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International Journal of Molecular... Apr 2022Retinitis pigmentosa (RP) is genetically heterogeneous retinopathy caused by photoreceptor cell death and retinal pigment epithelial atrophy that eventually results in... (Review)
Review
Retinitis pigmentosa (RP) is genetically heterogeneous retinopathy caused by photoreceptor cell death and retinal pigment epithelial atrophy that eventually results in blindness in bilateral eyes. Various photoreceptor cell death types and pathological phenotypic changes that have been disclosed in RP demand in-depth research of its pathogenic mechanism that may account for inter-patient heterogeneous responses to mainstream drug treatment. As the primary method for studying the genetic characteristics of RP, molecular biology has been widely used in disease diagnosis and clinical trials. Current technology iterations, such as gene therapy, stem cell therapy, and optogenetics, are advancing towards precise diagnosis and clinical applications. Specifically, technologies, such as effective delivery vectors, CRISPR/Cas9 technology, and iPSC-based cell transplantation, hasten the pace of personalized precision medicine in RP. The combination of conventional therapy and state-of-the-art medication is promising in revolutionizing RP treatment strategies. This article provides an overview of the latest research on the pathogenesis, diagnosis, and treatment of retinitis pigmentosa, aiming for a convenient reference of what has been achieved so far.
Topics: Genetic Therapy; Humans; Induced Pluripotent Stem Cells; Pathology, Molecular; Photoreceptor Cells; Retinitis Pigmentosa
PubMed: 35563274
DOI: 10.3390/ijms23094883 -
Cold Spring Harbor Perspectives in... Mar 2022This overview of the molecular pathology of lung cancer includes a review of the most salient molecular alterations of the genome, transcriptome, and the epigenome. The... (Review)
Review
This overview of the molecular pathology of lung cancer includes a review of the most salient molecular alterations of the genome, transcriptome, and the epigenome. The insights provided by the growing use of next-generation sequencing (NGS) in lung cancer will be discussed, and interrelated concepts such as intertumor heterogeneity, intratumor heterogeneity, tumor mutational burden, and the advent of liquid biopsy will be explored. Moreover, this work describes how the evolving field of molecular pathology refines the understanding of different histologic phenotypes of non-small-cell lung cancer (NSCLC) and the underlying biology of small-cell lung cancer. This review will provide an appreciation for how ongoing scientific findings and technologic advances in molecular pathology are crucial for development of biomarkers, therapeutic agents, clinical trials, and ultimately improved patient care.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; High-Throughput Nucleotide Sequencing; Humans; Liquid Biopsy; Lung Neoplasms; Mutation; Pathology, Molecular
PubMed: 34751163
DOI: 10.1101/cshperspect.a037812 -
Neuro-oncology Aug 2021The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the... (Review)
Review
The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.
Topics: Brain; Central Nervous System; Central Nervous System Neoplasms; Humans; Pathology, Molecular; World Health Organization
PubMed: 34185076
DOI: 10.1093/neuonc/noab106 -
International Journal of Molecular... May 2022Similar to other malignancies, TCGA network efforts identified the detailed genomic picture of skin melanoma, laying down the basis of molecular classification. On the... (Review)
Review
Similar to other malignancies, TCGA network efforts identified the detailed genomic picture of skin melanoma, laying down the basis of molecular classification. On the other hand, genome-wide association studies discovered the genetic background of the hereditary melanomas and the susceptibility genes. These genetic studies helped to fine-tune the differential diagnostics of malignant melanocytic lesions, using either FISH tests or the myPath gene expression signature. Although the original genomic studies on skin melanoma were mostly based on primary tumors, data started to accumulate on the genetic diversity of the progressing disease. The prognostication of skin melanoma is still based on staging but can be completed with gene expression analysis (DecisionDx). Meanwhile, this genetic knowledge base of skin melanoma did not turn to the expected wide array of target therapies, except the BRAF inhibitors. The major breakthrough of melanoma therapy was the introduction of immune checkpoint inhibitors, which showed outstanding efficacy in skin melanoma, probably due to their high immunogenicity. Unfortunately, beyond , mutations and tumor mutation burden, no clinically validated predictive markers exist in melanoma, although several promising biomarkers have been described, such as the expression of immune-related genes or mutations in the IFN-signaling pathway. After the initial success of either target or immunotherapies, sooner or later, relapses occur in the majority of patients, due to various induced genetic alterations, the diagnosis of which could be developed to novel predictive genetic markers.
Topics: Genome-Wide Association Study; Humans; Melanoma; Pathology, Molecular; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35628196
DOI: 10.3390/ijms23105384 -
Journal of Thoracic Oncology : Official... Jan 2023We review research regarding the epidemiology, risk factors, genetic susceptibility, molecular pathology, and early detection of SCLC, a deadly tumor that accounts for... (Review)
Review
We review research regarding the epidemiology, risk factors, genetic susceptibility, molecular pathology, and early detection of SCLC, a deadly tumor that accounts for 14% of lung cancers. We first summarize the changing incidences of SCLC globally and in the United States among males and females. We then review the established risk factor (i.e., tobacco smoking) and suspected nonsmoking-related risk factors for SCLC, and emphasize the importance of continued effort in tobacco control worldwide. Review of genetic susceptibility and molecular pathology suggests different molecular pathways in SCLC development compared with other types of lung cancer. Last, we comment on the limited utility of low-dose computed tomography screening in SCLC and on several promising blood-based molecular biomarkers as potential tools in SCLC early detection.
Topics: Male; Female; Humans; Lung Neoplasms; Genetic Predisposition to Disease; Pathology, Molecular; Early Detection of Cancer; Risk Factors; Small Cell Lung Carcinoma
PubMed: 36243387
DOI: 10.1016/j.jtho.2022.10.002 -
Technology in Cancer Research &... 2020This review aims to summarize the latest knowledge on factors, diagnosis, and treatment of pancreatic cancer, and aims to promote further research on this under-studied... (Review)
Review
This review aims to summarize the latest knowledge on factors, diagnosis, and treatment of pancreatic cancer, and aims to promote further research on this under-studied malignant tumor. At present, we urgently need to identify high-risk patients with precancerous diseases through screening approaches, so that medical professionals and the general public may better understand prevention strategies or early detection measures. Pancreatic cancer is a highly invasive malignant tumor with a fatal risk, mainly seen in men and older adults (60-85 years old). Pancreatic cancer is now increasingly observed in young patients. Because the disease has no early symptoms and can quickly invade surrounding tissues and organs, it is one of the deadliest cancers. With a view to identify the important factors for the development of pancreatic cancer, previous studies have found that smoking, alcohol, and chronic pancreatitis are considered high-risk factors. Recent studies have shown that abnormal metabolism of human microorganisms, blood type, and glucose and lipid levels are also important factors in the development of pancreatic cancer. Identifying early diagnosis options is an important way to improve detection and survival rates of pancreatic cancer. None of the many tumor markers associated with pancreatic cancer are highly specific, which also indicates further research is required to improve the early detection rate. Future directions in terms of treatment evaluating the relationship between the microbiology-free system and immunotherapy will bring a major breakthrough and is expected to bring exciting clinical applications in improving the life-cycle of pancreatic cancer patients.
Topics: Animals; Biomarkers, Tumor; Combined Modality Therapy; Diagnostic Imaging; Disease Management; Disease Susceptibility; Endoscopy; Genetic Predisposition to Disease; Humans; Pancreatic Neoplasms; Pathology, Molecular; Prognosis; Risk Factors; Treatment Outcome
PubMed: 33357065
DOI: 10.1177/1533033820962117 -
International Journal of Molecular... Sep 2023Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by... (Review)
Review
Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by changes in bone homeostasis, which lead to reduced bone mass, impaired bone quality, and an increased risk of fractures. The pathophysiology of osteoporosis is complex and multifactorial, involving imbalances in hormones, cytokines, and growth factors. Understanding the cellular and molecular mechanisms underlying osteoporosis is essential for appropriate diagnosis and management of the condition. This paper provides a comprehensive review of the normal cellular and molecular mechanisms of bone homeostasis, followed by an in-depth discussion of the proposed pathophysiology of osteoporosis through the osteoimmunological, gut microbiome, and cellular senescence models. Furthermore, the diagnostic tools used to assess osteoporosis, including bone mineral density measurements, biochemical markers of bone turnover, and diagnostic imaging modalities, are also discussed. Finally, both the current pharmacological and non-pharmacological treatment algorithms and management options for osteoporosis, including an exploration of the management of osteoporotic fragility fractures, are highlighted. This review reveals the need for further research to fully elucidate the molecular mechanisms underlying the condition and to develop more effective therapeutic strategies.
Topics: Humans; Pathology, Molecular; Osteoporosis; Osteoporotic Fractures; Bone Density; Bone and Bones
PubMed: 37834025
DOI: 10.3390/ijms241914583 -
BMJ (Clinical Research Ed.) Oct 2023Although the past two decades have produced exciting discoveries in the genetics and pathology of amyotrophic lateral sclerosis (ALS), progress in developing an... (Review)
Review
Although the past two decades have produced exciting discoveries in the genetics and pathology of amyotrophic lateral sclerosis (ALS), progress in developing an effective therapy remains slow. This review summarizes the critical discoveries and outlines the advances in disease characterization, diagnosis, imaging, and biomarkers, along with the current status of approaches to ALS care and treatment. Additional knowledge of the factors driving disease progression and heterogeneity will hopefully soon transform the care for patients with ALS into an individualized, multi-prong approach able to prevent disease progression sufficiently to allow for a dignified life with limited disability.
Topics: Humans; Amyotrophic Lateral Sclerosis; Pathology, Molecular; Disease Progression
PubMed: 37890889
DOI: 10.1136/bmj-2023-075037 -
Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges.Genes Jun 2020Identification of the cystic fibrosis transmembrane conductance regulator gene and its numerous variants opened the way to fantastic breakthroughs in diagnosis,... (Review)
Review
Identification of the cystic fibrosis transmembrane conductance regulator gene and its numerous variants opened the way to fantastic breakthroughs in diagnosis, research and treatment of cystic fibrosis (CF). The current and future challenges of molecular diagnosis of CF and CFTR-related disorders and of genetic counseling are here reviewed. Technological advances have enabled to make a diagnosis of CF with a sensitivity of 99% by using next generation sequencing in a single step. The detection of heretofore unidentified variants and ethnic-specific variants remains challenging, especially for newborn screening (NBS), CF carrier testing and genotype-guided therapy. Among the criteria for assessing the impact of variants, population genetics data are insufficiently taken into account and the penetrance of CF associated with variants remains poorly known. The huge diversity of diagnostic and genetic counseling indications for studies makes assessment of variant disease-liability critical. This is especially discussed in the perspective of wide genome analyses for NBS and CF carrier screening in the general population, as future challenges.
Topics: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Genetic Counseling; Genotype; Humans; Infant, Newborn; Neonatal Screening; Pathology, Molecular; Penetrance
PubMed: 32512765
DOI: 10.3390/genes11060619 -
International Journal of Molecular... Mar 2023Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative... (Review)
Review
Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions.
Topics: Humans; Pathology, Molecular; Oxidative Stress; Sleep Apnea, Obstructive; Antioxidants; Biomarkers; Hypoxia
PubMed: 36982552
DOI: 10.3390/ijms24065478