The Role of Chronic Inflammation in Pediatric Cancer

Cancers, Journal Year: 2025, Volume and Issue: 17(1), P. 154 - 154

Published: Jan. 6, 2025

Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result tissue fibrosis genetic alterations that contribute to pathogenesis of human diseases such as cancer. Recent scientific advancements exploring underlying mechanisms malignant cellular transformations cancer progression have exposed significant disparities between pediatric adult-onset cancers. For instance, cancers tend lower mutational burdens arise actively developing tissues, where cell-cycle dysregulation leads gene, chromosomal, fusion gene development not seen counterparts. As such, findings adult cannot be directly applied cancers, unique mutations inherent etiologies remain poorly understood. Here, we review processes chromosomal instability, tumor microenvironment, tumorigenesis transformation explore current therapeutic interventions maintain and/or restore inflammatory homeostasis.

Language: Английский

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Survival strategies: How tumor hypoxia microenvironment orchestrates angiogenesis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116783 - 116783

Published: May 25, 2024

During tumor development, the itself must continuously generate new blood vessels to meet their growth needs while also allowing for invasion and metastasis. One of most common features tumors is hypoxia, which drives process angiogenesis by regulating microenvironment, thus adversely affecting prognosis patients. In addition, overcome unsuitable environments growth, such as nutrient deficiency, hyperacidity, immunosuppression, microenvironment (TME) coordinates in several ways restore supply oxygen nutrients remove metabolic wastes. A growing body research suggests that hypoxia interact through a complex interplay crosstalk, inextricably linked TME. Here, we review TME's positive contribution from an angiogenesis-centric perspective considering objective impact hypoxic phenotypes status limitations current angiogenic therapies.

Language: Английский

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Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8163 - 8163

Published: July 26, 2024

Bone metastases, a common and debilitating consequence of advanced cancers, involve complex interplay between malignant cells the bone microenvironment. Central to this interaction are interleukins (ILs), group cytokines with critical roles in immune modulation inflammation. This review explores dualistic nature pro-inflammatory anti-inflammatory emphasizing their molecular mechanisms, pathological impacts, therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, IL-8, have been identified key drivers promoting osteoclastogenesis, tumor proliferation, angiogenesis. These create favorable environment for cancer cell survival degradation, contributing progression metastatic lesions. Conversely, including IL-4, IL-10, IL-13, exhibit protective by modulating responses inhibiting osteoclast activity. Understanding these opposing effects is crucial developing targeted therapies aimed at disrupting processes metastases. Key signaling pathways, NF-κB, JAK/STAT, MAPK, mediate actions influencing survival, recruitment, remodeling. Targeting pathways presents promising avenues. Current treatment strategies, use denosumab, tocilizumab, emerging agents like bimekizumab ANV419, highlight potential interleukin-targeted mitigating However, challenges resistance, side effects, long-term efficacy remain significant hurdles. also addresses diagnostic prognostic biomarkers, offering insights into patient stratification personalized approaches. Interleukins multifaceted that depend on context, environment, types, cellular interactions. Despite substantial progress, gaps research persist, particularly regarding precise mechanisms which influence niche broader clinical implications. While not exhaustive, overview underscores metastases highlights need continued fully elucidate interactions Addressing will be essential advancing our understanding patients.

Language: Английский

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IL-1 Superfamily Across 400+ Species: Therapeutic Targets and Disease Implications

Biology, Journal Year: 2025, Volume and Issue: 14(5), P. 561 - 561

Published: May 17, 2025

An important area of interest for therapeutic development is the IL-1 superfamily, a critical group immune regulators with profound implications in variety disorders. This study clarifies evolutionary patterns family members by thoroughly analyzing more than 400 animal species, demonstrating their ancient roots that extend back to earliest vertebrates. Important results show that, although ligands expanded significantly over evolution mammals, corresponding receptors remained remarkably structurally conserved. Identifying both lineage-specific adaptations and evolutionarily conserved residues provides vital information treatment design. These findings point possibility two different strategies: addressing species-specific variants may allow targeted interventions, whereas focusing on motifs result broad-acting treatments. The also identified less well-known species as useful models comprehending early systems. In addition advancing our knowledge function autoimmune, inflammatory, carcinogenic illnesses, this research lays groundwork potent therapeutics creating an framework family.

Language: Английский

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Characterization of the malignant cells and microenvironment of infantile fibrosarcoma via single-cell RNA sequencing

Translational Pediatrics, Journal Year: 2024, Volume and Issue: 13(4), P. 596 - 609

Published: April 1, 2024

Background: Infantile fibrosarcoma (IFS) is the most prevalent soft tissue sarcoma in children under 1 year old and known for its rapid growth. The tumor lacks specific immunohistochemical marker a general view of microenvironment (TME). Its primary therapeutic intervention places patients at risk disability or mutilation. This study aimed to elucidate universal transcriptional characteristics IFS explore novel targets diagnosis therapy using single-cell RNA sequencing (scRNA-seq). Methods: Fresh samples scRNA-seq were collected from four before other treatments administered. We conducted cell clustering, inferring copy number variation (InferCNV) analysis, gene differential expression function evaluation, Pearson correlation cell-cell ligand-receptor interaction analysis investigate distinct ecosystem IFS. Results: According resolution data, we depicted atlas IFS, which comprised 14 populations. Through comparison with normal cells, malignant cells distinguished, potential markers (POSTN, IGFBP2 CTHRC1) identified. also found various functional subtypes, three exhibited cancer stem (CSCs) phenotypes, investigated interplay between these subtypes nonmalignant TME Endothelial macrophages dominate communication landscape within microenvironment, promoting tumorigenesis via multiple receptor-ligand interactions. Conclusions: provides comprehensive characterization transcriptome cellular level, offering valuable insights clinically significant advancements treatment

Language: Английский

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