RESUMO
A negative multiparametric magnetic resonance imaging (mpMRI)-guided prostate biopsy in patients with suspected prostate cancer (PC) results in clinical uncertainty, as the biopsy can be false negative. The clinical challenge is to determine the optimal follow-up and to select patients who will benefit from repeat biopsy. In this study, we evaluated the rate of significant PC (sPC, Gleason score ≥7) and PC detection in patients who received a follow-up mpMRI/ultrasound-guided biopsy for persistent PC suspicion after a negative mpMRI/ultrasound-guided biopsy. We identified 58 patients at our institution that underwent repeat targeted biopsy in case of PI-RADS lesions and systematic saturation biopsy between 2014 and 2022. At the initial biopsy, the median age was 59 years, and the median prostate specific antigen level was 6.7 ng/mL. Repeat biopsy after a median of 18 months detected sPC in 3/58 (5%) patients and Gleason score 6 PC in 11/58 (19%). Among 19 patients with a downgraded PI-RADS score at the follow-up mpMRI, none had sPC. In conclusion, men with an initial negative mpMRI/ultrasound-guided biopsy had a high likelihood of not harboring sPC at repeat biopsy (95%). Due to the small size of the study, further research is recommended.
RESUMO
Precise clonal and functional assessments of the T cell receptor (TCR) repertoire diversity require paired TCRα and TCRß gene sequence information at monoclonal level. However, available single-cell strategies are typically limited in throughput and often do not provide full-length DNA templates for direct gene cloning. Here, we describe a high-throughput strategy for the unbiased amplification and automated sequence analysis of paired TCRα and TCRß genes from primary mouse T cells. The platform links cell phenotype and TCR gene sequence information at single-cell level. Furthermore, it enables direct functional analyses through the efficient cloning of both genes and the generation of stable TCR expressing cell lines. This highly efficient workflow is a powerful tool to determine the diversity and quality of the murine T-cell repertoire in various settings, for example in vaccine development, infectious diseases, autoimmunity, or cancer.
Assuntos
Genes Codificadores da Cadeia alfa de Receptores de Linfócitos T/genética , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Linfócitos T/fisiologia , Animais , Células Clonais , Camundongos , Fenótipo , Análise de Célula ÚnicaRESUMO
Short linear motifs (SLiMs) are protein binding modules that play major roles in almost all cellular processes. SLiMs are short, often highly degenerate, difficult to characterize and hard to detect. The eukaryotic linear motif (ELM) resource (elm.eu.org) is dedicated to SLiMs, consisting of a manually curated database of over 275 motif classes and over 3000 motif instances, and a pipeline to discover candidate SLiMs in protein sequences. For 15 years, ELM has been one of the major resources for motif research. In this database update, we present the latest additions to the database including 32 new motif classes, and new features including Uniprot and Reactome integration. Finally, to help provide cellular context, we present some biological insights about SLiMs in the cell cycle, as targets for bacterial pathogenicity and their functionality in the human kinome.
Assuntos
Bases de Dados de Proteínas , Células Eucarióticas/metabolismo , Interações Hospedeiro-Patógeno/genética , Anotação de Sequência Molecular , Proteínas/química , Software , Motivos de Aminoácidos , Animais , Bactérias/genética , Bactérias/metabolismo , Sítios de Ligação , Ciclo Celular/genética , Células Eucarióticas/citologia , Células Eucarióticas/microbiologia , Células Eucarióticas/virologia , Fungos/genética , Fungos/metabolismo , Humanos , Internet , Modelos Moleculares , Plantas/genética , Plantas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas/genética , Proteínas/metabolismo , Vírus/genética , Vírus/metabolismoRESUMO
Hyaluronan (HA) is a simple but diverse glycosaminoglycan. It plays a major role in aging, cellular senescence, cancer, and tissue homeostasis. In which way HA affects the surrounding tissues greatly depends on the molecular weight of HA. Whereas high molecular weight HA is associated with homeostasis and protective effects, HA fragments tend to be linked to the pathologic state. Furthermore, the interaction of HA with its binding partners, the hyaladherins, such as CD44, is essential for sustaining tissue integrity and is likewise related to cancer. The naked mole rat, a rodent species, possesses a special form of very high molecular weight (vHMW) HA, which is associated with the extraordinary cancer resistance and longevity of those animals. This review addresses HA and its diverse facets: from HA synthesis to degradation, from oligomeric HA to vHMW-HA and from its beneficial properties to the involvement in pathologies. We further discuss the functions of HA in the naked mole rat and compare them to human conditions. Though intensively researched, this simple polymer bears some secrets that may hold the key for a better understanding of cellular processes and the development of diseases, such as cancer.
