Frequency and Correlation of Common Genes Copy Number Alterations in Childhood Acute Lymphoblastic Leukemia with Prognosis

OBJECTIVE: It was shown by genomic profiling that despite no detectable chromosomal abnormalities a proportion of children with pre-B acute lymphoblastic leukemia harbors copy number alterations (CNA) of genes playing role in B-cell development and function. The aim of the study was to determine the frequency of CNA in pediatric acute lymphoblastic leukemia and correlate these findings with clinical outcome. METHODS: DNA extracted from peripheral blood or bone marrow at diagnosis/relapse of fifty newly diagnosed children with precursor B-cell acute lymphoblastic leukemia was analyzed for CNA with multiplex ligation-dependent probe amplification. RESULTS: The analysis revealed 76 CNA in 24 patients most frequently found in PAR1 (17%), CDKN2A/B (15.7%) and PAX5 (14.4%) genes. There were significant CNA co-occurrences between PAX5, CDKN2A/B, BTG1, ETV6, PAR1 or XP22 genes, (p <0.020) and the high-risk group. There was a significant correlation between EBF1, RB1, and IKZF1 alterations and bone marrow relapse. Patients with CNA in screened genes are more likely to succumb to their disease except for those with PAR1 or XP22 genes (p <0.050). CONCLUSION: The multiplex ligation-dependent probe amplification could be considered as an independent diagnostic tool allowing prompt identification of patients at high risk of treatment failure and, subsequently, a more adequate treatment approach

Magnetohyperthermia-synergistic glioma cancer therapy enabled by magnetic graphene oxide nanoheaters: promising nanostructure for in vitro and in vivo applications

Abstract In the present study, a magnetohyperthermia (MH)-based therapy is introduced as an effective treatment for deep-seated tumors especially glioma, which combines the magnetothermal effect and the reactive oxygen species (ROS) induced with magnetic graphene oxide (GOMNPs) nanoheaters to overcome the issue of limited therapeutic efficacy in the current magnetothermal therapeutic strategy. Magnetic graphene oxide nanoheaters with a size of 34 nm and a surface charge of − 35 mV showed very little toxicity under in vitro and ex vivo circumstances based on MTT and hemolysis assay, respectively. The application of GOMNPs under an alternating magnetic coil (AMC) showed that they had high specific absorption rate (SAR, P < 0.01), with enhanced level of ROS production within the tumor microenvironment. The results confirmed a significant increase in the SAR in blood compared to culture media (P < 0.01), which indicates the improvement of magnetohyperthermia performance in in vivo conditions compared to in vitro. A significant therapeutic efficacy was achieved with a dosage of 30 mg/kg of GOMNPs following 3 therapeutic courses under alternating magnetic field (AMF) compared to AMF alone (P < 0.05). GOMNPs exhibited a strong anti-glioma effect by inhibiting tumor growth, and increasing the survival ratio by inducing apoptotic cell death (P < 0.05). The Bax/Bcl2 protein and gene ratio confirmed a higher rate of apoptotic death in the MH-treated group (P < 0.05). Combination of magnetohyperthermia with conventional modalities may offer tremendous clinical advantages compared to the currently available methods. Graphical Abstrac

Non-coding RNA-mediated epigenetic alterations in Grave's ophthalmopathy: A scoping systematic review

Background: It is becoming more and more apparent that Grave's Ophthalmopathy (GO) pathogenesis may be aided by epigenetic processes such as DNA methylation modifications, histone tail covalent modifications, and non-coding RNA (ncRNA)-based epigenetic processes. In the present study, we aimed to focus more on the miRNAs rather than lncRNAs due to lack of investigations on these non-coding RNAs and their role in GO's pathogenesis. Methods: A six-stage methodology framework and the PRISMA recommendation were used to conduct this scoping review. A comprehensive search was conducted across seven databases to discover relevant papers published until February 2022. The data extraction separately, and quantitative and qualitative analyses were conducted. Results: A total of 20 articles were found to meet inclusion criteria. According to the results, ncRNA were involved in the regulation of inflammation (miR-146a, LPAL2/miR-1287–5p axis, LINC01820:13/hsa miR-27b-3p axis, and ENST00000499452/hsa-miR-27a-3p axis), regulation of T cell functions (miR-146a/miR-183/miR-96), regulation of glycosaminoglycan aggregation and fibrosis (miR-146a/miR-21), glucocorticoid sensitivity (miR-224–5p), lipid accumulation and adipogenesis (miR-27a/miR-27b/miR-130a), oxidative stress and angiogenesis (miR-199a), and orbital fibroblast proliferation (miR-21/miR-146a/miR-155). Eleven miRNAs (miR-146a/miR-224–5p/miR-Let7d-5p/miR-96–5p/miR-301a-3p/miR-21–5p) were also indicated to have the capacity to be used as biomarkers. Conclusions: Regardless of the fact that there is significant documentation of ncRNA-mediated epigenetic dysfunction in GO, additional study is needed to thoroughly comprehend the epigenetic connections concerned in disease pathogenesis, paving the way for novel diagnostic and prognostic tools for epigenetic therapies among the patients

Magnetic Hyperthermia as an adjuvant cancer therapy in combination with radiotherapy versus radiotherapy alone for recurrent/progressive glioblastoma: a systematic review

Abstract Introduction Hyperthermia therapy (HT) is a recognized treatment modality, that can sensitize tumors to the effects of radiotherapy (RT) and chemotherapy by heating up tumor cells to 40–45 °C. The advantages of noninvasive inductive magnetic hyperthermia (MH) over RT or chemotherapy in the treatment of recurrent/progressive glioma have been confirmed by several clinical trials. Thus, here we have conducted a systematic review to provide a concise, albeit brief, account of the currently available literature regarding this topic. Methods Five databases, PubMed/Medline, Embace, Ovid, WOS, and Scopus, were investigated to identify clinical studies comparing overall survival (OS) following RT/chemotherapy versus RT/chemotherapy + MH. Results Eleven articles were selected for this systematic review, including reports on 227 glioma patients who met the study inclusion criteria. The papers included in this review comprised nine pilot clinical trials, one non-randomized clinical trial, and one retrospective investigation. As the clinical trials suggested, MH improved OS in primary glioblastoma (GBM), however, in the case of recurrent glioblastoma, no significant change in OS was reported. All 11 studies ascertained that no major side effects were observed during MH therapy. Conclusion Our systematic review indicates that MH therapy as an adjuvant for RT could result in improved survival, compared to the therapeutic outcomes achieved with RT alone in GBM, especially by intratumoral injection of magnetic nanoparticles. However, heterogeneity in the methodology of the most well-known studies, and differences in the study design may significantly limit the extent to which conclusions can be drawn. Thus, further investigations are required to shed more light on the efficacy of MH therapy as an adjuvant treatment modality in GBM. Keywords Magnetic hyperthermia · Glioma · Clinical Trial · Overall survival · Systematic Revie