Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Inhibition of the Notch Pathway Promotes Flap Survival by Inducing Functional Neoangiogenesis(2015) Abbas, Ozan Luay; Borman, Huseyin; Terzi, Yunus K.; Terzi, Aysen; Bayraktar, Nilufer; Ozkan, Burak; Yazici, Ayse C.; 0000-0002-7886-3688; 0000-0003-3093-8369; 0000-0002-1225-1320; 0000-0002-3132-242X; 0000-0001-5612-9696; 25180956; Y-8758-2018; AAI-5063-2020; F-7546-2013; AAS-6810-2021; B-4372-2018Objective The Notch pathway seems to function as an antiangiogenic factor, negatively regulating the sprouting effect of vascular endothelial growth factor (VEGF). This function is well defined in embryonic and tumor vasculature. However, little is known about its function in ischemia-induced angiogenesis. In the first part of this study, we investigated the role of Notch in reparative angiogenesis after ischemia. In the second part, we hypothesized that anti-Notch therapy will result in increased angiogenic sprouting. We analyzed the effect of Notch inhibition in the induction of angiogenic sprouting. Methods In the first part, we investigated the effect of ischemia on the Notch ligand delta-like ligand 4 (DLL4). Twenty rats were divided equally into 2 groups. In the surgery group, dorsal skin flap was used as model of ischemia. In the control group, no surgical procedure was performed. DLL4 and VEGF gene expressions were assessed. Immunohistochemical staining was used for detection of DLL4 in tissue materials. Plasma levels of VEGF and DLL4 were measured. In the second part, we investigated the effect of Notch inhibition using a gamma-secretase inhibitor (GSI) on inducing neoangiogenesis. Twenty rats were assigned to 2 equal groups. In all animals, dorsal skin flap was raised and sutured back into its bed. Animals in the GSI-treated group received GSI intravenously after surgery for 3 days. Saline was administered in the control group. Necrotic area measurements, microangiography, and histologic evaluations were performed to compare groups. Results In the first part, VEGF and DLL expressions increased in ischemic tissues (P < 0.01). Immunohistochemical analysis revealed that DLL4 expression was upregulated in capillary endothelial cells after ischemia. Plasma levels for VEGF and DLL4 were higher in the animals that underwent surgery (P < 0.01). In the second part, GSI treatment resulted in higher flap survival rates (P < 0.05). Microscopic analysis exhibited increase in the number of microvascular structures after GSI treatment (P < 0.05). Microangiographic evaluation showed that neovascularization increased in the GSI-applied flaps. Conclusions We present an evidence for the importance of the Notch pathway in the regulation of ischemia-induced angiogenesis. Notch inhibition promotes flap survival by creating a neovasculature that has an increase in vascular density.Item The effect of adipose stromal vascular fraction on transverse rectus abdominis musculocutaneous flap: an experimental study(2016) Ataman, Murat Gorkem; Uysal, Cagri A.; Ertas, Nilgun Markal; Bayraktar, Nilufer; Terzi, Aysen; Borman, Huseyin; 0000-0002-7886-3688; 0000-0001-6236-0050; 0000-0002-1225-1320; 27010192; Y-8758-2018; AAJ-2949-2021; F-7546-2013Item Effect of long-term intermittent hypothermia on random skin flap viability and new vessel formation(2020) Caglar, Ibrahim Baris; Ozkan, Burak; Albayati, Abbas; Uysal, Ahmet Cagri; Ertas, Nilgun Markal; 0000-0001-6236-0050; 0000-0003-2806-3006; AAJ-2949-2021; AAC-3344-2021Background: Preconditioning is the improving the overall viability of the flaps before surgery. Hypothermia is one of preconditioning methods. In literature, the effect of short time hypothermia in skin flap viability has been studied. However, there is no information about the effects of long-term application of hypothermia on skin flap viability. In this study, we investigated the effect of long-term local hypothermia on flap viability and new vessel formation on random pattern skin flaps. Materials and Methods: Thirty-six adult male Sprague-Dawley rats were used. The flap model was, 3 cm x 9 cm sized random pattern skin flap. Three groups were composed as control group, continuous hypothermia induction group with ice bags, and intermittent hypothermia induction with chloroethyl spray. Flaps were raised on the 15th day of hypothermia sessions. Flap viability was measured in the software program. Microangiography and blood vascular endothelial growth factor (VEGF) levels were assessed for the detection of new vessel formation. Results: Average flap viabilities were found to be 64.87% in Group I, 57.69% in Group II, and 62.22% in Group III. The difference between Group II and other groups were statistically significant. When microangiographies were examined macroscopically, diameters, and amount of vascular branches of vessels in Group II were found to be higher than other groups. The difference between blood VEGF levels day 1 values among groups was not statistically significant. When day 4 values were compared to baseline values difference in Group III was statistically significant. At days 7 and 15, differences between groups and corresponding baseline values were not statistically significant. Conclusion: Continuous long-term application of hypothermia with ice-water bags causes a significant increase in neovascularization in random pattern skin flaps without an increase in skin flap viability. Hence, we can say that 2 weeks of hypothermia on random pattern skin flaps is not an efficient preconditioning method in clinical use.Item Expression of maspin in testis tumors with germ cells and its relation with angiogenesis factors(2016) Celik, Huseyin; Turunc, Tahsin; Bal, Nebil; Hasirci, Eray; Akay, Alaaddin; Pekircioglu, Cetin Levent; 27513425Background/aim: We aimed to evaluate the importance of maspin expression in testicular tumors with germ cells, its effect on prognosis, and the relation with angiogenesis factors. Materials and methods: The paraffin blocks of the orchiectomy materials of 32 patients who had undergone orchiectomy due to testicular tumors were taken within the scope of the study. The specimens of the cases included in the study group were reexamined under light microscope. Results: While just one maspin-positive sample was found in the seminoma cases, maspin stained positively in 6 of the nonseminoma germ cell tumors (NSGCTs). No statistical difference was found between maspin and tumor stage, size, alpha fetoprotein values, vascular endothelial growth factor, Ki-67, and CD31. A statistically positive correlation was only determined between maspin and p53 (P < 0.001). Conclusion: Maspin protein, whose expression in some tumors is accepted as a poor prognostic factor, is also expressed in testicular tumors with germ cells. However, according to our study, it is difficult to say whether this protein is a favorable or poor prognostic factor in testicular tumors and to understand how the effect mechanism works. The positive correlation between maspin and p53 in the NSGCTs makes us think that maspin might have displayed an effect on the p53 pathway.