Biomedical subjects

Douglas K Trask

Publications and source records attributed to Douglas K Trask.

10 recordsLinked to original sources

PubMed2007

Differential activity of sulindac metabolites against squamous cell carcinoma of the head and neck is mediated by p21waf1/cip1 induction and cell cycle inhibition.

Sulindac sulfide and sulindac sulfone have demonstrated anti-neoplastic and chemo-preventive activity against various human tumors, but few studies have examined the relative effectiveness of these drugs against squamous cell carcinoma of the head and neck (SCCHN). These compounds are metabolites of the nonsteroidal anti-inflammatory drug sulindac and differ in their ability to inhibit cyclooxygenase-2 (COX-2) enzyme function. Sulindac sulfide (the sulindac metabolite with COX-2 inhibitory function) demonstrated strong cell growth inhibition as measured by MTT and growth assays in UM-SCC-1 and SCC-25 cells, while sulindac sulfone had only moderate effect. Growth inhibition by sulindac sulfide was associated with a significant increase in percent G cells and activation of caspase-3. Sulindac sulfide induced expression of p21wafl/cipl in a dose-dependent fashion, decreased cyclin D1 protein levels, and increased Rb hypophosphorylation. p21waf1/cip1 protein levels increased without a significant increase in wild-type p53, suggesting that sulindac sulfide induces a p53-independent pathway regulating p2lwafl/ciP1 protein levels in SCCHN. Sulindac sulfide also induced dose-dependent expression of PPAR-gamma. In contrast, sulindac sulfone did not significantly alter apoptosis, cell cycle distribution or G1 checkpoint protein expression at doses below 200 microM. These results demonstrate the differential activity of sulindac metabolites and support the hypothesis that sulindac sulfide induced perturbations in SCCHN cellular proliferation could be regulated both by p21waf1/cip1-dependent cytostatic and caspase-dependent cytotoxic pathways.

Apoptosis↗

PubMed2005

Long-term quality of life for surgical and nonsurgical treatment of head and neck cancer.

OBJECTIVE: To compare the long-term, health-related quality-of-life outcomes in patients with advanced head and neck cancer (HNC) treated with surgery and postoperative radiation therapy (SRT) or concurrent chemotherapy and radiation therapy (CRT). DESIGN: Matched-pair study comparing patients with advanced HNC treated with SRT or CRT at least 12 months after treatment. Patients completed 2 validated surveys addressing HNC-specific outcomes and depressive symptoms and provided information on employment and tobacco and alcohol use. Results for the 2 groups were compared using paired-sample t test and chi2 analysis. SETTING: University-based study. PATIENTS: Patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, and larynx who underwent SRT or received CRT. MAIN OUTCOME MEASURES: Head and neck cancer-specific health-related quality of life from the Head and Neck Cancer Inventory and level of depressive symptoms from the Beck Depression Inventory. RESULTS: The matching process resulted in 27 patients in each treatment group. The HNC-specific domain scores (with higher scores representing better outcomes) for CRT vs SRT were eating, 37.8 vs 40.8 (P = .69); speech, 65.1 vs 56.0 (P = .23); aesthetics, 80.3 vs 69.2 (P = .14); and social disruption, 69.7 vs 70.6 (P = .90). Overall health-related quality of life was 64.0 with SRT and 55.0 with CRT (P = .142). For the Beck Depression Inventory (with higher scores representing worse outcomes), patients who underwent SRT had a mean score of 9.6 compared with 11.6 for patients who received CRT (P = .42). CONCLUSION: As nonsurgical means of treating HNC have become more aggressive and surgical techniques have become more focused on function preservation and rehabilitation, the overall health-related quality of life resulting from these different approaches is similar.

Combined Modality Therapy↗

PubMed2005

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.

Collagen↗

PubMed2005

Reversal of cisplatin resistance with a BH3 mimetic, (-)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL.

Organ preservation protocols in head and neck squamous cell carcinoma (HNSCC) are limited by tumors that fail to respond. We observed that larynx preservation and response to chemotherapy is significantly associated with p53 overexpression, and that most HNSCC cell lines with mutant p53 are more sensitive to cisplatin than those with wild-type p53. To investigate cisplatin resistance, we studied two HNSCC cell lines, UM-SCC-5 and UM-SCC-10B, and two resistant sublines developed by cultivation in gradually increasing concentrations of cisplatin. The cisplatin-selected cell lines, UM-SCC-5PT and UM-SCC-10BPT, are 8 and 1.5 times more resistant to cisplatin than the respective parental cell lines, respectively. The parental lines overexpress p53 and contain p53 mutations but the cisplatin-resistant cell lines do not, indicating that cells containing mutant p53 were eliminated during selection. Bcl-x(L) expression increased in the cisplatin-resistant lines relative to the parental lines, whereas Bcl-2 expression was high in the parental lines and decreased in the cisplatin-resistant lines. Thus, cisplatin selected for wild-type p53 and high Bcl-x(L) expression in these cells. We tested a small-molecule BH3 mimetic, (-)-gossypol, which binds to the BH3 domain of Bcl-2 and Bcl-x(L), for activity against the parental and cisplatin-resistant cell lines. At physiologically attainable levels, (-)-gossypol induces apoptosis in 70% to 80% of the cisplatin-resistant cells but only in 25% to 40% of the parental cells. Thus, cisplatin-resistant cells seem to depend on wild-type p53 and Bcl-x(L) for survival and BH3 mimetic agents, such as (-)-gossypol, may be useful adjuncts to overcome cisplatin resistance in HNSCC.

Antineoplastic Agents↗

PubMed2005

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.

Acanthoma↗

PubMed2004

Molecular profiling and the identification of genes associated with metastatic oral cavity/pharynx squamous cell carcinoma.

OBJECTIVE: To investigate differences in gene expression profiles between oral cavity/oropharynx squamous cell carcinoma (OC/OP SCC) primary tumors that have metastasized to cervical lymph nodes and nonmetastatic OC/OP SCC tumors. DESIGN: Oligonucleotide microarray analysis of primary tumors was used to produce gene expression profiles. Profile comparisons between metastatic and nonmetastatic tumors were performed using principal component analysis, t test, and fold change differences. A similar comparison between metastatic tumors and noncancer oral mucosa samples was performed to ensure tumor origin. SUBJECTS: A prospective cohort of 20 patients with previously untreated OC/OP SCC who underwent pathologic staging following surgical resection and lymphadenectomy. RESULTS: Of the approximately 9600 genes profiled, 101 demonstrated significant expression differences between the metastatic and nonmetastatic tumors (fold change > or =1.5; P<.01). Among this subset, 57 genes also exhibited significant differences between metastatic tumors and normal mucosa samples (fold change > or =1.5; P<.05). This profile included genes related to the extracellular matrix, adhesion, motility, inflammation, and protease inhibition. Collagen type 11 alpha-1 (COL11A1) demonstrated the greatest differential expression between metastatic and nonmetastatic OC/OP SCC tumors (fold change=7.61; P=.002). Tissue inhibitor of metalloproteinase 1 (TIMP-1) also demonstrated increased expression in metastatic tumors (fold change=3.3; P=.003). CONCLUSIONS: Metastatic OC/OP SCC has a distinct gene expression profile compared with nonmetastatic OC/OP SCC and normal oral mucosa. This metastatic profile includes genes related to the extracellular matrix, adhesion, motility, and protease inhibition. Knowledge gained through tumor gene expression profiling may facilitate early detection of aggressive tumors and targeted therapeutic interventions.

Carcinoma, Squamous Cell↗

PubMed2004

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

BACKGROUND: 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. METHODS: In vitro [(125)I] iodide accumulation and efflux from cells was determined after treatment with an NIS-expressing adenovirus (Ad-NIS). A clonogenic survival assay and tumor growth experiment that used athymic mice were used to demonstrate the in vitro and in vivo cytotoxicity of Ad-NIS treatment and [(131)I] iodide delivery. RESULTS: Head and neck squamous cell carcinoma (HNSCC) cell lines treated with Ad-NIS exhibit significant amounts of radioiodide accumulation and retention. In vitro HNSCC cell survival was significantly diminished after NIS gene delivery followed by administration of [(131)I] iodide. Moreover, NIS gene transfer/[(131)I] iodide administration dramatically attenuated HNSCC tumor formation in athymic mice. CONCLUSIONS: Our data demonstrate the feasibility of genetically targeted radiotherapy by use of the NIS gene as a possible therapeutic intervention in head and neck cancer.

Adenoviridae↗

PubMed2003

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.

Aged↗

PubMed2002

Presentation, treatment, and outcome of oral cavity cancer: a National Cancer Data Base report.

BACKGROUND: 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. METHODS: This study used the National Cancer Data Base (NCDB) to evaluate associations between demographic and disease characteristics, treatment, and survival for patients with oral cavity cancer in the United States. Of patients diagnosed between 1985 and 1996, 58,976 were extracted from the NCDB. ANOVAs were performed on selected cross-tabulations, and relative survival was used to calculate outcome. RESULTS: Median age of patients was 64.0 years. Men made up 60.2% of patients. Pathologic diagnosis was squamous cell carcinoma (SCC) in 86.3% of cases. Younger patients had a much higher frequency of non-SCC, and this was related to survival in these patients. African-Americans (independent of income), lower income patients, and patients with higher grade disease were seen more frequently with advanced-stage SCC. Five-year relative survival for SCC cases was lower for older patients, men, and African-Americans. CONCLUSIONS: This study addressed many issues related to oral cancer that have been previously discussed in the literature. The demographic, site, stage, histologic, and survival data available for this large number of cases in the NCDB allowed an accurate characterization of the contemporary status of oral cancer in the United States.

Adult↗

PubMed2002

Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ preservation.

OBJECTIVES/HYPOTHESIS: Induction chemotherapy and definitive radiation therapy in advanced laryngeal cancer has been shown to achieve survival rates that are similar to total laryngectomy and postoperative radiation therapy. In patients with advanced laryngeal cancer, quality of life can be significantly enhanced by treatment regimens that preserve the larynx. However, which patients will respond best to organ preservation protocols remains unknown. The Bcl-2 family proteins are involved in control of apoptosis and, potentially, tumor response to chemotherapy. STUDY DESIGN: Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome. METHODS: To determine whether Bcl-2 family proteins were predictive of successful organ preservation, immunohistochemical analysis of tissue specimens from 47 patients with advanced laryngeal cancer from the U.S. Department of Veterans Affairs Cooperative Study Program (VA CSP-268) were evaluated for the expression of Bcl-2, Bcl-X(L), and Bax protein expression. Tumor response was classified as either complete or partial/nonresponse after induction chemotherapy. Protein expression was correlated with tumor response, organ preservation, and overall patient survival. RESULTS: The Bcl-2 protein was expressed at high levels in only 15% of specimens, but five of seven tumors with high Bcl-2 showed complete response (P = .10). The majority of tumors expressed high levels of Bcl-X(L) (74%). Reduced expression of Bcl-X(L) was associated with a complete response (P = .143) and with larynx preservation (P = .06). Most patients (81%) had increased levels of Bax expression. Reduced expression of Bax was associated with a complete response rate (P = .074), but there was no correlation between Bax expression and larynx preservation. CONCLUSIONS: The findings indicate that laryngeal cancer cells typically produce high levels of only one of the apoptosis protective proteins, Bcl-2 or Bcl-X(L). Prospective studies of larger numbers of patients are under way to determine whether Bcl-X(L) expression will be a useful marker predicting larynx preservation.

Antineoplastic Combined Chemotherapy Protocols↗