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Multiple myeloma, a current incurable plasma cell malignancy, is a leading cause in the development and progression of multiple myeloma. Here we review the use of bromodomain inhibitors to target the IRF4-MYC axis by combinatorially inhibiting their known epigenetic regulators, BRD4 and CBP/EP300. We found reduced IRF4 mRNA levels for downstream target genes for all inhibitors over a time period of 72 hours, but not significantly decreased IRF4 protein expression or mRNA levels. In MM cells, a long-lived IRF4 protein was discovered by further investigation. Despite the autofeedback positive regulatory loop between IRF4 and MYC, bromodomain inhibitors are not cost-effective at tackling IRF4 in MM, and that new therapeutic approaches should not concentrate on the direct inhibition or degradation of IRF4 in MM.
Source link: https://doi.org/10.1002/hon.3016
Group 1: t or t; Group 2: t or t; Group 1: t or t; Group 2: t; or t/del; Group 3: t/del; Group 2: del; Group 1: del; Group 1: del; Group 1: t/del; Group 1: t/del; Group 1: t/del; Group 3: del; Group 2: del; Group 1: t; Group 1: t/t; del; T/t/del; Group 1: del; t; Group 1: t; Group 1: t; del; PFS and OS were significantly poorer in Group 3 among transplant-eligible patients, and even worse in those with gain after stratification by transplantation. According to real-world KMR results, del, R-ISS stage, and a number of cytogenetic abnormalities were among the risk factors for poor prognosis of MM patients.
Source link: https://doi.org/10.1007/s12185-022-03332-w
We investigated the incidence of bone marrow fibrosis in 91 newly diagnosed Japanese multiple myeloma patients, determining the effects of fibrosis on clinical characteristics and therapeutic outcomes. The presence of bone marrow fibrosis in laboratory results, the percentage of plasma cells in bone marrow or cytogenetic studies did not influence laboratory results, nor did it have a role in bone marrow or cytogenetic studies. MM cells derived from bone marrow fibrosis patients showed that expression of CD49e, an alpha5/beta1 integrin, was downregulated in MM cells derived from bone marrow fibrosis patients. Five of the original 34 patients were re-evaluated for fibrosis grading after treatment, but five of them showed a decrease in fibrosis.
Source link: https://doi.org/10.1007/s12185-022-03373-1
Multiple myeloma is a disease associated with the deregulation of microRNAs and genes in the bone marrow microenvironment, which has been implicated in multiple myeloma formation. We discovered 112 hub genes related to five major clusters in MM. In addition, we discovered 9 upregulated hub genes and 52 downregulated hub genes in MM that is primarily targeted by DEmiRs. The expression of DEmiRs targeted two hub genes are correlated with MM patients' survival prognosis. In addition, the expression level of CDKN2A is closely associated with immune signatures, including CD4+ Regulatory T cells, T cell exhaustion, MHC Class I, immune checkpoint genes, macrophages, neutrophils, and TH2 cells in the TME of MM. Identifying key genes and miRNA-mRNA regulatory networks can provide new molecular insights into the tumor immune microenvironment in MM.
Source link: https://doi.org/10.1080/16078454.2022.2068873
According to newer clinical studies, extended intensified therapy may help patients with HRCAs achieve MRD-negativity, which may lead to improved outcomes. Tumor characteristics are largely responsible for determining tumor characteristics, because of the disease's natural course and drug sensitivity. This paper reviews the clinical and pharmacological characteristics of newly diagnosed MM with HRCAs, focusing on HRCAs that are the most relevant in clinical research, as well as current optimal therapeutic approaches for newly diagnosed HRCAs.
Source link: https://doi.org/10.1007/s12185-022-03353-5
Background: Andrographolide is a diterpenoid component of the plant Andrographis paniculata that is known for its anti-tumor activity against a variety of cancer cells. Methods: We investigated Andro's influence on the tenability of the human leukemia monocytic cell line THP-1 and the human multiple myeloma cell line H929. Andro reduced the profitability of THP-1 and H929 in a dose-dependent manner. Whereas Ara-C and VCR increased the percentages of cells in the G0/G1 and G2/M phases, respectively, Andro had no or no apparent effect on cell cycle progression. Andro induces ROS-dependent apoptosis in monocytic leukemia THP-1 and multiple myeloma H929 cells, underlining its potential as a therapeutic agent for treating hematopoietic tumors. The increased toxicity in H929 cells, which is different from those of Ara-C and VCR, is prompting further research into the use of Andro against multiple myeloma.
Source link: https://doi.org/10.12688/f1000research.53595.2
Multiple myeloma is an incurable hematological disorder, but medical advances in the last two decades have markedly improved the prognosis. Whole-body low-dose computed tomography is replacing traditional skeletal examination by whole-body X-rays. In addition, magnetic resonance imaging and positron-emission tomography have become common diagnostic tools for MM diagnosis, as well as the investigation of myeloma cell proliferation, extramurlary disease, treatment effectiveness, and prognosis.
Source link: https://doi.org/10.1007/s12185-022-03360-6
Approximately 2 years of diagnosis, there is a predicted group of patients with crabification within two years of emergence, and these patients are slated for medical intervention before the onset of potentially irreversible complications. The analysis of clinical trial results as well as uniform eligibility helps determine whether a given patient should be eligible for therapeutic intervention outside of a clinical trial.
Source link: https://doi.org/10.1080/10428194.2022.2068008
Both LC-MRM/MS based aimed and GC-MS untargeted approaches were used in the present study to find metabolomic alterations in the serum of an MM cohort compared to healthy controls. A total of 54 metabolites were found to be significantly different in the MM cohort, out of which, 26 metabolites were discovered from LC-MRM/MS based targeted testing, while 28 metabolites were identified from the GC-MS based untargeted study. Six metabolites from both the experiments could be predicted as marker metabolites to distinguish MM subjects with higher specificity and sensitivity, according to the receiver operating characteristic curve analysis.
Source link: https://doi.org/10.1039/c9ra04458b
Multiple Myeloma is a plasma cell myeloma. Long-coding RNA prostate cancer associated transcript 1 has been shown to be linked to various forms of cancer. Furthermore, PCAT1 knockdown reduced cell proliferation, cell cycle progression, and the protein kinase B and -catenin signaling pathway, but cell death was induced cell death by regulating MTDH. According to this, PCAT1 stimulated cell growth in multiple myeloma by opening the AKT/-catenin signaling pathway through the miR-363-3p/MTDH axis.
Source link: https://doi.org/10.1039/c9ra06188f
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