生存素反义寡核苷酸在恶性肿瘤治疗中的研究进展

生存素(survivin,SVV)是目前恶性肿瘤基因治疗研究中的新靶点.应用反义寡核苷酸技术(ASODN)等治疗方法可以抑制SVV的表达,从而抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡、增强肿瘤细胞对化疗药物的敏感性.近年应用SVV-ASODN对恶性肿瘤的研究已成为肿瘤治疗领域的研究热点,这将为恶性肿瘤的治疗提供新的理论基础.     

BRAF基因序列特异性shRNA质粒载体的构建

目的构建BRAF基因序列特异性的短发卡RNA(Short Hairpin RNA,shRNA)质粒载体。方法根据文献已发表的BRAF基因序列,设计合成3条BRAF特异性的shRNA编码序列(其中一条shRNA特异性针对黑素瘤中最常见的BRAF V599E错义突变设计)和一条与人基因组无同源性的阴性对照shRNA编码序列。将退火后的双链shRNA编码序列重组于pGenesil-1质粒中,进行双酶切和测序鉴定。结果双酶切显示shRNA编码序列被成功插入pGenesil-1质粒中,测序结果证实插入片断与设计序列完全一致。结论所设计的shRNA编码序列被正确插入质粒骨架,成功构建了BRAF基因序列特异性的shRNA质粒载体。     

PTEN基因在皮肤肿瘤中的研究进展

PTEN基因是一个抑癌基因,其缺失、突变和表达减少可存在多种皮肤肿瘤中.PTEN基因主要通过PI3K/Akt、FAK/p130途径及Shc/ras/MARK途径影响细胞的分化、凋亡、移动及信号转导等方面,参与皮肤肿瘤的发生发展,与皮肤肿瘤的恶性转化有着密切的关系.因此,PTEN基因在保持皮肤内环境稳定和抑制皮肤肿瘤的发生方面起着重要的作用.概述紫外线辐射对PTEN功能的调节及PTEN基因在多种皮肤肿瘤发生发展中的作用.     

免疫检查点在皮肤肿瘤中的研究进展

近年来研究发现,免疫检查点(CTLA-4、PD-1、TIM-3、TIGIT和LAG-3等)表达于免疫细胞表面,与肿瘤的增殖、侵袭和转移紧密相关。免疫检查点抑制剂,已广泛地应用于皮肤肿瘤的临床治疗,并取得了显著的疗效。本文将从免疫检查点的类型、作用机制、其在皮肤肿瘤中的研究及临床应用等方面进行系统综述。     

紧密连接在皮肤肿瘤中的研究进展

紧密连接是上皮细胞间、内皮细胞间连接的主要结构之一,参与细胞屏障功能、维持极性和物质转运及信号转导,维护生理稳态.近年来,越来越多的研究发现,紧密连接与上皮细胞来源的肿瘤关系密切.皮肤肿瘤是一类上皮细胞源性肿瘤,多种皮肤肿瘤组织出现角质形成细胞间紧密连接相关蛋白表达异常、紧密连接结构及功能异常,这可能对皮肤肿瘤的发生发展起关键作用,由此推测紧密连接在皮肤肿瘤的诊断、鉴别诊断、治疗和预后方面发挥重要作用.     

生存素在寻常型银屑病皮损中的表达

目的：探讨生存素（survivin）在银屑病皮损中的表达及意义。方法：应用免疫组织化学技术（IHC）检测38例寻常型银屑病患者皮损与14例正常人皮肤中生存素的表达。结果：36例银屑病皮损中可检测到生存素,而正常皮肤无生存素表达,生存素在进行期皮损中的表达高于稳定期。结论：生存素可能参与了银屑病的发病过程。     

炎性小体在皮肤肿瘤中的研究进展

【摘要】 炎性小体是一种细胞内多蛋白复合物,是固有免疫应答的组成部分。炎性小体的功能异常可以导致机体免疫失衡,并与许多疾病密切相关。研究表明,炎性小体与基底细胞癌、鳞状细胞癌、Kaposi肉瘤及恶性黑素瘤等皮肤肿瘤有一定相关性,提示炎性小体异常活化造成的持续炎症反应及免疫应答失衡是皮肤肿瘤发生、发展、侵袭及转移的重要环节。本文概述炎性小体在皮肤肿瘤发病机理中的研究进展。     

环氧合酶-2在皮肤肿瘤中的研究进展

环氧合酶 - 2是前列腺素合成的限速酶。研究显示环氧合酶 - 2的过度表达与多种肿瘤的发生、发展密切相关。就环氧合酶 - 2的结构特征、生物学特性、与肿瘤发生发展的关系、在皮肤肿瘤中的研究进展及其在肿瘤预防和治疗中的应用前景进行综述     

血管紧张素受体Ⅰ在某些皮肤肿瘤中的免疫组化研究

血管紧张素受体Ⅰ(angitotension type-1,AT1)是肾素血管紧张素Ⅱ的特异性受体之一,它可介导肾素血管紧张素调节血压和水盐平衡。近年来报道AT1亦与细胞增殖关系密切。在本实验中,我们采用免疫组化方法研究了AT1在皮肤基底细胞上皮瘤(BCE),鳞状细胞癌(SCC),角化棘皮瘤(KA)中的表达情况,探讨其在表皮肿瘤发生中的作用。     

肿瘤坏死因子拮抗剂在治疗非银屑病性皮肤病中的临床应用

肿瘤坏死因子拮抗剂通过阻断肿瘤坏死因子与其受体的结合而阻止胞内信号的传递、下游炎症因子的激活及细胞增殖而达到抗炎作用。用于临床的肿瘤坏死因子拮抗剂主要包括英夫利昔单抗（IFX）、依那西普( ENT)、阿达木单抗( ADA)等,在皮肤科中已广泛应用于非银屑病的治疗,本文对其进行了综述。     

短发卡RNA对人黑素瘤细胞BRAF基因的沉默作用

目的构建BRAF基因序列特异性的短发卡RNA(shRNA)质粒载体,检测其对人黑素瘤细胞BRAF基因的干扰作用。方法设计2条BRAF基因序列特异性的shRNA编码序列和1条非特异性阴性对照序列,插入质粒pGenesil-1,双酶切和测序鉴定。用构建成功的3条质粒转染人黑素瘤细胞株A375和M14,分别采用RT-PCR和蛋白印迹检测其BRAF基因的mRNA和蛋白表达。结果所设计的shRNA序列被正确插入质粒pGenesil-1。非特异性对照质粒neg对黑素瘤细胞BRAF基因表达不产生干扰,2条序列特异性质粒braf1和braf2抑制了BRAF基因mRNA和蛋白的表达,其中braf1干扰效果最为明显,最高抑制率可达90%。结论质粒介导的shRNA可成功干扰人黑素瘤细胞BRAF基因的表达,其抑制时间可持续至少1个月。     

Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma

The newly described apoptosis inhibitor survivin is expressed in many human cancers and appears to play a critical part in both apoptosis regulation and cell cycle progression. Its potential role in malignant melanoma is unknown. In a panel of 30 malignant melanomas, survivin was strongly expressed in all cases (15 of 15) of metastatic malignant melanomas and 13 of 15 cases of invasive malignant melanomas by immunohistochemistry. In invasive malignant melanomas, survivin was also expressed in the in-situ component of the lesion. Survivin expression was found in all cases (11 of 11) of nevi, but not in melanocytes in sections of normal skin. The apoptosis inhibitor bcl-2 was expressed in 26 of 30 cases, but generally at lower levels than that of infiltrating lymphocytes. The mitotic index, as assessed by MIB-1 staining, was consistently higher in metastatic than invasive malignant melanomas. Assessment of apoptotic index by in situ end-labeling revealed extremely low rates of apoptosis in most malignant melanomas. Survivin expression by western blotting was detected in four human metastatic malignant melanoma cell lines but not in cultured normal human melanocytes. Transfection of both YUSAC-2 and LOX malignant melanoma cells with green fluorescence protein-conjugated survivin anti-sense or green fluorescence protein-conjugated survivin dominant negative mutant (Cys84Ala) [corrected] resulted in increased apoptosis in the absence of other genotoxic stimuli. Two-color flow cytometry confirmed that YUSAC-2 cells transfected with survivin anti-sense expressed less endogenous survivin and exhibited an increased fraction of cells with sub-G1 DNA content. These data demonstrate that apoptosis inhibition by survivin may participate in the onset and progression of malignant melanomas, and suggest that therapeutic targeting of survivin may be beneficial in patients with recurrent or metastatic disease.     

颈动脉体瘤的诊断与综合治疗

目的探讨颈动脉体瘤的诊断以及术前介入栓塞联合手术切除的综合治疗。方法12例颈动脉体瘤患者入院前均行彩色多普勒超声检查,术前均行颈动脉CTA检查,并进行图像三维重建,且于术前在选择性数字减影血管造影（DSA）下行分支动脉栓塞术,其中2例患者行血管外膜下颈动脉体瘤剥离切除,8例行肿瘤并颈外动脉切除,2例行肿瘤并颈内、外动脉切除和颈内动脉重建。结果1例患者出现患侧面部麻木、吐字略欠清晰,2周后恢复。余均未出现与手术相关的并发症。12例患者均临床治愈,随访2个月。1年,均无复发。结论人院前后行血管多普勒超声、cT血管造影（CTA）及图象三维重建等检查以明确诊断,术前DSA下栓塞分支动脉,以减少术中失血,术前明确瘤体与颈内外动脉的解剖关系,合理选择治疗方式,采用恰当的术式,对于颈动脉体瘤治疗是必要的。     

玫瑰痤疮的治疗进展

玫瑰痤疮药物治疗包括抗生素类、维A酸类、免疫抑制剂、α肾上腺素受体激动剂、抗幽门螺杆菌药物及ε氨基己酸(ACA)等,此外多种类型的激光已经越来越多地用于玫瑰痤疮的治疗。本文将对以上内容进行综述。     

结节性痒疹治疗进展

结节性痒疹的治疗主要包括局部治疗、光疗和系统治疗，近年来出现了一些新的治疗方法，如神经激肽-1受体（NK-1R）拮抗剂、白介素-31受体（IL-31R）拮抗剂、Dupilumab和μ-阿片受体拮抗剂/κ-阿片受体激动剂等。本文対结节性痒疹的治疗进展进行综述。     

Update in the treatment of herpes zoster

The systemic treatment of herpes zoster shortens the healing process, and prevents or alleviates pain and other acute or chronic complications, especially when it is administered in the first 72 hours after symptoms appear. This treatment is especially indicated in patients over the age of 50 and in those who, regardless of age, have head and neck involvement, especially in herpes zoster ophthalmicus. The drugs approved in Europe for the systemic treatment of herpes zoster are aciclovir, valaciclovir, famciclovir and brivudine. Brivudine shows greater effectiveness against the varicella-zoster virus than aciclovir and its derivatives, and can be given just once a day for seven days, compared to multiple doses of the latter. As opposed to the others, brivudine is a non-nephrotoxic drug that should not be administered to immunodepressed patients or to those being treated with 5-fluorouracil. The treatment of herpes zoster to reduce pain should be combined with analgesics and neuroactive agents (amitriptyline, gabapentin, etc). While corticosteroids are of dubious efficacy in the treatment of post-herpes neuralgia, the intensity and duration of the pain can be reduced with some topical treatments (capsaicin, lidocaine patches, etc). Finally, this review discusses treatment guidelines for special locations (cranial nerves) and different subpopulations (children, pregnant women, immunodepressed patients, etc).     

Subungual glomus tumor: clinical manifestations and outcome of surgical treatment

Surgical excision is the treatment of choice for subungual glomus tumor. However, the anatomical location has inherent difficulties. We report the outcomes of surgical treatments for subungual glomus tumor. Sixteen patients, who were seen over an eight-year period (1995-2003) and confirmed as gloums tumor by histopathologic examination were reviewed. The most common subjective symptom was pain induced by contact in 81%. The tumor presented as a discolorated spot or subungual nodule and 38% of tumors were acccompanied with nail dystrophy. All tumors showed discolorated spots or subungual nodules. As shown in the Table 2, the dystrophic nail change was found in 38% of tumors. Differently oriented incisions were made according to the location of tumor, matrix, or bed. The original nail plate was restored in eight patients. Thirteen patients (81%) had cosmetically excellent nail plates, and three patients (19%) had partial distal splits of nail plates. There was no recurrence. Our series suggests that a transungual approach with nail avulsion and an incision selected according to the tumor location can produce an excellent outcome with minimal postoperative complications. Dressing with a trimmed nail plate may also be beneficial in managing the wound and preventing postoperative nail deformity.     

黄褐斑的治疗进展

目前黄褐斑的治疗方法众多,主要包括药物治疗、化学剥脱、光电疗法及中医中药等,单一疗法均疗效欠佳。目前认为综合治疗有较好的治疗效果,本文就黄褐斑的治疗进展作一综述。     

儿童白癜风治疗进展

白癜风治疗方法很多,但一般而言,儿童及青少年患者治疗效果要优于成人。白癜风治疗的关键在于稳定疾病进展、促使皮损复色,本文对临床常用治疗儿童白癜风的方法进行了综述。