Browsing by Author "Guven, Mustafa"

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Addressing Radiotherapy-Induced Fibrosis: the Potential of Platelet-Rich Plasma and Infliximab for Improved Breast Cancer Management
(Springer, 2024) Binici, Serhat; Guven, Mustafa; Ozdemir, Abdulselam; Ilik, Zehra Akman; Demirhan, Birhan; Uygur, Serhat; Iliklerden, Umit Haluk
Breast cancer treatment encompasses various therapeutic modalities, including surgery, radiotherapy, and chemotherapy. Breast-conserving surgery has been an integral part of breast cancer management. However, radiotherapy, an important component of breast cancer management, can lead to complications, particularly fibrosis, affecting reconstructive surgery outcomes. We conducted an in vivo study using 48 female Wistar Albino rats, employing segmental mastectomy and radiotherapy to simulate post-mastectomy conditions. The rats were divided into six groups: control, mastectomy, mastectomy + radiotherapy, mastectomy + platelet-rich plasma (PRP) + radiotherapy, mastectomy + infliximab + radiotherapy, and mastectomy + infliximab + PRP + radiotherapy. Edema, hyperemia, inflammation, and fibrosis were assessed as indicators of tissue response. Histopathological analysis revealed that mastectomy + infliximab and mastectomy + infliximab + PRP groups showed significant reductions in fibrosis compared to other groups. Edema, hyperemia, and inflammation were also less severe in these groups compared to the control group. Radiotherapy-induced fibrosis is a major concern in breast reconstruction. Our study suggests that local PRP application and systemic infliximab administration, either alone or in combination, could mitigate the adverse effects of radiotherapy. This approach has the potential to improve reconstructive outcomes in patients undergoing or having the possibility to undergo radiotherapy. This is the first study showing the effectiveness of infliximab and PRP combination on wound healing. The provided experimental rat model might offer guidance for further research. This study provides insights into optimizing outcomes in reconstructive breast surgery, paving the way for further research and clinical studies.
The Antagonistic Effects of Temozolomide and Trichostatin a Combination on Mgmt and Dna Mismatch Repair Pathways in Glioblastoma
(Humana Press inc, 2023) Guven, Mustafa; Taspinar, Filiz; Denizler-Ebiri, Farika Nur; Castresana, Javier S.; Taspinar, Mehmet
Glioblastoma is the most aggressive and fatal form of brain cancer. Despite new advancements in treatment, the desired outcomes have not been achieved. Temozolomide (TMZ) is the first-choice treatment for the last two decades and has improved survival rates. Emerging studies have shown that targeting epigenetics in glioblastoma can be beneficial when combined with clinically used treatments. Trichostatin A (TSA), a histone deacetylase inhibitor, has anti-cancer properties in various cancers. No data concerning the TMZ and TSA relationship was shown previously in glioblastoma therefore, we aimed to determine the likely therapeutic effect of the TMZ and TSA combination in glioblastoma. The T98G and U-373 MG, glioblastoma cell lines, were used in this study. TMZ and TSA cytotoxicity and combination index were performed by MTT assay. The expression of DNA repair genes (MGMT, MLH-1, PMS2, MSH2 and MSH6) was detected using RT-PCR. One-way analysis of variance (ANOVA) was used for statistical analysis. Combination index calculations revealed antagonistic effects of TMZ and TSA in terms of cytotoxicity. Antagonistic effects were more apparent in the T98G cell line, which is expressing MGMT relatively higher. MGMT and DNA Mismatch Repair (MMR) genes were upregulated in the T98G cell line, whereas downregulated in the U373-MG cell lines under TMZ and TSA combination treatment. It is concluded that MGMT might be playing a more active part than MMR genes in TMZ resistance to TMZ and TSA antagonism. This is the first study elucidating the TMZ and TSA relationship in cancer cell lines.
Cd133+/Cd44+prostate Cancer Stem Cells Exhibit Embryo-Like Behavior Patterns
(Elsevier Gmbh, 2021) Acikgoz, Eda; Soner, Burak Cem; Ozdil, Berrin; Guven, Mustafa
Cancer stem cells (CSCs), which act as an important bridge between cancer formation and embryonic development, represent a small population associated with tumor initiation, drug resistance, metastasis and recurrence. CSCs have the ability to form spheroids in three-dimensional culture systems. Tumor spheroids derived from CSCs with symmetric and asymmetric division patterns were found to contain highly heterogeneous cell groups. The biological behavior patterns which some CSCs display serve as an important bridge between cancer formation and embryonic development. The cell population in the DU-145 prostate cancer cell line with surface markers CD133+/CD44+ was isolated by FACS. Prostate spheroids were formed by using agarose-coated plates. The morphological characteristics of the cell population within spheroid structure and the expression of Ki-67 and Caspase-3 were investigated by histochemical methods. In this study, we observed that CD133+/CD44+ prostate CSCs form different spheroid structures as well as normal spheroid structures: i) some spheroid structures formed with a highly transparent zone on the outer part of the spheroid, in addition to the normal spheroidal zones and ii) spheroidal structures obtained from prostate CD1334+/CD44+ CSCs that share the same microenvironment are hollow spheres similar to the blastula-like structure in the embryo. These spheroidal structures exhibiting embryo-like properties indicate that the expression of embryonic factors might be reiterated in CSCs. Further investigation of the formation mechanism of the transparent zone and the hollow sphere will shed light on the embryonic origin of prostate cancer and the design of new therapeutic strategies.
Evaluating Single-Dose Methotrexate Alone Versus Methotrexate With Letrozole for Treating Ectopic Pregnancy: a Comparative Study
(Springer Heidelberg, 2025) Aygar, Metin; Guven, Mustafa; Uygur, Serhat; Arslan, Ozgur; Karaaslan, Onur; Karaman, Erbil
PurposeEctopic pregnancy (EP) constitutes 1-2% of all pregnancies. Methotrexate (MTX) is commonly used in treating EP, but it has some limitations and potential side effects. Clinical studies have shown that letrozole, an aromatase inhibitor, may potentially be used in conjunction with MTX therapy. In our study, we explored the efficacy of adding letrozole to MTX in managing EP.MethodsBetween June 2021 and September 2022, a total of 60 patients diagnosed with EP at the Faculty of Medicine, Y & uuml;z & uuml;nc & uuml; Y & imath;l University, were randomly divided into two groups. Group 1 received MTX alone, while Group 2 received a combination of MTX and letrozole. The primary outcome measure was the change in serum beta-hCG levels. Secondary outcomes included the need for surgical intervention and the occurrence of side effects.ResultsBoth groups demonstrated similar success rates in treatment, and there was no significant difference between the MTX and MTX + letrozole groups regarding the need for surgical intervention. Although beta-hCG levels declined more rapidly in the MTX + letrozole group, these decreases were not statistically significant. The combination of MTX and letrozole in the treatment of ectopic pregnancy has shown similar efficacy to single-dose MTX.ConclusionLetrozole may offer a potential contribution to MTX therapy by providing a more pronounced reduction in beta-hCG levels, but further research with larger sample sizes and longer follow-up periods is needed to confirm these findings.
Impact of 18f-Fdg Pet/Ct in the Management Decisions of Breast Cancer Board on Early-Stage Breast Cancer
(Springer int Publ Ag, 2024) Ozdemir, Abdulselam; Guven, Mustafa; Binici, Serhat; Uygur, Serhat; Toktas, Osman
Purpose Breast cancer is the most common malignancy accounting for 11.7% of all cancer cases, with a rising incidence rate. Various diagnostic methods, including 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), play a crucial role in breast cancer diagnosis and staging. However, the unnecessary use of advanced imaging techniques such as PET/CT in early-stage breast cancer can have negative effects on both economics and patients. We aimed to investigate the impact of PET/CT on the management decisions of early-stage breast cancer patients by the breast cancer tumor board.Methods A retrospective analysis was performed on a cohort of 81 patients with early-stage breast cancer who were evaluated by breast cancer tumor board from January 2015 to December 2020. Demographic, clinical, and radiographic data, along with surgical procedures and treatment options, were documented and analyzed.Results The results showed that 18F-FDG PET/CT had a moderate impact on treatment decisions of breast cancer tumor board, as only treatment decisions were changed in 14,86% of the patients. The surgical procedure decision of breast cancer tumor board changed in 12.35% of patients, while 87.65% of patients had consistent decisions before and after PET/CT. Pathological assessments revealed invasive ductal carcinoma as the most prevalent tumor type, and molecular subtypes were predominantly luminal B. PET/CT use had limited impact on surgical procedures and did not significantly alter treatment decisions of breast cancer tumor board in this early-stage breast cancer cohort.Conclusions In conclusion, this study highlights the importance of adherence to the guidelines and appropriate use of PET/CT in early-stage breast cancer management. PET/CT should be reserved for cases where it is clinically warranted, considering the potential economic burden and minimal impact on treatment decisions of breast cancer tumor board in this patient population.
Linking Cdh1 Snps To Gastric Cancer Risk: a Comprehensive Analysis of Rs16260, Rs13689, and Rs9929218
(Springer, 2024) Aslan, Firat; Almali, Necat; Kaya, Zehra; Guven, Mustafa; Sahin, Elif Sena; Ozdemir, Abdulselam; Uygur, Serhat
Objective Single nucleotide polymorphisms (SNPs) are linked to carcinogenesis. Pathogenic variants in the CDH1 gene are associated with gastric cancer. This study examines the genotype and allele frequencies of three SNPs (rs16260, rs13689, and rs9929218) in the CDH1 gene and their relationship with gastric cancer risk. Materials and methods The study involved 105 gastric cancer patients with pathology results and 105 healthy controls. Clinical, histopathological, and demographic data were collected and compared between the two groups. Results No significant differences were found for rs16260 (- 160 C > A) and rs9929218 (G > A) between patients and controls (p > 0.05). For rs13689 (T > C), the T allele frequency was 90% in patients versus 69% in controls, while the C allele frequency was 10% in patients versus 31% in controls. A significant difference was observed for this SNP, with a higher T allele frequency in patients (OR = 4.03 CI95% 2.4-6.7, p < 0.0001) compared with controls, suggesting a fourfold increased risk of gastric cancer. Genotype frequencies were 80% wild-type (TT) and 20% heterozygous-type (TC) in patients, and 58% TT, 22% TC, and 20% mutant-type (CC) in controls (p < 0.0001). The frequencies of non-C allele carriers (TT) were present in 80% of patients versus 58.1% of controls (OR = 2.88 CI95% 1.56-5.34, p = 0.0006). Conclusion This study is the first to link the rs13689 SNP's T allele and TT genotype with increased gastric cancer risk. Our results suggest that the rs13689 T allele may contribute significantly to disease susceptibility, while the rs16260 CC genotype and rs9929218 GG genotype may influence risk in smokers.
Metformin Eliminates Cd133high Prostate Cancer Stem Cells Via Cell Cycle Arrest and Apoptosis
(Kare Publ, 2021) Acikgoz, Eda; Cakir, Mustafa; Guven, Mustafa; Oktem, Gulperi
Objectives: Cancer stem cells (CSCs), a small subpopulation of tumors, are responsible for chemo-radioresistance, metastasis, and cancer recurrence. The main aim of the present study is to investigate the potential effects of metformin on prostate CSCs (PCSCs). Methods: Flow cytometry was used to isolate cells with co-expression of CD133 and CD44. Sorted PCSCs were treated with different concentrations of metformin to determine the effects of metformin on cell viability using MTT assay. The association of cells exposure to metformin with apoptotic cell death and caspase activity, as well as cell cycle, were performed using the Muse Cell Analyzer. Results: In our study, for the first time we demonstrated the anti-cancer effects of metformin on PCSCs. Our results revealed that treatment with metformin reduced cell viability in CD133(high)/CD44(high) cells in a dose- and time-dependent manner. Metformin significantly induced early apoptosis and triggered the activity of several caspases associated with the apoptotic process. Metformin significantly altered the cell cycle distribution in CD133(high)/CD44(high) cells, leading to G0/G1 phase arrest. Conclusion: The results of the study revealed that metformin triggers cell death and apoptosis and modulates cell cycle distribution in CD133(high)/CD44(high) PCSCS. The present study raises the possibility that metformin is a potential anti-cancer agent for targeting PCSCs.