Growth inhibition of human tumor xenografts in nude mice by treatment with the antitumor agent 4,6-benzylidene-d1-D-glucose (P-1013).
4,6-Benzylidene-d1-D-glucose, P-1013, a deuterated benzaldehyde derivative which acts as a reversible protein synthesis inhibitor in vitro, was evaluated for antitumor effects in two human tumor xenografts implanced s.c. in nude mice. The drug, dissolved in isotonic saline, was given p.o. daily for several weeks. For evaluation of drug efficacy, mean tumor volume growth curves were generated and tumor volume doubling time (TD) as well as per cent change in tumor size for the treated tumors compared to control (T/C) were calculated. P-1013 at 90 mg/kg for 49 days was effective against SK-OV-3 human ovarian carcinoma (T/C 47% at day 40 and 50% increase in TD). P-1013 at 90 mg/kg also suppressed growth of PANC-1 human pancreatic carcinoma in two experiments (T/C 44 and 50%, 20 and 40% increase in TD, respectively). There was no indication of systemic toxicity in mice receiving P-1013. Histological examinations of each tumor showed that P-1013 treatment of pancreatic xenografts reduced tumor volume without inducing greater necrosis than that comparable to respective control tumors. For the ovarian xenograft, the histological examination indicated a higher fraction of tumors with more than 50% necrotic tissue in two of the P-1013-treated groups compared with the control group (Fisher exact test, p = 0.12). It is possible that P-1013, in addition to inhibiting the rate of tumor volume growth, also induces tumor necrotization in the ovarian xenograft.
Dunsaed
C B
CB
Department of Tissue Culture, Norwegian Radium Hospital, Montebello, Oslo.
Dornish
J M
JM
Aastveit
T E
TE
Nesland
J M
JM
Pettersen
E O
EO
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005947:Glucose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis / Q000473:pathology; D009368:Neoplasm Transplantation / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous / Q000473:pathology
D000970:Antineoplastic Agents; C013844:benzylidene glucose; D005947:Glucose