Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors.

Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. Here, we performed protein tyrosine kinase (PTK) profiling using PamChip® technology. The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib. Briefly, our results showed that 36 kinase substrates differs (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. In our assay, tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients.

Photodynamic therapy with methyl aminolevulinate for atypial carcinoma in situ of the penis.

OBJECTIVE: Photodynamic therapy (PDT) has been investigated as an alternative treatment for cutaneous squamous cell carcinoma in situ (CIS), also known as Bowen's disease. Atypia of the squamous epithelium is graded, with the most severe atypia being equivalent to CIS. CIS on the penis is regarded as a premalignant condition and is seen either in isolation or in conjunction with carcinoma of the penis. MATERIAL AND METHODS: A group of 10 patients with atypia/CIS were treated with PDT between December 2002 and April 2005. The group consisted of five patients with primary lesions and five with atypia after an organ-preserving operation for carcinoma of the penis. RESULTS: Eight patients were treated once, one twice and one six times. When complete remission was not achieved, a biopsy was taken for diagnosis. Three of the 10 patients had histopathological residual disease after a median follow-up period of 20 months (range 15-36 months). The first week after treatment could be painful but the cosmetic results were excellent. There was almost no loss of substance or fibrosis in the treated area, and sensitivity was restored to normal after approximately 1 month. CONCLUSIONS: In our experience, PDT for CIS seems to be a promising treatment modality with regard to cancer control, organ preservation, cosmetics and functional results. As with laser therapy of these lesions, careful follow-up is mandatory. Larger studies are needed and are planned.