Oral lactoferrin results in T cell-dependent tumor inhibition of head and neck squamous cell carcinoma in vivo.

PURPOSE: Human lactoferrin is a naturally occurring glycoprotein that inhibits cancer growth. Our purpose was to evaluate recombinant human lactoferrin as a chemotherapeutic agent against head and neck squamous cell carcinoma. EXPERIMENTAL DESIGN: Controlled experiments both in vitro and in the murine model evaluating both the effect and mechanism of lactoferrin on cancer growth. RESULTS: In both human and murine cell lines, lactoferrin induced dose-dependent growth inhibition. Using flow cytometric analysis, lactoferrin was shown to induce G(1)-G(0) growth arrest. This arrest seemed to be modulated by down-regulation of cyclin D1. In the in vitro model, luminex data revealed that lactoferrin inhibited cellular release of proinflammatory and prometastatic cytokines, including interleukin-8, interleukin-6, granulocyte macrophage colony-stimulating factor, and tumor necrosis factor-alpha. Lactoferrin up-regulated the cellular activation of nuclear factor-kappaB within 4 h of cellular exposure. In C3h/HeJ mice implanted with SCCVII tumors, orally delivered lactoferrin inhibited tumor growth by 75% compared with control mice. Immunohistochemical analysis of harvested tumors revealed up to 20-fold increases of lymphocytes within treated animals. When mice were depleted of CD3(+) cells, all lactoferrin-induced tumor inhibition was abrogated. CONCLUSION: We conclude that human recombinant lactoferrin can inhibit the growth of head and neck squamous cell carcinoma via direct cellular inhibition as well as systemically via immunomodulation. Our data support the study of human lactoferrin as an immunomodulatory compound with therapeutic potential.

Sites of attachment of Schneiderian papilloma: a retrospective analysis.

BACKGROUND: Inverted papilloma is a benign sinonasal tumor that arises from a localized attachment site. These attachment sites, however, have not been fully characterized in the literature. The objective of this research was to determine the specific distribution of attachment sites in patients with sinonasal papilloma. METHODS: Retrospective analysis of adult patients with sinonasal papilloma presenting to the University of Virginia between 1999 and 2010. These patients were reviewed and compared to historical controls with regard to histologic subtype and pedicle attachment site. RESULTS: A total of 83 patients were identified with 90 sites of attachment. For inverted/cylindrical papilloma, sites of attachment included the maxillary sinus (42%), ethmoid sinus (18%), nasal cavity (15%), middle/superior turbinate (12%), frontal sinus (10%), sphenoid sinus (1.5%), and cribriform plate (1.5%). Specific attachment sites within each group were identified, including 5 at the infraorbital nerve. The distribution of attachment sites differed significantly from historical controls resected via an open approach (p = 0.001), but did not differ significantly from historical controls endoscopically resected (p = 0.696). A comparison of more specific sites of attachments could not be performed due to the lack of this information in the literature. CONCLUSION: The distribution of attachment sites in patients with sinonasal papilloma has changed as the endoscope has enabled more detailed identification of pedicle attachment, which has implications for management.