HPV阳性宫颈癌组织中miR-34b的表达水平及其临床意义

目的:探讨miR-34b在HPV阳性宫颈癌组织中的表达水平及其对患者的临床意义。方法:收集65例HPV阳性宫颈癌组织标本和35例正常宫颈组织标本,采用Real-time PCR法测定miR-34b的相对表达水平,分析其与患者临床病理特征的关系以及对患者诊断、预后的价值。结果:miR-34b在HPV阳性宫颈癌组织中的相对表达量明显低于正常宫颈组织,差异具有统计学意义（t=9.549,P＜0.05）;在HPV阳性宫颈癌患者中,miR-34b的相对表达量与患者的年龄、病理类型、肿瘤分级均无明显关系（P＞0.05）,与患者的肿瘤大小、FIGO分期、淋巴结是否转移显著相关,差异具有统计学意义（χ2=4.996、5.925、5.824,P＜0.05）;进行ROC曲线分析,发现miR-34b区分HPV阳性宫颈癌细胞与正常宫颈细胞的AUC为0.871（95%CI:0.773~0.970,P=0.000）,灵敏度为90.24%,特异度为79.17%;对HPV阳性宫颈癌患者随访3年,发现miR-34b高表达患者的OS、DFS均显著高于低表达患者,差异具有统计学意义（χ2=5.856、5.919,P＜0.05）。结论:miR-34b在HPV阳性宫颈癌组织中呈低表达,可能为HPV阳性宫颈癌筛查、诊断和治疗提供帮助,具体情况还有待进一步研究。     

miR-155-5p和ELK3在胆囊癌组织中的表达及其临床意义

目的:分析miR-155-5p和ELK3在胆囊癌组织中的表达水平，并探讨其表达与胆囊癌临床病理特征及预后的关系。方法:收集2014年1月至2015年5月在本院进行手术治疗的45例胆囊癌患者的肿瘤组织和癌旁非肿瘤组织，采用RT-PCR检测组织中miR-155-5p和ELK3 mRNA表达水平，采用免疫组织化学染色法检测组织中ELK3蛋白表达情况，分析肿瘤组织中miR-155-5p和ELK3表达水平的关系，分析miR-155-5p和ELK3表达水平与胆囊癌患者肿瘤大小、转移、浸润等病理特征及3年总生存率的关系。结果:肿瘤组织中miR-155-5p、ELK3 mRNA表达水平及ELK3蛋白阳性率均高于癌旁非肿瘤组织（P＜0.05）；肿瘤组织中miR-155-5p和ELK3表达水平呈正相关（P=0.002）；miR-155-5p表达水平与肿瘤大小、组织分化程度、淋巴结转移、远处转移、血管浸润、胆管侵犯、肝脏侵犯有关（P＜0.05），ELK3阳性率与FIGO分期、淋巴结转移、血管浸润、胆管侵犯和肝脏侵犯有关（P＜0.05）；miR-155-5p高表达组患者3年总生存率低于miR-155-5p低表达组患者（P＜0.05），ELK3阳性表达患者3年生存率低于ELK3阴性表达患者（P＜0.05）。结论:胆囊癌组织中miR-155-5p和ELK3表达上调，与胆囊癌转移、侵袭等恶性生物学行为及不良预后密切相关，可作为胆囊癌临床预后预测的检测指标。     

miR-141和lncRNA-H19在宫颈癌中的表达及临床意义

目的:检测宫颈癌组织中微小RNA-141（miR-141）与长链非编码RNA-H19（lncRNA-H19）表达情况，并探究其临床意义。方法:选取2013年9月至2014年12月本院确诊收治的宫颈癌患者62例，取宫颈癌组织及癌旁组织；取血清检测肿瘤指标鳞状细胞癌抗原（SCCA）。利用实时定量PCR（qRT-PCR）法检测宫颈癌及癌旁组织中miR-141、lncRNA-H19表达情况，采用全自动化学发光免疫分析仪检测患者血清SCCA水平。结果:与癌旁组织相比，宫颈癌组织中miR-141和lncRNA-H19表达水平显著升高；宫颈癌组织中miR-141表达与患者临床分期、血清SCCA水平显著相关；宫颈癌组织中lncRNA-H19表达与患者有无淋巴结转移、血清SCCA水平显著相关；Pearson分析发现，宫颈癌组织中miR-141和lncRNA-H19表达水平显著正相关；miR-141低表达患者3年总生存率为37.50%，显著高于miR-141高表达者的8.00%；lncRNA-H19低表达患者3年总生存率为41.67%，显著高于lncRNA-H19高表达者的13.16%。结论:miR-141和lncRNA-H19在宫颈癌组织中的表达显著升高，与宫颈癌疾病严重程度有关，可能作为判断宫颈癌患者预后的生物指标。     

血清miR-153和miR-142-3p表达在宫颈癌诊断和预后评估中的价值

摘 要：［目的］ 探讨宫颈癌患者血清miR-153及miR-142-3p的表达及其在宫颈癌诊断和预后评估中的价值。［方法］ 选取2014年1月至2017年3月收治的宫颈癌患者142例，采用实时荧光定量聚合酶链反应（RT-PCR）检测宫颈癌患者血清miR-153及miR-142-3p表达水平。绘制ROC曲线分析miR-153及miR-142-3p对宫颈癌诊断的截断值，并以此为标准将宫颈癌患者分为高表达和低表达，对两组临床病理特征进行比较。采用多因素Cox回归模型分析影响宫颈癌患者术后预后不良的危险因素。［结果］ 宫颈癌组血清miR-153（0.76±0.38 vs 1.92±0.95）及miR-142-3p（2.14±1.06 vs 8.15±3.20）表达水平明显低于对照组（P<0.01）。血清miR-153及miR-142-3p表达水平诊断宫颈癌的最佳截断值分别为1.31和4.93，AUC分别为0.817（95%CI：0.755～0.878）和0.850（95%CI：0.791～0.912）。血清miR-153及miR-142-3p低表达与宫颈癌患者的临床分期、分化程度、浸润深度、淋巴结转移及脉管浸润有关（P<0.05）。miR-153及miR-142-3p低表达与宫颈癌患者生存期短有关（P<0.01）。多因素Cox回归模型分析显示，临床分期、浸润深度、淋巴结转移、miR-153＜1.32及miR-142-3p＜4.93是影响宫颈癌患者预后不良的独立危险因素。［结论］ 血清miR-153及miR-142-3p表达水平在宫颈癌患者中明显下调，miR-153及miR-142-3p有望作为宫颈癌诊断及预后评估的生物学标志物。     

宫颈癌组织中miR-183与GSPT1的表达及临床意义

目的 探讨宫颈癌组织中微小RNA (miR)-183与细胞周期G1到S期的转换1 (GSPT1)的表达及与预后的关系。方法 收集2014年1月至2016年12月接受根治性手术的91例宫颈癌患者。采用实时荧光定量PCR检测91例宫颈癌和癌旁组织中miR-183和GSPT1的表达。分析宫颈癌组织中miR-183与GSPT1表达的相关性,并采用生物信息学方法预测两者之间的结合位点。进一步分析miR-183和GSPT1表达与宫颈癌临床病理特征及预后的关系。结果 宫颈癌组织中miR-183的表达（0.521±0.065）低于癌旁组织（1.241±0.286）,差异有统计学意义（P=0.000）。宫颈癌组织中GSPT1的表达（2.034±0.374）高于癌旁组织（0.708±0.157）,差异有统计学意义（P=0.000）。宫颈癌组织中miR-183与GSPT1的表达呈负相关（r=-0.621,P=0.001）。生物信息学预测结果显示,GSPT1 mRNA第981至987碱基存在与miR-183相互作用的位点。宫颈癌组织中miR-183和GSPT1表达与FIGO分期、分化程度、肌层浸润和淋巴结转移有关（P＜0.05）,与年龄和病理类型无关（P>0.05）。全组1、3、5年无病生存率分别为86.8%、73.6%和61.5%。miR-183高表达组1、3、5年无病生存率分别为91.1%、86.6%和80.0%,优于miR-183低表达组的82.6%、60.9%和43.5%,差异有统计学意义（P=0.012）。GSPT1高表达组1、3、5年无病生存率分别为86.0%、60.4%和39.5%,低于GSPT1低表达组的87.5%、85.4%和81.2%,差异有统计学意义（P=0.007）。结论 宫颈癌组织中miR 183表达降低,GSPT1表达升高,两者共同促进宫颈癌进展,有望成为宫颈癌预后评估的标志物。     

SLUG、ZEB1在宫颈癌组织中的表达及与预后的关系

目的:探讨锌指转录因子（SLUG）和锌指E盒结合蛋白1（zinc finger E-box binding protein 1，ZEB1）在宫颈癌组织中的表达及与临床病理特征和预后的关系。方法:选取本院2015年12月至2018年12月期间经手术切除的85例宫颈癌标本，另选92例宫颈低级别上皮内病变（low-grade squamous intraepithelial lesion，LSIL）患者作为LSIL组，108例良性病变行子宫全切患者作为对照组。采用免疫组化法测定受试者宫颈组织中SLUG和ZEB1表达水平，分析二者表达水平与宫颈癌临床病理特征的关系，对所有术后患者进行随访，分析二者表达水平对宫颈癌患者预后的影响。结果:宫颈癌组织中SLUG和ZEB1阳性表达率分别为85.88%（73/85）和82.35%（70/85），显著高于对照组、LSIL组，差异有统计学意义（P＜0.05），LSIL组显著高于对照组（P＜0.05）。SLUG和ZEB1在宫颈癌组织中的表达水平与宫颈癌的分化程度、临床分期、淋巴转移、浸润程度有关（P＜0.05）。术后随访发现，SLUG高表达、ZEB1高表达宫颈癌患者术后生存率均显著低于SLUG低表达、ZEB1低表达患者（P＜0.05）。COX多因素分析表明，低分化、有浸润（≥1/2）、SLUG高表达、ZEB1高表达是影响宫颈癌患者不良预后的独立危险因素（P＜0.05）。结论:在宫颈癌组织中SLUG和ZEB1表达水平显著升高，与宫颈癌的分化程度、淋巴转移、浸润程度及术后生存率有关，有望成为评定宫颈癌患者预后的临床指标。     

CK10和CK17在早期宫颈癌组织中的表达及其预测预后的价值

目的:CK10和CK17在早期宫颈癌组织中的表达及其预测预后价值的意义。方法:采用标准免疫组化SP法检测CK10和CK17在60例正常宫颈组织、60例宫颈上皮内瘤变和120例宫颈癌组织中的表达情况。结果:CK10的阳性表达定位于细胞质,在正常宫颈组织、CIN、宫颈癌患者中阳性表达率分别为80.00%、50.00%和21.67%,三组相比差异有显著统计学意义（P<0.001）。CK17的阳性表达定位于细胞质,三组阳性表达率分别为0%、46.67%和80.00%,三组相比差异显著（P<0.001）。χ2检验分析宫颈癌组织中CK17的表达与患者FIGO分期、是否有淋巴结转移、病理分型、组织分化无关（P>0.05）;CK10的表达与患者FIGO分期、是否有淋巴结转移、病理分型无关,与组织分化程度有关（P=0.021）。Kaplan-Meier生存分析显示:早期宫颈癌手术治疗患者的1年、3年、5年生存率分别为:100%、96.7%、93.3%;CK10 阴性组和阳性组5年生存率分别为91.5%和100%;CK17阴性组和阳性组5年生存率分别为100%和91.7%,差异均无统计学意义（P>0.05）。单因素分析显示CK10及CK17的表达和预后无关（P>0.05）,年龄、是否淋巴结转移、FIGO分期、组织分化、病理分型均与预后相关（P<0.05）。根据CK17和CK10的表达情况将患者分为四组,CK17阳性CK10阴性组患者1年、3年、5年生存率分别为:100%、94.9%、89.7%,余CK17阳性CK10阳性组、CK17阴性CK10阳性组、CK17阴性CK10阴性组5年生存率分别为:100%、100%、100%,差异无统计学意义（P=0.211）。结论:CK10的表达水平与宫颈病变严重程度呈负相关,CK17的表达水平与宫颈病变严重程度呈正相关,两者可能参与了宫颈癌的发生发展,但CK17和CK10在预测宫颈癌患者预后方面的价值不大,而年龄、是否淋巴结转移、FIGO分期、组织分化、病理分型是影响患者预后的重要因素。     

lncRNA DGCR5 在食管鳞状细胞癌组织中的表达及其临床意义

目的：探讨长链非编码RNA DiGeorge 综合征临界区基因5（digeorge syndrome critical region gene 5，DGCR5）在食管鳞状细胞癌（esophageal squamous cell cancinoma，ESCC）组织中的表达及其与患者临床病理特征和预后的相关性。方法：利用生物信息学方法对TCGA数据库中ESCC数据集的DGCR5 表达进行分析。收集2016 年8 月至2017 年3 月河北医科大学第四医院手术切除60 例ESCC患者的癌及癌旁组织标本，用qPCR检测ESCC组织中DGCR5 的表达水平，分析DGCR5 表达与ESCC患者临床病理特征和预后的相关性。结果：TCGA数据库分析结果显示，DGCR5 在ESCC组织中的表达水平显著高于正常食管组织（P<0.01）。ESCC组织中DGCR5 表达水平显著高于癌旁组织（P<0.01）。DGCR5 表达水平与ESCC患者TNM分期和淋巴结转移呈显著性相关（均P<0.05）。Kaplan-Meier 单因素分析显示，高表达DGCR5 的ESCC 患者2 年生存率显著低于低表达DGCR5 患者（P<0.05）。结论：DGCR5 在ESCC组织中呈高表达状态，共表达与TNM分期、淋巴结转移及预后不良密切相关，可能成为ESCC早期诊断及预后判断的分子标志物。     

miR-133a-3p在胃癌组织和血浆中的表达及其对胃癌细胞增殖的影响

[摘要] 目的：检测miR-133a-3p 在胃癌组织及患者血浆中的表达水平及其对胃癌细胞增殖的影响,并探讨其与患者预后的关系。方法：收集河北医科大学第四医院普外科2012 年5 月至2013 年5 月胃癌手术切除的组织标本及术前外周静脉血标本52例,每例组织标本采集肿瘤组织(非坏死部分)和配对的癌旁组织。采用实时荧光定量RT-PCR（RT-qPCR）法检测miR-133a-3p 在胃癌组织、癌旁组织、血浆及健康体检者血浆（35 例）的表达情况,分析miR-133a-3p 的表达水平与胃癌患者中位DFS及临床病理特征的关系。CCK-8 法检测过表达或沉默miR-133a-3p 对胃癌SGC7901 细胞增殖的影响。结果：miR-133a-3p 在胃癌组织中的表达明显降低（P<0.01）,其表达水平与肿瘤TNM分期、肿瘤侵润深度（T）、淋巴结转移（N）及脉管瘤栓相关（P<0.01）;在胃癌患者血浆中的表达明显升高（P<0.01）,其表达水平与肿瘤TNM分期、淋巴结转移（N）及脉管瘤栓相关（P<0.05）;与患者血清中CA199的表达水平正相关（P<0.01）。胃癌组织中miR-133a-3p 高表达组患者中位DFS 明显高于低表达组（20.8 vs 14.8 个月,P<0.05）。血浆中miR-133a-3p 的高表达组患者中位DFS明显低于低表达组（14.4 vs 20.3 个月,P<0.05）。过表达miR-133a-3p 可明显抑制SGC7901 细胞的增殖能力,同样沉默其表达可明显促进SGC701 细胞的增殖能力（均P<0.05）。结论：miR-133a-3p 可明显抑制胃癌细胞SGC7901 的增殖能力,在胃癌组织和血浆中存在明显异常表达,其表达与患者预后明显相关,可作为胃癌早诊早治及患者临床预后判定的潜在标志物。     

高危人乳头状瘤病毒感染宫颈癌患者miR-34a-5p表达及意义

摘 要：［目的］ 探讨高危人乳头状瘤病毒（high risk human papillomavirus，HR-HPV）感染宫颈癌患者组织及血清miR-34a-5p的表达以及血清miR-34a-5p对宫颈癌的诊断价值。［方法］ 采用RT-PCR检测70例HR-HPV阳性宫颈癌组织和癌旁组织、100例HR-HPV阳性宫颈癌患者血清、80例HR-HPV阳性宫颈上皮内瘤病变(CIN)患者血清、80例健康体检者血清中miR-34a-5p的表达水平。Pearson法分析组织和血清中miR-34a-5p表达量的相关性，分析miR-34a-5p与宫颈癌临床病理特征的关系，分析血清miR-34a-5p诊断宫颈癌的价值。［结果］ 宫颈癌组织miR-34a-5p相对表达量明显低于癌旁组织（P＜0.05）。宫颈癌患者血清miR-34a-5p相对表达量明显低于CIN患者和正常人（P＜0.05），CIN患者血清miR-34a-5p相对表达量明显低于正常人（P＜0.05）。癌组织miR-34a-5p相对表达量与淋巴结转移有关(P<0.05)。血清miR-34a-5p相对表达量与淋巴结转移和远处转移有关(P<0.05)。miR-34a-5p在癌组织与血清中的相对表达量呈正相关（r=0.459，P＜0.05）。血清miR-34a-5p诊断宫颈癌的ROC曲线下面积为0.860（95%CI：0.803~0.917）。［结论］ HR-HPV宫颈癌患者血清miR-34a-5p下调，与癌组织miR-34a-5p表达呈正相关，有望成为宫颈癌诊断的分子标志物。     

The medically important dematiaceous fungi and their identification

Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum).     

Orale Langzeitbehandlung von Onychomykosen mit Ketoconazol

Zusammenfassung: An der Studie zur Wirksamkeit und Anwendungssicherheit von Ketoconazol nahmen 27 Männer im Alter von 20 bis 80 (Median: 57) Jahre, davon 18 mit Onychomykosen und 9 als KontroUen bei den Laborwertbestimmungen, teil. Während des ersten Behandlungsmonats erhielten je 9 Patienten 200 mg und 400 mg Ketoconazol täglich. Danach wurden beide Gruppen 6 Monate mit 200 mg/d weiterbehandelt. Die klinische Beurteilung sowie hämatologische, biochemische und Plasmaspiegeluntersu-chungen erfolgten mindestens monafich, mykologische Untersuchungen wurden vor Aufnahme und bei Beendigung der Therapie vorgenommen. Erne letzte klinische Unter-suchung erfolgte 1 Jahr nach Beginn der Studie. Nach 7 Monaten Behandlung wurden 23 von 30 Nägeln mit “gebessert” bis “stark gebessert” beurteilt, nach dem behandlungsfreien Intervall galt dies für 28 von 30 Nägeln. Die Plasmaspiegel waren mit 200 mg/d ausreichend und uber den Behandlungszeit-raum konstant. Dies spricht für gute orale Resorption und Abwesenheit von Enzyminduktion. Die Laborwerte zeigten im Vergleich zu den Kontrollen und den Werten vor Behandlung keine signifikanten Abweichungen, so daß myelo-, nephro- und hepatotoxische Wirkungen von 400 bzw. 200 mg/d ausgeschlossen werden können. Der Lipidhaushalt wurde nicht beeinfluat und es trat unter Therapie als Folge der Ketoconazolwirkung lediglich Lanosterin im Serum auf. Nach Beendigung der Therapie ging der Lanosteringehalt schnell zurück. Damit erweist sich Ketoconazol in den angewandten Dosen als ein gut verträgliches und zur Langzeitbehandlung von Onychomykosen geeignetes Antimykotikum. Summary: Twenty-seven males with a median age of 57 (range: 20 to 80) years took part in this study on the efficacy and safety of ketoconazole. Eighteen men suffered from onychomycosis; nine served as controls in the safety evaluation. During the first month of treatment, nine patients received 200 mg and the nine other 400 mg ketoconazole daily. Then the treatment was uniformly continued with 200 mg/d for 6 months. Clinical evaluation and haematological, biochemical and plasma level investigations were carried out at least at monthly intervals; mycological controls were performed at the start and end of therapy. A final clinical evaluation was carried out one year after the start of the study. After 7 months of treatment, moderate or definite clinical improvement was obtained in 23 out of 30 nails. After 5 more months without antimycotic treatment this was the case in 28 of 30 nails. Plasma levels obtained with 200 mg ketoconazole daily were adequate and constant during the entire treatment period. This indicates a good oral resorption as well as the absence of induction of hepatic enzymes. The laboratory values did not show significant deviations as compared with the controls or with the pretreatment values. This excludes myelo-, nephro- and hepatotoxic effects of 400 and 200 mg ketoconazole daily. The lipid metabolism was not influenced, the only difference was the occurrence of lanosterol in the serum, which is a result of the mechanism of action of ketoconazole. After the medication period the lanosterol levels subsided rapidly. In the applied doses ketoconazole is a well-tolerated and effective drug for the systemic long-term treatment of onychomycosis.     

Laboratory Techniques Alternative to In Vivo Experiments for Studying the Liberation, Penetration and Fungicidal Action of Topical Antimycotic Agents in the Skin, Including Ciclopiroxolamine

Summary: Short-term experiments on excised skin (human, pig) gave the following results: 1. In the tissue activity test with direct inoculation (D-TAT) commercial preparations of the non-azole antimycotics ciclopiroxolamine, tolnaftate and naftifine, produced higher inhibitory activity against Trichophyton mentagrophytes (standard strain) in various levels of the horny layer than were produced by the azole antimycotics econazole, miconazole, clotrimazole, oxiconazole and bifonazole. Fast drying solutions of antimycotics invariably gave higher inhibitory activities than creams. In the ultrafiltration tissue activity test (UFT- TAT) against Candida albicans (2 strains), antimycotic agents ranked in order of effectiveness as follows: ciclopiroxolamine – most of the azole antimycotics – bifonazole and naftifine. 2. In tests of fungicidal activity against T. mentagrophytes (2 strains) and Microsporum gypseum (1 strain) the first step was to inoculate the skin surface. After the horny layer had been penetrated by fungal mycelia, antimycotic agents of documented fungicidal potency, chiefly in the form of creams, were applied to the skin surface and left to act for up to 18 hours. The horny layer and epidermis were then scraped off and the concentration of viable fungi was determined. Ciclopiroxolamine cream and lotion produced by far the greatest diminution in viable fungi; creams containing oxiconazole and naftifine were moderately effective and those containing tioconazole and bifonazole produced a relatively small decrease in viable fungi. To avoid erroneous results it is important to homogenize and dilute the skin scrapings; if this is not done certain antimycotics will give misleadingly high fungal killing rates. At this early stage the scatter of results is still wide and minor differences in efficacy cannot as yet be detected with certainty. 3. From the results of various comparative tests it is evident that pig skin can be used as a substitute for human skin in the tests listed under 1. and 2. above. This discovery may make a valuable contribution towards limiting the need for experiments on living animals and trials on human beings. Zusammenfassung: In Kurzzeitversuchen an exzidierter Haut (Mensch, Schwein) wurde gefunden: 1. Im Gewebeaktivitätstest mit direkter Inokulation (D-GAT) wurde mit Handelspräparaten der Nichtazol-Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine höhere Hemmaktivität gegenüber Trichophyton mentagrophytes (Standard-Stamm) erzielt als mit solchen der Azol-Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Lösungen von Antimykotika ergaben durchweg höhere Hemmaktivitäten als Cremes. Im Ultrafiltrations-Gewebeaktivitätstest (UFT-GAT) gegenüber Candida albicans (2 Stämme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie-Testen gegenüber T. mentagrophytes (2 Stämme) und Microsporum gypseum (1 Stamm) wurde zunächst die Hautoberfläche inokuliert. Nach Durchdringung der Hornschicht mit Pilzmyzelien wirkten auf die Hautoberfläche bis zu 18 Stunden lang überwiegend Cremes von als fungizid publizierten Antimykotika ein. Während sich in abgeschabter Hornschicht und Epidermis der so bearbeiteten Hautoberflächen mit Ciclopiroxolamin-Creme und -Lotion die weitaus höchste Verminderung lebensfähiger Keime ergab, bewirkten Cremes mit Oxiconazol und Naftifin eine mittlere und solche mit Tioconazol und Bifonazol eine relativ niedrige Keimeliminierung. Zur Vermeidung von fehlerhaften Ergebuissen mußten Homogenisierung und Verdünnung der Hautschabsel erfolgen, anderenfalls bei mehreren Antimykotika eine zu hohe Keimabtötung vorgetäuscht worden wäre. Wegen der vorerst noch hohen Streuung der Ergebnisse können kleinere Wirksamkeitsunterschiede noch nicht sicher erfaßt werden. 3. Nach dem Ergebnis verschiedener Vergleichstests kann in den Testen zu 1. und 2. Schweinehaut als Ersatz für Haut vom Menschen dienen und dürfte damit wesentlich zur Einschränkung von Versuchen am lebenden Tier und von Prüfungen am Menschen beitragen.     

Efficiency of crude and purified fungal antigens in serodiagnosis to discriminate mycotic from other respiratory diseases

Mycotic immunodiagnosis was performed in 186 hospitalized patients with different respiratory diseases, mostly considered as tuberculosis and others with a doubtful diagnosis. Crude histoplasmin, coccidioidin, paracoccidioidin, blastomycin, candidin, aspergillin, and sporotrichin, as well as purified polysaccharide-protein complexes (PPC) of Histoplasma capsulatum, Coccidioides immitis, and Paracoccidioides brasiliensis were used as antigens. Immune tests used included skin test (ST), gel immunodiffusion (ID), counterimmunoelectrophoresis (CIE), complement fixation (CF), and ELISA. A possible association with candidosis was observed in 17% of patients with tuberculosis and diabetes; one presumptive paracoccidioidomycosis, one confirmed aspergillosis, and six cases of active histoplasmosis were determined. Candidin ST showed 29% of positive reactions with an increased frequency in patients between 31 and 55 years of age. CF test showed the highest positivity percentages with crude antigens, specially for Candida antigen (26.3%) and histoplasmin (18.2%). Cross reactions were evident with crude antigens but decreased when PPC's were used in ELISA.     

Isoconazole nitrate in the treatment of tropical dermatomycoses

Summary. A total of 54 patients with culturally proven tropical dermatomycoses, comprising 23 with various types of dermatophytoses, one with foot infection due to Trichosporon beigelii and one with foot infection due to Geotrichum candidum , two with candidoses of the groin and 27 with pityriasis versicolor, were included in a clinical trial of efficacy of 1% isoconazole cream (Travogen^R, Schering, Berlin, Germany). Five patients were not evaluable. A clinical and mycological cure was achieved in 29 cases in 3–4 weeks. In 15 (31%) of the remaining patients treatment was required for 5–6 weeks, while another three patients required treatment for 8 weeks. In two patients the disease proved to be resistant to treatment with the drug.
Zusammenfassung. Insgesamt 54 Patienten mit kulturell gesicherter Dermatomykose, (23 unterschiedliche Dermatophytosen, eine Trichosporon beigelii - und eine Geotrichum candidum -Fußinfektion, 2 Candidosen der Leistengegend und 27 Pityriasis versicolor) wurden in einer klinischen Wirksamkeits-studie mit 1% iger Isoconazol-Creme (Travogen^R, Schering, Berlin, Deutschland) behandelt. Fünf Patienten waren nicht auswertbar. Eine klinische und mykologische Heilung wurde bei 47 von 49 Patienten (96%) erreicht. Bei 29 patienten (59%) wurde die Heilung bereits nach 3–4 Wochen Behandlung erreicht. Weitere 15 Patienten (31%) benötigten 5–6 Wochen und drei Patienten 8 Wochen Behandlungsdauer. Zwei Mykosesituationen erwiesen sich als therapieresistent.     

Large-scale molecular characterization and analysis of gastric cancer

The recent effort by The Cancer Genome Atlas （TCGA） Network has revealed that gastric cancer, which is a leading cause of cancerrelated deaths worldwide with a 5-year survival rate less than 25%, is a much more heterogeneous disease than previously thought. And yet, conventional treatment approaches and clinical trials have assumed it is a single disease. Although it is well known that under the microscope, gastric cancer cells appear quite different, the current classification scheme recognizes two main categories of gastric cancer： diffuse and intestinal.     

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma''s compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.