Chemoprevention of mammary carcinoma by LGD1069 (Targretin): an RXR-selective ligand.

Recently, 9-cis retinoic acid, a high affinity ligand for retinoic acid receptors and retinoid X-receptors (RXRs), was shown to have efficacy superior to all-trans retinoic acid as a chemopreventive agent in the N-nitroso-N-methylurea-induced rat mammary carcinoma model. To further explore the specific contribution RXR activation may play in suppression of carcinogenesis, the efficacy of LGD1069 (Targretin), an RXR-selective ligand, in the N-nitroso-N-methylurea-induced rat mammary tumor model was studied. LGD1069-treated animals showed a 90% reduction in tumor burden and tumor incidence compared with vehicle-treated rats with an efficacy similar to that achieved with tamoxifen. LGD1069 was very well tolerated during 13 weeks of chronic therapy with no classic signs of "retinoid-associated" toxicities. These data demonstrate that LGD1069, an RXR-selective ligand, can act as a highly effective and benign chemopreventive agent for mammary carcinoma.

Chronic peroral immunization of conventional laboratory rats with mutans streptococci leads to stable acquired suppression of salivary antibodies.

Prior investigations have demonstrated that salivary antibody responses to mutans streptococci are dose-dependent and temporary. The purpose of this study was to evaluate the stability of antibody suppression established by mutans streptococci. Streptococcus mutans 6715-15 was provided in food to conventional rats for 18 weeks. Antigen was withdrawn for 10 weeks and then resumed for an additional 6 weeks. Saliva and serum from nonimmunized controls and from experimental rats were tested with a quantitative enzyme-linked immunosorbent assay for IgA and IgG antibodies to whole bacterial cells and to soluble antigen. Results show that salivary antibodies were stimulated by primary peroral immunization, that IgA was the dominant isotype and that IgA antibodies were primarily directed against soluble antigen. This study also shows that immunity is not maintained, even while challenge continues, and that once suppression is established, immunized animals do not recover their ability to respond, even if exposure is stopped for 10 weeks before re-exposure.

Identification of spirochetes related to Treponema pallidum in necrotizing ulcerative gingivitis and chronic periodontitis.

BACKGROUND: Spirochetes are commonly associated with periodontal disease, but it is not known whether these treponemes are pathogenic or merely opportunistic. We sought to determine whether spirochetes present in periodontal disease share antigens thought to be unique to spirochetes that are known pathogens. METHODS: We examined dental plaque from 24 healthy subjects, from ulcerative sites in 17 patients with ulcerative gingivitis, and from areas of involvement in 19 patients with chronic periodontitis, using an immunocyto-chemical technique with monoclonal antibodies against pathogen-specific determinants on 47-kd and 37-kd molecules from Treponema pallidum subspecies pallidum. Serum was tested against T. pallidum by immunoblotting and by serologic assays for syphilis. RESULTS: Spirochetes with a pathogen-specific epitope on a 47-kd molecule were not found in plaque samples from any of the 24 healthy subjects, but they were identified in plaque samples from 11 of 17 patients with ulcerative gingivitis (P less than 0.001) and from 10 of 19 patients with periodontitis (P less than 0.01). Monoclonal antibodies directed against a 37-kd molecule reacted with spirochetes in plaque samples from 1 of 14 controls, from all 11 patients with gingivitis from whom samples could be obtained (P less than 0.001), and from 14 of 19 patients with periodontitis (P less than 0.001). Five of 18 normal subjects had IgG against 47-kd and 37-kd molecules, but none had IgG against 14-kd or 12-kd molecules from T. pallidum subspecies pallidum. Among 19 patients with ulcerative gingivitis, IgG was identified against 47-kd molecules in 15, against 37-kd molecules in 12, against 14-kd molecules in 4, and against 12-kd molecules in 15. CONCLUSIONS: The spirochetes found in dental plaque from patients with ulcerative gingivitis or chronic periodontitis have antigens that are thought to be unique to pathogenic treponemes. This close antigenic relation suggests that T. pallidum or a closely related organism may be involved in the pathogenesis of periodontal disease.

Chronic peroral administration of Streptococcus sobrinus to conventional laboratory rats produces cycling levels of salivary antibodies.

Conventional outbred rats were fed Streptococcus sobrinus for 24 weeks and ELISA was used to identify isotypes of antibodies against bacteria in saliva and serum. Quantities of antibodies from experimental rats were compared with values derived from the control population. Saliva IgM and IgA anti-S. sobrinus from experimental rats were greater than controls at week 3, were much less at week 9, but normal levels were found by week 13. IgG antibodies in saliva peaked at weeks 5 and 9 but fell to control levels by week 13. Relative levels of antibodies in saliva of experimental animals continued to cycle during weeks 13-24 but did not differ greatly from controls. Serum IgM and IgG antibodies to S. sobrinus were essentially like controls throughout the experiment. Serum IgA increased briefly during the first 12 weeks then returned to normal levels. The results suggest that prolonged peroral exposure to cariogenic bacteria ultimately leads to modulation of antibody around unimmunized control levels even though antigenic stimulation persists.