Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis.

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) are highly invasive tumours with frequent local and distant recurrence. Metastasis formation requires degradation of the extracellular matrix, which is fulfilled by membrane-associated proteases such as the urokinase plasminogen activator (uPA). WX-UK1 is a competitive active site inhibitor of the protease function of uPA that impairs on the capacity of tumour cells to invade in vitro. METHODS: In the present study, effects of combinations of WX-UK1 with matrix metalloprotease inhibitors (MMP, galardin) and cyclooxygenase-2 (COX-2, celecoxib) inhibitors on tumour cell proliferation, invasion, and angiogenesis induction were evaluated. Matrigel invasion chambers and a spheroid co-cultivation model with human fibroblast served to determine the invasive potential of both FaDu (SCCHN) and HeLa (cervical carcinoma) cells, each treated with combinations of Celecoxib, Galardin, and WX-UK1. RESULTS: Blocking of single protease systems resulted in a significant 50% reduction of tumour cell invasion using WX-UK1, while the triple combination was even more effective with 80% reduction of invasion. Additionally, a sprouting assay with HUVEC was used to test the anti-angiogenetic potential of the triple combination, resulting in a 40% decrease in the sprouting rate. CONCLUSIONS: A combined approach targeting different families of proteases and cyclooxygenases represents a promising adjuvant therapy.

Cytological and Immunocytological Monitoring of Oropharyngeal Dysplasia and Squamous Cell Carcinomas.

BACKGROUND/AIM: Due to the high recurrence rates of squamous cell carcinoma of the head and neck (SCCHN) and de-novo local secondary carcinomas, a close monitoring of patients is mandatory. In doubtful cases, a clearance by histological biopsy is necessary. This, however, bears potential complications. We analyzed the application of combined cytology and immunocytology in cytological brush smears for diagnosing pre-malignant and malignant lesions of the oral/oropharyngeal cavity. MATERIALS AND METHODS: Brush biopsies of 30 subsequently histologically-confirmed oral/oropharyngo-/laryngeal cavity cancer cases (all then in a recurrence status) and normal mucosa were obtained for routine cytology and immunocytology for cytokeratin-8 (CK-8). Additionally 20 samples with inflammatory lesions were investigated. RESULTS: Our results showed a high rate for positive prediction of oral/oropharyngo-/laryngeal dysplasia/cancer cases. Accordingly, 82% of all subsequently confirmed cases were detected by cytology alone (sensitivity). The specificity, however, of cytology was distinctly lower since several doubtful cases contained only inflammatory lesions (specificity 85%). The addition of CK-8-immunocytology did not increase the sensitivity, since the rate of detected cases by immunocytology was comparable to routine cytology (79%); however, the addition of immunocytology significantly increased the specificity (up to 90%). CONCLUSION: Routine cytology is a simple, non-invasive and cost-effective method for routine control and screening of dysplastic oral/oropharyngo-/laryngeal lesions. In doubtful cases, the addition of CK-8-immunocytology is very helpful for the distinction of reactive from neoplastic cases.