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https://www.readbyqxmd.com/read/28678784/personalized-rna-mutanome-vaccines-mobilize-poly-specific-therapeutic-immunity-against-cancer
#1
Ugur Sahin, Evelyna Derhovanessian, Matthias Miller, Björn-Philipp Kloke, Petra Simon, Martin Löwer, Valesca Bukur, Arbel D Tadmor, Ulrich Luxemburger, Barbara Schrörs, Tana Omokoko, Mathias Vormehr, Christian Albrecht, Anna Paruzynski, Andreas N Kuhn, Janina Buck, Sandra Heesch, Katharina H Schreeb, Felicitas Müller, Inga Ortseifer, Isabel Vogler, Eva Godehardt, Sebastian Attig, Richard Rae, Andrea Breitkreuz, Claudia Tolliver, Martin Suchan, Goran Martic, Alexander Hohberger, Patrick Sorn, Jan Diekmann, Janko Ciesla, Olga Waksmann, Alexandra-Kemmer Brück, Meike Witt, Martina Zillgen, Andree Rothermel, Barbara Kasemann, David Langer, Stefanie Bolte, Mustafa Diken, Sebastian Kreiter, Romina Nemecek, Christoffer Gebhardt, Stephan Grabbe, Christoph Höller, Jochen Utikal, Christoph Huber, Carmen Loquai, Özlem Türeci
T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient...
July 13, 2017: Nature
https://www.readbyqxmd.com/read/28657226/factors-associated-with-survival-after-relapse-in-patients-with-low-risk-endometrial-cancer-treated-with-surgery-alone
#2
Nazli Topfedaisi Ozkan, Mehmet Mutlu Meydanlı, Mustafa Erkan Sarı, Fuat Demirkiran, Ilker Kahramanoglu, Tugan Bese, Macit Arvas, Hanifi Şahin, Ali Haberal, Husnu Celik, Gonca Coban, Tufan Oge, Omer Tarik Yalcin, Özgür Akbayır, Baki Erdem, Ceyhun Numanoğlu, Nejat Özgül, Gökhan Boyraz, Mehmet Coşkun Salman, Kunter Yüce, Murat Dede, Mufit Cemal Yenen, Salih Taşkın, Duygu Altın, Uğur Fırat Ortaç, Hülya Aydın Ayık, Tayup Şimşek, Tayfun Güngör, Kemal Güngördük, Muzaffer Sancı, Ali Ayhan
OBJECTIVE: To determine factors influencing overall survival following recurrence (OSFR) in women with low-risk endometrial cancer (EC) treated with surgery alone. METHODS: A multicenter, retrospective department database review was performed to identify patients with recurrent "low-risk EC" (patients having less than 50% myometrial invasion [MMI] with grade 1 or 2 endometrioid EC) at 10 gynecologic oncology centers in Turkey. Demographic, clinicopathological, and survival data were collected...
June 16, 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28604701/elimination-of-large-tumors-in-mice-by-mrna-encoded-bispecific-antibodies
#3
Christiane R Stadler, Hayat Bähr-Mahmud, Leyla Celik, Bernhard Hebich, Alexandra S Roth, René P Roth, Katalin Karikó, Özlem Türeci, Ugur Sahin
The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies...
July 2017: Nature Medicine
https://www.readbyqxmd.com/read/28541637/prognostic-factors-and-treatment-outcomes-in-surgically-staged-non-invasive-uterine-clear-cell-carcinoma-a-turkish-gynecologic-oncology-group-study
#4
Mustafa Erkan Sarı, Mehmet Mutlu Meydanlı, Osman Türkmen, Günsü Kimyon Cömert, Ahmet Taner Turan, Alper Karalök, Hanifi Şahin, Ali Haberal, Eda Kocaman, Özgür Akbayır, Baki Erdem, Ceyhun Numanoğlu, Kemal Güngördük, Muzaffer Sancı, Mehmet Gökçü, Nejat Özgül, Mehmet Coşkun Salman, Gökhan Boyraz, Kunter Yüce, Tayfun Güngör, Salih Taşkın, Duygun Altın, Uğur Fırat Ortaç, Hülya Aydın Ayık, Tayup Şimşek, Macit Arvas, Ali Ayhan
OBJECTIVE: To assess the prognosis of surgically-staged non-invasive uterine clear cell carcinoma (UCCC), and to determine the role of adjuvant therapy. METHODS: A multicenter, retrospective department database review was performed to identify patients with UCCC who underwent surgical treatment between 1997 and 2016 at 8 Gynecologic Oncology Centers. Demographic, clinicopathological, and survival data were collected. RESULTS: A total of 232 women with UCCC were identified...
July 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28534349/an-overview-of-high-dose-chemotherapy-with-autologous-stem-cell-rescue-for-germ-cell-tumors-in-current-practice
#5
Sukru Ozaydın, Ugur Sahin, Nuri Karadurmus, Fikret Arpaci, Taner Demirer
Testicular cancer is a frequent tumor of adolescent and young adult males. Chemotherapy has been reported to provide cure rates as high as 80% even in the presence of advanced testicular cancer. Studies regarding testicular cancer started after the advent of high dose chemotherapy (HDC) plus atologous stem cell rescue (ASCR) for the treatment of solid tumors in 1980s. Testicular cancer is highly responsive to HDC. Einhorn et al. have reported long-lasting remissions reaching up to 40% among patients with platinum-refractory disease...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28490348/an-international-reproducibility-study-validating-quantitative-determination-of-erbb2-esr1-pgr-and-mki67-mrna-in-breast-cancer-using-mammatyper%C3%A2
#6
Zsuzsanna Varga, Annette Lebeau, Hong Bu, Arndt Hartmann, Frederique Penault-Llorca, Elena Guerini-Rocco, Peter Schraml, Fraser Symmans, Robert Stoehr, Xiaodong Teng, Andreas Turzynski, Reinhard von Wasielewski, Claudia Gürtler, Mark Laible, Kornelia Schlombs, Heikki Joensuu, Thomas Keller, Peter Sinn, Ugur Sahin, John Bartlett, Giuseppe Viale
BACKGROUND: Accurate determination of the predictive markers human epidermal growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for therapeutic decision making in early breast cancer. In this multicenter prospective study, we addressed the issue of inter- and intrasite reproducibility using the recently developed reverse transcription-quantitative real-time polymerase chain reaction-based MammaTyper® test...
May 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28432802/subsequent-malignancies-after-allogeneic-hematopoietic-stem-cell-transplantation
#7
Mehmet Gündüz, Mehmet Özen, Uğur Şahin, Selami Koçak Toprak, Sinem Civriz Bozdağ, Meltem Kurt Yüksel, Önder Arslan, Muhit Özcan, Taner Demirer, Meral Beksaç, Osman İlhan, Günhan Gürman, Pervin Topçuoğlu
We evaluated 979 patients for the development of post-transplant lymphoproliferative disease (PTLD) and solid malignancies after allogeneic hematopoietic stem cell transplantations (allo-HSCT) as a late complication. We found 15 (1.5%) subsequent malignancies; three of these malignancies were PTLD, and twelve were solid tumors. The median time from allo-HSCT to the development of PTLD was 9 (3-20) months and that from allo-HSCT to the development of solid tumors was 93 (6-316) months. The cumulative incidence of evolving subsequent malignancy in patients was 1...
April 22, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28416942/the-end-of-a-long-debate-methylenetetrahydrofolate-reductase-gene-polymorphisms-do-not-increase-thrombosis-risk
#8
Ugur Sahin, Muhit Ozcan
No abstract text is available yet for this article.
February 2017: Eurasian Journal of Medicine
https://www.readbyqxmd.com/read/28407950/dllme-spectrophotometric-determination-of-glyphosate-residue-in-legumes
#9
Emine Çetin, Serkan Şahan, Ahmet Ülgen, Uğur Şahin
A new separation and pre-concentration method for spectrophotometric determination of glyphosate herbicide was developed. Glyphosate was converted into dithiocarbamic acid with CS2, followed by copper in the presence of ammonia to promote complex formation. This complex was collected in a CH2Cl2 organic drop and absorbance measured at 435nm. The analytical parameters, such as the amount of NH3, Cu(II) and CS2, type of extraction solutions, and the ratio of dispersive and organic liquids were optimized. The calibration curve was linear in the range 0...
September 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28373809/a-child-with-kabuki-syndrome-and-autism-spectrum-disorder
#10
Mehmet Sertçelik, Çağatay Uğur, Aynur Şahin Aközel, Cihat Kağan Gürkan
Kabuki syndrome (KS) is characterized by skeletal abnormalities, short stature, characteristic facial features, postnatal growth delay, and mental retardation. There are only a few case reports that present the coexistence of KS with autism spectrum disorder (ASD) in the literature. Herein we present the case of a boy with KS and ASD and discuss the possible shared etiologies. A 4-year-old boy was brought by his parents with complaints of no speech, hyperactivity, enuresis complex, temper tantrum, self-injury, and harming people or objects...
September 2016: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/28247842/leukemia-inhibitory-factor-promotes-aggressiveness-of-chordoma
#11
Sukru Gulluoglu, Mesut Sahin, Emre Can Tuysuz, Cumhur Kaan Yaltirik, Aysegul Kuskucu, Ferda Ozkan, Fikrettin Sahin, Ugur Ture, Omer Faruk Bayrak
Chordomas are rare tumors of the spine and skull base that are locally destructive and resistant to chemo- and radiation therapy, with a poor prognosis and limited therapeutic options. Chordoma patients have a long life expectancy with high mortality from the disease. Cancer stem cells, which are known to exist in chordomas, have extensive proliferative and self-renewal potential, and are responsible for maintaining tumor heterogeneity along with chemotherapy and radiotherapy resistance. The leukemia inhibitory factor has multiple functions in stem-cell biology, the immune response, and cancer, and is potentially a key molecule that allows cancer stem cells to self-renew...
February 28, 2017: Oncology Research
https://www.readbyqxmd.com/read/28184327/the-effects-of-monosodium-glutamate-and-tannic-acid-on-adult-rats
#12
Ibrahim Ugur Calis, Didem Turgut Cosan, Faruk Saydam, Umut Kerem Kolac, Ahu Soyocak, Hulyam Kurt, Hasan Veysi Gunes, Varol Sahinturk, Fezan Sahin Mutlu, Zeynep Ozdemir Koroglu, Irfan Degirmenci
BACKGROUND: Monosodium glutamate (MSG) is a widely-used flavor enhancer and stabilizer in ready-made or packaged foods. The excessive use of MSG has been shown to increase oxidative stress in different organ systems and causes glucose metabolism disorders, obesity, and coronary diseases. OBJECTIVES: In this study, the antioxidant activity of tannic acid was investigated experimentally with respect to its protective effects against overdosed MSG-induced oxidative stress in rats...
October 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28158215/in-silico-analyses-and-global-transcriptional-profiling-reveal-novel-putative-targets-for-pea3-transcription-factor-related-to-its-function-in-neurons
#13
Başak Kandemir, Ugur Dag, Burcu Bakir Gungor, İlknur Melis Durasi, Burcu Erdogan, Eray Sahin, Ugur Sezerman, Isil Aksan Kurnaz
Pea3 transcription factor belongs to the PEA3 subfamily within the ETS domain transcription factor superfamily, and has been largely studied in relation to its role in breast cancer metastasis. Nonetheless, Pea3 plays a role not only in breast tumor, but also in other tissues with branching morphogenesis, including kidneys, blood vasculature, bronchi and the developing nervous system. Identification of Pea3 target promoters in these systems are important for a thorough understanding of how Pea3 functions. Present study particularly focuses on the identification of novel neuronal targets of Pea3 in a combinatorial approach, through curation, computational analysis and microarray studies in a neuronal model system, SH-SY5Y neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28088684/changes-in-electroencephalographic-characteristics-and-blood-brain-barrier-permeability-in-wag-rij-rats-with-cortical-dysplasia
#14
Deniz Sahin, Canan Ugur Yilmaz, Nurcan Orhan, Nadir Arican, Mehmet Kaya, Candan Gürses, Nurbay Ates, Bulent Ahishali
PURPOSE: This study investigated the effects of cortical dysplasia (CD) on electrophysiology and blood-brain barrier (BBB) permeability in WAG/Rij rats with genetic absence epilepsy. METHODS: Pregnant WAG/Rij rats were exposed to 145cGy of gamma-irradiation on embryonic day 17 to induce CD. An electroencephalogram was recorded from cortices subdurally in the offspring of the pregnant animals. Horseradish peroxidase (HRP) was used as determinant of BBB permeability...
February 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28079610/influence-of-the-localization-of-frontal-bone-defects-on-primary-stability-values-of-2-different-implant-designs-an-in-vitro-study
#15
Ugur Mercan, Hakan Bilhan, Deniz Gokce Meral, Sehnaz Kazokoglu, Gokce Aykol-Sahin, Onur Geckili
OBJECTIVES: The aim of this study was to determine the influence of different frontal bone defect localizations on primary stability values of 2 different implant designs. MATERIALS AND METHODS: Eight cow rib segments were prepared before implant installation, as 2 segments with coronal, 2 with middle, and 2 with apical defects and 2 with control. Thirty-two cylindrical and 32 tapered implants were placed in the remaining 4 segments. Implant stability measurements were performed using electronic percussive testing and resonance frequency analysis...
February 2017: Implant Dentistry
https://www.readbyqxmd.com/read/28058217/review-of-allogeneic-hematopoietic-stem-cell-transplantation-with-reduced-intensity-conditioning-in-solid-tumors-excluding-breast-cancer
#16
REVIEW
Nuri Karadurmus, Ugur Sahin, Bilgin Bahadir Basgoz, Fikret Arpaci, Taner Demirer
Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning (RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28011121/temporal-bone-paragangliomas-15-years-experience
#17
Mehmet Düzlü, Hakan Tutar, Recep Karamert, Furkan Karaloğlu, Muammer Melih Şahin, Mehmet Göcek, Mehmet Birol Uğur, Nebil Göksu
INTRODUCTION: Temporal bone paragangliomas (TBPs) are benign tumors arising from neural crest cells located along the jugular bulbus and the tympanic plexus. In general surgical excision, radiotherapy and wait-and-scan protocols are the main management modalities for TBPs. OBJECTIVE: In this paper we aim to present our clinical experience with TBPs and to review literature data. METHODS: The patients who were operated for tympanomastoid paraganglioma (TMP) or tympanojugular paraganglioma (TJP) in our clinic in the last 15 years were enrolled in the study...
December 8, 2016: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/27987153/discovery-and-subtyping-of-neo-epitope-specific-t-cell-responses-for-cancer-immunotherapy-addressing-the-mutanome
#18
Mustafa Diken, Mathias Vormehr, Christian Grunwitz, Sebastian Kreiter, Özlem Türeci, Ugur Sahin
Cancer accumulates 10s to 1000s of genomic mutations of which a fraction is immunogenic and may serve as an Achilles' heel of tumor cells. Mutation-specific T cells can recognize these antigens and destroy malignant cells. Strategies to immunotherapeutically address individual tumor mutations employing peptide or mRNA based vaccines are now actively investigated in mice and humans. An important step of determining the therapeutic potential of a mutanome vaccine is the detection of mutation reactive T-cell responses...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27987152/the-european-regulatory-environment-of-rna-based-vaccines
#19
Thomas Hinz, Kajo Kallen, Cedrik M Britten, Bruno Flamion, Ulrich Granzer, Axel Hoos, Christoph Huber, Samir Khleif, Sebastian Kreiter, Hans-Georg Rammensee, Ugur Sahin, Harpreet Singh-Jasuja, Özlem Türeci, Ulrich Kalinke
A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27903882/cap-analogs-modified-with-1-2-dithiodiphosphate-moiety-protect-mrna-from-decapping-and-enhance-its-translational-potential
#20
Malwina Strenkowska, Renata Grzela, Maciej Majewski, Katarzyna Wnek, Joanna Kowalska, Maciej Lukaszewicz, Joanna Zuberek, Edward Darzynkiewicz, Andreas N Kuhn, Ugur Sahin, Jacek Jemielity
Along with a growing interest in mRNA-based gene therapies, efforts are increasingly focused on reaching the full translational potential of mRNA, as a major obstacle for in vivo applications is sufficient expression of exogenously delivered mRNA. One method to overcome this limitation is chemically modifying the 7-methylguanosine cap at the 5' end of mRNA (m(7)Gppp-RNA). We report a novel class of cap analogs designed as reagents for mRNA modification. The analogs carry a 1,2-dithiodiphosphate moiety at various positions along a tri- or tetraphosphate bridge, and thus are termed 2S analogs...
November 16, 2016: Nucleic Acids Research
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