ABSTRACT
OBJECTIVE: To assess the impact of early relapse (ER) after autologous hematopoietic stem cell transplan-tation (AHSCT) on overall survival (OS) for multiple myeloma (MM) patients. METHODS: Clinical data of 37 patients with MM undergoing AHSCT in department of hematology of Shanxi Bethune Hospital from January 2012 to December 2017 were retrospectively analyzed. The effect of ER on OS of patients was analyzed. The effects of international staging system (ISS) staging, cytogenetics, pre-transplant efficacy, minimal residual disease, and age on OS of the patients were also analyzed respectively. RESULTS: Among the 37 patients, 13 cases (35.1%) had ER, and 24 cases (64.9%) had non-ER. 3 patients with ER had extramedullary disease, but none with non-ER showed extramedullary disease. More than or equal to very good partial rate (VGPR) in patients with ER and without ER were 3 cases (23.1%) and 15 cases (62.5%), respectively, and the curative effect of the former was significantly lower than that of the latter (P<0.05). The median follow-up time was 31 (12-96) months, and median OS time was 93 months in all the patients. The median survival time of patients with ER was 17 months, and the median progression free survival was 7 months, both were significantly shorter than 93 months and 38 months of patients with non-ER (P<0.05). Univariate analysis showed that the OS was affected by ER, cytogenetic abnormalities (FISH), and ≥VGPR before transplantation. Multivariate analysis showed that ER was an independent prognostic factor. CONCLUSION: The prognosis of patients with ER after AHSCT in newly diagnosed MM is poor. ER is an independent prognostic factor of survival.
Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Prognosis , Recurrence , Retrospective Studies , Transplantation, Autologous , Treatment OutcomeABSTRACT
BACKGROUND AND AIMS: Genistein, a principal component of soybean isoflavones, plays an important role in the prevention of atherosclerosis. However, the detailed mechanisms have not been fully investigated. The aims of this study were to evaluate the anti-atherosclerotic effect and investigate potential pharmacological mechanism of genistein. METHODS: A model of oxidized low-density lipoprotein (ox-LDL)-induced injury in on human umbilical vein endothelial cells (HUVECs) was established to evaluate the protective role of genistein. Macrophage/monocyte chemoattractant protein-1 (MCP-1), vascular cellular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) secretion and their messenger RNA transcription were observed via enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase PCR (RT-PCR). Meanwhile, the study investigated the role of Nrf2/HO-1 pathway during the process. RESULTS: Pretreatment with genistein markedly reduced ox-LDL-induced MCP-1, VCAM-1 and ICAM-1 secretion and mRNA transcription, which was further decreased by the inducer of HO and reversed by the inhibitor of HO; additionally, the effects were accompanied with upregulating HO-1 mRNA and protein expression and markedly abolished with Nrf2 siRNA. CONCLUSIONS: Anti-inflammatory effect of genistein on endothelial cells may be associated with the activation of Nrf2/HO-1 pathway.
Subject(s)
Chemokine CCL2/metabolism , Genistein/pharmacology , Heme Oxygenase-1/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Intercellular Adhesion Molecule-1/biosynthesis , Lipoproteins, LDL/pharmacology , Vascular Cell Adhesion Molecule-1/biosynthesis , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cell Survival/drug effects , Chemokine CCL2/biosynthesis , Chemokine CCL2/genetics , Down-Regulation/drug effects , Heme Oxygenase-1/genetics , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/enzymology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , NF-E2-Related Factor 2/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
OBJECTIVE: Genistein could inhibit the development of atherosclerosis. This study explored the role of PI3K/AKT signaling during genistein promoted eNOS activation. METHODS: Human umbilical vein endothelial cells (HUVECs) were incubated with ox-LDL (100 mg/L), then treated with genistein (100 nmol/L) for 5, 10, 15, 30 and 60 min. The production of NO was assessed by Griess reaction in cell culture supernatant. The mRNA expression of endothelial nitric oxide synthase (eNOS) was detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of eNOS and phosphorylation eNOS(Ser(1179)) were determined by Western blot. The effect of genistein on phosphorylation eNOS(Ser(1179)) level was also observed in the presence of LY294002 or NSC154020 (PI3K and AKT inhibitors). RESULTS: The concentration of NO and the expression level of phosphorylation eNOS(Ser(1179)) were significantly increased in ox-LDL + genistein treated cells than ox-LDL treated cells (all P < 0.05), and the peak effects were observed at 15 min, however, eNOS mRNA and non-phosphorylated eNOS protein expression were similar between the two groups (P > 0.05). Furthermore, the expression level of phosphorylation eNOS(Ser(1179)) was significantly lower in PIK3/AKT inhibitors LY294002 and NSC154020 treated cells compared with ox-LDL + genistein treated cells (all P < 0.05). CONCLUSION: Genistein could promote the activity of eNOS through increasing phosphorylation eNOS(Ser(1179)) level through PI3K/AKT pathway.
