Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer DOI Creative Commons
Tomislav Ivanović, Dorotea Božić, Benjamin Benzon

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 709 - 709

Published: Feb. 25, 2023

Gastric cancer (GC) therapies include gastrectomy and chemoradiotherapy. The tumor immune microenvironment (TME) has implications for potential immunotherapy. We analyzed the expression of PD-L1, CD8, CTLA-4 IFN-γ in regional lymph node (LN) patients with GC compared it clinical pathological data. Paraffin blocks were collected from 97 undergoing gastrectomy/lymphadenectomy GC. Double immunohistochemistry was performed CD8 PD-L1 double immunofluorescence IFN-γ. Statistical significance set at p < 0.05. cells associated intestinal type (p = 0.046), density macrophages + T 0.001, both). median number CD8+ higher PD-L1-positive than -negative tumors. A cut-off 28.5 one high-magnification field predicted tumors (AUROC 0.797, sensitivity 74.2%, specificity 77.3%). found 37 GCs positively CTLA4+ lymphocytes LN 0.027) CTLA4+/IFN-γ+ (all 0.001). overall survival (OS) 17 months. In group deceased patients, metastases correlated lower OS (RHO -0.314, 0.008). TME suppressive CTLA4+/IFNγ+ LN.

Language: Английский

Deciphering the Role of Cancer Stem Cells: Drivers of Tumor Evolution, Therapeutic Resistance, and Precision Medicine Strategies DOI Open Access
Mohamed El‐Tanani, Syed Arman Rabbani, Shakta Mani Satyam

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 382 - 382

Published: Jan. 24, 2025

Cancer stem cells (CSCs) play a central role in tumor progression, recurrence, and resistance to conventional therapies, making them critical focus oncology research. This review provides comprehensive analysis of CSC biology, emphasizing their self-renewal, differentiation, dynamic interactions with the microenvironment (TME). Key signaling pathways, including Wnt, Notch, Hedgehog, are discussed detail highlight potential as therapeutic targets. Current methodologies for isolating CSCs critically examined, addressing advantages limitations advancing precision medicine. Emerging technologies, such CRISPR/Cas9 single-cell sequencing, explored transformative unraveling heterogeneity informing strategies. The also underscores pivotal TME supporting survival, promoting metastasis, contributing resistance. Challenges arising from CSC-driven dormancy analyzed, along strategies mitigate these barriers, novel therapeutics targeted approaches. Ethical considerations integration artificial intelligence designing CSC-specific therapies essential elements future manuscript advocates multi-disciplinary approach that combines innovative advanced therapeutics, collaborative research address complexities CSCs. By bridging existing gaps knowledge fostering advancements personalized medicine, this aims guide development more effective cancer treatment strategies, ultimately improving patient outcomes.

Language: Английский

Citations

1
Helicobacter pylori CagA protein induces gastric cancer stem cell‐like properties through the Akt/FOXO3a axis DOI
Zheng-Wei Chen,

Zhebin Dong,

Hanting Xiang

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(3)

Published: Feb. 8, 2024

Abstract The presence of Helicobacter pylori ( H. ) infection poses a substantial risk for the development gastric adenocarcinoma. primary mechanism through which exerts its bacterial virulence is cytotoxin CagA. This has potential to induce inter‐epithelial mesenchymal transition, proliferation, metastasis, and acquisition stem cell‐like properties in cancer (GC) cells infected with CagA‐positive . Cancer (CSCs) represent distinct population capable self‐renewal generating heterogeneous tumor cells. Despite evidence showing that CagA can CSCs‐like characteristics GC cells, precise triggers (GCSCs) remains uncertain. study reveals exhibit properties, such as heightened expression CD44, specific surface marker CSCs, increased ability form spheroids. Furthermore, we have observed activates PI3K/Akt signaling pathway CagA‐dependent manner, our findings suggest this activation associated induced by CagA, released during infection, manner. Additionally, inhibits transcription FOXO3a relocates it from nucleus cytoplasm activating pathway. regulatory function Akt/FOXO3a axis transformation into stemness state was successfully demonstrated.

Language: Английский

Citations

8
Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation DOI Creative Commons
Chien‐Hsing Lee, Hsin‐Yi Tsai, Chun‐Lin Chen

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(6), P. 1350 - 1350

Published: June 8, 2022

Chemotherapy is the treatment of choice for gastric cancer; however, currently available therapeutic drugs have limited efficacy. Cancer stemness and tumor microenvironment may play crucial roles in growth chemoresistance. Glucose-regulated protein 78 (GRP78) an endoplasmic reticulum chaperone facilitating folding cell homeostasis during stress participate Isoliquiritigenin (ISL) a bioactive flavonoid found licorice. In this study, we demonstrated role GRP78 cancer evaluated GRP78-mediated inhibition, regulation, chemosensitivity promotion by ISL. ISL not only suppressed stem cell-like characteristics, stemness-related expression, cancer-associated fibroblast activation but also xenograft animal studies. The findings indicated that promising candidate clinical use combination chemotherapy.

Language: Английский

Citations

25
Cold atmospheric plasma: Novel opportunities for tumor microenvironment targeting DOI Creative Commons
Xiaofeng Dai,

Kaiyuan Zhu

Cancer Medicine, Journal Year: 2023, Volume and Issue: 12(6), P. 7189 - 7206

Published: Feb. 10, 2023

With mounting preclinical and clinical evidences on the prominent roles of tumor microenvironment (TME) played during carcinogenesis, TME has been recognized used as an important onco-therapeutic target past decade. Delineating our current knowledge components their functionalities can help us recognize novel opportunities establish treatment modalities towards desirable anti-cancer outcome. By identifying focusing primary cellular in TME, that is, tumor-infiltrating lymphocytes, tumor-associated macrophages, cancer-associated fibroblasts mesenchymal stem cells, we decomposed categorized therapeutic approaches utilizing traits these components, forecasted possible benefits cold atmospheric plasma, a redox modulating tool with selectivity against cancer may convey by targeting TME. Our insights open avenue for control taking advantages homeostasis immunostasis.

Language: Английский

Citations

16
A pan-cancer landscape of IGF2BPs and their association with prognosis, stemness and tumor immune microenvironment DOI Creative Commons
Wei Shao, Hui Zhao, Shoudu Zhang

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 4, 2023

Background The human insulin-like growth factor 2 mRNA binding proteins 1–3 (IGF2BP1–3, also called IMP1–3) play essential roles in regulation, including its splicing, translocation, stability, and translation. However, knowledge regarding the involvement of IGF2BPs tumor immunity stemness across cancer types is still lacking. Methods In this study, we comprehensively analyzed pan-cancer multi-omic data to determine correlation protein expression with various parameters such as mutation frequency, prognostic value, microenvironment (TME), checkpoint blockade, immune infiltration, drug sensitivity. Validation samples glioma cells were performed by quantitative real-time (qRT)-PCR, immunofluorescence staining. Investigation functional role IGF2BP3 stem cells(GSCs) sphere formation, cytotoxicity, transwell, wound healing assays. Results We found that IGF2BP1 3 are either absent or expressed at very low levels most normal tissues. IGF2BP1-3 can be re-expressed a broad range diverse cell lines, where their often correlates poor prognosis. Immunofluorescence staining qRT-PCR analyses showed IGF2BP2 higher tissues than adjacent Moreover, associated TME pan-cancer. Remarkably, participated maintenance self-renewal (GSCs). Knockdown attenuated GSC proliferation, invasion, migration. Conclusions Our systematic study confirmed identification therapeutic targets highlighted need association stemness, TME, which contribute drug-discovery research. Especially, preliminary studies demonstrate potential negative regulator tumorigenesis modulating stemness.

Language: Английский

Citations

15
Role of IL-6/STAT3 Axis in Resistance to Cisplatin in Gastric Cancers DOI Creative Commons
Simona Laurino, Mariarita Brancaccio, Tiziana Angrisano

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 694 - 694

Published: Feb. 24, 2023

Gastric cancer, the second most common cause of death worldwide, is characterized by poor prognosis and low responsiveness to chemotherapy. Indeed, multidrug resistance, based mainly on cellular molecular factors, remains one limiting factors current approach gastric cancer (GC) therapy. We employed a comprehensive gene expression analysis through data mining publicly available databases assess role signal transducer activator transcription 3 (STAT3) in drug efficiency. It has been proposed that cells are less sensitive these drugs because they develop resistance agents activating alternative signalling pathways responsible for overcoming pharmacological inhibition. Our study evaluated hypothesis STAT3 response cisplatin reduces reaction drug. Consistent with this hypothesis, inhibition interleukin 6 (IL-6)/STAT3 combination therapy prevented both activation more lethality than induction single agent. The suggest IL-6/STAT3 axis block associated treatment may represent strategy overcome resistance.

Language: Английский

Citations

14
3D Cell Models in Radiobiology: Improving the Predictive Value of In Vitro Research DOI Creative Commons
Francesca Antonelli

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10620 - 10620

Published: June 25, 2023

Cancer is intrinsically complex, comprising both heterogeneous cellular composition and extracellular matrix. In vitro cancer research models have been widely used in the past to model study cancer. Although two-dimensional (2D) cell culture traditionally for research, they many limitations, such as disturbance of interactions between environments changes morphology, polarity, division mechanism, differentiation motion. Moreover, 2D are usually monotypic. This implies that tumor ineffective at accurately recapitulating complex aspects growth, well their radiation responses. Over decade there has significant uptake three-dimensional (3D) by researchers, highlighting a complementary studies effects on tumors, especially conjunction with chemotherapy. The introduction 3D approaches aims vivo tissue positioning itself halfway animal models, thus opening up new possibilities response mechanisms healthy tissues.

Language: Английский

Citations

14
Wnt signaling in gastric cancer: current progress and future prospects DOI Creative Commons
Ruyue Han, Jing Yang, Yingying Zhu

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 7, 2024

Levels of the Wnt pathway components are abnormally altered in gastric cancer cells, leading to malignant cell proliferation, invasion and metastasis, poor prognosis chemoresistance. Therefore, it is important understand mechanism signaling cancer. We systematically reviewed molecular mechanisms development; summarize progression challenges research on agents pathway.

Language: Английский

Citations

5
Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer DOI Creative Commons
Zhiyuan Xu, Qiuli Chen,

Lilu Shu

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Aug. 8, 2022

Gastric cancer is the fourth most frequent and has a high death rate. Immunotherapy represented by PD-1 brought hope for treatment of advanced gastric cancer. Methylation m6A genes linked to onset progression numerous cancers, but there are few studies on The main purpose this study aims analyze relationship between RNA methylation regulators, PD-L1, prognosis tumor immune microenvironment (TIME) in Cancer Genome Atlas (TCGA) Genotype Tissue Expression (GTEx) databases were used acquire transcriptomic data clinical information from patients. changes regulator expression levels tissues normal studied. Consensus clustering analysis was separate samples into two categories. We employed Least Absolute Shrinkage, Selection Operator (LASSO) Cox regression analysis, Gene Set Enrichment Analysis (GSEA), cBioPortal PD-L1 TIME In tissues, majority regulatory factors considerably overexpressed. Two subgroups (Cluster1/2) based consensus 21 regulators. significantly higher they with METTL3, WTAP, HNRNPD, ZC3H7B, METTL14, FTO, PCIF1, HNRNPC, YTHDF1 YTDHF2. Cluster1 showed large increase resting memory CD4+ T cells, naïve B active NK Mast cells. Cluster2 shown be involved critical signaling pathways, including base excision repair, cell cycle, nucleotide degradation, spliceosome pathways. RiskScores prognostic have been found as independent indicators. amount tumor-infiltrating cells dynamically affected copy number regulators associated TIME.

Language: Английский

Citations

21
An update to experimental and clinical aspects of tumor-associated macrophages in cancer development: hopes and pitfalls DOI Creative Commons
Arash Salmaninejad, Sepideh Mehrpour Layeghi, Zeinab Falakian

et al.

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 13, 2024

Tumor-associated macrophages (TAMs) represent one of the most abundant tumor-infiltrating stromal cells, and their normal function in tumor microenvironment (TME) is to suppress cells by producing cytokines which trigger both direct cell cytotoxicity antibody-mediated immune response. However, upon prolonged exposure TME, classical these so-called M1-type TAMs can be converted another type, "M2-type," are recruited so that they promote growth metastasis. This reason why accumulation TME correlated with poor prognosis cancer patients. Both M1- M2-types have high degree plasticity, M2-type reprogrammed for therapeutic purposes. characteristic introduces as promising target developing novel treatments. In addition, inhibition blocking recruitment well depletion inducing apoptosis, other approaches effective immunotherapy cancer. this review, we summarize potential targeted provide an up-to-date about strategies targeting TAMs.

Language: Английский

Citations

4