Background Non‐small cell lung cancer (NSCLC) is a major cause of cancer‐related mortality and is frequently accompanied by metastasis. The crucial roles of genes in lung cancer have attracted attention. Thus, this study aimed to investigate the effects of RAD51AP1 on the epithelial–mesenchymal transition (EMT) and metastasis of NSCLC. Methods The positive expression rate of the RAD51AP1 protein was examined. NSCLC cells were transfected with a series of plasmids to alter the expression of RAD51AP1 to clarify the influence of RAD51AP1 on EMT and metastasis in NSCLC, as well as NSCLC cell migration, invasion, apoptosis, proliferation, and cloning. An in vivo experiment was conducted to determine the oncogenicity of human NSCLC cells in nude mice. Results RAD51AP1 was highly expressed in NSCLC tissues. Furthermore, we found promotion of N‐cadherin, vimentin, fibronectin, MMP‐2, OPN, CD62, and TMP‐2, but inhibition of E‐cadherin, occludin, cytokeratin in the context of elevated RAD51AP1 expression. An in vivo experiment also confirmed that silencing of RAD51AP1 could inhibit NSCLC tumor formation and growth. Conclusion Our results revealed that RAD51AP1 silencing suppressed the EMT and metastasis of NSCLC, thereby highlighting its potential as a promising novel target for NSCLC treatment.
Ibrutinib is reported effective in the management of refractory/relapsed primary central nervous system lymphoma but it has adverse effects. Orelabrutinib has received its first approval for the treatment of refractory/relapsed lymphoma either alone or with chemotherapy in China. The objectives of the retrospective study were to evaluate the efficacy and safety of treatment a combination of orelabrutinib (150 mg/day) and rituximab (250 mg/m2 per week), versus orelabrutinib alone (100 mg twice a day) and ibrutinib alone (560 mg/day) among patients with refractory/relapsed primary central nervous system lymphoma. Patients received 150 mg/day orelabrutinib with 250 mg/m2 rituximab/week (RO cohort, n = 105) or 100 mg twice in a day orelabrutinib (OB cohort, n = 107) or 560 mg/day ibrutinib (IB cohort, n = 117) until intolerable toxicity. Patients of the OB cohort continue treatment(s) for longer time than those patients of the RO and the IB cohorts (P < .05 for both). Overall response rate (complete response + partial response) and disease control rates (complete response + partial response + no signs of progressive response) were higher for patients of the RO cohort than those of the IB cohort (P < .0001 for both). The disease control rate was higher for patients of the OB cohort than those of the IB cohort (P = .0062). The overall response rate was higher for patients of the RO cohort than those of the OB cohort (P = .0188). Progression-free survival (from the initiation of disease treatment(s) to disease progression) of patients of the RO and OB cohorts were higher than those of the IB cohort (P < .0001 for both). Overall survival (from the initiation of disease treatment(s) to death) of the patients of the IB cohort was fewer than those of the RO (P = .0444) and the OB (P = .0163) cohorts. Ibrutinib cause bleeding events, and orelabrutinib caused leukopenia, purpura diarrhea, fatigue, and drowsiness. Rituximab and ibrutinib cause fungal infections, atrial fibrillation, bacterial and viral infection(s), hypertension, and tumor lysis syndrome. A total of 150 mg/day oral orelabrutinib plus 250 mg/m2 intravenous rituximab/week is efficacious and safe for patients with refractory/relapsed primary central nervous system lymphoma (Level of Evidence: IV; Technical Efficacy Stage: 5).
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