RESUMO
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, which caused many patients to lose their precious lives. FOXO3 was a suppressor in various cancers, however, the role and mechanism of FOXO3 in DLBCL remain unclear. METHODS: Bioinformatics analysis was used to offer information FOXO3 expression and its expression for prognosis of DLBCL patients. The abundance of genes and proteins was evaluated using RT-qPCR and western blot. Cell proliferation and apoptosis was detected by CCK-8 and flow cytometry. The interactions among FOXO3, miR-34b, and HSPG2 were predicted by TransmiR and Starbase and validated using dual luciferase reporter assay, ChIP assay, and RIP assay. RESULTS: Our findings revealed that FOXO3 expression was abnormally declined in DLBCL cells. FOXO3 upregulation restrained cell proliferation and promoted cell apoptosis of DLBCL cells, while miR-34b inhibitor eliminated these influences. Similarly, miR-34b mimic suppressed malignant behaviors of DLBCL cells, which were abolished by HSPG2 overexpression. Mechanically, FOXO3 induced miR-34b expression through interacting with miR-34b promoter and HSPG2 was a targeted gene of miR-34b. CONCLUSION: FOXO3 attenuated the capability of cell proliferation and promoted cell apoptosis rate of DLBCL cells through affecting miR-34b/HSPG2 axis, therefore inhibiting DLBCL progression.
RESUMO
Over the last 20 years, breakthroughs in accessible therapies for the treatment of multiple myeloma (MM) have been made. Nevertheless, patients with MM resistant to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies have a very poor outcome. Therefore, it is necessary to explore new drugs for the treatment of MM. This review summarizes the mechanism of action of selinexor, relevant primary clinical trials, and recent developments in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma. Selinexor may be useful for the treatment of refractory MM.
The Potential and Challenges of Selinexor in the Treatment of Multiple Myeloma Multiple myeloma (MM) is a plasma-cell neoplasm that presents with a variety of clinical manifestations, including bone destruction, anemia, renal dysfunction, and hypercalcemia, which pose a serious threat to people's health. Over the past 20 years, the survival of MM patients has significantly improved thanks to the development of several new treatments. However, the disease remains incurable, and almost all patients eventually develop a disease that is ineffective against available treatments. Therefore, an important area of research is the discovery of drugs with novel mechanisms of action to overcome the resistance mechanisms of current drugs. Selinexor is an oral XPO1 inhibitor that exerts anti-tumor activity through a novel mechanism. Here, we review the current clinical trials evaluating its role in the treatment of multiple myeloma and have a discussion of its mechanism, adverse events, challenges, and limitations. Selinexor is a promising drug. It may be a good addition to the treatment of relapsed and refractory multiple myeloma, but more research is needed to unlock its further potential.
RESUMO
The relationship between metabolites and multiple myeloma (MM) is becoming a research focus in the field. In this study, we performed metabolic profiling of multiple myeloma and identified potential metabolites associated with clinical characteristics, therapeutic efficacy, and prognosis of the disease. Fifty-five patients with newly-diagnosed multiple myeloma and thirty-seven healthy controls from August 2016 to October 2017 were randomly collected. The serum metabolic profiling was investigated by gas chromatography-mass spectrometry (GC-MS) technique and underwent statistical analysis. Twenty-seven metabolites were found to be significantly different between healthy controls and multiple myeloma patients. Eleven metabolites were significantly elevated, while sixteen metabolites were decreased in the multiple myeloma population. Metabolic changes were also observed in patients with renal impairment and bone destruction. Levels of urea were significantly decreased after treatment while levels of hypotaurine showed significant increase in the good-effect group (P<0.05), but not in the no-good-effect group (P>0.05). In multivariate statistical analyses, high cysteine and high hypotaurine are independent risk factors for poor treatment outcome. After adjustment for critical clinical characteristics, patients with high levels of glycolic acid and xylitol were found to be less likely to experience disease progression. Multiple myeloma demonstrates different metabolic characteristics compared with the healthy population. Among multiple myeloma patients, renal impairment and bone destruction showed additional metabolic characteristics. Cysteine and hypotaurine have value in predicting the treatment outcome, while glycolic acid and xylitol may be important prognostic factors for multiple myeloma.
