Medical Oncology, Journal Year: 2025, Volume and Issue: 42(3)
Published: Feb. 21, 2025
Language: Английский
Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 180 - 197
Published: Feb. 1, 2024
The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, newly developed strategies have not achieved universal success and HCC patients frequently exhibit therapeutic resistance to these therapies. Precision represents a paradigm shift cancer recent years. This approach utilizes unique molecular characteristics individual patient personalize modalities, aiming maximize efficacy while minimizing side effects. Although precision shown multiple types, its application remains infancy. In this review, we discuss key aspects HCC, including biomarkers, classifications, heterogeneity tumor microenvironment. We also propose future directions, ranging from revolutionizing current methodologies personalizing therapy through functional assays, which will accelerate next phase advancements area.
Language: Английский
Citations
124
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11295 - 11295
Published: July 10, 2023
Discovered almost 40 years ago, the potent vasoconstrictor peptide endothelin-1 (ET-1) has a wide range of roles both physiologically and pathologically. In recent years, there been focus on contribution ET-1 to disease. This led development various ET receptor antagonists, some which are approved for treatment pulmonary arterial hypertension, while clinical trials other diseases have numerous yet, most part, unsuccessful. However, given vast physiological impact ET-1, it is surprising disappointing that therapeutics targeting pathway remain limited. Strategies aimed at pathways influencing synthesis release could provide new therapeutic avenues, yet research using cultured cells in vitro had little follow up intact ex vivo preparations. article summarises what currently known about synthesis, storage as well role several including cardiovascular diseases, COVID-19 chronic pain. Unravelling identifying targets potential treat many whether through disease prevention, slowing progression or reversing pathology.
Language: Английский
Citations
44
Cell, Journal Year: 2024, Volume and Issue: 187(25), P. 7045 - 7063
Published: Dec. 1, 2024
Cells are essential to understanding health and disease, yet traditional models fall short of modeling simulating their function behavior. Advances in AI omics offer groundbreaking opportunities create an virtual cell (AIVC), a multi-scale, multi-modal large-neural-network-based model that can represent simulate the behavior molecules, cells, tissues across diverse states. This Perspective provides vision on design how collaborative efforts build AIVCs will transform biological research by allowing high-fidelity simulations, accelerating discoveries, guiding experimental studies, offering new for cellular functions fostering interdisciplinary collaborations open science.
Language: Английский
Citations
16
Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)
Published: Aug. 6, 2024
Abstract The tumor microenvironment demonstrates great immunophenotypic heterogeneity, which has been leveraged in traditional immune-hot/cold categorization based on the abundance of intra-tumoral immune cells. By incorporating spatial contexture, immunophenotype was further elaborated into immune-inflamed, immune-excluded, and immune-desert. However, mechanisms underlying these different phenotypes are yet to be comprehensively elucidated. In this review, we discuss how cells interact collectively shape landscape from perspectives cells, extracellular matrix, cancer metabolism, summarize potential therapeutic options according distinct immunophenotypes for personalized precision medicine.
Language: Английский
Citations
14
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: Jan. 9, 2025
Acute Myeloid Leukemia (AML) with KMT2A rearrangements (KMT2Ar), found on chromosome 11q23, is often called KMT2A-rearranged AML (KMT2Ar-AML). This variant highly aggressive, characterized by rapid disease progression and poor outcomes. Growing knowledge of epigenetic changes, especially lactylation, has opened new avenues for investigation management this subtype. Lactylation plays a significant role in cancer, inflammation, tissue regeneration, but the underlying mechanisms are not yet fully understood. research examined influence lactylation gene expression within KMT2Ar-AML, initially identifying twelve notable lactylation-dependent differentially expressed genes (DEGs). Using advanced machine learning techniques, six key lactylation-associated (PFN1, S100A6, CBR1, LDHB, LGALS1, PRDX1) were identified as essential prognostic evaluation linked to relevant pathways. The study also suggested PI3K inhibitors Pevonedistat possible therapeutic options modulate immune cell infiltration. Our findings confirm critical KMT2Ar-AML identify that may serve biomarkers diagnosis treatment. In addition highlighting need further validation clinical settings, these contribute our understanding KMT2Ar-AML's molecular mechanisms.
Language: Английский
Citations
1
Head & Neck, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 24, 2025
ABSTRACT Background To correlate between immunohistochemical expression of tumor‐infiltrating lymphocytes (TILs), tumor‐associated macrophages (TAMs), and natural killer (NK) cells with the AJCC 8th edition TNM staging system other disease‐modifying clinico‐pathological variables. Methods The representative histology sections tumor invasive margin (IM) core (TC) were selected according to International Immuno‐Oncology Biomarker Working Group subjected immunohistochemistry antibodies for TILs (CD3, CD8, FOXP3), NK Cells (CD57), TAMs (CD68, CD163) pan‐leukocyte marker (CD45). Histo‐immuno‐density‐intensity (HIDI) scoring was calculated as a product proportion intensity staining. Ordinal‐ordinal continuous‐ordinal variables correlated using Kendall's tau‐b (τb), binary‐ordinal Rank‐Biserial (r rb ) statistics. Results A total 111 patients included in study. None clinical pathological parameters showed strong correlation any immune infiltrates including staging. Conclusion We hypothesize an independent activity immunology disease prognosis. Trial Registration CTRI/2020/07/026335
Language: Английский
Citations
1
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Feb. 3, 2025
Language: Английский
Citations
1
Immunological Reviews, Journal Year: 2023, Volume and Issue: 320(1), P. 166 - 198
Published: Aug. 7, 2023
Adoptive T-cell transfer (ACT) therapies, including of tumor infiltrating lymphocytes (TILs) and T cells gene-modified to express either a cell receptor (TCR) or chimeric antigen (CAR), have demonstrated clinical efficacy for proportion patients cancer-types. The field ACT has been driven forward by the success CD19-CAR therapy against various advanced B-cell malignancies, curative responses some leukemia patients. However, relapse remains problematic, in particular lymphoma. Moreover, variety reasons, relative limited non-hematological solid tumors. Indeed, addition pre-infusion challenges lymphocyte collection manufacturing, failure can be attributed several biological processes post-transfer including, (i) inefficient trafficking, infiltration, expansion retention, (ii) chronic exposure coupled with insufficient costimulation resulting exhaustion, (iii) range barriers microenvironment (TME) mediated both suppressive immune infiltrate, (iv) heterogeneity loss, down-regulation presentation machinery, (v) gain intrinsic mechanisms resistance such as apoptosis, (vi) forms toxicity other adverse events Affinity-optimized TCRs improve function innovative CAR designs well gene-modification strategies used coengineer specificity, safety, into cells. Coengineering designed not only directly support transferred cells, but also block TME harness endogenous innate adaptive immunity. Here, we review selection remarkable coengineering strategies, tools, receptors, gene-cargo, that developed recent years augment control ACT, more which are advancing clinic.
Language: Английский
Citations
17
Med, Journal Year: 2024, Volume and Issue: 5(6), P. 530 - 549
Published: March 27, 2024
Language: Английский
Citations
7
Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1727 - 1727
Published: April 29, 2024
The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays crucial role in driving progression, shaping treatment responses, influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) stroma, highlighting its key constituents their dynamic contributions. We examine how significant changes within cSCC ECM—specifically, alterations fibronectin, hyaluronic acid, laminins, proteoglycans, collagens—promote cancer metastasis, drug resistance. composition TME is also explored, detailing intricate interplay cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, various immune populations. These diverse players modulate development, angiogenesis, responses. Finally, we emphasize TME’s potential as therapeutic target. Emerging strategies discussed this include harnessing system (adoptive transfer, checkpoint blockade), hindering disrupting CAF activity, manipulating ECM components. approaches underscore vital that deciphering interactions advancing therapy. Further research illuminating these relationships will uncover new avenues for developing more effective treatments cSCC.
Language: Английский
Citations
7