Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
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Review Citation - WoS: 9Citation - Scopus: 7Micrornas and Long Non-Coding Rnas as Novel Targets in Anti-Cancer Drug Development(Bentham Science Publishers, 2023) Çetinkaya, Melisa; Baran, YusufNon-coding RNAs comprise the majority of RNAs that have been transcribed from the human genome, and these non-coding RNAs have essential regulatory roles in the cellular processes. They have been discovered to influence the expression of the genes, including tumor-suppressive and oncogenes, that establish the non-coding RNAs as novel targets for anti-cancer drug development. Among non-coding RNAs, microRNAs have been extensively studied in terms of cancer biology, and some microRNA-based therapeutics have been reached in clinical studies. Even though most of the research regarding targeting non-coding RNAs for anti-cancer drug development focused on microRNAs, long non-coding RNAs have also started to gain importance as potential therapeutic targets for cancer therapy. In this chapter, the strategies and importance of targeting microRNAs and long non-coding RNAs will be described, along with the clinical studies that involve microRNA-based cancer therapeutics and preclinical studies that involve long non-coding RNA-based therapeutics. Finally, the delivery strategies that have great importance in the effective delivery of the non-coding RNA-based cancer therapeutics, hence the therapy's effectiveness, will be described.Research Project Biyolojik-kimyasal reaksiyonların benzetimi için Monte Carlo teknikleri(TÜBİTAK - Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, 2012) Altınkaya, Mustafa Aziz; İnal, Fikret; Baran, YusufKimyasal reaksiyonların stokastik modellemesi, reaksiyondaki molekül sayılarının az olduğu durumda, her bir molekülün ne zaman reaksiyona gireceğinin tam olarak belirlenememesi nedeniyle yalnızca makroskopik ölçekte doğru olan gerekirci yönteme göre daha başarılıdır. Gillespie’nin geliştirdiği stokastik benzetim algoritması (SBA) Monte Carlo teknikleriyle sistemdeki bir sonraki reaksiyonun hangi reaksiyon olacağını ve ne zaman gerçekleşeceğini belirlemektedir. Ancak SBA’nın molekül sayıları arttıkça işlem yoğunluğu çok artmaktadır. Bu durumda, sistemdeki her reaksiyonu her molekülün mevcut konsantrasyonunu koruması koşulunu bozmayacak miktarda çok kez ateşleyerek, reaksiyon sistemindeki her molekülün miktarını tau peryodu ile güncelleyen tau-atlama algoritması işlem yoğunluğunu önemli ölçüde azaltmaktadır. Her bir reaksiyon kanalının tau aralığında ateşlenme adedini belirleyen Poisson değişken, reaksiyona girme eğilimi ile tau'nun çarpımı çok büyüdüğünde Gauss gibi davranmaya başlar. Bu durumda reaksiyondaki konsantrasyonları belirleyen stokastik türev denklemi Kimyasal Langevin Denklemi’ne (KLD) karşılık gelir. KLD’deki Gauss sürecin yerine Levy (alfa) - kararlı daha dürtün bir sürecin konması, KLD’nin tanımladığı Brown hareketini Levy uçuşuna dönüştürür. Kimyasal Langevin-Levy Denklemi (KLLD) olarak tanımlanan bu denklem az sayıdaki molekülün bulunduğu biyokimyasal reaksiyonları daha iyi modelleyebilir. Maltozdan glukoz elde edilen bir Michaelis-Menten sistemi ve daha çok reaksiyon içeren laktuloz hidrolizi sırasındaki enzimatik transgalaktosilasyon reaksiyonlarında KLLD’nin SBA ve KLD’ye kıyasla daha fazla gerekirci eğriden sapmaya neden olduğu ancak aynı ortalama davranışın takip edildiği görülmektedir. Bu çalışma biyokimyasal reaksiyon benzetininde KLLD’ye dayalı tau-atlamanın kullanılabileceğini göstermiştir.Article Citation - WoS: 3Citation - Scopus: 3Her2-Specific Peptide (ltvspwy) and Antibody (herceptin) Targeted Core Cross-Linked Micelles for Breast Cancer: a Comparative Study(MDPI, 2023) Bayram, N.N.; Ulu, G.T.; Abdulhadi, N.A.; Gürdap, S.; İşoğlu, İ.A.; Baran, Yusuf; İşoğlu, S.D.This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfobetaine ((N-3-sulfopropyl-N,N-dimethylamonium)ethyl methacrylate), while the core part is formed by another block, consisting of AEMA (2-aminoethyl methacrylamide), DEGMA (di(ethylene glycol) methyl ether methacrylate), and a vinyl-functionalized, acid-sensitive cross-linker. Following this, a targeting agent (peptide (LTVSPWY) and antibody (Herceptin®)), in varying amounts, were coupled to the micelles, and they were characterized by 1H NMR, FTIR (Fourier-transform infrared spectroscopy), Zetasizer, BCA protein assay, and fluorescence spectrophotometer. The cytotoxic, cytostatic, apoptotic, and genotoxic effects of doxorubicin-loaded micelles were investigated on SKBR-3 (human epidermal growth factor receptor 2 (HER2)-positive) and MCF10-A (HER2-negative). According to the results, peptide-carrying micelles showed a higher targeting efficiency and better cytostatic, apoptotic, and genotoxic activities than antibody-carrying and non-targeted micelles. Also, micelles masked the toxicity of naked DOX on healthy cells. In conclusion, this nanocarrier system has great potential to be used in different drug-targeting strategies, by changing targeting agents and drugs. © 2023 by the authors.Review Citation - WoS: 96Citation - Scopus: 112Therapeutic Potential of Luteolin on Cancer(MDPI, 2023) Çetinkaya, Melisa; Baran, YusufCancer is a global concern, as the rate of incidence is increasing each year. The challenges related to the current chemotherapy drugs, such as the concerns related to toxicity, turn to cancer therapeutic research to discover alternative therapy strategies that are less toxic to normal cells. Among those studies, the use of flavonoids-natural compounds produced by plants as secondary metabolites for cancer therapy-has been a hot topic in cancer treatment. Luteolin, a flavonoid that has been present in many fruits, vegetables, and herbs, has been identified to exhibit numerous biological activities, including anti-inflammatory, antidiabetic, and anticancer properties. The anticancer property of Luteolin has been extensively researched in many cancer types and has been related to its ability to inhibit tumor growth by targeting cellular processes such as apoptosis, angiogenesis, migration, and cell cycle progression. It achieves this by interacting with various signaling pathways and proteins. In the current review, the molecular targets of Luteolin as it exerts its anticancer properties, the combination therapy that includes Luteolin with other flavonoids or chemotherapeutic drugs, and the nanodelivery strategies for Luteolin are described for several cancer types.Article Citation - WoS: 25Citation - Scopus: 38Biodiversity: the Overlooked Source of Human Health(Elsevier, 2023) Linhares, Yuliya; Kaganski, Alexander; Agyare, Christian; Aksan Kurnaz, Işıl; Neergheen, Vidushi; Kolodziejczyk, Bartlomiej; Baran, YusufBiodiversity is the measure of the variation of lifeforms in a given ecological system. Biodiversity provides ecosystems with the robustness, stability, and resilience that sustains them. This is ultimately essential for our survival because we depend on the services that natural ecosystems provide (food, fresh water, air, climate, and medicine). Despite this, human activity is driving an unprecedented rate of biodiversity decline, which may jeopardize the life-support systems of the planet if no urgent action is taken. In this article we show why biodiversity is essential for human health. We raise our case and focus on the biomedicine services that are enabled by biodiversity, and we present known and novel approaches to promote biodiversity conservation.Research Project Hormona dirençli prostat kanseri hücrelerinde dosetaksel ve seramidin induklediği apoptozisde seramid genlerinin ve ürünlerinin eksprersyon düzeylerinin araştırılması(2011) Baran, YusufBu araştırmada, androjenden bağımsız prostat kanser hücrelerinin durdurulması yönünde önemli rol oynayan LASS geni ve glukosilseramid sentaz (GSS), sfingozin kinaz-1 (SK-1) genlerinin ekspresyon düzeyleri tespit edilerek, seramid/sfingozin-1-fosfat ve seramid/glukozilseramid'in muhtemel rolleri incelendi. Dosetaksel, C8:seramid, GSS ve SK-1 inhibitörünün sitotoksik etkileri XTT hücre proliferasyon tekniği kullanılarak araştırıldı. Mitokondri zar potensiyeli (MZP) ve kaspaz-3 enzim aktivitesindeki değişiklikler kaspaz-3 ve JC-1 MMP kiti kullanılarak ölçüldü. Seramid metabolize eden genlerin ekspresyon düzeyleri RT-PCR kullanılarak incelendi. Bulunan sonuçların birbirini doğruladığı üzere, DU-145 ve PC-3 prostat kanser hücrelerinde, C8:seramid ve GSS, SK-1 inhibitörleri ile dosetaksel kombinasyonlarının, sitotoksik ve kaspaz-3 enzim aktivitesini arttırarak ve mitokondri zar potansiyelini bozarak önemli ölçüde sinerjistik etki ortaya çıkardıkları tespit edilmiştir. Bulunan sonuçlar, izobalogram analizleri ile de doğrulanmıştır. Daha da önemlisi, RT-PCR sonuçları dosetaksel ile muamele edilen hücrelerde, GSS ve SK-1 genlerinin ekspresyonlarında azalma ve LASS genlerinin ekspresyonlarında ise artış olduğunu göstermiştir. Elde edilen bu veriler, androjenden bağımsız prostat kanser hücrelerinde dosetakselin indüklediği apoptozda, seramid metabolize eden genlerin ve gen ürünlerinin önemli rolleri olduğunu anlamamıza yardım etmiştir.Conference Object Peptıde Targeted Core Cross-lınked Mıcelles For Dox Delıvery To Her2 Expressıng Cancer Cells(Mary Ann Liebert, 2022) Bayram, Nazende Nur; Ulu, Gizem Tuğçe; Gürdap, Seda; İşoğlu, İsmail Alper; Baran, Yusuf; Dinçer İşoğlu, SevilIn this study, we prepared a novel targeted and extra stable micellar nanocarrier that can facilitate intracellular drug release. First, ((N-3-sulfopropyl-N, N-dimethylammonium)ethyl methacrylate was synthesized by RAFT polymerization, and it was followed by copolymerization of macroCTA with AEM in the presence of an aciddegradable cross-linker. Then, a peptide estimated by phage display for HER-2 recognition was incorporated into these core cross-linked micelles with carbodiimide reaction.Article Citation - WoS: 2Citation - Scopus: 3Investigating the Potential Therapeutic Role of Targeting Stat3 for Overcoming Drug Resistance by Regulating Energy Metabolism in Chronic Myeloid Leukemia Cells(Mashhad University of Medical Sciences, 2022) Tezcanlı Kaymaz, Burçin; Günel, Nur Selvi; Söğütlü, Fatma; Özateş Ay, Neslihan Pınar; Baran, Yusuf; Gündüz, Cumhur; Biray Avcı, ÇığırObjective(s): STATs are one of the initial targets of emerging anti-cancer agents due to their regulatory roles in survival, apoptosis, drug response, and cellular metabolism in CML. Aberrant STAT3 activity promotes malignancy, and acts as a metabolic switcher in cancer cell metabolism, contributing to resistance to TKI nilotinib. To investigate the possible therapeutic effects of targeting STAT3 to overcome nilotinib resistance by evaluating various cellular responses in both sensitive and nilotinib resistant CML cells and to test the hypothesis that energy metabolism modulation could be a mechanism for re-sensitization to nilotinib in resistant cells. Materials and Methods: By using RNAi-mediated STAT3 gene silencing, cell viability and proliferation assays, apoptotic analysis, expressional regulations of STAT mRNA transcripts, STAT3 total, pTyr705, pSer727 protein expression levels, and metabolic activity as energy metabolism was determined in CML model K562 cells, in vitro. Results: Targeting STAT3 sensitized both parental and especially nilotinib resistant cells by decreasing leukemic cell survival; inducing leukemic cell apoptosis, and decreasing STAT3 mRNA and protein expression levels. Besides, cell energy phenotype was modulated by switching energy metabolism from aerobic glycolysis to mitochondrial respiration in resistant cells. RNAi-mediated STAT3 silencing accelerated the sensitization of leukemia cells to nilotinib treatment, and STAT3-dependent energy metabolism regulation could be another underlying mechanism for regaining nilotinib response. Conclusion: Targeting STAT3 is an efficient strategy for improving the development of novel CML therapeutics for regaining nilotinib response, and re-sensitization of resistant cells could be mediated by induced apoptosis and regulation in energy metabolism.Article Citation - WoS: 139Granulocytic Sarcoma: a Systematic Review(e-Century Publishing Corporation, 2013) Yılmaz, Asu Fergün; Saydam, Güray; Şahin, Fahri; Baran, YusufGranulocytic sarcoma also called myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid leukemia. It is observed during the course of myeloproliferative disorders especially in chronic myeloid leukemia and myelodysplastic syndromes. In some rare circumstances, it is detected before clinical signs of leukemia or other diseases. When the bone marrow biopsy reveals no other hematologic malignancies, the granulocytic sarcoma is described as nonleukemic, primary or isolated. It is observed at any part of the body but the most common locations are soft tissues, bone, peritoneum and lymph nodes. Presenting signs or symptoms are mainly due to mass effect of the tumor and dysfunction of the organ, or the tissue that is affected. The diagnosis is performed by biopsy of the tumor. The tumor consists of immature granulocytic cells, which could be documented by H&E, immunohistochemistry, and flow cytometric methods. Fluorescence in-situ hybridization and molecular analysis are also performed. The optimal time and type of treatment is not clear. Surgery could be an option especially for tumors, which cause organ dysfunction and/or obstruction. Systemic treatment should be considered in all patients because without systemic treatment, relapses and progression to acute myeloid leukemia is the ultimate fate of the disease in many cases. Cytarabine-containing remission-induction chemotherapies have been the most applied therapeutic strategies, but it is not clear whether the consolidation therapies are required or not, and what kind of regimens are appropriate. The role of hematopoietic stem cell transplantation (HSC) as a consolidation regimen is not clear, but, after the relapse of the disease with or without bone marrow involvement, HSC transplantation should be considered in suitable patients after the reinduction performed by AML chemotherapies. There is only limited data about the role of radiotherapy in these patients. It could be used in patients with relapsed disease, organ dysfunction which should be quickly relieved and inadequate response to chemotherapy. The effect of radiotherapy on overall survival is not known. New prospective studies and clinical trials are needed to generate guidelines for the treatment of primary granulocytic sarcomas.Article Citation - WoS: 15Changes in Molecular Biology of Chronic Myeloid Leukemia in Tyrosine Kinase Inhibitor Era(e-Century Publishing Corporation, 2013) Cömert, Melda; Baran, Yusuf; Saydam, GürayChronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by a reciprocal translocation between long arms of chromosomes 9 and 22 t(9; 22) that generates the BCR-ABL fusion gene. If left untreated, newly diagnosed chronic phase CML patients finally progress to accelerated and blastic phase. After the introduction of tyrosine kinase inhibitors (TKIs), treatment strategies of CML changed dramatically. However, the development of resistance to TKIs started to create problems over time. In this review, the current information about CML biology before and after imatinib mesylate treatment is summarized.