NGF-TrkA Axis Enhances PDGF-C-Mediated Angiogenesis in Osteosarcoma via miR-29b-3p Suppression: A Potential Therapeutic Strategy Using Larotrectinib

Life, Journal Year: 2025, Volume and Issue: 15(1), P. 99 - 99

Published: Jan. 15, 2025

Angiogenesis plays a critical role in osteosarcoma (OS) growth and metastasis. While nerve factor (NGF) is implicated cancer progression, its OS angiogenesis remains unclear. This study explored NGF’s effects on the underlying molecular mechanisms. Analysis of GEO (GSE16088) data identified five markers significantly upregulated tissues. In vitro experiments demonstrated that NGF enhanced HUVEC tube formation by upregulating platelet-derived C (PDGF-C) expression suppressing microRNA-29b-3p (miR-29b-3p). The results assays confirmed stimulation increased angiogenic capacity MG63/NGF cells compared to MG63 cells. Furthermore, larotrectinib, TrkA inhibitor, effectively reduced migration invasion abilities dose-dependent manner. These findings suggest NGF-TrkA axis promotes PDGF-C-mediated inhibiting miR-29b-3p signaling. Larotrectinib could serve as potential therapeutic agent targeting NGF-mediated OS, offering promising avenue for treatment.

Language: Английский

Harnessing myeloid cells in cancer

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 6, 2025

Cancer-associated myeloid cells due to their plasticity play dual roles in both promoting and inhibiting tumor progression. Myeloid with immunosuppressive properties a critical role anti-cancer immune regulation. Cells of different origin, such as associated macrophages (TAMs), neutrophils (TANs), derived suppressor (also called MDSCs) eosinophils are often expanded cancer patients significantly influence survival, but also the outcome therapies. For this reason, variety preclinical clinical studies modulate activity these have been conducted, however without successful date. In review, pro-tumor cells, cell-specific therapeutic targets, vivo on cell re-polarization impact immunotherapies/genetic engineering addressed. This paper summarizes ongoing trials concept chimeric antigen receptor macrophage (CAR-M) therapies, suggests future research perspectives, offering new opportunities development novel treatment strategies.

Language: Английский

Cordyceps sinensis mycelium Refined Polysaccharides Regulate PI3K/AKT/mTOR Pathway to Inhibit Hepatocellular Carcinoma and Its Synergistic Effect on Cyclophosphamide

Pharmacognosy Magazine, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Background Cordyceps sinensis is a unique and precious traditional Chinese medicine. The fermented mycelia of C. are obtained from the medicinal strains isolated by liquid-submerged fermentation, which have similar pharmacological effects to natural . Polysaccharide one main components artificial , has anti-tumor currently used in adjuvant treatment various cancers. However, anti-hepatoma efficacy polysaccharides underlying mechanism not been reported, synergistic effect combined with cyclophosphamide (CTX) remains be explored. Purpose Investigating refined polysaccharide 1 (CP1) mycelium on PI3K/AKT/mTOR pathway HepG2 hepatocellular carcinoma cells, its detoxifying when CTX. Materials Methods subcutaneous transplantation tumor model human nude mice was established. volume weight were recorded, inhibition rates calculated. Enzyme-linked immunosorbent assay (ELISA) examine levels necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF) secretions cancerous tissues. Immunohistochemical methods identify expression BAX BCL-2 genes associated apoptosis Western blotting protein phosphoinositide 3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) signaling pathway. Mice had their peripheral blood collected for standard testing. Results Tumor suppression percentages CP1 high-, medium-, low-dosage categories stood at 46.60%, 45.18%, 36.84%, respectively. increased secretion TNF-α decreased VEGF, IL-6, IL-1β There decrease anti-apoptotic B-cell lymphoma-2 (BCL-2) an increase pro-apoptotic BCL2-associated X (BAX). phosphorylation PI3K, AKT, mTOR proteins within CTX, high, medium, low doses conjunction CTX groups 71.29%, 77.63%, 76.98%, 75.24%, In receiving along there elevation spleen coefficient count leukocytes, neutrophils, lymphocytes blood. Conclusion can significantly effectively inhibit carcinoma, may related combination alleviate bone marrow

Language: Английский