Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control
Peer-Reviewed Publication
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Cancer remains a leading cause of death globally, with lung cancer being particularly lethal. Despite advancements in diagnostics and therapies, the five-year survival rates for advanced tumors have seen minimal improvement, largely due to therapeutic resistance. This resistance can be genetic or nongenetic, with the latter being less understood but increasingly recognized for its role in treatment failure. Non-genetic resistance is associated with resistant cancer cells that have innate or acquired drug resistance traits. These cells are often found in heterogeneous tumors and include cancer stem-like cells (CSCs), cells undergoing epithelial-to-mesenchymal transition (EMT), partial EMT cells, and drug-tolerant persisters (DTPs). NOTCH signaling plays a crucial role in tumorigenesis and therapeutic resistance, with its activation linked to drug resistance in various cancers.
This study demonstrates that the activities of soil extracellular enzymes were significantly altered in the alpine meadow, but not significantly in the swamp meadow, which coincided with the SOC content of these grasslands.
Research team proposed DeepSwarm, a collective deep learning framework integrating swarm intelligence for bidirectional optimization of data acquisition and processing. It improves accuracy and resource efficiency in IoT scenarios, showing significant results in video analysis and federated learning.
Key findings
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What is known and what is new?
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• Severity of COVID-19 was also more serious in subjects stricken with sarcoidosis.
What is the implication, and what should change now?
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Background: Recent evidence suggests that postoperative adjuvant radiotherapy (PORT) may enhance survival outcomes in patients with pN2 non-small cell lung cancer (NSCLC), particularly when evaluating through examined lymph nodes (ELNs) and lymph node ratio (LNR). This study aims to explore the impact of ELNs and LNR on the efficacy of postoperative radiotherapy in pN2 stage NSCLC patients through a multicenter retrospective cohort analysis, providing valuable insights for clinical treatment decisions.
Methods: Data were meticulously extracted from the Surveillance, Epidemiology, and End Results (SEER) 17 registry spanning 2015 to 2019. The study specifically targeted pN2 stage NSCLC patients who underwent surgical intervention and lymph node biopsy, involving an analysis of 1,875 patients while excluding those with incomplete data. The impact of PORT on overall survival (OS) was assessed, stratified by ELNs and LNR. Statistical analyses employed X-tile software to categorize LNR into three distinct groups, and Cox proportional hazard models were utilized to evaluate the influence of various factors on OS.
Results: The Cox proportional hazards model revealed a significant survival advantage associated with PORT, demonstrating a 22% higher mortality rate in the non-PORT group [hazard ratio (HR) =1.22, 95% confidence interval (CI): 1.02–1.46, P=0.03] and up to 31% higher in the fully adjusted model (HR =1.31, 95% CI: 1.09–1.58, P=0.004). PORT notably improved survival in patients with ELNs <10, particularly when LNR ≤0.2 (HR =4.15, P=0.03) and LNR ≥0.53 (HR =1.83, P=0.01). Kaplan-Meier survival curves corroborated these findings.
Conclusions: Our findings indicate that the number of ELNs and the LNR could serve as valuable criteria for selecting pN2 NSCLC patients who may benefit from PORT. PORT has been linked to improved survival outcomes in pN2 stage NSCLC, with a particular emphasis on its efficacy in patients with ELNs <10 and an LNR of ≤0.2.
Keywords: Postoperative adjuvant radiotherapy (PORT); examined lymph nodes (ELNs); lymph node ratio (LNR); non-small cell lung cancer (NSCLC); Surveillance, Epidemiology, and End Results (SEER)