Vascular endothelial growth factor levels in ovarian cyst fluid correlate with malignancy.

Ovarian cancer is a richly vascularized neoplasm with solid and cystic components. The purpose of this study was to determine whether cyst fluid could be used to quantitatively evaluate production of angiogenic factors in ovarian lesions. ELISA was used to measure vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cyst fluid of patients with ovarian cancer (n = 13), benign cysts and cystadenomas (n = 23), borderline tumors (n = 5), and functional cysts (n = 8). VEGF levels were markedly elevated in the fluid of malignant cysts (38.5+/-8.2 ng/ml) as compared with benign (1.6+/-0.4 ng/ml; P < 0.001), borderline (5.7+/-1.5 ng/ml; P < 0.001), or functional cysts (3.8+/-2.0 ng/ml; P < 0.001). The presence of VEGF in cancer cells was confirmed by immunohistochemistry. Follow-up of patients with malignant and borderline lesions demonstrated a correlation between VEGF levels in cyst fluid and tumor recurrence (P = 0.03). bFGF in malignant cysts was either undetectable or very low (0.3+/-0.2 ng/ml), and no significant differences were found in bFGF levels among malignant, benign, borderline, and functional cysts. This study demonstrates that ovarian malignancy is associated with dramatic elevation of VEGF levels in ovarian cyst fluid. Conversely, there is no correlation between cyst fluid bFGF levels and malignant transformation. The high levels of VEGF in malignant cysts are consistent with the hypothesis that this growth factor plays an important role in ovarian cancer related-angiogenesis and tumor progression and represents a potentially important target of antiangiogenic therapy.

Vascular endothelial growth factor in ovarian cancer.

Tumor growth requires nutrients and oxygen. Both nutrients and oxygen are provided via the vasculature. Thus, when a tumor increases in volume, new blood vessels must form and invade the expanding tumor. This process, called angiogenesis, has theoretical significance in the context of ovarian cancer for two reasons. First, the process of angiogenesis and vessel regression occurs in a tightly controlled way as part of normal ovarian function. This suggests that at least some ovarian cells are primed to produce the paracrine stimulus needed for new blood vessel growth and that, on transformation, this capability is present early in tumor development. Second, the characteristically large size of ovarian tumors indicates that angiogenesis is mandatory to sustain the tumor. In this article, we review the experimental and clinical correlative data that support the hypothesis that ovarian cancers are highly angiogenic. Because a critical component of angiogenesis is the paracrine and autocrine production of vascular endothelial cell growth factor, there is substantial focus on this topic.

Endogenous regulation of angiogenesis in the rat aorta model. Role of vascular endothelial growth factor.

The purpose of this study was to investigate the role of vascular endothelial growth factor (VEGF) in the rat aorta model of angiogenesis. Freshly cut aortic rings generated microvascular outgrowths in serum-free collagen gel culture. Angiogenesis was reduced to 10% when the explants were embedded in collagen 10 to 14 days after excision from the animal. Immunochemical studies of conditioned medium demonstrated secretion of VEGF by the aortic cultures. Levels of VEGF decreased during the second week of culture when the explants became quiescent and microvessels stopped growing. Treatment of quiescent aortic rings with exogenous VEGF stimulated angiogenesis and restored microvascular growth to values observed in cultures of freshly cut explants. Reverse transcriptase polymerase chain reaction of vasoformative collagen gel cultures of rat aorta demonstrated the expression of the alternatively spliced isoforms VEGF165, VEGF189, and the high affinity VEGF receptor flk-1. Reverse transcriptase-polymerase chain reaction of rat aorta-derived cell strains confirmed the presence of VEGF165 and VEGF189 in endothelial cells, smooth muscle cells, and fibroblasts. The flk-1 receptor was expressed by endothelial cells but not by fibroblasts or smooth muscle cells, which is consistent with the endothelial target specificity of VEGF. The spontaneous angiogenic response of freshly cut aortic rings was inhibited by 70% with a neutralizing antibody against VEGF, whereas nonimmune IgG had no effect (P < 0.001). These findings provide evidence for a VEGF-mediated autocrine/paracrine regulation of angiogenesis in the rat aorta model.

Bacterial contamination of arterial lines. A prospective study.

One hundred seventeen patients had indwelling arterial illness for hemodynamic monitoring and blood sampling. The duration of catheterization varied from 25 to 439 hours, during which time no components of the system were replaced. In contrast to other reports, our study showed no instance of contamination of transducer dome fluid when the continuous flush device was located just distal to the transducer. The sampling stopcock showed bacterial growth in 16.2% of patients. In the one case in which the arterial catheter tip, stopcock, and patient's blood showed the same organism, culture of the transducer fluid was negative. Our results suggest that elimination of a static inline fluid column and proper aseptic sampling technique limit risk to the patient of transmitted bacterial infection from the fluid in the system. Routine changes of components of the system are not indicated and a substantial cost saving can be achieved.