DNA Damage: From Threat to Treatment

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1665 - 1665

Published: July 10, 2020

DNA is the source of genetic information, and preserving its integrity essential in order to sustain life. The genome continuously threatened by different types lesions, such as abasic sites, mismatches, interstrand crosslinks, or single-stranded double-stranded breaks. As a consequence, cells have evolved specialized damage response (DDR) mechanisms integrity. By orchestrating multilayer signaling cascades specific for type lesion that occurred, DDR ensures information preserved overtime. In last decades, repair been thoroughly investigated untangle these complex networks pathways processes. result, key factors identified control coordinate circuits time space. first part this review, we describe critical processes encompassing sensing resolution. second part, illustrate consequences partial complete failure machinery. Lastly, will report examples which knowledge has instrumental develop novel therapies based on editing technologies, CRISPR-Cas.

Language: Английский

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Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1681 - 1681

Published: March 25, 2022

Our body is constantly exposed to pathogens or external threats, but with the immune response that our can develop, we fight off and defeat possible attacks infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as existence of a tumour also cause system (IS) be put on alert. Indeed, link between immunology cancer evident these days, IS being used one important targets for treating cancer. able eliminate those abnormal damaged cells found in body, preventing uncontrolled proliferation lead However, several cases, escape IS. It has been observed cells, extracellular matrix, blood vessels, fat various molecules could support growth development. Thus, developing receives structural support, irrigation energy, among other resources, making its survival progression possible. All components accompany help survive grow are called microenvironment (TME). Given importance presence development process, review will focus TME: cells. Immune anti-tumour protecting us against cells; nevertheless, they behave pro-tumoural thus promoting survival. In review, pro-tumour immunity discussed. addition, TME influence dual effect analysed.

Language: Английский

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MutationalPatterns: the one stop shop for the analysis of mutational processes

BMC Genomics, Journal Year: 2022, Volume and Issue: 23(1)

Published: Feb. 15, 2022

The collective of somatic mutations in a genome represents record mutational processes that have been operative cell. These can be investigated by extracting relevant patterns from sequencing data.

Language: Английский

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Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 24, 2021

Traditionally, immunoglobulin (Ig) was believed to be produced by only B-lineage cells. However, increasing evidence has revealed a high level of Ig expression in cancer cells, and this is named cancer-derived Ig. Further studies have shown that shares identical basic structures with B cell-derived but exhibits several distinct characteristics, including restricted variable region sequences aberrant glycosylation. In contrast Ig, which functions as an antibody the humoral immune response, exerts profound protumorigenic effects via multiple mechanisms, promoting malignant behaviors mediating tumor escape, inducing inflammation, activating aggregation platelets. Importantly, shows promising potential for application diagnostic therapeutic target patients. review, we summarize progress research area discuss perspectives applying novel management

Language: Английский

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Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 14, 2021

The DNA damage response (DDR) is an organized network of multiple interwoven components evolved to repair damaged and maintain genome fidelity. Conceptually the DDR includes sensors, transducer kinases, effectors genomic stability accurate transmission genetic information. We have recently gained a substantially improved molecular mechanistic understanding how are interconnected inflammatory immune responses stress. shapes both innate adaptive pathways: (i) in context immunity, mainly enhance cytosolic sensing its downstream STimulator INterferon Genes (STING)-dependent signaling; (ii) needed for assembly diversification antigen receptor genes that requisite T B lymphocyte development. Imbalances between impair tissue homeostasis lead replication transcription stress, mutation accumulation, even cell death. These impacts from defects can then drive tumorigenesis, secretion cytokines, aberrant responses. Yet, deficiency or inhibition also directly Furthermore, plus higher load tumor cells synergistically produce primarily tumor-specific neoantigens, which powerfully targeted cancer immunotherapy by employing checkpoint inhibitors amplify Thus, elucidating DDR-immune interplay may provide critical connections harnessing immunomodulatory effects improve efficacy radiation chemotherapies, blockade, combined therapeutic strategies.

Language: Английский

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The immune cell atlas of human neuroblastoma

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(6), P. 100657 - 100657

Published: June 1, 2022

Understanding the complete immune cell composition of human neuroblastoma (NB) is crucial for development immunotherapeutics. Here, we perform single-cell RNA sequencing (scRNA-seq) on 19 NB samples coupled with multiplex immunohistochemistry, survival analysis, and comparison normal fetal adrenal gland data. We provide a comprehensive landscape characterize cell-state changes from tissue to NB. Our analysis reveals 27 subtypes, including distinct subpopulations myeloid, NK, B, T cells. Several different types demonstrate benefit. In contrast adult cancers previous studies, show an increase in inflammatory monocyte state when contrasting tumor tissue, while no differences cytotoxicity exhaustion score cells, nor Treg activity, are observed. receptor-ligand interaction highly complex interactive network microenvironment which highlight several interactions that suggest future therapeutic studies.

Language: Английский

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Production of monoclonal antibodies for therapeutic purposes: A review

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 120, P. 110376 - 110376

Published: May 25, 2023

Language: Английский

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Molecular characterization and complexity of the immunoglobulin repertoire in the silver-black fox (Vulpes vulpes)

BMC Veterinary Research, Journal Year: 2025, Volume and Issue: 21(1)

Published: March 28, 2025

Immunoglobulins, a class of globulins with antibody properties, play crucial role in the body's defense against pathogens. In this study, we analyzed gene loci structure Silver-black fox using comparative genomics approach. The mechanisms expression diversity and its preferences were investigated through Next-generation sequencing (NGS). results revealed 32 potentially functional VH genes, 9 Vκ 17 Vλ DH 3 JH 6 Jκ 11 Jλ located on different scaffolds. Subsequently, 5'RACE PE300 bipartite used to obtain reads expressed repertoire foxes rearrangement events. analysis indicated strong preference use V genes J by fox. main ways V(D)J recombination somatic hypermutation (SHM). hypermutated region SHM was not only concentrated CDR but also had higher mutation rate FR region. types G > A, C T, T C, A G. findings study could serve as theoretical foundation for deeper understanding immunoglobulins, which is significant enriching knowledge immunogenetics providing support future studies vaccine design

Language: Английский

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Human RecQ Helicases in DNA Double-Strand Break Repair

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Feb. 25, 2021

RecQ DNA helicases are a conserved protein family found in bacteria, fungus, plants, and animals. These play important roles multiple cellular functions, including replication, transcription, repair, telomere maintenance. Humans have five helicases: RECQL1, Bloom syndrome (BLM), Werner helicase (WRN), RECQL4, RECQL5. Defects BLM WRN cause autosomal disorders: (BS) (WS), respectively. Mutations RECQL4 associated with three genetic disorders, Rothmund–Thomson (RTS), Baller–Gerold (BGS), RAPADILINO syndrome. Although no disorders been reported due to loss of RECQL1 or RECQL5, dysfunction either gene is tumorigenesis. Multiple genetically independent pathways evolved that mediate the repair double-strand break (DSB), pivotal each them. The importance DSB supported by observations defective can chromosomal aberrations, genomic instability, senescence, cell death, which ultimately lead premature aging, neurodegeneration, In this review, we will introduce human family, describe detail their provide relevance between diseases.

Language: Английский

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Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies

Cancers, Journal Year: 2021, Volume and Issue: 13(15), P. 3819 - 3819

Published: July 29, 2021

Cells respond to genotoxic stress through a series of complex protein pathways called DNA damage response (DDR). These monitoring mechanisms ensure the maintenance and transfer correct genome daughter cells selection repair, cell cycle regulation, programmed death processes. Canonical or non-canonical DDRs are highly organized controlled play crucial roles in stability diversity. When altered mutated, proteins these networks lead many diseases that share common features, tumor formation. In recent years, technological advances have made it possible benefit from principles DDR target eliminate cancer cells. new types treatments adapted different sensitivity could combination therapies maximal efficiency.

Language: Английский

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