Antitumor vaccination in patients with head and neck squamous cell carcinomas with autologous virus-modified tumor cells.

Prognosis of patients with advanced head and neck squamous cell carcinomas (HNSCC) is still poor. Therefore, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe in HNSCC patients. Furthermore, we determined the influence on disease-free survival and overall survival and the vaccination-induced antitumor reactivity. In a nonrandomized pilot study, 20 patients were vaccinated postoperatively. Vaccine was prepared from the tumor cell cultures of patients by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and vaccine was applied up to five times. Antitumor immune reactivity was determined in the skin by delayed type hypersensitivity skin reaction and in the blood by enzyme-linked immunospot assay. Establishment of tumor cell cultures was successful in about 80% of the cases. After vaccination, we observed no severe side effects. Percentages of survival of vaccinated patients with stage III and stage IV tumors (n = 18) were 61% at 5 years. Immune monitoring revealed significant increases of antitumor delayed type hypersensitivity reactivity especially in disease-free patients, and in a significant proportion of vaccinated patients the presence of tumor-reactive T-cells in the peripheral blood even 5 to 7 years after the last vaccination. Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and may improve the prognosis of HNSCC patients with advanced tumors. This could be supported by antitumor immune responses that we observed especially in long-term surviving patients.

Expression of SGLT-1 in preneoplastic and neoplastic lesions of the head and neck.

Tumors show an increased glucose uptake that is mediated by glucose transport proteins. We have analyzed the expression of the sodium-dependent glucose co-transporters SGLT-1 and-2 in short-term cultures of squamous cell carcinomas of the head and neck (HNSCC) by RT-PCR. Distribution of the SGLT-1 protein in HNSCC tissues was investigated by immunohistochemistry. While we observed in 17/36 HNSCC short-term cultures the SGLT-1 mRNA, we found no SGLT-2 expression. SGLT-1 mRNA expression occurred preferentially in cultures originating from moderately and well differentiated HNSCC. In tumor tissues a heterogeneous SGLT-1 staining restricted to differentiated tumor cells was seen in 27/30 HNSCC analyzed. In normal mucosa SGLT-1 staining was also confined to differentiated compartments and lacked in dysplastic areas. Our data indicate a differentiation-dependent expression of SGLT-1 in HNSCC. This is important knowledge for the planning of glucose-targeting therapies and suggest SGLT-1 as a differentiation marker in head and neck tissues.

Expression profiles of angiogenic growth factors in squamous cell carcinomas of the head and neck.

Inhibition of angiogenesis by blocking angiogenic cytokines or their pathways has become a major target in experimental cancer therapies. This therapeutical approach requires a profound knowledge of growth factor profiles that contribute to tumor growth and progression. The respective knowledge is presently rather incomplete for head and neck squamous cell carcinomas (HNSCC). Therefore we studied expression of several angiogenic cytokines including VEGF, bFGF, PDGF-AB, PDGF-BB, G-CSF and GM-CSF in HNSCC in vivo and in vitro. In tumor tissues expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 15 tissue-corresponding HNSCC cultures revealed that VEGF, PDGF-AB and less frequently GM-CSF were secreted in high amounts of up to 13 ng/ml/10(6) cells. Twenty percent of the HNSCC cultures expressed only 1 cytokine in biologically active amounts, 60% 2 or 3 and 20% expressed the maximum of 4 cytokines simultaneously. Interestingly, we observed a distinct cytokine pattern: HNSCC cells secreting only 1 or 2 cytokines presented always with either VEGF and/or PDGF-AB, while G-CSF and GM-CSF were secreted primarily together with VEGF and PDGF-AB. The number of cytokines expressed by HNSCC cells correlated with the microvessel density of the original tumor and with the clinical outcome: tumors producing at least 3 cytokines revealed a significantly poorer patient prognosis. Our data indicate a major role for VEGF and PDGF-AB in HNSCC and that the additional secretion of G-CSF or GM-CSF might contribute to a poorer prognosis in patients suffering from these tumors.

Hearing loss in Usher syndrome type II is nonprogressive.

Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. In the literature, a possible progression of the moderate to severe hearing loss in Usher syndrome type II (Usher II) is controversial. We studied the development of the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type II intraindividually and interindividually by repeatedly performing complete audiological and neuro-otologic examinations. Our data show a very characteristic slope of the hearing curve in all Usher II patients and no clinically relevant progression of the hearing loss over up to 17 years. The subjective impression of a deterioration of the communicative abilities of Usher II patients must therefore be attributed to the progressive visual loss. The patients should be reassured that changes in their hearing abilities are unlikely and should be provided with optimally fitted modern hearing aids.