Browsing by Subject "Tumors"

Now showing 1 - 7 of 7

Open Access
Amphiphilic peptide coated superparamagnetic iron oxide nanoparticles for in vivo MR tumor imaging
(Royal Society of Chemistry, 2016) Ozdemir, A.; Ekiz, M. S.; Dilli, A.; Güler, Mustafa O.; Tekinay, A. B.
Magnetic resonance imaging (MRI) is a noninvasive imaging technique that provides high spatial resolution and depth with pronounced soft-tissue contrast for in vivo imaging. A broad variety of strategies have been employed to enhance the diagnostic value of MRI and detect tissue abnormalities at an earlier stage. Superparamagnetic iron oxide nanoparticles (SPIONs) are considered to be suitable candidates for effective imaging due to their small size, versatile functionality and better biocompatibility. Here, we demonstrate that coating SPIONs with proline-rich amphiphilic peptide molecules through noncovalent interactions leads to a water-dispersed hybrid system suitable as an MRI contrast agent. Cellular viability and uptake of amphiphilic peptide coated SPIONs (SPION/K-PA) were evaluated with human vascular endothelial cells (HUVEC) and estrogen receptor (ER) positive human breast adenocarcinoma (MCF-7) cells. The efficiency of SPION/K-PA as MRI contrast agents was analyzed in Sprague-Dawley rats with mammary gland tumors. MR imaging showed that SPION/K-PA effectively accumulated in tumor tissues, enhancing their imaging potential. Although nanoparticles were observed in reticuloendothelial system organs (RES) and especially in the liver and kidney immediately after administration, the MR signal intensity in these organs diminished after 1 h and nanoparticles were subsequently cleared from these organs within two weeks. Histological observations also validated the accumulation of nanoparticles in tumor tissue at 4 h and their bioelimination from the organs of both healthy and tumor-bearing rats after two weeks.
Open Access
A bifunctional photosensitizer for enhanced fractional photodynamic therapy: singlet oxygen generation in the presence and absence of light
(Wiley-VCH Verlag, 2016) Turan, I. S.; Yildiz, D.; Turksoy, A.; Gunaydin, G.; Akkaya, E. U.
The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy (PDT) is self-limiting, as the already low oxygen concentrations within tumors is further diminished during the process. In certain applications, to minimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allow time for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that a photosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT. Thus, in the light cycle, the endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle, the endoperoxide undergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As a result, the photodynamic process can continue in the dark as well as in the light cycles. Cell-culture studies validated this working principle in vitro.
Open Access
Diagnosis of gastric carcinoma by classification on feature projections
(Elsevier, 2004) Güvenir, H. A.; Emeksiz, N.; İkizler, N.; Örmeci, N.
A new classification algorithm, called benefit maximizing classifier on feature projections (BCFP), is developed and applied to the problem of diagnosis of gastric carcinoma. The domain contains records of patients with known diagnosis through gastroscopy results. Given a training set of such records, the BCFP classifier learns how to differentiate a new case in the domain. BCFP represents a concept in the form of feature projections on each feature dimension separately. Classification in the BCFP algorithm is based on a voting among the individual predictions made on each feature. In the gastric carcinoma domain, a lesion can be an indicator of one of nine different levels of gastric carcinoma, from early to late stages. The benefit of correct classification of early levels is much more than that of late cases. Also, the costs of wrong classifications are not symmetric. In the training phase, the BCFP algorithm learns classification rules that maximize the benefit of classification. In the querying phase, using these rules, the BCFP algorithm tries to make a prediction maximizing the benefit. A genetic algorithm is applied to select the relevant features. The performance of the BCFP algorithm is evaluated in terms of accuracy and running time. The rules induced are verified by experts of the domain. © 2004 Elsevier B.V. All rights reserved.
Open Access
Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development
(Elsevier B.V., 2017) Bayyurt, B.; Tincer, G.; Almacioglu, K.; Alpdundar, E.; Gursel, M.; Gursel, I.
Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading. Furthermore, they protect cargo from enzymatic cleavage while providing stability, and enhancing biological activity. Herein, we aimed to develop a liposomal carrier system co-encapsulating TLR3 (polyinosinic-polycytidylic acid; poly(I:C)) and TLR9 (oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs; CpG ODN) ligands as immunoadjuvants together with protein antigen. To demonstrate that this depot system not only induce synergistic innate immune activation but also boost antigen-dependent immune response, we analyzed the potency of dual ligand encapsulated liposomes in long-term cancer protection assay. Data revealed that CpG ODN and poly(I:C) co-encapsulation significantly enhanced cytokine production from spleen cells. Activation and maturation of dendritic cells as well as bactericidal potency of macrophages along with internalization capacity of ligands were elevated upon incubation with liposomes co-encapsulating CpG ODN and poly(I:C). Immunization with co-encapsulated liposomes induced OVA-specific Th1-biased immunity which persisted for eight months post-booster injection. Subsequent challenge with OVA-expressing tumor cell line, E.G7, demonstrated that mice immunized with liposomes co-encapsulating dual ligands had significantly slower tumor progression. Tumor clearance was dependent on OVA-specific cytotoxic memory T-cells. These results suggest that liposomes co-encapsulating TLR3 and TLR9 ligands and a specific cancer antigen could be developed as a preventive cancer vaccine. ï¿½ 2017 Elsevier B.V.
Open Access
Feasibility of freehand CT and 3-T MR guided brain aspiration biopsies with 18/20-gauge coaxial needles
(Springer, 2022-07) Algın, Oktay; Ayberk, G.
Background and purpose: An accurate histopathological examination with minimal neuronal damage is essential for optimizing treatment strategies of central nervous system lesions. We investigated the feasibility and safety of CT and 3-tesla (3 T) MR-guided freehand brain aspiration biopsies with 18/20-gauge coaxial needles in performing a single imaging unit. Materials and methods: We reviewed CT and 3 T-MR guided freehand aspiration biopsies with 18/20-gauge coaxial needles of 33 patients (11-female and 22-male, mean and median ages: 53 years, min–max 21–79 years) in our tertiary hospital within an 8-year-period were included in this retrospective study. Lesion sizes, diagnostic yield, morbidity, and mortality rates of these biopsies without a scalp incision, surgical burr-hole, or stereotactic-instrumentation/neuro-navigation guidance were assessed. All biopsies were performed with local anesthesia and sedation within a single imaging unit of our radiology department. All free-hand biopsies were done as in-patient procedures and the patients were closely observed after the biopsies. Results: The mean diameter of the lesions was 27 mm (median 25; range 15–46 mm). The diagnostic yield of all free-hand brain biopsies was 88% [one inconclusive result (90%) for 3 T-MR; three inconclusive results (87%) for CT]. There was no major hemorrhage or hematoma, no clinical deterioration, or no infection in our patients on early- and late-phase examinations. Postprocedural minor hemorrhage with a ≤ 2 cm diameter was observed in two patients. The morbidity rate of the study population is 6%. There was no procedure-related infection or mortality in the post-procedural 3 weeks. Conclusions: Freehand CT or 3 T-MR guided aspiration biopsy was a safe and feasible method for pathological diagnosis of intracranial lesions. Biopsy workflow was simplified with this technique. It could be considered a valuable alternative for stereotaxic biopsies, especially for centers that do not have stereotaxic equipment or experience. © 2022, The Author(s) under exclusive licence to Japan Radiological Society.
Open Access
Local delivery of doxorubicin through supramolecular peptide amphiphile nanofiber gels
(Royal Society of Chemistry, 2017) Cinar, G.; Ozdemir, A.; Hamsici, S.; Gunay, G.; Dana, A.; Tekinay, A. B.; Güler, Mustafa O.
Peptide amphiphiles (PAs) self-assemble into supramolecular nanofiber gels that provide a suitable environment for encapsulation of both hydrophobic and hydrophilic molecules. The PA gels have significant advantages for controlled delivery applications due to their high capacity to retain water, biocompatibility, and biodegradability. In this study, we demonstrate injectable supramolecular PA nanofiber gels for drug delivery applications. Doxorubicin (Dox), as a widely used chemotherapeutic drug for breast cancer treatment, was encapsulated within the PA gels prepared at different concentrations. Physical and chemical properties of the gels were characterized, and slow release of the Dox molecules through the supramolecular PA nanofiber gels was studied. In addition, the diffusion constants of the drug molecules within the PA nanofiber gels were estimated using fluorescence recovery after the photobleaching (FRAP) method. The PA nanofiber gels did not show any cytotoxicity and the encapsulation strategy enhanced the activity of drug molecules on cellular viability through prolonged release compared to direct administration under in vitro conditions. Moreover, the local in vivo injection of the Dox encapsulated PA nanofiber gels (Dox/PA) to the tumor site demonstrated the lowest tumor growth rate compared to the direct Dox injection and increased the apoptotic cells within the tumor tissue for local drug release through the PA nanofiber gels under in vivo conditions.
Open Access
Remote-controlled release of singlet oxygen by the plasmonic heating of endoperoxide-modified gold nanorods: towards a paradigm change in photodynamic therapy
(Wiley-VCH Verlag, 2016) Kolemen, S.; Ozdemir, T.; Lee, D.; Kim, G. M.; Karatas, T.; Yoon, J.; Akkaya, E. U.
The photodynamic therapy of cancer is contingent upon the sustained generation of singlet oxygen in the tumor region. However, tumors of the most metastatic cancer types develop a region of severe hypoxia, which puts them beyond the reach of most therapeutic protocols. More troublesome, photodynamic action generates acute hypoxia as the process itself diminishes cellular oxygen reserves, which makes it a self-limiting method. Herein, we describe a new concept that could eventually lead to a change in the 100 year old paradigm of photodynamic therapy and potentially offer solutions to some of the lingering problems. When gold nanorods with tethered endoperoxides are irradiated at 808 nm, the endoperoxides undergo thermal cycloreversion, resulting in the generation of singlet oxygen. We demonstrate that the amount of singlet oxygen produced in this way is sufficient for triggering apoptosis in cell cultures. EPT sees the light: When gold nanorods with tethered endoperoxides are irradiated with near-infrared light, the endoperoxides undergo thermal cycloreversion, resulting in the generation of singlet oxygen. The amount of singlet oxygen generated by these nanocomposites is sufficient for triggering apoptosis in cell cultures.