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Tesi etd-08132021-144441


Tipo di tesi
Tesi di laurea magistrale
Autore
TASSAROTTI, GIULIA
URN
etd-08132021-144441
Titolo
PLATINUM-BASED AGENTS FOR COLORECTAL CANCER TREATMENT: A ROLE OF Ca2+ AND Mg2+ IN CONTROLLING SIDE-EFFECTS?
Dipartimento
FARMACIA
Corso di studi
SCIENZE DELLA NUTRIZIONE UMANA
Relatori
relatore Dott. Marzo, Tiziano
relatore Dott.ssa Barresi, Elisabetta
Parole chiave
  • calcium
  • cancer
  • chemoresistance
  • magnesium
  • metallodrugs side effects
  • metals-homeostasis
  • neuropathy
  • platinum-based anticancer drugs
Data inizio appello
04/10/2021
Consultabilità
Completa
Riassunto
Platinum-based anticancer therapy is used in about 50 % of clinical protocols worldwide. In this view, cisplatin, carboplatin and oxaliplatin are essential drugs. However, their use is accompanied by side effects often limiting the treatments. In the first part of this work through a bioinorganic experimental approach we studied the mode of activation of cisplatin, carboplatin and oxaliplatin. Then, based on the obtained results we discuss the implication and the possible chemotherapy regimens improvements for the overcoming of side-effects. Specifically, we focused the attention on the case of oxaliplatin. At variance with cisplatin and carboplatin, oxaliplatin is used almost exclusively in colorectal cancer (CRC) treatment.
The bioinorganic studies we have carried out and literature search, shown that oxaliplatin has an activation profile different from cisplatin and carboplatin. This aspect, together with recent evidences reporting as oxaliplatin exerts its anticancer effects through a DNA-independent manner might responsible for its different anticancer profile. Moreover, when oxaliplatin undergoes activation by releasing its labile ligand, i.e. oxalate, this latter strongly chelates the physiological Mg2+ and Ca2+ ions, in turn essential for many biological functions. As consequence, the treatment of patients with oxaliplatin often determines severe acute or chronic neuropathies. Accordingly, we also investigated literature to understand how the calcium or magnesium supplements in cancer patients may modulate and help in controlling the induced neuropathy thus improving the quality of life.
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