肺癌多药耐药机制的研究现状

多药耐药性(MDR)一直困扰着作为肺癌主要治疗手段之一的化学治疗。本通过复习近几年国外献,简要概述肺癌多药耐药机制的研究现状。MDR机制研究最多的是P-糖蛋白(P—gp)机制,但多药耐药相关蛋白(MRP)、各胱甘肽-S-转移酶(GST)、拓朴异构酶Ⅱ(TopoⅡ)等耐药机制也与肺癌MDR机制有密切的关系。从目前研究结果来看，肺癌MDR机制可能是多种机制并存.     

肺癌耐药机制研究进展

肺癌是人类最常见的恶性肿瘤之一，严重危害着人们的健康，药物治疗是癌症患者包括手术治疗后患者的主要疗法或辅助疗法，但由于肿瘤基因的不稳定性、表达的异质性和肿瘤细胞的高突变率，耐药性一直是肿瘤治疗中的一个主要问题，肿瘤细胞普遍存在多药耐药现象。耐药性的产生与多种因素相关，包括：①多药耐药基因及P—gp表达增加；②多药耐药相关基因及多药耐药相关蛋白表达增加；③肺耐药相关基因及肺耐药相关蛋白表达     

肺癌化疗多药耐药与逆转策略

恶性肿瘤化疗失败的主要原因是多药耐药的发生。研究表明,多药耐药的机制十分复杂,P-gp、TopoⅡ、GST-π、金属硫蛋白(metallothionein,MT)及p53基因突变等是肺癌产生多药耐药的物质基础。本文重点介绍非小细胞肺癌耐药因子及耐药逆转的对策,以指导临床化疗药物的筛选及治疗方案的优化,有助于提高肺癌患者的生存期和生存率。     

多药耐药相关蛋白在非小细胞肺癌表达的研究

目的：研究多药耐药相关蛋白在非小细胞肺癌的表达情况及其两者关系。方法：应用单克隆抗体ＱＣＲＬ－１行ＬＳＡＢ免疫组化法研究６１例非小细胞肺癌组织中多药耐药相关蛋白表达水平。结果：肺癌组织中多药耐药相关蛋白表达的总阳性率为６８．９２％；癌旁正常肺组织呈阴性或弱阳性表达；高和中分化肺癌多药耐药相关蛋白表达的阳性率高于低分化癌（Ｐ＜０．００５）；Ⅰ－Ⅱ期肺癌多药耐药相关蛋白表达的阳性率高于Ⅲ－Ⅳ期者（Ｐ＜０．０１）。结论：表明多药耐药相关蛋白是非小细胞肺癌多药耐药的重要参与因素。     

肺癌耐药机制研究的新进展

肺癌是最常见的恶性肿瘤之一，75％的患者就诊时已是晚期，失去了手术机会，因此化疗成为肺癌重要的治疗手段，它能明显延长肺癌患者总的生存率，减轻症状，提高生活质量。然而肿瘤细胞对药物的耐受性却导致了肺癌化疗的失败。过去大量的研究发现，肺癌耐药的产生与多药耐药基因(MDR)和P-糖蛋白(P—gp)表达的增加，多药耐药相关蛋白基因(MRP)、肺耐药蛋白基因(LRP)及它们产物表达的增加，以及拓扑异构酶(TopoⅡ)表达下降和谷胱甘肽(GSH)及谷胱甘肽S转移酶(GST)系统表达增加等机制有关。     

转运蛋白及其介导的肿瘤多药耐药研究

 引言 究发现,MDR 的出现与肿瘤细胞内药物聚集降低有关,表明药物转运的改变(外排增加) 可能是产生耐药的原因。参与药物外排机制的膜转运蛋白主要有: P-蛋白( P-qP) 、多药耐药相关蛋白(MRP) 、乳腺癌耐药蛋白(BCRP) ) 和肺耐药蛋白(L RP) 等。前三者同属于A TP 结合盒(adenosinetriphosphate - binding cassette ,ABC) 膜转运蛋白超家族成员[ 1 ] 。药物转运介导的多药耐药是近年来耐药研究领域的一大热点,本文就转运蛋白及其介导的多药耐药研究作一综述。     

MRP3／ABCC3的特点及其在肿瘤细胞耐药性方面的作用

化疗是肿瘤综合治疗的主要方法之一，但癌细胞的多药耐药（multidrug resistance，MDR）严重影响患者的化疗效果，耐药癌细胞的存在也是患者术后复发、远处转移直至死亡的根本原因。国内外已经发现了一些MDR相关分子，如P-糖蛋白、多药耐药相关蛋白、谷胱甘肽S转移酶、拓扑异构酶、凋亡相关蛋白等。其中多药耐药相关蛋白3（MRP3／ABCC3）显示了在多种肿瘤细胞包括肺癌中的非小细胞肺癌（non—small cell lung cancer，NSCLC）中与耐药的相关性。     

多药耐药相关蛋白在肺癌中的研究进展

多药耐药相关蛋白（ＭＲＰ）是一种可引起肿瘤多药耐药现象的蛋白,广泛存在于多种正常组织和肿瘤细胞中,是谷胱甘肽－Ｓ－共轭物转运泵,起到外排药物的作用,并参与药物重新分布。ＭＲＰ的表达与肺癌临床化疗敏感性及预后有关,是肿瘤细胞生物学恶性行为的标志。逆转肿瘤的耐药性可以提高患者的治愈率。     

乳腺癌耐药蛋白(BCRP/ABCG2)的研究进展

肿瘤细胞产生的多药耐药特性严重影响癌症的化疗疗效,研究肿瘤细胞耐药相关蛋白的生理功能及其对药物的转运机制,寻找高效的多药耐药蛋白抑制剂是提高肿瘤化学治疗效果的重要途径.乳腺癌耐药蛋白(BCRP/ABCG2)是介导肿瘤细胞耐药的一种重要蛋白,在肿瘤细胞多药耐药的形成中起关键作用,本文就BCRP/ABCG2蛋白的结构特点、生理功能、在多药耐药中的作用及其抑制剂等方面作一综述.     

HL-60/VCR多药耐药细胞株耐药机制的研究

背景与目的：白血病细胞对化疗药物的耐药是白血病治疗失败的主要原因,多药耐药细胞株为白血病多药耐药机制和逆转多药耐药性的研究提供了良好的模型。为探讨药物诱导产生多药耐药机制,我们对HL-60/VCR细胞的耐药机制进行了研究。方法：应用流式细胞术和一组抗体,对药物敏感细胞株HL-60和多药耐药细胞株HL-60/VCR细胞的耐药相关蛋白P-gp、MRP、LRP、BCRP、GST-π,以及凋亡调节蛋白bcl-2、bax、bcl-x、bad的表达进行分析。结果：在HL-60/VCR细胞株中,耐药相关蛋白P-gp、MRP、BCRP、GST-π分别是其在HL-60细胞株中的18.62、1.19、1.50、1.32倍,而LRP无变化。凋亡抑制蛋白bcl-2、bcl-x分别是其在HL-60细胞株中的2.48、1.25倍,凋亡调节蛋白bad是HL-60细胞株中的1.08倍;而凋亡诱导蛋白bax反而降低,是HL-60细胞株中的0.88倍。结论：多种机制参与HL-60/VCR的多药耐药,涉及耐药蛋白P-gp、MRP、BCRP和GST-π的表达增强,而且凋亡调节蛋白bcl-2、bax、bcl-x、bad均可能参与其耐药机制的形成。     

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.