Avtor/Urednik		Zupančič, Daša; Vidmar, Gaj; Jezernik, Kristijan
Naslov		Melatonin prevents the development of hyperplastic urothelium induced by repeated doses of cyclophosphamide
Tip		članek
Vir		Virchows Arch
Vol. in št.		Letnik 454, št. 6
Leto izdaje		2009
Obseg		str. 657-66
Jezik		eng
Abstrakt		Repeated cyclophosphamide (CP) chemotherapy increases the risk of developing bladder cancer, which could be due to the extremely rapid proliferation of urothelial cells observed in hyperplastic urothelium induced by CP treatment. We investigated the effect of melatonin on the development of urothelial hyperplasia induced by repeated CP treatment. Male ICR mice were injected with CP (150 mg/kg) or melatonin (10 mg/kg) with CP once a week for 3, 4 and 5 weeks. Transmission and scanning electron microscopy, immunohistochemistry and Western blot analysis were used to study the ultrastructure, apoptosis, proliferation and differentiation of urothelial cells. Repeated doses of CP caused the development of hyperplastic urothelium with up to ten cell layers and increased proliferation and apoptotic indices regarding Ki-67 and active caspase-3 immunohistochemistry, respectively. Scanning electron microscopy observations, cytokeratin and asymmetrical unit membrane immunohistochemistry and Western blot analysis showed a lower differentiation state of superficial urothelial cells. Melatonin co-treatment prevented the development of hyperplastic urothelium, statistically significantly decreased proliferation and apoptotic indices after four and five doses of CP and caused higher differentiation state of superficial urothelial cells.
Deskriptorji		ANIMALS ANTINEOPLASTIC AGENTS ANTINEOPLASTIC AGENTS, ALKYLATING APOPTOSIS CYCLOPHOSPHAMIDE DRUG ANTAGONISM DRUG SCREENING ASSAYS, ANTITUMOR HYPERPLASIA KI-67 ANTIGEN MELATONIN MICE MICE, INBRED ICR PRECANCEROUS CONDITIONS UROTHELIUM