Mini's research interests include cancer pharmacology, tumor drug resistance, and the pharmacogenomics of anticancer therapies, with a focus on colorectal cancer, other gastrointestinal neoplasms, leukemia, and lymphoma. He was the director of the Unit of Translational Oncology at Careggi University Hospital and the head of the Laboratory of Cancer Pharmacology and Chemotherapy at the University of Florence.
Education
Mini earned an M.D. from the University of Florence in 1977.[1] In 1980, he received a specialty degree in Oncology from the University of Modena, followed by a Ph.D. in Pharmacology and Toxicology in 1988 from the University of Florence.[2]
Career
Mini's academic career includes his appointment as a research scientist at the Departments of Pharmacology and Medicine of the Yale University School of Medicine from 1981 to 1984. He was appointed as a lecturer at the University of Siena from 1983 to 1987, and then began working as a lecturer at the University of Ferrara in 1988, a position he held until 1992. He was appointed as an associate professor of pharmacology at the University of Florence from 1992 to 2001,[2] and then as professor of Pharmacology from 2001 to 2008.[1] He was appointed as the professor of Medical Oncology at the University of Florence in 2008, and later as an emeritus professor there.[3]
Mini was the chairman of the Cancer Section of the International Society of Chemotherapy from 2007 to 2013.[1] Between 2011 and 2020, he was appointed as director of the Specialty School of Medical Oncology at the University of Florence.[2] He held these positions until his retirement in 2022, after which he continued as the scientific lead of funded research projects. Since 2018, he has been the coordinator of the Oncological Pharmacology Working Group of the Italian Society of Pharmacology.[4][5]
Research
Mini's research contributed to clarifying the mechanisms of methotrexate (MTX), an antifolate chemotherapy agent and immunosuppressant that works by inhibiting an enzyme called dihydrofolate reductase (DHFR).[6][7] In related research, it was demonstrated that polyglutamylation of methotrexate contributes to its selective cytotoxic effect.[8]
Mini proposed that administering MTX before 5-fluorouracil(5-FU) produces a synergistic effect, since the polyglutamated MTX can replace 5,10-CH2-THF in the ternary complex.[9] He further indicated that alterations in the balance of polyglutamylated MTX forms often lead to the development of drug resistance.[10] His studies have led to the recognition of leucovorin as a biomodulator of 5-FU cytotoxicity in preclinical experiments prompting a surge of phase I and II clinical investigations.[11]
Mini, through his research, highlighted the negative role of permeability glycoprotein(P-gp), an ABC transporter with extensive substrate specificity in anticancer therapy for leukemia and other solid tumors.[12] He then modified anticancer drugs to reduce P-gp-mediated efflux[13] and underlined the need for creating drugs that are non-P-gp substrates to counter cancer resistance hindrances.[14] In a collaborative study, he explored reversing multidrug resistance in a highly doxorubicin-resistant human colorectal adenocarcinoma cell line. The study investigated long-term treatment with an equimolar mixture of three unmodified antisense oligonucleotides targeting adjacent sites on P-gpmRNA (messenger RNA), delivered via a synthetic cationic lipid.[15] He showed that the combination could downregulate P-gp mRNA in the doxorubicin-resistant cell line.[16] Mini also explored the potential of gold-based complexes for their use as metallodrugs in cancer.[17]
Selected articles
Pizzorno, G; Mini, E; Coronnello, M; McGuire, J J; Moroson, B A; Cashmore, A R; Dreyer, R N; Lin, J T (1988). "Impaired polyglutamylation of methotrexate as a cause of resistance in CCRF-CEM cells after short-term, high-dose treatment with this drug". Cancer Research. 48 (8): 2149–2155. PMID2450647.
^Ortenberg, R.; Rozenblatt-Rosen, O. (March 2000). "The extremely halophilic archaeon Haloferax volcanii has two very different dihydrofolate reductases". Molecular Microbiology. 35 (6): 1501. doi:10.1046/j.1365-2958.2000.01815.x. PMID10760149.
^Fabre, I.; Fabre, G.; Goldman, I. D. (1984). "Polyglutamylation, an important element in methotrexate cytotoxicity and selectivity in tumor versus murine granulocytic progenitor cells in vitro". Cancer Research. 44 (8): 3190–3195. PMID6204743.
^Isacoff, William H.; Borud, Katrina (1997). "Chemotherapy for the Treatment of Patients with Metastatic Colorectal Cancer: An Overview". World Journal of Surgery. 21 (7): 748–762. doi:10.1007/S002689900301. PMID9276707.
^
Szabó, Ildikó; Orbán, Erika; Schlosser, Gitta; Hudecz, Ferenc; Bánóczi, Zoltán (2016). "Cell-penetrating conjugates of pentaglutamylated methotrexate as potential anticancer drugs against resistant tumor cells". European Journal of Medicinal Chemistry. 115: 361–368. doi:10.1016/j.ejmech.2016.03.034. PMID27031212.
^Binkhathlan, Ziyad; Lavasanifar, Afsaneh (2013). "P-glycoprotein Inhibition as a Therapeutic Approach for Overcoming Multidrug Resistance in Cancer: Current Status and Future Perspectives". Current Cancer Drug Targets. 13 (3): 326–346. doi:10.2174/15680096113139990076. PMID23369096.
^Hussaini, Sunusi Y.; Haque, Rosenani A.; Razali, Mohd R. (2019). "Recent progress in silver(I)-, gold(I)/(III)- and palladium(II)-N-heterocyclic carbene complexes: A review towards biological perspectives". Journal of Organometallic Chemistry. 882: 96–111. doi:10.1016/j.jorganchem.2019.01.003.
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