Douglas K. Trask

Presentation, treatment, and outcome of oral cavity cancer: A national cancer data base report

Oral cancer has been identified as a significant public health threat. Systematic evaluation of the impact of this disease on the US population is of great importance to health care providers and policy makers.

National survey of head and neck verrucous carcinoma : Patterns of presentation, care, and outcome

Verrucous carcinoma is distinguished by controversy regarding appropriate diagnosis and treatment. This study provides a contemporary survey of demographics, patterns of care, and outcome for this disease in the United States.

Celecoxib Toxicity Is Cell Cycle Phase Specific

Celecoxib inhibits proliferation and induces apoptosis in human tumors, but the molecular mechanisms for these processes are poorly understood. In this study, we evaluated the ability of celecoxib to induce toxicity in head and neck squamous cell carcinomas (HNSCC) and explored the relationships between celecoxib-induced cell cycle inhibition and toxicity in HNSCC. Celecoxib inhibited the proliferation of UM-SCC-1 and UM-SCC-17B cells both in vitro and in vivo, accompanied by G(1) phase cell cycle arrest and apoptosis. Celecoxib induced p21(waf1/cip1) at the transcriptional level independent of wild-type p53 function, leading to decreased expression of cyclin D1 and hypophosphorylation of Rb, with subsequent marked downstream decreases in nuclear E2F-1 protein expression and E2F transactivating activity by luciferase reporter assay. Cell cycle phase-specific cytometric sorting showed that celecoxib induced clonogenic toxicity preferentially to cells within the S phase greater than G(1) and G(2) phases. Levels of p21(waf1/cip1) and cyclin D1 protein were reduced in the S phase compared with the G(1) and G(2) phases, suggesting a possible protective role for p21(waf1/cip1) expression in celecoxib toxicity. In conclusion, we show that celecoxib has marked antiproliferative activity against head and neck cancer cells through transcriptional induction of p21(waf1/cip1) and G(1) phase accumulation leading to S phase-specific clonogenic toxicity. We additionally show that a profound inhibition of nuclear E2F function provides a possible mechanism for this S phase-specific toxicity.

Validation of tissue microarrays using p53 immunohistochemical studies of squamous cell carcinoma of the larynx.

Tissue microarrays are a powerful new tissue-conserving technology in the study of cancer, allowing simultaneous study of a large number of tumor specimens. We sought to ascertain the utility of tissue microarrays in head and neck cancer pathology using squamous cell carcinoma of the larynx as a model system. Whole-specimen slides from 44 different laryngeal squamous cell carcinomas were stained for p53 expression. Microarrays were then generated by taking six 0.6-mm core biopsies from each of the 44 specimens. The whole sections and the microarrays were independently scored for p53 expression. Twenty-three (53%) of the 44 tumor specimens were positive for p53. Forty-four of the 264 core biopsies (17%) were not given a score because of the lack of tumor cells. Seventy-eight percent of the individual discs on the microarray had scores in agreement with those of the whole-section slides. Among biopsy discs with tumor cells present, 94.5% were in agreement with the whole-section slide. The average probability that four randomly chosen biopsy discs, considered together, would accurately identify the presence of p53 staining in a whole section was 0.97 (95% CI .93–1.0). We conclude that tissue microarrays for squamous cell carcinomas can accurately represent immunohistochemical results of whole-slide specimens when four or more samples are used. Tissue microarrays are an important technique that may be applied to immunohistochemical studies of head and neck cancer.

Transnasal, Endoscopic Vocal Fold Augmentation

The practice of injection laryngoplasty under local anesthesia has become more common as both the indications for the procedure and the number of injectable substances increased. Modifications to the injection techniques used for vocal fold augmentation have been described over the last decade that reflect changes in the established percutaneous and transoral approaches. These percutaneous and transoral injection techniques for the treatment of dysphonia secondary to glottic incompetence are well described and provide an adequate approach for most cases. However, these traditional methods may be difficult to master, require great patient tolerance, and may be impossible to perform when anatomic or physiologic barriers exist. We describe a new application of the fiberoptic transnasal endoscope to perform laryngeal injection using a flexible needle through a port in the endoscope. This technique is easily mastered and readily tolerated by patients who would not be candidates for the other injection techniques under local anesthesia. We present our favorable experience with this technique and identify its shortcomings coupled with recommendations to address future technical modifications.

GRO: A Novel Chemotactic Cytokine

Cytokines are small secreted regulatory peptides that act primarily in a paracrine fashion to provide a signalling system between different cell types. Although cytokine functions were initially associated with myeloid and lymphocytic responses to infection, current studies are demonstrating regulatory functions in growth and differentiation as well. Our studies with the GRO gene represent one of the first to describe a novel cytokine expressed by fibroblasts and epithelial cells as well as cells of the immune system, with regulatory functions both in growth and in the inflammatory response (1, 2, 3).

Modulation of Cellular Invasion by VEGF-C Expression in Squamous Cell Carcinoma of the Head and Neck

OBJECTIVE To determine how vascular endothelial growth factor C (VEGF-C) affects tumor cell invasion and motility in squamous cell carcinoma of the head and neck (SCCHN). DESIGN A molecular biology study. The VEGF-C coding sequence was cloned into an expression vector and stably transfected into the SCCHN cell line SCC116 to create the SCC116-VEGFC line. RNA interference (RNAi) was used to block VEGF-C expression. An adenoviral system for expressing VEGF-C RNAi was developed and tested. SETTING An academic hospital laboratory. MAIN OUTCOME MEASURES Relative VEGF-C RNA levels were determined by real-time quantitative reverse transcriptase-polymerase chain reaction, and protein expression was evaluated by Western blot. Cellular invasion was evaluated by 24-hour semipermeable membrane transit assay. RESULTS SCC116-VEGFC cells had markedly increased expression of VEGF-C protein and RNA compared with normal SCC116 controls. SCC116-VEGFC cells produced marked increases in cellular invasion and motility compared with SCC116 cells. Blockade of VEGF-C expression by transfection of a VEGF-C RNAi expression plasmid into both SCC116 and SCC116-VEGFC cells induced a 38% decrease in SCCHN invasion and motility as tested by a semipermeable membrane invasion assay. We developed an adenoviral expression system for VEGF-C RNAi, which also induced a dose-dependent decrease in cellular invasion in the highly invasive DM12 cell line. CONCLUSIONS These studies demonstrate that intracellular VEGF-C levels modulate in vitro SCCHN motility and invasion. Further work is needed to clarify the specific receptors and signaling pathways that are involved in SCCHN motility. Molecular therapies that inhibit the VEGF-C pathway may have clinical potential in the treatment of lymphatic metastasis in SCCHN.

Genetically targeted radiotherapy of head and neck squamous cell carcinoma using the sodium-iodide symporter (NIS)

Gene therapy that uses delivery of the sodium‐iodide symporter (NIS) gene followed by radioiodide administration has been proposed as a novel form of radiotherapy for nonthyroidal cancers.

Relative non-steroidal anti-inflammatory drug (NSAID) antiproliferative activity is mediated through p21-induced G1 arrest and E2F inhibition.

This study was performed to compare the relative antineoplastic activity of 10 different non‐steroidal anti‐inflammatory drugs (NSAIDs) in clinical use, and to investigate the underlying mechanisms of this activity in a squamous cell carcinoma of the head and neck model (SCCHN). A standard 5‐day MTT assay was used to calculate IC50 values in UM‐SCC‐1 cells for 10 NSAIDs, including celecoxib, rofecoxib, sulindac sulfide, sulindac sulfone, indomethacin, ketoprofen, flurbiprofen, naproxen, piroxicam, and aspirin. Celecoxib, a COX‐2 specific inhibitor, was by far the most potent NSAID, with an IC50 of 39.9 ± 1.1 µM, followed by sulindac sulfide (116.5 ± 2.34 µM). Celecoxib and sulindac sulfide also induced more activation of caspase‐3 than any other NSAID. Cell cycle analysis showed that celecoxib and sulindac sulfide both induced a 3‐fold increase in G1 phase distribution, and this correlated with strong induction of p21waf1/cip1, inhibition of cyclin D1, and hypophosphorylation of Rb. Celecoxib and sulindac sulfide treatment induced strong downstream inhibition of E2F transactivating activity as determined by a luciferase reporter assay. These data demonstrate the wide range of activity of various NSAID agents, and reveal a mechanism of action through cell cycle inhibition and induction of apoptosis.

Oral Melanoacanthoma: A Case Report, a Review of the Literature, and a New Treatment Option

Objectives: Oral melanoacanthoma is a rare condition that presents as a pigmented, painful lesion, most commonly on the buccal mucosa. Argon plasma coagulation is a new treatment option for benign oral lesions and is hypothesized to be efficacious for this rare mucosal disorder. Methods: Treatment of a case and a review of the English-language literature were performed. Results: One patient received a diagnosis of oral melanoacanthoma, and argon plasma coagulation treatment resulted in ablation of the lesion with excellent mucosal healing. A review of the literature demonstrated that this lesion is most commonly associated with black (90.9%), adult female (69.7%) patients and is most commonly located on the buccal mucosa (64.7%). Conclusions: Oral melanoacanthoma is a rare, benign mucosal lesion that may require surgical intervention for symptomatic relief. Argon plasma coagulation is a relatively safe and effective means of treating this lesion. Argon plasma coagulation treatment may be expanded to include other benign, superficial lesions of the oral mucosa.