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Yusuf TUTAR

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Dr. Yusuf TUTAR currently continues his research in University of Health Sciences, Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry- Mektebi Tıbbiye-i Sahane Turkey. He is also the head of Molecular Medicine Program. He obtained his M.Sc. and Ph.D. at Oregon State University and Texas Tech University respectively. He pursued his postdoctoral study at National Institutes of Health (NIH/NIDDK), USA. His research focuses on Biochemistry, Biophysics, Genetics, and Molecular Biology with specialization in the fields of drug design, protein structure-function, protein folding, prion, microrna, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression and characterization by spectroscopic and calorimetric methods.

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University of Alabama - Tuscaloosa

Armando Salvatore

McGill University

Benjamin Isakhan

Deakin University

Zenonas Tziarras

University of Cyprus

Rudolph (Rudi) Matthee

University of Delaware

Stockholm University

Marmara University

Joas Wagemakers

Utrecht University

University of California, Davis

Georgetown University

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Papers by Yusuf TUTAR

Introductory Chapter: Molecular Mechanism of Cancer Metastasis

Cancer Metastasis - Molecular Mechanism and Clinical Therapy

CO-releasing properties and anticancer activities of manganese complexes with imidazole/benzimidazole ligands

Journal of Coordination Chemistry, Sep 21, 2016

Carbon monoxide (CO) is an important signaling molecule which plays significant roles in the path... more Carbon monoxide (CO) is an important signaling molecule which plays significant roles in the pathogenesis of cancer. CO is produced by enzymatic degradation of heme in mammals. Heme oxygenase 1 (HO-1) catalyzes the breakdown of heme into CO, ferrous iron and biliverdin. CO induces HO-1 and inhibits cell proliferation. Cancer cells exposed to several stress factors (hypoxia, reactive oxygen species, cis-platin, and oxidative stress), and HO-1 displays cytoprotective role against oxidative stress and inhibits apoptosis, metastases, angiogenesis and cell proliferation processes. Therefore, metal containing CO-releasing molecules (CORMs) have been designed as an effective cancer treatment strategy. CORMs are responsible for releasing controlled amounts of CO to cells and tissues. Thus, we synthesized [Mn(CO) 3 (bpy)L]X manganese containing CORMs [bpy = 2,2'-bipyridine, X = hexafluorophosphate (PF 6), trifluoromethanesulfonate (OTf), L = imidazole, methylimidazole, benzimidazole, N-benzylbenzimidazole, N-(4-chlorobenzyl)benzimidazole] to release CO in human invasive ductal breast (MCF-7) cell line. In vitro experiments indicated that the compounds inhibited cell proliferation and exhibited cytotoxic effect on breast cancer cells. Moreover, side groups of the compounds enhanced the anti-cancer effects in MCF-7 cell line. These manganese containing

Silver(I) Complexes Based on Oxadiazole-Functionalized α-Aminophosphonate: Synthesis, Structural Study, and Biological Activities

Molecules, Nov 22, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more

Noncoding RNAs in Cancer Theranostics: From Molecular Basis to Therapeutic Implications

Current Pharmaceutical Biotechnology

Triad pyrazole–thiazole–coumarin heterocyclic core effectively inhibit HSP and drive cancer cells to apoptosis

Journal of Biomolecular Structure and Dynamics

Drugs and Drug Candidates for the Treatment of Lymphoma

Lymphoma

Cancer is the biggest health problem worldwide due to its high mortality rate. Lymphoma is define... more Cancer is the biggest health problem worldwide due to its high mortality rate. Lymphoma is defined as a group of malignant diseases that is caused by clonal proliferation of lymphocytes and is classified under two major groups: Hodgkin lymphoma and non-Hodgkin lymphoma. Genetic predisposition and some environmental factors constitute risk factors. Symptoms of the disease include unexplained fever, swelling of lymph glands, swollen abdomen, tiredness, loss of appetite, frequent infections, and weight loss. Positron emission tomography (PET) and computed tomography (CT) scans, along with MRI, are widely used for the diagnosis of lymphoma. Advanced blood and lymph node biopsy tests are used to evaluate treatment effect on blood cells and to confirm the diagnosis of lymphoma, respectively. Current treatment options include chemotherapy, radiotherapy, and bone marrow/stem cell transplantation. Development of new treatment options for cancer medications includes small molecules and monocl...

Circular Dichroism

Essential Techniques for Medical and Life Scientists: A Guide to Contemporary Methods and Current Applications- Part II, 2020

Frontiers in Protein and Peptide Sciences

Recent advances in (therapeutic protein) drug development

F1000Research, 2017

Therapeutic protein drugs are an important class of medicines serving patients most in need of no... more Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing) product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016).

Editorial: MicroRNA-related polymorphisms in infectious and inherited diseases

Frontiers in Genetics

Plasma Medicine - Concepts and Clinical Applications

In the past 20 years, cold atmospheric pressure plasmas (CAPs) have become a new promising way fo... more In the past 20 years, cold atmospheric pressure plasmas (CAPs) have become a new promising way for many biomedical applications, such as disinfection, cancer treatment, root canal treatment, wound healing, and other medical applications. Among these applications, investigations of plasma for skin wound healing has gained huge success both in vitro and in vivo experiments, and also the mechanism behind it has been studied by many groups. In this chapter, we summarize the state-of-the-art progress in wound healing by CAPs. The plasma devices developed for wound healing, the interactions between plasmas and microorganisms/cells/tissues, the in vitro and in vivo treatments, the clinical trials, and biosafety issues are all included.

A Medium for Facilitating Hepatitis B Virus Detection and Replication of the Virus

In this study, we tested a chemical mixture causing hepatitis virus to grow in excessive amounts.... more In this study, we tested a chemical mixture causing hepatitis virus to grow in excessive amounts. We obtained this chemical mixture by disintegrating albumin and invertase enzymes separately in supercritical environments, using acidic methanol as solvent. Then we used this mixture as a medium for hepatitis B virus. The chemical mixture caused the hepatitis B virus to multiply almost 80-100 times after 120 minutes. The real surprising result of the study occurred after carrying out bacterial tests with the same chemical mixture, its effect on cancer cells were also investigated. But no effect was observed neither on cancer cells, nor on bacteria. In other word, we developed a speci c medium for the hepatitis virus. In this way, we decided that a method that can reduce the detection limit of PCR device to 1 IU/mL could be developed. This study will be an important milestone in developing vaccines against viruses as well.

Designing Specific HSP70 Substrate Binding Domain Inhibitor for Perturbing Protein Folding Pathways to Inhibit Cancer Mechanism

Anti-Cancer Agents in Medicinal Chemistry, 2021

Background: HSP70 is a survival factor for tumor cells in transformation and in tumor progression... more Background: HSP70 is a survival factor for tumor cells in transformation and in tumor progression as well as in anti-apoptotic response. Objective: Several inhibitors targeting HSP70 ATPase function displayed off-target affect but PES which targets HSP70 substrate binding domain prevents tumor cell survival prominently. However, PES may not bind HSP70 in the absence of nucleotide. This research aimed to design a unique inhibitor molecule that work both in the presence and absence of nucleotides to amplify inhibition. Methods: A set of chimeric coumarine-pyrazole derivatives determined by in silico techniques and synthesized to elucidate their inhibitory effects. Cell viability experiments displayed KBR1307 as the most efficient inhibitor. A set of characterization experiments performed, and results compared to that of PES agent. Binding constant, ATP hydrolysis rate, and percent aggregation determined in the presence and absence of inhibitors. Results: In silico docking experiments ...

Involvement of Metabolites and Non-coding RNAs in Diseases

Current Pharmaceutical Biotechnology

: Non-coding RNAs have a role in gene regulation and cellular metabolism control. Metabolism prod... more : Non-coding RNAs have a role in gene regulation and cellular metabolism control. Metabolism produces metabolites which are small molecules formed during the metabolic process. So far, direct relation between metabolites and genes are not fully established however, pseudogenes and their progenitor genes regulate health and disease states. Other non-coding RNAs also contribute to this regulation at different cellular processes. Accumulation and depletion of metabolites accompany the dynamic equilibrium of health and disease state. In this chapter, metabolites, their roles in the cell, and the link between metabolites and non-coding RNAs are discussed.

Experimental MicroRNA Targeting Validation

Methods in Molecular Biology, 2021

microRNAs (miRNAs) have recently been recognized as a new dimension of posttranscriptional regula... more microRNAs (miRNAs) have recently been recognized as a new dimension of posttranscriptional regulation. It is well defined that most human protein-coding genes are regulated by one or more miRNAs. Therefore, it is crucial to identify genes targeted by the miRNAs to better understand their functions. Although bioinformatics tools have the ability to identify target candidates it is still essential to identify physiological targets by experimental approaches. Currently, the majority of miRNA-target experimental validation approaches assess the changes in target expression in mRNA or protein level upon miRNA upregulation or downregulation. Additionally, finding out direct physical interactions between miRNAs and their targets is also among the experimental techniques. In this chapter we reviewed the existing experimental techniques for miRNA target identification by considering their advantages and potential drawbacks.

Computational Analysis of Drug Resistance Network in Lung Adenocarcinoma

Anti-Cancer Agents in Medicinal Chemistry

Background: Lung cancer is a significant health problem and accounts for one-third of the deaths ... more Background: Lung cancer is a significant health problem and accounts for one-third of the deaths worldwide. A great majority of these deaths are caused by non-small cell lung cancer (NSCLC). Chemotherapy is the leading treatment method for NSCLC, but resistance to chemotherapeutics is an important limiting factor that reduces the treatment success of patients with NSCLC. Objective: In this study, the relationship between differentially expressed genes affecting the survival of the patients, according to the bioinformatics analyses, and the mechanism of drug resistance is investigated for non-small cell lung adenocarcinoma patients. Methods: Five hundred thirteen patient samples were compared with fifty-nine control samples. The employed dataset was downloaded from The Cancer Genome Atlas (TCGA) database. The information on how the drug activity altered against the expressional diversification of the genes was extracted from the NCI-60 database. Four hundred thirty-three drugs with k...

The role of serum levels of selenium, superoxide dismutase, catalase and thiobarbituric acid reactive substances in the association between Hashimoto's thyroiditis and papillary thyroid cancer

Assessment of plasma and tissue fibronectin EIIIB splice variant expressions measured serially with RT-PCR in a wound model of rabbits

Turkish Journal of Trauma and Emergency Surgery, 2020

BACKGROUND: Fibronectin (FN) is an indispensable part of the extracellular matrix. During regener... more BACKGROUND: Fibronectin (FN) is an indispensable part of the extracellular matrix. During regeneration or wound healing, the plasma form of FN is incorporated into the fibrin clots to form a temporary fibrin-FN matrix, and also locally synthesized cellular FN migrates to the clot to regenerate the injured tissue. We aimed to examine wound tissue FN EIIIB and plasma FN EIIIB expression levels in an experimental wound healing model in rabbits. METHODS: Plasma and tissue EIIIB splice variant expressions were measured serially with RT-qPCR in a cutaneous wound model of rabbits. RESULTS: Tissue FN expression increased as beginning on day 3 and continued to increase on days 6 and 9, reaching maximum expression at day 12 before starting to decrease. On the contrary to the tissue levels, plasma FN levels gradually decreased until day 15 when expression returned to the initial values. CONCLUSION: The findings of the current study support that tissue EIIIB expression level increases during wound healing; and plasma EIIIB expression level decreases minimal changed. This is in contrast to reports where plasma FN provisionally helps ECM formation. Therefore, our data show an essential role of EIIIB at the tissue level in accelerating the wound healing process. The RT-qPCR method in our experimental setup can provide more accurate and precise results compared to the antibody-based methods.

Anticancer activities of manganese-based photoactivatable CO-releasing complexes (PhotoCORMs) with benzimidazole derivative ligands

Transition Metal Chemistry, 2017

Carbon monoxide is an important signaling molecule which is produced by heme oxygenase-1. CO show... more Carbon monoxide is an important signaling molecule which is produced by heme oxygenase-1. CO shows antiproliferative activity against cancer cells; hence, activation of HO-1 is a significant inhibition strategy against tumor formation and survival of cancer cells. In this work, manganese-based CO-releasing molecules (CORMs) were designed and synthesized to inhibit breast cancer cell proliferation. Human invasive ductal breast cancer cells (MCF-7) were treated with the synthesized CORMs to investigate the effect of the complexes on breast cancer survival under UV light. In vitro experiments indicated that the complexes inhibited breast cancer cell proliferation, and further, the antiproliferative effects were increased under UV light. Thus, these novel CORMs may provide a drug template for the treatment of invasive ductal breast cancer.

<strong>Heat Shock Proteins in Targeted  Cancer Chemotherapy</strong>

Proceedings of 2nd International Electronic Conference on Medicinal Chemistry, 2016

Heat shock proteins (Hsps) are important biological targets in th next generation of cancer treat... more Heat shock proteins (Hsps) are important biological targets in th next generation of cancer treatments. Hsps play vital roles in protein hemostasis pathways (proper folding and stabilization of nascent proteins, inhibition of protein aggregation, degradation of aggregated proteins, signal transduction and protein translocation) in eukaryotic and prokaryotic cells. Hsps are found in different cellular compartments and their expression level is increased in response to cellular and external stress factors (tumorogenesis, UV light, hypoxia, oxidative, infection, stress, fever, temperature variation) [1]. Therefore, pathogenesis of diseases is related with expression level of Hsps. Hsps are over-expressed in cancer cells, and especially, Hsp27, Hsp70 and Hsp90 are involved in all phases of tumorogenesis (apoptosis, metastases, angiogenesis, invasion, and cell differentiation). Hsp27, Hsp70 and Hsp90 ensure stabilization, activation and proper folding of the oncogenic proteins in cancer cells. Therefore, inhibition of Hsps emerged as a significant therapeutic strategy for targeted cancer treatments. Inhibition of Hsp90 chaperone activity has been significant drug- targeted for the past 30 years in cancer treatment. Now, approximately 20 different compounds are in clinical phase studies [2,3]. Clinical and pre-clinical studies demonstrated that inhibition of Hsp90 activity is not enough by itself. Inhibition of Hsp90 triggers expression of Hsp70 and complements inhibited Hsp90 chaperone activity. Moreover, Hsp27 controls and regulates key points of the apoptotic pathway in cancer cells. Therefore, in addition to Hsp90 inhibition, blocking of Hsp70 and Hsp27 chaperone activities is a remarkable therapeutic strategy for cancer treatment [4]. In our lab, we designed and synthesized novel pyrimidine and coumarin derivatives as Hsp90 inhibitors. Pyrimidine analogs interrupted Hsp90 ATP hydrolysis process through disrupting N terminal domain (NTD) conformational change [5]. Coumarin derivatives inhibited C terminal domain (CTD) of Hsp90, and blocked dimerization process [6]. ACKNOWLEDGEMENTS The authors gratefully acknowledge the financial support received from the Scientific and Technological Research Council of Turkey, TUBITAK (Grant # 114Z365). REFERENCES [1] Tutar, L.; Tutar, Y. Heat shock proteins; an overview. Curr. Pharm.Biotechnol., 2010, 11, 216-222. [2] Ozgur, A.; Tutar, Y. Heat shock protein 90 inhibitors in oncology. Curr.Proteo., 2014, 11, 2-16. [3] Ozgur, A.; Tutar, Y. Heat Shock Protein 90 Inhibition in Cancer Drug Discovery: From Chemistry to Futural Clinical Applications. Anticancer Agents Med. Chem., 2016, 16, 280-90. [4] Tutar, Y. Inhibition of Heat Shock Protein 70 and 90 (Hsp70 And Hsp90) in Target Specific Cancer Treatment. Adv. Tech. Biol. Med., 2015, 3. [5] Koca, I.; Ozgur, A.; Er, M.; Gumus, M.; Coskun, K.A.; Tutar, Y. Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis. Eur. J. Med. Chem., 2016, 122, 280-290. [6] Koca I, Gumus M, Ozgur A, Disli A, Tutar Y. A novel approach to inhibit heat shock response as anticancer strategy by coumarine compounds containing thiazole skeleton. Anticancer Agents Med. Chem., 2015, 15, 916-930.

Introductory Chapter: Molecular Mechanism of Cancer Metastasis

Cancer Metastasis - Molecular Mechanism and Clinical Therapy

CO-releasing properties and anticancer activities of manganese complexes with imidazole/benzimidazole ligands

Journal of Coordination Chemistry, Sep 21, 2016

Carbon monoxide (CO) is an important signaling molecule which plays significant roles in the path... more Carbon monoxide (CO) is an important signaling molecule which plays significant roles in the pathogenesis of cancer. CO is produced by enzymatic degradation of heme in mammals. Heme oxygenase 1 (HO-1) catalyzes the breakdown of heme into CO, ferrous iron and biliverdin. CO induces HO-1 and inhibits cell proliferation. Cancer cells exposed to several stress factors (hypoxia, reactive oxygen species, cis-platin, and oxidative stress), and HO-1 displays cytoprotective role against oxidative stress and inhibits apoptosis, metastases, angiogenesis and cell proliferation processes. Therefore, metal containing CO-releasing molecules (CORMs) have been designed as an effective cancer treatment strategy. CORMs are responsible for releasing controlled amounts of CO to cells and tissues. Thus, we synthesized [Mn(CO) 3 (bpy)L]X manganese containing CORMs [bpy = 2,2'-bipyridine, X = hexafluorophosphate (PF 6), trifluoromethanesulfonate (OTf), L = imidazole, methylimidazole, benzimidazole, N-benzylbenzimidazole, N-(4-chlorobenzyl)benzimidazole] to release CO in human invasive ductal breast (MCF-7) cell line. In vitro experiments indicated that the compounds inhibited cell proliferation and exhibited cytotoxic effect on breast cancer cells. Moreover, side groups of the compounds enhanced the anti-cancer effects in MCF-7 cell line. These manganese containing

Silver(I) Complexes Based on Oxadiazole-Functionalized α-Aminophosphonate: Synthesis, Structural Study, and Biological Activities

Molecules, Nov 22, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more

Noncoding RNAs in Cancer Theranostics: From Molecular Basis to Therapeutic Implications

Current Pharmaceutical Biotechnology

Triad pyrazole–thiazole–coumarin heterocyclic core effectively inhibit HSP and drive cancer cells to apoptosis

Journal of Biomolecular Structure and Dynamics

Drugs and Drug Candidates for the Treatment of Lymphoma

Lymphoma

Cancer is the biggest health problem worldwide due to its high mortality rate. Lymphoma is define... more Cancer is the biggest health problem worldwide due to its high mortality rate. Lymphoma is defined as a group of malignant diseases that is caused by clonal proliferation of lymphocytes and is classified under two major groups: Hodgkin lymphoma and non-Hodgkin lymphoma. Genetic predisposition and some environmental factors constitute risk factors. Symptoms of the disease include unexplained fever, swelling of lymph glands, swollen abdomen, tiredness, loss of appetite, frequent infections, and weight loss. Positron emission tomography (PET) and computed tomography (CT) scans, along with MRI, are widely used for the diagnosis of lymphoma. Advanced blood and lymph node biopsy tests are used to evaluate treatment effect on blood cells and to confirm the diagnosis of lymphoma, respectively. Current treatment options include chemotherapy, radiotherapy, and bone marrow/stem cell transplantation. Development of new treatment options for cancer medications includes small molecules and monocl...

Circular Dichroism

Essential Techniques for Medical and Life Scientists: A Guide to Contemporary Methods and Current Applications- Part II, 2020

Frontiers in Protein and Peptide Sciences

Recent advances in (therapeutic protein) drug development

F1000Research, 2017

Therapeutic protein drugs are an important class of medicines serving patients most in need of no... more Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing) product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016).

Editorial: MicroRNA-related polymorphisms in infectious and inherited diseases

Frontiers in Genetics

Plasma Medicine - Concepts and Clinical Applications

In the past 20 years, cold atmospheric pressure plasmas (CAPs) have become a new promising way fo... more In the past 20 years, cold atmospheric pressure plasmas (CAPs) have become a new promising way for many biomedical applications, such as disinfection, cancer treatment, root canal treatment, wound healing, and other medical applications. Among these applications, investigations of plasma for skin wound healing has gained huge success both in vitro and in vivo experiments, and also the mechanism behind it has been studied by many groups. In this chapter, we summarize the state-of-the-art progress in wound healing by CAPs. The plasma devices developed for wound healing, the interactions between plasmas and microorganisms/cells/tissues, the in vitro and in vivo treatments, the clinical trials, and biosafety issues are all included.

A Medium for Facilitating Hepatitis B Virus Detection and Replication of the Virus

In this study, we tested a chemical mixture causing hepatitis virus to grow in excessive amounts.... more In this study, we tested a chemical mixture causing hepatitis virus to grow in excessive amounts. We obtained this chemical mixture by disintegrating albumin and invertase enzymes separately in supercritical environments, using acidic methanol as solvent. Then we used this mixture as a medium for hepatitis B virus. The chemical mixture caused the hepatitis B virus to multiply almost 80-100 times after 120 minutes. The real surprising result of the study occurred after carrying out bacterial tests with the same chemical mixture, its effect on cancer cells were also investigated. But no effect was observed neither on cancer cells, nor on bacteria. In other word, we developed a speci c medium for the hepatitis virus. In this way, we decided that a method that can reduce the detection limit of PCR device to 1 IU/mL could be developed. This study will be an important milestone in developing vaccines against viruses as well.

Designing Specific HSP70 Substrate Binding Domain Inhibitor for Perturbing Protein Folding Pathways to Inhibit Cancer Mechanism

Anti-Cancer Agents in Medicinal Chemistry, 2021

Background: HSP70 is a survival factor for tumor cells in transformation and in tumor progression... more Background: HSP70 is a survival factor for tumor cells in transformation and in tumor progression as well as in anti-apoptotic response. Objective: Several inhibitors targeting HSP70 ATPase function displayed off-target affect but PES which targets HSP70 substrate binding domain prevents tumor cell survival prominently. However, PES may not bind HSP70 in the absence of nucleotide. This research aimed to design a unique inhibitor molecule that work both in the presence and absence of nucleotides to amplify inhibition. Methods: A set of chimeric coumarine-pyrazole derivatives determined by in silico techniques and synthesized to elucidate their inhibitory effects. Cell viability experiments displayed KBR1307 as the most efficient inhibitor. A set of characterization experiments performed, and results compared to that of PES agent. Binding constant, ATP hydrolysis rate, and percent aggregation determined in the presence and absence of inhibitors. Results: In silico docking experiments ...

Involvement of Metabolites and Non-coding RNAs in Diseases

Current Pharmaceutical Biotechnology

: Non-coding RNAs have a role in gene regulation and cellular metabolism control. Metabolism prod... more : Non-coding RNAs have a role in gene regulation and cellular metabolism control. Metabolism produces metabolites which are small molecules formed during the metabolic process. So far, direct relation between metabolites and genes are not fully established however, pseudogenes and their progenitor genes regulate health and disease states. Other non-coding RNAs also contribute to this regulation at different cellular processes. Accumulation and depletion of metabolites accompany the dynamic equilibrium of health and disease state. In this chapter, metabolites, their roles in the cell, and the link between metabolites and non-coding RNAs are discussed.

Experimental MicroRNA Targeting Validation

Methods in Molecular Biology, 2021

microRNAs (miRNAs) have recently been recognized as a new dimension of posttranscriptional regula... more microRNAs (miRNAs) have recently been recognized as a new dimension of posttranscriptional regulation. It is well defined that most human protein-coding genes are regulated by one or more miRNAs. Therefore, it is crucial to identify genes targeted by the miRNAs to better understand their functions. Although bioinformatics tools have the ability to identify target candidates it is still essential to identify physiological targets by experimental approaches. Currently, the majority of miRNA-target experimental validation approaches assess the changes in target expression in mRNA or protein level upon miRNA upregulation or downregulation. Additionally, finding out direct physical interactions between miRNAs and their targets is also among the experimental techniques. In this chapter we reviewed the existing experimental techniques for miRNA target identification by considering their advantages and potential drawbacks.

Computational Analysis of Drug Resistance Network in Lung Adenocarcinoma

Anti-Cancer Agents in Medicinal Chemistry

Background: Lung cancer is a significant health problem and accounts for one-third of the deaths ... more Background: Lung cancer is a significant health problem and accounts for one-third of the deaths worldwide. A great majority of these deaths are caused by non-small cell lung cancer (NSCLC). Chemotherapy is the leading treatment method for NSCLC, but resistance to chemotherapeutics is an important limiting factor that reduces the treatment success of patients with NSCLC. Objective: In this study, the relationship between differentially expressed genes affecting the survival of the patients, according to the bioinformatics analyses, and the mechanism of drug resistance is investigated for non-small cell lung adenocarcinoma patients. Methods: Five hundred thirteen patient samples were compared with fifty-nine control samples. The employed dataset was downloaded from The Cancer Genome Atlas (TCGA) database. The information on how the drug activity altered against the expressional diversification of the genes was extracted from the NCI-60 database. Four hundred thirty-three drugs with k...

The role of serum levels of selenium, superoxide dismutase, catalase and thiobarbituric acid reactive substances in the association between Hashimoto's thyroiditis and papillary thyroid cancer

Assessment of plasma and tissue fibronectin EIIIB splice variant expressions measured serially with RT-PCR in a wound model of rabbits

Turkish Journal of Trauma and Emergency Surgery, 2020

BACKGROUND: Fibronectin (FN) is an indispensable part of the extracellular matrix. During regener... more BACKGROUND: Fibronectin (FN) is an indispensable part of the extracellular matrix. During regeneration or wound healing, the plasma form of FN is incorporated into the fibrin clots to form a temporary fibrin-FN matrix, and also locally synthesized cellular FN migrates to the clot to regenerate the injured tissue. We aimed to examine wound tissue FN EIIIB and plasma FN EIIIB expression levels in an experimental wound healing model in rabbits. METHODS: Plasma and tissue EIIIB splice variant expressions were measured serially with RT-qPCR in a cutaneous wound model of rabbits. RESULTS: Tissue FN expression increased as beginning on day 3 and continued to increase on days 6 and 9, reaching maximum expression at day 12 before starting to decrease. On the contrary to the tissue levels, plasma FN levels gradually decreased until day 15 when expression returned to the initial values. CONCLUSION: The findings of the current study support that tissue EIIIB expression level increases during wound healing; and plasma EIIIB expression level decreases minimal changed. This is in contrast to reports where plasma FN provisionally helps ECM formation. Therefore, our data show an essential role of EIIIB at the tissue level in accelerating the wound healing process. The RT-qPCR method in our experimental setup can provide more accurate and precise results compared to the antibody-based methods.

Anticancer activities of manganese-based photoactivatable CO-releasing complexes (PhotoCORMs) with benzimidazole derivative ligands

Transition Metal Chemistry, 2017

Carbon monoxide is an important signaling molecule which is produced by heme oxygenase-1. CO show... more Carbon monoxide is an important signaling molecule which is produced by heme oxygenase-1. CO shows antiproliferative activity against cancer cells; hence, activation of HO-1 is a significant inhibition strategy against tumor formation and survival of cancer cells. In this work, manganese-based CO-releasing molecules (CORMs) were designed and synthesized to inhibit breast cancer cell proliferation. Human invasive ductal breast cancer cells (MCF-7) were treated with the synthesized CORMs to investigate the effect of the complexes on breast cancer survival under UV light. In vitro experiments indicated that the complexes inhibited breast cancer cell proliferation, and further, the antiproliferative effects were increased under UV light. Thus, these novel CORMs may provide a drug template for the treatment of invasive ductal breast cancer.

<strong>Heat Shock Proteins in Targeted  Cancer Chemotherapy</strong>

Proceedings of 2nd International Electronic Conference on Medicinal Chemistry, 2016

Heat shock proteins (Hsps) are important biological targets in th next generation of cancer treat... more Heat shock proteins (Hsps) are important biological targets in th next generation of cancer treatments. Hsps play vital roles in protein hemostasis pathways (proper folding and stabilization of nascent proteins, inhibition of protein aggregation, degradation of aggregated proteins, signal transduction and protein translocation) in eukaryotic and prokaryotic cells. Hsps are found in different cellular compartments and their expression level is increased in response to cellular and external stress factors (tumorogenesis, UV light, hypoxia, oxidative, infection, stress, fever, temperature variation) [1]. Therefore, pathogenesis of diseases is related with expression level of Hsps. Hsps are over-expressed in cancer cells, and especially, Hsp27, Hsp70 and Hsp90 are involved in all phases of tumorogenesis (apoptosis, metastases, angiogenesis, invasion, and cell differentiation). Hsp27, Hsp70 and Hsp90 ensure stabilization, activation and proper folding of the oncogenic proteins in cancer cells. Therefore, inhibition of Hsps emerged as a significant therapeutic strategy for targeted cancer treatments. Inhibition of Hsp90 chaperone activity has been significant drug- targeted for the past 30 years in cancer treatment. Now, approximately 20 different compounds are in clinical phase studies [2,3]. Clinical and pre-clinical studies demonstrated that inhibition of Hsp90 activity is not enough by itself. Inhibition of Hsp90 triggers expression of Hsp70 and complements inhibited Hsp90 chaperone activity. Moreover, Hsp27 controls and regulates key points of the apoptotic pathway in cancer cells. Therefore, in addition to Hsp90 inhibition, blocking of Hsp70 and Hsp27 chaperone activities is a remarkable therapeutic strategy for cancer treatment [4]. In our lab, we designed and synthesized novel pyrimidine and coumarin derivatives as Hsp90 inhibitors. Pyrimidine analogs interrupted Hsp90 ATP hydrolysis process through disrupting N terminal domain (NTD) conformational change [5]. Coumarin derivatives inhibited C terminal domain (CTD) of Hsp90, and blocked dimerization process [6]. ACKNOWLEDGEMENTS The authors gratefully acknowledge the financial support received from the Scientific and Technological Research Council of Turkey, TUBITAK (Grant # 114Z365). REFERENCES [1] Tutar, L.; Tutar, Y. Heat shock proteins; an overview. Curr. Pharm.Biotechnol., 2010, 11, 216-222. [2] Ozgur, A.; Tutar, Y. Heat shock protein 90 inhibitors in oncology. Curr.Proteo., 2014, 11, 2-16. [3] Ozgur, A.; Tutar, Y. Heat Shock Protein 90 Inhibition in Cancer Drug Discovery: From Chemistry to Futural Clinical Applications. Anticancer Agents Med. Chem., 2016, 16, 280-90. [4] Tutar, Y. Inhibition of Heat Shock Protein 70 and 90 (Hsp70 And Hsp90) in Target Specific Cancer Treatment. Adv. Tech. Biol. Med., 2015, 3. [5] Koca, I.; Ozgur, A.; Er, M.; Gumus, M.; Coskun, K.A.; Tutar, Y. Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis. Eur. J. Med. Chem., 2016, 122, 280-290. [6] Koca I, Gumus M, Ozgur A, Disli A, Tutar Y. A novel approach to inhibit heat shock response as anticancer strategy by coumarine compounds containing thiazole skeleton. Anticancer Agents Med. Chem., 2015, 15, 916-930.