Comparison of Expression Signature of Histone Deacetylases (HDACs) in Mesenchymal Stem Cells from Multiple Myeloma and Normal Donors

Ahmadvand, Mohammad,Noruzinia, Mehrdad,Soleimani, Masoud,Abroun, Saeid Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7

Background: Histone acetylation in chromatin structures plays a key role in regulation of gene transcription and is strictly controlled by histone acetyltransferase (HAT) and deacetylase (HDAC) activities. HDAC deregulation has been reported in several cancers. Materials and Methods: The expression of 10 HDACs (including HDAC class I and II) was studied by quantitative reverse transcription-PCR (qRT-PCR) in a cohort of mesenchymal stem cells (MM-MSCs) from 10 multiple myeloma patients with a median age 60y. The results were compared with those obtained for normal donors. Then, a coculture system was performed between MM-MSCs and u266 cell line, in the presence or absence of sodium butyrate (NaBT), to understand the effects of HDAC inhibitors (HDACi) in MM-MSCs on multiple myeloma cases. Also, the interleukin-6 (IL-6) and vascular endothelial growth factor (VEGFA) gene expression level and apoptotic effects were investigated in MM-MSCs patients and control group following NaBT treatment. Results: The results indicated that upregulated (HDACs) and downregulated (IL6 and VEGFA) genes were differentially expressed in the MM-MSCs derived from patients with multiple myeloma and ND-MSCs from normal donors. Comparison of the MM-MSCs and ND-MSCs also showed distinct HDACs expression patterns. For the first time to our knowledge, a significant increase of apoptosis was observed in coculture with MM-MSCs treated with NaBT. Conclusions: The obtained findings elucidate a complex set of actions in MSCs in response to HDAC inhibitors, which may be responsible for anticancer effects. Also, the data support the idea that MSCs are new therapeutic targets as a potential effective strategy for MM.

FAS-670A>G gene polymorphism and the risk of allograft rejection after organ transplantation: a systematic review and meta-analysis

Mohammad Masoud Eslami,Ramazan Rezaei,Sara Abdollahi,Afshin Davari,Mohammad Ahmadvand 대한혈액학회 2021 Blood Research Vol.56 No.1

The association between the risk of allograft rejection after organ transplantation and FAS gene polymorphism has been evaluated previously. However, inconsistent results have been reported. Hence, we conducted the most up-to-date meta-analysis to evaluate this association. All eligible studies reporting the association between FAS-670A>G polymorphism and the risk of allograft rejection published up to December 2019 were extracted using a comprehensive systematic database search in the Web of Science, Scopus, and PubMed. The pooled odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated to determine the association strength. This meta-analysis included six case-control studies with 277 patients who experienced allograft rejection and 1,001 patients who did not experience allograft rejection (controls) after organ transplantation. The overall results showed no significant association between FAS-670A>G polymorphism and the risk of allograft rejection in five genetic models (dominant model: OR=0.81, 95% CI=0.58‒1.12; recessive model: OR=0.10, 95% CI=0.80‒1.53; allelic model: OR=0.96, 95% CI=0.79‒1.18; GG vs. AA: OR=0.92, 95% CI=0.62‒1.36; and AG vs. AA: OR=0.75, 95% CI=0.52‒1.08). Moreover, subgroup analysis according to ethnicity and age did not reveal statistically significant results. Our findings suggest that FAS-670A>G polymorphism is not associated with the risk of allograft rejection after organ transplantation.

Development of Gold-Coated Magnetic Nanoparticles as a Potential MRI Contrast Agent

Ali Reza Montazerabadi,Mohammad Ali Oghabian,Rasoul Irajirad,Samad Muhammadnejad,Davoud Ahmadvand,Hamid Delavari H,Seyed Rabie Mahdavi 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2015 NANO Vol.10 No.4

Gold-coated superparamagnetic iron oxide nanoparticles (SPIONs) coated with methylpolyethylene glycol (mPEG) are synthesized and investigated as a magnetic resonance (MR) imaging contrast agent. The synthesized mPEG-core@shells are characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), vibrating sample magnetometry (VSM), zeta-potential analysis and X-ray diffraction (XRD). In addition, the transverse relaxivity of the mPEG-core@shells is measured using a 3 T MRI scanner. The cytotoxicity of the mPEG-core@shells is tested in the LNCaP cell line using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results show that the mPEG-core@shell particles are semispherical with hydrodynamic size of ~65 nm and a transverse relaxivity of 162.3 mM-1 S-1. The mPEG-core@shell particles demonstrate good stability in biological media without any significant in vitro cytotoxicity under high cellular uptake conditions. Finally, in vivo imaging shows that mPEG-core@shells are a potential contrast agent for use in early-stage detection.

Clinical significance of cell-free DNA as a prognostic biomarker in patients with diffuse large B-cell lymphoma

Mahsa Eskandari,Saba Manoochehrabadi,Hossein Pashaiefar,Mohammad Ali Zaimy,Mohammad Ahmadvand 대한혈액학회 2019 Blood Research Vol.54 No.2

BackgroundCell-free DNA (cfDNA) has the potential to serve as a non-invasive prognostic biomarker in some types of neoplasia. The investigation of plasma concentration of cfDNA may re-veal its use as a valuable biomarker for risk stratification of diffuse large B-cell lymphoma (DLBCL). The present prognostic value of plasma cfDNA has not been widely confirmed in DLBCL subjects. Here, we evaluated cfDNA plasma concentration and assessed its potential prognostic value as an early DLBCL diagnostic tool.MethodscfDNA concentrations in plasma samples from 40 patients with DLBCL during diagnosis and of 38 normal controls were determined with quantitative polymerase chain reaction (qPCR) for the multi-locus L1PA2 gene.ResultsStatistically significant elevation in plasma cfDNA concentrations was observed in pa-tients with DLBCL as compared to that in normal controls (P<0.05). A cutoff point of 2.071 ng/mL provided 82.5% sensitivity and 62.8% specificity and allowed successful discrimination of patients with DLBCL from normal controls (area under the curve=0.777; P=0.00003). Furthermore, patients with DLBCL showing higher concen-trations of cfDNA had shorter overall survival (median, 9 mo; P=0.022) than those with lower cfDNA levels. In addition, elevated cfDNA concentration was significantly asso-ciated with age, B-symptoms, International Prognostic Index (IPI) score, and different stages of disease (all P<0.05).ConclusionQuantification of cfDNA with qPCR at the time of diagnosis may allow identification of patients with high cfDNA concentration, which correlates with aggressive clinical out-comes and adverse prognosis.

Altered expression of MALAT1 lncRNA in chronic lymphocytic leukemia patients, correlation with cytogenetic findings

Abdolrahim Ahmadi,Saeid Kaviani,Marjan Yaghmaie,Hossein Pashaiefar,Mohammad Ahmadvand,Mahdi Jalili,Kamran Alimoghaddam,Mohammad Eslamijouybari,Ardeshir Ghavamzadeh 대한혈액학회 2018 Blood Research Vol.53 No.4

BackgroundRecent studies have devoted much attention to non-protein-coding transcripts in relation to a wide range of malignancies. MALAT1, a long non-coding RNA, has been reported to be associated with cancer progression and prognosis. Thus, we here determined MALAT1 gene expression in chronic lymphocytic leukemia (CLL), a genetically heteroge-neous disease, and explored its possible relationships with cytogenetic abnormalities.MethodsMALAT1 expression level was evaluated using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) on blood mononuclear cells from 30 non-treated CLL patients and 30 matched healthy controls. Cytogenetic abnormalities were de-termined in patients by fluorescence in situ hybridization (FISH).ResultsMALAT1 expression level was up-regulated in the CLL group compared to healthy controls (P=0.008). Del13q14, followed by Del11q22, were the most prevalent cytogenetic abnormalities. We found no association between the FISH results and MALAT1 ex-pression in patients.ConclusionAltered expression of MALAT1 is associated with CLL development. Further investigations are required to assess the relationship between this long non-coding RNA and CLL patient survival and prognosis.

Upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in patients with primary non-M3 AML is associated with a worse prognosis

Saba Manoochehrabadi,Morteza Talebi,Hossein Pashaiefar,Soudeh Ghafouri‑Fard,Mohammad Vaezi,Mir Davood Omrani,Mohammad Ahmadvand 대한혈액학회 2024 Blood Research Vol.59 No.1

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with an unfavorable outcome. The present research aimed to identify novel biological targets for AML diagnosis and treatment. In this study, we performed an in-silico method to identify antisense RNAs (AS-RNAs) and their related co-expression genes. GSE68172 was selected from the AML database of the Gene Expression Omnibus and compared using the GEO2R tool to find DEGs. Antisense RNAs were selected from all the genes that had significant expression and a survival plot was drawn for them in the GEPIA database, FOXD2-AS1 was chosen for further investigation based on predetermined criteria (logFC ≥|1| and P < 0.05) and its noteworthy association between elevated expression level and a marked reduction in the overall survival (OS) in patients diagnosed with AML. The GEPIA database was utilized to investigate FOXD2- AS1-related co-expression and similar genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) function analysis of the mentioned gene lists were performed using the DAVID database. The protein–protein interaction (PPI) network was then constructed using the STRING database. Hub genes were screened using Cytoscape software. Pearson correlation analysis was conducted using the GEPIA database to explore the relationship between FOXD2-AS1 and the hub genes. The transcription of the selected coding and non-coding genes, including FOXD2-AS1, CDC45, CDC20, CDK1, and CCNB1, was validated in 150 samples, including 100 primary AML non-M3 blood samples and 50 granulocyte colony stimulating factor (G-CSF)-mobilized healthy donors, using quantitative Real-Time PCR (qRT-PCR). qRT-PCR results displayed significant upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in primary AML non-M3 blood samples compared to healthy blood samples (P = 0.0032, P = 0.0078, and P = 0.0117, respectively). The expression levels of CDC20 and CCNB1 were not statistically different between the two sets of samples (P = 0.8315 and P = 0.2788, respectively). We identified that AML patients with upregulation of FOXD2-AS1, CDK1, and CDC45 had shorter overall survival (OS) and Relapse-free survival (RFS) compared those with low expression of FOXD2-AS1, CDK1, and CDC45. Furthermore, the receiver operating characteristic (ROC) curve showed the potential biomarkers of lnc -FOXD2-AS1, CDC45, and CDK1 in primary AML non-M3 blood samples. This research proposed that the dysregulation of lnc-FOXD2-AS1, CDC45, and CDK1 can contribute to both disease state and diagnosis as well as treatment. The present study proposes the future evolution of the functional role of lnc-FOXD2-AS1, CDC45, and CDK1 in AML development.