International Journal of Molecular and Cellular Medicine最新文献

{"title":"An Intricate Relationship Between miR-155-5p Expression and Oxidative Stress in Bladder Cancer Patients Treated with Calmette-Guerin Immunotherapy.","authors":"Mohammad Mehdi Darzi, Nahid Neamati, Farzin Sadeghi, Ali Bijani, Emadoddin Moudi","doi":"10.22088/IJMCM.BUMS.13.2.186","DOIUrl":"10.22088/IJMCM.BUMS.13.2.186","url":null,"abstract":"<p><p>Treatment failure after intravesical instillation of Bacillus Calmette-Guerin immunotherapy (BCG) for non-muscle-invasive bladder cancer (BCa) occurs frequently. The exact effects of BCG on cellular redox status and gene expression remain unclear. We assessed oxidative stress biomarkers and changes in miR-155-5p expression in response to BCG. Twenty-seven patients with BCa were recruited for measuring tissue and serum malondialdehyde (MDA) and total antioxidant capacity (TAC) levels, and tissue expression of miR-155-5p at two-time points: pre and 6 weeks post BCG. Recurrence of BCa was observed after 20 months. R statistical software was used for paired comparisons of biomarkers, as well as the correlation between variables. Significant increases in TAC were observed after BCG (P= <0.001). Tissue MDA levels were significantly reduced (P= 0.003). miR-155-5p was slightly overexpressed after BCG (median fold change=1.3, P=0.25). At the 20-month follow-up, it was observed that improved MDA and TAC changes were significant only in patients without recurrence of BCa. In patients with recurrence, the pre-treatment expression ratio of miR-155-p5 was positively correlated with TAC (R=0.63, P= 0.032) and negatively correlated with MDA (R=-0.72, P=0.037). In patients with recurrence of BCa pre-treatment miR-155-5p showed negative correlation with its expression changes after BCG (R=-0.78, P=0.004). Conclusions: Treatment with BCG has some beneficial effects on the oxidative stress status, which is probably modulated by miR-155-5p. A well-controlled oxidative balance may enhance overall survival of BCa. Considering its high recurrence rate, our pilot experiment can open a window toward better management of patients with BCa.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 2","pages":"186-197"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of the Sensitivity of the Acute Lymphoblastic Leukemia Cells to ABT-737 by Formononetin.","authors":"Yusef Abbasi, Marziyeh Pooladi, Roya Nazmabadi, Jamal Amri, Helia Abbasi, Razieh Aghabeygi, Hadi Karami","doi":"10.22088/IJMCM.BUMS.13.3.259","DOIUrl":"10.22088/IJMCM.BUMS.13.3.259","url":null,"abstract":"<p><p>Overexpression of (myeloid leukemia cell differentiation protein 1) Mcl-1 is associated with the reduction of ABT-737 toxicity and secondary resistance. In this study, the effect of formononetin (biochanin B) on Mcl-1 expression, cell growth, apoptosis, and ABT-737 sensitivity of the acute lymphoblastic leukemia (ALL) cells was investigated. In this experimental study, the cell proliferation and MTT assays were used to investigate the effect of formononetin on cell growth and survival. qRT-PCR was performed for the measurement of gene expression. Hoechst 33342 staining and caspase-3 activity assay were used for the determination of apoptosis. Our data showed that formononetin and ABT-737 both led to a significant reduction in the IC₅₀ value and synergistically reduced the cell growth and survival relative to single treatment. Overexpression of Mcl-1 was found after the treatment with ABT-737. Formononetin decreased the expression of B-cell lymphoma 2 (Bcl-2) and Mcl-1 and increased the Bcl-2-associated protein x (Bax) and P21 expression. Moreover, formononetin enhanced the apoptotic effect of ABT-737 in ALL cells. In summary, formononetin showed anti-carcinogenic activities in human ALL cells <i>via</i> suppression of cell growth and survival. Formononetin enhanced the apoptotic effect of ABT-737, with contribution by inhibition of the Mcl-1 expression.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 3","pages":"259-271"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An In Silico Study of Transforming Growth Factor-β Inhibitors: A Potential Target for Diabetic Nephropathy Treatment with Active Compounds from the Active Fraction of Physalis angulata.","authors":"Ika Rahayu, Nur Arfian, Kris Herawan Timotius, Mae Sri Hartati Wahyuningsih","doi":"10.22088/IJMCM.BUMS.13.3.234","DOIUrl":"10.22088/IJMCM.BUMS.13.3.234","url":null,"abstract":"<p><p>Transforming growth factor beta (TGF-β) initiates epithelial-mesenchymal transition (EMT) in tubular and glomerular epithelial cells, resulting in excessive production and deposition of extracellular matrix through its interaction with TGF-β receptors, which play a crucial role in TGF-β signaling involving two receptor types, namely TGF-β type I (TβRI) and type II (TβRII). EMT contributes to the pathogenesis of interstitial renal fibrosis, a marker of end-stage kidney disease. This study aimed to identify the bioactive compounds in the active fraction of <i>P. angulata</i> and evaluate their ability to inhibit the TGF-β activity and their potential as drug candidates. The active components in the active fraction of <i>P. angulata</i> were analyzed using gas chromatography-mass spectrometry (GC-MS). The bioactive compound structures were obtained from the PubChem database, while the protein targets, TβRI and TβRII, were retrieved from the Protein Data Bank (PDB). The molecular docking analyses were performed using PyRx 0.8 and Discovery Studio. SwissADME was used to evaluate ligand properties and druglikeness. Three dominant active compounds were identified, namely palmitic acid, campesterol, and stigmasterol. <i>In silico</i> studies demonstrated strong energy bonds existed between TβRI and palmitic acid, campesterol, stigmasterol, and SB431542 with binding energy values of -5.7, -10, -9.4, and -10.9 kcal/mol, respectively. Similarly, they strongly bound to TβRII with binding energy values of -5.2, -7.1, -7.5, and -6.1 kcal/mol, respectively. All compounds meet Lipinski's criteria for druglikeness. Among the identified active compounds, campesterol exhibited the highest affinity for TβRI, while stigmasterol exhibited a strong affinity for TβRII. These findings suggested that the three compounds have potential as drug candidates.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 3","pages":"234-247"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico and In vitro Evaluations of the Antibacterial Activities of HIV-1 Nef Peptides against <i>Pseudomonas aeruginosa</i>.","authors":"Eman Koosehlar, Hassan Mohabatkar, Mandana Behbahani","doi":"10.22088/IJMCM.BUMS.13.1.46","DOIUrl":"10.22088/IJMCM.BUMS.13.1.46","url":null,"abstract":"<p><p>One of the burning issues facing healthcare organizations is multidrug-resistant (MDR) bacteria. <i>P. aeruginosa</i> is an MDR opportunistic bacterium responsible for nosocomial and fatal infections in immunosuppressed individuals. According to previous studies, efflux pump activity and biofilm formation are the most common resistance mechanisms in <i>P. aeruginosa</i>. The aim of this study was to propose new antimicrobial peptides (AMPs) that target <i>P. aeruginosa</i> and can effectively address these resistance mechanisms through <i>in silico</i> and <i>in vitro</i> assessments. Since AMPs are an attractive alternative to antibiotics, in vitro experiments were carried out along with bioinformatics analyses on 19 Nef peptides (derived from the HIV-1 Nef protein) in the current study. Several servers, including Dbaasps, Antibp2, CLASSAMP2, ToxinPred, dPABBs and ProtParam were used to predict Nef peptides as AMPs. To evaluate the binding affinities, a molecular docking analysis was performed with the HADDOCK web server for all Nef peptide models against two effective proteins of <i>P. aeruginosa</i> (MexB and PqsR) that play a role in efflux and quorum sensing. Moreover, the antibacterial and antibiofilm activity of the Nef peptides was investigated in a resistant strain of <i>P. aeruginosa</i>. The results of molecular docking revealed that all Nef peptides have a significant binding affinity to the abovementioned proteins. Nef-Peptide-19 has the highest affinity to the active sites of MexB and PqsR with the HADDOCK scores of -136.1 ± 1.7 and -129.4 ± 2, respectively. According to the results of <i>in vitro </i>evaluation, Nef peptide 19 showed remarked activity against <i>P. aeruginosa</i> with minimum inhibitory and bactericidal concen-trations (MIC and MBC) of 10 µM and 20 µM, respectively. In addition, biofilm inhibitory activity was observed at a concentration of 20 µM. Finally, Nef peptide 19 is proposed as a new AMP against <i>P. aeruginosa</i>.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 1","pages":"46-63"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin Co-treatment with Low Dose Methotrexate Increases the Cell Cycle Arrest and Ameliorates the Methotrexate-induced Inflammatory Response in NALM-6.","authors":"Nastaran Moridi, Mahsa Najafzadeh, Mahtab Sayedi, Seyed Mehdi Sajjadi","doi":"10.22088/IJMCM.BUMS.13.2.133","DOIUrl":"10.22088/IJMCM.BUMS.13.2.133","url":null,"abstract":"<p><p>Methotrexate (MTX), an antimetabolite agent, is widely used for acute lymphoblastic leukemia treatment, despite its association with significant organ dysfunction. Astaxanthin (AST) is a natural carotenoid which has recently been emerged as a promising anti-tumor and anti-inflammatory agent. In this study, we aimed to evaluate the effectiveness of astaxanthin and low-dose methotrexate co-treatment in acute lymphoblastic leukemia cell line. The expression of Dihydrofolate reductase (DHFR), Thymidylate synthase (TYMS), apoptotic, anti-apoptotic as well as inflammatory genes was investigated using qRT-PCR. Flow cytometry was performed for cell cycle quantitative evaluation. Clonogenic assay was used to assess NALM6 cells proliferation capacity following treatment with AST, MTX, and co-treatment. To compare the antioxidant property of each group, the ferric ion reducing anti-oxidant power assay was performed. A reduction in viability was observed in the presence of MTX, AST, and their combined treatment. Both AST alone and in combination with MTX caused cell cycle arrest and a reduction in the expression of DHFR and TYMS. While MTX, AST, and their combination could reduce STAT3 and BCL-XL gene expression, they could act as positive regulators for the expression of BAX and CASP3, TNFα, and IL6. AST and MTX co-treatment inhibited the colony formation ability<i>.</i> FRAP assay also revealed that AST and AST+MTX increased the antioxidant capacity. Our data suggests that AST can improve MTX treatment efficacy and their combination therapy can be considered as a promising strategy for the management of acute lymphoblastic leukemia.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 2","pages":"133-146"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Losartan as a Reproposing Therapeutic Agent in Acute Respiratory Distress Syndrome: Modulating Inflammatory Responses and Cytokine Production.","authors":"Khate Sripratak, Phumin Chamsodsai, Jeeraprapa Siriwaseree, Kiattawee Choowongkomon, Lueacha Tabtimmai","doi":"10.22088/IJMCM.BUMS.13.2.120","DOIUrl":"10.22088/IJMCM.BUMS.13.2.120","url":null,"abstract":"<p><p>Seeking a new drug has become a significant milestone in drug discovery. However, it might not be immediately used in urgent situations or during a pandemic. Acute Respiratory Distress Syndrome (ARDS) contributes to mild-to-severe symptoms in patients due to cytokine storms, leading to morbidity and mortality. Hypertension is recognized as an independent risk factor for the severity of ARDS regarding to both ACE Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) treatment, although the precise mechanism remains unclear. In this study, murine macrophage cell lines (RAW264.7) and alveolar epithelial type II-like cell lines (A549) were utilized to investigate the effect of Losartan (LOS). LOS attenuated nitric oxide production in a dose-dependent manner and collectively reduced intracellular reactive oxygen species (ROS) compared to Diclofenac under LPS-stimulation conditions. For ADRS-mimicking conditions, LPS-induced inflammatory A549 cells were performed to monitor the effect of LOS. The results showed that LOS exhibited a protective effect by increasing cell viability and decreasing intracellular ROS levels. Notably, a high dose of LOS increased intracellular ROS levels. Moreover, LOS treatment downregulated NF-kappaB activation and AT1R at the protein level. Correspondingly, proinflammatory mediator cytokines (TNF-alpha and IL-8) were downregulated, but not IL-6, during LOS treatment. Hence, LOS may provide substantial benefits to ARDS patients by modulating proinflammatory cytokine production through AT1R downregulation and NF-kappaB inactivation. The mechanistic insight into LOS's anti-inflammatory effect holds promise for reducing mortality rates among ARDS patients.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 2","pages":"120-132"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating miRNA-106b-5p As a Potential Biomarker for Coronary Artery Disease.","authors":"Rosita Azar Bahadori, Dina Shabani, Elham Arjmandrad, Mahsa Kazerani, Mina Rohani, Zohreh Ramazani Karim, Masoud Ali-Kheyl, Reza Nosratabadi, Hossein Pourghadamyari, Mohammad Ali Zaemi","doi":"10.22088/IJMCM.BUMS.13.3.325","DOIUrl":"10.22088/IJMCM.BUMS.13.3.325","url":null,"abstract":"<p><p>Coronary artery diseases (CAD) represent a significant global health concern and are recognized as a primary contributor to mortality on a worldwide scale. Early diagnosis of CAD is one of promising goal to manage this disorder. Recent investigations have highlighted the pivotal involvement of microRNAs (miRNAs) in diverse health conditions, notably CAD. The principal objective of this investigation was to identify appropriate miRNAs that could be employed for the early detection of CAD<b>.</b> In the present study, we analyzed dataset of CAD (GSE113079) and 100 differentially expressed mRNAs (DEmRNAs) were detected. The miRNAs that have a significant interaction with DEmRNAs were chosen. By computational prediction method, 5 miRNAs (miR-106b-5p, miR-20a-3p, miR-17-3p, miR-146a-5p, and miR-155-3p) were selected. Finally, we assessed the anticipated expression levels of microRNAs in CAD patients and healthy control groups. Our findings revealed a statistically significant elevation solely in the expression level of miR-106b-5p within the CAD group when compared to the control group (p>0.001). Our study demonstrated an elevation in the expression of miR-106b-5p in individuals diagnosed with CAD. This microRNA may be used as a diagnostic biomarker in patients with CAD. However, further investigations are needed to confirm these results.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 3","pages":"325-336"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the Cardiogenic Potential of Human Mesenchymal Stem Cells via Extracellular Matrix Proteins.","authors":"Galina Chizhikova, Mikhail Khotin, Natalya Bildyug","doi":"10.22088/IJMCM.BUMS.13.4.337","DOIUrl":"10.22088/IJMCM.BUMS.13.4.337","url":null,"abstract":"<p><p>Current <i>in vitro</i> models of cardiogenic differentiation include a variety of manipulations and stimulating agents, which interfere with the application of such models for preclinical drug testing. So, the aim of this study was to develop an approach for cardiogenic differentiation <i>in vitro</i> with a minimum of manipulations and to assess the influence of the extracellular matrix protein collagen IV on the cardiogenic potential of human mesenchymal stem cells (MSCs). Cardiogenic markers were analyzed by immunofluorescence staining and Western blot analysis. The results showed that collagen IV increased the cardiac marker GATA4 and altered the level of muscle actin isoforms, α-smooth muscle actin and α-cardiac muscle actin, in two different lines of human MSCs. The results indicate that the use of matrices containing collagen IV may increase the cardiogenic potential of human MSCs and may be a promising approach to obtain an <i>in vitro</i> model for cardiogenic differentiation suitable for preclinical drug discovery.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 4","pages":"337-349"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding RNA in the Regulation of Gastric Cancer Tumorigenesis: Focus on microRNAs and Exosomal microRNAs.","authors":"Niyousha Vakilzadehian, Yasamin Moradi, Omer Qutaiba B Allela, Ali Fawzi Al-Hussainy, Ali M Ali Al-Nuaimi, Rouaida Kadhim A Al-Hussein, Mahmood Jasem Jawad, Hossein Gandomkar, Samaneh Moradi","doi":"10.22088/IJMCM.BUMS.13.4.417","DOIUrl":"10.22088/IJMCM.BUMS.13.4.417","url":null,"abstract":"<p><p>Gastric cancer has become the leading type of cancer on an international scale, with metastatic cancer being the leading cause of mortality associated with this illness. Consequently, methods for early detection have been established, mainly through the use of non-invasive biomarkers present in different bodily fluids. Exosomes are distinct extracellular vehicles that transport cellular signals over long distances via diverse contents. They may be readily seen in bodily fluids due to their secretion by gastric cancer cells or cells in the gastric cancer-tumor microenvironment. Given this context, multiple biological and functional features of human tumors, especially gastric cancer, are intricately connected to exosomal non-coding RNAs (ncRNAs). Exosomal microRNAs play a crucial role in several stages of gastric cancer progression, facilitating the transfer of genetic information between cancer cells and other cells. This process regulates tumor angiogenesis, growth, metastasis, immunological responses, and medication resistance. They engage with several regulatory complexes that have different enzymatic activities. These complexes then alter the chromatin landscapes, including changes to nucleosomes, DNA methylation, and alterations to histones. This research delves into the essential regulatory mechanisms of exosomes in gastric cancer. Furthermore, the existing understanding of the functions of exosomal miRNAs in this context was evaluated, aiming to confirm their potential significance in identifying biomarkers, elucidating their roles in immune evasion and drug resistance, and ultimately evaluating therapeutic strategies.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 4","pages":"417-435"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-6-Methylguanine-DNA Methyltransferase, C-MYC, and EBER Status in Diffuse Large B-Cell Lymphoma of Central Nervous System.","authors":"Alireza Sadeghipour, Hadi Mohagheghian, Sajjadeh Movahedinia, Farid Kosari, Ahmad Monabati","doi":"10.22088/IJMCM.BUMS.13.4.361","DOIUrl":"10.22088/IJMCM.BUMS.13.4.361","url":null,"abstract":"<p><p>Diffuse Large B-cell Lymphoma (DLBCL), the most common type of primary central nervous system lymphoma (PCNSL), is a rare aggressive subtype of DLBCL with a poorly understood biology. This study aimed to investigate the prevalence of O-6-Methylguanine-DNA Methyltransferase (MGMT), <i>C-MYC</i> and Epstein-Barr virus Encoded RNA (EBER) positivity in CNS-DLBCLs. Using tissue microarray method, formalin-fixed paraffin-embedded blocks of 76 cases of confirmed PCNS-DLBCL and 2 cases of immunodeficiency-related CNS DLBCL were examined for EBER and <i>C-MYC</i> by chromogenic in situ hybridization (CISH), and for MGMT, CD10, BCL2, BCL6, MUM1 and Ki67 by Immunohistochemistry (IHC). The results were analyzed in association with histopathologic and demographic characteristics. The majority of the tumors were of non-germinal center B-cell (non-GCB) type. Loss of MGMT expression on IHC, as a surrogate marker of MGMT methylation, was detected in about 68.9% of PCNSLs. Preserved MGMT expression was found to occur more frequently in males and in MUM1-negative and GCB-type tumors. EBER positivity was exclusively seen in immunodeficient cases. Low <i>C-MYC</i> amplification was detected in 18% of cases and showed association with BCL2 and Ki67 expression. We concluded that loss of MGMT expression is a common phenomenon in PCNSLs. Epstein-Barr virus (EBV) may not be commonly detected in PCNS-DLBCL as frequently as in systemic DLBCL, but its expression is inevitable in CNS-DLBCLs of immunocompromised ones. Maintained MGMT expression is associated with less aggressive histopathologic features. Further studies are warranted to confirm the prognostic significance of loss of MGMT expression in PCNSLs and its potential use for predicting therapeutic response to alkylating agents in PCNSLs.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 4","pages":"361-373"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}