细胞病理学综合展望

IF 0.7
G. Su
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The invention of the microscope in the 19th century was undoubtedly another force that propelled pathology and medicine forward, moving us from organbased to cell-based pathology with this “new technology”. Along with the microscope, other technological advances such as tissue fixation, embedding, microtomes, and biological stains, all enabled the practice of histopathology possible. However, for a century, despite the improvement of microscopes and a plethora of ancillary diagnostic tests (i.e. electron microscopy, fluorescent microscopy, immunohistochemistry, cytogenetics), the importance of detecting morphological abnormalities remained constant and central to scientific discoveries, journal publications, and patient care as research focuses moved from organs to cells, from organelles to chromosomes. In recent decades, we have seen an explosion of technologies in science, which enabled comparisons of normal vs. diseased states at molecular levels. Soon, analyses of DNA (single nucleotide polymorphism profiling, whole exome sequencing, cell-free DNA screening, etc.), RNA (RNA-Seq, single cell RNA-Seq, miRNA-Seq, ribosome profiling, etc.), protein (protein microarray, mass spectrometry, quantitative proteomics, etc.), epigenome (ChIPSeq, whole-genome bisulphite sequencing), and metabolome (MS-based metabolites or lipid profiles) at various depths and throughputs became a common practice in experimental approaches and journal publications [4,5]. These molecular analyses not only can identify dysfunctional genes and/or pathways that are responsible or have contributed to the diseased state and structural abnormalities that can be visualized grossly or under a microscope, but may also offer insights for personalized medicine. For instance, in the era of precision medicine for cancer treatment, we have come to recognize that not only there are differential sensitivities to a given therapy among patients, there exists cellular heterogeneity in a patient’s tumor. Therefore, a histological diagnosis of cancer in a patient can be complemented by molecular analyses to devise a personalized therapy that matches the tumor’s molecular profile. It is also the hope that advances in liquid biopsies and artificial intelligence will someday replace the need for tissue biopsy in disease diagnosis, although many obstacles remained [6]. Cell pathology can be defined at cellular, organelle, and molecular levels, and can be detected by histological analysis, functional assays, or molecular analyses. Genetic mutations, epigenetic changes, or metabolic dysfunction can all contribute to the pathogenesis of a disease. 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引用次数: 0

摘要

病理学是最古老的医学学科之一,可以追溯到5000年前的埃及医学和中医[1,2]。在古代,疾病的记录依赖于对解剖学的理解和对偏离正常生理的异常现象的观察。在接下来的几个世纪里,人们通过观察病理状况和尸检积累了大量的知识,正是这些丰富的信息奠定了我们今天所看到的现代医学的基础。早期病理以形态异常为主。骨折、异常肿块、皮肤变色等随机记录在19世纪的现代病理学中演变为系统的大体解剖学[2,3]。19世纪显微镜的发明无疑是推动病理学和医学向前发展的另一股力量,通过这种“新技术”,我们从以器官为基础的病理学转向了以细胞为基础的病理学。随着显微镜的发展,其他技术的进步,如组织固定、包埋、显微切片和生物染色,都使组织病理学的实践成为可能。然而,一个世纪以来,尽管显微镜和大量辅助诊断测试(如电子显微镜、荧光显微镜、免疫组织化学、细胞遗传学)得到了改进,但随着研究重点从器官转移到细胞、从细胞器转移到染色体,检测形态异常的重要性仍然保持不变,并成为科学发现、期刊出版和患者护理的核心。近几十年来,我们看到了科学技术的爆炸式发展,可以在分子水平上比较正常和患病状态。很快,DNA分析(单核苷酸多态性分析、全外显子组测序、无细胞DNA筛选等)、RNA分析(RNA- seq、单细胞RNA- seq、miRNA-Seq、核糖体分析等)、蛋白质分析(蛋白质微阵列、质谱分析、定量蛋白质组学等)、表观基因组分析(ChIPSeq、全基因组亚硫酸盐测序)、和代谢组(基于质谱的代谢物或脂质谱)在不同深度和通量成为实验方法和期刊出版物中的常见做法[4,5]。这些分子分析不仅可以识别出导致疾病状态和结构异常的功能失调基因和/或途径,这些功能失调基因和/或途径可以在肉眼或显微镜下观察到,而且还可以为个性化医疗提供见解。例如,在癌症治疗的精准医学时代,我们已经认识到,不仅患者对特定疗法的敏感性存在差异,而且患者的肿瘤也存在细胞异质性。因此,癌症患者的组织学诊断可以通过分子分析来补充,从而设计出与肿瘤分子特征相匹配的个性化治疗。人们也希望液体活检和人工智能的进步有一天能取代疾病诊断中组织活检的需要,尽管仍存在许多障碍[6]。细胞病理学可以在细胞、细胞器和分子水平上定义,并且可以通过组织学分析、功能分析或分子分析来检测。基因突变、表观遗传改变或代谢功能障碍都可能导致疾病的发病机制。目前,疾病的诊断通常包括体格检查、大体检查、组织学检查和分子检查。以当前的COVID-19为例,该疾病的出现最初是由于SARS-CoV-2感染患者肺部病理异常而引起的[7],最终导致了基于pcr的诊断检测的发展。全面开展细胞和分子研究、体外和体内实验、人体和动物研究,共同了解和抗击新冠肺炎。我们认识到细胞的异常状态可以以多方面的方式呈现,因此我们的《细胞病理学》杂志包含了细胞病理学的解剖学、细胞学、分子学、计算学、机械生物学和有机体研究,因为只有通过包括*Gloria H. Su,美国纽约哥伦比亚大学欧文医学中心赫伯特·欧文综合癌症中心耳鼻咽喉头颈外科病理与细胞生物学系,e-mail: gs2157@cumc.columbia.edu
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comprehensive outlook of Cell Pathology
Pathology is one of the oldest medical disciplines, one that can be arguably rooted early in Egyptian medicine and Traditional Chinese Medicine 5,000 years ago [1,2]. In ancient times, documentation of diseases relied on the understandings of anatomy and observations of abnormalities that deviated from normal physiology. For many centuries ensued, vast knowledge was accumulated from observations of pathological conditions and autopsies, it is this wealth of information that laid the foundation for the modern medicine we see today. In the early beginning, pathology focused on morphological abnormalities. Random documentation of broken bones, abnormal masses, skin discoloration evolved into systematic gross anatomy in modern pathology in the 19th century [2,3]. The invention of the microscope in the 19th century was undoubtedly another force that propelled pathology and medicine forward, moving us from organbased to cell-based pathology with this “new technology”. Along with the microscope, other technological advances such as tissue fixation, embedding, microtomes, and biological stains, all enabled the practice of histopathology possible. However, for a century, despite the improvement of microscopes and a plethora of ancillary diagnostic tests (i.e. electron microscopy, fluorescent microscopy, immunohistochemistry, cytogenetics), the importance of detecting morphological abnormalities remained constant and central to scientific discoveries, journal publications, and patient care as research focuses moved from organs to cells, from organelles to chromosomes. In recent decades, we have seen an explosion of technologies in science, which enabled comparisons of normal vs. diseased states at molecular levels. Soon, analyses of DNA (single nucleotide polymorphism profiling, whole exome sequencing, cell-free DNA screening, etc.), RNA (RNA-Seq, single cell RNA-Seq, miRNA-Seq, ribosome profiling, etc.), protein (protein microarray, mass spectrometry, quantitative proteomics, etc.), epigenome (ChIPSeq, whole-genome bisulphite sequencing), and metabolome (MS-based metabolites or lipid profiles) at various depths and throughputs became a common practice in experimental approaches and journal publications [4,5]. These molecular analyses not only can identify dysfunctional genes and/or pathways that are responsible or have contributed to the diseased state and structural abnormalities that can be visualized grossly or under a microscope, but may also offer insights for personalized medicine. For instance, in the era of precision medicine for cancer treatment, we have come to recognize that not only there are differential sensitivities to a given therapy among patients, there exists cellular heterogeneity in a patient’s tumor. Therefore, a histological diagnosis of cancer in a patient can be complemented by molecular analyses to devise a personalized therapy that matches the tumor’s molecular profile. It is also the hope that advances in liquid biopsies and artificial intelligence will someday replace the need for tissue biopsy in disease diagnosis, although many obstacles remained [6]. Cell pathology can be defined at cellular, organelle, and molecular levels, and can be detected by histological analysis, functional assays, or molecular analyses. Genetic mutations, epigenetic changes, or metabolic dysfunction can all contribute to the pathogenesis of a disease. Presently, diagnosis of a disease often encompasses a combination of physical, gross, histological, and molecular examinations. Take the current COVID-19 as an example, the emergent of the disease was first noted for the abnormal pathology of the lungs in SARS-CoV-2 infected patients [7], which eventually led to the development of PCR-based diagnostic tests. To understand and combat COVID-19 take concerted efforts of comprehensive cellular and molecular investigations, in vitro and in vivo experiments, human and animal studies. We recognize that abnormal state of cells can be presented in a multifaceted manner, therefore it is only fitting that our journal, Cell Pathology, embraces anatomical, cellular, molecular, computation, mechanobiological, and organismal investigations of cell pathology, because only through inclu*Corresponding author: Gloria H. Su, Department of Pathology and Cell Biology, Department of Otolaryngology and Head and Neck Surgery, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, USA, e-mail: gs2157@cumc.columbia.edu
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