Let-7靶基因KRAS结合区rs712多态性与脑胶质瘤发生相关性的研究

目的:探讨let-7靶基因KRAS结合区rs712多态性在脑胶质瘤患者和健康对照人群中的分布及与脑胶质瘤临床特征的相关性。方法:采用聚合酶链反应-限制性片段长度多态性检测153例脑胶质瘤患者(脑胶质瘤组)和204例健康人群(对照组)KRAS rs712多态性。结果:对照组中GG、GT和TT基因型频率分别为67.2%、29.9%和2.9%;脑胶质瘤组中各基因型频率分别为54.2%、36.6%和9.2%。与GG基因型相比,TT和GT/TT基因型显著增加了脑胶质瘤的发病风险,TT与GG相比,χ2=7.93,OR=3.85,95%CI为1.43～10.41,P=0.005;GT/TT与GG相比,χ2=6.16,OR=1.73,95%CI为1.12～2.66,P=0.013。对照组中G和T等位基因频率分别为82.1%和17.9%;脑胶质瘤组中分别为72.5%和27.5%。与G等位基因相比,T等位基因显著增加了脑胶质瘤的发病风险,χ2=9.31,OR=1.74,95%CI为1.22～2.48,P=0.002。根据脑胶质瘤临床病理分级进行亚组分析发现,GT/TT基因型和T等位基因在Ⅲ～Ⅳ级脑胶质瘤患者的频率均显著高于在Ⅰ～Ⅱ级患者中的频率。GT/TT与GG相比,χ2=4.40,OR=1.99,95%CI为1.04～3.81,P=0.036;T与G相比,χ2=5.51,OR=1.83,95%CI为1.10～3.04,P=0.019。结论:KRAS rs712等位基因多态性可能是脑胶质瘤的易感因素。     

PIM1启动子区基因多态性与非小细胞肺癌易感性的相关性研究

原癌基因PIM1通过活化下游基因,参与细胞增殖、分化及肿瘤形成。本研究旨在探讨中国人群PIM1基因启动子区（-1 882A>T）单核苷酸多态性与非小细胞肺癌易感性的相关性。方法:应用聚合酶链反应-直接测序法检测25例患者及25例正常对照者的PIM1基因启动子区多态性,应用聚合酶链反应-直接测序法检测206例非小细胞肺癌患者以及189例正常对照者-1 882A>T多态性位点的基因型,并进行病例、对照相对危险度分析。结果:等位基因-1 882T在肺癌患者和健康对照者中频率分别为6.8%和11.0%,等位基因分布频率在两组间存在显著性差异（P=0.025）。相对危险度分析显示携带TA+TT基因型者发生非小细胞肺癌的风险明显低于携带AA基因型者（OR=0.568,95%CI=0.335～0.962,P=0.034）。结论:中国人中PIM1基因启动子区单核苷酸多态性（-1 882A>T）与非小细胞肺癌发生可能有关,T等位基因的存在可能降低肺癌发生的风险,可能是发生非小细胞肺癌的保护性因素。      

转化生长因子βⅠ型受体多态性与食管鳞状细胞癌发病风险的关联

目的：探讨转化生长因子βI型受体（transforming growth factor-beta receptor type 1 gene,TGFBR1）＊6A和Int7G24A多态性与中国北方人群食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）遗传易感性的关系。方法：选择482名食管鳞癌患者和584名正常健康体检者作对照,分别采用PCR和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）的方法,检测两组受试者外周血单个核细胞染色体DNA中,TGFBR1第1外显子＊6A和第7内含子Int7G24A的多态性分布情况。同时对ESCC患者术后的切除肿瘤组织采用免疫组织化学方法检测TGFBR1的蛋白表达情况,并与其基因型进行相关分析。结果：TGFBR1基因＊6A多态性位点的基因型及等位基因型频率,在ESCC患者组和对照组之间,其分布差异均无统计学意义（P〉0.05）。TGFBR1基因Int7G24A多态性位点的基因型和等位基因型频率,在ESCC组和对照组间分布的差异均具有统计学意义（P〈0.05）,A等位基因携带者患ESCC的风险是G等位基因的1.38倍（经性别、年龄和上消化道肿瘤家族史校正后的OR=1.38,95%CI=1.04～1.75）,与GG基因型相比,携带AA基因型可显著增加ESCC的发病风险（校正后的OR=2.23,95%CI=1.19～3.81）。当按肿瘤分期进行分层分析时发现,与GG基因型相比,Ⅲ期和Ⅳ期ESCC患者中携带GA和AA基因型可显著增加发病风险（校正后的OR=1.61,95%CI=1.10～2.21）。ESCC组织中TGFBR1的蛋白阳性表达率（32.1%）显著低于癌旁正常组织（97.7%）（P〈0.01）,TGFBR1在ESCC中的蛋白表达与＊6A和Int7G24A位点的基因型之间无明显相关性（P〉0.05）。结论：转化生长因子βI型受体Int7G24A位点A等位基因可能是我国北方人群食管癌的遗传易感基因,携带A等位基因的个体可增加食管鳞癌的发病风险。     

肿瘤坏死因子基因多态性与多发性骨髓瘤易感性关系的研究

目的:探讨肿瘤坏死因子α(TNF-α)和肿瘤坏死因子β(TNF-β)基因多态性与多发性骨髓瘤(MM)易感性的关系.方法:采用聚合酶链反应-连接测序技术检测86例MM患者和172例健康对照者TNF-α(TNF-α-857、TNF-α-308和TNF-α-238位点)和TNF-β(TNF-β +252位点)基因多态性,以非条件Logistic回归分析计算比值比(OR)及95％可信区间(CI),从而评估不同基因型与MM风险之间的相关性.结果:MM组TNF-α-857 TT基因型及T等位基因频率显著高于对照组,病例组与对照组TT基因型频率分别为5.8％和1.2％,T等位基因频率分别为17.4％和9.6％.携带TNF-α-857 TT型者发生MM风险增高为5.78倍(OR=5.78,95％CI:1.09～30.6,P=0.039),携带TNF-α-857 T等位基因者发生MM风险增高为1.99倍(OR=1.99,95％CI:1.17～3.39,P=0.011),其他基因位点多态性未见与MM具有显著相关性.结论:在目前样本条件下,TNF-α-857位点T等位基因或TT基因型与MM发病风险增高具有相关性.     

2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国东北汉族绝经前妇女乳腺癌风险关系

背景与目的：乳腺癌作为中国女性最常见的恶性肿瘤,每年的新发数量和死亡数量分别占全世界的12.2%和9.6%,但与中国乳腺癌患者明显相关的基因多态位点至今尚不清楚。本研究旨在探讨2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国北方汉族绝经前妇女乳腺癌风险关系,为预防和治疗乳腺癌提供循证依据。方法：采用多重单碱基延伸单核苷酸多态性分型技术(SNaPshot)分析方法,检测了280例绝经前乳腺癌患者和287例绝经前正常对照者2q35 rs13387042和8q24 rs13281615多态性位点基因型,并比较不同基因型和等位基因与乳腺癌风险的关系。结果：2q35 rs13387042多态性位点基因型频率在乳腺癌和对照样本之间差异有统计学意义(P=0.017);8q24 rs13281615多态性位点基因型频率在乳腺癌和对照样本之间差异无统计学意义(P=0.967)。Logistic回归分析结果显示,对于2q35 rs13387042位点,与GG相比,GA和GA+AA基因型携带者显著增加乳腺癌的患病风险(OR=1.793,95%CI：1.177～2.733,P=0.007;OR=1.691,95%CI：1.122～2.550,P=0.012),而AA携带者与乳腺癌的患病风险无关(OR=0.572,95%CI：0.104～3.153,P=0.521);与G等位基因相比,A等位基因显著增加乳腺癌的患病风险(OR=1.505,95%CI：1.033～2.193,P=0.033)。对于8q24rs13281615位点,与AA相比,AG、GG和AG+GG基因型携带者与乳腺癌的患病风险无关(OR=0.992,95%CI：0.660～1.490,P=0.968;OR=1.047,95%CI：0.642～1.708,P=0.853;OR=1.007,95%CI：0.682～1.487,P=0.971);与A等位基因相比,G等位基因不增加乳腺癌患病风险(OR=1.021,95%CI：0.809～1.288,P=0.863)。结论：本实验证实2q35 rs13387042多态性位点能够增加中国北方汉族绝经前妇女乳腺癌易感风险,而8q24 rs13281615多态性位点与中国北方汉族绝经前妇女乳腺癌易感性无明显相关性。     

晚期非小细胞肺癌患者XPG基因及MDR1基因单核苷酸多态性与铂类化疗疗效的相关性

目的探讨DNA修复基因XPG以及多药耐药基因MDR1的单核苷酸多态性与晚期非小细胞肺癌患者对铂类为主的化疗方案敏感性的关系。方法经病理确诊的晚期NSCLC患者101例,采用DDP为主的化疗方案,化疗2～3个周期后进行临床疗效评价。以PCR-RLFP方法进行XPG、MDR-1的基因型分析,比较不同基因型对化疗敏感性的影响。结果携带MDR1-3435等位基因C/C的患者的化疗有效率为57.8%,显著高于至少携带1个T等位基因的26.8%（OR=0.272,95%CI=0.117～0.635,P（0.05））;携带MDR1-2677至少1个T等位基因的患者的化疗有效率12.8%要显著低于其他基因型患者的58.1%（OR=17.999,95%CI=4.938～65.599,P（0.01）;而XPG各基因型与化疗敏感性的关系没有显著性的差异。结论MDR1基因多态性与NSCLC患者对铂类药物的化疗敏感性相关,基因XPG的多态性是否与铂类药物化疗的敏感性是否具有相关性尚需进一步的研究。     

E2F1基因多态性与宫颈癌风险关联性研究

摘 要：［目的］ 选取E2F1基因中rs3213172、rs3213173和rs3213176三个多态性位点,研究其与宫颈癌的关联性。［方法］ 选取2016—2019年贵州省人民医院肿瘤科确诊为宫颈癌的149例患者为病例组,选取同期同院参加正常体检的健康女性206人为对照组。采用通用探针法对E2F1基因中的多态位点rs3213172、rs3213173和rs3213176进行基因分型,研究这些多态性位点的等位基因、基因型及构建的单倍型在对照组和病例组中分布频率的差异。［结果］ E2F1基因中的多态性位点rs3213172 CT基因型在病例组和对照组间分布频率差异有统计学意义,可能是宫颈癌发生的危险因素 (OR=1.57,95%CI：1.00～2.48);多态位点rs3213173和rs321317的等位基因和基因型在病例组和对照组中的分布频率差异无统计学意义（P>0.05）。单倍型分型结果显示,rs3213172-rs3213173-rs3213176的单倍型C-T-G可能是宫颈癌发生的保护性因素（OR=0.66,95%CI：0.47～0.93）;单倍型T-T-G可能是宫颈癌发生的风险因素（OR=2.49,95%CI：1.35～4.59）。［结论］ E2F1基因中的多态位点rs3213172可能与宫颈癌的发病风险有关。     

EGFR基因rs763317多态性与胃癌遗传易感的相关性研究

目的:探讨EGFR基因第一内舍子区rs763317位点单核苷酸多态性(SNP)与江西地区汉族人群胃癌遗传易感性的相关性.方法:应用MassARRAY(R)SNP分型技术检测138例胃癌患者和170名正常对照EGFR基因多态位点rs763317的基因型.用χ2检验统计分析病例组和对照组基因型和等位基因的频率;采用非条件Logistic回归分析,计算比数比(OR)和95%CI,评价多态性位点与胃癌遗传易感性的相关性.结果:EGFRrs763317多态位点AA、AG和GG基因型在胃癌人群中的分布频率为5.8%、52.2%和42.0%,与对照组(2.4%,31.8%和65.9%)相比差异有统计学意义,P≤0.001.与rs763317 GG基因型相比,携带AA或AG基因型的个体能显著增加患胃癌的发病危险(OR=3.909,95%CI:1.108～13.786;OR=2.540,95%CI:1.565～4.123).等位基因A在胃癌患者的分布频率显著高于正常对照组(OR=3.277,95%CI:1.103～9.738).结论:首次发现EGFR基因第一内含子区rs763317位点多态性与江西地区汉族人群胃癌的遗传易感性相关.     

CYPlAl和CYPlA2基因多态性与汉族女性乳腺癌的关系

目的 探讨CYP1A1基因MspⅠ位点与CYP1A2基因C734A位点多态性与汉族女性乳腺癌的关系.方法 应用聚合酶链反应-限制性片段长度多态性技术和限制性核酸内切酶酶切的方法,检测2011年9月至2012年8月在四川省医学科学院四川省人民医院确诊的144例女性乳腺癌患者（乳腺癌组）和152例同期健康体检正常女性（对照组）CYP1A1基因MspⅠ与CYP1A2基因C734A多态性位点的基因型,用χ2检验比较两组等位基因频率的差异.结果 在乳腺癌组与对照组中,CYP1A1基因MspⅠ位点T等位基因频率分别为0.73和0.65,两者差异有统计学意义（χ2=4.94,P=0.03）,C等位基因与T等位基因相比,乳腺癌发病风险OR为0.67 （95%CI：0.47～0.96）;CYP1A2基因C734A位点C等位基因频率分别为0.26和0.29,两者差异无统计学意义 （χ2=0.63,P=0.43）.将乳腺癌组按照ER、PR表达与否进一步分组后,CYP1A1基因MspⅠ与CYP1A 2基因C734A 2个多态性位点的等位基因频率在ER（＋）与ER（-）组之间以及PR（＋）与PR（-）组之间差异均无统计学意义[ER（＋）组比ER（-）组：χ2=0.34、0.01;PR（＋）组比PR（-）组：χ2=0.60、0.68;P均〉0.05].结论 汉族女性CYP1A1基因MspⅠ位点多态性与乳腺癌相关联.     

白细胞介素-1B 基因多态性、幽门螺杆菌感染与胃癌发生的相关性

 目的 探讨湖南衡阳地区白细胞介素-1B（IL-1B）基因多态性与胃癌的关系以及幽门螺杆菌（Helicobacter pylori,HP）感染后胃癌发生的易感基因型。方法 52例胃癌患者癌旁正常胃粘膜组织和55例慢性胃炎患者胃粘膜组织,均经快速尿素酶和PCR检测HP,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析技术,进行基因型检测,并对C/C、T/T进行测序,比较各基因型在胃癌组和胃炎组中的分布差异。结果 IL-1B-31T、IL-1B-511T等位基因和IL-1B-31T/T、IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为1.97（95%CI=1.15-3.59）、2.52（95%CI=1.45-4.39）和2.71（95%CI=1.10-6.66）、3.33（95%CI=1.14-9.73）。在伴有HP感染的群体中进行比较,IL-1B-31位点各基因型未见明显差异;但IL-1B-511T等位基因和IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为2.16（95%CI=1.10-4.23）和3.43（95%CI=1.01-11.62）。结论 在湖南衡阳地区IL-1B-31T/T、IL-1B-511T/T基因型与胃癌发病风险相关,在HP被感染后IL-1B-511T/T基因型可能为湖南衡阳地区胃癌易感基因型。     

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).     

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.     

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.     

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.     

Endometrial cancers and predisposition

As nearly 5% of all endometrial cancers occur because of a predisposition, this possibility has systematically to be explored. The hallmarks of predisposition, a young age at diagnosis, a personal or a familial history of cancer, have to be searched systematically. The identification of a predisposition in a family has a major impact on the management of the proband or his relatives. The endometrial cancer main predisposition is Lynch's syndrome. In this review, we will focus on this condition and describe its clinical manifestations, the underlying molecular mechanisms, the cancer risks and the management guidelines. We will also get onto some far less frequent other predispositions.