Person: ALASONYALILAR DEMİRER, AYLİN
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ALASONYALILAR DEMİRER
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AYLİN
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Publication Effect of dickkopf-1 (DKK-1) and SP600125, a JNK inhibitor, on wnt signaling in canine prostate cancer growth and bone metastases(Mdpi, 2021-07-27) Supsavhad, Wachiraphan; Hassan, Bardes B.; Simmons, Jessica K.; Dirksen, Wessel P.; Elshafae, Said M.; Kohart, Nicole A.; Demirer, Aylin A.; Rosol, Thomas J.; ALASONYALILAR DEMİRER, AYLİN; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı.; ERL-7504-2022Human Dickkopf-1 (Dkk-1) upregulates a noncanonical Wnt/JNK pathway, resulting in osteoclast stimulation, cell proliferation, and epithelial-to-mesenchymal transition (EMT) of cancer cells. Ace-1-Dkk-1, a canine prostate cancer (PCa) cell line overexpressing Dkk-1, was used to investigate Wnt signaling pathways in PCa tumor growth. SP600125, a JNK inhibitor, was used to examine whether it would decrease tumor growth and bone tumor phenotype in canine PCa cells in vitro and in vivo. Ace-1-Vector(YFP-Luc) and Ace-1-Dkk-1(YFP-Luc) cells were transplanted subcutaneously, while Ace-1-Dkk-1(YFP-Luc) was transplanted intratibially into nude mice. The effects of Dkk-1 and SP600125 on cell proliferation, in vivo tumor growth, and bone tumor phenotype were investigated. The mRNA expression levels of Wnt/JNK-related genes were measured using RT-qPCR. Dkk-1 significantly increased the mRNA expression of Wnt/JNK-signaling-related genes. SP600125 significantly upregulated the mRNA expression of osteoblast differentiation genes and downregulated osteoclastic-bone-lysis-related genes in vitro. SP600125 significantly decreased tumor volume and induced spindle-shaped tumor cells in vivo. Mice bearing intratibial tumors had increased radiographic density of the intramedullary new bone, large foci of osteolysis, and increased cortical lysis with abundant periosteal new bone formation. Finally, SP600125 has the potential to serve as an alternative adjuvant therapy in some early-stage PCa patients, especially those with high Dkk-1 expression.Publication Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone(Elsevier, 2019-12-01) Kohart, Nicole A.; Elshafae, Said M.; Supsahvad, Wachirapan; Alasonyalılar-Demirer, Aylin; Panfil, Amanda R.; Xiang Jingyu; Dirksen, Wessel P.; Veis, Deborah J.; Green, Patrick L.; Weilbaecher, Katherine N.; Rosol, Thomas J.; ALASONYALILAR DEMİRER, AYLİN; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı; EKS-2415-2022Adult T-cell leukemia/lymphoma has a unique relationship to bone including latency in the marrow, and development of bone invasion, osteolytic tumors and humoral hypercalcemia of malignancy. To study these conditions, we established and characterized a novel mouse model of ATL bone metastasis. Patient-derived ATL cell lines including three that do not express HTLV-1 oncoprotein Tax (ATL-ED, RV-ATL, TL-0m1), an in vitro transformed human T-cell line with high Tax expression (HT-1RV), and an HTLV-1 negative T-cell lymphoma (Jurkat) were injected intratibially into NSG mice, and were capable of proliferating and modifying the bone microenvironment. Radiography, mu CT, histopathology, immunohistochemistry, plasma calcium concentrations, and qRT-PCR for several tumor-bone signaling mRNAs were performed. Luciferase-positive ATL-ED bone tumors allowed for in vivo imaging and visualization of bone tumor growth and metastasis over time. ATL-ED and HT-1RV cells caused mixed osteolytic/osteoblastic bone tumors, TL-Oml cells exhibited minimal bone involvement and aggressive local invasion into the adjacent soft tissues, Jurkat cells proliferated within bone marrow and induced minimal bone cell response, and RV-ATL cells caused marked osteolysis. This mouse model revealed important mechanisms of human ATL bone neoplasms and will be useful to investigate biological interactions, potential therapeutic targets, and new bone-targeted agents for the prevention of ATL metastases to bone.Publication Parathyroid hormone-related protein promotes bone loss in T-cell leukemia as well as in solid tumors(Taylor & Francis, 2020-01-28) Kohart, Nicole A.; Elshafae, Said M.; Demirer, Aylin A.; Dirksen, Wessel P.; Breitbach, Justin T.; Shu, Sherry T.; Xiang, Jingyu; Weilbaecher, Katherine N.; Rosol, Thomas J.; ALASONYALILAR DEMİRER, AYLİN; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı.; ERL-7504-2022Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are important factors that increase bone resorption and hypercalcemia in adult T-cell leukemia (ATL). We investigated the role of PTHrP and MIP-1 alpha in the development of local osteolytic lesions in T-cell leukemia through overexpression in Jurkat T-cells. Injections of Jurkat-PTHrP and Jurkat-MIP-1 alpha into the tibia and the left ventricle of NSG mice were performed to evaluate tumor growth and metastasis in vivo. Jurkat-pcDNA tibial neoplasms grew at a significantly greater rate and total tibial tumor burden was significantly greater than Jurkat-PTHrP neoplasms. Despite the lower tibial tumor burden, Jurkat-PTHrP bone neoplasms had significantly greater osteolysis than Jurkat-pcDNA and Jurkat-MIP-1 alpha neoplasms. Jurkat-PTHrP and Jurkat-pcDNA cells preferentially metastasized to bone following intracardiac injection, though the overall metastatic burden was lower in Jurkat-PTHrP mice. These findings demonstrate that PTHrP induced pathologic osteolysis in T-cell leukemia but did not increase the incidence of skeletal metastasis.Publication Postmortem findings on a group of Pica pica (Passeriformes: Corvidae)(Ankara Üniversitesi, 2019-01-01) Girişgin, Ahmet Onur; Alasonyalılar Demirer, Aylin; Büyükcangaz, Esra; Khider, Mohammed; Birlik, Sezen; İpek, Volkan; GİRİŞGİN, AHMET ONUR; ALASONYALILAR DEMİRER, AYLİN; BÜYÜKCANGAZ, ESRA; Khider, Mohammed; BİRLİK, SEZEN; İpek, Volkan; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Parazitoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Mikrobiyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0002-0020-2708; 0000-0001-5874-7797; AAL-2323-2020; B-5286-2017; ABZ-7197-2022; AAB-9963-2020; EKS-2415-2022; DAZ-7569-2022Common magpies (Corvidae: Pica pica) distribute through rural and urban areas of Turkey. Because of their distribution in urbanised regions, magpies may have some potential infectious agents which may relate to domestic animals and humans. In this study, eight common magpies brought to the animal hospital in need of medical intervention were examined for endoparasites and bacteria in a one-year period. Additionally, histopathologic examinations with related organs were carried out along with endo-parasitical, cytological and microbial examination the following necropsy. As results of the necropsies, three parasite species including two helminths and one protozoan (Passerilepis sp., Brachylaima sp., Isospora rochalimai, respectively) were identified, while Staphylococcus xylosus, S. sciuri, Escherichia coli, Klebsiella pneumonia, Salmonella spp. were isolated after microbiological examination. Histopathology revealed that subacute focal mycotic pneumonia, chronic nonpurulent granulomatous gastroenteritis, verminous enteritis, and the presence of paratyphoid nodules in liver. Both of the parasites and bacteria are the first records for Turkey's helminth/bacterial fauna in wild birds.