Biomarkers for Angiogenesis in Renal Cell Carcinoma and Neuro-endocrine Tumours.

The growth of renal cell carcinoma and neuroendocrine tumours depends on
angiogenesis. Vascular Endothelial Growth Factor (VEGF) has a stimulating role
in angiogenesis and catecholamines probably have a regulating role in
angiogenesis. Serotonine (5-HT) stimulates angiogenesis. Yet, the netto-effect
of dopamine (DA) is unknown; activation of the DA receptor D1 stimulates
angiogenesis, but on the other hand activation of the DA receptor D2 inhibits
angiogenesis. These catecholamines are stored in the granules of thrombocytes.
Our hypothesis is that the concentration catecholamines in thrombocytes of
patients differ from the concentrations catecholamines in thrombocytes of
healthy controls.
Angiogenesis inhibitors and mTOR inhibitors are the standard treatment of
patients with renal cell carcinoma, and in the future will be the standard
treatment of patients with neuroendocrine tumours. Because this medication
influences angiogenesis, we want to investigate whether the concentration DA
and 5-HT in thrombocytes differs between patients before start of a treatment
cycle and during a treatment cycle.

To analyse the concentration catecholamines in thrombocytes of patients with
clear cell renal cell carcinoma and low grade neuroendocrine tumours. To
compare these concentrations with the concentrations catecholamines in
thrombocytes of healthy controls. To analyse the concentration catecholamines
in thromocytes of patients with clear cell renal cell carcinoma and patients
with low grade neuroendocrine tumours before start of a treatment cycle and
during a treatment cycle.

This is a crossectional study. We obtain 10 mL blood of 20 patients with renal
cell carcinoma and 20 patients with a neuroendocrine tumour. The blood is drawn
twice: once during a treatment cycle with angiogenesis inhibitors or mTOR
inhibitors, and once before start of a treatment cycle. We will use this blood
to isolate thrombocytes and to measure the concentration catecholamines in
these thrombocytes. The concentration catecholamines in thrombocytes of the
healthy controls are available.

Blood samples will be obtained from the patients during routine check at the
outpatient clinic, when blood will be obtained for the follow-up. The methods
used are minimal invasive and no serious adverse effects of this procedure is
known.
In the future, we hope that the concentrations catecholamines in thromocytes
can be used as biomarkers for treatment response and control on efficacy of the
treatment.