Angiogenesis is essential for tumor growth and progression and is mediated by positive and negative regulators of vessel growth. Since angiogenic mediators found in patient's serum have been postulated to reflect the angiogenic potential of a malignant tumor, the angiogenic stimulators activity such as vascular endothelial growth factor (VEGF) and angiogenesis inhibitors such as endostatin have been evaluated in the serum of patients with colorectal caner (CRC) with and without liver metastases, in an attempt to study the prognostic value of the above parameters. The present work was conducted on thirty six patients with colorectal cancer and twelve control subjects. The patients' group included twenty localized colorectal cancer patients all of them had radical surgical resection. The second patients' group consisted of sixteen colorectal cancer patients with liver metastases. The serum endostatin and VEGF levels were significantly higher in the patients with colorectal cancer versus healthy controls. When compared according to tumor stage, the liver metastatic group had significantly higher levels of serum endostatin and VEGF versus the localized invasive group (without distant metastasis). Both groups of patients with localized invasive cancer and patients with liver metastasis had significantly higher mean serum endostatin and VEGF levels versus healthy controls. Serum endostatin and VEGF levels in localized invasive group decreased significantly after resection of the tumor. There was a significant positive correlation between preoperative endostatin and VEGF levels in all cancer patients. High preoperative VEGF and endostatin levels were strongly associated with the tumor size, tumor grade, lymph node metastases and subsequent recurrence. Significant positive correlation was, also, detected between endostatin levels and number as well as volume of hepatic metastases.The previous results denote that serum levels of endostatin, and VEGF were elevated and positively correlated in patients with CRC. The elevation was associated with the stage of CRC, greater disease burden and subsequent recurrence. Thus, elevation of serum levels of endostatin, and VEGF might be considered as indicators of tumor invasion and metastasis in the future. Thus, the present study demonstrates the prognostic utility of measuring angiogenic and antiangiogenic factors before resection of colorectal cancer.
The aim of the present work was to investigate the relationship between serum melatonin levels and other markers of oxidant/antioxidant balance in epileptic children before and after treatment with the antiepileptic drug valproic acid (VPA). The study was conducted on twenty epileptic children prior to starting therapy, as well as on another twenty age and sex matched epileptic children receiving treatment with the antiepileptic drug VPA, for a minimum duration of one year. Fifteen age and sex matched healthy children were included as a control group. Serum melatonin, zinc, copper, and malondialdehyde (MDA) concentrations and erythrocyte superoxide dismutase (SOD) activity were measured in all subjects. Mean levels of melatonin and MDA were significantly increased while SOD activity was significantly decreased in both untreated and treated epileptics versus control. However, the melatonin and SOD were significantly lower in treated versus untreated epileptics. The serum zinc levels were significantly lower while the serum copper levels were significantly higher in treated versus untreated epileptics. Melatonin was negatively correlated to MDA and copper and positively correlated to SOD. It thus seems possible that oxidant stress is associated with epilepsy and is aggravated with VPA therapy leading to relative reduction in melatonin (in treated versus untreated epileptics) and absolute reduction in erythrocytic SOD and serum zinc concentrations.
21137 Background: As opposed to mature blood vessels, the early sprouts (lacking the pericyte coverage) are selectively obliterated after Vascular Endothelial Growth Factor (VEGF) antagonists (e.g. Bevacizumab BV). Microvessel density (MVD) has been widely used to assess tumor vasculature however; it does not give an indication of the degree of vessel maturity since it assesses endothelial cells irrespective to the pericyte coverage. With the introduction of BV for treatment of metastatic colon, lung and breast cancers, predictive markers to guide patient selection are desirable but lacking. Methods: To assess the maturity of tumor vascular beds we used double-labeling immunohistochemistry to colocalize endothelial cells (CD31+) and pericytes (aSMA+) in archived material from colorectal liver metastasis (n=13). None of these subjects received BV or chemotherapy prior to sampling. To represent various regions within a section, counts were performed in designated-low, and -high vascular regions. IVP, the main study endpoint, was estimated in both regions, and then averaged by two independent pathologists without particular training in angiogenesis. Results: There was a considerable degree of heterogeneity in the IVP within this group (SD 12.5, mean 26.6). However, the agreement between the 2 pathologists was relatively high with an intra-class correlation coefficient of 0.655. Conclusions: Considerable tumoral vascular heterogeneity exists in colorectal liver metastasis. IVP may predict therapeutic benefits from BV. In this era of anti-angiogenic therapy and in view of the toxicity and the financial burden of these agents, better patient selection using biologically relevant techniques such as the one described here need to be considered. IVP is a candidate tool with multiple advantages; it utilizes abundantly available material (subject to reconfirmation or testing in different settings), does not require particular training and appears reproducible. No significant financial relationships to disclose.
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