@article{MTMT:34883229, title = {LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment}, url = {https://m2.mtmt.hu/api/publication/34883229}, author = {Karkas, Réka and Abdullah, Khaldoon Sadiq Ahmed and Kaizer, László and Ürmös, A and Raya, May and Tiszlavicz, Lilla Györgyi and Pankotai, Tibor and Nagy, István and Mátés, Lajos and Sükösd, Farkas}, doi = {10.1097/PGP.0000000000001035}, journal-iso = {INT J GYNECOL PATHOL}, journal = {INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY}, volume = {44}, unique-id = {34883229}, issn = {0277-1691}, abstract = {Cervical intraepithelial neoplasia (CIN) represents a spectrum of preinvasive squamous lesions within the cervical epithelium, whose identification is a diagnostic challenge due to subtle histomorphological differences among its categories. This study explores ORF1p, a nucleic acid-binding protein derived from long interspersed nuclear element-1 (LINE-1), as a potential biomarker for enhancing CIN diagnosis. A comprehensive analysis of 143 cervical specimens, encompassing CIN I (n=20), CIN II (n=46), CIN III (n=14), invasive cancer (n=32), and nondysplastic cases (normal cervical epithelia (n=24) and atrophy (n=7) were conducted. ORF1p, Ki67, and p16 expressions were evaluated using immunohistochemistry. ORF1p immunopositivity was detected in the vast majority [110/112 (98.2%)] of dysplastic and neoplastic (CIN and invasive cancer) specimens, whereas 19/24 (79.2%) of normal cervical specimens lacked ORF1p expression. The observed pattern of ORF1p expression showed a progressively increasing extent and intensity with advancing CIN grades. CIN I exhibited mild ORF1p expression in the lower one or two-thirds of the cervical epithelium [14/16 (87.5%)], whereas CIN II demonstrated moderate to strong ORF1p expression spanning the lower two-thirds [29/46 (63.0%)]. Pronounced transepithelial ORF1p immunopositivity characterized CIN III cases [13/14 (92.8%)] and cervical cancer [30/32 (93.8%)]. These findings propose ORF1p as a valuable indicator even for detecting CIN I, effectively discerning them from normal cervical tissue (p < 0.0001). Our findings underscore the potential of ORF1p as an early diagnostic marker for cervical neoplasia.}, year = {2025}, eissn = {1538-7151}, pages = {22-30}, orcid-numbers = {Pankotai, Tibor/0000-0001-9810-5465} } @article{MTMT:36160409, title = {When Antlers Grow Abnormally: A Hidden Disease Behind Common Cervid Trophy Deformities, Introducing Pedunculitis Chronica Deformans}, url = {https://m2.mtmt.hu/api/publication/36160409}, author = {Sükösd, Farkas and Lakatos, István and Ürmös, Ádám and Karkas, Réka and Sükösd, Ákos and Palánki, Gábor and Arany Tóth, Attila and Erdélyi, Károly and Misó, Mihály and Gőbölös, Péter and Posta, Katalin and Kovács, Ferenc and Ferenczi, Szilamér and Horváth, Győző and Szemethy, László and Szőke, Zsuzsanna}, doi = {10.3390/ani15111530}, journal-iso = {ANIMALS-BASEL}, journal = {ANIMALS}, volume = {15}, unique-id = {36160409}, abstract = {For centuries, the most prevalent antler abnormalities observed worldwide have been attributed to trauma. However, detailed pathological investigation of these cases has not yet been carried out. In free-living fallow deer (Dama dama), we identified a chronic osteomyelitis-like condition—Pedunculitis Chronica Deformans (PCD)—using pathological and radiological diagnostics. We propose that inflammation during post-casting wound healing and consequent scar formation can trigger the development of PCD. In this study, we characterize the pathomorphology of PCD and introduce a scoring system to describe its severity. Furthermore, we describe the histoanatomy of the junction between the pedicle and the surrounding skin—an area essential for the integrity of the integument—which, when compromised, may predispose cervids to PCD. Our findings suggest that the most common antler abnormality results from a pathological fracture associated with PCD, which can be further complicated by fatal meningoencephalitis and brain abscesses. PCD-related lesions, while less frequently observed, can also be identified in roe deer (Capreolus capreolus) and red deer (Cervus elaphus), with species-specific differences. These findings overlap with cases reported in other cervid species, suggesting a more general disorder of antler formation. Describing this condition provides a basis for assessing its epidemiology and understanding its relevance to wildlife health.}, year = {2025}, eissn = {2076-2615}, orcid-numbers = {Erdélyi, Károly/0000-0002-5992-4844; Posta, Katalin/0000-0003-2790-1741; Horváth, Győző/0000-0002-4818-1096; Szőke, Zsuzsanna/0000-0001-9302-1115} } @article{MTMT:33708483, title = {Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy}, url = {https://m2.mtmt.hu/api/publication/33708483}, author = {Imre, Gergely and Takács, Bertalan Vilmos and Czipa, Erik and Drubi, Andrea and Jaksa, Gábor and Latinovics, Dóra and Nagy, Andrea and Karkas, Réka and Hudoba, Liza and Vásárhelyi, Bálint Márk and Pankotai-Bodó, Gabriella and Blastyák, András and Hegedűs, Zoltán and Germán, Péter and Bálint, Balázs and Abdullah, Khaldoon Sadiq Ahmed and Kopasz, Anna Georgina and Kovács, Anita Kármen and Nagy, László and Sükösd, Farkas and Pintér, Lajos and Rülicke, Thomas and Barta, Endre and Nagy, István and Haracska, Lajos and Mátés, Lajos}, doi = {10.1016/j.omtm.2023.03.003}, journal-iso = {MOL THER-METH CLIN D}, journal = {MOLECULAR THERAPY-METHODS AND CLINICAL DEVELOPMENT}, volume = {29}, unique-id = {33708483}, abstract = {DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development for gene therapy. For the side-by-side evaluation of the piggyBac and Sleeping Beauty systems—the only DNA transposons currently employed in clinical trials—during therapeutic intervention, we treated the mouse model of tyrosinemia type I with liver-targeted gene delivery using both transposon vectors. For genome-wide mapping of transposon insertion sites we developed a new next-generation sequencing procedure called streptavidin-based enrichment sequencing, which allowed us to identify approximately one million integration sites for both systems. We revealed that a high proportion of piggyBac integrations are clustered in hot regions and found that they are frequently recurring at the same genomic positions among treated animals, indicating that the genome-wide distribution of Sleeping Beauty-generated integrations is closer to random. We also revealed that the piggyBac transposase protein exhibits prolonged activity, which predicts the risk of oncogenesis by generating chromosomal double-strand breaks. Safety concerns associated with prolonged transpositional activity draw attention to the importance of squeezing the active state of the transposase enzymes into a narrower time window.}, year = {2023}, eissn = {2329-0501}, pages = {145-159}, orcid-numbers = {Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Pankotai-Bodó, Gabriella/0000-0001-5548-6026; Kovács, Anita Kármen/0000-0001-9805-1647; Barta, Endre/0000-0002-6753-0714} } @article{MTMT:32773206, title = {A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver}, url = {https://m2.mtmt.hu/api/publication/32773206}, author = {Kopasz, Anna Georgina and Pusztai, Dávid and Karkas, Réka and Hudoba, Liza and Abdullah, Khaldoon Sadiq Ahmed and Imre, Gergely and Pankotai-Bodó, Gabriella and Migh, Ede and Nagy, Andrea and Kriston, András and Germán, Péter and Drubi, Andrea and Molnár, Anna and Fekete, Ildikó and Dani, Virág Éva and Ocsovszki, Imre and Puskás, László and Horváth, Péter and Sükösd, Farkas and Mátés, Lajos}, doi = {10.1186/s12915-022-01262-x}, journal-iso = {BMC BIOL}, journal = {BMC BIOLOGY}, volume = {20}, unique-id = {32773206}, issn = {1741-7007}, abstract = {Understanding the contribution of gene function in distinct organ systems to the pathogenesis of human diseases in biomedical research requires modifying gene expression through the generation of gain- and loss-of-function phenotypes in model organisms, for instance, the mouse. However, methods to modify both germline and somatic genomes have important limitations that prevent easy, strong, and stable expression of transgenes. For instance, while the liver is remarkably easy to target, nucleic acids introduced to modify the genome of hepatocytes are rapidly lost, or the transgene expression they mediate becomes inhibited due to the action of effector pathways for the elimination of exogenous DNA. Novel methods are required to overcome these challenges, and here we develop a somatic gene delivery technology enabling long-lasting high-level transgene expression in the entire hepatocyte population of mice.}, year = {2022}, eissn = {1741-7007}, orcid-numbers = {Abdullah, Khaldoon Sadiq Ahmed/0000-0001-9980-3724; Pankotai-Bodó, Gabriella/0000-0001-5548-6026; Dani, Virág Éva/0000-0001-9715-2569; Ocsovszki, Imre/0000-0003-1290-996X} }