No abstract

p63 expression may be a marker of basal/progenitor cells in tumors of epidermis and epidermal appendages, and may be a diagnostic marker of these tumors.

Cytokeratin (CK), filaggrin (filament aggregating protein), and p63 expression and cellular distribution during reepithelialization has not been systemically studied in the healing stage of human cutaneous wounds. We examined these proteins by immunohistochemical methods in 12 cases of skin ulcer, using seven anti-keratin antibodies, anti-filaggrin, and anti-p63 antibody. At the edge of the wound in skin ulcers, CK1 and 10 expression was reduced, while CK14, 16, and 17 expression was raised. Beneath the wound bed, all layers of the epidermal tongue, deriving from sweat ducts, were positive for CK14 and 17. Both cytokeratins were also found in basal and luminal cells of the dermal duct. CK expression by epithelia continuous with hair follicles showed that, CK14, 16, and 17 were present, and CK1 and 10 were absent. Filaggrin expression was elevated in reepithelialized epithelium. Expression of p63 expression was verified in the suprabasal layer in reepithelialized epithelia. CK, filaggrin, and p63 expression in the reepithelialization stage at the wound edge and at epidermal appendages remaining in the wound bed is undifferentiated and hyperproliferative. The presence of CK14 and 17 in the remaining epidermal appendages in the pathological wound may be important in epidermal replacement.

We compared the effects of identical amounts but different proportions of dietary n-3 polyunsaturated fatty acids (PUFAs) on N-methyl-N-nitrosourea (MNU)-induced mammary cancer in a rat model. The ability of dietary docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to suppress mammary cancer was evaluated. Female Sprague-Dawley rats were randomly assigned to three groups and maintained on diets containing 10% fatty acid consisting of EPA, a 1:1 mixture of EPA-plus-DHA, or DHA. The experimental diet was started after administration of MNU at 49 days of age, and the rats were maintained on the respective diets until the largest mammary tumor reached >1 cm in diameter or until the end of the study period (20 wk after MNU). All histologically detected mammary carcinomas were evaluated, irrespective of size. The DHA diet was associated with significant suppression of the carcinogenic effect of MNU compared with the EPA and EPA-plus-DHA diets: tumor incidence decreased to 23% (3/13) compared with 73% (11/15) and 65% (12/17) (P < 0.01 and P < 0.05, respectively); tumor multiplicity decreased to 0.23 compared with 1.67 and 1.59 (P < 0.01 and P < 0.05, respectively). There was no significant difference in tumor latency among the DHA, EPA, and EPA-plus-DHA groups (119, 105, and 117 days, respectively). Over 20 wk, the fatty acid composition of serum and mammary fat tissue reflected differences in the dietary n-3 PUFAs. Although DHA suppressed MNU-induced mammary carcinogenesis more effectively than EPA, generalized steatosis including mammary fat tissue appeared in all three groups.

The effect of monoterpene perillyl alcohol (POH) on cell growth, cell cycle progression, and expression of cell cycle-regulatory proteins in estrogen receptor (ER)-positive (KPL-1 and MCF-7) and ER-negative (MKL-F and MDA-MB-231) human breast cancer cell lines was examined. POH inhibited cell proliferation in a dose-dependent manner in all cell lines tested. POH at a dose of 500 micro M had a cytostatic effect, in which growth inhibition was due to accumulation of cells in G1-phase. Cell cycle progression was preceded by a decrease in G1 cyclins (cyclin D1 and E), followed by an increase in p21(Cip1/Waf1) and a decrease in proliferating cell nuclear antigen level. Levels of p53 and cyclin A were unchanged. POH at a dose of 75 mg/kg administered intraperitoneally three times a week throughout the entire 6-week experimental period suppressed orthotopically transplanted KPL-1 tumor cell growth and regional lymph node metastasis in a nude mouse system. POH inhibited both ER-positive and -negative human breast cancer cell growth in vitro, and suppressed growth and metastasis in vivo.