共查询到19条相似文献,搜索用时 171 毫秒
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廖伟华 《国际医学放射学杂志》2012,35(2):151-156
抗肿瘤药物的研发正经历着从细胞毒性治疗向更具选择性的靶向致癌基因治疗转变,影像学生物标志物逐渐成为抗肿瘤药物研发的代理观察终点.就影像学技术在抗肿瘤药物研发中应用的必要性、在药物研发不同阶段的作用,以及应用于药物研发中的各种影像学技术、方法 予以综述. 相似文献
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核与辐射事故发生时,快速评估人体吸收的辐射剂量对于伤员的分类和救治极为重要。为制定有效的辐射损伤救治方案和研发抗辐射新药,辐射损伤相关生物标志物的研究引起了研究者的浓厚兴趣。通过辐射损伤相关生物标志物的变化评估辐射吸收剂量或抗辐射药物的有效性成为研究的热点。笔者围绕近年来用于评估辐射吸收剂量和抗辐射药物有效性的生物标志物展开综述。 相似文献
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高分子杭肿瘤药物可以对药物的治疗剂量进行有效控制或控制药物在体内病灶部位选择性释放。能够增强药物有效利用率,降低药物毒副作用,减少给药频率。生物可降解型分子载体,控制释放药物和生物可降解型高分子载体靶向药物是近年来研究的重点。本文着重从抗肿瘤活性高分子和高分子载体靶向抗肿瘤药物的研究进行踪述。 相似文献
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微小RNA(microRNA,miRNA)是一类具有调控基因表达功能的内源性非编码RNA。miRNA具有组织特异性表达,并在各类肿瘤和癌组织异常表达,参与癌细胞增殖、迁移、侵袭、转移、凋亡以及肿瘤干细胞成瘤能力。miRNA既具有基因治疗研发潜力,也可作为抗癌和抗肿瘤治疗靶点应用到癌症的防治。miRNA能够被癌细胞分泌到微环境和外周血,可作为新型生物标志物,研发应用于癌症的早期诊断和预后。本文对国内外miRNA基础研究和临床研发的最新进展作一综述,并客观、科学分析miRNA在调控肿瘤发生和癌转移领域的转化研究和应用前景。 相似文献
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目的 鉴定食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)甲基化生物标志物,预测ESCC患者预后。方法 从癌症基因组图谱数据库(the cancer genome atlas, TCGA)下载ESCC和正常样本基因组甲基化数据及临床信息。所有ESCC样本随机分为验证组和训练组。采用Cox比例风险回归模型和随机生存森林算法在训练组中鉴定甲基化生物标志物。并使用时间依赖性ROC曲线来评估该模型的性能。在验证组中对该模型进行验证。通过GO功能注释,探讨DNA甲基化标志物的生物学功能。结果 鉴定出差异甲基化基因283个,并从中筛选出与生存相关的4个甲基化基因(RRAGB、SYP、ERCC6L和RNASEH2CP1)作为预后的生物标志物。训练组和验证组ROC曲线下面积(AUC)分别为0.984和0.83。该生物标志物能够将训练组患者分为高风险组、低风险组,并在验证组中得到相似的结果。多因素Cox回归分析表明,甲基化基因生物标志物是ESCC患者预后的独立预测因素。功能分析表明,这些标志物基因参与转录调控与DNA结合。结论 筛选出预测ESCC预后的甲基化基因标志物,是独立的预后预测因子。 相似文献
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中药及提取物抗肿瘤的研究进展 总被引:1,自引:0,他引:1
肿瘤的发生率和死亡率呈逐年上升趋势,已成为人类健康的杀手。化疗是肿瘤治疗的主要手段之一,但是由于化疗药物的开发周期长以及研发费用昂贵,且临床毒副作用大,制约了其应用。中草药及其提取物由于毒副作用小、药理作用独特,已成为抗肿瘤药物及抗肿瘤辅助药物。其抗肿瘤的机制包括抑制肿瘤细胞生长、诱导肿瘤细胞凋亡、诱导肿瘤细胞分化、抗肿瘤血管生成、逆转肿瘤细胞多药耐药以及增强机体免疫力等方面。本文综述近年有关中药及提取物的发展现状和其抗肿瘤作用的研究进展。 相似文献
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目的 寻找一种有效的甲基化基因生物标志物,用于肺腺癌的预后预测。方法 从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载219例肺腺癌和29例正常肺组织样本DNA甲基化数据及临床信息,采用Cox比例风险回归模型进行DNA甲基化生物标志物的鉴定,使用时间依赖性受试者工作特征(receiver operating characteristic,ROC)曲线评估该模型的性能,通过基因本体论(Gene Ontology,GO)进行功能注释,探讨DNA甲基化标志物的生物学功能。结果 基因差异甲基化分析,鉴定了160个差异甲基化基因。通过Cox回归分析,筛选出生存相关的4个DNA甲基化基因(AF131215.8、AL021918.1、RP11.386G11.3和ZNF382)作为肺腺癌预后生物标志物。Kaplan-Meier和ROC分析显示,患者总生存期比较低风险组(1.97年)明显高于高风险组(0.54年),差异比较具有统计学意义(P<0.001),并且具有很好的预测能力(AUCSignature=0.793)。多因素Cox回归分析结果表明筛选出生存相关的生物标志物是独立预后因子。GO功能注释显示,这些基因主要参与转录激活活性、RNA聚合酶Ⅱ启动子转录、蛋白质异源二聚体活性和RNA聚合酶Ⅱ启动子转录的正调控等。结论 鉴定出4个DNA甲基化基因作为预测肺腺癌预后的生物标志物并且是独立预后因子。 相似文献
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The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates--thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of "personalized medicine". A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may--if properly validated--serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's "critical path initiative". 相似文献
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药物代谢是细胞解毒机制的重要组成部分之一,其中主要涉及两种酶:Ⅰ和Ⅱ相药物代谢酶。谷胱甘肽S转移酶(GST)是一种重要的Ⅱ相药物代谢酶,可与Ⅰ相药物代谢酶一起催化药物形成高水溶性终产物。所以,GST能够抵御内源性和外源性亲电子物质的损害,并在抗肿瘤过程中发挥重要作用。编码GST的基因至少分布在7条染色体上,构成了一个超基因家族,编码具有GST活性的蛋白。GST有许多功能,传统观点认为,细胞中的GST可发挥防御内、外源性毒性化合物损害的作用。另外,GST在肿瘤细胞中高表达,可介导谷胱甘肽结合至大量抗癌药物底物上,导致肿瘤耐药的发生。 相似文献
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Ian F. Tannock 《International journal of radiation biology》2013,89(2):335-355
SummaryScheduling of chemotherapy is limited by damage to normal tissues, and tolerated schedules are dependent on normal tissue recovery. Most anticancer drugs are more toxic to proliferating cells and the fall and recovery of granulocyte counts after chemotherapy may be explained by the effect of drugs on rapidly proliferating precursor cells in the bone marrow. It is argued that serious toxicity due to myelosuppression most often occurs because of damage to proliferating precursors that may be recognized in bone marrow rather than to stem cells. In contrast, therapy that is aimed at producing cure or long-term remission of tumours must be directed at killing tumour stem cells. The evidence that tumours contain a limited population of cells which can repopulate the tumour after treatment (and are therefore tumour stem cells) is reviewed critically. While there is quite strong evidence for a limited population of target cells, evidence from studies on metastases suggests that the tumour cells which may express this stem cell property may change with time. The stem cell concept has major implications for predictive assays. Although colony-forming assays appear to have a sound biological background for predicting tumour response, technical problems prevent them from being used routinely in patient management.Cells in tumours are known to be heterogeneous and at least three types of heterogeneity may influence tumour response to drug treatment: the development of subclones with differing properties including drug resistance; variation in cellular properties due to differentiation during clonal expansion; and variation in properties due to nutritional status and micro-anatomy. Heterogeneity in drug distribution within solid tumours may occur because of limited drug penetration from blood vessels, and nutrient-deprived cells in solid tumours may be expected to escape the toxicity of some anticancer drugs as well as being resistant to radiation because of hypoxia. This may occur both because nutrient-deprived cells have a low rate of cell proliferation, and also because of poor drug penetration to them. There is a need for improved understanding of the mechanisms that lead to cell death in tumours. If these mechanisms were understood, it might be possible to simulate them by therapeutic manoeuvres. Recent research from our laboratory suggests that the combination of low extracellular pH and hypoxia may be very toxic to cells in nutrient-deprived regions. Drugs which limit the cell's ability to survive in regions of acid pH may provide strategy for therapy of nutrient-deprived cells. 相似文献
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Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis;a process known as tumor angiogenesis.Angiogenesis is largely involved in tumor survival,progression and spread,which are known to be significantly attributed to treatment failures.Over the past decades,efforts have been made to understand the difference between nor-mal and tumor vessels.It has been demonstrated that tumor vasculature is structurally immature with chaotic and leaky phenotypes,which provides opportunities for developing novel anticancer strategies.Targeting tumor vasculature is not only a unique therapeutic interven-tion to starve neoplastic cells,but also enhances the efficacy of conventional cancer treatments.Vascular dis-rupting agents(VDAs) have been developed to disrupt the already existing neovasculature in actively growing tumors,cause catastrophic vascular shutdown within short time,and induce secondary tumor necrosis.VDAs are cytostatic;they can only inhibit tumor growth,but not eradicate the tumor.This novel drug mechanism has urged us to develop multiparametric imaging biomark-ers to monitor early hemodynamic alterations,cellular dysfunctions and metabolic impairments before tumor dimensional changes can be detected.In this article,we review the characteristics of tumor vessels,tubulin-destabilizing mechanisms of VDAs,and in vivo effects of the VDAs that have been mostly studied in preclinical studies and clinical trials.We also compare the differ-ent tumor models adopted in the preclinical studies on VDAs.Multiparametric imaging biomarkers,mainly diffu-sion-weighted imaging and dynamic contrast-enhanced imaging from magnetic resonance imaging,are evalu-ated for their potential as morphological and functional imaging biomarkers for monitoring therapeutic effects of VDAs. 相似文献
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PET and drug research and development. 总被引:5,自引:0,他引:5
The use of PET to examine the behavioral, therapeutic and toxic properties of drugs and substances of abuse is emerging as a powerful new scientific tool. PET provides a new perspective on drug research by virtue of its ability to directly assess both pharmacokinetic and pharmacodynamic events in humans and in animals. These parameters can be assessed directly in the human body both in healthy volunteers and in patients. Moreover, the new generation of high-resolution, small-animal cameras hold the promise of introducing imaging in the early stages of drug development and make it possible to carry out longitudinal studies in animals and to study genetically altered animals. This places PET in a unique position to contribute significantly to the process of drug development through understanding the molecular mechanisms underlying drug action while addressing some very practical questions such as determining effective drug doses for clinical trials for new drugs, determining the duration of drug action and examining potential drug interactions. 相似文献
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Clinical imaging has the potential to provide key biomarkers to inform decision-making in drug development. There is considerable optimism that emerging functional imaging techniques will substantially add to the conventional morphological depiction of disease. The discovery, development and qualification of clinical imaging biomarkers remain a considerable undertaking. Once an imaging biomarker is developed, it must be implemented with a high degree of consistency to ensure the collection of robust clinical trial data. The aim of such a development and implementation process is to deliver sufficient confidence in an imaging biomarker to support "go/no-go" decisions made in a drug development programme. This article outlines the drug development process, with a focus on the current impact of clinical imaging on drug development and its probable future direction. 相似文献
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Y Sugai T Hosoya K Yamaguchi Y Kubota 《Nihon Igaku Hōshasen Gakkai zasshi. Nippon acta radiologica》1992,52(9):1258-1272
Balloon occluded arterial infusion therapy (BOAI) with anticancer drugs has been performed widely for urinary bladder cancer. It is expected that a dense anticancer drug would perfuse the territory of the vesical arteries under occlusion of the bilateral internal iliac arteries. In balloon occluded internal iliac arteriography, however, contrast media are gradually washed out in spite of complete occlusion of the bilateral internal iliac arteries. This washout process takes place via collateral flow to the acute occlusion and varies according to the position of occlusion and arterial variations in branching. We wondered whether anticancer drug administered by BOAI would perfuse the territory of the vesical arteries as expected. We analyzed the washout process of balloon occluded internal iliac arteriography in 41 patients with urinary bladder cancer in whom preoperative BOAI had been performed. We estimated the hemodynamics and perfusion of the anticancer drug to the urinary bladder on the basis of analysis of balloon occluded internal iliac arteriography in each case. Perfusion scintigraphy and histological examination of surgical specimens of urinary bladder cancer (21 cases) confirmed the validity of our estimates. In some cases it was presumed that the anticancer drug did not reach the territory of the vesical arteries. 相似文献