ABSTRACT
Vascular endothelial growth factor receptor (VEGFR-2), a member of the super family of protein tyrosine kinase receptors, plays a vital role in the regulation of tumor metastasis and angiogenesis. Several VEGFR-2 inhibitors have been marketed as antitumor drugs and a range of inhibitors are undergoing clinical or preclinical studies. According to the principle of multi-targeted pharmacolgy, in the field of tumor treatment, nonselective drugs targeting on more than one kinase to inhibit different cell pathways can be more effective than drugs specific for one kinase. Multi-target treatment does not mean abandonment of selectivity, but a precise selectivity for several kinases related to tumor, which is also a big challenge in the development of small molecular antitumor drugs. This paper reviews briefly the advances in research of the VEGFR-2 inhibitors and selectivity strategy in recent years.
ABSTRACT
<p><b>BACKGROUND</b>Extra glucose load in peritoneal dialysis is an important cause of newly-occurred diabetic mellitus, which initiates insulin treatment in some of the dialytic patients. The purpose of this study was to discuss the influence of the peritoneal transfer status on fasting blood glucose in non-diabetic nephropathy patients who are on continuous ambulatory peritoneal dialysis (CAPD).</p><p><b>METHODS</b>One hundred and forty-five patients with total KT/V per week over 2.0 were recruited, including 60 males and 85 females. Fasting blood glucose (FBG), creatinine, blood urea nitrogen (BUN), blood albumin, blood lipid profile and blood C-reactive protein (CRP) were analyzed at the beginning of the peritoneal dialysis and after 12 months. A peritoneal equilibration test (PET) was carried out at the 3rd month of CAPD, and meantime residual renal function, peritoneal solute clearance rate, ultrafiltration volume and urine volume were also evaluated.</p><p><b>RESULTS</b>Twenty-one cases were identified as a low transfer group (L), 32 cases as a low average transfer group (LA), 58 cases as a high average transfer group (HA) and 34 cases as a high transfer group (H). At the end of the 12th month, 83 cases had elevated FBG. Through stepwise multiple regression analysis we found the FBG level in these patients was positively related to glucose load and CRP, and negatively related to glucose absorption in the peritoneum (D/D(0)) and blood albumin (P < 0.05). Kaplan-Meier analysis during a 48-month follow-up found the morbidity of hyperglycemia to be 17/34 cases (50.1%) in the high transfer group, 20/58 cases (34.5%) in the high average transfer group, 11/32 cases (34.3%) in the low average transfer group, and 1/21 cases (5.4%) in the low transfer group.</p><p><b>CONCLUSIONS</b>Patients with high peritoneal transfer capacity might have the highest morbidity from hyperglycemia among patients with these four different peritoneal transfer status. Glucose load, baseline CRP and FBG level before peritoneal dialysis, and D/D0 can efficiently predict hyperglycemia in CAPD patients.</p>