International Journal of Molecular and Cellular Medicine最新文献

{"title":"SLC7A11 Inhibitors Represent a Promising Therapeutic Target by Facilitating the Induction of Ferroptosis in Breast Cancer.","authors":"Rojin Azizi, Hanan Hassan Ahmed, Radhwan Abdul Kareem, Waam Mohammed Taher Waam, Mariem Alwan, Mahmood Jasem Jawad, Atheer Khdyair Hamad, Satinik Darzi","doi":"10.22088/IJMCM.BUMS.14.1.496","DOIUrl":"10.22088/IJMCM.BUMS.14.1.496","url":null,"abstract":"<p><p>It is predicted with near certainty that an estimated 310,720 women will be diagnosed with invasive breast carcinoma in 2024, while the number of men will be significantly lower at around 2,800, highlighting the alarming prevalence of this cancer across the sexes. The Solute Carrier Family 7 Member 11(SLC7A11) gene is vital for the exchange of extracellular cystine for glutamate at a 1:1 ratio and its expression is significantly increased in various tumors. Numerous research studies have shown that SLC7A11 expression is fine-tuned at several levels, contributing to its pharmacological functions in tumors, such as maintaining cellular redox balance, promoting cell proliferation, and influencing ferroptosis. Many studies suggest that reducing SLC7A11 expression and activity may be beneficial for cancer treatment, making it a promising target for therapy. However, recent findings also suggest that inhibiting SLC7A11 in certain scenarios may increase the survival of cancer cells and promote drug resistance. This review begins with a brief overview of the properties of SLC7A11, including its structural features and physiological functions, followed by a summary of its potential regulators. We then delve deeper into its role in cancer, particularly breast cancer, and explore the relationships between SLC7A11 and ferroptosis, proliferation, metastasis, and therapeutic resistance. Consequently, more customized therapeutic approaches should be considered when targeting SLC7A11 in the context of breast cancer. Thus, high expression of SLC7A11 is associated with poor prognosis in breast cancer, and various inhibitors have been identified that can effectively target this transporter. Innovative therapeutic strategies, including immunotherapies targeting SLC7A11, can potentially reduce tumor growth and metastasis in breast cancer models.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"14 1","pages":"496-516"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691849","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":"Innovative Approaches for Molecular Targeted Therapy of Breast Cancer: Interfering with Various Pathway Signaling.","authors":"Mahyar Haki, Reihaneh Bayat","doi":"10.22088/IJMCM.BUMS.14.1.533","DOIUrl":"10.22088/IJMCM.BUMS.14.1.533","url":null,"abstract":"<p><p>Breast cancer encompasses a diverse array of conditions classified as hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer subtypes, dictating treatment approaches. The therapeutic strategies commonly involve addressing estrogen receptors (ER) and HER2, which have exhibited efficacy in managing cancer. Nevertheless, the prevalence of resistance to these therapies, whether inherent or acquired, persists despite the introduction of novel treatment modalities. Progress in comprehending the biology of tumors has facilitated the identification of fresh targets, such as inhibitors targeting different pathways like phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR), cell-cycle regulation, heat shock protein, and epigenetic pathways, demonstrating encouraging outcomes in clinical experiments. For example, the mTOR inhibitor everolimus has been sanctioned for ER+ breast cancer and resistance to aromatase inhibitors in the advanced or metastatic phase. Triple-negative breast cancer, characterized by the absence of estrogen receptors, progesterone receptors, and HER2, currently lacks established targeted therapies. While poly (ADP-ribose) polymerase inhibitors exhibit effectiveness in BRCA-related cancers, their efficiency in addressing triple-negative breast cancer residues is uncertain. This paper furnishes a comprehensive outline of the principal targeted therapies presently employed or under exploration for breast cancer treatment within the three clinical subsets.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"14 1","pages":"533-551"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691841","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":"Possible Trace of HTLV-1 Virus in Modulation of Cbl-b, ITCH, and PP2A Suppressor Genes.","authors":"Atefeh Bahavar, Abdolvahab Moradi, Hamed Mohammadi, Mehdi Norouzi, Sara Khodayar, Sayed-Hamidreza Mozhgani, Alijan Tabarraei","doi":"10.22088/IJMCM.BUMS.14.1.472","DOIUrl":"10.22088/IJMCM.BUMS.14.1.472","url":null,"abstract":"<p><p>For almost 40 years, human T-lymphotropic virus type 1 (HTLV-1) has posed a persistent challenge in managing the major diseases associated with HTLV-1. Intracellular inhibitors are critical regulators of T cell activation, and their function can be influenced by viruses. Because of less studied aspects of HTLV-1 in T cell activation, we evaluated three suppressor genes in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic carriers (ACs). Thirty samples were collected from three groups from 10/09/2022 to 03/27/2024. To confirm all the samples, ELISA and PCR tests were done. The isolation of peripheral blood mononuclear cells (PBMCs), RNA extraction, and cDNA synthesis were conducted. Subsequently, the expression of <i>Tax trans-activator, HTLV-1 bZIP factor (HBZ), protein phosphatase 2 A (PP2A),</i> and two E3 ligases, including <i>Casitas B</i> <i>lymphoma-b (Cbl-b)</i> and <i>itchy E3 Ubiquitin protein ligase (ITCH),</i> was measured via Real-time PCR. This survey showed a significant increase in ITCH among individuals with HAM/TSP and ACs compared to the healthy group. The <i>PP2A</i> mRNA expression level was upregulated in the ACs; in contrast, the expression levels were approximately similar in the HAM/TSP and healthy groups. Also, the mean expression level of <i>Cbl-b</i> was higher in the ACs than in the other groups; however, it was not statistically significant. Our findings demonstrated that the intercellular suppressor genes could be dysregulated during the HTLV-1 infection, probably as part of the virus's strategic goals. The findings can be helpful for future investigation in the diagnosis and treatment area.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"14 1","pages":"472-482"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691843","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":"Improvement of the Antimicrobial and Antibiofilm Activity of AH Plus Sealer with Chitosan Nanoparticles and Arginine against Enterococcus faecalis and Candida albicans.","authors":"Elham Khoshbin, Hamed Karkehabadi, Mohammad Yousef Alikhani, Amirhossein Rajabnia","doi":"10.22088/IJMCM.BUMS.14.1.483","DOIUrl":"10.22088/IJMCM.BUMS.14.1.483","url":null,"abstract":"<p><p>The success of endodontic treatments can be significantly impaired by persistent microbial pathogens, especially <i>Enterococcus</i> <i>faecalis</i> (<i>E</i>. <i>faecalis</i>) and <i>Candida</i> <i>albicans</i> (<i>C</i>. <i>albicans</i>). The aim of this study was to investigate how the incorporation of chitosan nanoparticles (CsNPs) and arginine (Arg) can enhance the antimicrobial and antibiofilm efficacy of AH Plus, a widely used epoxy resin-based root canal sealer. The CsNPs were synthesized by ionotropic gelation and assessed for their size, morphology, chemical structure, and cytotoxicity. The antimicrobial effectiveness of the modified sealers was evaluated against <i>E</i>. <i>faecalis</i> and <i>C</i>. <i>albicans</i> by determining the minimum inhibitory concentration, minimum bactericidal concentration, minimum fungicidal concentration, and agar diffusion method. Additionally, antibiofilm activity was assessed using a microtiter plate assay. Characterization of the CsNPs revealed an average size of 144 ± 12.8 nm by scanning electron microscopy and 182.4 nm by dynamic light scattering with a zeta capacitance of +49.2 mV. CsNPs maintained more than 68% cell viability at 625 μg/mL after 24 and 48 hours. Adding CsNPs and Arg significantly enhanced the impact of AH Plus sealer on antimicrobial and antibiofilm, especially at elevated additive concentrations. This study suggests that AH Plus sealers containing CsNPs and Arg may offer a promising approach to enhance endodontic treatment outcomes by efficiently combating resistant root canal infections.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"14 1","pages":"483-495"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691938","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":"Extracellular Signal-Regulated Kinase Inhibitor SCH772984 Augments the Anti-Cancer Effects of Gemcitabine in Nanoparticle Form in Pancreatic Cancer Models.","authors":"Gauthami G Nair, Elena D Linster, Priyanka Ray, Mohiuddin A Quadir, Katie M Reindl","doi":"10.22088/IJMCM.BUMS.13.3.220","DOIUrl":"10.22088/IJMCM.BUMS.13.3.220","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor response to the limited treatment options currently available. Hence, there is a need to identify new agents that could enhance the efficacy of existing treatments. This study investigated a combination therapy using gemcitabine (GEM) and SCH772984, an extracellular signal-regulated kinase (ERK) inhibitor, in both free form and nanoparticle-encapsulated form for PDAC treatment. Cell viability and Matrigel growth assays were used to determine the anti-proliferative and cytotoxic effects of GEM and SCH772984 on PDAC cells. Additionally, western blotting was used to determine the degree to which SCH772984 engaged ERK in PDAC cells. Lastly, immunohistochemistry and hematoxylin and eosin (H&E) staining were used to determine how GEM and SCH772984 affected expression of Ki-67 cell proliferation marker in PDX (patient derived xenograft) PDAC tissues. PDAC cell lines (MIA PaCa-2 and PANC-1) treated with the combination of free GEM and SCH772984 showed reduction in cell viability compared to cells treated with free GEM or SCH772984 administered as a single agent. Encapsulated forms of GEM and SCH772984 caused a greater reduction in cell viability than the free forms. Interestingly, co-administration of GEM and SCH772984 in separate nanoparticle (NP) systems exhibited the highest reduction in cell viability. Western blotting analysis confirmed ERK signaling was inhibited by both free and encapsulated SCH772984. Importantly, GEM did not interfere with the inhibitory effect of SCH772984 on phosphorylated ERK (pERK). Collectively, our studies suggest that combination therapy with GEM and SCH772984 effectively reduced PDAC cell viability and growth, and co-administration of NP encapsulated GEM and SCH772984 in separate NP systems is an effective treatment strategy for PDAC.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 3","pages":"220-233"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568783","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":"Cytoprotective Effect of Gallic Acid against Injuries Promoted by Therapeutic Ionizing Radiation in Preosteoblast Cells.","authors":"Renata Sousa Leite, Rogério Gonçalves da Rocha, Angeliny Tamiarana Lima Tabosa, Emisael Stênio Batista Gomes, Laís Santiago, Danillo Costa Rodrigues, Sérgio Henrique Sousa Santos, André Luiz Sena Guimarães, Lucyana Conceição Farias","doi":"10.22088/IJMCM.BUMS.13.1.19","DOIUrl":"10.22088/IJMCM.BUMS.13.1.19","url":null,"abstract":"<p><p>Gallic acid (GA) is a powerful antioxidant extracted from plants of the Brazilian Cerrado. Oxidative stress plays an important role in the occurrence of radiation-induced osteonecrosis in patients treated for head and neck cancer. There is a need to develop research aimed at developing complementary therapies to prevent or reverse bone damage. The aim of the present study was to investigate the effect of GA in preosteoblasts exposed to therapeutic ionizing radiation. MC3T3-E1 preosteoblast cells were treated with 10 µM GA and exposed to 6 Gy ionizing radiation. We performed <i>in vitro</i> assays of cell proliferation, oxidative stress analysis by detection of reactive oxygen species, and alkaline phosphatase assay. GA at lower concentrations was able to significantly increase proliferation and inhibit radiation-induced generation of reactive oxygen species in osteoblast precursor cells, despite ionizing radiation-induced injury. Furthermore, GA significantly increased alkaline phosphatase at a dose of 6 Gy. The findings suggested that GA could attenuate ionizing radiation-induced injuries in osteoblast precursor cells. Moreover, <i>in vivo</i> studies are needed to better investigate the role of GA in osteonecrosis, especially in cancer patients undergoing radiotherapy or taking antiresorptive drugs.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 1","pages":"19-28"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999853","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":"Evaluations of Biomarkers CDX1 and CDX2 in Gastric Cancer Prognosis: A Meta-analysis.","authors":"Azadeh Khayyat, Mohammad Ali Esmaeil Pour, Olia Poursina, Seyed Amir Zohouri, Pragya Virendrakumar Jian, Neel Patel, Ami Amin","doi":"10.22088/IJMCM.BUMS.13.1.1","DOIUrl":"10.22088/IJMCM.BUMS.13.1.1","url":null,"abstract":"<p><p>CDX1 and CDX2 are homeobox-type transcription factors that are potential biomarkers and are associated with prognostic significance in intestinal-type gastric cancer early disease before lymph node metastasis is associated with better prognosis. In addition, the genes IDH 1 and IDH 2 previously known to be involved in brain cancer are implicated in cancer-related molecular signatures as a result new targeted personalized therapies may be possible. Our retrospective study determined the correlation between CDX markers and clinicopathologic data including survival in patients with gastric cancer. This study included studies from 1997 to December 2022 a meta-analysis to provide odds ratios (ORs) and relative risks (RRs). We discussed in detail the impact of IDH 1/2 on the prognosis of gastric cancer outcomes and potential therapeutic strategies. Our meta-analysis included 20 studies identifying 11,163 patients with gastric cancer. We found that CDX 1 overexpression was associated with better overall survival (pooled HR: 1.28) and CDX 2 expression and better 3-year survival (pooled HR: 1.64) and 5-year survival was the pooled HR was correlated 1 94 with both showing statistical correlation. Evidence suggests that IDH 1/2 mutations and CDX 1/2 overexpression are closely associated with metabolic abnormalities epigenetic changes and mutations evidence suggests the potential for novel targeted therapies in gastric cancer. CDX 1/2 overexpression is associated with a favorable prognosis in gastric cancer cases. Further studies are needed to explore the clinical significance of IDH 1/2 mutations and CDX 1/2 expression.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 1","pages":"1-19"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999875","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":"Anti-tumor Effects of Recombinant Clostridium α-Toxin on Breast Cancer: An <i>In Vitro</i> and <i>In Vivo</i> Study.","authors":"Nahid Rezaei Khozani, Mohammad Shayesteh Pour, Mina Yekani, Seyed Hossein Hejazi, Mahmood Saffari","doi":"10.22088/IJMCM.BUMS.13.4.404","DOIUrl":"10.22088/IJMCM.BUMS.13.4.404","url":null,"abstract":"<p><p>Cancer is the second leading cause of death worldwide, surpassed only by cardiovascular diseases. This study investigated the anticancer effects of recombinant <i>Clostridium</i> α-toxin on breast cancer, both <i>in vitro and in vivo</i>. The entire coding sequence of a codon-optimized <i>α-toxin</i> was designed, cloned into the pET28a (+) vector, and expressed as recombinant α-toxin in <i>Escherichia</i> <i>coli</i> (<i>E. coli</i>) BL 21(DE3) cells transformed with the recombinant plasmid. The recombinant α-toxin was purified using Ni²⁺ affinity chromatography, and its accuracy and purity were confirmed through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The anticancer effects of purified α-toxin were then assessed <i>in</i> <i>vitro</i> and animal models against MCF-7 breast cancer cells. Protein analysis confirmed the presence of a 48 kDa band corresponding to the recombinant α-toxin. Additionally, the IC₅₀ values of α-toxin against MCF-7 cells at 24, 48, and 72 h were 407.3±2.392 μg/mL, 287.3±5.411 μg/mL, and 258.1±4.671 μg/mL, respectively. <i>In vivo,</i> results demonstrated a significant reduction in mean cancer nodule size following α-toxin treatment (<i>p</i><0.001). These findings suggest that α-toxin may serve as a promising candidate for breast cancer therapy.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 4","pages":"404-416"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079924","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":"Evaluation of the Immune Checkpoints, TIM-3 and PD-1, as well as Anti-Inflammatory Cytokines IL-10, and TGF-β along with Diseases Activity in Chronic Spontaneous Urticaria.","authors":"Hadi Sadeghi, Javad Ghaffari, Javad Rajabi, Monireh Golpour, Torsten Zuberbier, Sadegh Fattahi, Hossein Asgarian-Omran, Alireza Rafiei","doi":"10.22088/IJMCM.BUMS.13.1.64","DOIUrl":"10.22088/IJMCM.BUMS.13.1.64","url":null,"abstract":"<p><p>Chronic spontaneous urticaria (CSU) is a skin disease caused by mast cells that produce inflammatory mediators. Immune checkpoint receptors such as program death-1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (TIM-3) are essential for the pathophysiology of many autoimmune and allergic diseases. The aim of this study was to investigate the expression of PD-1 and TIM-3 in CSU patients and their relationship to the anti-inflammatory cytokines (TGF-β and IL-10). In the current study, peripheral blood mononuclear cells (PBMCs) from CSU patients and healthy individuals were used and the Urticaria Activity Score 7 (UAS7) was used to assess disease severity. TaqMan-based RT-PCR was used to assess the expression of TIM-3 and PD-1 as well as the anti-inflammatory cytokines transforming growth factor-β (TGF-β) and IL-10. The protein concentrations of TGF-β and IL-10 were also measured by ELISA. The relationship between the expression of TIM-3 and PD-1 as well as TGF- β and IL-10 and the severity of the disease was investigated. The results showed that PD-1 mRNA expression was significantly increased in CSU patients (P<0.0001), while TGF- β and IL-10 levels were higher in CSU patients, but this difference was not significant (p=0.638, p= 0.798). The increase in protein level of IL-10 was significant (P<0.0001). There was also a positive correlation between the expression of PD-1 and TGF- β molecules and disease activity (P=0.0043, P=0.0018). In conclusion, the study found that the immune system expresses inhibitory molecules and anti-inflammatory cytokines to control disease severity. The higher expression of PD-1 molecules and IL-10 is associated with disease severity, suggesting that the immune system is trying to control inflammation and reduce disease severity.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 1","pages":"64-78"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999856","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":"Diversity of Memory CD8⁺ T Cells in Tumor-Draining Lymph Nodes from Patients with Bladder Cancer.","authors":"Ali Ariafar, Zahra Mansourabadi, Shahin Rasekh, Maryam Fakhimi, Zahra Faghih","doi":"10.22088/IJMCM.BUMS.13.2.147","DOIUrl":"10.22088/IJMCM.BUMS.13.2.147","url":null,"abstract":"<p><p>The role of memory T cells in orchestrating memory responses to previously known tumor antigens is well documented. The aim of this study was to assess the frequency of different memory T cell subsets in tumor-draining lymph nodes of patients with bladder cancer (BC) and their prognostic significance. Mononuclear cells were isolated from 50 tumor-draining lymph nodes of untreated patients with BC and stained with antibodies against the markers CD8, CD95, CD45RO and CCR7. Data were collected using the FACSCalibur flow cytometer and analyzed using FlowJo software. Among the CD8⁺ cytotoxic lymphocytes, the frequency of different subsets was determined including total memory cells (CD8⁺CD45RO⁺CD95⁺), T central memory (TCM: CD8⁺CCR7⁺CD45RO⁺CD95⁺), T effector memory (TEM: CD8⁺CCR7^-CD45RO⁺CD95⁺), T stem cell memory (TSCM: CD8⁺CCR7⁺CD45RO^-CD95⁺) and naïve T cells (CD8⁺CCR7⁺CD45RO^-CD95^-). The analysis revealed that on average 49.32±20.15 (between 1.62% and 87.20%) percent of CD8⁺ lymphocytes in draining lymph nodes of BC had a memory phenotype. TCM cells showed the highest frequency (34.71±17.04), while TSCM cells (7.51±8.53) demonstrated the lowest. The total frequency of memory cells tended to be higher in patients with tumor invasion to muscle layer (P=0.052) and stage III (P=0.042) than in patients without invasion and stage I. The TCM subset was more frequent in patients with necrotic tumors than in patients without necrosis (P=0.048). TSCM significantly increased in patients with N2 compared to N0 (P=0.042). Conversely, the ratio of TSCM cells to total memory cells was higher in lower tumor stages (P=0.059), tumors without muscle invasion (P=0.026) and low T grouping (P=0.043). Overall the data indicated an increase in the frequency of memory T cells and their TSCM and TCM cells with tumor progression. In contrast, the ratio of TSCM to total memory cells was higher in less advanced tumors. These results suggest that the immune system is frequently exposed to tumor antigens and strives to create a memory T cell reservoir, but this is suppressed by inhibitory factors provided by the tumor. These findings emphasize the importance of understanding the dynamic interplay between memory T cell subsets and BC progression.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 2","pages":"147-159"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055565","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}