[Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study].

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

LncRNA PCAT1 enhances cell proliferation, migration and invasion by miR-508-3p/NFIB axis in diffuse large B-cell lymphoma.

OBJECTIVE: In previous studies, PCAT1 has been proved to be a key carcinogenic driver in hepatocellular carcinoma. However, the regulatory mechanism of PCAT1 remains poorly understood in diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The expression of PCAT1, miR-508-3p and NFIB in DLBCL was detected by RT-qPCR assay. CCK-8 assay and transwell assay were used to measure cell proliferation, migration and invasion of DLBCL cells. Western blot assay was used to explore the protein expression of NFIB. Dual-Luciferase reporter assay was applied to measure the correlation between PCAT1, miR-508-3p and NFIB. RESULTS: PCAT1 was demonstrated to be upregulated in DLBCL tissues and cell lines. Besides, PCAT1 expression was associated with clinical stage and IPI score of DLBCL patients. Moreover, overexpression of PCAT1 promoted DLBCL cell proliferation, migration and invasion in vitro. Mechanistic investigation displayed that PCAT1 interplayed with miR-508-3p, while NFIB was a target gene of miR-508-3p. Further, miR-508-3p was in a downtrend while NFIB was increased in DLBCL tissues and cell lines. MiR-508-3p overexpression repressed DLBCL cell growth and metastasis, while PCAT1 overexpression reversed the inhibitory effect of miR-508-3p on the progression of DLBCL. Moreover, NFIB silencing suppressed DLBCL cell proliferation, migration and invasion, whereas PCAT1 vector or miR-508-3p knockdown destroyed the inhibitory of si-NFIB on the progression of DLBCL. CONCLUSIONS: Taken together, our findings validated that PCAT1 acted as completive endogenous RNA by sponging miR-508-3p and upregulating NFIB to facilitate DLBCL cell proliferation, migration and invasion.

Long non-coding RNA NEAT1 regulates Hodgkin's lymphoma cell proliferation and invasion via miR-448 mediated regulation of DCLK1.

OBJECTIVE: To explore whether long non-coding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) could regulate Hodgkin's lymphoma (HL) cell proliferation and invasion through miR-448, which could target doublecortin like kinase 1 (DCLK1) and mediate DCLK1 expression. PATIENTS AND METHODS: Expressions of NEAT1, miR-448 and DCLK1 were evaluated by qRT-PCR or Western blot assay. Cell Counting Kit-8 (CCK-8) and transwell assay were utilized to detect cell proliferation and invasion capability in L428 cells respectively. The target relationship between NEAT1, miR-448 and DCLK1 was confirmed by Luciferase reporter assay. RESULTS: QRT-PCR results showed that NEAT1 expressed higher in HL tissues and cell lines than that in controls. In vitro experiments, NEAT1 downregulation could decrease cell proliferation and invasion capability in L428 cells. NEAT1 directly interacted with miR-448 and negatively regulated it. Moreover, DCLK1 was confirmed as a target of miR-448. DCLK1 expression was increased in L428 cells and positively regulated by NEAT1. NEAT1 overexpression upregulated the protein level of DCLK1 in L428 cells according to Western blot analysis. Additionally, DCLK1 overexpression could reverse the suppression on cell proliferation and invasion capability induced by NEAT1 knockdown or miR-448 overexpression. CONCLUSIONS: NEAT1 might be contributed to HL progression by promoting cell proliferation and invasion capability via miR-448 mediated DCLK1 expression.

The anti-cancer effects of cisplatin on hepatic cancer are associated with modulation of miRNA-21 and miRNA-122 expression.

OBJECTIVE: Cisplatin is an effective chemotherapeutic drug to treat hepatic cancer, but its efficacy is marred by extensive adverse effects. Micro (mi) RNAs are small regulatory RNAs that may be used as molecular targets to better fine-tune chemotherapy in hepatic cancer. In this study, we examined to what extent the anti-cancer effects of cisplatin are associated with expressions of miRNA (miR)-21 and miR-122. MATERIALS AND METHODS: The growth-inhibiting effects of cisplatin on the human hepatic cell line HepG2 were assessed by MTT assay, while cell apoptosis was documented using DAPI staining. Also, we tested the effects of cisplatin on tumour growth in a mouse tumour xenograft model. Finally, we quantified expression levels of miR-21 and miR-122 in cisplatin-treated HepG2 cells. RESULTS: We observed that cisplatin significantly decreased the growth of HepG2 cells (p < 0.05 vs control cells) at all tested concentration (5-80 µg/ml) after 24 or 48 hours of treatment. Microscopic studies demonstrated apoptotic signs in cisplatin-treated cells. In the mouse tumour xenograft model, tumour weights and volumes were significantly (p < 0.05 untreated animals) lower after treatment with cisplatin. Also, treatment of HepG2 cells for 48 hours with 20 µg/ml cisplatin was associated with significant decreases in miR-21 expression levels and up-regulation of miR-122. CONCLUSIONS: The anti-cancer effects of cisplatin are associated with down-regulation of miR-21 expression and up-regulation of miR-122.