WOS
Permanent URI for this collectionhttps://hdl.handle.net/11443/932
Browse
16 results
Search Results
Item Multi-center real-world comparison of the fully automated Idylla (TM) microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer(SPRINGER, 2021-01-01) Velasco, Ana; Tokat, Fatma; Bonde, Jesper; Trim, Nicola; Bauer, Elisabeth; Meeney, Adam; de Leng, Wendy; Chong, George; Dalstein, Veronique; Kis, Lorand L.; Lorentzen, Jon A.; Tomic, Snjezana; Thwaites, Keeley; Putzova, Martina; Birnbaum, Astrid; Qazi, Romena; Primmer, Vanessa; Dockhorn-Dworniczak, Barbara; Hernandez-Losa, Javier; Soares, Fernando A.; Gertler, Asaf A.; Kalman, Michal; Wong, Chris; Carraro, Dirce M.; Sousa, Ana C.; Reis, Rui M.; Fox, Stephen B.; Fassan, Matteo; Brevet, Marie; Merkelbach-Bruse, Sabine; Colling, Richard; Soilleux, Elizabeth; Teo, Ryan Yee Wei; D'Haene, Nicky; Nolet, Serge; Ristimaki, Ari; Vaisanen, Timo; Chapusot, Caroline; Soruri, Afsaneh; Unger, Tina; Wecgowiec, Johanna; Biscuola, Michele; Frattini, Milo; Long, Anna; Campregher V, Paulo; Matias-Guiu, XavierMicrosatellite instability (MSI) is present in 15-20\% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla (TM) MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla (TM) testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla (TM) results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla (TM) MSI Assay were equally distributed over the seven biomarkers, and 84.48\% of the MSI-high samples had >= 5 mutated biomarkers, while 98.25\% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla (TM) MSI Assay and immunohistochemistry was 96.39\% (988/1025)Item Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice(NATURE PORTFOLIO, 2021-01-01) Turan, Raife Dilek; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Karakus, Gozde Sir; Ozer, Samed; Abanuz, Selen; Cakirsoy, Didem; Tumentemur, Gamze; Demir, Sevda; Seyis, Utku; Kuzay, Recai; Elek, Muhammer; Kocaoglu, Miyase Ezgi; Ertop, Gurcan; Arbak, Serap; Elmas, Merve Acikel; Hemsinlioglu, Cansu; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Kayhan, Cavit Kerem; Tokat, Fatma; Akpinar, Gurler; Kasap, Murat; Kocagoz, Ayse Sesin; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ince, Umit; Ovali, ErcumentThe SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10(13) or 10(14) viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.Item Preclinical Assessment of Efficacy and Safety Analysis of CAR-T Cells (ISIKOK-19) Targeting CD19-Expressing B-Cells for the First Turkish Academic Clinical Trial with Relapsed/Refractory ALL and NHL Patients(GALENOS YAYINCILIK, 2020-01-01) Tastan, Cihan; Kancagi, Derya Dilek; Turan, Raife Dilek; Yurtsever, Bulut; Cakirsoy, Didem; Abanuz, Selen; Yilanci, Muhammet; Seyis, Utku; Ozer, Samed; Mert, Selin; Kayhan, Cavit Kerem; Tokat, Fatma; Elmas, Merve Acikel; Birdogan, Selcuk; Arbak, Serap; Yalcin, Koray; Sezgin, Aslihan; Kizilkilic, Ebru; Hemsinlioglu, Cansu; Ince, Umit; Ratip, Siret; Ovali, ErcumentObjective: Relapsed and refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) are the focus of studies on hematological cancers. Treatment of these malignancies has undergone recent transformation with the development of new gene therapy and molecular biology techniques, which are safer and well-tolerated therapeutic approaches. The CD19 antigen is the most studied therapeutic target in these hematological cancers. This study reports the results of clinical-grade production, quality control, and in vivo efficacy processes of ISIKOK-19 cells as the first academic clinical trial of CAR-T cells targeting CD19-expressing B cells in relapsed/refractory ALL and NHL patients in Turkey. Materials and Methods: We used a lentiviral vector encoding the CD19 antigen-specific antibody head (FMC63) conjugated with the CD8-CD28-CD3 zetaItem IRF4-Rearranged Large B-Cell Lymphoma on Waldeyer's Ring: A Case Report(GALENOS YAYINCILIK, 2020-01-01) Buyuktas, Deram; Ornek, Serdar; Tokat, Fatma; Tecimer, Tulay; Ferhanoglu, BurhanItem Immune Thrombocytopenia in a Child with Neuroblastoma(HINDAWI LTD, 2017-01-01) Ikizoglu, Hasan Tarkan; Ayan, Inci; Tokat, Fatma; Tecimer, Tulay; Tekant, Gonca TopuzluThrombocytopenia is a frequent finding in patients with solid tumors. It is usually caused by bone marrow infiltration or by myelosuppression due to anticancer therapyItem Primary pericardial extragastrointestinal stromal tumor: A case report and literature review(SPANDIDOS PUBL LTD, 2015-01-01) Arpaci, Taner; Tokat, Fatma; Arpaci, Rabia Bozdogan; Akbas, Tugana; Ugurluer, Gamze; Yavuz, SinanGastrointestinal stromal tumors (GISTs) are the most prevalent mesenchymal tumors of the gastrointestinal tract. GISTs are considered to originate from the interstitial cells of Cajal, the pacemakers of the peristaltic activity of the gastrointestinal tract. More than 95\% of GISTs express KIT protein and discovered on GIST-1. GISTs may also be encountered in locations outside the gastrointestinal tract, in which case they are referred to as extra-GISTs (EGISTs) and often behave more aggressively. This is the case report of a primary pericardial EGIST in a 53-year-old male patient, confirmed by immunohistochemistry. To the best of our knowledge, this is the third case of EGIST diagnosed above the diaphragm, without being associated with the esophageal wall. Two cases of primary EGIST arising from the pleura were reported previously. In addition, this is the first reported case of an EGIST originating from the pericardium.Item EML4-ALK-positive lung adenocarcinoma presenting an unusual metastatic pattern in a 29-year-old woman who is alive and well in her third year follow up: A case report(ELSEVIER SCIENCE BV, 2017-01-01) Tokat, Fatma; Zeren, Handan; Barut, Pinar; Tansan, Sualp; Ince, UmitNon-small cell lung cancer (NSCLC) is a frequent tumor entity with high mortality. Although several newly discovered chromosomal translocations and mutations opened new horizons for targeted therapy, literature still lacks large series of NSCLC with chromosomal abberations and their correlations with histological and clinical features. We present a case of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive adenocarcinoma of the lung with an unusual metastatic pattern in a 29-year-old young woman. Conclusion: Young adult non-smoker female patients with an unexplained pleural effusion and signs of metastatic disease should alert the physicians straight away for all types of malignancies including lung cancer. Any skin lesions should be evaluated carefully, biopsies should be done to exclude metastasis in urgency. On the other hand, an uncommon clinical presentation of a lung cancer requires corresponding molecular testing rapidly in order to offer the best treatment option. (C) 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.Item MITNET: a novel dataset and a two-stage deep learning approach for mitosis recognition in whole slide images of breast cancer tissue(SPRINGER LONDON LTD, 2022-01-01) Cayir, Sercan; Solmaz, Gizem; Kusetogullari, Huseyin; Tokat, Fatma; Bozaba, Engin; Karakaya, Sencer; Iheme, Leonardo Obinna; Tekin, Eren; Yazici, Cisem; Ozsoy, Gulsah; Ayalti, Samet; Kayhan, Cavit Kerem; Ince, Umit; Uzel, Burak; Kilic, OnurMitosis assessment of breast cancer has a strong prognostic importance and is visually evaluated by pathologists. The inter, and intra-observer variability of this assessment is high. In this paper, a two-stage deep learning approach, named MITNET, has been applied to automatically detect nucleus and classify mitoses in whole slide images (WSI) of breast cancer. Moreover, this paper introduces two new datasets. The first dataset is used to detect the nucleus in the WSIs, which contains 139,124 annotated nuclei in 1749 patches extracted from 115 WSIs of breast cancer tissue, and the second dataset consists of 4908 mitotic cells and 4908 non-mitotic cells image samples extracted from 214 WSIs which is used for mitosis classification. The created datasets are used to train the MITNET network, which consists of two deep learning architectures, called MITNET-det and MITNET-rec, respectively, to isolate nuclei cells and identify the mitoses in WSIs. In MITNET-det architecture, to extract features from nucleus images and fuse them, CSPDarknet and Path Aggregation Network (PANet) are used, respectively, and then, a detection strategy using You Look Only Once (scaled-YOLOv4) is employed to detect nucleus at three different scales. In the classification part, the detected isolated nucleus images are passed through proposed MITNET-rec deep learning architecture, to identify the mitosis in the WSIs. Various deep learning classifiers and the proposed classifier are trained with a publicly available mitosis datasets (MIDOG and ATYPIA) and then, validated over our created dataset. The results verify that deep learning-based classifiers trained on MIDOG and ATYPIA have difficulties to recognize mitosis on our dataset which shows that the created mitosis dataset has unique features and characteristics. Besides this, the proposed classifier outperforms the state-of-the-art classifiers significantly and achieves a 68.7\% F1-score and 49.0\% F1-score on the MIDOG and the created mitosis datasets, respectively. Moreover, the experimental results reveal that the overall proposed MITNET framework detects the nucleus in WSIs with high detection rates and recognizes the mitotic cells in WSI with high F1-score which leads to the improvement of the accuracy of pathologists' decision.Item A Review on Cutaneous and Musculoskeletal Manifestations of CLOVES Syndrome(DOVE MEDICAL PRESS LTD, 2022-01-01) Durmaz, Emel Ozturk; Demircioglu, Deniz; Dikmen, Pinar Yalinay; Alanay, Yasemin; Alanay, Ahmet; Demirkesen, Cuyan; Tokat, Fatma; Karaarslan, ErcanCLOVES syndrome is a novel sporadic mosaic segmental overgrowth syndrome, currently categorized under the canopy of PROS (PIK3CA-related overgrowth spectrum) disorders. All PROS disorders harbor heterozygous postzygotic activating somatic mutations involving the PIK3CA gene. As an upstream regulator of the PI3K/AKT/mTOR signal transduction pathway, activating mutations of PIK3CA gene commence in uncontrolled growth of cutaneous, vascular (capillaries, veins, and lymphatics), adipose, neural, and musculoskeletal tissues. The excessive growth is segmental, patchy, asymmetric, and confined to body parts affected by the mutation. The term `CLOVES' is an acronym denoting congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis) and/ or skeletal anomalies. The syndrome is characterized by an admixture of overgrown tissues, derived mainly from mesoderm and neuroectoderm. Among PROS disorders, CLOVES syndrome represents the extreme end of the spectrum with massive affection of almost the entire body. The syndrome might judiciously be treated with medications hampering with the PI3K/AKT/mTOR signal transduction pathway. This article aims at reviewing the cutaneous and musculoskeletal manifestations of CLOVES syndrome, as the paradigm for PROS disorders. CLOVES syndrome and other PROS disorders are still misdiagnosed, underdiagnosed, underreported, and undertreated by the dermatology community.Item Has the COVID-19 Pandemic Affected Breast Cancer Stage and Surgical Volume?(FRONTIERS MEDIA SA, 2022-01-01) Kara, Halil; Arikan, Akif Enes; Dulgeroglu, Onur; Tutar, Burcin; Tokat, Fatma; Uras, CihanBackgroundThis study investigates the effects of COVID-19 on the breast cancer stage and the volume of breast cancer surgery in a specialized breast institute. MethodsData of 332 patients who were diagnosed and treated for breast cancer between December 2019 and November 2020 were evaluated retrospectively according to periods of pandemic. ResultsA significant decrease in the number of operations, especially upfront surgeries rather than surgeries after neoadjuvant chemotherapy, was detected in the early period of the COVID-19 pandemic. It was found that patients with complaints were mostly admitted during this period (p = 0.024). No statistical significance was found for age, sex, side of the tumor, type of tumor, surgery to breast, and axilla. Following the early period of the pandemic, it was observed that patients with mostly luminal, early-stage, and less axillary nodal involvement (p < 0.05) were admitted, and as a result, it was founded that upfront surgeries increased, although no change in TNM staging was observed. However, it did affect the decision of initial treatment. Thus, the number of upfront surgeries was significantly higher than the NCT group (p = 0.027) following the early period. ConclusionSurgical volume is significantly affected in the early period of the COVID-19 pandemic. To overcome overload due to delayed surgeries related to pandemics, some hospitals should be spared for oncological treatments. Following the early period, mostly luminal type, early-stage patients were admitted, probably because of increased self-awareness and short wave duration, but the breast cancer stage was not affected.