Expression of P33ING1b protein in colorectal cancer

Background: Colorectal cancer [CRC] is the second most common malignancy in the world. However, its mortality rate can be reduced if diagnosed early. P33ING1b is a tumor suppressor protein, which plays a role in growth control and apoptosis. Suppression of p33ING1b is associated with the loss of cellular growth control. However, p33 ING1b expression in CRC and its correlations with clinicopathological factors have been less studied. The aim of this study was to examine p33ING1b expression in patients with CRC and evaluate its potential correlations with clinicopathological factors

Methods: P33ING1b protein expression was examined in 70 cases of CRC tissue samples and their corresponding neighboring normal tissues by immunhistochemistry. Moreover, p33ING1b expression in CRC and its correlations with clinicopathological variables including patients' sex and age, tumor type, location, stage, and differentiation grade were examined

Results: P33ING1b expression was significantly lower in tumor samples compared with the normal adjacent samples [p<0.002]

Conclusion: Low expression of P33ING1b in patients with colorectal cancer, may be an important molecular event in the pathogenesis of colorectal cancer. Our data suggest that reduced expression of p33ING1b may be contribute to tumor genesis and accompanied by the loss of cellular growth control. In fact cell growth is out of control in lower expression of P33 and dysfunctional program cell death. P33 expression might explain the etiology of CRC for reducing the expression of tumor suppressor proteins

Combination of salermide and cholera toxin b induce apoptosis in MCF-7 but not in MRC-5 cell lines

Sirtuin1 is an enzyme that deacetylates histones and several non-histone proteins including P53 during the stress. P300 is a member of the histone acetyl transferase family and enzyme that acetylates histones. Hereby, this study describes the potency combination of Salermide as a Sirtuin1 inhibitor and cholera toxin B [CTB] as a P300 activator to induce apoptosis Michigan Cancer Foundation-7 [MCF-7] and MRC-5. Cells were cultured and treated with a combination of Salermide and CTB respectively at concentrations of 80.56 and 85.43 micro mol/L based on inhibitory concentration 50 indexes at different times. The percentage of apoptotic cells were measured by flow cytometry. Real-time polymerase chain reaction was performed to estimate the messenger ribonucleic acid expression of Sirtuin1 and P300 in cells. Enzyme linked immunosorbent assay and Bradford protein techniques were used to detect the endogenous levels of total and acetylated P53 protein generated in both cell lines. Our findings indicated that the combination of two drugs could effectively induced apoptosis in MCF-7 significantly higher than MRC-5. We showed that expression of Sirtuin1 and P300 was dramatically down-regulated with increasing time by the combination of Salermide and CTB treatment in MCF-7, but not MRC-5. The acetylated and total P53 protein levels were increased more in MCF-7 than MRC-5 with incubated combination of drugs at different times. Combination of CTB and Salermide in 72 h through decreasing expression of Sirtuin1 and P300 genes induced acetylation of P53 protein and consequently showed the most apoptosis in MCF-7 cells, but it could be well-tolerated in MRC-5. Therefore, combination of drugs could be used as an anticancer agent

Association of TP53 gene codon 72 polymorphism with endometriosis risk in Isfahan

Endometriosis is a female health disorder that occurs when cells from the lining of the uterus grow in other areas of the body. The cause of endometriosis is unknown. The purpose of this study was to investigate TP53 gene codon 72 polymorphism in women with endometriosis and compared it with healthy samples in Isfahan. We undertook a case-control study to examine the possible association of the TP53 gene codon 72 polymorphism with the risk of endometriosis in Isfahan. Ninety whole blood specimens from normal people as controls and ninety endometriosis specimens were analyzed. p53 codon 72 genotypes were identified using allele-specific polymerase chain reaction. Frequency of genotype Arg/Arg [Arginine/Arginine] in the samples of endometriosis was 28.9% and in healthy samples 42.2%. Frequency of genotype Pro/Pro [Proline/Proline] in the samples of endometriosis was 15.6% and in healthy ones. Frequency of heterozygote's Arg/Pro was 55.6% in endometriosis samples and 54.45% in healthy ones 3.3%. By comparing statistical genotype Pro/Pro with two other genotypes in both groups there was a statistical meaningful difference between control group and endometriosis group. [p=0.009, CI=95%, OR=5.34 [1047-19.29]]. Recent research shows that genotype Pro/Pro codon72 exon4 TP53 gene may be one predisposing genetic factor for endometriosis in Isfahan

Characterization and Prognostic Value of Mutations in Exons 5 and 6 of the p53 Gene in Patients with Colorectal Cancers in Central Iran

BACKGROUND/AIMS: We aimed to investigate the relation-ships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran. METHODS: Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months. RESULTS: Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p<0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p<0.01). CONCLUSIONS: Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease.

Expression of alkaline phosphatase during ostesgenic differentiation of rat bone marrow stromal cells

Bone marrow contains a population of stem cells capable of differentiating to osteoblast and forming the bone nodule by dexamethasone. The stromal cells of bone marrow obtained from 4 to 6 weeks old Spruge-Dawely male rats were grown in primary culture for 7 days and subcultured for 18 days. The cells were cultured in either DMEM medium containing 15 percent fetal calf serum and antibiotics as the controls or the above medium supplemented with Osteogenic supplements [OS]: include 10 mM Na-Beta glycerophosphate [Na-Beta Gp][5] 10 nM dexamethasone [Dex] and 50 g/ml ascordic acid [AsA] as the examined cultures. After 6, 12 and 18 days of grow up in subculture, the cultures were examined for mineralization and alkaline phosphatase [Apase] expression. Mesenchymal stem cells [MSCs] in examined cultures underwent a dramatic change in cellular morphology and a significant increase in Apase activity by day 12. The deposition of a calcified matrix on the surface of the culture flasks became evident between days 12 and 18. The addition of osteogenic supplements [OS] to MSCs cultures induced Apase expression that contributes to cellular differentiation and mineralization of extracellular matrix