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Biomedicines Apr 2024In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac... (Review)
Review
In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac inflammation of the myocardium in the absence of multiorgan involvement and with a poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. The revision of original histologic sections by Schmorl showed cases with lymphocytes and others with giant-cell inflammatory histotypes. The in vivo diagnosis of myocarditis became possible thanks to right cardiac catheterization with endomyocardial biopsy (EMB). The gold standard for diagnosis was achieved with the employment of immunohistochemistry and molecular investigation by Polymerase Chain Reaction (PCR), which allows for the detection of viruses as causal agents. Both RNA and DNA were revealed to be cardiotropic, with a common receptor (CAR). A protease, coded by coxsackie virus, disrupts the cytoskeleton and accounts for cell death. Unfortunately, vaccination, despite having been revealed to be effective in animal experiments, has not yet entered the clinical field for prevention. Cardiac Magnetic Resonance turned out to be a revolutionary tool for in vivo diagnosis through the detection of edema (inflammatory exudate). Myocarditis may be fulminant in terms of clinical presentation but not necessarily fatal. The application of ExtraCorporeal Membrane Oxygenation (ECMO) allows for relieving the overloaded native heart.
PubMed: 38672187
DOI: 10.3390/biomedicines12040832 -
Neuro-oncology Oct 2023In the 5th edition of the WHO CNS tumor classification (CNS5, 2021), multiple molecular characteristics became essential diagnostic criteria for many additional CNS...
In the 5th edition of the WHO CNS tumor classification (CNS5, 2021), multiple molecular characteristics became essential diagnostic criteria for many additional CNS tumor types. For those tumors, an integrated, "histomolecular" diagnosis is required. A variety of approaches exists for determining the status of the underlying molecular markers. The present guideline focuses on the methods that can be used for assessment of the currently most informative diagnostic and prognostic molecular markers for the diagnosis of gliomas, glioneuronal and neuronal tumors. The main characteristics of the molecular methods are systematically discussed, followed by recommendations and information on available evidence levels for diagnostic measures. The recommendations cover DNA and RNA next-generation-sequencing, methylome profiling, and select assays for single/limited target analyses, including immunohistochemistry. Additionally, because of its importance as a predictive marker in IDH-wildtype glioblastomas, tools for the analysis of MGMT promoter methylation status are covered. A structured overview of the different assays with their characteristics, especially their advantages and limitations, is provided, and requirements for input material and reporting of results are clarified. General aspects of molecular diagnostic testing regarding clinical relevance, accessibility, cost, implementation, regulatory, and ethical aspects are discussed as well. Finally, we provide an outlook on new developments in the landscape of molecular testing technologies in neuro-oncology.
Topics: Humans; Brain Neoplasms; Pathology, Molecular; Mutation; Glioma; World Health Organization
PubMed: 37279174
DOI: 10.1093/neuonc/noad100 -
Clinics in Laboratory Medicine Jun 2024Gliomas are the most common adult and pediatric primary brain tumors. Molecular studies have identified features that can enhance diagnosis and provide biomarkers.... (Review)
Review
Gliomas are the most common adult and pediatric primary brain tumors. Molecular studies have identified features that can enhance diagnosis and provide biomarkers. IDH1/2 mutation with ATRX and TP53 mutations defines diffuse astrocytomas, whereas IDH1/2 mutations with 1p19q loss defines oligodendroglioma. Focal amplifications of receptor tyrosine kinase genes, TERT promoter mutation, and loss of chromosomes 10 and 13 with trisomy of chromosome 7 are characteristic features of glioblastoma and can be used for diagnosis. BRAF gene fusions and mutations in low-grade gliomas and histone H3 mutations in high-grade gliomas also can be used for diagnostics.
Topics: Humans; Biomarkers, Tumor; Brain Neoplasms; Glioma; Isocitrate Dehydrogenase; Mutation; Brain
PubMed: 38821638
DOI: 10.1016/j.cll.2023.08.009 -
International Journal of Molecular... Nov 2023This Special Issue of the () focuses on 'Genetic and Molecular Regulations of Neuronal Activity' [...].
This Special Issue of the () focuses on 'Genetic and Molecular Regulations of Neuronal Activity' [...].
PubMed: 38003381
DOI: 10.3390/ijms242216191 -
Histopathology Jan 2024Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational... (Review)
Review
Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational research and new drug development, which has promoted our understanding of the molecular pathology of lung cancer. According to the driver alterations, different characteristics have been revealed, such as differences in ethnic prevalence, median age and alteration patterns. Consequently, beyond traditional chemoradiotherapy, molecular-targeted therapy and treatment with immune check-point inhibitors (ICI) also became available major therapeutic options. Interestingly, clinical results suggest that the recently established therapies target distinct lung cancer proportions, particularly between the EGFR/ALK and PD-1/PD-L1-positive subsets, e.g. the kinase inhibitors target driver mutation-positive tumours, whereas driver mutation-negative tumours respond to ICI treatment. These therapeutic efficacy-related differences might be explained by the molecular pathogenesis of lung cancer. Addictive driver mutations promote tumour formation with powerful transformation performance, resulting in a low tumour mutation burden, reduced immune surveillance, and subsequent poor response to ICIs. In contrast, regular tobacco smoke exposure repeatedly injures the proximal airway epithelium, leading to accumulated genetic alterations. In the latter pathway, overgrowth due to alteration and immunological exclusion against neoantigens is initially balanced. However, tumours could be generated from certain clones that outcompete immunological exclusion and outgrow the others. Consequently, this cancer type responds to immune check-point treatment. These pathogenic differences are explained well by the two-compartment model, focusing upon the anatomical and functional composition of distinct cellular components between the terminal respiratory unit and the air-conducting system.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Pathology, Molecular; Lung Neoplasms; Carcinoma; Mutation; B7-H1 Antigen
PubMed: 37936491
DOI: 10.1111/his.15080 -
Clinics in Laboratory Medicine Jun 2024
Topics: Humans; Pathology, Molecular; Molecular Diagnostic Techniques
PubMed: 38821650
DOI: 10.1016/j.cll.2024.03.001 -
Expert Review of Molecular Diagnostics 2023Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell neoplasms characterized by the driver mutations JAK2, CALR, and MPL. These... (Review)
Review
INTRODUCTION
Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell neoplasms characterized by the driver mutations JAK2, CALR, and MPL. These mutations cause constitutive activation of JAK-STAT signaling, which is central to pathogenesis of MPNs. Next-generation sequencing has further expanded the molecular landscape allowing for improved diagnostics, prognostication, and targeted therapy.
AREAS COVERED
This review aims to address current understanding of the molecular diagnosis of MPN not only through improved awareness of the driver mutations but also the disease modifying mutations. In addition, other genetic factors such as clonal hematopoiesis of indeterminate potential (CHIP), order of mutation, and mutation co-occurrence are discussed and how these factors influence disease initiation and ultimately progression. How this molecular information is incorporated into risk stratification models allowing for earlier intervention and targeted therapy in the future will be addressed further.
EXPERT OPINION
The genomic landscape of the MPN has evolved in the last 15 years with integration of next-generation sequencing becoming the gold standard of MPN management. Although diagnostics and prognostication have become more personalized, additional studies are required to translate these molecular findings into targeted therapy therefore improving patient outcomes.
Topics: Humans; Pathology, Molecular; Myeloproliferative Disorders; Signal Transduction; Mutation; Genomics; Neoplasms
PubMed: 37999991
DOI: 10.1080/14737159.2023.2277370 -
Clinics in Laboratory Medicine Jun 2024Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and... (Review)
Review
Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and genomic heterogeneity. It typically harbors high rates of somatic mutations with considerable genomic and transcriptional complexity and heterogeneity that is reflective of its varied histomorphologic and clinical features. This review provides an update on the recent advances in the molecular characterization and novel molecular taxonomy of urothelial carcinoma and variant histologies.
Topics: Humans; Carcinoma, Transitional Cell; Mutation; Urinary Bladder Neoplasms; Urologic Neoplasms; Urothelium
PubMed: 38821640
DOI: 10.1016/j.cll.2023.08.010 -
Drug Discovery Today Dec 2023Dysbiosis-associated molecular pathology is significantly involved in developing and perpetuating metabolic disorders, disrupting host energy regulation, and triggering... (Review)
Review
Dysbiosis-associated molecular pathology is significantly involved in developing and perpetuating metabolic disorders, disrupting host energy regulation, and triggering inflammatory signaling cascades, insulin resistance, and metabolic dysfunction. Concurrently, numerous phytoconstituents are able to interact with the gut microbiota and produce bioactive metabolites that influence host cellular pathways, inflammation, and metabolic processes. These effects include improved insulin sensitivity, lipid metabolism regulation, and suppression of chronic inflammation, highlighting the therapeutic potential of phytoconstituents against metabolic abnormalities. Understanding this symbiotic relationship and the underlying molecular cascades offers innovative strategies for tailored interventions and promising therapeutic approaches to address the growing burden of metabolic disease.
Topics: Humans; Gastrointestinal Microbiome; Inflammation; Insulin Resistance; Metabolic Diseases
PubMed: 37949428
DOI: 10.1016/j.drudis.2023.103824 -
Child's Nervous System : ChNS :... Sep 2023Pineal parenchymal tumors in children are rare. They consist of two main types, pineoblastoma (PB) and pineal parenchymal tumor of intermediate differentiation (PPTID),... (Review)
Review
Pineal parenchymal tumors in children are rare. They consist of two main types, pineoblastoma (PB) and pineal parenchymal tumor of intermediate differentiation (PPTID), which are World Health Organization (WHO) grade 4 and grade 2-3 respectively. PBs are divided into four distinct molecular groups: PB-miRNA1, PB-miRNA2, PB-RB1, and PB-MYC/FOXR2. PB-RB1 and PB-MYC/FOXR2 affect young children and are associated with a dismal prognosis. PB-miRNA1 and PB-miRNA2 groups affect older children and follow a more favorable course. They are characterized by mutually exclusive alterations in genes involved in miRNA biogenesis, including DICER1, DROSHA, and DGCR8. They may be sporadic or may represent one manifestation of DICER1 syndrome. PB-RB1 tumors show alterations in the RB1 gene and may develop in the setting of congenital retinoblastoma, a condition known as "trilateral retinoblastoma." In the pediatric population, PPTIDs typically affect adolescents. They are characterized by small in-frame insertions in the KBTBD4 gene which is involved in ubiquitination.
Topics: Adolescent; Humans; Child; Child, Preschool; Pinealoma; Brain Neoplasms; Pineal Gland; Pathology, Molecular; Retinoblastoma; MicroRNAs; RNA-Binding Proteins; Retinal Neoplasms; Ribonuclease III; DEAD-box RNA Helicases; Forkhead Transcription Factors
PubMed: 35972537
DOI: 10.1007/s00381-022-05637-x