Introduction: Head and neck squamous cell carcinoma (HNSCC) is a devastating and deadly disease, largely because it is diagnosed in late stage. Cure rates, currently at 50%, could increase to >80% with early detection. In this study, we evaluate soluble CD44 (solCD44) as an early detection tool for HNSCC by determining whether it reliably distinguishes HNSCC from benign disease of the upper aerodigestive tract. Methods: We carried out the solCD44 ELISA on oral rinses from 102 patients with HNSCC and 69 control patients with benign diseases of upper aerodigestive tract to determine the sensitivity and specificity of the test for differentiating HNSCC from benign disease. Furthermore, we did a pilot study using methylation-specific PCR primers on oral rinses from 11 HNSCC patients with low solCD44 levels and 10 benign disease controls.

This series equals the largest pediatric series of HIV-associated parotid gland BLEC in the English literature. One patient in our series also demonstrated PGL; there were no cases of BLEL. A classification system based on morphology is proposed to help resolve the confusion in terminology used to describe this entity. Most pediatric HIV-infected patients with parotid gland BLEC can be treated with observation and antiretroviral medication therapy. For others, who are symptomatic or more concerned about their cosmetic appearance, sclerotherapy may offer a reasonable option. Radiation therapy and surgery should be reserved for select cases.

Purpose: To determine the nature and potential pharmacologic reversibility of deficient TP53 expression and function in head and neck squamous cell carcinomas (HNSCC) with wild-type TP53, previously associated with decreased sensitivity to cisplatin therapy. Experimental Design: TP53 genotype, mRNA and protein expression, TP53-induced p21 expression, and TP53 DNA^binding and reporter gene function were determined in a panel of nine previously characterized HNSCC cell lines from the University of Michigan squamous cell carcinoma (UM-SCC) series. The genotoxic drug doxorubicin and the anti-inflammatory and antimalarial drug quinacrine, previously identified as inducers of TP53, were used to examine the nature and potential reversibility of deficient TP53 expression and function. The specific role of inducibleTP53 on function and cellular proliferation was confirmed using selectiveTP53 inhibitor pifithrin-a or short hairpin RNA knockdown. The capability of quinacrine to sensitize HNSCC to the cytotoxic effects of cisplatin was assessed. Results: UM-SCC cell lines with wild-type TP53 genotype underexpressed TP53 mRNA and protein when compared with normal human keratinocytes or UM-SCC with mutant TP53. Although doxorubicin failed to induce TP53 expression or functional activity, quinacrine induced TP53 mRNA and protein expression, increased TP53 reporter activity and p21 protein expression, and induced growth inhibition in these wild-type TP53 cell lines. Quinacrineinduced TP53 reporter activity and growth suppression were attenuated by pifithrin-a and TP53 short hairpin RNA knockdown. Furthermore, quinacrine sensitized UM-SCC to cisplatin in vitro. Conclusions: Deficient TP53 mRNA and protein expression underlies decreased function in a subset of HNSCC with wild-type TP53 and can be restored together with cisplatin sensitization by quinacrine. TP53, a tumor suppressor gene important in regulating cellcycle arrest, apoptosis, and therapeutic sensitivity, represents one of the most common targets for alterations underlying the development of cancer, including head and neck squamous cell carcinomas (HNSCC; refs. 1 -5). Mutation of TP53 occurs in f40% to 50% of HNSCC, resulting in altered TP53 expression and function (3 -5). In HNSCC that retain wild-type TP53 genotype, approximately one half expressed detectable TP53 protein, whereas approximately one half exhibited deficient expression by immunohistochemistry (6). In the latter subset of HNSCC that retain wildtype TP53 genotype, the alterations resulting in a defect in TP53 expression or function have been shown to include protein inactivation after infection with human papilloma virus (HPV), defects of p16INK4a and other components of the DNA damage response pathway, or unknown mechanisms. As a consequence, the differing nature and effects of these multiple alterations on TP53 expression and function likely contributed to the frequent discordance of results between studies using immunohistochemistry, genotyping, or other methods to define the role of TP53 in...

Meta-analysis of 1148 patients concludes that hemostasis during FESS is best conducted using TIVA, preoperative steroids, and topical local anesthetic at a 1:200,000 concentration.

Purpose: Gefitinib targeting of the epidermal growth factor receptor (EGFR) has shown limited activity in clinical trials of head and neck squamous cell carcinoma (HNSCC). To investigate the underlying molecular mechanism, the proteomic signatures and responses of EGFR and downstream signals have been studied in a panel of HNSCC cell lines and tumor specimens pre-and post-gefitinib treatment. Experimental Design:The IC 50 of gefitinib for HNSCC cell lines were determined using 3-(4,5-dmethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide proliferation assay. The effects of gefitinib on activation of EGFR and downstream signaling molecules were determined by Western blot, ELISA, and reverse-phase protein microarray (RPMA). The biomarkers involved in the signaling pathways were examined in HNSCC tumor specimens from patients in a phase I gefitinib trial. Results: In vitro, gefitinib inhibited cell proliferation with differing IC 50 , and suppressed activation of EGFR and downstream signaling molecules protein kinase B (AKT), extracellular signalregulated kinase 1/2, signal transducer and activator of transcription 3 (STAT3), and nuclear factor nB. The drug sensitivity was statistically correlated with activation of phosphorylated AKT (p-AKT) and phosphorylated STAT3 (p-STAT3) detected by ELISA, and consistent with results measured by RPMA. In patient samples, a broad suppression of activation of EGFR and downstream signaling molecules was observed in a molecular responder patient, in contrast to a lack of inhibition or increased activation of biomarkers in different pathways in nonresponder patients. Conclusions: Gefitinib sensitivity is correlated with p-AKT and p-STAT3 activation in HNSCC cell lines and tumor specimens. p-AKTand p-STAT3 could serve as potentially useful biomarkers and drug targets for further development of novel therapeutic agents for HNSCC.

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Intravenous administration of high-dose rFVIIa early after induction of hemorrhage decreased bleeding and prolonged survival. No evidence of thrombosis in vital organs was observed.

The real advantage of this novel use of the NB as a landmark to identify the AEA is that it is easy to use, unobtrusive, and is not time-consuming. This relationship between the NB and the AEA is consistent across genders and ethnicities and is more valuable than others presented previously, which may be more variable.