We hypothesized that systemic inhibition of VEGF impairs general function and causes rarefaction, which in turn leads to the development of hypertension in patients treated with antiangiogenic agents. This study was performed on a subset of patients enrolled into an open label, nonrandomized, two middle, phase I dose increasing Natural products study of oral telatinib. The purpose of this study was to search for possible mechanisms that trigger hypertension in patients treated with antiangiogenic therapy and to ensure our hypothesis that systemic inhibition of VEGF checks vascular function and causes rarefaction. Patients with advanced level solid tumors with no regular treatment available were qualified to receive study participation. MAPK phosphorylation Inclusion criteria were life span of at least 12 wk, WHO efficiency position of 0 to 2, age of 18 y or older, and adequate bone marrow, liver, and renal function. Exclusion standards were Urogenital pelvic malignancy history of cardiac infection, history of HIV, hepatitis B, or hepatitis C infection, active scientifically serious infection, serious nonhealing injury, ulcer, or bone fracture, symptomatic metastatic brain or meningeal cancers, pregnancy or breast feeding, therapy with any anticancer agent or investigational drug 4 wk before the very first measure, antiangiogenic therapies/VEGFR 2 inhibitors before enrollment. The medial side study was performed on people which were addressed in the Leiden University Medical Center. The analysis protocol was approved by the Medical Ethical Committee of the Leiden University Medical Center. All patients gave written informed consent. Telatinib can be an orally active, small molecule inhibitor of the VEGFR 2, VEGFR three tyrosine kinases, and the growth factors receptors platelet derived growth factor receptor a and c Kit. Telatinib was constantly given once daily or twice daily within an verbal formulation as solution or capsule. Patients were divided in to cohorts with cell cycle inhibitor increasing doses. Treatment continued until progressive illness, undesirable toxicity, death, permission withdrawal, or withdrawal from research at the discretion of the researcher. Telatinib was supplied by Bayer Pharmaceuticals Corporation. We assessed blood pressure, vascular function, and structure variables at baseline, and after 5 wk of therapy, as well as regular assessment of variables for protection, efficacy, and pharmacokinetics. Blood pressure, flow mediated dilation, nitroglycerin mediated dilation, aortic pulse wave velocity, skin blood flux with laser doppler flow, and capillary density with sidestream dark field imaging were assessed at baseline and after 5 wk of therapy with telatinib. All measurements were done by the same experienced researcher, each morning, in a quiet, temperature controlled room.
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