Epithelial and macrophage cell interaction in cervical cancer through single-cell RNA-sequencing and spatial analysis DOI Creative Commons
Zhichao Wang, Long Cheng, Guanghui Li

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 9, 2025

Background Cervical cancer (CC) is a major global health issue, ranking sixth in cancer-related mortality. The tumor microenvironment (TME) plays crucial role growth. This study explored the cellular composition and immunological landscape of CC using various genomic data sources. Methods Data from Cancer Genome Atlas Gene Expression Omnibus were analyzed, including single-cell RNA sequencing, spatial transcriptome analysis, survival data. set variation analysis (GSVA) identified pathways CD8+ cells, macrophages, epithelial cells. Immunohistochemistry assessed marker expression normal tissues. Tumor immune dysfunction exclusion (TIDE) scores differentiated high- low-macrophage groups. Cell–cell communication analyses highlighted interactions between macrophages Results Macrophage markers correlated with overall (OS) disease-free (DFS). Epithelial cell subgroups 1 4, along T associated OS. TIDE varied Specific ligand-receptor found subgroup 1. Triptolide was effective 1, while memantine more macrophages. Conclusion Epithelial-macrophage TME are for progression treatment, offering potential immunotherapeutic strategy.

Language: Английский

Helicobacter pylori and gastric cancer: mechanisms and new perspectives DOI Creative Commons

Yantao Duan,

Yonghu Xu,

Yi Dou

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 23, 2025

Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as major etiological agent, affecting an estimated 50% of the world's population. There has been rapidly expanding knowledge molecular and pathogenetic mechanisms H. over decades. This review summarizes latest research advances to elucidate underlying infection in gastric carcinogenesis. Our investigation reveals complex network involving STAT3, NF-κB, Hippo, Wnt/β-catenin pathways, which are dysregulated caused by pylori. Furthermore, we highlight role inducing oxidative stress, DNA damage, chronic inflammation, cell apoptosis—key cellular events that pave way for Emerging evidence also suggests effect on tumor microenvironment its possible implications immunotherapy. synthesizes current identifies gaps warrant further investigation. Despite progress our previous development pylori-induced cancer, comprehensive pylori's is crucial advancement prevention treatment strategies. By elucidating these mechanisms, aim provide more in-depth insights study pylori-related cancer.

Language: Английский

Citations

13
Immunometabolism in cancer: basic mechanisms and new targeting strategy DOI Creative Commons

Ranran Su,

Yingying Shao,

Manru Huang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 16, 2024

Abstract Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving microenvironment (TME) in which always lose the initial killing capacity, remains an unsolved dilemma even with development checkpoint therapies. In recent years, many studies on immunometabolism have been reported. The may facilitate anti-tumor immunotherapy from recurrent crosstalk between metabolism and immunity. Here, we discuss clinical core signaling pathways their inhibitors or agonists, as well specific functions these regulating immunity metabolism, some identified checkpoints. Understanding comprehensive advances helps to revise status quo cancer treatment.

Language: Английский

Citations

12
Hydrogen‐Bonded Organic Framework Nanoscintillators for X‐Ray‐Induced Photodynamic Therapy in Hepatocellular Carcinoma DOI Open Access

Lihui Gu,

Han Wu, Xu Li

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract X‐ray induced photodynamic therapy (X‐PDT) leverages penetrating to generate singlet oxygen ( 1 O 2 ) for treating deep‐seated tumors. However, conventional X‐PDT typically relies on heavy metal inorganic scintillators and organic photosensitizers produce , which presents challenges related toxicity energy conversion efficiency. In this study, highly biocompatible phosphorescent nanoscintillators based hydrogen‐bonded frameworks (HOF) are designed engineered, termed BPT‐HOF@PEG, enhance in hepatocellular carcinoma (HCC) treatment. BPT‐HOF@PEG functions simultaneously as both scintillator photosensitizer, effectively absorbing transferring abundant . Both vitro vivo investigations demonstrate that internalized efficiently produces significant quantities of upon irradiation. Additionally, exposure directly inflicts DNA damage, the synergistic effects these mechanisms result pronounced cell death substantial tumor growth inhibition, with a inhibition rate up 90.4% assessments. RNA sequencing analyses reveal induces apoptosis Hepa1‐6 cells while inhibiting proliferation, culminating death. Therefore, work highlights considerable potential efficient HOF nanoscintillators‐based promising therapeutic approach HCC, providing effective alternative negligible patients unresectable

Language: Английский

Citations

2
Dual Targeting of MEK1 and Akt Kinase Identified SBL‐027 as a Promising Lead Candidate to Control Cell Proliferations in Gastric Cancer DOI Open Access

Maha Alamodi Alghamdi,

Hemali Deshpande

Biotechnology and Applied Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

ABSTRACT Dual inhibition of Akt and MEK1 pathways offers a promising strategy to enhance treatment efficacy in gastric cancer. In this study, we employed computational approaches followed by vitro validations. Our results demonstrate that SBL‐027 exhibits robust enduring interactions with kinases, as evidenced atomistic molecular dynamics simulations mechanics Poisson–Boltzmann surface area (MM‐PBSA) based binding free energy estimates. The predicted Gibbs energies indicate highly favorable between both kinases. vitro, displayed an IC 50 value 195.20 nM against 239.10 enzymes. compound exhibited potent cell proliferation KATOIII SNU‐5 cells, GI values 490.70 615.14 nM, respectively. Moreover, induced increase the sub G 0 /G 1 population during cycle while facilitating early late‐phase apoptosis these lines. Notably, significantly reduced percentage dual‐positive cells expressing cancer cells. strong affinity, stability, thermodynamics along established highlight its potential lead for further preclinical clinical development.

Language: Английский

Citations

1
A Comprehensive Review of Nanoparticle-Based Drug Delivery for Modulating PI3K/AKT/mTOR-Mediated Autophagy in Cancer DOI Open Access
Md. Ataur Rahman, Maroua Jalouli,

Sujay Kumar Bhajan

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1868 - 1868

Published: Feb. 21, 2025

The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway plays a crucial role in regulation autophagy, cellular mechanism vital for homeostasis through degradation damaged organelles and proteins. dysregulation this is significantly associated with cancer progression, metastasis, resistance to therapy. Targeting PI3K/AKT/mTOR signaling presents promising strategy treatment; however, traditional therapeutics frequently encounter issues related nonspecific distribution systemic toxicity. Nanoparticle-based drug delivery systems represent significant advancement addressing these limitations. Nanoparticles enhance bioavailability, stability, targeted therapeutic agents, facilitating precise modulation autophagy cells. Functionalized nanoparticles, such as liposomes, polymeric metal-based nanocarriers, facilitate tumor tissues, minimizing off-target effects improving efficacy. These can deliver multiple agents concurrently, enhancing PI3K/AKT/mTOR-mediated oncogenic pathways. This review examines advancements nanoparticle-mediated that pathway, emphasizing their contribution precision side integration nanotechnology molecularly therapies substantial potential resistance. Future initiatives must prioritize optimization clinical translation patient outcomes.

Language: Английский

Citations

1
Therapeutic potential of flavonoids in gastrointestinal cancer: Focus on signaling pathways and improvement strategies (Review) DOI Creative Commons

Ye Ding,

Yong Yu

Molecular Medicine Reports, Journal Year: 2025, Volume and Issue: 31(4), P. 1 - 34

Published: Feb. 24, 2025

Flavonoids are a group of polyphenolic compounds distributed in vegetables, fruits and other plants, which have considerable antioxidant, anti‑tumor anti‑inflammatory activities. Several types gastrointestinal (GI) cancer the most common malignant tumors world. A large number studies shown that flavonoids inhibitory effects on cancer, they recognized as class potential drugs. Therefore, present review investigated molecular mechanisms treatment different GI summarized drug delivery systems commonly used to improve their bioavailability. First, classification therapeutic various human diseases were briefly introduced. Then, clarify mechanism action body, metabolic process body associated signaling pathways causing five discussed, well corresponding targets flavonoids. Finally, clinical settings, poor water solubility, low permeability inferior stability, lead absorption efficiency vivo. three widely summarized. Suggestions for improving bioavailability focus next stage research also put forward.

Language: Английский

Citations

1
Discovery of 5-Phenylthiazol-2-amine Derivatives as Novel PI4KIIIβ Inhibitors with Efficacious Antitumor Activity by Inhibiting the PI3K/AKT Axis DOI

Bichuan Wang,

Siyuan Hao, Fang Han

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

To develop novel PI4KIIIβ inhibitors and explore their antitumor activity, a series of 5-phenylthiazol-2-amine derivatives were synthesized by structural modifications PIK93. Biological assay results indicated that compounds 16 43 exhibited superior selective inhibitory antiproliferative activity than Mechanistic studies revealed the two inhibit PI3K/AKT pathway more effectively, thereby inducing cancer cell apoptosis, cycle arrest in G2/M phase autophagy. Importantly, vivo toxicity pharmacodynamics showed safety to commercially available axis inhibitor alpelisib, obviously small lung H446 xenograft models. Overall, this work highlights therapeutic potential treatment tumors, provides candidates viable drug development strategies for inhibitors.

Language: Английский

Citations

1
Gastric Cancer Signaling Pathways and Therapeutic Applications DOI Creative Commons
Mingfang Wu,

Shiman Yuan,

Kai Liu

et al.

Technology in Cancer Research & Treatment, Journal Year: 2024, Volume and Issue: 23

Published: Jan. 1, 2024

Gastric cancer (GC) is a prevalent malignant tumor and ranks as the second leading cause of death among patients worldwide. Due to its hidden nature difficulty in detection, GC has high incidence poor prognosis. Traditional treatment methods such systemic chemotherapy, radiotherapy, surgical resection are commonly used, but they often fail achieve satisfactory curative effects, resulting very low 5-year survival rate for patients. Currently, targeted therapy immunotherapy prominent areas research both domestically internationally. These hold promise GC. This article focuses on signaling pathways associated with development GC, well recent advancements applications immunotherapy. The aim provide fresh insights clinical

Language: Английский

Citations

6
Alkaloid-Based Modulators of the PI3K/Akt/mTOR Pathway for Cancer Therapy: Understandings from Pharmacological Point of View DOI

Fatima Zohra Mokhfi,

Md. Al Amin, Mehrukh Zehravi

et al.

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 402, P. 111218 - 111218

Published: Aug. 28, 2024

Language: Английский

Citations

5
Exosomal microRNA as a key regulator of PI3K/AKT pathways in human tumors DOI
Saade Abdalkareem Jasim, Abdulrahman T. Ahmed,

Aziz Kubaev

et al.

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(11)

Published: Oct. 14, 2024

Language: Английский

Citations

4