Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Locoregional Treatment in De Novo Bone-Only Metastatic Breast Cancer: Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a(MDPI, 2025) Soran, Atilla; Demirors, Berkay; Aytac, Ozgur; Ozbas, Serdar; Dogan, Lutfi; Lucci, AnthonyIntroduction: The impact of locoregional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (dnBOMBC) is controversial. This study aims to assess the effect of LRT on survival, utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with dnBOMBC were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Further, patients who received LRT were divided into two subgroups: those who received ST after LRT (LRT+ST group) and those who received ST prior to LRT (ST+LRT group). Factors associated with disease progression, including solitary or multiple bone metastases, were analyzed. Results: There was a total of 744 patients with dnBOMBC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32-66, 25-75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs. 55 (44, 66), p = 0.0001]. There were no significant differences in grade, HER2 status, triple-negative status, receipt of hormonal therapy, or intervention to metastatic sites. During follow-up, 58% (n = 217) of patients in the ST group and 32% (n = 120) of patients in the LRT group died (p < 0.001). Local progression was observed in 20% of the patients in the ST group, whereas 9% progressed in the LRT group (p = 0.0001). Systemic progression occurred more in the ST group; 66% (n = 244) compared to 41% (n = 152) of patients in the LRT group (p < 0.001). The hazard of death was 64% lower in the LRT group than in the ST group (HR: 0.36, 95% CI: 0.29-0.45, p < 0.0001). The burden of metastatic disease differed significantly between the two groups, with a higher rate of solitary bone metastases in the LRT group compared to the ST group (50% vs. 24%, p < 0.001). However, the LRT group had better overall survival (OS) for both solitary (HR: 0.38, 95% Cl: 0.26-0.55) and multiple (HR: 0.38, 95% Cl: 0.29-0.51) bone metastasis patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST. Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p < 0.05). Conclusions: Analysis of this large multi-institutional patient cohort provides further evidence that LRT is associated with longer OS and lower locoregional recurrence rates in patients with dnBOMBC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor.Conference Object Genetic Determinants of Musculoskeletal Adaptations To Unloading and Reloading(Institute of Electrical and Electronics Engineers Inc., 2019) Özçivici, Engin; Judex, StefanLack of weight bearing is one of the most critical limitations for long term health of bone tissue in space missions. In this study, we performed a series of Quantitative Trait Locus (QTL) analysis of musculoskeletal traits to define genomic modulators adaptations to mechanical unloading and subsequent reloading using a genetically heterogeneous (F2 BALBxC3H) female mouse population. The identified regions on genome contain genes that regulate musculoskeletal adaptations to weightlessness and further studies may help to categorize individuals that are at risk for greater tissue loss during weightlessness and/or low tissue recovery during reambulation.Article Citation - WoS: 46Citation - Scopus: 53Chitosan-Hybrid Poss Nanocomposites for Bone Regeneration: the Effect of Poss Nanocage on Surface, Morphology, Structure and in Vitro Bioactivity(Elsevier, 2020) Tamburacı, Sedef; Tıhmınlıoğlu, FundaPOSS, regarded as the smallest silica particle, is widely used as nanofiller in polymer systems. POSS-based nanocomposites are deduced as novel materials having potency for biomedical applications owing to the enhanced biocompatibility and physicochemical characteristics. The aim of this work was to integrate the beneficial features of chitosan (CS) and OctaTMA-POSS nanoparticle to design nanocomposite for bone tissue regeneration. The nanocomposite scaffolds were fabricated by freeze-drying. The effects of POSS incorporation on morphology and structure of CS matrix were examined. Bioactivity and osteogenic effects of the POSS nanoparticles were investigated with cytocompatibility, cell proliferation, alkaline phosphatase activity, osteocalcin production and biomineralization assays. PUSS incorporation altered the surface morphology by increasing surface roughness. Nanocomposite scaffolds with 82-90% porosity exhibited an increase in compression modulus of scaffolds (78-107 kPa) compared to control CS group (56 kPa). Results indicated that CS-POSS scaffolds were found cytocompatible with 3T3, MG-63 and Saos-2 cell lines. POSS incorporation showed promising effects on osteoblast adhesion and proliferation as well as increasing ALP activity, octeocalcin secretion and biomineralization of cells. (C) 2019 Elsevier B.V. All rights reserved.Article Citation - WoS: 27Citation - Scopus: 34Chitosan/Montmorillonite Composite Nanospheres for Sustained Antibiotic Delivery at Post-Implantation Bone Infection Treatment(IOP Publishing Ltd., 2019) Kımna, Ceren; Değer, Sibel; Tamburacı, Sedef; Tıhmınlıoğlu, FundaDespite the advancements in bone transplantation operations, inflammation is still a serious problem that threatens human health at the post-implantation period. Conventional antibiotic therapy methods may lead to some side effects such as ototoxicity and nephrotoxicity, especially when applied in high doses. Therefore, local drug delivery systems play a vital role in bone disorders due to the elimination of the disadvantages introduced by conventional methods. In the presented study, it was aimed to develop Vancomycin (VC) and Gentamicin (GC) loaded chitosan-montmorillonite nanoclay composites (CS/MMT) to provide required antibiotic doses to combat post-implantation infection. CS/MMT nanocomposite formation was supplied by microfluidizer homogenization and spherical drug carrier nanoparticles were obtained by electrospraying technique. Three factors; voltage, distance and flowrate were varied to fabricate spherical nanoparticles with uniform size. Emprical model was developed to predict nanosphere size by altering process variables. Nanospheres were characterized in terms of morphology, hydrodynamic size, zeta potential, drug encapsulation efficiency and release profile. Drug loaded nanospheres have been successfully produced with a size range of 180-350 nm. Nanocomposite drug carriers showed high encapsulation efficiency (80%-95%) and prolonged release period when compared to bare chitosan nanospheres. The drug release from nanocomposite carriers was monitored by diffusion mechanism up to 30 d. The in vitro release medium of nanospheres showed strong antimicrobial activity against gram-positive S. aureus and gram-negative E. coli bacteria. Furthermore, it was found that the nanospheres did not show any cytotoxic effect to fibroblast (NIH/3T3) and osteoblast (SaOS-2) cell lines. The results demonstrated that the prepared composite nanospheres can be a promising option for bone infection prevention at the post implantation period.Article Citation - WoS: 51Citation - Scopus: 60Biosilica Incorporated 3d Porous Scaffolds for Bone Tissue Engineering Applications(Elsevier Ltd., 2018) Tamburacı, Sedef; Tıhmınlıoğlu, FundaAs a natural and abundant silica mineral, diatomite particles (SiO2-nH2O) have been used in several areas such as filtration, photonics, sound and heat insulation, filler material and drug delivery due to its abundance, inexpensive cost, unique morphology and porous structure. But up to date, diatomite incorporated silica based scaffolds have not been used for bone tissue engineering applications. In the present study, the goal was to combine the useful biomaterial properties of both chitosan and diatomite as biocomposite organic/inorganic biomaterial for bone tissue engineering applications and optimize the silica content of the composites in order to obtain optimum morphological structure, high mechanical properties, enlarged surface area and enhanced cell proliferation. The effect of silica loading on the mechanical, morphological, chemical, and surface properties, wettability and biocompatibility of composite scaffolds were investigated. In addition, in vitro cytotoxicity and cellular activities including cell proliferation, ALP activity and biomineralization were investigated in order to determine biological activity of the composite scaffolds. Diatomite particles lead to enhancement in the water uptake capacity of scaffolds. Chitosan-silica composites exhibited 82–90% porosity. Wet chitosan-silica composite scaffolds exhibited higher compression moduli when compared to pure chitosan scaffold in the range of 67.3–90.1 kPa. Average pore size range of chitosan-diatomite composite scaffolds was obtained as 218-319 μm. In vitro results indicated that chitosan-diatomite composites did not show any cytotoxic effect on 3T3, MG-63 and Saos-2 cell lines. Scaffolds were found to be favorable for osteoblast proliferation. Diatomite incorporation showed promising effects on enhancing ALP activity as well as mineral formation on scaffold surface. Thus, the prepared scaffolds in this study can be considered prospective material for bone tissue engineering applications.Article Citation - WoS: 62Citation - Scopus: 72Diatomite Reinforced Chitosan Composite Membrane as Potential Scaffold for Guided Bone Regeneration(Elsevier Ltd., 2017) Tamburacı, Sedef; Tıhmınlıoğlu, FundaIn this study, natural silica source, diatomite, incorporated novel chitosan based composite membranes were fabricated and characterized for bone tissue engineering applications as possible bone regeneration membrane. The effect of diatomite loading on the mechanical, morphological, chemical, thermal and surface properties, wettability and in vitro cytotoxicity and cell proliferation on of composite membranes were investigated and observed by tensile test, atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), protein adsorption assay, air/water contact angle analysis and WST-1 respectively. Swelling studies were also performed by water absorption capacity determination. Results showed that incorporation of diatomite to the chitosan matrix increased the surface roughness, swelling capacity and tensile modulus of membranes. An increase of about 52% in Young's modulus was achieved for 10 wt% diatomite composite membranes compared with chitosan membranes. High cell viability results were obtained with indirect extraction method. Besides, in vitro cell proliferation and ALP activity results showed that diatom incorporation significantly increased the ALP activity of Saos-2 cells cultured on chitosan membranes. The novel composite membranes prepared in the present study with tunable properties can be considered as a potential candidate as a scaffold in view of its enhanced physical & chemical properties as well as biological activities for bone tissue engineering applications.Article Citation - WoS: 13Citation - Scopus: 13Genetic and Tissue Level Muscle-Bone Interactions During Unloading and Reambulation(International Society of Musculoskeletal and Neuronal Interactions, 2016) Judex, Stefan; Zhang, Weidong; Donahue, Leah Rae; Özçivici, EnginLittle is known about interactions between muscle and bone during the removal and application of mechanical signals. Here, we applied 3wk of hindlimb unloading followed by 3wk of reambulation to a genetically heterogeneous population of 352 adult mice and tested the hypothesis that changes in muscle are associated with changes in bone at the level of the tissue and the genome. During unloading and relative to normally ambulating control mice, most mice lost muscle and cortical bone with large variability across the population. During reambulation, individual mice regained bone and muscle at different rates. Across mice, changes in muscle and trabecular/cortical bone were not correlated to each other during unloading or reambulation. For unloading, we found one significant quantitative trait locus (QTL) for muscle area and five QTLs for cortical bone without overlap between mechano-sensitive muscle and cortical bone QTLs (but some overlap between muscle and trabecular QTLs). The low correlations between morphological changes in muscle and bone, together with the largely distinct genetic regulation of the response indicate that the premise of a muscle-bone unit that co-adjusts its size during (un)loading may need to be reassessed. © 2016, International Society of Musculoskeletal and Neuronal Interactions. All rights reserved.Article Citation - WoS: 32Citation - Scopus: 39Fluorine-18 Fluorodeoxyglucose Pet-Ct for Extranodal Staging of Non-Hodgkin and Hodgkin Lymphoma(Turkish Society of Radiology, 2014) Ömür, Özgür; Baran, Yusuf; Oral, Aylin; Ceylan, YeşimPurpose We aimed to evaluate the role of fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) involving care-dose unenhanced CT to detect extranodal involvement in patients with non-Hodgkin and Hodgkin lymphoma. Materials and Methods Lymphoma patients (35 Hodgkin lymphoma, 75 non-Hodgkin lymphoma) who were referred for 18F-FDG PET-CT imaging, following a diagnostic contrast-enhanced CT (CE-CT) performed within the last month, were included in our study. A total of 129 PET-CT images, and all radiologic, clinical, and pathological records of these patients were retrospectively reviewed. Results In total, 137 hypermetabolic extranodal infiltration sites were detected by 18F-FDG PET-CT in 62 of 110 patients. There were no positive findings by CE-CT that reflected organ involvement in 40 of 137 18F-FDG-positive sites. The κ statistics revealed fair agreement between PET-CT and CE-CT for the detection of extranodal involvement (κ=0.60). The organs showing a disagreement between the two modalities were the spleen, bone marrow, bone, and thyroid and prostate glands. In all lesions that were negative at CE-CT, there was a diffuse 18F-FDG uptake pattern in the PET-CT images. The frequency of extranodal involvement was 51% and 58% in Hodgkin and non-Hodgkin lymphoma patients, respectively. There was a high positive correlation between the maximum standardized uptake values of the highest 18F-FDG-accumulating lymph nodes and extranodal sites (r=0.67) in patients with nodal and extranodal involvement. Conclusion 18F-FDG PET-CT is a more effective technique than CE-CT for the evaluation of extranodal involvement in Hodgkin and non-Hodgkin lymphoma patients. PET-CT has a significant advantage for the diagnosis of diffusely infiltrating organs without mass lesions or contrast enhancement compared to CE-CT.Article Citation - WoS: 18Citation - Scopus: 21Genetic Loci That Control the Loss and Regain of Trabecular Bone During Unloading and Reambulation(John Wiley and Sons Inc., 2013) Judex, Stefan; Zhang, Weidong; Donahue, Leah Rae; Özçivici, EnginChanges in trabecular morphology during unloading and reloading are marked by large variations between individuals, implying that there is a strong genetic influence on the magnitude of the response. Here, we subjected more than 350 second-generation (BALBxC3H) 4-month-old adult female mice to 3 weeks of hindlimb unloading followed by 3 weeks of reambulation to identify the quantitative trait loci (QTLs) that define an individual's propensity to either lose trabecular bone when weight bearing is removed or to gain trabecular bone when weight bearing is reintroduced. Longitudinal in vivo micro-computed tomography (μCT) scans demonstrated that individual mice lost between 15% and 71% in trabecular bone volume fraction (BV/TV) in the distal femur during unloading (average: -43%). Changes in trabecular BV/TV during the 3-week reambulation period ranged from a continuation of bone loss (-18%) to large additions (56%) of tissue (average: +10%). During unloading, six QTLs accounted for 21% of the total variability in changes in BV/TV whereas one QTL accounted for 6% of the variability in changes in BV/TV during reambulation. QTLs were also identified for changes in trabecular architecture. Most of the QTLs defining morphologic changes during unloading or reambulation did not overlap with those QTLs identified at baseline, suggesting that these QTLs harbor genes that are specific for sensing changes in the levels of weight bearing. The lack of overlap in QTLs between unloading and reambulation also emphasizes that the genes modulating the trabecular response to unloading are distinct from those regulating tissue recovery during reloading. The identified QTLs contain the regulatory genes underlying the strong genetic regulation of trabecular bone's sensitivity to weight bearing and may help to identify individuals that are most susceptible to unloading-induced bone loss and/or the least capable of recovering.