Apoptosis induction by E2F-1 via adenoviral-mediated gene transfer results in growth suppression of head and neck squamous cell carcinoma cell lines.

E2F-1, a transcription factor by discovery, is thought to play a crucial role in regulating G1/S cell cycle progression. Its activity is modulated by complex formation with the retinoblastoma protein and related proteins. Overexpression of E2F-1 has been shown to induce apoptosis in quiescent fibroblasts. We constructed a recombinant E2F-1 adenovirus to test whether an overexpression of E2F-1 in head and neck squamous cell carcinoma cell lines would also induce apoptosis. Two cell lines, Tu-138 and Tu-167, were chosen for use in this study. Both cell lines harbor p53 mutations but express different levels of the retinoblastoma protein. Upon E2F-1 adenovirus infection, both cell lines expressed elevated levels of E2F-1 protein and then activated a pRb-chloramphenicol acetyltransferase reporter construct containing an E2F-1 binding motif. In vitro growth assay demonstrated that growth suppression by the E2F-1 protein was effective on both cell lines. Results from DNA fragmentation and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling analyses indicated apoptosis induction in cells infected with AdCMV-E2F-1. Moreover, ex vivo experiments in nude mice showed total suppression of tumor growth at sites that received cells infected AdCMV-E2F-1. An in vivo analysis of apoptosis using in situ end-labeling further demonstrated the induction of apoptosis by AdCMV-E2F-1 in tumor-bearing animals. These data indicate that overexpression of E2F-1 via an adenoviral vector suppresses in vitro and in vivo growth of head and neck squamous carcinoma cell lines through induction of apoptosis.

Severity staging in chronic sinusitis: are CT scan findings related to patient symptoms?

Chronic sinusitis is a prevalent problem. The symptoms of CS cause patients to seek medical attention, and therefore the presence of symptoms drives the use of health care resources. There is widespread clinical belief that computed tomography (CT) scan findings may be a reasonable proxy for disease severity in chronic sinusitis, and many authors have proposed that CT scan findings make up the key component in severity staging systems for chronic sinusitis. However, the relationship between symptom severity and CT scan findings in chronic sinusitis has not been well explained to date. To explore this relationship further, we examined data from consecutive patients with both a CT scan and a sinusitis symptom score, from ongoing prospective outcomes studies at two large academic centers in different cities (n = 254). CT scans were graded using two validated staging systems; symptom severity was assessed using two validated health status instruments and summary items. In addition, we explored multiple statistical modifications and permutations of CT staging to identify potential relationships between the two variables. In summary, no association between CT scan findings and symptom severity could be identified using both CT staging systems and patient-based symptom instruments. For instance, CT scans were examined: after eliminating normal scans, using different scoring algorithms, by worst side, by nonlinear association, when grouped into strata, and by eliminating patients with very severe disease; no statistical association was found between CT findings and patient-based symptoms using any of those techniques. Since symptom severity is a pivotal outcome measure in chronic sinusitis, these findings have significant implications for outcomes research and the development of severity staging systems.

Surgical outcomes in head and neck cancer patients 80 years of age and older.

BACKGROUND: Elderly patients over 80 years of age represent a growing population, some of whom have complex medical problems that are compounded by the presence of upper aerodigestive tract cancer. METHODS: Forty-three patients, aged 80 years and older, who were initially seen with head and neck squamous cell carcinoma from 1986 to 1992 at a tertiary-care center were compared with 79 similar patients, aged 65 years or younger, in a retrospective, case-control study. RESULTS: Median overall survival for the patients over 80 years of age was significantly lower than that for the controls (p = .001). However, their overall survival was similar to the actuarial survival for the general octogenarian population. Advanced age also adversely affected local control (p < .001) and disease-specific survival (p = .041). Although the older age group had a higher frequency of morbid preoperative conditions, there were no significant differences in perioperative or postoperative complications between the two groups. CONCLUSIONS: Careful preoperative staging and evaluation of associated medical illnesses, as well as skillful perioperative and postoperative management, are essential for reducing operative morbidity and mortality in the octogenarian patient. Successful outcome depends upon appropriate surgical management, treatment of concurrent illnesses, and minimization of postoperative complications. Individualized surgical management of the elderly head and neck cancer patient is effective, well tolerated, and clinically indicated for upper aerodigestive tract malignancies.