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Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2012)

Title: Effect of Xylitol-Wipe on Mutans Streptococci Virulence

Purpose: In a randomized clinical trial, we found a significant reduction of new caries in young children with daily use of xylitol-wipes over one year without reduction on mutans streptococci (MS) levels. The purpose of this study was to determine whether the use of xylitol-wipes for one year was due to selection of xylitol-resistant MS, altered the rate of acid production of MS and/or altered biofilm formation ability of MS.

Methods: Unique MS genotypes were isolated from the xylitol-wipe group and the placebo-wipe group at baseline and at 1 year. These isolates were examined for their xylitol sensitivity, rate of acid production and ability to form biofilm. Xylitol sensitivity was determined by comparing bacterial growth curves in TPY glucose broth with or without the addition of 1% xylitol. Acid production was monitored by the means of pH drop for 30 minutes after each isolate was grown in the presence of glucose. Sucrose dependent biofilm formation of each genotype was quantified using crystal violet assay.

Results: At one year, there was no significant difference in prevalence of xylitol-resistant MS genotypes between the xylitol-wipe and the placebo-wipe groups. There was significant decrease difference in plateau pH within each group from baseline to 1 year (p<0.05). The change in acid profile in the xylitol-wipe group from baseline to 1 year was similar to that observed in the caries vs. no caries group. There were no statistical significant differences in biofilm formation of MS isolated from the two wipe groups at baseline or one year (p>0.05).

Conclusions: This prospective randomized clinic trial has shown no correlation between caries reduction and selection of xylitol-resistant MS. Furthermore, xylitol-wipe use did not alter the ability of MS to form biofilm. However, there is evidence to suggest that after one year xylitol wipe use would select MS with decrease acid production ability. Future studies are needed to identify other possible mechanisms of caries prevention resulting from the use of xylitol-wipes in children.

    Cover page: Effect of Xylitol-Wipe on Mutans Streptococci Virulence
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2021)
    Although immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (PD-1), can deliver durable antitumor effects, most patients with cancer fail to respond. Recent studies suggest that ICI efficacy correlates with a higher load of tumor-specific neoantigens and development of vitiligo in patients with melanoma. Here, we report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes. Moreover, expansion of peripheral blood CD8+ T cell populations specific for melanocyte antigens was observed only in patients who responded to anti-PD-1 therapy, suggesting that ICI can promote breakdown of tolerance toward tumor-lineage self-antigens. In a mouse model of poorly immunogenic melanomas, spreading of epitope recognition toward wild-type melanocyte antigens was associated with markedly improved anti-PD-1 efficacy in two independent approaches: introduction of neoantigens by ultraviolet (UV) B radiation mutagenesis or the therapeutic combination of ablative fractional photothermolysis plus imiquimod. Complete responses against UV mutation-bearing tumors after anti-PD-1 resulted in protection from subsequent engraftment of melanomas lacking any shared neoantigens, as well as pancreatic adenocarcinomas forcibly overexpressing melanocyte-lineage antigens. Our data demonstrate that somatic mutations are sufficient to provoke strong antitumor responses after checkpoint blockade, but long-term responses are not restricted to these putative neoantigens. Epitope spreading toward T cell recognition of wild-type tumor-lineage self-antigens represents a common pathway for successful response to ICI, which can be evoked in neoantigen-deficient tumors by combination therapy with ablative fractional photothermolysis and imiquimod.
      Cover page: Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses
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