胃癌环氧化酶-2 、hMLH1 及hMSH2 微卫星不稳定与基因调控的关系

 目的 检测临床手术切除43例胃癌及相应正常组织COX-2、hMLH1和hMSH2微卫星不稳定状态MSI及三种基因启动子甲基化情况，并进一步探讨它们与胃癌发生的关系。方法 采用聚合酶链反应（PCR）技术检测5个位点的MSI状态；甲基化特异性PCR（Methylation specific PCR，MSP）方法检测胃癌及正常组织COX-2、hMLH1及hMSH2三种基因启动子CpG岛甲基化状态。结果 43例胃癌中MSI总检出率为48．84％（21／43），五个位点的MSI检出率无显著差别。COX-2和hMLH1基因启动子CpG岛甲基化在43例胃癌中分别有8例和13例，正常组织中未检测到。hMSH2基因启动子CpG岛在胃癌及正常组织中均未检测到甲基化。在MSI-H组hMLH1基因启动子CpG岛甲基化率显著高于MSS组（P〈0．01）；而在MSI-H和MSI-L组间以及MSI-L和MSS无差别。MSI-H组中COX-2基因启动子CpG岛甲基化8例，且有7例胃癌同时出现hMLH1和COX-2基因启动子CpG岛甲基化。结论 在MSI胃癌（尤其是MSI-H型胃癌）的发生、发展过程中可能同时出现了hMLH1和COX-2基因启动子CpG岛的甲基化（即表型遗传修饰）。MSI胃癌hMLH1基因启动子CpG岛甲基化率高于MSS胃癌，提示检测hMLH1基因启动子CpG岛甲基化对于判断肿瘤类型有一定意义。     

胃癌组织hMLH1启动子甲基化是造成其蛋白表达降低的主要原因

目的：通过研究胃癌中错配修复基因hMLH1启动子区5CpG岛甲基化及蛋白表达情况，探讨hMLH1启动子Ⅸ甲基化对蛋白表达的影响及在胃癌发病中的作用。方法：收集诊断明确且未经放化疗的胃癌手术切除标本41例及同病例癌旁黏膜。应用免疫组化SP法检测标本hMLH1蛋白表达情况。应用甲基化特异性PCR（MSP）榆测标本hMLH1启动子区甲基化情况。结果：胃癌组与癌旁组，hMLH1蛋白阳性表达率分别为58．54％（24／41）和80．49％（33／41）（P〈0．05）；启动子甲基化率分别为80．49％（33／41）和24．39％（10／41）（P〈0．05）；完全甲基化率分别为41．46％（17／41）和19．51％（8／41）（P〈0．05）；部分甲基化率分别为39．02％（16／41）和4．88％（2／41）（P〈0．05）。无论胃癌组织还是癌旁组织，完全甲基化病例均出现hMLH1蛋白表达缺失，部分甲基化病例和启动子未甲基化病例均有hMLH1蛋白表达。hMLHI基因启动子甲基化率与胃癌患者性别、年龄、癌组织分化程度、浸润深度和淋巴结转移均无明显相关性（P〉0．05）。结论：hM—LH1基因启动子甲基化是导致hMLH1蛋白表达降低的主要原因；胃黏膜hMLH1蛋白表达降低有助于胃癌的预警。     

胃癌组织和正常胃小凹上皮中抑癌基因E-cadherin hMLH1 APC和MGMT的过甲基化

目的探讨胃癌组织和癌旁正常胃小凹上皮中抑癌基因启动子区的甲基化状况。方法采用甲基化特异性PCR（MSP）方法,检测106例手术切除胃癌石蜡标本的胃癌组织和癌旁正常胃小凹上皮中E-cadherin、hMLH1、APC和MGMT4个抑癌基因启动子区的甲基化状态。结果在胃癌组织中,有1个以上基因甲基化者占72．6％;在正常胃小凹上皮中,有1个以上基因甲基化者占44．3％,二者差异有统计学意义（P〈0．01）。甲基化与胃癌组织的Laurén分型、分化程度和pTNM分期均有关（P〈0．05）,但与Ming’s分型尢关（P〉0．05）。结论E—cadherin、hMLH1、APC和MGMT基因启动子区甲基化普遍存在于胃癌组织和癌旁正常胃小凹上皮中,可能是胃癌发生发展的早期事件。     

原发胃癌中p15基因异常及启动子区甲基化状态

检测胃癌组织中p15基因异常及启动子甲基化状态。方法：p15基因及启动子区域，用PCR-SSCP、MSP（甲基化特异的PCR）法和测序等方法对100例胃癌患者的癌组织和癌旁组织进行检测。结果：9％的病例具有p15基因启动子区的高甲基化，p15基因发现两例DNA序列改变。结论：p15基因在胃癌中起一定作用且p15基因启动子区域高甲基化是胃癌中p15基因失活的重要原因。     

NSCLC患者血清中p16、DAP基因甲基化的研究

目的：探讨p16、死亡相关蛋白激酶（death-associated protein kinase,DAP）基因的异常甲基化作为非小细胞肺癌（NSCLC）患者诊断的基因标志物的可行性。方法：采用甲基化特异性PCR（MSP）法检测30例NSCLC患者肿瘤组织及对应血清中p16、DAP基因的异常甲基化，结果：NCSLC肿瘤中60．0％（18／30）检测出至少一个基因启动子呈甲基化改变，在18例肿瘤组织检测到异常甲基化的患者中，50．0％的患者（9／18）在血清中检测到相应的改变。所有的癌旁组织、健康对照组的血清中及正常肺组织均未检测到p16、DAP的甲基化，结论：检测NSCLC患者血清中p16、DAP基因异常甲基化有可能成为肺癌诊断的分了标志物。     

胃癌MSI、hMLH1基因甲基化及其蛋白表达研究

目的：通过研究散发性胃癌中错配修复基因hMLH1启动子区5’CpG岛甲基化及蛋白表达、微卫星不稳定性(MSI)发生的情况及各指标之间的关系，探讨hMLH1基因、MSI在胃癌发生过程中的作用，揭示胃癌发生的分子机制。方法：取标本55例，其中胃癌41例，正常组织(包括正常及浅表性胃炎)14例。酚／氯仿法提取DNA，PCR扩增一变性聚丙烯酰胺凝胶电泳-硝酸银染法检测BAT-26、D2S123两个位点的MSI，酶切产物特异性扩增法检测hMLH1基因启动子区5’CpG岛甲基化异常情况，免疫组化SP法检测hMLH1蛋白的表达。结果：胃癌组MSI发生率为51.2％(21／41)，显著高于正常组(P(0．05)胃癌组hMLH1基因启动子区5’CpG岛甲基化发生率为41．5％，其中88．5％表现为蛋白表达缺失或降低，正常组织中未发现甲基化。胃癌组MSI( )中，甲基化发生率81．0％。结论：hMLH1基因甲基化是导致胃癌组织出现MSI的重要因素，MSI在散发性胃癌发生、发展过程中发挥一定作用。由于错配修复基因甲基化而丧失修复功能，引起MSI的产生，促进肿瘤的发生。对胃癌组织中hMLH1基因、MSI的深入研究，可以为肿瘤早期发现、早期诊断提供信息。     

卵巢肿瘤组织和血清中RASSF1A基因甲基化检测及临床意义的研究

目的：检测卵巢肿瘤组织和血清中RASSF1A基因启动子区异常甲基化，探讨卵巢肿瘤组织和血清中RASSF1A基因甲基化与卵巢癌的关系。方法：收集新鲜的卵巢肿瘤组织及其对应的血清标本65例，10名健康志愿者血清标本。采用半巢式甲基化特异性PCR技术分别检测肿瘤组织DNA和血清游离DNA中RASSF1A基因启动子异常甲基化情况。结果：卵巢癌患者血清和癌组织中，RASSF1A基因甲基化的检出率分别为20．0％和31．4％。卵巢良性肿瘤组织和血清以及健康志愿者血清中，均未发生RASSF1A基因异常甲基化。肿瘤组织中，RASSF1A基因的甲基化状况与血清中出现RASSF1A基因甲基化关系密切，P〈0．01；卵巢癌患者血清和癌组织中，RASSF1A基因的甲基化异常改变与肿瘤的临床分期、细胞分化程度以及组织学类型无明显相关性，P〉0．05；与淋巴结转移密切相关，P〈0．05。结论：分析血清DNA的RASSF1A基因异常甲基化有可能成为辅助卵巢癌诊断的有效方法之一。     

原发胃癌中p15基因异常及启动子区甲基化状态

目的　检测胃癌组织中p15基因异常及启动子甲基化状态。方法　选择p15基因及启动子区域 ,用PCR -SSCP、MSP(甲基化特异的PCR)法和测序等方法对 10 0例胃癌患者的癌组织和癌旁组织进行检测。结果　 9%的病例具有p15基因启动子区的高甲基化 ,p15基因发现两例DNA序列改变。结论　p15基因在胃癌中起一定作用且p15基因启动子区域高甲基化是胃癌中p15基因失活的重要原因。     

乳腺癌患者外周血清中APC基因启动子甲基化异常的检测及其意义

背景与目的:检测肿瘤患者外周血中肿瘤相关标志物是当前肿瘤研究的热点之一,恶性肿瘤患者外周血中存在游离的肿瘤相关DNA已引起肿瘤学界的极大关注,人们曾在多种肿瘤患者血清中发现与原发肿瘤相同的DNA变异.本研究以APC(adenomatous polyposis coli)基因启动子甲基化作为肿瘤标志物,探讨乳腺癌患者外周血清中游离的肿瘤相关DNA与肿瘤组织及临床病理参数的相关性.方法:采用甲基化特异性PCR(methylation specific-PCR,MSP)方法,分别检测84例乳腺癌组织、癌旁正常腺体组织及外周血清中游离DNA APC基因启动子甲基化状况.结果:84例乳腺癌组织APC基因启动子甲基化频率为45.2%(38/84),相应外周血清中同样DNA变异阳性检出率为31.0%(26/84).外周血清中DNA甲基化变异与肿瘤组织的甲基化状况显著相关(r=0.977,P=0.002).检测外周血清中APC基因甲基化的敏感性为68.4%,特异性为97.8%.肿瘤组织及外周血清中游离DNA甲基化异常与临床分期、病理类型、肿块大小及受体状况无相关性(P＞0.05).肿瘤组织未检测到甲基化患者的血清中及健康人血清中均未检测到该基因甲基化变异.结论:乳腺癌患者外周血清中肿瘤相关DNA甲基化与肿瘤组织中相同基因的变异显著相关.     

巢式甲基化特异性PCR 检测食管癌病人血清中p16 基因启动子区过甲基化

 目的 检测食管鳞状细胞癌（squamous cell carcinoma，SCC）患者外周血血清中p16基因启动子区的甲基化状态，探讨p16基因启动子的过甲基化在食管鳞状细胞癌筛查及早期诊断中的意义。方法 利用巢式甲基化特异性PCR（nMSP）法检测食管鳞状细胞癌患者外周血血清与正常人血清中p16基因启动子的甲基化状态，并与普通甲基化特异性PCR（MSP）法进行了比较。结果 56例SCC血清样品中nMSP法发现34例p16基因启动子的过甲基化，MSP法只检出15例，而22例正常人血清中都未检测到p16基因启动子的过甲基化。测序结果进一步验证了方法的可靠性。结论 利用巢式MSP（nMSP）法检测外周血血清中p16基因启动子的甲基化，可为食管癌的筛查、早期诊断及预后判断提供有价值的信息。     

Ringworm in animals in a farm in Assiut

Bericht über das Auftreten von Hautmykosen bei Tieren auf der Farm der Landwirtschaftlichen Fakultät der Universität Assiut. Von 70 Kälbern waren 42 pilzkrank, davon 22 durch T. mentagrophytes, 20 durch T. verrucosum. Von 180 Kühen waren 8 pilzbefalien, sämtlich durch T. mentagrophytes. Von 2 kranken Bullen wurde T. verrucosum isoliert. Auch die 3 Pferde und 2 Maultiere der Farm waren pilzinfiziert; Erreger war in diesen Fällen T. equinum. Auch ein Kalb war von T. equinum befallen. Die gleiche Pilzart wurde ferner von 3 Tierpflegern isoliert, die Pilzherde am Hals und an den Armen aufwiesen.     

Statistical challenges in preprocessing in microarray experiments in cancer

Many clinical studies incorporate genomic experiments to investigate the potential associations between high-dimensional molecular data and clinical outcome. A critical first step in the statistical analyses of these experiments is that the molecular data are preprocessed. This article provides an overview of preprocessing methods, including summary algorithms and quality control metrics for microarrays. Some of the ramifications and effects that preprocessing methods have on the statistical results are illustrated. The discussions are centered around a microarray experiment based on lung cancer tumor samples with survival as the clinical outcome of interest. The procedures that are presented focus on the array platform used in this study. However, many of these issues are more general and are applicable to other instruments for genome-wide investigation. The discussions here will provide insight into the statistical challenges in preprocessing microarrays used in clinical studies of cancer. These challenges should not be viewed as inconsequential nuisances but rather as important issues that need to be addressed so that informed conclusions can be drawn.     

Trends in zygomycosis in children

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.     

Hemoglobin in lymphogranulomatosis in children

The peculiarities of hemoglobin content and properties in lymphogranulomatosis were studied in children by different methods. In most patients the content of fetal hemoglobin and methhemoglobin was found to increase and the rate of ferricyanide oxidation of hemoglobin also increases. Simultaneously, the rate of non-homogenicity of basic hemoglobin fractions was observed to increase on account of immunologically different components.     

Dermatomycosis in Goats in India

Summary: In an extensive survey involving 2176 goats 1.56% of goats manifested clinical lesions of ringworm infection. Animals below the age of 6 months were affected most (4.20%). The incidence of infection was higher during the winter months. T. verrucosum, T. mentagrophytes and M. gypseum were isolated from the skin scrapings of 12, 4, and 2 goats respectively. It is suggested that the infected animals could be a source of disease to human population in which the zoophilic dermatophyte invasion is characterized by severe inflammatory lesions of the skin. The zoonotic importance of different dermatophytes is stressed.
Zusammenfassung: In einer ausgedehnten Untersuchung an 2176 Ziegen wurden bei 1,56% klinische Zeichen einer Hautmykose festgestellt. Tiere, die jühger als 6 Monate alt waren, zeigten mit 4,20% am häfigsten Krankheitssymptome. In den Wintermonaten war die Erkrankungshäufigkeit am gröBten. T. vermcosum, T. mentagrophytes and M. gypseum wurden jeweils von 12,4 bzw. 2 Ziegen isoliert. Die inflzierten Tiere köinnen eine Infektionsquelle für die menschliche Bevölkerung darstellen und dort Mykosen mit stark entzündlichen Veränderungen auslösen. Die Bedeutung verschiedener Dermatophyten als Erreger von Zoonosen wird hervorgehoben.     

Sex hormones in women in rural China and in Britain

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.     

Temozolomide treatment in glioma--experiences in two university hospitals in Finland

Thirty-two patients with relapsing glioma were treated with temozolomide in two university hospitals in Finland. One patient (3%) had complete response and 9 (28%) partial response, with 8 patients (25%) showing stable disease. Median progression-free survival for these 18 patients (56%) was 7 months (range 2-11+). The remaining either had progressive disease (25%) or only clinical evaluation (19%). Karnofsky score improved in 34% of patients and decreased in 3%. Symptoms were alleviated in 44% and deteriorated in 9%. Grade 3-4 toxicity was detected in 9% of the patients. Only 4% of the days in treatment were spent in hospital. An average 1.8 neuroradiological investigations, 6.9 laboratory visits, and 5.3 visits to the oncologist were made. This study confirms that temozolomide has positive effects on the outcome of often heavily pretreated glioma patients. High drug costs are compensated by prolonged home care and even the possibility to maintain working capacity.