癌症与癌症的检测技术的发展
来源:癌症与癌症的检测技术的发展

摘要:目前,癌症已成为仅次于心脑血管疾病的第二号人类杀手,严重威胁着人类的生命。年都有一千万以上的人死于癌症,并且死亡人数在持续不断地增加。随着科技进步,人们对癌症的认识更加充实,而且不断有新的技术和手段对癌症的检测和治疗有进一步的突破。本文回顾了癌症的起因以及癌症诊治的发展,阐述癌症早期诊断的重要性并展望多种癌症早诊技术的快速发展。

关键词:肿瘤;癌症;诊断;治疗

Abstract: At present, cancer has become the second killer of the human, next to the cardiovascular and cerebrovascular diseases, threating to human life seriously. Every year more than ten million people died of cancer all over the world, and the number of deaths is increasing at a high rate. With the development of science and technology, the understanding of cancer is more and more logical, with numerous new technologies and therapies for the cancer detection and treatment. This paper reviews the causes of cancer and the development of cancer treatments, including the importance of cancer diagnosis and the development of cancer therapies.

keywordstumorcancerdiagnosistherapy

癌症是全世界致死率排名第二的疾病,仅次于心脑血管疾病。虽然各国科学家通过实验对癌症的治疗进行了大量的研究但迄今为止我们仍然无法克服癌症的诊断和治疗面临的挑战:首先癌症早期检测研究非常困难,现有的检测方法准确度低;其次就算确诊,目前无论是手术、化疗还是放疗等治疗手段,都会对身体造成很大的负担;最后一旦癌症发生转移,无论采用何种治疗方式都很难将其彻底治愈。癌细胞能肆虐横行在身体的任何器官。其中少数一些可能是无害并且可调控的,然而大部分癌细胞不但难以治疗并且危及生命。在体内无论多么精确完美的生物机制都会被癌细胞破坏而导致致命后果

人类历史上有关癌症的最早证据来自古埃及,公元前3000古埃及木乃伊中发现了骨肉瘤化石[1]。文献中最早被记载的是乳腺癌,可见于公元前1660年的埃及纸草文[2, 3]。公元前460- 370希腊医学之父希波克拉底最早提出了癌症的概念,并且用“carcinos”“carcinoma”描述非溃疡性和溃疡性的肿瘤。由于癌症的扩散性,“carcino”一词形象的描绘出了癌症扩散的形态:如同螃蟹四处张开钳子时的模样[2]。肿瘤不但可以存在于人体中,而且在动物和植物中也会生成。肿瘤可以解释为大量异常细胞组成的实心或者含有流动液体的肿块而这些异常细胞来源于不利因素长期作用的影响下而转化的正常细胞。这些异常细胞违背正常新陈代谢的规律,生长和死亡自由不可控因此导致细胞过度生长和形态异常。在长期的研究中,科学家将肿瘤分为了两类:良性肿瘤和恶性肿瘤。这两种类型的肿瘤都是由异常细胞组成的,但是良性肿瘤的生长速度比恶性肿瘤慢,良性肿瘤细胞缺乏迁移和侵袭邻近组织的能力。因此,良性肿瘤可以先通过手术切除,然后用化疗或放疗等治疗方式进一步彻底清除肿瘤细胞。脂肪瘤[4],软骨瘤[5],腺瘤[6]和错构瘤[7]是良性肿瘤的常见的例子。相反,恶性肿瘤也被称作癌症,与良性肿瘤不同的是它对周围器官具有强大的侵袭能力和转移能力[8]从而扩散甚至直接侵入周围的健康器官和组织,指数难以控制的生长速率导致增生和恶性的原因,此外,恶性肿瘤的基因组极度不稳定,整个基因组之间有104105高频繁的突变[9]。综上所述,癌症成为最致命的疾病之一

1618世纪文艺复兴为生物和医学领域提供了巨大的发展空间[10, 11]。科学家们能够完善的理解生理环境,用外科手术治疗癌症患者。在19世纪显微镜的出现帮助科学家对癌症的进一步研究[12]。显微镜的应用不仅使科学家更好地了解病变的组织而且还提高癌症手术的精度。到目前为止全世界已经发现数百种癌症,如乳腺癌,肝癌,肺癌,胰腺癌,食道癌和脑癌等[13]。关于癌症发生的理论原因有很多种学说例如体液学说[14]、淋巴学说[1]、胚芽学说[15]、慢性刺激学说[16]、创伤学说[17]和传染性疾病学说[18];科技的发展帮助人们更深入的认识到病毒[19]、化学致癌物质[20]、原癌基因的激活[21]和肿瘤抑制基因的失活[22]等因素能够导致癌症的原因,为癌症的研究提供了更多的理论依据。近年更令人鼓舞的是先进的科学技术为癌症的早期诊断提供了珍贵的机会,这对癌症的治疗意义匪浅,极大的提高了治疗的成功率和存活率。

大量的临床试验证明在癌变初期,癌症的早期诊断能很大提高癌症的治愈率癌症患者的生存率。癌症早期诊断是专门针对癌症早期患者的诊疗方法,一般通过检测仪器生物化学等方法检测癌症进一步了解确诊病情,最终制定出最佳治疗方案实现早发现早治疗的目的。目前,癌症早期检测的方法主要有以下几种:

1.血检:血检(blood test)是癌症诊断的最直接、最简便的方法。医生通过收集患者的血液样本,采取不同的方法对血液进行测试,收集血液样本的多种信息。(1)全血细胞计数(complete blood testCBC test,在全血细胞计数的测量方法中,会检测各种类型的血细胞数量,包括红细胞,白细胞和血小板的数量。虽然CBC检测的结果不能准确诊断癌症,但是这些结果可以显示一些潜在的异常症状,如红细胞数目降低造成的贫血以及血小板数目降低造成的伤口愈合能力变差等。(2)尿素和电解质检测(Urea and electrolytes testU&E test)。U&E测试是常用的生化试验可针对很多指标提供有用的信息例如血液pH值(酸中毒或碱中毒),免疫系统的异常蛋白(免疫球蛋白)及肾功能障碍。(3)肝功能检测(liver function testLF test)。肝功能检测也被称为肝酶检测,是检测炎症和肝脏损害的重要血液测试5)肿瘤标志物检测(tumor maker test)。肿瘤标志物是肿瘤产生的特定分子,它可以指示肿瘤的存在。由于不同种类的癌症会产生不同的肿瘤标志物,所以这些标志物为癌症类型的确定提供了必要的依据常见的肿瘤特异性标志物见表1。  

肿瘤标志物

肿瘤类型

癌胚抗原(CEA

结肠癌[23],胰腺癌[24],肺癌[25],肝癌[26],乳腺癌[27]

前列腺特异性抗原(PSA

前列腺癌[28]

糖链抗原19-9 CA19-9

胰腺癌[24],胆囊癌[29]

糖链抗原50CA50

胰腺癌[30],胃癌[31]

癌抗原125CA125

卵巢癌[32]

鳞状细胞癌抗原(SCC

子宫颈癌[33],肺癌[34]

组织多肽抗原(TPA

膀胱癌[35],卵巢癌[36],乳腺癌[37]

神经元特异性烯醇化酶(NSE

小细胞肺癌[25]

β2微球蛋白(β2M

骨髓瘤[38]

2.活检:活检是通过医疗手术取出患者的异常组织作为标本,通过显微镜下检查,以确定在可疑区域是否存在癌细胞的诊断方法。基于分析结果,可以确定切除的组织是正常组织、良性肿瘤组织还是恶性肿瘤组织。根据身体不同部位,利用不同类型的活检可获得好的结果,如细针穿刺活检[39](取少量的组织),针芯活检[40](取圆柱状的组织)真空辅助活检[41]自同一个可疑的地方的更多组织)图像引导活检(结合成像技术,如超声[42],荧光显微镜[43]CT扫描[44]X射线[45]外科手术活检[46](通过外科手术取出的可疑组织)和骨髓活检[47](测试血液疾病或血液癌的一小块骨髓组织)。

3.诊断影像学:诊断影像学是通过各种不同原理和方法的成像技术,使人体内部结构和器官形成影像,从而了解人体生理功能状况病理变化,最终达到诊断的目的[48]1895年,德国物理学家伦琴发现了X射线,奠定了医学诊断影像学的基础[49]X射线成像技术的成本低,其提供的信息是相对有限的。随着诊断影像学飞速发展至今放射诊断学仍是医学影像学中的主要内容,应用非常普遍。50年代到60年代科学家应用超声与核素扫描人体进行诊断检查,也就是超声成像[50]ultrasonography, USG它利用高频声波来形成人体器官的图像,能够更好的检测软组织,并区分实体瘤和液体填充囊肿美中不足的是超声成像不能区分良性肿瘤和恶性肿瘤。70年代末又相继出现了计算机断层扫描成像[51]Computed TomographyCT)和磁共振成像[52]Magnetic Resonance Imaging, MRI计算机断层扫描(CT)的发展为癌症诊断提供了更好的手段,它可以进一步显示人体内肿瘤的存在、大小和深度。磁共振成像(MRI是成像脑肿瘤的首选技术,不但可以精确检测脑肿瘤的存在,而且可以提供癌症的恶性状态[53]。此外,还有γ闪烁成像[54]γ-scintigraphy),正电子发射计算机断层显像[55] (Positron Emission Tomography, PET)和单光子发射体层成像[56, 57]Single Photon Emission Computed Tomography, SPECT)等新的成像技术也成功的应用在癌症的诊断影像学中。目前为止,已经有数十种诊断影像技术应用于癌症的检测,选择合适的诊断影像技术是提高癌症诊断准确性的关键之一

4.内窥镜检测法:内窥镜检测是用一种微小的仪器来诊断病人体内可疑区域的过程。内窥镜检查能够直接观察到被检查部位的真实情况,确定可疑病变的部位,并结合病理活检及细胞学检查对可疑病变部位进行更深一步检测,达到精确的诊断。内窥镜检测是上消化道癌变的首选检测方法它借助一条纤细、柔软的管子伸入胃中,医生可以直接观察食道、胃和十二指肠的病变,尤其针对微小的病变(如图1,胃镜检测为例)。目前有专为身体的不同部位设计的几种类型的内窥镜,如胃镜[58]、支气管镜[59]、膀胱镜[60]、子宫镜[61]和结肠镜[62]。此外,内窥镜检测和其它癌症诊断方法的结合,例如影像诊断和活检,可以提供更准确和有效的癌症诊断策略。

5.癌症纳米检测技术:纳米技术是近年来出现的一种新颖技术,主要研究尺寸在0.1-100 nm的材料的结构和性质,广泛应用于多个领域(如物理学、化学、电子学、食品科学、生物学以及医学)。纳米技术的应用,极大的促进了生物材料医学的进步,改善了癌症的诊断和治疗。通过国内外的研究表明,纳米技术在癌症的检测和治疗方面具有独特性质和优势1)许多纳米材料自身具有成像能力通过对纳米材料进行不同的修饰(包括肿瘤表面标志物、多肽、DNA以及化学小分子等),特异性识别体内病变组织。例如,表面带有叶酸修饰的ZnS:Mn/ZnS量子点能够特异性识别表面叶酸受体阳性的乳腺癌细胞系T47D,通过双光子共聚焦显微镜可以看到清晰稳定的荧光。其无毒性、特异性和荧光稳定性为表面叶酸受体呈阳性的癌细胞检测带来了新的空间[63]。(2)多种纳米材料的结合不但可以提升成像能力,而且可以进行药物运输多孔纳米硅颗粒(mesoporous silica nanoparticlesMSNs)是生物医学应用最具潜力的纳米材料,其高效的载药能力、无可媲美的生物相容性、可灵活调控的粒径及孔径和丰富的表面修饰可以满足生物医学应用的多种需求。例如,通过对装载荧光染料的多孔纳米硅颗粒表面修饰Fe3O4Fe3O4-MSNs),不但增强了体内磁共振成像,而且具有光学成像模式的能力。此外,Fe3O4-MSNs纳米颗粒能够高效的运输抗癌药物,实现癌症检测治疗的一体化[64]。(3)纳米材料的应用提高了癌症早期诊断的灵敏性。由于早期肿瘤的生物标志分子表达量低,而且在不同的病患中存在表达差异,因此传统的诊断技术无法准确诊断出早期癌症的存在。大量的纳米线和纳米管形成纳米微阵列,排列在一块芯片上,可以同时阅读大量蛋白质和核酸的信息,具有同时处理大量的多元化信息的能力[65]。由此研发出的DNA微阵列技术[66]和蛋白质组学的SELDI-TOP质谱技术[67]等微纳米技术极大的推动了生物医学的发展进程,为癌症的早期检测提供了新的发展前景。

迄今世界各国在癌症的预防、早期诊断以及治疗方面已经投入了大量的人力和物力,然而根据美国癌症协会对全球人类重大疾病的统计数据中可以看到,癌症的致死率呈指数上升,而且从全球致死率第五名(2002年)上升到全球致死率第二名(2012年),仅次于心血管疾病[68]。癌症如此严重的危害,主要是因为癌症的侵袭性、转移性和复发性,而且术后复发所引起的各种并发症也是患者死亡的重要原因。随着科技的进步科学家已经成功的利用血检、活检和诊断影像学等手段对部分癌症进行早期检测。近年来,功能化的纳米材料与癌症检测的结合推动了生物纳米医学的发展引起了科学界的广泛关注。然而目前的癌症诊断技术灵敏度和效率和普遍应用性依然差强人意。因此,为了提升癌症患者的治愈率和存活率癌症早期检测的发展和诊治有着更多的工作需要完善。

Acknowledgement

项目受国家自然科学基金(Nos. 21102007)和深圳市杰出青年基金(Nos.SW201110060)资助。

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