Published: Jan. 1, 2025
Language: Английский
Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)
Published: April 26, 2025
Gastric cancer (GC) is a prevalent digestive system tumor, the fifth most diagnosed worldwide, and leading cause of deaths. GC distinguished by its pronounced heterogeneity dynamically evolving tumor microenvironment (TME). The lack accurate disease models complicates understanding mechanisms impedes discovery novel drugs. A growing body evidence suggests that organoids, developed using organoid culture technology, preserve genetic, phenotypic, behavioral characteristics. organoids hold significant potential for predicting treatment responses in individual patients. This review provides comprehensive overview current clinical strategies GC, as well history, construction applications organoids. focus on role simulating TME to explore immune evasion intratumoral microbiota their guiding drug therapy facilitating screening. Furthermore, we summarize limitations underscore need continued technological advancements benefit both basic translational oncological research.
Language: Английский
Citations
0
Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(5)
Published: April 28, 2025
Abstract Background Gastric cancer (GC) exhibits high heterogeneity that relies on the oncogenic properties of cells and multicellular interactions in tumour microenvironment. However, GC their molecular characteristics are still largely unexplored. Methods We employed single‐cell spatial transcriptomics to comprehensively map intra‐tumoural within GC. Additionally, vitro experiments, clinical sample analyses, patient‐derived organoid models (PDOs) were conducted validate key interaction patterns between tumor stromal cells. Results Seven robust meta‐programs (MP1–MP7) defined with distinct biological significance distributions. MP3 MP4 intimately associated CD8 T skewed toward a cytotoxic or exhaustion state, while MP7, characterised by highest degree malignancy, harboured an immune lockdown microenvironment around it spatially myofibroblasts (myCAFs). Notably, we clarified interplay MP7 myCAFs, where induces chemotactic migration fibroblasts promoting transformation into myCAFs via GDF15/TGFBR2, turn, myCAFs‐derived RSPO3 up‐regulates EGR1 promote human PDOs. Ultimately, accumulation led fewer infiltration cells, resulting immune‐deprived diminished efficacy immunotherapy. based gene expression signatures predicted specific drugs verified more potent inhibitory effects Taselisib Lapatinib for than conventional at same concentration. Conclusion Taken together, these results deepened understanding paved way novel therapeutic strategies targeting loop treatment. Key points (MP1‐MP7) identified gastric cancer. was strongly correlated metastasis poor survival patients. promoted fibroblast creating MyCAFs induced RSPO3/EGR1 pathway, cell migration. inhibitors
Language: Английский
Citations
0
PLoS ONE, Journal Year: 2025, Volume and Issue: 20(5), P. e0322029 - e0322029
Published: May 2, 2025
Ado-trastuzumab emtansine (T-DM1), a conjugate of trastuzumab and the cytotoxic agent emtansine, has demonstrated significant antitumor efficacy in HER2-positive (HER2+) carcinoma. However, its effectiveness is limited against carcinoma cells with low HER2 expression (HER2-low). Here, we demonstrate that targeting autophagy enhances cytotoxicity T-DM1 HER2-low SGC7901 cells, highlighting potential modulation improving T-DM1-based therapies for carcinomas. Specifically, this study shows exhibits effects on but pharmacological inhibition cytotoxicity. Moreover, transmission electron microscopy revealed activation involved three key phases autophagic flux: formation, fusion, degradation autophagosomes, while immunoblot analysis confirmed reduction Akt/mTOR signaling. Furthermore, accelerated fusion lysosomes as shown by confocal microscopy. Collectively, these findings suggest alone induces cytotoxicity, combining it inhibitors cells. Mechanistically, increases binding to lysosomes, potentially facilitating release from conjugate. These results present novel strategy combines effectively treat gastric cancer, thereby broadening therapeutic scope encompass previously challenging cancer types.
Language: Английский
Citations
0
PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e18428 - e18428
Published: Nov. 11, 2024
Background Cancer-associated fibroblasts (CAFs) and hepatocellular carcinoma (HCC) cells interact to promote HCC progression, but the underlying mechanisms remain unclear. Serpin family E member 1 (SERPINE1) has conflicting roles in HCC, microRNAs (miRNAs) are known regulate tumor progression through intercellular communication. Therefore, we investigated potential involvement of miRNA/SERPINE1 axis crosstalk between CAFs cells. Methods In this study, candidate miRNAs targeting SERPINE1 3′ UTR were predicted using multiple miRNA databases. The mRNA expression Huh7 was assessed after co-culture with RT-qPCR. cell proliferation invasion detected siRNA. functions CAF-derived miR-642a-3p/SERPINE1 examined CCK-8, wound healing, transwell assays, western blot, dual-luciferase reporter assays. Moreover, a orthotopic xenograft model used investigate contribution miR-642a-3p knockdown HCC. Results decreased, while increased co-cultured CAFs. enhanced as well expression. overexpression promoted migration, invasion, epithelial-mesenchymal transition (EMT) by SERPINE1, yielded opposite effect. Rescue experiments confirmed that attenuated inhibitory effects on EMT Importantly, suppressed growth liver tumors. Conclusion facilitated cells, suggesting can be therapeutic target for
Language: Английский
Citations
3
Published: Jan. 1, 2025
Language: Английский
Citations
0