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Transforming growth factor-beta is known to be a potent autocrine growth inhibitor produced by a wide variety of cells, including cells of the immune system. Other investigators have noted that the growth of nontransformed keratinocytes is inhibited by transforming growth factor-beta, whereas various carcinoma cell lines are resistant to these effects. Head and neck squamous cell carcinoma cells are known to have surface receptors for this cytokine. We thus assessed the effect of transforming growth factor-beta on the growth of head and neck squamous cell carcinoma cell lines. Four head and neck squamous cell carcinoma cell lines were incubated with varying concentrations of transforming growth factor-beta, and cytotoxicity was evaluated with a methylene blue colorimetric assay. After culturing in transforming growth factor-beta for 4 days, inhibition of growth was detected in CAL-27 (maximal inhibition at 5.0 ng/ml), UMSCC-1, and UMSCC-19 (maximal inhibition at 50 ng/ml) cell lines. One other cell line, UMSCC-8 was found resistant to the inhibitory effects of transforming growth factor-beta. Kinetics analysis experiments revealed minimal inhibition before day 2 of incubation, at which time inhibition increased linearly to day 4. Assessment of double-stranded DNA fragmentation suggested that DNA fragmentation occurs before significant cytotoxicity. Electron microscopic analysis and gel electrophoresis of extracted DNA revealed morphologic features consistent with apoptotic cell death. Our findings indicate that transforming growth factor-beta significantly inhibits the growth of head and neck squamous cell carcinoma cell lines by inducing apoptotic cell death.

A database of questions and answers has been developed to assist residents in reviewing current topics in otolaryngology-head and neck surgery. Each question/item has an associated answer, general category, specific category, and reference that allows cross-referencing on the computer system. The user can search the database for categories of interest and obtain a specific subset of questions. This allows an efficient means of knowledge acquisition and review for Board examinations. Additional data entry is also facilitated to expand the database as desired. Currently there are more than 2300 items in the database.

Patients with head and neck squamous cell carcinomas (HNSCCs) manifest defects in cell-mediated immune function. Previous studies in this laboratory have demonstrated regional alterations in the immunocompetence of draining lymph nodes (LNs) in HNSCC patients. In this investigation, we studied functional activity of lymphocytes from lymph nodes in different locations in the radical neck dissections (RNDs) from patients undergoing operations for HNSCC. Lymphocytes from nodes close to the primary tumor ("near" lymph nodes or NLN) exhibited a significant decrease in interleukin-2 (IL-2)-activated cytotoxicity when compared to lymphocyts from distant nodes ("far" lymph nodes or FLN). In addition, co-culture experiments suggested the existence of a soluble regulatory factor, produced by lymph nodes, that inhibited the development of lymphokine-activated killer (LAK) cells in vitro. Further experiments with conditioned supernatants from the lymph node cells confirmed the presence of this soluble inhibitory factor. The inhibitory effect is significantly greater in NLNs than in FLNS. This hierarchical phenomenon suggests a regional network of immunosuppression in HNSCC patients. It is likely that tumor- and lymph node-induced suppression plays a role in limiting the efficacy of current immunotherapy protocols in human beings. A greater understanding of mechanisms of local inhibition of immune function will aid in improving adoptive immunotherapy for treatment of cancers in human beings.

Incubation of human peripheral blood lymphocytes (PBL) in the presence of interleukin-2 results in the generation of lymphokine-activated killer (LAK) cells that are highly cytotoxic to a variety of autologous and allogenic tumor targets. We have identified a noncytotoxic, soluble factor, produced by human squamous cell cancers of the head and neck, that profoundly inhibits the generation of LAK cytotoxicity. Inhibition of the generation of cytotoxicity was demonstrated with coculture of PBL and freshly disaggregated tumor cells in a Transwell two-chamber system. Alternatively, inhibition occurred when LAK cells were generated in the presence of tumor-conditioned supernatants alone. These effects were not observed with conditioned supernatants from autologous or allogenic lymphocytes, human fibroblasts, or the erythroleukemia cell line K562. The presence of this inhibitory factor(s) was not required during the entire period of LAK generation. Suppression of cytotoxicity, measured after 4 days of LAK generation, could also be demonstrated when the conditioned tumor supernatant was present in only the last 24 hours of incubation. Suppression is mediated by a heat-labile factor with a molecular weight of greater than 75 kd. These results suggest that LAK cytotoxicity may be significantly impaired by soluble immunoregulatory factors present within the tumor milieu of squamous cell carcinomas of the head and neck. Further characterization of these factors may lead to the development of more rational and effective forms of immunotherapy.

While metastatic tumors to the nose and the paranasal sinuses overall are unusual, metastasis to the sphenoid sinus is exceedingly rare. Presented are 26 cases of metastasis to the sphenoid sinus. Seven were treated at UCLA between 1955 and 1988, and 19 additional cases were discovered from a search of the medical literature. The patients ranged from 14 months to 79 years of age. The most common tumor sites from which sphenoid metastases arose were the prostate and the lung. In 11 of the 26 cases, the sphenoid sinus metastasis was the first presentation of malignancy. Patients manifested signs and symptoms that were indistinguishable from those from primary tumors of the sinus. They included headache, facial pain, visual changes, and single or multiple cranial neuropathies. While cure of patients with sphenoid metastasis has not been reported, significant palliation with resolution of morbidity is possible in many patients with radiation therapy. Although metastasis to the sphenoid sinus is an uncommon entity, when present, signs and symptoms relating to this metastasis are frequently the first presentation of disease. As such, patients with sphenoid sinus symptoms suggestive of sphenoid sinus malignancy should be vigorously evaluated for the possibility of primary as well as metastatic tumor of the sinus.