Topical chemoprevention of oral cancer with tretinoin "biofilm".

BACKGROUND: Oral cancer is a common malignancy. Chemoprevention is a promising treatment strategy but it produces systemic toxic effects. Topical application of chemopreventive agents is an attractive alternative that reduces toxic effects. This study is based on the hypothesis that topical application of mucosal adhesive film (MAF), as a means to deliver tretinoin, is effective and safe for oral cancer chemoprevention. SETTING: Randomized animal study conducted at the Boston University School of Medicine. DESIGN: This study uses the hamster cheek-pouch model to test efficacy and safety of the MAF/tretinoin patch for oral cancer prevention. The oral mucosa of 36 hamsters was painted with dimethylbenzanthracene to produce premalignant lesions. The 36 hamsters were divided into 3 groups of 12 hamsters each as follows: (1) control, no treatment; (2) systemic tretinoin (5.0 mg/kg per day, intraperitoneally); and (3) topically applied MAF/tretinoin patch (0.45 mg tretinoin/cm2, once daily). Treatments continued for 40 days. MAIN OUTCOME MEASURES: Tumor growth and burden were measured over time. The duration of MAF patch retention on mucosa and local tissue reaction to the treatment were also evaluated. RESULTS: The patch stayed on the mucosa for at least 5 hours with no evidence of inflammatory or other adverse reactions from the treated tissue. There was a significant difference in the tumor growth measurement between the control and systemic tretinoin groups (P<.001), and between the control and MAF patch groups (P<.001). CONCLUSIONS: This is the first study, to our knowledge, to use a polymer MAF technique for oral cancer prevention. The MAF/tretinoin patch is safe and effective for such chemoprevention in the hamster model.

The role of laser vascular targeting and retinoic acid in oral cancer inhibition.

OBJECTIVES/HYPOTHESIS: The study examines the role of the pulsed-dye laser at 585 nm, coupled with retinoic acid at therapeutic dose of 5.0 mg/kg body weight, in inhibiting chemically induced tumor growth in the hamster cheek pouch to determine whether pulsed-dye laser therapy can inhibit tumor growth and whether a combination of pulsed-dye laser and retinoic acid has a synergic effect on treatment efficacy. STUDY DESIGN: Randomized, prospective study of hamster model. METHODS: Forty-eight male golden Syrian hamsters were painted with 0.5% solution of 9,10-dimethyl-1,2-benzanthracene in acetone for 6 weeks to induce dysplasia in both sides of the cheek pouches. The hamsters were then randomly divided into four groups of 12 hamsters each as follows: (1) control group, (2) pulsed-dye laser treatment only (8.0 J/cm(2) and two pulses), (3) retinoic acid treatment only (5.0 mg/kg/d by intraperitoneal injection), and (4) combined pulsed-dye laser and retinoic acid treatment. The treatment period was 40 days. Tumors were measured throughout the study. RESULTS: The results indicated that retinoic acid and pulsed-dye laser each significantly delay tumor growth and reduce tumor volume when used alone. Tumor volumes were statistically different among the treatment groups. There was also a statistical difference in tumor volume between the retinoic acid treatment group and the combined pulsed-dye laser and retinoic acid treatment group. CONCLUSIONS: The study demonstrated the greater advantage of combining pulsed-dye laser with retinoic acid over using either retinoic acid or pulsed-dye laser alone for delay of oral cancer progression. Clinical trials are warranted to establish efficacy in humans.

Cancer "photo-chemoprevention" with pulsed dye laser and celecoxib.

BACKGROUND AND OBJECTIVES: Our previous study demonstrated the efficacy of pulsed dye laser (PDL) in inhibiting cancer growth. This study is to determine the synergic effect of PDL and Celecoxib, when they are combined for treatment of oral cancer. STUDY DESIGN/MATERIALS AND METHODS: Fifteen mice were inoculated with oral cell carcinoma and divided into three groups of five each (30 seeding sites/group): (1) control (no treatment), (2) PDL only, and (3) treatment with combined PDL and Celecoxib (1,500 ppm). The number and volume of tumors were counted and measured for 21 days. RESULTS: The combined treatment developed tumor at the slowest rate. On day 21, the average tumor volumes were (1) 483.6 mm(3) (control), (2) 312.1 mm(3) (PDL only), and (3) 151.4 mm(3) (combined treatment). CONCLUSIONS: A synergic effect was found in the combined treatment group. This study provides the first evidence of the efficacy of a new strategy for the treatment of oral cancer, namely, cancer "photo-chemoprevention."

Antiangiogenic and chemopreventive activities of celecoxib in oral carcinoma cell.

OBJECTIVES: Chemoprevention is a promising strategy to inhibit carcinoma before invasive tumors develop, but a new molecular target is desirable. Celecoxib is a newly developed cyclo-oxygenase (COX)-2 inhibitor with significantly less toxicity. The study was conducted to determine whether celecoxib is effective and safe in prevention of oral cancer. The antiangiogenic activity of celecoxib was studied to explore the potential mechanism involved. STUDY DESIGN: Randomized animal study. METHODS: The study consisted of two phases. In the phase 1,10 mice were used to determine the efficacy and safety of celecoxib with intradermal inoculation with oral carcinoma cells. The 10 mice were equally divided into two groups 5 mice (30 inoculated sites) in each group to receive 1,500 parts per million (ppm) celecoxib mixed in with the diet or to eat a normal diet, respectively, for 21 days. In phase 2, 10 more mice were inoculated to determine the effect of celecoxib on angiogenesis. Five mice received 3,000 ppm celecoxib in the diet, with the other five mice as control animals. The antiangiogenic activity was evaluated by comparing the density of newly growing microvessels after the inoculation. RESULTS: The results indicated that celecoxib significantly delayed cell growth and reduced tumor volume. There was statistical significance in the quantity of new vasculature in the tumor sites between the two groups. No toxic effect was found by means of measurement of body weight loss and microscopic dissection of organs. CONCLUSIONS: The study provided the first evidence to show the chemopreventive efficacy of celecoxib on oral cancer in a nude mouse model. Clinical trials are warranted to determine the efficacy in humans.