加强术后治疗和随访。     

卵巢上皮性肿瘤组织ATM基因表达缺失及其临床意义的探讨

目的:探讨卵巢上皮性肿瘤组织ATM基因的表达缺失及其临床意义。方法:应用荧光原位杂交技术(FISH),检测92例卵巢上皮性肿瘤及40例卵巢正常组织中ATM基因表达缺失情况,并分析其与临床病理参数的关系。结果:ATM基因在卵巢正常组织、良性肿瘤、交界性肿瘤和恶性肿瘤组织的表达缺失率分别为20.0%、25.0%、26.7%和64.3%,恶性组的表达缺失率明显高于其他组,差异有统计学意义,P<0.01;卵巢癌组织中ATM基因的表达缺失率与病理分级、病理分期及淋巴结转移有关(P<0.05),但与年龄、病理学类型无关,P>0.05。结论:ATM基因缺失可能与卵巢癌的发生机制有关,有可能成为卵巢癌治疗新的分子靶点。     

Rho家族在肿瘤组织的表达及临床意义

Rho即Ras相似物(Ras homologue),在细胞信号传导中具有重要的功能。近年来研究发现Rho家族成员在睾丸精细胞癌、结直肠癌、乳腺癌、胰腺导管腺癌、前列腺癌等癌组织中表达增加,参与多种肿瘤的发生发展过程,提示其可能成为一种新的肿瘤标志物,用于判断良恶性及判断肿瘤转移能力及估计预后,并为控制肿瘤转移提供新的靶点,具有潜在的重要临床价值。     

Manganese superoxide dismutase polymorphism and risk of skin cancer (United States)

Objective

We assessed whether the functional V16A polymorphism in the MnSOD gene is associated with skin cancer risk.

Methods

We conducted a nested case–control study (219 melanoma, 286 squamous cell carcinoma (SCC), and 300 basal cell carcinoma (BCC) cases, and 873 matched controls) within the Nurses’ Health Study. Genotyping was performed by the 5′ nuclease assay (TaqMan^®). We used logistic regression to model the association between the genotype and skin cancer risk.

Results and conclusions

Overall, there was no significant association between this polymorphism and the risk of each type of skin cancer. No significant interaction was observed between this polymorphism and sunburn history and constitutional susceptibility on skin cancer risk. For interactions between intakes of α-carotene and β-carotene and the MnSOD polymorphism on SCC, the inverse association of intake of either carotene with SCC risk was limited to the Val carriers, whereas no association was observed among women with the AA genotype. We observed an interaction between total vitamin C intake and the MnSOD polymorphism on melanoma risk. No interaction was observed for the intakes of other carotenoids, vitamin E, and vitamin A. Further research is needed to confirm these possible associations.

     

LYVE-1和CD31在卵巢上皮性肿瘤的表达及临床意义

目的 检测淋巴管内皮细胞特异性标志物LYVE-1和内皮细胞标记物CD31在卵巢上皮性肿瘤中的表达情况,探讨其与肿瘤转移的关系.方法 采用EnVision免疫组织化学二步法,分别检测卵巢上皮性癌30例,交界性卵巢肿瘤8例和良性卵巢囊腺瘤15例中的LYVE-1和CD31的表达,计数LYVE-1的阳性淋巴管数即MLC和CD31的微脉管密度即MVD.结果 卵巢上皮性癌LYVE-1和CD31的表达即MLC和MVD显著高于卵巢交界性肿瘤和良性肿瘤(P＜0.01).卵巢上皮性癌中组织学分级G3患者的MLC和MVD显著高于G1-G2(MLC,P＜0.05;MVD,P＜0.01);临床分期Ⅲ-Ⅳ期患者的MLC和MVD显著高于Ⅰ-Ⅱ期(P＜0.01);有淋巴结转移的MLC和MVD显著高于无淋巴结转移者(P＜0.01);卵巢上皮性癌MLC和MVD在不同的组织学类型中无显著性差异(P＞0.05).结论 LYVE-1和CD31在卵巢上皮性癌中的表达水平说明肿瘤组织中存在新生淋巴管和血管,它们在肿瘤转移过程中起重要作用.MLC和MVD可作为肿瘤转移的生物学指标,并且对卵巢上皮性肿瘤临床预后的评估有重要的指导意义.     

Differential expression of manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase in gastric adenocarcinoma and normal gastric mucosa.

AIMS: The biologic significance of antioxidant enzymes (AOEs) in gastric adenocarcinoma is still unclear. The aims of this study was to investigate the differential expression of AOEs in gastric carcinoma cells and non-cancerous counterparts and the relationship with the various clinicopathologic variables in gastric cancer patients. METHODS: Expression status of MnSOD, Cu/ZnSOD, and catalase was evaluated immunohistochemically in 120 paired gastric cancer and adjacent non-cancerous tissue. The tissues were fixed in absolute methanol immediately after surgical resection and immunohistochemistry was performed by microprobe system using tissuemicroarray slides. RESULTS: All AOEs revealed moderate to strong immunoreactivity in the parietal and intestinal metaplastic cells. Stromal cells in both cancer and non-cancerous tissue expressed MnSOD and catalase but Cu/ZnSOD. Immunoreactivity of MnSOD and catalase was increased in gastric carcinoma cells compared to their non-cancerous counterparts and revealed an association with intestinal type adenocarcinomas whereas immunoreactivity of Cu/ZnSOD did not reveal significant difference between cancer and non-cancerous mucosal cells. CONCLUSIONS: Expression of MnSOD, Cu/ZnSOD, catalas in gastric cancer cells and non-cancerous counterparts was different and increased MnSOD and possibly catalase may in part be responsible for the increased risk of intestinal type adenocarcinoma of the stomach.     

Induction of apoptosis and manganese superoxide dismutase gene by photodynamic therapy in cervical carcinoma cell lines

Background. Photodynamic therapy (PDT) is a cancer treatment modality in which systemic administration of a tumor-localizing photosensitizer is followed by irradiation of the tumor with visible light. Although PDT is undergoing clinical trials for various cancers, the mechanisms of its action are not fully understood. To investigate the mechanism of cell death by PDT, we performed in-vitro PDT, using Photofrin II as a photosensitizer, in two human cervical carcinoma cell lines, HeLa and CaSki. Methods. Cells were incubated with Photofrin II for 24 h, followed by illumination, using a YAG-OPO laser. Cell survivability after PDT was evaluated by an MTT assay. Cytotoxicity was assayed by measuring the release of lactate dehydrogenase (LDH) into the supernatant. DNA of the PDT-treated cells was electrophoresed in an agarose gel to determine fragmentation. In situ detection of apoptosis in the PDT-treated cells was performed by identification of the 3′-OH ends of DNA. In addition, induction of manganese superoxide dismutase mRNA (MnSOD) was analyzed in the PDT-treated cells. Results. The CaSki cells were more sensitive to this PDT treatment than were the HeLa cells. DNA fragmentation was observed with less than 5 μg/ml of Photofrin II in both cell lines, whereas PDT-induced cell membrane destruction, determined by LDH release, was observed only at 10 μg/ml. The MnSOD mRNA was induced in the HeLa cells in the early hours after PDT with a non-lethal dose of Photofrin II, but was reduced with a high dose, whereas the CaSki cells did not show any induction of the MnSOD gene by PDT. Conclusion. The present results suggest that PDT induces cell death by a mechanism involving membrane destruction and apoptosis. Differences in cell susceptibilities to PDT may depend upon a protective mechanism, such as MnSOD gene induction. Received: August 5, 1999 / Accepted: December 10, 1999     

Chemosensitisation by manganese superoxide dismutase inhibition is caspase-9 dependent and involves extracellular signal-regulated kinase 1/2

Chemoresistance and therapeutic selectivity are major obstacles to successful chemotherapy of ovarian cancer. Manganese superoxide disumutase (MnSOD) is an important antioxidant enzyme responsible for the elimination of superoxide radicals. We reported here that MnSOD was significantly elevated in ovarian cancer cells and its overexpression was one of the mechanisms that increased resistance to apoptosis in cancer cells. Knockdown of MnSOD by small-interfering RNA (siRNA) led to an increase in superoxide generation and sensitisation of ovarian cancer cells to the two front-line anti-cancer agents doxorubicin and paclitaxel whose action involved free-radical generation. This synergistic effect was not observed in non-transformed ovarian surface epithelial cells. Furthermore, our results revealed that this combination at the cellular level augmented activation of caspase-3 and caspase-9, but not caspase-8, suggesting involvement of an intrinsic apoptotic pathway. Evaluation of signalling pathways showed that MnSOD siRNA enhanced doxorubicin- and paclitaxel-induced phosphorylation of extracellular signal-regulated kinase 1/2. Akt activation was not affected. These results identify a novel chemoresistance mechanism in ovarian cancer, and show that combination of drugs capable of suppressing MnSOD with conventional chemotherapeutic agents may provide a novel strategy with a superior therapeutic index and advantage for the treatment of refractory ovarian cancer.