{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:55:26Z","timestamp":1784915726951,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian Ministry of Education and Research, CCCDI - UEFISCDI","award":["PN-III-P2-2.1-PED-2019-2893, within PNCDI III"],"award-info":[{"award-number":["PN-III-P2-2.1-PED-2019-2893, within PNCDI III"]}]},{"name":"First University Center (University of Brescia, Italy)","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is poorly beneficiated by intravenous chemotherapy due to inadequate availability of drugs at the tumor site. We previously demonstrated that human micro-fragmented adipose tissue (MFAT) and its devitalized counterpart (DMFAT) could be effective natural scaffolds to deliver Paclitaxel (PTX) to tumors in both in vitro and in vivo tests, affecting cancer growth relapse. Here we tested the efficacy of DMFAT-PTX in a well-established HCC in nude mice. MFAT-PTX and DMFAT-PTX preparations were tested for anti-cancer activity in 2D and 3D assays using Hep-3B tumor cells. The efficacy of DMFAT-PTX was evaluated after a single-shot subcutaneous injection near a Hep-3B growing tumor by assessing tumor volumes, apoptosis rate, and drug pharmacokinetics in an in vivo model. Potent antiproliferative activity was seen in both in vitro 2D and 3D tests. Mice treated with DMFAT-PTX (10 mg\/kg) produced potent Hep-3B growth inhibition with 33% complete tumor regressions. All treated animals experienced tumor ulceration at the site of DMFAT-PTX injection, which healed spontaneously. Lowering the drug concentration (5 mg\/kg) prevented the formation of ulcers, maintaining statistically significant efficacy. Histology revealed a higher number of apoptotic cancer cells intratumorally, suggesting prolonged presence of PTX that was confirmed by the pharmacokinetic analysis. DMFAT may be a potent and valid new tool for local chemotherapy of HCC in an advanced stage of progression, also suggesting potential effectiveness in other human primary inoperable cancers.<\/jats:p>","DOI":"10.3390\/cancers13215505","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T12:39:42Z","timestamp":1635856782000},"page":"5505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Giulio","family":"Alessandri","sequence":"first","affiliation":[{"name":"Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Foundation IRCCS Neurological Institute Carlo Besta, 20133 Milan, Italy"},{"name":"Department of Molecular and Translational Medicine, Clinical Microbiology and Virology Section, University of Brescia, 25127 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Pessina","sequence":"additional","affiliation":[{"name":"CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-8860","authenticated-orcid":false,"given":"Rita","family":"Paroni","sequence":"additional","affiliation":[{"name":"Clinical biochemistry and Mass Spectrometry Laboratory, Department of Health Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Bercich","sequence":"additional","affiliation":[{"name":"Department of Pathology, ASST Spedali Civili of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-1888","authenticated-orcid":false,"given":"Francesca","family":"Paino","sequence":"additional","affiliation":[{"name":"CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-8558","authenticated-orcid":false,"given":"Michele","family":"Dei Cas","sequence":"additional","affiliation":[{"name":"Clinical biochemistry and Mass Spectrometry Laboratory, Department of Health Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moris","family":"Cadei","sequence":"additional","affiliation":[{"name":"Section of Pathological Anatomy DMMT, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, Clinical Microbiology and Virology Section, University of Brescia, 25127 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Schiariti","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Foundation IRCCS Neurological Institute Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Restelli","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Foundation IRCCS Neurological Institute Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8346-000X","authenticated-orcid":false,"given":"Offer","family":"Zeira","sequence":"additional","affiliation":[{"name":"San Michele Veterinary Hospital, 26838 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-5995","authenticated-orcid":false,"given":"Carlo","family":"Tremolada","sequence":"additional","affiliation":[{"name":"Image Regenerative Clinic, Via Mascagni 14, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazario","family":"Portolani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2217\/imt-2021-0026","article-title":"Atezolizumab in advanced hepatocellular carcinoma: Good things come to those who 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