Orelabrutinib versus ibrutinib for patients with refractory/relapsed primary central nervous system lymphoma: An efficacy and safety analysis.

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/m 2 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/m 2 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/m 2 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).

Simultaneous quantification of pirarubicin, doxorubicin, cyclophosphamide, and vincristine in human plasma of patients with non-Hodgkin's lymphoma by LC-MS/MS method.

Pirarubicin (THP), doxorubicin (DOX), cyclophosphamide (CTX), and vincristine (VCR) are widely used in the treatment of patients with non-Hodgkin's Lymphoma. Herein, a precise and sensitive method was developed for the determination of THP, DOX, CTX and VCR in human plasma by high-performance liquid-chromatography-tandem mass spectrometry (LC-MS/MS). Liquid-liquid extraction was applied to extract THP, DOX, CTX, VCR, and the internal standard (IS, Pioglitazone) in plasma. Agilent Eclipse XDB-C18 (3.0 mm × 100 mm) was utilized and chromatographic separation was obtained in eight minutes. Mobile phases were composed of methanol and buffer (10 mM ammonium formate containing 0.1% formic acid). The method was linear within the concentration range of 1-500 ng/mL for THP, 2-1000 ng/mL for DOX, 2.5-1250 ng/mL for CTX, and 3-1500 ng/mL for VCR. The intra- and inter-day precisions of QC samples were found to be below 9.31 and 13.66%, and accuracy ranged from -0.2 to 9.07%, respectively. THP, DOX, CTX, VCR and the internal standard were stable in several conditions. Finally, this method was successfully utilized to simultaneously determine THP, DOX, CTX and VCR in human plasma of 15 patients with non-Hodgkin's Lymphoma after intravenous administration. Finally, the method was successfully employed in the clinical determination of THP, DOX, CTX, and VCR in patients with non-Hodgkin lymphoma after administration of RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens.

ZEB1 induces non-small cell lung cancer development by targeting microRNA-320a to increase the expression of RAD51AP1.

Lung cancer is the most prevalent cancer worldwide, with its mortality rate reported to be in millions annually; one of the two subtypes is non-small cell lung cancer (NSCLC). In this study, we investigated the interactions and expressions of zinc finger E-box binding homeobox 1 (ZEB1), microRNA-320a (miR-320a) and RAD51-associated protein 1 (RAD51AP1) in NSCLC tissues to determine the roles of ZEB1 in regulation of miR-320a and RAD51AP1 in the development and metastasis of NSCLC. First, the expression levels of miR-320a and ZEB1 were quantified in NSCLC tissues and cells. Transfection assay was conducted to identify the effects of miR-320a on the progression of NSCLC cells. The interaction of miR-320a with ZEB1 and RAD51AP1 was predicted and verified using dual-luciferase reporter gene assay and chromatin immunoprecipitation assay. Finally, subcutaneous xenograft tumors of 6-week mice and metastatic model tumors of 8-week mice were established to further explore the in vivo effect of miR-320a/ZEB1/RAD51AP1 on NSCLC. The findings revealed a lower expression of miR-320a in NSCLC tissues and cells, while this result was reversed regarding ZEB1 expression. ZEB1 suppressed miR-320a expression and upregulation of miR-320a resulted in the reduction of proliferation, invasion and metastasis rate of NSCLC cells, and promoted NSCLC cell apoptosis. ZEB1 promoted the expression of RAD51AP1 via inhibition of miR-320a, promoting tumor growth in vivo. ZEB1 transcriptionally inhibited the expression of miR-320a and upregulated the expression of RAD51AP1, thereby promoting metastasis in NSCLC.

[Over-expression of aquaporin 1 (AQP1) promotes cell proliferation and inhibits ß-catenin phosphorylation in human lung adenocarcinoma A549 cells].

Objective To investigate the effect of over-expression of aquaporin 1 (AQP1) gene on the proliferation of human lung adenocarcinoma A549 cells and its possible mechanism. Methods A lentiviral vector for over-expression of AQP1 was constructed, identified and used to infect A549 cells. Real-time quantitative PCR and Western blot analysis were performed to detect the expression of AQP1 mRNA and protein, respectively. In the AQP1-over-expressing A549 cells, MTT assay, clone formation assay and Western blot analysis were used to assess cell proliferation, cell clone forming ability, and ß-catenin phosphorylation level, respectively. Results The retroviral expression vector of AQP1 with a virus titer of (2.87±0.54)×108 IU/mL was obtained and A549 cells were infected with it to get a stable AQP1 over-expressing cell line. In this cell line, the AQP1 mRNA and protein levels were significantly raised, the cell proliferation ability was significantly improved, and the number of cell clones was significantly elevated. The total protein level of ß-catenin increased, but the phosphorylation of ß-catenin decreased significantly. Conclusion Over-expression of AQP1 promotes A549 cell proliferation and inhibits ß-catenin phosphorylation.

Silencing of RAD51AP1 suppresses epithelial-mesenchymal transition and metastasis in non-small cell lung cancer.

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.