Does administration of isosorbide mononitrate affect cellular proliferation in oral squamous cell carcinoma? A prospective randomized clinical study.
OBJECTIVE
There has been much interest in the role that the signaling molecule nitric oxide (NO) plays in cancer. NO has both tumor-promoting and tumor-inhibiting effects that are dependent on its local tissue concentration. In animal studies, the administration of exogenous NO has reduced both tumor growth and dissemination, and in vitro NO administration causes death of oral cancer cell lines. We evaluated the oral administration of the NO donor drug isosorbide mononitrate (ISMO) on cellular proliferation in patients with oral squamous cell carcinoma.


METHODS
A prospective randomized double-blind study was performed on 31 patients with biopsy-confirmed oral squamous cell carcinoma. Following incisional biopsy, patients were randomized to receive either ISMO (at a dose of 20 mg twice a day) or placebo tablets for 2 weeks before definitive resection. Cellular proliferation was compared between biopsy and resection specimens, using the immunohistochemical marker Ki-67.


RESULTS
No statistical difference was found between Ki-67 indices in initial biopsy and resection specimens after ISMO (P =.23) or placebo (P =.5) administration. There were no obvious clinical changes seen in the tumor during the clinical trial as a result of ISMO administration.


CONCLUSIONS
Although high concentrations of NO are cytotoxic, it is unlikely that administration of NO at an increased dose would be useful in the management of oral cancer because this would result in unacceptable systemic side effects. The possible manipulation of NO in oral cancer is discussed.
Downie
Ian P
IP
Salisbury District Hospital, Wilts, UK.
Umar
Tijjani
T
Boote
David J
DJ
Mellor
T K
TK
Hoffman
G R
GR
Brennan
Peter A
PA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D016009:Chi-Square Distribution; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D010919:Placebos; D011446:Prospective Studies
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D003692:Delayed-Action Preparations; D019394:Ki-67 Antigen; C440408:MIB-1 antibody; D020030:Nitric Oxide Donors; D010919:Placebos; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate