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Preclinical studies have shown that the inhibition of ornithine decarboxylase (ODC) by α-difluoromethylornithine (DFMO) and resultant decreases in tissue concentrations of polyamines (putrescine and spermidine) prevents neoplastic developments in many tissue types. Clinical studies of oral DFMO at 500 mg/m2/day revealed it to be safe and tolerable and resulted in significant inhibition of phorbol ester–induced skin ODC activity. Two hundred and ninety-one participants (mean age, 61 years; 60% male) with a history of prior nonmelanoma skin cancer (NMSC; mean, 4.5 skin cancers) were randomized to oral DFMO (500 mg/m2/day) or placebo for 4 to 5 years. There was a trend toward a history of more prior skin cancers in subjects randomized to placebo, but all other characteristics including sunscreen and nonsteroidal anti-inflammatory drug use were evenly distributed. Evaluation of 1,200 person-years of follow-up revealed a new NMSC rate of 0.5 events/person/year. The primary end point, new NMSCs, was not significantly different between subjects taking DFMO and placebo (260 versus 363 cancers, P = 0.069, two-sample t test). Evaluation of basal cell (BCC) and squamous cell cancers separately revealed very little difference in squamous cell cancer between treatment groups but a significant difference in new BCC (DFMO, 163 cancers; placebo, 243 cancers; expressed as event rate of 0.28 BCC/person/year versus 0.40 BCC/person/year, P = 0.03). Compliance with DFMO was >90% and it seemed to be well tolerated with evidence of mild ototoxicity as measured by serial audiometric examination when compared with placebo subjects. The analysis of normal skin biopsies revealed a significant (P < 0.05) decrease in 12-0-tetradecanoylphorbol-13-acetate–induced ODC activity (month 24, 36, and 48) and putrescine concentration (month 24 and 36 only) in DFMO subjects. Subjects with a history of skin cancer taking daily DFMO had an insignificant reduction (P = 0.069) in new NMSC that was predominantly due to a marked reduction in new BCC. Based on these data, the potential of DFMO, alone or in combination, to prevent skin cancers should be explored further. Cancer Prev Res; 3(1); 35–47

Perspective on this Article from A Randomized, Double-Blind, Placebo-Controlled Phase 3 Skin Cancer Prevention Study of α-Difluoromethylornithine in Subjects with Previous History of Skin Cancer

The disposal of municipal solid waste ash has become a significant economic and environmental issue. Municipal solid waste ash can be considered to have a fly ash and a bottom ash component. Municipal solid waste bottom ash (MSWBA) from a refuse-derived fuel facility was evaluated as a potential portland cement concrete ingredient. Portland cement–related ASTM methods and other analytical techniques such as X-ray diffraction were used. The sample MSWBA was found to be a marginal concrete aggregate. The sample MSWBA met most ASTM C 331 standards such as size gradation, but the high angularity and brittle nature of the MSWBA would significantly affect concrete workability. The MSWBA sulfate and chloride concentrations also were high enough to create potential sulfate attack and reinforcing steel corrosion problems. Iron removal and aggregate processes such as size control offer cost effective methods to improve MSWBA for use as an aggregate.

Preclinical studies have shown that the inhibition of ornithine decarboxylase (ODC) by α-difluoromethylornithine (DFMO) and resultant decreases in tissue concentrations of polyamines (putrescine and spermidine) prevents neoplastic developments in many tissue types. Clinical studies of oral DFMO at 500 mg/m2/day revealed it to be safe and tolerable and resulted in significant inhibition of phorbol ester–induced skin ODC activity. Two hundred and ninety-one participants (mean age, 61 years; 60% male) with a history of prior nonmelanoma skin cancer (NMSC; mean, 4.5 skin cancers) were randomized to oral DFMO (500 mg/m2/day) or placebo for 4 to 5 years. There was a trend toward a history of more prior skin cancers in subjects randomized to placebo, but all other characteristics including sunscreen and nonsteroidal anti-inflammatory drug use were evenly distributed. Evaluation of 1,200 person-years of follow-up revealed a new NMSC rate of 0.5 events/person/year. The primary end point, new NMSCs, was not significantly different between subjects taking DFMO and placebo (260 versus 363 cancers, P = 0.069, two-sample t test). Evaluation of basal cell (BCC) and squamous cell cancers separately revealed very little difference in squamous cell cancer between treatment groups but a significant difference in new BCC (DFMO, 163 cancers; placebo, 243 cancers; expressed as event rate of 0.28 BCC/person/year versus 0.40 BCC/person/year, P = 0.03). Compliance with DFMO was >90% and it seemed to be well tolerated with evidence of mild ototoxicity as measured by serial audiometric examination when compared with placebo subjects. The analysis of normal skin biopsies revealed a significant (P < 0.05) decrease in 12-0-tetradecanoylphorbol-13-acetate–induced ODC activity (month 24, 36, and 48) and putrescine concentration (month 24 and 36 only) in DFMO subjects. Subjects with a history of skin cancer taking daily DFMO had an insignificant reduction (P = 0.069) in new NMSC that was predominantly due to a marked reduction in new BCC. Based on these data, the potential of DFMO, alone or in combination, to prevent skin cancers should be explored further. Cancer Prev Res; 3(1); 35–47

The disposal of municipal solid waste ash has become a significant economic and environmental issue. A sample municipal solid waste bottom ash (MSWBA) was previously evaluated as a potential aggregate for concrete masonry units (CMUs). Test results indicate MSWBA could be used as an aggregate in concrete mixes to produce CMUs that meet ASTM C 90 standards when it is processed for maximum size and gradation and ferrous removal by magnetic separation. Techniques such as aggregate gradation and the addition of coal fly ash and other admixtures offer cost effective methods for performance improvements of mixes using MSWBA as an alternative to the use of additional cement. The MSWBA was found to be deficient in sand size particles and an aggregate blend of 35% sand and 65% MSWBA significantly increased both densities and strength. The addition of sand mitigated workability problems created by the very angular and irregular shape of the MSWBA, but the workability of all mixes using MSWBA was poorer than mixes with commercial aggregate. Twenty-eight-day compressive strengths of up to 2,440 psi (16.8 MPa) and a one year continuous mist cure strength of over 3,000 psi (20.7 MPa) were obtained from mixes using 10% cement, either microsilica or coal fly ash, and a plasticizer. A Class C coal fly ash and a masonry plasticizer both provided improved strengths at all ages. A 24-hour cycle atmospheric steam cure produced strength results averaging only 55% of all mixes compared with a mist cure at ages beyond 180 days. Although the sulfate content of the MSWBA exceeded recommended limits, different cement types all produced equivalent strengths.