RESULTS: Further investigation into CL bioactive fraction (II-F7) revealed significant dose-dependent growth inhibitory effects on MCF-7 cells, which were attributed to the induction of apoptosis, as evidenced by the presence of apoptotic bodies, fragmented DNA, and disruption of mitochondrial membrane potential. Additionally, treatment with CL bioactive fraction (II-F7) upregulated the expression of pro-apoptotic genes (DDIT3, GADD45G and HRK) and significantly increased the activities of caspase-8 and caspase-9.
CONCLUSION: Overall, this study suggests that bioactive fraction (II-F7) from CL extract has significant and selective cytotoxicity against MCF-7 cells through inducing apoptosis and has potential as a therapeutic agent for breast cancer treatment.
SIGNIFICANCE: Mutant HRAS drives metastasis of head and neck cancer by switching off the Hippo pathway to activate the YAP1-AXL axis and to stimulate lymphovascular angiogenesis.
METHODOLOGY: The present study investigates the effects of heterogeneous GNR distribution in a typical setup of GNR-PTT. Three cases were considered. Case 1 considered the GNRs at the tumour centre, while Case 2 represents a hypothetical scenario where GNRs are distributed at the tumour periphery; these two cases represent intratumoural accumulation with different degree of GNR spread inside the tumour. Case 3 is achieved when GNRs target the exposed tumoural surface that is invading the bladder wall, when they are delivered by intravesical instillation.
RESULTS: Results indicate that for a laser power of 0.6 W and GNR volume fraction of 0.01%, Case 2 and 3 were successful in achieving complete tumour eradication after 330 and 470 s of laser irradiation, respectively. Case 1 failed to form complete tumour damage when the GNRs are concentrated at the tumour centre but managed to produce complete tumour damage if the spread of GNRs is wider. Results from Case 2 also demonstrated a different heating profile from Case 1, suggesting that thermal ablation during GNR-PTT is dependant on the GNRs distribution inside the tumour. Case 3 shows similar results to Case 2 whereby gradual but uniform heating is observed. Cases 2 and 3 show that uniformly heating the tumour can reduce damage to the surrounding tissues.
CONCLUSIONS: Different GNR distribution associated with the different methods of introducing GNRs to the bladder during GNR-PTT affect the treatment outcome of bladder cancer in mice. Insufficient spreading during intratumoural injection of GNRs can render the treatment ineffective, while administered via intravesical instillation. GNR distribution achieved through intravesical instillation present some advantages over intratumoural injection and is worthy of further exploration.
MATERIALS AND METHODS: The STIM1 effect was assessed via dicersubstrate siRNA-mediated STIM1 knockdown. The effect of STIM1 knockdown on the expression of AKT and MAPK pathway-related genes and reactive oxygen species (ROS) generation-related genes was tested using real-time polymerase chain reaction. Cellular functions, including ROS generation, cell proliferation, and colony formation, were also evaluated following STIM1 knockdown.
RESULTS: The findings revealed that STIM1 knockdown reduced intracellular ROS levels via downregulation of NOX2 and PKC. These findings were associated with the downregulation of AKT, KRAS, MAPK, and CMYC. BCL2 was also downregulated, while BAX was upregulated following STIM1 knockdown. Furthermore, STIM1 knockdown reduced THP-1 cell proliferation and colony formation.
CONCLUSION: This study has demonstrated the role of STIM1 in promoting AML cell proliferation and survival through enhanced ROS generation and regulation of AKT/MAPK-related pathways. These findings may help establish STIM1 as a potential therapeutic target for AML treatment.