Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Functional Outcome in Late Adolescence/Early Adulthood of Patients with Autism Spectrum Disorderresand Its Relationships with Parental Burnout and Depression: A Preliminary Multi-Center, Cross-Sectional Study(2023) Kutuk, Meryem Ozlem; Soylemez, Tugba Eseroglu; Taner, Hande Ayraler; Altintas, Ebru; Kutuk, Ozgur; 37867841The aim of this study is to determine the functioning of adults with autism spectrum disorders (ASDs) diagnosed in childhood and depression and burnout levels among their parents. A total of 261 adults with ASDs and their parents were recruited for the study. Both parents completed the Beck Depression and Maslach Burnout Inventories and reported the functioning of their adult offspring with ASDs. Only 5.4 % of our sample reported "good" or "very good" outcomes. The most common psychiatric comorbidities were intellectual disabilities and attention-deficit/ hyperactivity disorder. Maternal burnout and depression scores were significantly elevated compared to those of fathers. There is an undeniable urgent need for more research to identify the needs of adults and families suffering from ASD. Modifications for those with ASD may have to be made for support in workplaces, achieving driving licenses, using public transportation and attendance at tertiary education.Item An Exploratory, Single-Center Study of Factors Associated with Child Marriage Among Syrian Female Adolescents Residing in Turkey(2022) Kutuk, Meryem Ozlem; Kilicaslan, Fethiye; Tufan, Ali Evren; Celik, Fatma; Gokcen, Cem; Bag, Harika Gozukara; Servi, Gulay; Karali, Mehtap; Bahsi, Gamze; Servi, Ceyhun; Alatli, Resat; Kandemir, Betul; Aytekin, Neslihan; Kutuk, Ozgur; https://orcid.org/0000-0001-9854-7220; AAH-1671-2019This exploratory study aimed to evaluate factors related with child marriage compared to unmarried status in female adolescent residents in a refugee camp in Turkey. The rate of child marriage and developmental status of offspring from those marriages were reported. A research team evaluated married female youth and their offspring for psychopathologies according to DSM-5 criteria and ascertained lifetime traumatic events among mothers. We compared the traumatic experiences and psychopathologies of married females and controls. Post-traumatic stress disorder (PTSD) was the most common diagnosis in both groups and child brides reported greater cumulative traumatic experiences and elevated rates of PTSD. More than one-tenth (i.e., 15.1%) of offspring of child brides displayed developmental delays and 12.1% were diagnosed with global developmental delay.Item Distinct Apoptotic Blocks Mediate Resistance to Panher Inhibitors in HER2+Breast Cancer Cells(2018) Karakas, Bahriye; Ozmay, Yeliz; Basaga, Huveyda; Gul, Ozgur; Kutuk, Ozgur; https://orcid.org/0000-0001-9854-7220; 29733883; AAH-1671-2019Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells. Cells were also cross-resistant to dacomitinib. BH3 profiles of HER2 + breast cancer cells efficiently predicted antiapoptotic protein dependence and development of resistance to panHER inhibitors. Reactivation of ERK1/2 was primarily responsible for acquired resistance in SKBR3 and ZR-75-30 cells. Adding specific ERK1/2 inhibitor SCH772984 to neratinib or dacomitinib led to increased apoptotic response in neratinib-resistant SKBR3 and ZR75-30 cells, but we did not detect a similar response in neratinib-resistant BT474 cells. Accordingly, suppression of BCL-2/BCL-XL by ABT-737 was required in addition to ERK1/2 inhibition for neratinib- or dacomitinib-induced apoptosis in neratinib-resistant BT474 cells. Our results showed that different mitochondrial apoptotic blocks mediated acquired panHER inhibitor resistance in HER2 + breast cancer cell lines as well as highlighted the potential of BH3 profiling assay in prediction of panHER inhibitor resistance in breast cancer cells.Item Sociodemographic and Clinical Features of Obsessive Compulsive Disorder in a Large Sample of Children and Adolescents from Turkey(2018) Kutuk, Meryem Ozlem; Tufan, Ali Evren; Erden, Sema; Aksu, Gulen Guler; Kilicaslan, Fethiye; Sogut, Figen; Kutuk, Ozgur; Toros, Fevziye; https://orcid.org/0000-0001-9854-7220; AAH-1671-2019Objective: Obsessive compulsive disorder (OCD) is a time-consuming and chronic disorder characterized by obsessions and compulsions that can start before age of eighteen and can be associated with significant impairments in academic, social and family functioning. In this study, our aim was to evaluate sociodemographic characteristics, clinical pictures and comorbid diagnoses of a large sample of children and adolescents who were diagnosed with OCD according to diagnostic criteria of DSM-IV-TR in a child and adolescent psychiatry outpatient clinic of a University Hospital. Methods: Patients who were first diagnosed at the study center with OCD according to DSM-IV-TR criteria were included. For inclusion, the primary diagnosis should be OCD as per DSM-IV-TR criteria and there must be concordance between at least 2 clinicians (one resident and the head of department) for diagnosis. Results: 440 cases were included in our study and the most common obsessions in our sample were contamination with dirt (48.8%), and exactness (23.8%) and most common compulsions were ordering/checking (42.4%) and washing/cleaning (32.0%). Most of the patients in our sample (78.0%) had a comorbid diagnosis and most common comorbidities were Attention-Deficit/ Hyperactivity Disorder (26.6%) and Generalized Anxiety Disorder (20.5%). Discussion: Accordingly, our results in terms of comorbidity, obsessions and compulsions are consistent with the literature. In conclusion, this is the largest study on a clinical sample of pediatric OCD from Turkey that we are aware of in terms of sample size, time frame and statistical power.Item A Novel Homozygous Nonsense Mutation in The Calpastatin (CAST) Gene Associated with Peeling Skin Phenotype in A Child(2018) Saricaoglu, Hayriye; Temel, Sehime; Zorlu, Ozge; Turkgenc, Burcu; Kutuk, Ozgur; Karakas, Bahriye; Kiran, Ummuhan; Erguner, Bekir; Yakicier, Cengiz; https://orcid.org/0000-0001-9854-7220; AAH-1671-2019Item Migraine and Associated Comorbidities are Three Times More Frequent in Children With ADHD and Their Mothers(2018) Kutuk, Meryem Ozlem; Tufan, Ali Evren; Guler, Gulen; Yalin, Osman Ozgur; Altintas, Ebru; Bag, Harika Gozukara; Uluduz, Derya; Toros, Fevziye; Aytan, Nurgul; Kutuk, Ozgur; Ozge, Aynur; https://orcid.org/0000-0002-2918-7871; https://orcid.org/0000-0001-5207-6240; https://orcid.org/0000-0003-2735-4805; https://orcid.org/0000-0001-9854-7220; 29921473; AAI-9626-2021; C-5074-2015; G-8832-2015; AAH-1671-2019Objective: Attention deficit and hyperactivity disorder (ADHD) is a neuro-developmental disorder related to internalizing and externalizing disorders as well as somatic complaints and disorders. This study was conducted to evaluate the prevalence of headache subtypes, epilepsy, atopic disorders, motion sickness and recurrent abdominal pain among children and adolescents with ADHD and their parents. Methods: In a multi-center, cross-sectional, familial association study using case-control design, treatment na ve children and adolescents between 6 and 18 years of age diagnosed with ADHD according to the DSM-5 criteria as well as age- and gender matched healthy controls and their parents were evaluated by a neurologist and analyzed accordingly. Results: 117 children and adolescents with ADHD and 111 controls were included. Headache disorder diagnosis was common for both patients and healthy controls (59.0% vs. 37.8%), with a significantly elevated rate in the ADHD group (p = 0.002). Migraine was found in 26.0% of ADHD patients and 9.9% of healthy controls. Tension headache was found in 32.4% of ADHD patients and 27.9% of healthy controls. Headache diagnosis was also found to be significantly more common in mothers of children with ADHD than control group mothers (90.5% vs. 36.6%, p < 0.001). Conclusion: Headache diagnoses and specifically migraines were significantly more common among children with ADHD and their mothers, while recurrent abdominal pain was elevated in both parents and ADHD patients. Migraine is an important part of ADHD comorbidity, not only for children but also for mothers. Motion sickness may be reduced among families of ADHD probands. (C) 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.Item Cytotoxic and Apoptotic Effects of Novel Pyrrolo[2,3-d]Pyrimidine Derivatives Containing Urea Moieties on Cancer Cell Lines(2018) Kilic-Kurt, Zuhal; Bakar-Ates, Filiz; Karakas, Bahriye; Kutuk, Ozgur; 0000-0003-2809-8946; 0000-0001-9616-4656; 0000-0001-9854-7220; 29866023; AAS-5399-2020; AAG-3843-2020; AFW-5486-2022; AAH-1671-2019Background: Pyrrolo[2,3-d]pyrimidines have been recently reported to have anticancer activities through inhibition of different targets such as, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, Janus Kinase (JAK), mitotic checkpoint protein kinase (Mps1), carbonic anhydrase, MDM-2. On the other hand, aryl urea moieties which are found in some tyrosine kinase inhibitors such as Sorafenib and Linifanib have aroused recent attention as responsible for anticancer activities. The aims of this paper are to synthesize pyrrolo[2,3-d]pyrimidine derivatives containing urea moiety and evaluate their anti-cancer activity against human lung cancer cell line (A549), prostate cancer cell line (PC3), human colon cancer cell line (SW480) and human breast cancer cell line (MCF-7). Methods: A series of new pyrrolo[2,3-d]pyrimidines containing urea moieties have been synthesized as Scheme 1. In vitro cytotoxicity of target compounds were evaluated against, SW480, PC3, A549 and MCF-7 human cancer cell lines using a MTT assay. In order to evaluate the mechanism of cytotoxic activity of compounds 9e, 10a and 10b, having the best cytotoxic activity, Annexin V binding assay, cell cycle analysis and western blot analysis were performed. Results: Among the target compounds, 10a (IC50 = 0.19 mu M) was found to be the most potent derivative against PC3 cells. Compound 10b and 9e showed the strong cytotoxic activity against MCF-7 and A549 cells with IC50 value of 1.66 mu M and 4.55 mu M, respectively. Flow cytometry data suggest that the cytotoxic activity of the compounds on cancer cells might be mediated by apoptosis revealing a significant increase in the percentage of late apoptotic cells and causing a cell cycle arrest at different stages. Western blot analysis of apoptosis marker demonstrated that these compounds induce apoptosis through the intrinsic pathway. Conclusion: Compound 9e displayed the strongest cytotoxicity against A549 cancer cell line, and induced late apoptosis in A549, as confirmed by cell cycle arrest in G0/G1 phase. In addition, compound 9e reduced expression of the anti-apoptotic protein Bcl-2 and enhanced expression of the pro-apoptotic protein Bax, besides increased caspase-9 and caspase-3, as well as cleavage of PARP levels. These results suggest that compound 9e showed a cytotoxic effect in A549 cells through activation of the mitochondrial apoptotic pathway. Further studies will be undertaken in our laboratory to improve cytotoxic activity of compound 9e and to identify the biological targets of 9e which are responsible for anticancer activity.Item Editorial: Cell Death and Targeted Cancer Therapies(2022) Bagci-Onder, Tugba; Kutuk, Ozgur; Chonghaile, Triona Ni; Knippschild, Uwe; 000829492900001Item Hedgehog Signal Defect Leading to Familial Exudative Vitreoretinopathy-Like Disease and Gastrointestinal Malformation(2022) Keskek, Nedime Sahinoglu; Akkoyun, Imren; Temiz, Abdulkerim; Kutuk, Ozgur; https://orcid.org/0000-0001-8544-103X; https://orcid.org/0000-0002-2860-7424; https://orcid.org/0000-0001-9854-7220; 35770050; T-4258-2017; AAK-7713-2021Objectives: The aim of the study was to present a new generic association presenting with gastrointestinal tract malformations (GTMs) and familial exudative vitreoretinopathy (FEVR)-like disease and review the genetics of Hedgehog signaling. Materials and Methods: Three neonates were diagnosed with FEVR-like retinal vascular disease upon routine ophthalmological examination during hospitalization in the neonatal surgical intensive care unit for GTMs. Generic analysis of the neonates was performed. Results: Gestational age of the neonates was 39, 38, and 39 weeks and birth weights were 3,500, 3,600, and 3,300 grams, respectively. All six eyes of the three infants were treated by laser photocoagulation. Recurrence was not seen in any of the eyes. Genetical analysis of all the neonates diagnosed with FEVR-like disease revealed defects in the Hedgehog pathway. Conclusion: FEVR is a genetically well-defined retinal vascular disease. The current study is the first to show an association between FEVR-like retinal vascular disease and GTMs. This study demonstrates the importance of the Hedgehog pathway in retinal vascular and gut development.Item High Depression Symptoms and Burnout Levels Among Parents of Children with Autism Spectrum Disorders: A Multi-Center, Cross-Sectional, Case-Control Study (Jan, 10.1007/s10803-021-04874-4, 2021)(2021) Kutuk, Meryem Ozlem; Tufan, Ali Evren; Kilicaslan, Fethiye; Guler, Gulen; Celik, Fatma; Altintas, Ebru; Gokcen, Cem; Karadag, Mehmet; Yektas, Cigdem; Mutluer, Tuba; Kandemir, Hasan; Buber, Ahmet; Topal, Zehra; Acikbas, Ufuk; Giray, Asli; Kutuk, Ozgur; 0000-0002-2918-7871; 0000-0001-9854-7220; 33591437; AAI-9626-2021
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