Browsing by Author "Donmez-Altuntas, Hamiyet"

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Characterization of Peripheral Blood T Follicular Helper (Tfh) Cells in Patients With Type 1 Gaucher Disease and Carriers
(Academic Press inc Elsevier Science, 2023) Uzen, Ramazan; Bayram, Fahri; Dursun, Huseyin; Kardas, Fatih; Cakir, Mustafa; Cucer, Nurhan; Donmez-Altuntas, Hamiyet
Background: Gaucher disease (GD) is the most common autosomal recessive lipid storage disease. In this study, the changes in TFH cells and IL-4 and IL-21 cytokines in blood samples of GD patients, carriers and healthy volunteers were investigated.Methods: Two pretreatment type 1 GD patients, 20 currently treated type 1 GD patients, 6 carriers, and 27 healthy volunteers were enrolled in the study. TFH cell (CD45RA- CD4+CXCR5+) number, phenotype (PD1, ICOS expression), and cytokine production (IL-21, IL-4) were assessed via flow cytometric assays.Results: No significant differences were found between the groups with respect to the number, frequency and PD1 or ICOS expression of TFH cells between healthy controls, patients and carriers. However, IL-4+ TFH cells were significantly reduced both in percent and number in the treated GD patients compared with healthy controls (p < 0.05). Interestingly, the IL-21+ TFH cell number was increased in treated GD patients. When TFH cells were examined based on CXCR3 expression, the frequency of the PD1+Th17-Th2-like fraction (CXCR3-) was found to be significantly increased in treated GD patients. Conclusion: To our knowledge, this is the first study to assess TFH cells in GD patients, and to show that the production of IL-4 and IL-21 by TFH cells and their subsets may be altered in type 1 GD patients.
Downregulation of Glutaminase 1 (Gls1) Inhibits Proliferation, Clonogenicity, and Migration of Aggressive Mda-Mb Breast Cancer Cells by Increasing P21 and Decreasing Integrin-Β1 Expression
(Erciyes Univ Sch Medicine, 2022) Akar, Sakine; Donmez-Altuntas, Hamiyet; Hamurcu, Zuhal
Objective: Glutamine metabolism is an important pathway in cell proliferation and tumor progression. The first enzyme to be converted in the process of glutamine metabolism, glutaminase 1 (GLS1), exhibits increased expression in many types of cancer, including breast cancer. Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high glutamine metabolic activity. The aim of this research was to examine the effects on glutamine metabolism and carcinogenic properties following small interfering RNA (siRNA)-mediated inhibition of GLS1 in glutamine-dependent TNBC.Materials and Methods: The effects on cell proliferation, migration, apoptosis, colony formation, and the cell cycle of MDA-MB-231 cells using different siRNAs targeting GLS1 were analyzed using an MTS assay, a wound-healing assay, clo-nogenic analysis, and annexin V and propidium iodide staining methods. The protein expression of GLS1, integrin beta 1 (beta 1), caspase-3, and p21 were examined using western blot analysis and flow cytometry.Results: The findings revealed that cell viability, migration, and colony formation were significantly suppressed in MDA-MB-231 cells transfected with 2 different GLS1 siRNAs. Furthermore, the results of flow cytometry and western blot analysis demonstrated that knockdown of GLS1 induced arrest in the G0/G1 phase of the cell cycle through the p21 signaling pathway, but did not induce apoptosis.Conclusion: GLS1 is needed for cell proliferation and promotes tumor progression and growth of MDA-MB 231 cells. siRNAs may provide a means to downregulate GLS1 and offer a promising target for breast cancer therapy.
A Newly Synthesized Benzimidazolium Salt: 1-(2 Chloride as a Potential Anticancer Agent for Colon Cancer Treatment, in Vitro Study
(Wiley, 2025) Bitgen, Nazmiye; Cakir, Mustafa; Akkoc, Senem; Donmez-Altuntas, Hamiyet
Colon cancer is one of the most common cancer-related deaths. Drug resistance is one of the biggest challenges in cancer treatment. Numerous pharmacological and biochemical investigations have documented the benzimidazole ring's anticancer, anti-inflammatory, and antioxidant properties. Within the scope of our project, the effect of newly synthesized benzimidazolium salt (BS) on cell proliferation was tested with MTT assay, and its effect on apoptosis and cell cycle was tested with annexin V and PI in the two different colon cancer cell lines (HT-29 and DLD-1). Our study examined the expressions of some genes related to apoptosis and, additionally, caspase activities with the multicaspase kit.BS showed an antiproliferative effect at lower doses in HT-29 colon cancer cells. When HT-29 cells were exposed to a 20 mu M dosage, they showed increased caspase activity and apoptosis compared to DLD-1 cells. HT-29 accumulated in the G2/M phase of the cell cycle, whereas DLD-1 cells accumulated more in the S phase. In HT-29 cells, colony formation was inhibited; however, in DLD-1 cells, this effect was insufficient.Based on the apoptosis-death pathway, BS is expected to have anti-cancer effects. As a result of this work, this chemical was thoroughly examined in two different colon cancer cell lines, and additional, more comprehensive initiatives are being planned in light of the information obtained from this study.
The Number and Frequency of Mucosal-Associated Invariant T (Mait), Γδ T, and Innate Lymphoid Cells (Ilcs) Altered in Patients With Type I Gaucher Disease
(Elsevier Science inc, 2025) Uzen, Ramazan; Bayram, Fahri; Dursun, Huseyin; Kardas, Fatih; Cakir, Mustafa; Cucer, Nurhan; Donmez-Altuntas, Hamiyet
Introduction: Gaucher disease (GD) is a rare lysosomal storage disease caused by mutations in the Glucocerebrosidase (GBA) gene. The innate immunopathology of GD beyond macrophage involvement is not well characterized. In the current study, the changes in ILC subsets, gamma delta T and MAIT cells, TNF-alpha and IFN-gamma cytokine levels in the peripheral blood of patients with Type 1 GD and GD carriers were evaluated. Methods: Peripheral blood mononuclear cells obtained from patients and controls were isolated using the Ficoll-Paque gradient method; after surface and intracellular staining, the cells were analyzed on FACSARIA III. Results: Our analyses revealed that CD8+ MAIT cells and CD8+ gamma delta T cells are reduced in the treated patients compared with the carriers. MAIT cell-specific IFN-gamma production and absolute counts of IFN-gamma+ MAIT cells significantly decreased in Type 1 GD patients who received ERT compared with healthy controls, which could be important indicators for the pathogenesis and severity of the disease. Additionally, total ILCs, particularly the ILC1 subset, were reduced in the Type I GD patients receiving ERT compared with healthy controls and the carriers. Conclusion: The changes observed in ILCs, gamma delta T cells, MAIT cells, TNF-alpha and IFN-gamma cytokine levels in both pre-and post-treatment Type 1 GD patients may play a vital role in the pathogenesis of GD.
Oxidative and Chromosomal Dna Damage in Patients With Type I Gaucher Disease and Carriers
(Pergamon-elsevier Science Ltd, 2023) Uzen, Ramazan; Bayram, Fahri; Dursun, Huseyin; Kardas, Fatih; Altin-Celik, Pinar; Cakir, Mustafa; Donmez-Altuntas, Hamiyet
Background and aims: Gaucher disease (GD) is caused by a genetic deficiency of the beta-glucocerebrosidase enzyme which results in the accumulation of glucosylceramide in macrophages. This accumulation may induce oxidative stress, resulting in DNA damage in patients with GD. The aim of this study was to assess plasma 8-hydroxy-2 '-deoxyguanosine (8-OHdG) levels and cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters in the peripheral blood lymphocytes of patients with GD and carriers, evaluate the possible associ-ations of these values with GD, and determine whether they can be used as potential biomarkers in GD.Methods: This study included 20 patients with type 1 GD, six carriers, and 27 age-and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of the patients with GD, carriers, and controls were evaluated and 8-OHdG levels in their plasma samples were measured.Results: CBMN-cyt assay parameters in patients with GD and carriers were not significantly different when compared with controls (p > 0.05). However, plasma 8-OHdG levels were found to be higher in both patients with GD and carriers than in control subjects (p < 0.01). Conclusions: Oxidative DNA damage may be a useful prognostic tool, whereas the CBMN-cyt assay cannot be used as a predictive biomarker of GD.
Β-Escin Reduces Cancer Progression in Aggressive Mda-Mb Cells by Inhibiting Glutamine Metabolism Through Downregulation of C-Myc Oncogene
(Springer, 2022) Akar, Sakine; Donmez-Altuntas, Hamiyet; Hamurcu, Zuhal
Background The c-myc oncogene, which causes glutamine dependence in triple negative breast cancers (TNBC), is also the target of one of the signaling pathways affected by beta-Escin. Methods and results We sought to determine how c-myc protein affects glutamine metabolism and the proteins, glutamine transporter alanine-serine-cysteine 2 (ASCT2) and glutaminase (GLS1), in beta-Escin-treated MDA-MB-231 cells using glutamine uptake and western blot analysis. Cell viability, colony formation, migration and apoptosis were also evaluated in MDA-MB-231 cells in response to beta-Escin treatment using MTS, colony forming, wound healing, and Annexin-V assay. We determined that beta-Escin decreased glutamine uptake and reduced c-myc and GLS1 protein expressions and increased the expression of ASCT2. In addition, this inhibition of glutamine metabolism decreased cell proliferation, colony formation and migration, and induced apoptosis. Conclusions In this study, it was suggested that beta-Escin inhibits glutamine metabolism via c-myc in MDA-MB-231 cells, and it is thought that as a result of interrupting the energy supply in these cells via c-myc, it results in a decrease in the carcinogenic properties of the cells. Consequently, beta-Escin may be promising as a therapeutic agent for glutamine-dependent cancers.