-
Pathologie (Heidelberg, Germany) Dec 2023Germ cell tumors (GCTs) are now considered a curable cancer, with a > 95% cure rate in all patients and about 90% cure rate in patients with metastatic disease. The... (Review)
Review
Germ cell tumors (GCTs) are now considered a curable cancer, with a > 95% cure rate in all patients and about 90% cure rate in patients with metastatic disease. The success of physicians in curing the disease is underpinned by multidisciplinary advances. Of relevance in this regard are the nowadays-applied homogeneous terminology based on pathologically better characterized testicular neoplasms and the development of a widely used risk stratification model for metastatic disease introduced by the International Germ Cell Cancer Collaborative Group in 1997 and updated in 2021. Non-pulmonary visceral metastases, high levels of the serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), and primary mediastinal non-seminoma are currently identified as determinants of poor prognosis. In addition, the presence of distinct microRNA profiles between seminomas and non-seminoma GCTs has opened up important perspectives in terms of noninvasive biomarkers that can be used in diagnosis and treatment monitoring.
Topics: Male; Humans; Testicular Neoplasms; alpha-Fetoproteins; Pathology, Molecular; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Seminoma
PubMed: 37975918
DOI: 10.1007/s00292-023-01264-8 -
Virchows Archiv : An International... Feb 2024Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular... (Review)
Review
Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular alterations of tumors of the anterior pituitary, thyroid and parathyroid glands, adrenal cortex, and adrenal medulla and paraganglia. All endocrine gland tumors enjoy a robust correlation between genotype and phenotype. High-throughput molecular analysis demonstrates that endocrine gland tumors can be grouped into molecular groups that are relevant from both pathologic and clinical point of views. In this review, genetic alterations have been discussed and tabulated with respect to their molecular pathogenetic role and clinicopathologic implications, addressing the use of molecular biomarkers for the purpose of diagnosis and prognosis and predicting response to molecular therapy. Hereditary conditions that play a key role in determining predisposition to many types of endocrine tumors are also discussed.
Topics: Humans; Pathology, Molecular; Endocrine Gland Neoplasms; Mutation; Thyroid Gland; Adrenal Gland Neoplasms
PubMed: 38108848
DOI: 10.1007/s00428-023-03713-4 -
International Journal of Molecular... Jul 2023Sarcoidosis is a complex inflammatory multisystem disease of unknown etiology that is characterised by epithelioid cell granulomatous lesions affecting various organs,... (Review)
Review
Sarcoidosis is a complex inflammatory multisystem disease of unknown etiology that is characterised by epithelioid cell granulomatous lesions affecting various organs, mainly the lungs. In general, sarcoidosis is asymptomatic, but some cases result in severe complications and organ failure. So far, no accurate and validated modelling for clinical and pathohistological manifestations of sarcoidosis is suggested. Moreover, knowledge about disease-specific diagnostic markers for sarcoidosis is scarce. For instance, pulmonary granulomatosis is associated with the upregulated production of proinflammatory molecules: TNF-α, IL-6, CXCL1, CCL2, CCL18, CD163, serum angiotensin-converting enzyme (sACE), lysozyme, neopterin, and serum amyloid A (SAA). Quantum dots (QDs) are widely applied for molecular diagnostics of various diseases. QDs are semiconductor nanoparticles of a few nanometres in size, made from ZnS, CdS, ZnSe, etc., with unique physical and chemical properties that are useful for the labelling and detection in biological experiments. QDs can conjugate with various antibodies or oligonucleotides, allowing for high-sensitivity detection of various targets in organs and cells. Our review describes existing experimental models for sarcoidosis (in vitro, in vivo, and in silico), their advantages and restrictions, as well as the physical properties of quantum dots and their potential applications in the molecular diagnostics of sarcoidosis. The most promising experimental models include mice with TSC2 deletion and an in silico multiscale computational model of sarcoidosis (SarcoidSim), developed using transcriptomics and flow cytometry of human sarcoid biopsies. Both models are most efficient to test different candidate drugs for sarcoidosis.
Topics: Humans; Animals; Mice; Sarcoidosis, Pulmonary; Quantum Dots; Pathology, Molecular; Sarcoidosis; Models, Theoretical
PubMed: 37511027
DOI: 10.3390/ijms241411267 -
Current Drug Delivery Jan 2024Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and...
Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and use bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.
PubMed: 38173212
DOI: 10.2174/0115672018286832231218112557 -
Pathologie (Heidelberg, Germany) May 2024Molecular pathological examinations of tumor samples encompass a wide range of diagnostic analyses. Especially in recent years, numerous new biomarkers have come to the... (Review)
Review
BACKGROUND
Molecular pathological examinations of tumor samples encompass a wide range of diagnostic analyses. Especially in recent years, numerous new biomarkers have come to the forefront-the analysis of which is crucial for therapy decisions.
OBJECTIVES
Within the field of molecular pathology, the demands of next generation sequencing (NGS)-based requirements have experienced massive growth in recent years. To meet this demand, methods are constantly being adapted and further developed. The following sections aim to illuminate how this trend arises and which analyses are gaining importance.
METHODS
The article provides an overview of the essential nucleic acid-based analysis techniques in the field of massive parallel sequencing. Terms such as DNA- and RNA-based techniques, as well as the associated analysis methods, are described, particularly with regard to their use in routine molecular pathological diagnostics.
RESULTS
The breadth of genomic sequencing has been steadily growing in recent years, particularly due to the increasing relevance of personalized medicine, along with the rising approvals of targeted therapeutics. This necessitates, among other things, the analysis of new biomarkers. The diagnostics as part of interdisciplinary molecular tumor boards (MTB) are now based on large gene panels (> 1 megabase). Furthermore, through the "Modellvorhaben Genomsequenzierung" § 64e, whole exome or whole genome sequencing has been made available for oncological patients. Given these developments, it is evident that future analyses will require the integration of additional omics fields, such as whole transcriptome analysis, epigenomics, and proteomics.
CONCLUSION
The challenges of personalized medicine along with the necessity of simultaneously assessing numerous new biomarkers require the implementation and execution of new techniques in molecular pathology whose complexity is steadily increasing.
Topics: Humans; High-Throughput Nucleotide Sequencing; Pathology, Molecular; Neoplasms; Biomarkers, Tumor; Precision Medicine
PubMed: 38619582
DOI: 10.1007/s00292-024-01326-5 -
Virchows Archiv : An International... Feb 2024Medical oncology is rapidly evolving with the implementation of personalized, targeted therapies. Advances in molecular diagnostics and the biologic understanding of... (Review)
Review
Medical oncology is rapidly evolving with the implementation of personalized, targeted therapies. Advances in molecular diagnostics and the biologic understanding of cancer pathophysiology led to the identification of specific genetic alterations as drivers of cancer progression. Further, improvements in drug development enable the direct interference with these pathways, which allow tailoring personalized treatments based on a distinct molecular characterization of tumors. Thereby, we are currently experiencing a paradigm-shift in the treatment of cancers towards cancer-type agnostic, molecularly targeted, personalized therapies. However, this concept has several important hurdles and limitations to overcome to ultimately increase the proportion of patients benefitting from the precision oncology approach. These include the assessment of clinical relevancy of identified alterations, capturing and interpreting levels of heterogeneity based on intra-tumoral or time-dependent molecular evolution, and challenges in the practical implementation of precision oncology in routine clinical care. In the present review, we summarize the current state of cancer-agnostic precision oncology, discuss the concept of molecular tumor boards, and consider current limitations of personalized cancer therapy. Further, we provide an outlook towards potential future developments including the implementation of functionality assessments of identified genetic alterations and the broader use of liquid biopsies in order to obtain more comprehensive and longitudinal genetic information that might guide personalized cancer therapy in the future.
Topics: Humans; Neoplasms; Precision Medicine; Pathology, Molecular; Medical Oncology; Oncologists
PubMed: 37982847
DOI: 10.1007/s00428-023-03702-7 -
Molecular Biology Reports Dec 2023SARS-CoV-2, a novel coronavirus within the Coronaviridae family, is the causative agent behind the respiratory ailment referred to as COVID-19. Operating on a global... (Review)
Review
SARS-CoV-2, a novel coronavirus within the Coronaviridae family, is the causative agent behind the respiratory ailment referred to as COVID-19. Operating on a global scale, COVID-19 has led to a substantial number of fatalities, exerting profound effects on both public health and the global economy. The most frequently reported symptoms encompass fever, cough, muscle or body aches, loss of taste or smell, headaches, and fatigue. Furthermore, a subset of individuals may manifest more severe symptoms, including those consistent with viral pneumonitis, which can be so profound as to result in fatalities. Consequently, this situation has spurred the rapid advancement of disease diagnostic technologies worldwide. Predominantly employed in diagnosing COVID-19, the real-time quantitative reverse transcription PCR has been the foremost diagnostic method, effectively detecting SARS-CoV-2 viral RNA. As the pandemic has evolved, antigen and serological tests have emerged as valuable diagnostic tools. Antigen tests pinpoint specific viral proteins of SARS-CoV-2, offering swift results, while serological tests identify the presence of antibodies in blood samples. Additionally, there have been notable strides in sample collection methods, notably with the introduction of saliva-based tests, presenting a non-invasive substitute to nasopharyngeal swabs. Given the ongoing mutations in SARS-CoV-2, there has been a continuous need for genomic surveillance, encompassing full genome sequencing and the identification of new variants through Illumina technology and, more recently, nanopore metagenomic sequencing (SMTN). Consequently, while diagnostic testing methods for COVID-19 have experienced remarkable progress, no test is flawless, and there exist limitations with each technique, including sensitivity, specificity, sample collection, and the minimum viral load necessary for accurate detection. These aspects are comprehensively addressed within this current review.
Topics: Humans; SARS-CoV-2; COVID-19; Pathology, Molecular; Pneumonia, Viral; RNA, Viral; Sensitivity and Specificity; COVID-19 Testing
PubMed: 37817022
DOI: 10.1007/s11033-023-08844-0 -
Applied and Environmental Microbiology Oct 2023is a leading cause of infectious diarrhea in humans and production animals and can be found in a variety of environmental sources. The prevalence and diversity of...
is a leading cause of infectious diarrhea in humans and production animals and can be found in a variety of environmental sources. The prevalence and diversity of multi-locus sequence type clade 5 strains of in Australian production animals suggest Australia might be the ancestral home of this lineage of One Health importance. To better understand the role of the environment in the colonization of humans and animals in Australia, it is important to investigate these endemic sources. This study describes the prevalence, molecular epidemiology, and biogeographic distribution of in soils of Western Australia. A total of 321 soil samples from remote geographical locations across the eight health regions of Western Australia were screened for and isolates characterized by PCR ribotyping and toxin gene profiling. was isolated from 31.15% of samples, with the highest prevalence in the Perth Metropolitan Health Region (49.25%, = 33/67). Overall, 52 different strains [PCR ribotypes (RTs)] were identified, with 14 being novel, and 38% (38/100) of isolates being toxigenic, the most common of which was RT014/020. Five unique novel isolates showed characteristics similar to clade 5. This is the first study of isolated from soils in Australia. The high prevalence and heterogeneity of strains recovered suggest that soils play a role in the survival and environmental dissemination of this organism, and potentially its transmission among native wildlife and production animals, and in community and hospital settings.IMPORTANCE is a pathogen of One Health importance. To better understand the role of the environment in human and animal colonization/infection, it is critical that autochthonous reservoirs/sources of be investigated. This is the first study of isolated from soils of Western Australia (WA). Here, the ecology of in WA is described by examining the geographic distribution, molecular epidemiology, and diversity of isolated from soils across WA.
Topics: Animals; Humans; Australia; Clostridioides difficile; Clostridioides; Molecular Epidemiology; Clostridium Infections; Ribotyping; Clostridium
PubMed: 37823643
DOI: 10.1128/aem.00379-23 -
The Journal of Molecular Diagnostics :... Dec 2023The use of clinical molecular diagnostic methods for detecting microbial pathogens continues to expand and, in some cases, supplant conventional identification methods... (Review)
Review
Exploring the Utility of Multiplex Infectious Disease Panel Testing for Diagnosis of Infection in Different Body Sites: A Joint Report of the Association for Molecular Pathology, American Society for Microbiology, Infectious Diseases Society of America, and Pan American Society for Clinical...
The use of clinical molecular diagnostic methods for detecting microbial pathogens continues to expand and, in some cases, supplant conventional identification methods in various scenarios. Analytical and clinical benefits of multiplex molecular panels for the detection of respiratory pathogens have been demonstrated in various studies. The use of these panels in managing different patient populations has been incorporated into clinical guidance documents. The Association for Molecular Pathology's Infectious Diseases Multiplex Working Group conducted a review of the current benefits and challenges to using multiplex PCR for the detection of pathogens from gastrointestinal tract, central nervous system, lower respiratory tract, and joint specimens. The Working Group also discusses future directions and novel approaches to detection of pathogens in alternate specimen types, and outlines challenges associated with implementation of these multiplex PCR panels.
Topics: Humans; United States; Pathology, Molecular; Molecular Diagnostic Techniques; Multiplex Polymerase Chain Reaction; Communicable Diseases
PubMed: 37757952
DOI: 10.1016/j.jmoldx.2023.08.005 -
Pathologie (Heidelberg, Germany) May 2024
Topics: Humans; Austria; Pathology, Molecular; Pathology, Clinical; Societies, Medical
PubMed: 38661930
DOI: 10.1007/s00292-024-01325-6