{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:12:04Z","timestamp":1767625924286,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T00:00:00Z","timestamp":1595635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009414","name":"Istituto Oncologico Veneto","doi-asserted-by":"publisher","award":["5 per mille"],"award-info":[{"award-number":["5 per mille"]}],"id":[{"id":"10.13039\/501100009414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["DOR Department of Surgery Oncology and Gastroenterology"],"award-info":[{"award-number":["DOR Department of Surgery Oncology and Gastroenterology"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Besides its canonical role in stabilizing telomeres, telomerase reverse transcriptase (TERT) may promote tumor growth\/progression through extra-telomeric functions. Our previous in vitro studies demonstrated that short-term TERT inhibition by BIBR1532 (BIBR), an inhibitor of TERT catalytic activity, negatively impacts cell proliferation and viability via telomeres\u2019 length-independent mechanism. Here we evaluate the anti-proliferative and pro-apoptotic effects of short-term telomerase inhibition in vivo in wild-type (wt) and tert mutant (terthu3430\/hu3430; tert\u2212\/\u2212) zebrafish embryos, and in malignant human B cells xenografted in casper zebrafish embryos. Short-term Tert inhibition by BIBR in wt embryos reduced cell proliferation, induced an accumulation of cells in S-phase and ultimately led to apoptosis associated with the activation of DNA damage response; all these effects were unrelated to telomere shortening\/dysfunction. BIBR treatment showed no effects in tert\u2212\/\u2212 embryos. Xenografted untreated malignant B cells proliferated in zebrafish embryos, while BIBR pretreated cells constantly decreased and were significantly less than those in the controls from 24 to up to 72 h after xenotransplantation. Additionally, xenografted tumor cells, treated with BIBR prior- or post-transplantation, displayed a significant higher apoptotic rate compared to untreated control cells. In conclusion, our data demonstrate that short-term telomerase inhibition impairs proliferation and viability in vivo and in human malignant B cells xenografted in zebrafish, thus supporting therapeutic applications of TERT inhibitors in human malignancies.<\/jats:p>","DOI":"10.3390\/cancers12082052","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T04:39:50Z","timestamp":1595824790000},"page":"2052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anti-Proliferative and Pro-Apoptotic Effects of Short-Term Inhibition of Telomerase In Vivo and in Human Malignant B Cells Xenografted in Zebrafish"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3760-1478","authenticated-orcid":false,"given":"Silvia","family":"Giunco","sequence":"first","affiliation":[{"name":"Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}]},{"given":"Manuela","family":"Zangrossi","sequence":"additional","affiliation":[{"name":"Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}]},{"given":"Francesca","family":"Dal Pozzolo","sequence":"additional","affiliation":[{"name":"Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV\u2013IRCCS, 35128 Padova, Italy"}]},{"given":"Andrea","family":"Celeghin","sequence":"additional","affiliation":[{"name":"Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}]},{"given":"Giovanni","family":"Ballin","sequence":"additional","affiliation":[{"name":"Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}]},{"given":"Maria Raffaella","family":"Petrara","sequence":"additional","affiliation":[{"name":"Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}]},{"given":"Aamir","family":"Amin","sequence":"additional","affiliation":[{"name":"Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0803-8236","authenticated-orcid":false,"given":"Francesco","family":"Argenton","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35128 Padova, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-7183","authenticated-orcid":false,"given":"Miguel","family":"Godinho Ferreira","sequence":"additional","affiliation":[{"name":"Institute for Research on Cancer and Aging of Nice (IRCAN), UMR7284 U1081 UNS, Universit\u00e9 C\u00f4te d\u2019Azur, 06107 Nice CEDEX 2, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6435-7509","authenticated-orcid":false,"given":"Anita","family":"De Rossi","sequence":"additional","affiliation":[{"name":"Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"},{"name":"Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV\u2013IRCCS, 35128 Padova, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1038\/nm1006-1133","article-title":"Telomeres and telomerase: The path from maize, Tetrahymena and yeast to human cancer and aging","volume":"12","author":"Blackburn","year":"2006","journal-title":"Nat. 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