[Effect of autologous hematopoietic stem cell transplantation on minimal residual disease in patients with multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on minimal residual disease (MRD) in patients with multiple myeloma (MM). Method: From August 2018 to August 2021, 92 patients newly diagnosed with MM who had received either the bortezomib combined with cyclophosphamide and dexamethasone (VCD) or the bortezomib, lenalidomide and dexamethasone (VRD) induction regimens followed by sequential ASCT were assessed for overall survival (OS) and the MRD negative rate. The differences in efficacy at 100 days after transplantation were assessed according to factors, including age, risk stratification, target organ damage, and pre-transplant regimen, etc. Results: Among the 92 patients, there were 45 males and 47 females, with a median age of 57.3 (35-67) years. Fifty-seven patients received the VCD regimen, and 35 received VRD as induction regimen. Forty-three patients received busulphan combined with cyclophosphamide and etoposide (BCV), and 49 patients received high-dose melphan (HDM) regimen as pre-transplantation treatment. After transplantation, the total complete remission (CR) rate of 92 patients increased from 23.9% (22/92) to 58.7% (54/92), and the MRD negative rate increased from 4.4% (4/92) to 33.7% (31/92), and the differences were statistically significant (all P<0.05). After transplantation, the MRD negative rates of patients with PR, VGPR and ≥CR before transplantation were 17.6% (6/34), 33.3% (12/36) and 59.1% (13/22), respectively (P=0.006). The CR rates of patients with or without plasmacytoma at initial diagnosis were 36.4% (4/11) and 65.4% (53/81), respectively (P=0.029), and the MRD negative rates were 18.2% (2/11) and 39.5% (32/81), respectively (P=0.037), and the differences were statistically significant. The MRD negative rates in high-risk patients and standard-risk group were 30.5% (12/28) and 42.9% (18/59), respectively (P=0.258). For patients who achieved efficacy above VGPR before transplantation, the MRD negative rates after transplantation in VCD-induced group and VRD group were 29% (9/31) and 59.3% (16/27), respectively (P=0.033), and in BCV group and HDM group were 24% (6/25) and 57.6% (19/33), respectively (P=0.016), the differences between the groups were both statistically significant. Conclusion: ASCT can overcome the adverse factors such as high-risk cytogenetic abnormalities, and significantly improve the CR rate and MRD negative rate of MM patients. However, the benefit for patients with plasmacytoma at initial diagnosis is not as good as that of patients without.

Effect of RRS1 gene knockdown on BT549 cell line proliferation and apoptosis in breast cancer.

The RRS1 regulator of ribosome synthesis has recently been reported a new target gene linked to cancer development. This study therefore investigates RRS1effectsb on BT549 cell proliferation and apoptosis in breast cancer. Western blot (WB) and real - time quantitative PCR (qPCR) were used to detect the relative expression of RRS1 in breast cancer cells BT-549 and the normal HMEC mammary gland epithelial cells. BT-549 cells were cultured and infected with retroviruses and RRS1 expression was detected by qPCR and WB. The MTT assay, Caspase-3/7 and flow cytometry (FCM) then detected growth and apoptosis in the BT549 breast cancer BT cell. WB detected the expression of Bcl-2 and Bax genes related to apoptosis at the protein level, and MTT assay confirmed that RRS1 knockdown significantly decreased cell viability (p<0.05) and induced apoptosis which was rescued by shRNA-RRS1 expression. The amount of caspase-3 increased significantly and apoptosis was obvious. The apoptotic cells amount analyzed by FCM was significantly increased and RRS1 knockdown also decreased the expression of apoptosis related protein bcl-2 and simultaneously increased the expression of Bax (p<0.05). Finally, the RRS1 gene was highly expressed in breast cancer cell line BT549 and its knockdown significantly reduced proliferation and apoptosis in BT549 cell. These results suggest that RRS1 is a novel gene related to breast cancer and has an important role in breast cancer proliferation and apoptosis.

Aspirin inhibits MMP-9 mRNA expression and release via the PPARalpha/gamma and COX-2/mPGES-1-mediated pathways in macrophages derived from THP-1 cells.

In present study, we investigated the effects of aspirin on matrix metalloproteinase (MMP)-9 mRNA expression and release and its possible mechanisms in macrophages derived from THP-1 cells. The macrophages were divided into different groups and treated with different drugs, the mRNA expression of MMP-9, peroxisome proliferator-activated receptor (PPAR) alpha and gamma, cyclooxygenase (COX)-2, membranebound prostaglandin E synthase (mPGES)-1 in macrophages were examined with reverse-transcription polymerase chain reaction, and the protein expressions of PPAR alpha and gamma, mPGES-1 were detected by Western-blot, the levels of MMP-9 and PGE(2) in cultured supernatants were determined with enzyme-linked immunosorbent assay. The results indicated that after the macrophages were incubated with aspirin for 24h, the MMP-9 mRNA expression and release were decreased, while the PPAR alpha/gamma mRNA and protein expression was increased, respectively, and PPAR alpha/gamma agonists could also decrease MMP-9 mRNA expression and release. Additionally, the COX-2 mRNA expression, mPGES-1 mRNA and protein expression in macrophages were all decreased after incubation with aspirin for 24h and the PGE(2) release was also decreased. The macrophages stimulated with PGE(2) for 24h might increase the MMP-9 mRNA expression and release. When PGE(2) plus PPAR alpha agonist or PPAR gamma agonist were simultaneously used, the stimulation of MMP-9 mRNA expression and release by PGE(2) was significantly decreased. It might be concluded that aspirin could inhibit the MMP-9 gene expression and release through the PPARalpha/gamma and COX-2/mPGES-1-mediated pathways and the two pathways might be partly overlapped and even be interrelated.