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Ageing Research Reviews May 2017The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline... (Review)
Review
The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome. But for a new chemical entity, knowing what endpoints to measure remains a formidable challenge. For economy's sake, and to achieve results in a reasonable time frame, surrogate markers of lifespan and healthy aging are desperately needed. This review provides a comprehensive analysis of molecular endpoints that are currently being used as indices of age-related phenomena (e.g., morbidity, frailty, mortality) and proposes an approach for validating and prioritizing these endpoints.
Topics: Aging; Biomarkers; Humans; Life Expectancy; Longevity; Pathology, Molecular
PubMed: 27721062
DOI: 10.1016/j.arr.2016.09.012 -
Clinics in Laboratory Medicine Jun 2024
Topics: Humans; Pathology, Molecular; Molecular Diagnostic Techniques
PubMed: 38821650
DOI: 10.1016/j.cll.2024.03.001 -
Archives of Pathology & Laboratory... Mar 2018- In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the...
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
CONTEXT
- In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing.
OBJECTIVE
- To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update.
DESIGN
- The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations.
RESULTS
- Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline.
CONCLUSIONS
- The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes ( ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.
Topics: Humans; Antineoplastic Agents; Genetic Testing; Lung Neoplasms; Molecular Targeted Therapy; Pathology, Molecular; Patient Selection; Protein Kinase Inhibitors; United States; Systematic Reviews as Topic
PubMed: 29355391
DOI: 10.5858/arpa.2017-0388-CP -
Molecular Oncology Oct 2014Molecular Pathology (MP) is at the heart of modern diagnostics and translational research, but the controversy on how MP is best developed has not abated. The lack of a... (Review)
Review
Molecular Pathology (MP) is at the heart of modern diagnostics and translational research, but the controversy on how MP is best developed has not abated. The lack of a proper model or trained pathologists to support the diagnostic and research missions makes MP a rare commodity overall. Here we analyse the scientific and technology areas, in research and diagnostics, which are encompassed by MP of solid tumours; we highlight the broad overlap of technologies and analytical capabilities in tissue research and diagnostics; and we describe an integrated model that rationalizes technical know-how and pathology talent for both. The model is based on a single, accredited laboratory providing a single standard of high-quality for biomarker discovery, biomarker validation and molecular diagnostics.
Topics: Animals; Biomarkers, Tumor; Computational Biology; Humans; Neoplasms; Pathology, Molecular; Tissue Banks; Translational Research, Biomedical
PubMed: 25160635
DOI: 10.1016/j.molonc.2014.07.021 -
Surgical Pathology Clinics Sep 2021
Topics: Humans; Molecular Diagnostic Techniques; Pathology, Molecular
PubMed: 34373102
DOI: 10.1016/j.path.2021.05.014 -
International Journal of Molecular... Mar 2023Molecular pathology, diagnostics and therapeutics are three closely related topics of critical importance in medical research and clinical practice [...].
Molecular pathology, diagnostics and therapeutics are three closely related topics of critical importance in medical research and clinical practice [...].
Topics: Pathology, Molecular
PubMed: 36902493
DOI: 10.3390/ijms24055063 -
Clinics in Laboratory Medicine Dec 2013This article provides an overview of the application of molecular diagnostic methods to red cell and platelet compatibility testing. The advantages and limitations of... (Review)
Review
This article provides an overview of the application of molecular diagnostic methods to red cell and platelet compatibility testing. The advantages and limitations of molecular methods are evaluated compared with traditional serologic methods. The molecular bases of clinically significant red cell and platelet antigens are presented. Current recommendations for reporting molecular assay results and distinctions between genotype and phenotype are discussed.
Topics: Humans; Pathology, Molecular; Transfusion Medicine
PubMed: 24267187
DOI: 10.1016/j.cll.2013.08.004 -
Current Molecular Medicine 2019Over the last few years, we have seen constant development of molecular pathology for the care of patients with cancer. The information obtained from molecular data has... (Review)
Review
Over the last few years, we have seen constant development of molecular pathology for the care of patients with cancer. The information obtained from molecular data has transformed our thinking about the biological diversity of cancers, particularly in the field of ophthalmic oncology. It has reoriented the way in which therapeutic decisions and decisions concerning patient surveillance are made, both in the area of pediatric cancers, including rhabdomyosarcoma and retinoblastoma, and adult cancers, such as uveal melanoma and lymphomas. A better definition of the molecular classification of these cancers and of the different biological pathways involved is essential to the understanding of both the pathologist and the onco-ophthalmologist. Molecular tests based on targeted or expanded analysis of gene panels are now available. These tests can be performed with tumor tissue or biofluids (especially blood) to predict the prognosis of tumors and, above all, the benefit of targeted therapies, immunotherapy or even chemotherapy. Looking for the BAP1 mutation in uveal melanoma is essential because of the associated metastatic risk. When treating retinoblastoma, it is mandatory to assess the heritable status of RB1. Conjunctival melanoma requires investigation into the BRAF mutation in the case of a locally advanced tumor. The understanding of genomic alterations, the results of molecular tests and/or other biological tests predictive of a therapeutic response, but also of the limits of these tests with respect to the available biological resources, represents a major challenge for optimal patient management in ophthalmic oncology. In this review, we present the current state of knowledge concerning the different molecular alterations and therapeutic targets of interest in ophthalmic oncology.
Topics: Animals; Biomarkers, Tumor; Diagnosis, Differential; Disease Susceptibility; Eye Neoplasms; Humans; Molecular Diagnostic Techniques; Neoplasm Grading; Neoplasm Staging; Pathology, Molecular; Phenotype; Pigmentation
PubMed: 31418658
DOI: 10.2174/1566524019666190726161044 -
Virchows Archiv : An International... Aug 2017The raid evolution in molecular pathology resulting in an increasing complexity requires careful reporting. The need for standardisation is clearer than ever. While... (Review)
Review
The raid evolution in molecular pathology resulting in an increasing complexity requires careful reporting. The need for standardisation is clearer than ever. While synoptic reporting was first used for reporting hereditary genetic diseases, it is becoming more frequent in pathology, especially molecular pathology reports too. The narrative approach is no longer feasible with the growing amount of essential data present on the report, although narrative components are still necessary for interpretation in molecular pathology. On the way towards standardisation of reports, guidelines can be a helpful tool. There are several guidelines that focus on reporting in the field of hereditary diseases, but it is not always feasible to extrapolate these to the reporting of somatic variants in molecular pathology. The rise of multi-gene testing causes challenges for the laboratories. In order to provide a continuous optimisation of the laboratory testing process, including reporting, external quality assessment is essential and has already proven to improve the quality of reports. In general, a clear and concise report for molecular pathology can be created by including elements deemed important by different guidelines, adapting the report to the process flows of the laboratory and integrating the report with the laboratory information management system and the patient record.
Topics: Humans; Pathology, Molecular; Research Design
PubMed: 28343306
DOI: 10.1007/s00428-017-2108-0 -
Der Pathologe Mar 2015
Topics: Forecasting; Germany; Humans; Neoplasms; Pathology, Molecular; Quality Assurance, Health Care
PubMed: 25758105
DOI: 10.1007/s00292-015-0008-0