Comparative evaluation of Sensititre YeastOne vs. the NCCLS M27A protocol and E-test for antifungal susceptibility testing of yeasts

A recently developed microdilution method (Sensititre) YeastOne) may represent a valid alternative to the National Committee for Clinical Laboratory Standards (NCCLS) method for routine testing. The Medical Mycology Committee of the Associazione Microbiologi Clinici Italiani (AMCLI) decided to evaluate its reproducibility and reliability compared with the NCCLS M27A protocol and the E-test. Nineteen strains each of Candida albicans and Ca. parapsilosis, isolated from systemic infections, were tested against amphotericin B, flucytosine, ketoconazole, itraconazole, and fluconazole. All the participating laboratories tested the YeastOne panels, while the E-test and the NCCLS method were performed by two laboratories each. Interlaboratory reproducibility showed a good correlation (from 95% for amphotericin B to 92.5% for flucytosine). The agreement between NCCLS and YeastOne ranged from 95 (ketoconazole and itraconazole) to 100% (amphotericin B and flucytosine), whereas the agreement between E-test and YeastOne ranged from 72.5 (fluconazole) to 100% (amphotericin B and flucytosine). The Sensititre YeastOne panels appear to be an excellent alternative to both the E-test and the NCCLS protocol for antifungal susceptibility testing.     

H3K27M及其甲基化在弥漫性脊髓胶质瘤中的表达及与预后的关系

目的 探讨可催化组蛋白H3第27位(histone H3 lysine 27?to?methionine mutations,H3K27M)及其甲基化在弥漫性脊髓胶质瘤中的表达及其与预后的关系.方法 选择武汉大学中南医院2016年1月—2019年1月收治的75例弥漫性脊髓胶质瘤患者为研究对象,采用免疫组化和染色质免疫沉...     

A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile,H3K27me3 loss and frequent alteration of EGFR

BackgroundMalignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern.MethodsHere, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas.Results EGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations.ConclusionsOur findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.     

Misonidazole-a drug for trial in radiotherapy and oncology.

Misonidazole is an hypoxic cell radiosensitizer with promise in clinical radiotherapy. The concentrations which may be achieved in plasma, in tumors and in normal tissues are discussed. The toxic effects of misonidazole are described and schemes for the safe administration in man detailed.     

Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas

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Histone H3.3 K27M Accelerates Spontaneous Brainstem Glioma and Drives Restricted Changes in Bivalent Gene Expression

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肝癌及癌前病变中p27蛋白和mRNA的表达

[目的]研究肝细胞癌(HCC)及癌前病变中细胞周期负性调控因子p27的表达及其意义.[方法]应用免疫组织化学S-P染色法和原位分子杂交法检测正常肝组织、慢性肝炎、肝硬化、癌周肝硬化和肝癌组织中p27蛋白及其mRNA的表达,并对结果进行计算机图像定量分析.[结果]p27蛋白在正常肝组织和慢性肝炎中呈低表达,在肝硬化和癌周肝硬化中表达明显增强,而在肝癌中表达明显下降,与前4组比较差异有显著性(P＜0.05).p27mRNA在非肝癌组织中表达均较强,在肝癌中表达明显减弱,与前4组比较差异有显著性(P＜0.05).正常肝组织、慢性肝炎和肝硬化中p27蛋白阳性信号主要定位于胞核,而癌周肝硬化和HCC中主要定位于胞浆.随着HCC的分化程度降低,p27蛋白和p27mRNA的表达减弱,差异有显著性(P＜0.05).[结论]p27表达下降可能参与了HCC的发生,且与HCC的分化有关.p27的胞浆定位可能与HCC的早期发生有关.     

p27与消化道肿瘤及其应用前景

p27具有多种生物学功能.其表达下降与消化道肿瘤的发生、发展、侵袭密切相关,并可作为独立的预后判定指标.p27及人工修饰构建的p27突变体在肿瘤基因治疗中有着广泛的应用前景.     

Serum and Prostatic Tissue Concentrations of Moxifloxacin in Patients Undergoing Transurethral Resection of the Prostate

Abstract

The spectrum of pathogens causing chronic bacterial prostatitis comprises Gram-negative, Gram-positive and atypical microorganisms. Because of its broad spectrum of activity, the group 4 fluoroquinolone moxifloxacin might be a suitable antibiotic for treatment of bacterial prostatitis. The aim of this prospective study was to investigate the penetration of moxifloxacin into prostatic tissue in patients with benign prostatic hyperplasia.

Patients received a single dose of moxifloxacin 400 mg in an 1 hour lasting infusion (250 ml) for perioperative prophylaxis before undergoing transurethral resection of the prostate (TURP). Serum concentrations were determined in all patients before infusion, at the end of infusion (time point 0), 0.5, 1 and 2 h after the end of infusion. Patients were randomized for tissue sampling either 0, 0.5, 1 or 2 h after the end of infusion. At beginning of TURP approximately 1 g of tissue was sampled for analysis. Concentrations of moxifloxacin in serum and tissue were determined by HPLC.

39 patients were evaluated. Median serum and prostatic tissue concentrations peaked at 0 h (4.94 mg/ L and 8.50 mg/ kg, respectively). The lowest concentrations were quantified at 2 h after the end of infusion (2.46 mg/ L and 3.88 mg/ kg, respectively). The prostatic tissue concentrations of moxifloxacin were approximately twice as high as in corresponding serum. At the end of infusion the tissue and serum concentrations seemed to be already equilibrated, as their ratios did not differ significantly during the time of investigation.

After an intravenous infusion of 400 mg the serum and prostatic tissue concentrations of moxifloxacin were well above the MIC values of most important prostatic pathogens. The high tissue/ serum ratio and the extended antibacterial spectrum suggests active concentration in the prostate which may translate into increased efficacy compared to group 2 and 3 fluoroquinolones in the treatment of chronic bacterial prostatitis.     

胃癌组织MCM7和p27蛋白表达及其临床意义的探讨

目的:探讨微小染色体维持蛋白7(MCM7)和p27蛋白在胃癌组织中的表达及其意叉.方法:采用免疫组化法检测MCM7和p27蛋白在20例正常胃黏膜、30例低级别非典型增生、80例胃癌组织中的表达,并以标记指数(LI)量化及其表达.结果:MCM7和p27蛋白在正常胃黏膜、低级别非典型增生和胃癌组织中的表达之间差异均有统计学意叉(P＜0.05);MCM7的LI在胃癌组织中表达与临床分期、浆膜浸润、术后复发,肝转移及淋巴结转移密切相关(P＜0.05),与肿瘤大小和组织学分级无关(P＞0.05).p27的LI在胃癌组织中表达与临床分期、肝转移和淋巴结转移密切相关(P＜0.05),与浆膜浸润、术后复发,肿瘤大小和组织学分级无关(P＞0.05).胃癌组织中MCM7和p27的LI表达呈显著负相关(γ=-0.313,P=0.005).结论:MCM7的表达升高和p27蛋白的表达下降与胃癌的发生及发展密切相关,检测MCM7和p27有助于判断胃癌恶性程度及预后.     

PTEN表达在胃癌发生及分化中的作用

目的:探讨PTEN的表达与胃黏膜癌变及癌细胞分化程度的关系.方法: 采用免疫组织化学方法对胃癌组织、癌前病变和对照组正常胃黏膜进行PTEN表达的检测.结果: 胃癌组PTEN阳性率为53.3%,较正常组和癌前病变组明显下降(P <0.01);低分化组PTEN阳性率为36.0%,显著低于胃癌高中分化组 (P <0.01);高中分化组PTEN阳性率与癌前病变组无差异(P>0.05).结论: PTEN与胃癌的分化程度密切相关,可作为判断胃癌恶性程度的指标.     

p27在50例宫颈癌中的表达及意义

[目的]探讨p27在宫颈癌中的表达及其临床意义。[方法]应用免疫组化法检测50例宫颈癌、25例宫颈上皮内瘤样变（CIN）和10例正常宫颈组织石蜡包埋组织中p27蛋白的表达。[结果]p27在宫颈癌中的阳性表达率为32.00%（16/50）,在CIN中的阳性表达率为56.00%（14/25）,在正常宫颈组织中的阳性表达率为80.00%（8/10）,三者比较差异有统计学意义（P〈0.01）。p27高表达与宫颈癌患者的年龄、临床分期、病理类型、组织学分级均无相关性（P〉0.05）。[结论]p27在宫颈癌低表达,其可作为宫颈癌癌前病变的生物学标志物。     

p27表达水平与非小细胞肺癌预后关系的Meta分析

目的：采用Meta分析的方法，探讨p27在非小细胞肺癌（NSCLC）预后中的作用。方法：检索PubMed、CNKI中研究p27表达与NSCLC预后关系的文献，收集每篇文献的相对危险比（HR）及95％可信区间（95％CI），应用Meta分析Dersimonian—Laird模型对文献进行定量综合分析。结果：共入选7篇文献，累计NSCI。C病例888例，其中p27阳性表达443例，阳性率49．9％。对入选7篇文献进行一致性检验，文献具有异质性（Q=102．13，P=0．000），合并相对危险比为1．21（95％可信区间：1．13～1．29，P=0．000）。结论：p27的阳性表达可能是NSCLC的良好预后因素。     

细胞周期蛋白D2和p27^kipl在非小细胞肺癌中的表达及意义

目的探讨细胞周期蛋白D2(cyclin D2)和p27kipl在非小细胞肺癌(NSCLC)中的表达及意义.方法采用免疫组化S-P法检测63例非小细胞肺癌(NSCLC)组织中cyclin D2和p27kipl的表达情况.结果 63例NSCLC中cyclin D2和p27kipl阳性表达率分别为39.7%和54.0%,与正常支气管黏膜比较差异有显著性(P<0.05).p27kipl的表达与NSCLC的分化程度、淋巴结转移以及临床病理分期相关(P<0.05).cyclin D2与p27kipl的表达呈显著负相关.结论 cyclin D2和p27kipl的异常表达与NSCLC的发生有密切关系.p27kipl还与NSCLC的进展有关,并可作为估计预后的重要指标.     

胃癌中cyclinD2和p27kipl的表达及其意义

目的探讨cyclinD2、p27kipl的表达与胃癌发生发展的关系.方法用免疫组化方法检测cyclinD2和p27kipl在120例胃癌、20例胃粘膜非典型增生、30例正常胃粘膜中的表达.结果 cyclinD2在正常胃粘膜、非典型增生、胃癌中阳性表达率分别是3.3%、10%、和34.2%,胃癌与正常胃粘膜及非典型增生相比有显著性差异(P＜0.01),p27kipl在正常胃粘膜、非典型增生、胃癌中表达分别是100%、90%、和52.5%.胃癌与其他两组比较有显著性差异(P＜0.01),p27kipl表达缺失和cyclinD2胞浆阳性者与胃癌的分化程度、浸润深度、淋巴结转移有关(P＜0.01).cyclinD2和p27kipl表达呈负相关.结论 cyclinD2和p27kipl与胃癌的发生有密切关系,p27kipl的表达缺失及cyclinD2胞浆阳性者与胃癌的进展有关,p27kipl可作为估计预后的重要指标.     

p27和ILK在胃癌及癌前病变中的表达及意义

目的:探讨p27和ILK在胃癌及癌前病变中的表达及其与胃癌病理参数之间的关系. 方法: 用免疫组化技术(SP法)对正常胃黏膜(normal gastric mucosa,NGM)、慢性浅表性胃炎(chronic superficial gastritis,CSG)、慢性萎缩性胃炎(chronic atrophia gastritis,CAG)伴肠上皮化生、慢性萎缩性胃炎伴非典型增生各20例和胃癌(gastric carcinoma,GC)60例标本进行免疫组织化学染色,分析p27和ILK的表达与胃癌临床和病理的关系. 结果: p27和ILK表达阳性率分别为:NGM组100%和5%,CSG组85%和10%,CAG伴肠化组70%和20%,CAG伴非典型增生组45%和30%,胃癌组38.3%和40%.胃癌组和CAG伴非典型增生组p27阳性率显著低于其他组(P＜0.05),ILK阳性率则显著高于其他组(P＜0.05).p27和ILK在胃癌中的表达与肿瘤分化程度、浸润深度及肿瘤临床分期相关,p27蛋白的表达还与有无淋巴结转移相关.p27和ILK在胃癌中的表达呈显著负相关(r=-0.768,P＜0.05). 结论: 检测胃癌组织中p27和ILK的表达有助于判断肿瘤的进展程度,两者联合检测有助于判断肿瘤预后.     

CD44v6、p27表达与大肠癌临床病理学因素的关系

Objective To observe the expression and reveal clinical significance of CD44v6 and p27 in colorectal carcinoma.Methods Collecting 50 cases of fresh specimen of colorectal carcinoma and normal mucous from excision operation.CD44v6 expression was detected by means of FCM in 50 cages of colorectal carcinoma and corresponding normal mucous.p27 protein was studied by SP immunohistochemical method.Analysis of statistics was performed by combining clinical and patholoical materials.Results CD44v6 and p27 expression in colorectal carcinoma was significantly higher than that in normal mucous (P＜0.01).As well as the expression of CD44v6 and p27 was obviously associated with differentiated grade,lymph node metastasis,distant metastasis and Dukes stage(P＜0.05).The expression of CD44v6 was not evidently correlated with the depth of tumor invasion(P＞0.05).but the expression of p27 Was correlated with the depth of tumor invasion(P＜0.05).Conclusion The expression of CD44v6 and p27 is markedly related with clinicopathological characters of colorectal carcinoma.CD44v6 expression and p27 expression axe obvious negative relationship in colorectal carcinoma.There is a certain value of reference for assessing the malignant grade and the potential of recurrence and metastasis,evaluating patient prognosis and selecting rational treatment after operation.     

CKS1和p27在乳腺癌中的表达及其意义

目的 探讨CKS1和p27在乳腺癌中的表达情况及其临床意义。方法 应用免疫组织化学SP法检测149例乳腺癌患者组织标本中CKS1和p27的表达水平,结合临床病理资料进行统计学分析。结果 乳腺癌组织中CKS1的表达与淋巴结转移和临床分期有统计学意义（P<0.05）。p27的表达与淋巴结转移显著负相关（P<0.05）,与临床分期和肿瘤分化程度无相关性。多因素分析发现临床分期（P<0.01）、淋巴结转移（P<0.01）、CKS1（P<0.01）和p27（P<0.01）的表达对预后的影响有统计学意义。CKS1与p27表达呈显著负相关（P<0.05）。结论 CKS1和p27可能在乳腺癌的发生发展中发挥重要的作用,二者将来可能作为乳腺癌治疗的靶点之一。