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Dendrimers based electrochemical biosensors 基于树突聚合物的电化学生物传感器
Pub Date : 2015-01-01 DOI: 10.4103/2349-3666.240618
S. Nigam, S. Chandra, D. Bahadur
Electrochemical biosensors are portable devices that permit rapid detection and monitoring of biological, chemical and toxic substances. In the electrochemical biosensors, the bioreceptor is incorporated into the transducer surface; and when in contact with the analyte, generates measurable signals proportional to the analyte concentration. Materials with high surface area, high reactivity, and easy dispersability, are most suited for use in biosensors. Dendrimers are nanomaterial gaining importance for fabrication of electrochemical biosensors. These are synthetic macromolecules with regularly branched tree-like and globular structure. The potential applications of dendrimers as biosensors are explored due to their geometric symmetrical structure, chemical stability, controlled shape and size, and varied surface functionalities, with adequate functional groups for chemical fixation. The current review provides multi-faceted use of dendrimers for developing effective, rapid, and versatile electrochemical sensors for biomolecules. The redox centers in the dendrimers play an important role in the electron transfer process during immobilization of biomolecules on the electrodes. This has led to an intensive use of dendrimer based materials for fabrication of electrochemical sensors with improved analytical parameters. The review emphasizes development of new methods and applications of electrochemical biosensors based on novel nanomaterials.
电化学生物传感器是一种便携式设备,可以快速检测和监测生物、化学和有毒物质。在电化学生物传感器中,生物受体被整合到传感器表面;当与分析物接触时,产生与分析物浓度成正比的可测量信号。具有高表面积、高反应性和易分散性的材料最适合用于生物传感器。树状大分子是一种在电化学生物传感器制造中越来越重要的纳米材料。这些合成大分子具有规则的枝状和球状结构。由于树状大分子具有几何对称结构、化学稳定性、形状和大小可控、表面官能团多样、具有足够的化学固定官能团等特点,探索了其作为生物传感器的潜在应用。本文综述了树状大分子在开发高效、快速、通用的生物分子电化学传感器方面的多角度应用。枝状大分子的氧化还原中心在生物分子固定在电极上的电子传递过程中起着重要的作用。这导致了大量使用基于树枝状聚合物的材料来制造具有改进分析参数的电化学传感器。综述了基于新型纳米材料的电化学生物传感器的新方法和应用。
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引用次数: 6
Identification of therapeutic targets for cancer: Proteomic technologies and strategies are the key to success 癌症治疗靶点的鉴定:蛋白质组学技术和策略是成功的关键
Pub Date : 2015-01-01 DOI: 10.4103/2349-3666.240653
R. Govekar
With the emergence of the field of ‘omics’ a new era of systematic global profiling of cellular molecules has been initiated in biology. Different ‘omics’ approaches have been extensively used to identify biomarkers for better diagnosis and prognosis, therapeutic strategies and monitoring response to therapy in diverse types of cancers. Proteomics is the approach of choice for identification of therapeutic targets. This is because therapeutic modulation of expression, post-translational modification and activity of a protein can directly rectify the derangement in the disease-causing cellular pathway. The current review scans literature on tumor proteomics to understand the influence of developments in proteomics technology and study approaches on identification of targets for therapy. Diversity of tumor types, molecular heterogeneity in pathologically indistinguishable tumors provides ample challenge to assess the strength of proteomics in identification of drug targets. The review highlights comparative proteomic profiling by gel-based or gel free approach, in tumor and normal tissues or chemo-resistant/sensitive tumor tissues have identified differentiator proteins, with potential as targetsas therapeutic targets. Further, along with evolution in proteomic technologies for identification and quantification of proteins, various tools for functional analysis of proteins have contributed to strategies for target identification. It also suggests that future advances in quantitative, functional and structural proteomics isare necessary to widen the search for therapeutic targets.
随着“组学”领域的出现,生物学开始了一个系统的全球细胞分子分析的新时代。不同的“组学”方法已被广泛用于识别生物标志物,以更好地诊断和预后,治疗策略和监测对不同类型癌症的治疗反应。蛋白质组学是鉴定治疗靶点的首选方法。这是因为治疗性地调节蛋白质的表达、翻译后修饰和活性可以直接纠正致病细胞通路中的紊乱。本文回顾了肿瘤蛋白质组学的相关文献,以了解蛋白质组学技术和研究方法的发展对肿瘤治疗靶点确定的影响。肿瘤类型的多样性和病理上难以区分的肿瘤的分子异质性为评估蛋白质组学在识别药物靶点方面的优势提供了充分的挑战。该综述强调了通过凝胶或无凝胶方法在肿瘤和正常组织或耐药/敏感肿瘤组织中的比较蛋白质组学分析已经确定了分化蛋白,具有作为治疗靶点的潜力。此外,随着鉴定和定量蛋白质的蛋白质组学技术的发展,蛋白质功能分析的各种工具有助于目标鉴定的策略。这也表明,定量、功能和结构蛋白质组学的未来发展对于扩大对治疗靶点的研究是必要的。
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引用次数: 0
Cancer gene therapy: Prospects of using human sodium iodide symporter gene in non-thyroidal cancer 肿瘤基因治疗:利用人碘化钠同转运体基因治疗非甲状腺癌的前景
Pub Date : 2015-01-01 DOI: 10.4103/2349-3666.240655
S. Dutta, A. De
Gene therapy is one of the promising therapeutic strategies evolved rapidly in the frontier of translational biology in cancer. To overcome the off target effect of conventional cancer therapies it is the most flourishing approach in present epoch. Various researches in this context are ongoing to eradicate devastating cancer cells with minimal or no side effects. Of the various gene therapy protocols developed, a set of genes called suicide genes, are being actively pursued as potential strategy. Briefly, this strategy involves tumor targeted delivery of a therapy/reporter gene to convert a systematically administered pro-drug into a cytotoxic drug which in turn induces tumor cell death. Additionally, advancement in small animal imaging modalities facilitates real-time monitoring of the delivered transgene by using appropriate imaging probe developed against the transgene. Non-invasive monitoring helps to realize precise transgene delivery and also aid to understand therapy response. In this background, we have reviewed potential suicide genes frequently explored for cancer treatment, which supports both diagnostic and therapeutic applications with special emphasis on sodium iodide symporter (NIS). Apart from its natural expression in thyroid, NIS protein expression has raised the possibility of using radioiodide therapy and diagnosis in few non-thyroidal cancers as well. In this review, we also covered various challenges to get NIS gene therapeutics from bench to bedside in various non-thyroidal cancers.
基因治疗是在肿瘤转化生物学研究的前沿迅速发展起来的有前景的治疗策略之一。为了克服常规肿瘤治疗的脱靶效应,它是当今最蓬勃发展的方法。在此背景下,各种各样的研究正在进行中,以最小或没有副作用的方式根除毁灭性的癌细胞。在已开发的各种基因治疗方案中,一组被称为自杀基因的基因正被积极地作为潜在的策略进行研究。简而言之,该策略涉及肿瘤靶向递送治疗/报告基因,将系统给药的前药转化为细胞毒性药物,进而诱导肿瘤细胞死亡。此外,小动物成像方式的进步通过使用针对转基因开发的适当成像探针,促进了对传递的转基因的实时监测。非侵入性监测有助于实现精确的转基因传递,也有助于了解治疗反应。在此背景下,我们回顾了癌症治疗中经常发现的潜在自杀基因,这些基因支持诊断和治疗应用,特别强调了碘化钠同调体(NIS)。除了在甲状腺中自然表达外,NIS蛋白的表达也提高了在少数非甲状腺癌中使用放射性碘治疗和诊断的可能性。在这篇综述中,我们还涵盖了将NIS基因疗法从实验室应用到临床治疗各种非甲状腺癌的各种挑战。
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引用次数: 2
Areca nut use and cancer in India 在印度槟榔的食用和癌症
Pub Date : 2015-01-01 DOI: 10.4103/2349-3666.240652
Prakash C. Gupta, C. Ray
Areca nut is widely used in India and the consumption has increased over the past two decades, with availability in new dry packaged forms (pan masala, gutka, mawa). Recent reports of increasing mouth cancer incidence have suggested an association with areca nut consumption. Here we have reviewed the evidence for carcinogenicity of areca nut, including epidemiological studies, several animal studies and mechanistic evidence. Studies primarily from India, providing odds ratios (ORs) or relative risks for precancers or cancer with use of areca nut without inclusion of tobacco is the focus of the review. Six case-control studies on oral submucous fibrosis (OSF) had significantly elevated ORs for use of areca nut in various forms. Six case-control studies on head and neck cancers, primarily oral cancer reported elevated ORs for chewing of betel quid without tobacco. Eight case control studies on oral cancer have reported elevated and significant ORs for betel quid with tobacco. A significant risk in oral cancer was noted in gutka users. Animal studies confirmed correlation between development of precancers or cancers and exposure to areca nut or pan masala without tobacco. Mechanistic evidence shows a role for areca nut alkaloids, polyphenols and copper in promoting carcinogenesis. Our review emphasizes control policies on areca nut products and appropriate mass communication programs for awareness of hazards of areca nut with emphasis on areca nut per se.
槟榔果在印度被广泛使用,在过去二十年中消费量有所增加,有了新的干包装形式(pan masala, gutka, mawa)。最近的报告表明,口腔癌发病率的增加与槟榔果的食用有关。本文综述了槟榔致癌性的证据,包括流行病学研究、一些动物实验和机理证据。主要来自印度的研究提供了使用槟榔果而不包括烟草的癌症前期或癌症的优势比(ORs)或相对风险,这是综述的重点。六项关于口腔粘膜下纤维化(OSF)的病例对照研究表明,使用各种形式的槟榔可显著提高口服口服盐的风险。六项关于头颈部癌症(主要是口腔癌)的病例对照研究报告,咀嚼不含烟草的槟榔液会导致ORs升高。8例口腔癌病例对照研究报告了含烟草的槟榔液的ORs升高和显著升高。gutka使用者患口腔癌的风险显著。动物研究证实了癌症前期或癌症的发展与接触槟榔或无烟草的pan masala之间的相关性。机制证据表明槟榔生物碱、多酚和铜在促进癌变中的作用。我们的综述强调槟榔产品的控制政策和适当的大众传播计划,以提高人们对槟榔危害的认识,重点是槟榔本身。
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引用次数: 12
Visual inspection with acetic acid as a screening test for cervical cancer 醋酸目视检查作为宫颈癌的筛查试验
Pub Date : 2014-04-01 DOI: 10.4103/2349-3666.240658
Srabani Mittal, J. Biswas, P. Basu
Visual inspection with acetic acid (VIA) has been extensively investigated and accepted as potential alternative to cytology or Human Papilloma Virus (HPV) screening in limited resource settings. In developing countries, VIA may have several advantages over cytology or HPV screening. The consumables of the test are low-cost and readily available. VIA has potential of achieving large population coverage, as the test can be performed by a wide range of trained health care personnel and requires basic health infrastructure. It is a real-time test and offers logistic advantage of providing treatment for screen positive women during the same visit leading to high treatment coverage. The sensitivity and specificity estimates of VIA generally fall within the range of those reported for cytology and HPV testing. Randomized controlled trials evaluating test performance of VIA have demonstrated reduction in cervical cancer incidence and mortality in study population. The major limitation of VIA is that it is a subjective test and accuracy is dependent on the skill of trained providers. Low specificity and sub-optimal positive predictive value results in unnecessary referrals and/or treatment which can offset the perceived low cost of the test. VIA based screening programs are required to have clearly defined measurable indicators and a framework to identify the program strengths and weaknesses. Quality assurance of VIA is challenging specially because there is limited information on the test performance in multi-provider real programmatic setting. High quality training, periodic refresher courses, expertise of trained providers and close monitoring of performance indicators are required to ensure good quality VIA.
在资源有限的情况下,醋酸目视检查(VIA)已被广泛研究并被接受为细胞学或人乳头瘤病毒(HPV)筛查的潜在替代方法。在发展中国家,VIA可能比细胞学或HPV筛查有几个优势。该测试的耗材成本低且容易获得。由于该检测可由广泛的训练有素的卫生保健人员进行,并且需要基本的卫生基础设施,因此具有实现大规模人口覆盖的潜力。这是一种实时检测,提供了在同一次就诊期间为筛查阳性妇女提供治疗的后勤优势,从而提高了治疗覆盖率。VIA的敏感性和特异性估计通常落在细胞学和HPV检测报告的范围内。评估VIA测试性能的随机对照试验表明,在研究人群中,宫颈癌发病率和死亡率有所降低。VIA的主要限制是它是一种主观测试,准确性取决于训练有素的提供者的技能。低特异性和次优阳性预测值导致不必要的转诊和/或治疗,这可以抵消该测试的低成本。基于VIA的筛选项目需要有明确定义的可衡量指标和框架来确定项目的优势和劣势。VIA的质量保证是具有挑战性的,特别是因为在多提供商的实际编程设置中,有关测试性能的信息有限。高质量的培训、定期进修课程、受过培训的提供者的专业知识和密切监测绩效指标是确保高质量VIA的必要条件。
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引用次数: 2
Molecular basis of reprogramming: Modulation by microRNAs 重编程的分子基础:microrna的调节
Pub Date : 2014-01-01 DOI: 10.4103/2349-3666.240998
Akshata Raut, Aparna P Khanna
Induced pluripotent stem cells (iPSCs) have opened up a new avenue for customized regenerative medicine. iPSCs can be generated by forced expression of transcription factors, Oct4, Sox2, c-Myc and KIf4. Although reprogramming techniques are well documented, one of the major concerns has been the poor efficiency of reprogramming. The reprogramming efficiency can be enhanced using various chemical compounds and vector systems. However, low reprogramming efficiencies and use of viral based vector systems limit clinical application of iPSCs. microRNAs (miRNAs) are extensively studied due to their critical role in numerous biological activities like cell cycle regulation, growth control and apoptosis. Discovery of embryonic stem cell (ESC) specific unique miRNAs, encouraged researchers to study contribution of miRNAs towards embryonic stem cell development, differentiation and somatic cell reprogramming (SCR). Depletion of mouse embryonic fibroblast (MEF) enriched miRNAs like miR-29a, miR-21 and let-7, are necessary to enhance reprogramming. Furthermore, up regulation of miR-200, miR-106a/b miR-120, miR-93 miR-301, miR-17, miR-721, miR-29b is required for mesenchymal-to-epithelial transition (MET), a critical initial event during the generation of iPSCs from fibroblasts. The expression of embryonic stem cell specific miRNAs like miR-290/miR-302 cluster, miR-367/miR372 is crucial to maintain pluripotent status of iPSCs. In this review, we discuss contribution of miRNAs to generation of iPSCs, their defined role in maintenance of pluripotent state, transcriptional regulatory networks and epigenetic factors to modulate reprogramming.
诱导多能干细胞(iPSCs)为个性化再生医学开辟了一条新的途径。iPSCs可以通过强制表达转录因子Oct4、Sox2、c-Myc和KIf4来生成。虽然重编程技术有很好的文献记载,但一个主要的问题是重编程的低效率。使用不同的化合物和载体系统可以提高重编程效率。然而,低重编程效率和基于病毒的载体系统的使用限制了iPSCs的临床应用。microRNAs (miRNAs)因其在细胞周期调节、生长控制和细胞凋亡等众多生物活动中发挥的关键作用而被广泛研究。胚胎干细胞(ESC)特异性独特mirna的发现,鼓励了研究人员研究mirna对胚胎干细胞发育、分化和体细胞重编程(SCR)的贡献。小鼠胚胎成纤维细胞(MEF)富集的mirna如miR-29a、miR-21和let-7的缺失对于增强重编程是必要的。此外,miR-200、miR-106a/b、miR-120、miR-93、miR-301、miR-17、miR-721、miR-29b的上调是间充质向上皮转化(MET)所必需的,这是成纤维细胞生成iPSCs过程中的一个关键初始事件。胚胎干细胞特异性mirna如miR-290/miR-302集群、miR-367/miR372的表达对于维持iPSCs的多能状态至关重要。在这篇综述中,我们讨论了mirna对iPSCs产生的贡献,它们在维持多能状态中的作用,转录调控网络和调节重编程的表观遗传因子。
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引用次数: 0
Current Status of Cancer Burden: Global and Indian Scenario 癌症负担的现状:全球和印度的情况
Pub Date : 2014-01-01 DOI: 10.4103/2349-3666.240996
D. Saranath, A. Khanna
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引用次数: 98
An update on cancer prevention approaches 癌症预防方法的最新进展
Pub Date : 2014-01-01 DOI: 10.4103/2349-3666.241001
G. Maru
Majority of human cancers are caused, mediated and modified by environmental and lifestyle factors; and the multi-factorial, multi-step and multi-path process of carcinogenesis involves a series of genetic and epigenetic events. In spite of tremendous advancement in understanding of the molecular basis of cancer and identification of several environmental carcinogens, avoidance of exposure to carcinogens and early detection and/or successful treatment for most cancers have met with limited success. Based on the susceptibility to modulations of the multi-step process of carcinogenesis by a multitude of environmental compounds, lifestyle changes and host factors, and the demonstrated success of prevention of certain infectious diseases and cardiovascular events, cancer preventive interventions are receiving increasing attention. Several cancer preventive interventions such as vaccination, chemoprevention, weight control and lifestyle changes have been implemented. The current review focuses on several approaches and agents that have been scrutinized by way of randomized clinical trials in humans for their cancer prevention potential. Successful chemopreventive agents include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-α-reductase inhibitors for prostate cancer, non-steroidal antiinflammatory drugs (NSAIDs) for colorectal lesions and vaccines for viruses that are associated with cervical and liver cancers. Several experimentally proven chemopreventive agents have been observed to lack efficacy with and without toxicity. In spite of numerous chemoprevention trials, the number of successful agents is rather small. Identifying novel approaches and chemopreventives holds tremendous potential for reducing the burden of cancer.
大多数人类癌症是由环境和生活方式因素引起、介导和改变的;肿瘤发生是一个多因素、多步骤、多途径的过程,涉及一系列遗传和表观遗传事件。尽管在了解癌症的分子基础和确定几种环境致癌物方面取得了巨大进展,但避免接触致癌物和早期发现和/或成功治疗大多数癌症方面取得的成功有限。基于多种环境化合物、生活方式改变和宿主因素对多步骤致癌过程的调节的易感性,以及在预防某些传染病和心血管事件方面取得的成功,癌症预防干预措施正受到越来越多的关注。一些癌症预防干预措施,如疫苗接种、化学预防、体重控制和生活方式的改变已经实施。目前的综述集中在几种方法和药物上,这些方法和药物已经通过人类随机临床试验来审查其癌症预防潜力。成功的化学预防药物包括针对乳腺癌的选择性雌激素受体调节剂和芳香化酶抑制剂,针对前列腺癌的5-α-还原酶抑制剂,针对结直肠癌病变的非甾体抗炎药(NSAIDs),以及针对宫颈癌和肝癌相关病毒的疫苗。一些经实验证实的化学预防剂已被观察到在有毒性和没有毒性的情况下缺乏疗效。尽管有许多化学预防试验,但成功的药物数量相当少。确定新的方法和化学预防措施对减轻癌症负担具有巨大的潜力。
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引用次数: 1
Single nucleotide polymorphisms in human health and disease: Towards resolution of a conundrum 人类健康和疾病中的单核苷酸多态性:解决一个难题
Pub Date : 2014-01-01 DOI: 10.4103/2349-3666.240660
Narendra Joshi
Single nucleotide polymorphisms, also referred to as Single nucleotide variants remain single most dominant feature of variations in the human genome. The large numbers, stability and presence at easily detectable frequencies make them the most suitable potential markers for association studies in human health and disease. The study of these common genetic variants has now evolved and given rise to the understanding of less frequently encountered ‘rare’ variants of varying minor allele frequencies. The acceptance of role of rare single nucleotide variants in human diseases appears to coincide with the phasing out of the term ‘mutation’ in the dbSNP. The contribution of rare variants helps resolve the enigma of heritability of complex traits to a great extent. Integration of analysis of rare and common variants with the support of technological innovations and improved strategies for data analyses is expected to yield better and reliable association data. By virtue of their relatively stronger impact on the phenotype compared to that of the common variants, rare variants are likely to be better candidates as markers of association as well as targets for intervention strategies while providing mechanistic insights into the underlying biological processes. Starting with discussion of the basics of single nucleotide variants, this review summarizes concepts and principles of approaches used to study their association with parameters in health and diseases including cancer. Implications for studies in Indian population are discussed.
单核苷酸多态性,也被称为单核苷酸变异,仍然是人类基因组变异的最主要特征。数量多,稳定性好,存在频率易检测,使其成为人类健康和疾病关联研究中最合适的潜在标记物。对这些常见遗传变异的研究现在已经得到了发展,并引起了对不同小等位基因频率的不太常见的“罕见”变异的理解。人们接受罕见的单核苷酸变异在人类疾病中的作用,似乎与dbSNP中“突变”一词的逐步淘汰是一致的。稀有变异的贡献在很大程度上有助于解开复杂性状遗传力之谜。在技术创新和改进的数据分析策略的支持下,将罕见和常见变异的分析集成在一起,有望产生更好和可靠的关联数据。与常见变异相比,罕见变异对表型的影响相对更大,因此它们可能是更好的关联标记和干预策略目标的候选者,同时提供了对潜在生物学过程的机制见解。从讨论单核苷酸变异的基础开始,本文综述了用于研究它们与健康和疾病(包括癌症)参数关联的方法的概念和原理。讨论了对印度人口研究的启示。
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引用次数: 1
Ovarian cancer: An ever challenging malady 卵巢癌:一种极具挑战性的疾病
Pub Date : 2014-01-01 DOI: 10.4103/2349-3666.240659
Smrita Chaudhury, A. Maheshwari, P. Ray
Ovarian cancer is the fifth leading cause of cancer related deaths in women with a five year survival rate of only 30–40%. Amongst the three broad subgroups of ovarian cancer, epithelial ovarian cancer is the most common and is divided in mainly five subtypes based histology and clinical behaviour. In patients when the disease is still confined to ovaries, surgery alone is curative for more than 90% patients. Unfortunately, most women are diagnosed with advanced stage disease and recurs in majority despite of debulking surgery and initial response to chemotherapy. Thus ovarian cancer is still a challenge to clinicians which gets more complicated due to asymptomatic nature of the early stage disease and frequent development of resistance to standard therapies. Therefore, researchers worldwide are engaged in identifying markers for early detection of ovarian cancer, investigating molecular mechanisms of chemoresistance, improving detection methods and developing novel therapeutic measures. In this review, we attempt to discuss the contemporary research and challenges associated with epithelial ovarian cancer along with the future improvements in various areas such as early detection of ovarian cancer through Multiplex-Methylation specific PCR (MSP) assay and Serial Analysis of Gene expression (SAGE) assay and identifying new biomarkers, facilitating personalised chemotherapy regime by various chemo-response assays, novel drugs and targeted therapies which will aid in enhancing the overall survival rate in future and overcome this deadly gynaecologic disease.
卵巢癌是妇女癌症相关死亡的第五大原因,5年生存率仅为30-40%。在卵巢癌的三大亚群中,上皮性卵巢癌是最常见的,并根据组织学和临床行为主要分为五个亚型。在疾病仍局限于卵巢的患者中,90%以上的患者仅手术即可治愈。不幸的是,大多数女性被诊断为晚期疾病,尽管进行了减脂手术和化疗的初步反应,但大多数患者仍会复发。因此,卵巢癌仍然是临床医生面临的一个挑战,由于早期疾病的无症状性和对标准治疗的频繁耐药性,卵巢癌的治疗变得更加复杂。因此,世界各地的研究人员都致力于寻找卵巢癌早期检测的标志物,研究化疗耐药的分子机制,改进检测方法和开发新的治疗措施。在这篇综述中,我们试图讨论与上皮性卵巢癌相关的当代研究和挑战,以及未来在各个领域的改进,如通过多重甲基化特异性PCR (MSP)检测和基因表达序列分析(SAGE)检测早期检测卵巢癌,识别新的生物标志物,通过各种化学反应分析促进个性化化疗方案,新型药物和靶向治疗将有助于提高未来的总体生存率,并克服这种致命的妇科疾病。
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引用次数: 3
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