TY - JOUR AU - Karkas, Réka AU - Abdullah, Khaldoon Sadiq Ahmed AU - Kaizer, László AU - Ürmös, A AU - Raya, May AU - Tiszlavicz, Lilla Györgyi AU - Pankotai, Tibor AU - Nagy, István AU - Mátés, Lajos AU - Sükösd, Farkas TI - LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment JF - INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY J2 - INT J GYNECOL PATHOL VL - 44 PY - 2025 IS - 1 SP - 22 EP - 30 PG - 9 SN - 0277-1691 DO - 10.1097/PGP.0000000000001035 UR - https://m2.mtmt.hu/api/publication/34883229 ID - 34883229 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Fund, Hungary [2021-1.1.4-GYORSITOSAV- 2022-00018]; New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund, Hungary [UNKP-23-3] Funding text: The project was, in part, funded by the 2021-1.1.4-GYORSITOSAV- 2022-00018 project of the National Research, Development and Innovation Fund, Hungary. R.K. was supported by the UNKP-23-3 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund, Hungary. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Imre, Gergely AU - Takács, Bertalan Vilmos AU - Czipa, Erik AU - Drubi, Andrea AU - Jaksa, Gábor AU - Latinovics, Dóra AU - Nagy, Andrea AU - Karkas, Réka AU - Hudoba, Liza AU - Vásárhelyi, Bálint Márk AU - Pankotai-Bodó, Gabriella AU - Blastyák, András AU - Hegedűs, Zoltán AU - Germán, Péter AU - Bálint, Balázs AU - Abdullah, Khaldoon Sadiq Ahmed AU - Kopasz, Anna Georgina AU - Kovács, Anita Kármen AU - Nagy, László AU - Sükösd, Farkas AU - Pintér, Lajos AU - Rülicke, Thomas AU - Barta, Endre AU - Nagy, István AU - Haracska, Lajos AU - Mátés, Lajos TI - Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy JF - MOLECULAR THERAPY-METHODS AND CLINICAL DEVELOPMENT J2 - MOL THER-METH CLIN D VL - 29 PY - 2023 SP - 145 EP - 159 PG - 15 SN - 2329-0501 DO - 10.1016/j.omtm.2023.03.003 UR - https://m2.mtmt.hu/api/publication/33708483 ID - 33708483 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Kopasz, Anna Georgina AU - Pusztai, Dávid AU - Karkas, Réka AU - Hudoba, Liza AU - Abdullah, Khaldoon Sadiq Ahmed AU - Imre, Gergely AU - Pankotai-Bodó, Gabriella AU - Migh, Ede AU - Nagy, Andrea AU - Kriston, András AU - Germán, Péter AU - Drubi, Andrea AU - Molnár, Anna AU - Fekete, Ildikó AU - Dani, Virág Éva AU - Ocsovszki, Imre AU - Puskás, László AU - Horváth, Péter AU - Sükösd, Farkas AU - Mátés, Lajos TI - A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver JF - BMC BIOLOGY J2 - BMC BIOL VL - 20 PY - 2022 IS - 1 PG - 17 SN - 1741-7007 DO - 10.1186/s12915-022-01262-x UR - https://m2.mtmt.hu/api/publication/32773206 ID - 32773206 N1 - Funding Agency and Grant Number: Momentum Programme of the Hungarian Academy of Sciences [LP2015-5/2015]; National Research, Development and Innovation Office (Hungary)National Research, Development & Innovation Office (NRDIO) - Hungary [GINOP-2.3.2-15-2016-00024]; LENDULET-BIOMAG [2018342]; European Regional Development FundEuropean Commission [GINOP-2.3.2-15-201600026]; COMPASS-ERA PerMed H2020; CZI Deep Visual Proteomics; H2020-DiscovAir; ELKH-Excellence grant; New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development and Innovation Fund [UNKP-20-3-SZTE-84]; Szeged Scientists Academy under Hungarian Ministry of Innovation and Technology [FEIF/646-4/2021-ITM_SZERZ]; New National Excellence Program of the Ministry for Innovation and Technology of Hungary [UNKP-20-2 -SZTE-438] Funding text: This work was supported by the Momentum Programme of the Hungarian Academy of Sciences [LP2015-5/2015] and by the National Research, Development and Innovation Office (Hungary) grant [GINOP-2.3.2-15-2016-00024]. PH, EM, and AK acknowledge support from the LENDULET-BIOMAG Grant [2018342], from the European Regional Development Fund (GINOP-2.3.2-15-201600026), from COMPASS-ERA PerMed H2020, from CZI Deep Visual Proteomics, from H2020-DiscovAir, and from ELKH-Excellence grant. RK was supported by the UNKP-20-3-SZTE-84 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. AGK was supported by the Szeged Scientists Academy under the sponsorship of the Hungarian Ministry of Innovation and Technology (FEIF/646-4/2021-ITM_SZERZ) and the New National Excellence Program of the Ministry for Innovation and Technology of Hungary (UNKP-20-2 -SZTE-438). AB - 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. LA - English DB - MTMT ER -