ABSTRACT
PURPOSE: To elucidate the mechanism of neoangiogenesis in human retinal pigment epithelium under oxidative stress. METHODS: Paraquat was added to cultured human retinal pigment epithelium (HRPE) for 72 hours to induce oxidative stress milieu. Expression and production of angiogenic factors, including vascular endothelial growth factor (VEGF) and pigment epithelial derived factor (PEDF), was checked by RT-PCR and Western blot, respectively. The induction of neoangiogenesis was monitored by both tube formation in ECV 304 cell and migration assay of human fetal dermal microvascular endothelial cells. RESULTS: Competitive RT-PCR showed that PEDF gene in paraquat-treated HRPE was expressed at a significantly lower level than in non-treated HRPE. However, Western blot showed a significant increase of VEGF production (p<0.05) and a decrease of PEDF production (p<0.05). Moreover, angiogenesis was dose-dependently increased when the various concentrations of paraquat were added to HRPE. CONCLUSIONS: Taken together, oxidative stress by addition of paraquat caused HRPE to produce more VEGF and less PEDF, thereby leading to neoangiogenesis, and suggesting that the neovascularization in age-related macular degeneration (AMD) is caused by destroying the balance of angiogenic factors in HRPE such as VEGF and PEDF; that is, in oxidative stressed HRPE, more VEGF is released and less PEDF, as compared to normal HRPE.
Subject(s)
Humans , Angiogenesis Inducing Agents , Blotting, Western , Endothelial Cells , Macular Degeneration , Oxidative Stress , Paraquat , Retinal Pigment Epithelium , Vascular Endothelial Growth Factor AABSTRACT
p53 is a tumor suppressor gene product identified in a wide range of tumor including colorectal carcinoma. Genetic alterations in the p53 tumor suppressor gene are common in human colorectal carcinoma. bcl-2 is a protooncogene that inhibits apoptosis. The products of mutant p53 gene and bcl-2 have been associated with prognosis in several malignancies including colorectal carcinomas. This study was undertaken to evaluate values of p53 and bcl-2 oncoproteins as prognostic factors relative to clinicopathological factors and correlation of their expression. Analyses were made on achieval pathologic tissues of 80 patients with colorectal carcinomas including 34 patients able to follow-up over 5 years. The oncoproteins were localized using commercially available monoclonal antibodies:DO-7 for p53, clone124 for bcl-2. Expression of bcl-2 was cytoplasmic, whereas nuclear p53 expression was localized in carcinoma cells. The patients were 17 to 83 years of age. The expression of p53 and bcl-2 was determined respectively in 30 (37.5%) and 21 (26.3%)cases. The expression of p53 nuclear expression was not correlated with tumor location, size, histologic grade, Duke's classification, regional lymph node metastasis and tumor recurrence. The cytoplasmic expression of bcl-2 was not correlated with tumor location, size, histologic grade, Duke's classification, regional lymph node metastasis and recurrence. Univariate analysis showed that patients with p53 nuclear expression were not associated with poorer overall survival than patients with p53 negative, and also showed in patients with bcl-2 expression. The expression of p53 did not affect to that of bcl-2. We concluded that the p53 nuclear and bcl-2 cytoplasmic expression were not independent prognostic factors in colorectal carcinomas. Evidence of reciprocity of bcl-2 and p53 expression was not found.
Subject(s)
Humans , Apoptosis , Classification , Colorectal Neoplasms , Cytoplasm , Follow-Up Studies , Genes, p53 , Genes, Tumor Suppressor , Lymph Nodes , Neoplasm Metastasis , Oncogene Proteins , Prognosis , RecurrenceABSTRACT
It is recognized that rebleeding of traumatic hyphema may predispose patients to several complications including decreased visual acuity. We reviewed the medical records of 92 patients(92 eyes) with the diagnosis of nonperforating traumatic hyphema. The relative efficiencies of Aminocaproic acid and systemic Predisolone for reducing rate of rebleeding and their side effects were evaluated under the statistical analysis. Fourty-seven patients received an oral dosage of 50 mg/kg of Aminocaproic acid every 4 hours for 5 days(up to a maximum 30 gm/day), and fourty-five patients took an oral dosage of 0.6 mg/kg of Prednisolone daily in two devided doses. The frequency of rebleeding was not statistically significantly different between the aminocaproic acid treated group(4.3%, 2/47 patients) and the prednisolone treated group(6.7%, 3/45 patients). The developing rates of their acute adverse reaction were statistically different between the aminocaproic acid treated group(44.7%, 21/47 patients) and the prednisolone treated group(20%, 9/45 patients).