| The differentiation between malignant and benign ascites is a common clinical problem of considerable importance for further diagnostic and therapeutic procedures. Cytological examination, despite its high specificity, has been found to have a low sensitivity in the diagnosis of malignant ascites due to the high percentage of false negative results. So it is indispensable to find appropriate cancerous marks in ascites.Angiogenesis is essential for tumor invasion and metastasis. Tumor cells have been shown to secrete a variety of angiogenic factors and thereby induce the local formation of new blood capillaries. Among these factors, vascular endothelial growth factor (VEGF, also called vascular permeability factor, VPF), a bifunctional cytokine, enhancing vascular permeability and stimulating endothelial growth, is recognized as one of the most important molecules in the growth invasion metastasis and recurrence of human tumors.However, tumor invasion and metastasis is considered to be a complex and multi-step process. Since the initial observation that a splice variant of CD44 (CD44V) could endow nonmetastasizing cells with metastatic potential, many studies have demonstrated that CD44V, especially splice variant 6 of CD44 (CD44V6), probably promoting cancer cells to adhere to vascular endothelium and base membranes and enhancing moving ability of cancer cells, is most likely responsible for the invasion and metastasis of several tumors systems.Although tumor invasion and metastasis is considered to be a dynamic, complex and multi-step process, proteolytic degradation of the extracellular maxtrix (ECM) made of interstitial matrix and basement membrane is the essential step. In the disruption of the ECM, the contribution of matrix metalloproteinase (MMPs) of proteolytic enzymes is direct and important in that it catalyzes the hydrolysis of numerous ECM molecules. While in the matrix metalloproteinase, type IV collagenase, one of the most important member of MPPs family, including a 72 kD enzyme resembling matrix metalloproteinase-2, MMP-2, also named gelatinase A and a 92 kD enzyme resembling matrix metalloproteinase-9, MMP-9, also named gelatinase B, has been demonstrated closely associating with several tumors systems and linking to invasive potential of tumor cells. For type IV collagenase can degrade not only interstitial matrix, but also basement membrane.And malignant ascites is the direct and prominent manifestation of advancedmalignant disease that is associated with invasion and metastasis of peritoneal cavity by tumor cells. Thus it is reasonable to hypothesize that VEGF, CD44V6 and type IV collagenase (MMP-2, MMP-9)can be detected in malignant ascites. In the present study, we detected VEGF, CD44V6 levels using a sandwich enzyme-linked immunoadsorbent assay and MMP-2, MMP-9 activity by gelatin zymography in peritoneal fluid and ascites. We believe this work would be helpful to provide scientific basis for clinic diagnosis and treatment of malignant ascites. To our knowledge, this is the first study to elucidate a correlation among VEGF, sCD44v6, type IV collagenase and malignant ascites.The protocol of this research would be carried out as follows:1. To detect LDH, cytologic examination of the ascites and complex indexed in serum by department of clinical laboratory and pathology2. Levels and changes of soluble VEGF in peritoneal fluid and ascites3. Concentrations and changes of of sCD44V6 in peritoneal fluid and ascites4. To determine type IV collagenase activity by gelatin zymography5. To investigate mutual relationship among VEGF, CD44V6 and type IV collagenase in malignant ascitesIn the present study, we found that VEGF protein levels were markedly higher in malignant ascites than those in benign ascites, which was consistent with the previous results, and possessed a high sensitivity and specificity to diagnose malignant ascites. Meanwhile, we also found that VEGF levels in malignant ascites from patients with ovarian cancer were higher than those with gastric can... |
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