The significance of autologous hematopoietic stem cell transplantation on immunoglobulin reconstitution and prognosis in elderly patients with multiple myeloma.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (ASCT) is a crucial method used in patients with multiple myeloma (MM). This study aims to evaluate the role of ASCT in immunoglobulin (Ig) reconstitution and long-term outcomes in patients aged ≥ 60 years. METHODS: From March 2008 to May 2019, 93 patients aged ≥ 60 years who were diagnosed with MM and underwent ASCT were retrospectively analyzed. All patients underwent follow-ups and the deadline for follow-up was October 31, 2022. The Ig levels were measured using the immune turbidimetry method at 3, 6, and 12 months after transplantation. Patients who died or experienced relapse were excluded from the analysis. The prognostic value of Ig levels was estimated using the Kaplan-Meier survival curve and Cox regression method. RESULTS: No patients died, and all patients with complications showed improvements after treatment. Patients in the Ig reconstitution group had a lower international staging system (ISS) stage, whereas those in the immunoparesis group had a higher ISS stage. The median duration of follow-up was 36 (range, 13-120) months. The Ig reconstitution within 12 months indicated a longer overall survival and progression-free survival outcomes. The detection of Ig levels was an independent indicator for the prognosis of MM. DISCUSSION AND CONCLUSION: The Ig reconstitution within 12 months of ASCT could predict the overall outcomes of patients with MM aged ≥ 60 years.

[The Molecular Mechanism of LncRNA HOTAIR Regulating the Proliferation, Invasion and Migration of Lymphoma Cells through Target Gene miR-20a-5p].

OBJECTIVE: To investigate the effects of lncRNA HOTAIR on the proliferation, invasion and migration of lymphoma cells through target gene miR-20a-5p and its molecular mechanism. METHODS: After synthesizing HOTAIR siRNA and siRNA NC plasmids, they were transfected into lymphoma Raji cells, respectively. The expression of HOTAIR mRNA was detected by RT-qPCR. The proliferation, invasion and migration of lymphoma Raji cells were detected by CCK-8 assay, Transwell assay and cell scratch healing assay, respectively. The target gene of lncRNA HOTAIR was predicted by miRcode software, and the relationship between HOTAIR and target gene was analyzed by dual luciferase assay. After synthesis of miR-20a-5p inhibitor and inhibitor NC, Raji cells were transiently transfected. The expression of miR-20a-5p was detected by RT-qPCR, and the effects of down-regulation of miR-20a-5p on the proliferation, invasion and migration of Raji cells were analyzed. The overexpression plasmid of lncRNA HOTAIR and miR-20a-5p mimics were transfected into Raji cells simultaneously to analyze the proliferation, invasion and migration ability of Raji cells. After overexpression or down-regulation of miR-20a-5p, the expression of JAK/STAT3 signaling pathway related proteins was analyzed. RESULTS: HOTAIR expression in Raji cells was decreased after transfection of HOTAIR siRNA (P<0.01), and miR-20a-5p expression was also decreased after transfection of miR-20a-5p inhibitor (P<0.01). HOTAIR had a targeting and negative regulation relationship with miR-20a-5p (r=-0.826). Silencing HOTAIR promoted the expression of miR-20a-5p and inhibited the proliferation, invasion and migration of Raji cells. Down-regulation of miR-20a-5p expression promoted the proliferation, invasion and migration of Raji cells. Effect of HOTAIR overexpression on the proliferation, invasion and migration of Raji cells could be reversed by up-regulation of miR-20a-5p. Down-regulation of miR-20a-5p expression activated the intracellular JAK/STAT3 signaling pathway. CONCLUSION: HOTAIR affects the proliferation, invasion and migration of lymphoma cells by targeting miR-20a-5p, and its mechanism may be related to the activation of JAK/STAT3 signaling pathway.

The role of mesenchymal stem cells in promoting the transformation of androgen-dependent human prostate cancer cells into androgen-independent manner.

Mesenchymal stem cells (MSCs) play an important role in the development of human prostate cancer (PCa). However, the role of MSCs in the transformation of androgen-dependent human PCa cells into androgen-independent manner has been poorly understood. In this study, we investigated the underlying mechanism of MSCs in promoting PCa cells from androgen-dependent into androgen-independent manner. Firstly, we demonstrated that MSCs could affect the transformation of androgen-dependent human PCa cells into androgen-independent manner in vivo and in vitro. Then we found a substantial expression of TGF-ß in MSCs. TGF-ß blockade could significantly inhibit the promotive function of MSCs in PCa cells. Besides that, we also demonstrated androgen might inhibit the expression of TGF-ß in MSCs. Furthermore, we found that either overexpression of SSEA-4 or the number of SSEA-4 positive MSCs in PCa tissues was associated with a shorter cancer-free survival interval (CFSI) and a worse overall survival (OS). Our results suggest that androgen blockade treatment in clinical PCa therapy may elicit the expression of TGF-ß in MSCs, which will result in the transformation of androgen-dependent human PCa cells into androgen-independent manner.