Τίτλος:
Preclinical studies on NSC290205 aza-steroid alkylator activity in
combination with adriamycin against lymphoid leukaemia
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
NSC290205 (A) is an hybrid synthetic antineoplastic ester that is a
combination of a D-lactam derivative of androsterone and an alkylating
derivative of N,N-bis(2-chloroethyl)aniline. We tested NSC290205 for
synergistic antileukaemic activity with adriamycin (ADR), (i) in vitro
against the human lymphoid leukaemia cell lines: CCRF-CEM, MOLT-4, and
RPMI-8226, (ii) in vivo against P388 lymphocytic and L1210 lymphoid
murine leukaemias (at incipient and advanced phase). Our results
indicated significant cytostatic and cytotoxic synergy of NSC290205 and
ADR in vitro. We further examined these results in vivo by replacing
cyclophosphamide in the standard CHOP (cyclophosphamide,
hydroxydaunomycin, Oncovin, prednisone) regimen with NSC290205 (AHOP)
and comparing the efficiency of these two regimens in vivo. Although
treatment of P388 and L1210 with cyclophosphamide or NSC290205 alone
yielded equivalent results, AHOP produced a clear benefit for survival
compared with CHOP against advanced leukaemias, confirming the in vitro
observations [higher percentage increase in median lifespan of treated
animals over the untreated (control): 188% and 239% in L1210, 308%
and 353% in P388, P < 0.01, for CHOP and AHOP respectively]. AHOP also
proved to be more genotoxic and cytostatic than CHOP, inducing higher
sister chromatid exchange levels and cell division delays on P388 cells
in vivo. NSC290205 showed superior antineoplastic potential against
lymphoid leukaemia and significant synergy with ADR, producing an
excellent therapeutic outcome.
Συγγραφείς:
Trafalis, DTP
Tsavdaridis, D
Camoutsis, C
Karayiani, V and
Mourelatos, D
Chrysogelou, E
Dalezis, P
Athanassiou, A and
Pangalis, GA
Papageorgiou, A
Περιοδικό:
British Journal of Haematology
Εκδότης:
Wiley-Blackwell Publishing Ltd
Λέξεις-κλειδιά:
lactam steroid; CHOP; P388; L1210; human leukaemia cell lines
DOI:
10.1111/j.1365-2141.2004.05315.x
