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    Clinicopathological relationship of Stanniocalcin-2 (STC2) expression in breast carcinomas
    (2024) Yuceer, Ramazan Oguz; Kıran, Mehmet; Udul, Perihan; Edızsoy, Akay
    Aim: To assess Stanniocalcin-2 (STC-2) expression in breast cancer and explore its correlation with clinicopathological parameters and prognostic factors. Materials and Methods: In this study, immunohistochemical STC2 staining was performed on 38 breast carcinoma patients who underwent modified radical mastectomy between March 2017 and November 2022. We examined its association with various prognostic factors, including age, histopathological subtype, histological grade, T stage, nodal metastasis, distant metastasis, lymphovascular invasion, tumor-infiltrating lymphocytes, hormonal status, HER2 status, Ki67 expression. Results: The mean age was 63.4 ± 14.9 (min. 43–max. 98). High STC2 expression was found in 22 (57.9%) patients, while low STC2 expression was found in 16 (42.1%) patients. Age, histopathological subtype, histological grade, T stage, nodal metastasis, distant metastasis, lymphovascular invasion, tumor-infiltrating lymphocytes, hormonal status, HER2 status, and Ki67 expression were similar in the high and low STC2 expression groups. Overall survival (OS) was significantly higher in those with high STC2 expression (p<0.05). However, STC2 expression did not correlate with progression-free survival (PFS) (p>0.05). In univariate and multivariate Cox regression analysis for overall OS, STC2 expression, nodal metastasis, tumor-infiltrating lymphocytes (TIL), histological type, and PFS were identified as independent risk factors for poor OS. In univariate and multivariate Cox regression analysis for PFS, T stage, nodal metastasis, distant metastasis, TIL, histological type, and PFS were independent risk factors for poor PFS. Conclusion: STC2 expression positively correlated with overall survival in breast carcinomas, suggesting that STC2 can be considered a favorable prognostic factor in this context.
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    Evaluation of the Effects of Locally Applied Resveratrol and Cigarette Smoking on Bone Healing
    (Mdpi, 2024) Iskender, Muhsin Firat; Cina, Muge; Camli, Sevket Tolga; Ciris, Ibrahim Metin; Yuceer, Ramazan Oguz
    Background: Bone healing is a complex process controlled by various mechanisms. It is known that cigarette smoking (CS) negatively affects bone healing by disrupting many of these mechanisms. In an effort to find ways to eliminate these negative effects caused by CS, studies have been conducted on various vitamins, antioxidants, and medications. Since high doses and repeated injections are required to increase the therapeutic effect of conventional drug applications, controlled drug delivery systems have been developed to avoid such problems. This study aimed to investigate the effects of resveratrol (RES), which has been made into a controlled drug delivery system, on bone healing in rats that were experimentally exposed to cigarette smoke to create a chronic smoking model. Methods: After establishing a chronic CS model by exposing the subjects to cigarette smoke of six cigarettes/day for four weeks, monocortical critical size defects of 3 mm (SD +/- 0.02 mm) in diameter were created in the femur using a trephine bur. During the operation, the defects in RES groups were filled locally with a gel-formed solution of RES (50 mu M) and Pluronic F-127 (14 mu L). CS exposure was continued during the bone healing period after surgery. All groups were sacrificed one month after the operation, and femur samples were taken. Results: The obtained samples were examined by histomorphometric and immunohistochemical techniques; osteoblast count, new bone area, macroscopic filling score, vascularization, and proliferation were evaluated. Conclusion: The results of this study indicate that CS negatively affects bone healing and that local application of RES reduces this effect.
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    Exploring the Prognostic Role of Trop-2, CD47, and CD163 Expression Levels on Survival Outcomes in Patients with Triple-Negative Breast Cancer
    (MDPI, 2025) Yuceer, Ramazan Oguz; Aydin, Sedanur; Gelir, Iclal; Koc, Tulay; Tuncer, Ersin; Ucar, Mahmut
    Background: This study evaluated the prognostic impact of Trop-2, CD47, and CD163 expression on clinical outcomes in triple-negative breast cancer (TNBC) and investigated their interactions with tumor progression. Methods: A retrospective cohort of 92 patients with TNBC was analyzed. The expression scores for Trop-2, CD47, and CD163 were categorized as negative/low (0-3 points) or high (4-6 points). The primary endpoint was overall survival (OS). Results: The median age of the cohort was 50 years old. High Trop-2 expression was observed in 55.4% of the patients and was significantly associated with advanced disease stage (p < 0.001). High CD47 expression (44.6%) was correlated with advanced stage (p = 0.044), whereas high CD163 expression (45.7%) was associated with advanced stage (p = 0.021), absence of comorbidities (p = 0.022), and lower pT stage (p = 0.023). Moderate positive correlations were found between Trop-2 and CD47 (p = 0.022), Trop-2 and CD163 (p = 0.037), and CD47 and CD163 (p < 0.001), respectively. Kaplan-Meier survival analysis revealed that patients with low Trop-2 expression exhibited significantly prolonged OS (p = 0.021) and progression-free survival (PFS) (p = 0.026) compared to those with high Trop-2 expression. Univariate and multivariate analyses revealed significant associations between OS and PFS for Trop-2, lymphovascular invasion, and BRCA status. Conclusions: Trop-2 expression is a significant prognostic factor for TNBC and is correlated with worse outcomes. Although CD47 and CD163 showed trends for poorer prognosis, their significance was not confirmed. These findings offer promising prospects for future studies on combined antibody-drug conjugates (ADCs), as they may present opportunities to address multiple resistance mechanisms in the management of TNBC and enhance clinical outcomes.
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    Prognostic Biomarkers in Isocitrate Dehydrogenase Wild-Type Glioblastoma: A Focus on B7-H3
    (MDPI, 2025) Yuceer, Ramazan Oguz; Kaya, Seyhmus; Balci, Sema Nur; Egilmez, Hatice Reyhan; Yilmaz, Mukaddes; Erdis, Eda
    Background: Isocitrate dehydrogenase (IDH) wild-type (wt) glioblastoma is an aggressive malignancy associated with poor clinical outcomes, marked by high heterogeneity and resistance to treatment. This study aims to investigate the prognostic significance of B7-H3 expression in IDH wt glioblastoma and its potential association with clinical outcomes, including overall survival (OS) and progression-free survival (PFS). Additionally, the relationship between B7-H3 and PD-L1 expression was explored. Methods: A retrospective cohort of 86 IDH wt glioblastoma patients, all of whom underwent surgery, radiotherapy, and temozolomide treatment, was analyzed. B7-H3 expression was quantified using an immunoreactivity score (IRS), classifying samples as low (IRS <= 4) or high (IRS > 4). PD-L1 expression was evaluated based on tumor and immune cell staining, with >5% positivity indicating significant expression. Results: High B7-H3 expression was significantly associated with poorer OS and PFS. Co-expression of B7-H3 and PD-L1 was prevalent, particularly among younger male patients with unifocal tumors; however, PD-L1 expression did not show a significant correlation with clinical outcomes. Conclusions: B7-H3 appears to be a promising prognostic biomarker in IDH wt glioblastoma and may serve as a target for developing combination therapies, integrating B7-H3-targeting treatments with immune checkpoint inhibitors. Further prospective studies are necessary to validate these findings and to explore potential therapeutic strategies.
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    The Prognostic Significance of CD47, CD68, and CD163 Expression Levels and Their Relationship with MLR and MAR in Locally Advanced and Oligometastatic Nasopharyngeal Carcinoma
    (MDPI, 2024) Aydin, Asim Armagan; Yuceer, Ramazan Oguz; Yildirim, Senay; Unlu, Ahmet; Kayikcioglu, Erkan; Kocer, Murat
    Background: This study aimed to assess the prognostic and predictive implications of CD47, CD68, and CD163, biomarkers of tumor-associated macrophages (TAMs), on the treatment efficacy and clinical outcomes of nasopharyngeal carcinoma (NPC). Additionally, the prognostic value of TAM-related indices, such as the monocyte-to-lymphocyte ratio (MLR) and monocyte-to-albumin ratio (MAR), was evaluated. Methods: A retrospective cohort of 54 patients with locally advanced or oligometastatic NPC treated with concurrent chemoradiotherapy (CCRT), with or without induction chemotherapy, was analyzed. Patients were categorized based on the cumulative expression scores for CD47, CD68, and CD163: negative/low (0-3 points) and high (4-6 points). MLR and MAR were also stratified as low MLR (<0.545) vs. high MLR (>= 0.545) and low MAR (<16.145) vs. high MAR (>= 16.145). The primary endpoint was overall survival (OS). Results: High CD47, CD68, and CD163 expression levels were correlated with advanced clinical stage, reduced CCRT response, and elevated MLR and MAR. These TAM biomarkers were linearly correlated with each other and with established risk factors such as advanced age and elevated EBV-DNA levels. Kaplan-Meier analysis revealed that patients with low TAM expression had significantly longer OS and progression-free survival (PFS) than those with high TAM expression. Multivariate analysis identified high CD163, MLR, and MAR levels as independent adverse prognostic factors for OS. Elevated MLR is an independent risk factor for both OS and PFS in patients with NPC. Conclusions: CD47, CD68, and CD163 are significant prognostic markers in NPC, with higher levels being associated with poorer OS and PFS. Elevated MLR and MAR values also predict worse outcomes, underscoring their value as prognostic tools. CD163 and MLR are particularly strong predictors, highlighting the crucial role of TAMs in NPC management and suggesting that CD163 is a potential therapeutic target within the immune checkpoint pathway.
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    The role of C4d expression in the diagnosis of bullous pemphigoid: a clinical and histopathological study
    (Springer, 2025) Kaya, Seyhmus; Yuceer, Ramazan Oguz; Tosun, Mustafa; Mustafaeva, Reikhan
    Inflammatory processes play a crucial role in both autoimmune and non-autoimmune skin diseases. The complement system contributes to these processes, with both well-established and yet-to-be-confirmed effects. The relationship between C4d, an intermediate product of the complement system, and skin diseases remains an area of ongoing investigation. While the presence and role of C4d in autoimmune and non-autoimmune skin diseases have been explored using immunohistochemical methods, the topic remains inconclusive. Bullous pemphigoid is an autoimmune skin disorder characterized by subepidermal blistering, predominantly affecting the elderly population. This study aims to evaluate the potential of C4d as an alternative immunohistochemical marker to the gold-standard diagnostic method, direct immunofluorescence, in diagnosing Bullous pemphigoid. Additionally, C4d staining patterns were analyzed in correlation with clinical data to assess its prognostic significance. In this retrospective study, the histomorphological, clinical, and demographic data of 43 patients diagnosed with Bullous pemphigoid were analyzed. Immunohistochemical assessment of C4d expression and staining patterns was conducted. The findings suggest that C4d may serve as a potential diagnostic and prognostic marker. C4d expression was significantly more frequent in lesions located on the upper extremities and in patients with higher eosinophil scores. Furthermore, patients with high eosinophil scores were more likely to receive systemic treatment. This study demonstrates that C4d could contribute significantly to the diagnostic process, particularly in cases where immunofluorescence studies are limited.
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    Unraveling the Predictive Value of the Novel Global Immune-Nutrition-Inflammation Index (GINI) on Survival Outcomes in Patients with Grade 4 Adult-Type Diffuse Gliomas
    (Mdpi, 2024) Aydin, Asim Armagan; Yuceer, Ramazan Oguz
    Background: This investigation evaluated the predictive and prognostic efficacy of the newly developed global immune-nutrition-inflammation index (GINI) in patients with grade 4 adult-type diffuse gliomas, comparing it with other established indices such as the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV). Method: A retrospective cohort included 198 patients diagnosed with isocitrate dehydrogenase (IDH)-mutant gr4 (grade 4) astrocytoma and IDH-wt (wilde-type) glioblastoma (GBM) gr4 treated with surgical resection, radiotherapy, and temozolomide. Patients were stratified into two groups based on their GINI values: low GINI (<5815) and high GINI (>= 5815). The primary endpoint was overall survival (OS). Results: High GINI was significantly associated with older age, poor performance status, multifocal tumors, and higher SII, SIRI, and PIV values (p < 0.005). The GINI demonstrated strong correlations with SII (r = 0.694), SIRI (r = 0.516), and PIV (r = 0.657) (p < 0.001). Patients with high GINI exhibited poorer OS (5.0 vs. 17.0 months) and PFS (5.0 vs. 13.0 months) in comparison to those with low GINI. Kaplan-Meier survival analysis revealed significantly prolonged OS and PFS among patients with low GINI (p < 0.001). Multivariate analysis identified high GINI as an independent negative risk factor for both PFS and OS. Conclusions: GINI is a robust predictor of clinical outcomes in IDH-mutant gr4 astrocytoma and IDH-wt GBM gr4, highlighting the crucial impact of nutrition and cancer cachexia. It shows superior prognostic value relative to the SII, SIRI, and PIV.