Ahmad Zare Bidaki, Pouran Pourhakkak, F. Montazeri, S. Kalantar, S. Hoseini, Abolfazl Dehghanpour, M. Emtiazy
{"title":"Examining the Effect of Extract of Oak Fruit Jaft on AGS Cell Lines","authors":"Ahmad Zare Bidaki, Pouran Pourhakkak, F. Montazeri, S. Kalantar, S. Hoseini, Abolfazl Dehghanpour, M. Emtiazy","doi":"10.18502/ijpho.v13i3.13128","DOIUrl":"https://doi.org/10.18502/ijpho.v13i3.13128","url":null,"abstract":"Background: Gastrointestinal carcinoma comprises 5% of all pediatric cancer in children. Given that the possible and beneficial effect of the Jaft extract in the treatment of gastric cancer is not known and there is no comprehensive study in this regard, this study aimed to assess the effect of Jaft extract on gastric cancer cell lines. \u0000Materials and Methods: In this case-control study, oak fruit was collected from the mountains of Lorestan province. A gastric cancer (AGS) cell line was obtained from the Institute Pasteur cell bank and was cultured. After the preparation of the ethanolic extract of Jaft, the cell viability of the gastric cancer cells treated with Jaft extract was investigated by MTT assay. Quantitative Reverse Transcription PCR was used for assessing the expression of BAX, and BCL2 genes. \u0000Results: The half maximal inhibitory concentration (IC50) value of Jaft extract was 162 µg/ml. The BAX gene expression was different between the case and control groups. In this regard, the expression of the BAX gene was increased in the concentration of 162 (P<0.01) and 250 µg/ml (P<0.001) of Jaft extract compared to the control group. The BCL2 expression was different between the two groups (P<0.05). In this regard, the expression of the BCL2 gene was decreased in the concentration of 162 and 250 µg/ml of Jaft extract compared to the control group. \u0000Conclusion: It was found that Jaft extract increased the apoptosis of gastric cancer cells; therefore, it seems that the hydroalchoholic extract of Jaft is an appropriate anticancer medication.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"189 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134178909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mona Delkhah, J. Arasteh, L. Koochakzadeh, S. Rostami
{"title":"Evaluatin of Association of rs4986790 and rs4986791 Single-Nucleotide Polymorphisms in TLR4 with Febrile Neutropenia in Childhood Acute Lymphoblastic Leukemia","authors":"Mona Delkhah, J. Arasteh, L. Koochakzadeh, S. Rostami","doi":"10.18502/ijpho.v13i3.13129","DOIUrl":"https://doi.org/10.18502/ijpho.v13i3.13129","url":null,"abstract":"Background: Infections cause significant complications and, in severe cases, death in patients with childhood Acute Lymphoid Leukemia (ALL). Toll-like receptors (TLRs) play a crucial role in initiating innate immune responses. Previous studies indicate the role of TLR4 gene polymorphisms in the increased risk of infection in adults and children. This study investigated the potential association between Asp299Gly (rs4986790) and Thr399Ile (rs4986791) polymorphisms in the TLR4 gene with febrile neutropenia, as a hallmark of infection, in children with ALL. \u0000Material and Methods: This cross-sectional study was performed on 51 ALL child patients, with age (mean±s.d.) 5.2 ± 3.4 years. Genotype analysis of rs4986790 and rs4986791 polymorphisms in the TLR4 gene was evaluated by ARMS- PCR and PCR-RFLP, respectively. Statistical analysis was performed using SPSS software. P-values <0.05 were considered significant. \u0000Results: The rs4986790 and rs4986791 polymorphisms were detected in 5.8% and 7.8% of ALL patients, respectively. The mean of recurrence of febrile neutropenia in patients without TLR4 rs4986790 and TLR4 rs4986791 polymorphisms was 3.1 ±2 and 3 ±1.9, respectively, while in patients with TLR4 rs4986790 and TLR4 rs4986791 polymorphisms, they were 4.6 ± 3 and 5.2 ±2.8, respectively (P = 0.09). No association was found between TLR4 rs4986790 and rs4986791 polymorphisms and the number of febrile neutropenia recurrences (P = 0.4). \u0000Conclusion: Although rs4986790 and rs4986791 polymorphisms were detected in ALL patients, these polymorphisms were not associated with febrile neutropenia. It is suggested to investigate other polymorphisms in immune system-related genes and their role in febrile neutropenia.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"111 5 Pt 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130748560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Sadat Yazdanparast, Mohammad Mahdi Ghilian, E. Sheikhpour
{"title":"The management and approach to osteosarcoma in children: A mini-review article","authors":"Maryam Sadat Yazdanparast, Mohammad Mahdi Ghilian, E. Sheikhpour","doi":"10.18502/ijpho.v13i3.13133","DOIUrl":"https://doi.org/10.18502/ijpho.v13i3.13133","url":null,"abstract":"Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The onset of OS is associated with local pain and swelling as well as joint dysfunction, occasionally. The most common location for OS is around the knee joint. These patients often tend to receive medical attention following physical exercise and trauma. The affected population is mainly teenagers, children, and young adults with age range of 10-30 years. \u0000OS can be diagnosed via different approaches. The main serum markers for pediatric OS are insulin‑like growth factor (IGF‑1 and IGFBP‑3), anti‑ki57 antibody, tumor necrosis factor (TNF)‑β and sTNF‑R, T3, CD44, vascular endothelial growth factor, serum amyloid A, CXC chemokines, bone alkalin phosphatase, Interleukin (IL‑2, IL‑4, IL‑8), interferon gamma (IFN-γ), TNF‑α, and free polyamines. \u0000Given that there is no comprehensive review literature regarding OS management in our country, this study aimed to assess a survey on the management and approach of OS in children. In this regard, we have discussed the epidemiology, etiology, type, clinical feature, diagnosis, and OS therapy.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125847123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Z. Moradi, M. Barati, M. Azad, A. Safari, Bahram Chahardouli, M. Rezvany
{"title":"DNA Methylation and the Expression of the Tumor-Suppressor Genes Protocadherin-10 and Reprimo in Pediatric Acute Lymphoblastic Leukemia","authors":"Z. Moradi, M. Barati, M. Azad, A. Safari, Bahram Chahardouli, M. Rezvany","doi":"10.18502/ijpho.v13i2.12342","DOIUrl":"https://doi.org/10.18502/ijpho.v13i2.12342","url":null,"abstract":"Background: Acute lymphoblastic leukemia (ALL) is the most prevalent hematologic malignancy among children. DNA methylation is well known to play a role in the initiation and progression of cancer. This research aimed to characterize the epigenetic inactivation and gene expression of Protocadherin-10 (PCDH10) and Reprimo (RPRM) in pediatric acute lymphoblastic leukemia, which is associated with epigenetic silencing in human cancers. \u0000Materials and Methods: This case-control study included 21 children (mean age, 4.5 years) with new cases of ALL. In addition, 15 patients with ALL were selected following treatment. Samples of bone marrow were extracted from each patient. Prior to and following treatment, 15 paired samples were analyzed. In addition, ALL patients were compared to 18 normal controls in a case study. MS-HRM and quantitative real-time PCR were utilized to examine the DNA-promoter methylation and gene expression of two TSGs from each group. \u0000Results: Expression of PCDH10 was significantly up regulated in treatment ALL group compared to the new cases of ALL patients (P= 0.0119), PCDH10 gene expression was higher in the normal control group than in the new cases of ALL (P <0.0001). RPRM gene, also had a slightly increase in gene expression in treatment ALL group compared to the new cases of ALL (P =0.0412). RPRM gene expression was higher in the normal control group than in the new cases of ALL) P = 0.0372). There was an increase in methylation in both PCDH10 and RPRM genes in new cases of ALL groups compared with treatment ALL group and normal group (P<0.0001 for both genes). \u0000Conclusions: New cases of ALL were associated with high DNA methylation level and low gene expression of PCDH10 and RPRM genes.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"292 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127413360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Amini, Mohammad Faranoush, M. Paridar, A. Kazemi, M. Rezvani, M. Safa
{"title":"Synergistic Anti-Cancer Effects of Second-Generation Proteasome Inhibitor Carfilzomib with Doxorubicin and Dexamethasone Via p53-Mediated Apoptosis in Pre-B Acute Lymphoblastic Leukemia Cells","authors":"Ali Amini, Mohammad Faranoush, M. Paridar, A. Kazemi, M. Rezvani, M. Safa","doi":"10.18502/ijpho.v13i2.12339","DOIUrl":"https://doi.org/10.18502/ijpho.v13i2.12339","url":null,"abstract":"Background: The ubiquitin-proteasome system (UPS) plays a crucial role in regulating the levels and functions of a large number of proteins in the cell, which are important for cancer cell growth and survival. The proteasome is highly activated in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is the most common malignancy in children. The attempt to inhibit proteasome as a therapeutic strategy has been successful for some malignancies. \u0000Materials and Methods: In this experimental study, human BCP-ALL cell lines NALM-6 and SUP-B15 were treated with carfilzomib with and without the chemotherapeutic agents. The XTT assay evaluated the viability of the cells. Cell cycle analysis and apoptosis assay were assessed by flow cytometry. RQ-PCR and western blotting evaluated the expression of pro-/anti-apoptotic signals. A drug combination study for synergistic or additive effects of carfilzomib with doxorubicin or dexamethasone was performed. \u0000Results: We observed that carfilzomib alone induced G2/M cell cycle arrest and caspase-dependent apoptosis in the human BCP-ALL cells (NALM-6 and SUP-B15). Gene and protein expression analysis indicated the upregulation of pro-apoptotic as well as downregulation of the cell survival and proliferative signals (P-value<0.05). The synergy of carfilzomib with doxorubicin or dexamethasone was revealed in BCP-ALL cells. \u0000Conclusion: Our results indicated that proteasome inhibition induces p53-mediated apoptosis in BCP-ALL cells. Since carfilzomib has a synergistic effect with anti-leukemic agents doxorubicin and dexamethasone in BCP-ALL cells, this combined-modality approach might be befitting for patients who do not respond well to conventional chemotherapy.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"9 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132467656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Collin Dubick, V. Sakhalkar, S. Nair, Mark Boudreau, Om V. Sakhalkar
{"title":"Pediatric B Cell Acute Lymphoblastic Leukemia presenting with Paraneoplastic Acute Disseminated Encephalomyelitis","authors":"Collin Dubick, V. Sakhalkar, S. Nair, Mark Boudreau, Om V. Sakhalkar","doi":"10.18502/ijpho.v13i2.12344","DOIUrl":"https://doi.org/10.18502/ijpho.v13i2.12344","url":null,"abstract":"Acute Disseminated Encephalomyelitis (ADEM) is a monophasic demyelinating disease most often triggered by infection or immunization, though associations with malignancy and stem cell transplant have been described. We described the case of a four-year-old boy with new-onset neurological symptoms associated with ADEM, acute leukemia, and equivocal evidence of Mycoplasma pneumoniae infection. He responded to a short course of antibiotics and chemotherapy for B cell acute lymphoblastic leukemia (B-ALL) that included a prolonged course of high dose steroids with immunosuppressive therapy. This case illustrated a possible association between paraneoplastic ADEM and leukemia in pediatric patients.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126572690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hassan Boustani, Nasser Abbasi, A. Ghotaslou, O. K. Ghalesardi, F. Zaker, M. Shahidi
{"title":"Inhibition of MDM2 Using Idasanutlin (RG-7388) enhances the Chemo-sensitivity of B-ALL Cells to Daunorubicin","authors":"Hassan Boustani, Nasser Abbasi, A. Ghotaslou, O. K. Ghalesardi, F. Zaker, M. Shahidi","doi":"10.18502/ijpho.v13i2.12341","DOIUrl":"https://doi.org/10.18502/ijpho.v13i2.12341","url":null,"abstract":"Background: Although significant advances have been made in the treatment of cancer, a significant number of patients with acute lymphoblastic leukemia (ALL) show resistance to treatment. Thus, it is necessary to seek novel therapeutic agents to overcome this problem. Studies have indicated that the expression level of mouse double minute 2 (MDM2), a negative regulator of p53, is markedly elevated in patients with refractory or recurrent ALL. Thus, targeting MDM2 using a specific inhibitor, Idasanutlin, can increase the activity of p53. This study evaluated the possible synergistic effect of Idasanutlin and Daunorubicin on the induction of apoptosis in NALM-6 cells. \u0000Materials and methods: In this fundamental study, the anti-proliferative effects of Idasanutlin on NALM-6 cells, either alone or in combination with Daunorubicin, were confirmed by MTT(methyl-thiazol-tetrazolium) assay, Annexin/PI apoptosis assay, and cell cycle analysis. Quantitative reverse transcription-PCR (qRT-PCR) and Western blot analyses were applied to elucidate the molecular mechanisms underlying the anti-leukemic activity of Idasanutlin. \u0000Results: Idasanutlin synergistically enhanced Daunorubicin-induced apoptosis and activated caspase-3, thereby activating programmed cell death in a dose-dependent manner (P<0.001). The treatment of NALM-6 cells with Idasanutlin caused cell cycle arrest in the G1 phase by an increase in the expression of p21 (P<0.001). Moreover, a significant increase was detected in the expression of pro-apoptotic genes (P<0.001), as well as a remarkable decrease in the expression of anti-apoptotic (P<0.01) and multidrug resistance1 (MDR1) genes (P<0.01). \u0000Conclusions: It seems that Idasanutlin can cooperatively promote daunorubicin-induced apoptosis in NALM-6 cells. These findings open up a new horizon in the application of Idasanutlin in combination with Daunorubicin to overcome drug resistance in patients with ALL.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132785799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Sadeqi Nezhad, A. Rajabzadeh, Ali Dehghani Firoozabadi
{"title":"CAR T-cell Therapy of Hematologic Malignancies: An Update in Targeted Antigens","authors":"M. Sadeqi Nezhad, A. Rajabzadeh, Ali Dehghani Firoozabadi","doi":"10.18502/ijpho.v13i2.12343","DOIUrl":"https://doi.org/10.18502/ijpho.v13i2.12343","url":null,"abstract":"Immunotherapy with genetically engineered T-cells that express the chimeric antigen receptor (CAR) has raised hopes for the treatment of pediatric malignancies. Although CAR T-cell development is on a fast-moving pace and evolution, the context of exploring novel targetable antigens has been neglected. In this review study, we analyze the prominent hematologic antigens targeted by engineered T-cells in both preclinical and clinical aspects. Furthermore, we discuss the outcomes of CAR-based therapy in hematologic cancers from different viewpoints of treatment and provide some critical features for additional considerations. Almost certainly, most of the engineered T-cells redirected against hematologic disorders aim at conventional target antigens rather than targeting an ideal target antigen that is exclusively expressed on cancerous cells and restricted to normal tissues. CAR-based clinical trials in hematologic cancers have often dealt with CD19, followed by BCMA, CD22, and CD20 antigens. Besides, most of the scFvs used in the CAR structure are derived from murine antibodies, which may raise the concern about immunogenicity by reducing the persistence of modified T-cells. Nevertheless, short- and long-term life-threatening toxicities and the development of escape mechanisms that result in resistance and antigen loss are not thoroughly understood yet. The ultimate goal of using modified CAR T-cells is to make them effective and curative. Therefore, a better understanding of all the features pertaining to target antigens is imperative. Also, the methods to identify candidate target antigens and manage the associated obstacles of CAR T-cells should be evaluated and prioritized.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"53 4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129399075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amirreza Jahanshahi, Amirataollah Hiradfar, Shabnam Mahboubi, A. H. Hosseinpour Feizi, Abolhassan Shakeri Bavil, Ali Mostafavijabbari, Hamid Reza Yousefi Nodeh, S. Raeisi
{"title":"The Predictive Value of Abdominal Ultrasonography Compared to CT Scan for the Evaluation of Pediatric Lymphoma","authors":"Amirreza Jahanshahi, Amirataollah Hiradfar, Shabnam Mahboubi, A. H. Hosseinpour Feizi, Abolhassan Shakeri Bavil, Ali Mostafavijabbari, Hamid Reza Yousefi Nodeh, S. Raeisi","doi":"10.18502/ijpho.v13i2.12337","DOIUrl":"https://doi.org/10.18502/ijpho.v13i2.12337","url":null,"abstract":"Background: Given the children's susceptibility to the harmful radiation of computerized tomography (CT) scans, ultrasonography can be a good alternative in staging pediatric lymphoma. The present study aimed to assess the predictive value of abdominal ultrasonography compared to CT scan in children with lymphoma. \u0000Materials and Methods: Fifty-two children with confirmed lymphoma were included in the present cross-sectional analytical study and underwent CT scan. The staging was performed based on the involvement pattern, lymph nodes, liver involvement, spleen involvement, and lymph node sizes. Then, the patients underwent ultrasonography followed by re-staging. The data were analyzed by SPSS 26. p-value less than 0.05 was considered statistically significant. \u0000Results: The included patients consisted of 32 (61.5%) boys and 20 (38.5%) girls with the median age of 6.0 years (4.3-8.0). The number of the patients with positive paraaortic lymphadenopathy, iliac chain lymphadenopathy, mesenteric lymphadenopathy, increased liver size, changed liver parenchyma, increased spleen size, changed spleen parenchyma, increased kidney size, and changed kidney parenchyma evaluated by sonography and CT scan were 24 (46.2%) and 26 (50.0%), 3 (5.8%) and 3 (5.8%), 34 (65.4%) and 34 (65.4%), 49 (94.2%) and 48 (92.3%), 23 (44.2%) and 23 (44.2%), 45 (68.2%) and 21 (31.8%), 48 (92.3%) and 48 (92.3%), 50 (96.2%) and 50 (96.2%), and 49 (94.2%) and 48 (92.3%), respectively (p ≤ 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of abdominal ultrasonography staging compared to CT scan were 100%, more than 90%, more than 75%, and 100%, respectively. \u0000Conclusion: Due to the sufficient sensitivity and specificity, ultrasonography has the potential to be applied instead of CT scan for the abdominal staging of pediatric lymphoma.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124155540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Trichostatin A on the Histone Deacetylases (HDACs), Intrinsic Apoptotic Pathway, p21/Waf1/Cip1, and p53 in Human Neuroblastoma, Glioblastoma, Hepatocellular Carcinoma, and Colon Cancer Cell Lines","authors":"M. Sanaei, F. Kavoosi","doi":"10.18502/ijpho.v13i2.12338","DOIUrl":"https://doi.org/10.18502/ijpho.v13i2.12338","url":null,"abstract":"Background: The aberrant and altered patterns of gene expression play an important role in the biology of cancer and tumorigenesis. DNA methylation and histone deacetylation are the most studied epigenetic mechanisms. Histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA) and trichostatin A (TSA) are a group of anticancer compounds for the treatment of solid and hematological cancers. Previously, we reported the effect of two HDACIs, valproic acid (VPA) and TSA, on colon cancer and hepatocellular carcinoma (HCC), respectively. The aim of the current in vitro study is to investigate the effects of TSA on the intrinsic apoptotic pathway, p21/Waf1/Cip1 (p21), p53, and histone deacetylases (HDACs) 1, 2 and 3 in human neuroblastoma LAN-1, glioblastoma GBM-29, HCC SMMC7721, and colon cancer COLO 201 cell lines. \u0000Materials and methods: In this lab-trial study, all three cell lines were seeded at the density of 3 × 105 cells per well and incubated for 24 hours. Then, the cells were treated with TSA based on IC50 values for 24 hours except in the control groups; the control cells were treated with the equal amounts of the DMSO solvent. Subsequently, cell viability, cell apoptosis and gene expression were determined by three techniques including MTT assay, flow cytometry assay, and qRT-PCR. \u0000Results: The result of qRT-PCR indicated that TSA could increase the expression levels of Bid, BimEL, Noxa, p21, and p53 genes and decrease those of Bcl-xL, RIP, Mcl-1, XIAP, HDACs 1, 2 and 3 significantly (P < 0.0001) by which it inhibited cell growth and induced significant cell apoptosis in LAN-1, GBM-29, SMMC7721, and COLO 201 cell lines (p value<0.001). \u0000Conclusion: TSA can affect cell apoptotic via the intrinsic apoptotic pathway in LAN-1, GBM-29, SMMC7721, and COLO 201 cell lines.","PeriodicalId":129489,"journal":{"name":"Iranian Journal of Pediatric Hematology & Oncology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129367324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}