Outcomes Following Isolated Limb Infusion for Melanoma. A 14-Year Experience

Background  Isolated limb infusion (ILI) is a minimally invasive technique for delivering regional chemotherapy in patients with advanced and metastatic melanoma confined to a limb. It is essentially a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation. Methods  From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1993 and 2007 were identified. In all patients a cytotoxic drug combination of melphalan and actinomycin-D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Results  The majority of patients (62%) were female. Their average age was 74 years (range 29–93 years). Most patients had MD Anderson stage III disease (134/185). The overall response rate was 84% [complete response (CR) rate 38%, partial response rate 46%]. Median response duration was 13 months (22 months for patients with CR; P = 0.01). Median follow-up was 20 months and median survival was 38 months. In those patients with a CR, the median survival was 53 months (P = 0.005). CR rate and survival time decreased with increasing stage of disease. On multivariate analysis significant factors for a favorable outcome were achievement of CR, stage of disease, thickness of primary melanoma, the CO₂ level in the isolated circuit, and a Wieberdink limb toxicity score of III (considerable erythema and edema). Conclusion  The response rates and duration of response after ILI are comparable to those achieved by conventional ILP. ILI is a minimally invasive alternative to the much more complex and morbid conventional ILP technique for patients with advanced metastatic melanoma confined to a limb.     

circFNDC3B通过抑制miR147表达促进恶性黑素瘤迁移与侵袭

【摘要】目的 探究正常表皮黑素细胞和恶性黑素瘤细胞中环状RNA circFNDC3B的表达水平及其对恶性黑素瘤A2058细胞迁移和侵袭的影响。方法 RT-QPCR实验检测恶性黑素瘤A2058和A375细胞和正常表皮黑素HEMaLP细胞中circFNDC3B表达水平;siRNAs敲低恶性黑素瘤A2058细胞中circFNDC3B的表达;转染siNC和sicircFNDC3B的A2058细胞分别为对照组和实验组,应用细胞划痕实验比较细胞迁移距离,应用免疫印迹实验检测Ecadherin和Ncadherin表达,应用RT QPCR进行检则miRNAs表达。结果 与正常表皮黑素细胞HEMaLP相比,circFNDC3B在恶性黑素瘤细胞中的表达上调。沉默A2058细胞中circFNDC3B 表达后,细胞的迁移和侵袭能力均显著降低（P＜0.05）,Ecadherin表达显著增强,Ncadherin表达显著减弱,抑癌性miRNA miR147表达升高。结论 circFNDC3B在恶性黑素瘤细胞中高表达,可通过抑制miR147表达促进上皮间质转化,进而促进细胞迁移及侵袭。     

大剂量干扰素辅助治疗口腔黏膜恶性黑色素瘤的效果及安全性研究

目的 研究大剂量干扰素辅助治疗口腔黏膜恶性黑色素瘤的临床效果,探讨治疗应用的安全性。方法 选取我院于2017年11月～2018年11月收治的80例口腔黏膜恶性黑色素瘤患者作为研究对象,按照治疗方法不同分为两组,每组40例。对照组患者仅采用单纯手术治疗,治疗组在此基础上采用大剂量干扰素辅助治疗。观察两组患者生存情况、疾病复发情况以及毒副反应。结果 治疗组患者生存期限及无复发生存期明显长于对照组,治疗组复发率为5.00%,明显低于对照组的22.50%,差异有统计学意义(P0.05)。两组患者毒副反应比较差异无统计学意义(P0.05)。结论 口腔黏膜恶性黑色素瘤患者予以大剂量干扰素辅助疗法安全有效,值得临床推广。     

组织内AEG-1表达情况对葡萄膜黑色素瘤病理特征的影响

目的 探究组织内星形胶质细胞活化基因-1(AEG-1)表达情况对葡萄膜恶性黑色素瘤(UM)病理特征的影响。方法 选取2016年3月～2018年8月我院眼科诊治的62例(62眼)于病理室存放的UM石蜡组织标本纳入研究组。并选取同期20例(20眼)因外部原因受伤采取眼球摘除术但少量UM或绝大部分葡萄膜组织正常的石蜡组织标本作为对照组。对比分析两组患者AEG-1基因表达情况以及AEG-1表达情况与UM病理特征的相关性。结果 UM组织中AEG-1 mRNA相对表达量为(1.09±0.05),正常葡萄膜膜组织中AEG-1 mRNA相对表达量为(1.01±0.12),差异有统计学意义(P0.05);研究组62例(62眼)AEG-1阳性表达为37眼(59.68%),阴性表达为25眼(40.32%);对照组20例(20眼)AEG-1均呈阴性表达,差异有统计学意义(P0.05);肿瘤高度8 mm、累及睫状体、侵犯巩膜导管、眼外生长、视盘受累以及继发视网膜脱落与AEG-1高表达均有明显相关性(P0.05)。结论 UM高度8 mm、累及睫状体、侵犯巩膜导管、眼外生长、继发视网膜脱落及视盘受累病理特征均与AEG-1的高表达具有密切联系,显著影响UM转移风险和预后,为UM临床诊断和治疗提供有效参考。     

Brain metastases of malignant melanoma in Chinese: report of 23 cases

Background Patients with melanoma metastasized to the central nervous system have a poor prognosis. Because the incidence of malignant melanoma in the Oriental is lower than that in the Caucasian population, brain metastases of malignant melanoma are rarely reported in Asia. Here we present our experience of brain metastasis of melanoma in an Asian perspective. Methods From 1990 to 2003, 369 patients with melanoma were treated in our hospital, 26 of them were diagnosed as having central nervous system involvement. Of the 26 cases, the clinical history, image, and pathologic findings of 23 patients were analyzed; the other 3 were excluded because of incomplete clinical data. Results Among the 369 patients with melanoma, 45% （167/369） developed lower extremity melanoma, and 27.1% （100/369） had acral lentiginous melanoma （ALM）; while in the 23 patients with brain metastases, 34.7% （8/23） had lower extremity melanoma, and 34.7% （8/23） had ALM. Among the 23 patients, 17 had acute hemorrhage into the tumor, 8 initially presented with a single cerebral metastatic lesion, and 15 had multiple brain lesions. Ten of them received surgery, 3 underwent stereotactic radiosurgery, and 16 received whole brain radiation. During follow-up, only 2 patients survived for more than 1 year, the median survival period was 5 months. The longest follow-up period was 11 years. Conclusions Compared with the Caucasian, Chinese patients with melanoma have a different proportion of melanoma subtype and higher incidence rates of lower extremities melanoma and ALM. However, their clinical presentation and prognosis are similar. The patients, who have excisable single or multiple brain lesions or limited extracranial disease and who are activelv treated, mav survive Ionoer.     

内质网应激PERK-eIF2α-ATF4信号通路在延缓APP/PS1小鼠移植瘤生长中的作用

探讨内质网应激（ERS）及内质网自噬对移植黑色素瘤模型淀粉样蛋白前体蛋白（APP）/早老素1（PS1）小鼠移植瘤生长的抑制作用,并阐明蛋白激酶R样内质网激酶（PERK）-真核翻译起始因子2α（eIF2α）-活化转录因子4（ATF4）通路在其抑制作用中的可能机制。     

MAGE-3逆抗原转染树突状细胞的抗胃癌免疫效率

目的构建逆抗原表达载体,以获得理想的肿瘤疫苗。方法运用RT-PCR方法合成MAGE-3cDNA,分别将RANTES基因分泌段前导序列和受体Fc段克隆至MAGE-3cDNA两端(pS-MAGE-3-Fc)再转染入DC表达,将致敏的DC与外周血T细胞和胃癌细胞共培养,观察产生的免疫效应。结果转染pS-MAGE-3-Fc的DC诱导的刺激淋巴细胞增殖反应和CTL杀伤效应均显著高于转染pMAGE-3的转染组和对照组(P<0.05)。结论逆抗原策略是理想的肿瘤疫苗策略,能够显著提高肿瘤免疫效率。     

伴脉络膜脱离的原发性孔源性视网膜脱离术前局部和全身应用皮质类固醇激素效果比较

目的 比较伴脉络膜脱离的原发性孔源性视网膜脱离玻璃体手术前局部和全身应用皮质类固醇激素治疗的手术成功率和视功能改变.方法 连续观察38例38眼原发性孔源性视网膜脱离伴脉络膜脱离并行玻璃体手术治疗患者.其中局部应用激素组(A组)11例,术前应用醋酸强的松龙眼液点眼每小时1次,用药(4.91±1.51) d;全身激素治疗组(B组)27例,术前地塞米松静脉滴注15 mg,3 d后剂量递减,术前用药(5.67±1.88)d.结果 一次手术视网膜脱离复位率A组为54.5%,B组为63.0%;再次手术成功率A组为80.0%,B组为100%.A组70%患者术后视力提高,20%视力保持不变,B组68%患者术后视力提高,24%视力保持不变.初次手术后视网膜脱离复发的15例患者中,14例系因玻璃体视网膜增殖形成所致.结论 伴脉络膜脱离的原发性孔源性视网膜脱离玻璃体手术前局部激素治疗组的手术成功率趋势上低于全身激素治疗组.两组的最终视功能改善结果无差异.术后视网膜脱离复发的主要原因系玻璃体视网膜增殖所致.     

溶氧反馈-补料分批技术高密度培养基因重组MAGE1/HSP70/MAGE3工程菌

目的 建立人黑色素瘤抗原MAGE1/HSP70/MAGE3融合蛋白基因重组工程菌E.coli.BL21/pET-MHM的高密度发酵工艺.方法 以摇瓶发酵结果为基础,扩大至NBS Bioflo Ⅳ 20 L发酵罐发酵,利用溶氧反馈-补料分批培养技术,对影响工程菌生长及目的蛋白表达的因素如发酵培养基、活化时间、诱导浓度及时间、pH值及分批补加营养物质等进行优化.结果 保持培养过程中40%的溶解氧,采用半合成培养基、活化至对数生长期时0.2 mmol/L IPTG诱导5 h以及以甘油为碳源连续流加补料的条件发酵,连续3批重复发酵,最终菌密度D(600)均达45～50时,菌体量可提高至70 g/L以上,目的蛋白的表达量占菌体蛋白总量的38%以上.结论 确定了周期短、产率高且稳定可靠的发酵工艺.     

血管生成因子在咽喉部恶性黑色素瘤的表达及与血管生成的关系

目的　研究血管内皮生长因子 (VEGF)、碱性成纤维细胞生长因子 (b FGF)、转化生长因子β1 (TGF-β1 )及其受体和肿瘤源性粘附因子 (TAF)在咽喉部恶性黑色素瘤中的表达特点 ,以及它们与肿瘤内微血管密度(MVD)和病人预后的关系。　方法　应用免疫组织化学和形态计量方法检测 2 8例咽喉部恶性黑色素瘤 MVD、VEGF、b FGF、TGF- β1 及其受体和 TAF的表达 ,并应用多因素 Cox比例风险模型检测上述因素和病人预后的关系。　结果　 2 8例咽喉部恶性黑色素瘤中 ,VEGF阳性 19例 (6 7.9% ) ,b FGF阳性 2 1例 (75 .5 % ) ,TGF- β1 阳性 16例 (5 7.1% ) ,TAF阳性 18例 (6 4.3% )。血管生成因子与其受体表达具有一致性 ,并与 MVD值显著相关。Cox模型分析显示 MVD和 VEGF是影响咽喉部恶性黑色素瘤的重要因素 (P<0 .0 5 )。　结论　 VEGF、b FGF、TGF- β1 和TAF是咽喉部恶性黑色素瘤中血管生成的重要因子 ,并通过促进血管生成影响病人的预后。其中 MVD和 VEGF是评估咽喉部恶性黑色素瘤病人预后的重要指标。