ABSTRACT
Background: The effect of proteasome inhibitors on atherosclerosis is known to vary depending on the atherosclerosis stage. Previous studies have shown that the highest proteasome expression in atherosclerotic lesions is at the progression stage. Adhesion molecules play a role in the progression stage of atherosclerosis, but no studies have analyzed the effect of proteasome inhibitors on the expression of adhesion molecules at this stage. Methods: This experimental study aimed to analyze the effect of a proteasome inhibitor, namely bortezomib, on the vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule1 (ICAM-1) expressions in blood vessels of rat model of atherosclerosis at the progression stage. This study used 18 male Wistar rats divided into three groups, i.e. group I that is the control group given standard feed, group II induced by atherosclerosis, and group III induced by atherosclerosis and given bortezomib. Atherosclerosis induction was performed using vitamin D3 (700,000 IU/kg) orally by gastric intubation on the 1st day and atherogenic feed given for four days. Bortezomib 50 µg/kgBW/day was administered intra-peritoneally. The expression of VCAM-1 and ICAM-1 molecules was measured using immunohistochemistry and analyzed quantitatively using Adobe Photoshop software. Results: The statistical test showed differences in VCAM-1 expression between atherosclerosis + Bortezomib group and atherosclerosis group, but there were no differences in the expression of ICAM-1 and atherosclerotic lesions between the groups. Conclusion: Administration of bortezomib 50µg/kg for four days in progressive atherosclerosis model rats can inhibit VCAM-1 expression, although it does not affect ICAM-1 expression and cannot inhibit atherosclerotic lesion formation.
ABSTRACT
Macrovascular diabetes complications are generally caused by a process called atherosclerosis. Evidences suggest that to initiate atherosclerosis, oxidated low-density lipoprotein (oxLDL) has to promote the expression of adhesion molecule. Several studies have evidenced the relevance of oxidative stress and atherosclerosis. However, the protective effect of alpha-lipoic acid (ALA) at atherosclerosis still needs to be explored. This study is aimed at investigating the concentration of plasma oxLDL and the expression of adhesion molecule of type 2 diabetes mellitus (DM) using rat model. Eighteen male rats were segregated into three groups labeled as control group, DM group and DM+ALA group. Type 2 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg) followed by nicotinamide (110 mg/kg). ALA was administered at a dose of 60 mg/kg body weight/day throughout the feeding period of 3 weeks. Plasma oxLDL concentration was measured by enzyme-linked immunosorbent assays and expression of vascular cell adhesion molecule-1 (VCAM-1) was measured by immunohistochemistry. Expression of abdominal aortic adhesion molecule was assessed by calculation with Adobe Photoshop CS3. Analysis of variance test was used to compare the concentration of plasma oxLDL and expression of adhesion molecule. A P-value of 0.05 was considered statistically significant. Plasma oxLDL was lower in diabetic rat+ALA compared with the diabetic rat. Percentage of area VCAM-1 in DM+ALA group was lower than DM group. There were no significant differences between groups in intensity of VCAM-1. In conclusion, ALA showed protective effects against early atherosclerosis in diabetic rats.
ABSTRACT
BACKGROUND: Human papilloma virus infection is associated with genesis and malignant potential of cervical cancer. E6 and E7 oncogens are known to bind to p53 and retinoblastoma gene products, abrogating their functions as tumor suppressors, leading to an abnormal cell cycle machinery. Roles of the p53 homolog p63 have also been postulated, E6 expression leading to TAp63b degradation allowing anchorage independent growth. Molecular studies correlated with clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and need to be clarified. AIM: To investigate expression of p53 and p63 in cervical squamous cell carcinomas in correlation with age, FIGO staging, morphology, and cancer cell proliferation. MATERIALS AND METHODS: Expression of p53 and p63 immunohistochemical staining in a total of 56 paraffin-embedded tissues of cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia, was evaluated for correlation with clinicopathological parameters. The Mann-Whitney test was used to compare the percentage of p53 and p63 expression with patient age, FIGO staging and morphology and to compare mean p53 and p63 expression. The Spearman correlation test was applied to correlate p53 and p63 expression with that of Ki-67. A p-value of <0.05 was considered statistically significant. RESULTS: There were significant associations between p53 expression with age (p=0.019) and FIGO staging (p=0.026), but not with with morphology or Ki-67 expression. There were no links between p63 expression and age, morphology, FIGO staging or Ki-67. CONCLUSIONS: This study indicated that p53 has a prognostic value in cervical squamous cell carcinomas given the relation with FIGO staging.
