Browsing by Author "Bozkurt, KK"

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    Protective role of adrenomedullin in heterotopic ovarian transplant
    Erdemoglu, E; Gürgen, SG; Erdemoglu, E; Bozkurt, KK; Oyar, EO
    Purpose of investigation: To study adrenomedullin (ADM) in preventing ischemia and morphological changes in heterotopically transplanted ovary. Materials and Methods: Forty female Sprague-Dawley rats were divided into four groups. In groups 1 and 2 each ovary was transplanted to the corresponding inguinal region by heterotopic transplantation. In groups 3 and 4, ovaries were left intact without transplantation. Treatment was injected to left inguinal region. ADM was given in groups 1 and 3 and placebo was given in groups 2 and 4. Left ovaries showing local treatment effect in heterotopic transplantation was designated as A (1A, 2A, 3A, and 4A), right ovaries showing systemic treatment effect were designated as (1B, 2B,3B, and 4B). Main outcome measures were ischemia, follicle count, and CD 31 expression. Results: Ovaries treated with local ADM (group 1A) were in consonance with normal rat ovaries. The ovaries of rats in group 1B and placebo treated transplant group (groups 2A, 2B) exhibited varying effects of ischemia. The mean follicle numbers in groups 1A, 1B, 2A, 2B were 28 3.3, 16.8 2.5, 17.7 2.1, 16.4 2.9, respectively. The mean follicle number in groups 3A, 3B, 4A, and 4B were 27.7 2.0, 28.3 2.2, 28.3 2.2, 27.8 1.9, respectively. Corpus luteum number and CD31 expression was found to be significantly higher in group 1A. Conclusion: Subcutaneous injection of ADM to heterotopic ovarian graft site causes vasodilatation and increases angiogenesis and may protect ovarian graft against hypoxic damage.
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    Agnostic Biomarkers in Molecular Pathology
    Yilmaz, ZS; Cakir, Y; Kececi, SD; Bozkurt, KK; Ertunc, O; Ozturk, RG; Tan, A
    Advances in molecular techniques have revealed that different molecular mechanisms are responsible for the behavior of cancer cells. Molecular alterations play a critical role in both the differential diagnosis of cancer and in the development of targeted therapies. Studies have identified the same potentially targetable mutations across various tumor types, supporting the emergence of tumor-agnostic therapies. To date, five biomarkers have been approved for tumor-agnostic therapy: microsatellite instability (MSI), neurotrophic tyrosine receptor kinase (NTRK) fusion, tumor mutation burden (TMB), BRAFV600E mutation, and rearranged during transfection (RET) fusions. The United States Food and Drug Administration (FDA) has approved pembrolizumab for MSI-high tumors or tumors with a high TMB. Larotrectinib and entrectinib have been approved for the treatment of NTRK gene fusion-positive tumors. Additionally, the combination of dabrafenib and trametinib has been approved for BRAFV600E mutations, and selpercatinib has been approved for RET fusion-positive cancers as of 2022. Positive responses to agnostic therapy, a significant milestone in cancer treatment, depend on the identification of new agnostic biomarkers. Ongoing research is focused on defining additional molecular changes, such as programmed death-ligand 1 (PD-L1), Kirsten rat sarcoma virus (KRAS), neuregulin 1 (NRG1), fibroblast growth factor receptor (FGFR), anaplastic lymphoma kinase (ALK), AKT serine/threonine kinase (AKT), human epidermal growth factor receptor 2 (HER2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and breast cancer gene (BRCA), as potential agnostic biomarkers in various cancer types.