TLRs signaling pathway regulation, antibacterial and apoptotic activity of largemouth bass ECSIT during Edwardsiella piscicida infection

Aquaculture, Journal Year: 2024, Volume and Issue: 595, P. 741615 - 741615

Published: Sept. 16, 2024

Language: Английский

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Binding of interleukin-1 receptor antagonist to cholinergic receptor muscarinic 4 promotes immunosuppression and neuroendocrine differentiation in prostate cancer

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217090 - 217090

Published: June 28, 2024

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective responses. interleukin-1 (IL-1) receptor antagonist (IL1RN), key anti-inflammatory molecule, plays significant role in suppressing IL-1-related inflammatory Our research investigates the oncogenic IL1RN PCa, particularly its interactions with muscarinic acetylcholine 4 (CHRM4), involvement driving pathways M2-like macrophage polarization within PCa TME. We demonstrate following androgen deprivation therapy (ADT), IL1RN-CHRM4 interaction activates MAPK/AKT signaling pathway. activation upregulates transcription factors E2F1 MYCN, stimulating production creating positive feedback loop increases CHRM4 abundance both cells macrophages. ADT-driven IL1RN/CHRM4 axis significantly enhances checkpoint markers associated neuroendocrine differentiation treatment-resistant outcomes. Higher serum are increased disease aggressiveness advanced patients. Additionally, elevated correlate better clinical outcomes immunotherapy. Clinical correlations between expression patients organoid models highlight their potential as therapeutic targets. data suggest targeting could be promising strategy for managing progression enhancing treatment

Language: Английский

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Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, m6A modification and diverse cell death mechanisms

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Unraveling the Guardian: p53’s Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12928 - 12928

Published: Dec. 1, 2024

DNA damage can lead to mutations that alter the function of oncogenes or tumor suppressor genes, thus promoting development cancer. p53 plays a multifaceted and complex role in response cancer progression is known as 'guardian gene'. When occurs, activated through series post-translational modifications, which stabilize protein enhance its transcription factor. It regulates processes including cell cycle checkpoints, repair apoptosis, thereby preventing spread damaged maintaining genome integrity. On one hand, initiate arrest induce cells enter G1/S G2/M with from continuing proliferate gaining time for repair. At same time, promote activation pathways, base excision repair, nucleotide other ensure integrity genetic material. If too severe will trigger apoptosis process eliminate potential risks time. also pivotal progression. Mutations gene are frequently found many cancers, mutated not only loses normal but may even acquire pro-cancer activity. Therefore, we discuss therapeutic strategies targeting pathway, such use small-molecule drugs restore wild-type p53, inhibition negative regulatory factors synthetic lethality approaches p53-deficient tumors. This review therefore highlights important genomic stability

Language: Английский

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Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2232 - 2232

Published: March 1, 2025

The integrity of p53 machinery is crucial for platinum activity, while mutation frequent in high-grade serous ovarian cancer (HGS-OC). This study aimed to evaluate the link between mutations, sensitivity (PS), and platinum-free interval (PFI) patients with HGS-OC. We prospectively analyzed 159 consecutive women who underwent surgery. somatic mutational status BRCA, HRD, TP53 (according structural, hotspot, functional classification) was evaluated. Among enrolled patients, 82.4% cases were TP53-mutated (MT), 27.8% BRCA-MT. distribution categories did not differ significantly BRCA-MT wild-type (WT) cases. In entire population, proportion PS lower TP53-MT compared TP53-WT (p = 0.0208), nonsense/frameshift/splicing missense 0.0319), loss-of-function (LOF) GOF 0.0048) MT For structural mutations different PR patients. Conversely, BRCA WT differed a multivariate regression analysis, LOF found be independent negative predictors (HR: 0.1717; 95% CI: 0.0661-0.4461; p-value: 0.0003). Kaplan-Meier curves showed PFI overall population (log-rank p 0.0020) BRCA-WT 0.0140). Via COX testing, it that independently associated decreased 0.0036). conclusion, our data show HGS-OC harboring poorest prognostic subgroup regarding PFI. Further studies are needed confirm findings.

Language: Английский

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Tumor-derived CCL15 regulates RNA m6A methylation in cancer-associated fibroblasts to promote hepatocellular carcinoma growth

Cancer Letters, Journal Year: 2024, Volume and Issue: 611, P. 217420 - 217420

Published: Dec. 27, 2024

Language: Английский

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Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

Cells, Journal Year: 2024, Volume and Issue: 13(11), P. 924 - 924

Published: May 27, 2024

Induction of apoptosis represents a promising therapeutic approach to drive tumor cells death. However, this poses challenges due the intricate nature cancer biology and mechanisms employed by survive escape immune surveillance. Furthermore, molecules released from apoptotic phagocytes in microenvironment (TME) can facilitate progression evasion. Apoptosis is also pivotal mechanism modulating strength duration anti-tumor T-cell responses. Combined strategies including molecular targeting apoptosis, promoting immunogenic cell death, immunosuppressive cells, affecting energy pathways potentially overcome resistance enhance outcomes. Thus, an effective for within TME should delicately balance selective induction while safeguarding survival, metabolic changes, functionality T crucial involved regulation. Enhancing persistence effectiveness may bolster more resilient enduring response, ultimately advancing outcomes treatment. This review delves into topics multifaceted issue suggests drugs druggable targets possible combined therapies.

Language: Английский

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Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 3, 2024

Abstract Background While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates role fibrinogen-like protein 1 (FGL1) driving ESCC following exposure. Methods FGL1 expression cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact on invasion migration assessed through Transwell wound healing assays. In vivo, metastatic potential response to scrutinized nude mice models. Comprehensive RNA sequencing functional experiments elucidated intricate mechanism associated with FGL1. Results Radiation induced upregulation FOXO4, intensifying migration. Targeted knockdown effectively alleviated these characteristics both vitro vivo. depletion concurrently suppressed IMPDH1 expression. Rescue underscored that robustly reversed pro-invasive effects by cells. tissues exhibited heightened mRNA levels, demonstrating correlation patient survival. Conclusions Radiation-induced propels IMPDH1, proposing therapeutic target mitigate post-radiotherapy patients.

Language: Английский

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Progress in deciphering the role of p53 in diffuse large B-cell lymphoma: mechanisms and therapeutic targets

American Journal of Cancer Research, Journal Year: 2024, Volume and Issue: 14(7), P. 3280 - 3293

Published: Jan. 1, 2024

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype, accounting for 30%-40% of non-Hodgkin in adults. The mechanisms underlying DLBCL occurrence are extremely complex, and involve receptor (BCR) Toll-like (TLR) signaling pathways, as well genetic abnormalities other factors. With development high-throughput sequencing, an increasing number abnormal genes have been identified DLBCL. Among them, tumor protein p53 (

Language: Английский

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Recent Research Advances on the Hippo‐Yki Pathway of Crustaceans: Current Knowledge and Potential Applications in Crustacean Aquaculture

Reviews in Aquaculture, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 19, 2024

ABSTRACT The Hippo‐YAP/Yki pathway is critical for the regulation of physiological responses in various biological processes from invertebrates to mammals. Crustaceans, particular shrimp and crabs, are important food sources worldwide. In response needs crustacean aquaculture disease control, regulatory mechanisms life activities, especially immunity, have been increasingly emphasized. Emerging clues suggest that Hippo‐Yki immunity regeneration crustaceans. this review, structure, activation pattern, mechanism pathogen invasion, crosstalk with other signaling cascades crustaceans summarized its similarities differences those mammals Drosophila investigated. Based on this, roles immune limb further discussed, application potential strategies pharmacologically or biologically targeting control breeding theoretically explored.

Language: Английский

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