1.Expression of p53 protein in rheumatoid arthritis synovium. An immunohistochemical analysis.
Young Ho LEE ; Jong Dae JI ; Aeree KIM ; Chul Hwan KIM ; Gwan Gyu SONG
The Korean Journal of Internal Medicine 1999;14(1):59-65
OBJECTIVES: Mutation of p53 may play a role in manifestation of rheumatoid arthritis synovium, but several studies on p53 expression in synovial tissues of rheumatoid arthritis showed conflicting results. We investigated the amount and pattern of p53 positive cells in rheumatoid arthritis synovium, in comparison with osteoarthritis synovium, by using immunohistochemistry with two other monoclonal antibodies for p53. METHODS: Synovial tissues from 9 patients with rheumatoid arthritis and 5 patients with osteoarthritis were examined for p53 expression by immunohistochemistry with 2 monoclonal antibodies for p53, DO-1 and DO-7. Histologic features of inflammation were also scored and compared with p53 expression. RESULTS: There was no significant difference between inflammatory scores in both groups. In the synovial tissues of rheumatoid arthritis patients, p53 positive cells were detected in 3 out of 9 samples(33%) and p53 expressions were restricted to inflammatory mononuclear cells, but synovial lining cells, subsynovial fibroblast-like cells and vascular endothelial cells were p53 negative. p53 expressions in osteoarthritis synovial tissues as control were observed in 2 out of 5 samples(40%) and the amount and pattern of p53 positive cells were comparable to those seen in rheumatoid arthritis synovial tissues. There was no demonstrable correlation between the synovial tissues of both groups with respect to inflammation scores and expression of p53 protein. CONCLUSION: Our findings suggest that altered p53 expression may not play a significant role in the manifestation of rheumatoid arthritis synovium. However these data need to be strengthened by increasing the number of samples and molecular biology approaches.
Arthritis, Rheumatoid/metabolism*
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Arthritis, Rheumatoid/genetics
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Comparative Study
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Gene Expression
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Genes, p53
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Human
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Immunohistochemistry
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Osteoarthritis/metabolism
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Osteoarthritis/genetics
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Protein p53/metabolism*
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Protein p53/genetics
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Synovial Membrane/metabolism
2.Effect of wild-type p53 gene on the number and proteins of centrosome in leukemic K562 cells.
Hong-bin WANG ; Wen-li FENG ; Shi-feng HUANG ; Wen-jun TIAN ; Wei-xi CAO ; Zong-gan HUANG
Chinese Journal of Hematology 2009;30(5):326-331
OBJECTIVETo observe the effect of recombinant adenovirus-mediated wild-type p53 gene on the number and proteins of centrosome in K562 cells. To explore the possibility of application of wild-type p53 gene therapy in the treatment of chronic myeloid leukemia.
METHODSThe recombinant adenoviruses carrying wild-type p53 gene (Ad5 wtp53), mutant p53 gene (Ad5 mtp53) or the green fluorescent protein (GFP) gene was repeatedly amplified and co-infected into K562 cells with cation polybrene. The optimal infection titer and infection time of the recombinant adenoviruses were determined by MTT assay, p53 mRNA and protein expression were determined by RT-PCR and Western blot respectively. The centrosomal structural protein gamma-tubulin and the spindle protein alpha-tubulin were marked simultaneously by indirect immunofluorescence staining, and the expression of the centrosomal gamma-tubulin protein, the mitosis and the number of centrosome were observed under the laser confocal microscopy.
RESULTSInfection efficiency with recombinant adenoviruses was facilitated by polybrene in K562 cells, and 4 microg/ml polybrene was chosen. The optimal adenovirus infection titer was 20,000 MOI and the optimal infection time was 72 hours. p53 mRNA and P53 protein can be expressed in K562 cells by Ad5wtp53 and Ad5mtp53. Both the expression of the centrosomal gamma-tubulin protein and the number of centrosomes were decreased after Ad5wtp53 infection.
CONCLUSIONThere is sustained expression of P53 protein in K562 cells after its infection by Ad5wtp53. Wild-type P53 protein can lead to the down-regulation of the number of centrosomes and the expression of centrosomal gamma-tubulin protein in K562 cells.
Adenoviridae ; genetics ; Centrosome ; metabolism ; Genes, p53 ; genetics ; Genetic Vectors ; Humans ; K562 Cells ; Transfection ; Tubulin ; metabolism ; Tumor Suppressor Protein p53 ; metabolism
3.p53 protein overexpression in astrocytic neoplasms.
Mee Yon CHO ; Soon Hee JUNG ; Tai Seung KIM
Yonsei Medical Journal 1995;36(6):521-526
Abnormalities of the p53 gene are the most common molecular change in human cancer. In the central nervous system, mutant p53 gene is frequently identified in the tumors with astrocytic differentiation. To investigate the relation between histologic subtypes and p53 protein overexpression, we examined 81 cases of astrocytic neoplasms (24 benign astrocytoma, 28 anaplastic astrocytoma and 29 glioblastoma multiforme) using the standard immunohistochemical method. All were formalin-fixed and paraffin-embedded tissue. The p53 immunoreactivity was found in 4/24 benign astrocytoma, 18/28 anaplastic astrocytoma, 22/29 glioblastoma multiforme. The degree of immunoreactivity closely correlated with histologic subtypes (p< 0.001). Overall p53 protein expression was most frequently detected in glioblastoma multiforme, but strong immunoreactivity (3+) was more frequently found in the anaplastic astrocytoma than in glioblastoma multiforme. Although the frequency of p53 protein expression is low, 4 benign astrocytoma showed distinct nuclear staining. In conclusion the malignant progression of astrocytic neoplasms may be associated with increasing expression of p53 protein.
Astrocytoma/*metabolism
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Brain Neoplasms/*metabolism
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Glioblastoma/*metabolism
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Human
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Immunohistochemistry
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Protein p53/*metabolism
4.Correlation and expression of COX-2 and P53 protein in basal cell carcinoma of eyelid.
Zhixiong, CHEN ; Jiong, YANG ; Qiong, HUANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(3):383-6
The correlation between the expression of COX-2 and p53 protein in basal cell carcinoma (BCC) of eyelid and apoptosis was investigated. Specimens of BCC were collected from 40 cases (aged 28-68 y) at the Department of Pathology, Renmin Hospital of Wuhan University, and Department of Pathology, Zhongnan Hospital of Wuhan University during from 1999 to 2006. Five specimens of paracancerous tissues served as control group. Immunohistochemical staining was performed to detect the expression of COX-2 and p53 in the tissues. The average absorbance (A) and the average positive area rate of COX-2 and p53 protein were measured by image analysis. The positive area rate of COX-2 and p53 protein was analyzed by linear correlation analysis. It was found that COX-2 and p53 proteins were highly expressed in BCC of eyelid, and weakly expressed in paracancerous tissues. Image analysis revealed that the expression of COX-2 and p53 proteins in BCC of eyelid was significantly higher than that in paracancerous tissues (P<0.01). Spearman rank correlation analysis demonstrated a positive correlation between the expression of COX-2 and p53 (r=0.113, P=0.421). It was concluded that COX-2 can increase the expression of p53 protein, therefore suppressing apoptosis.
Apoptosis
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Carcinoma, Basal Cell/*metabolism
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Cyclooxygenase 2/*metabolism
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Eyelid Neoplasms/*metabolism
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Tumor Suppressor Protein p53/*metabolism
5.Expression level of p53 in Tumor Tissue of Patients with Acute Leukemia and Its Clinical Significance.
Journal of Experimental Hematology 2015;23(5):1240-1244
OBJECTIVETo study the expression level of p53 in tumor tissue of patients with acute leukemia (AL) and its clinical significance.
METHODSFrom April 2013 to April 2015, 80 patients with AL in our hospital were chosen as leukemia group, at the same time, 50 patients with non-hematologic diseases were chosen as control group. All the patients were detected by bone marrow smear mean and p53 staining. The positive rate of p53 and staining score were compared between 2 groups. The clinical data of leukemia group were collected, and the correlation of clinical features with p53 expression was analyzed.
RESULTSIn the control group, the positive rate of p53 was 6.00%, the staining score was (0.2 ± 0.1); in the leukemia group, the positive rate of p53 was 73.75%, the staining score was (1.9 ± 0.4), the difference was statistically significant (P < 0.05). The expression of p53 significantly correlated with the blood routine indicators, clinical manifestation, multiple infiltration and curative effects (P < 0.05), and the p53 expression not correlated statistically with the sex, age, anamnesis, family history (P > 0.05).
CONCLUSIONCompared with the patients with non-hematologic diseases, the expression level of p53 in the AL patients increases significantly, the p53 expression correlates significantly with the blood routine indicators, clinical manifestation and curative effect of the patients.
Acute Disease ; Case-Control Studies ; Humans ; Leukemia ; metabolism ; Tumor Suppressor Protein p53 ; metabolism
6.Pro-apoptotic function of hepatitis B virus X protein.
The Korean Journal of Hepatology 2010;16(2):112-122
Infection of hepatitis B virus (HBV) is a main cause of liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Among the HBV-encoded proteins, the HBV X protein (HBx) has been suspected to be strongly involved in HBV-associated liver pathogenesis. HBx, a virally encoded multifunctional regulator, has been shown to induce apoptosis, anti-apoptosis, proliferation, and transformation of cells depending on the cell lines, model systems used, assay protocols, and research groups. Among the several activities of HBx, the pro-apoptotic function of HBx will be discussed in this review. Given that the disruption of apoptosis pathway by HBx contributes to the liver pathogenesis, a better understanding of the molecular interference in the cellular pro-apoptotic networks by HBx will provide useful clues for the intervention in HBV-mediated liver diseases.
*Apoptosis
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Hepatitis B/etiology
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Liver Diseases/metabolism/virology
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Trans-Activators/*metabolism
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Tumor Necrosis Factors/metabolism
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Tumor Suppressor Protein p53/metabolism
7.Immunohistochemical evaluation of mutant p53 protein over-expression in non-mucinous adenocarcinoma in-situ and invasive adenocarcinoma, NOS of lung.
Yayan CUI ; Jie ZHANG ; Jiping DA ; Honglei ZHANG ; Dong CHEN
Chinese Journal of Pathology 2015;44(3):175-178
OBJECTIVETo study the over-expression of mutant p53 protein in non-mucinous adenocarcinoma in-situ (NMAIS) and invasive adenocarcinoma, NOS of lung.
METHODSImmunohistochemical study for p53 protein was performed on 17 cases of NMAIS and 70 cases of invasive adenocarcinoma, NOS of lung. The difference in p53 over-expression between the two tumor subtypes was analyzed.
RESULTSThe over-expression of mutant p53 protein was observed in 0 case (0%) of NMAIS and 37 cases (52.9%) of invasive adenocarcinoma, NOS of lung. The difference was of statistical significance (P = 0.000).
CONCLUSIONMutant p53 protein over-expression may play a role in the progression of NMAIS to invasive adenocarcinoma, NOS.
Adenocarcinoma ; metabolism ; Adenocarcinoma in Situ ; metabolism ; Humans ; Immunohistochemistry ; Mutant Proteins ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism
8.Progress of p53 gene.
Chinese Journal of Pathology 2004;33(6):559-561
9.Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.
Si-Nai LI ; Zi-Hao LIU ; Ming-Xue ZHOU ; Wei-Hong LIU ; Xiao-Lei LAI ; Ping LI ; Lei ZHANG ; Ju-Ju SHANG ; Sheng-Lei QIU ; Yan LOU ; Yu-Pei TAN ; Wen-Long XING ; Hong-Xu LIU
Chinese journal of integrative medicine 2023;29(12):1099-1110
OBJECTIVE:
To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.
METHODS:
A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.
RESULTS:
DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).
CONCLUSION
DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice
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Animals
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Tumor Suppressor Protein p53/metabolism*
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Endothelial Cells/metabolism*
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Exosomes/metabolism*
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bcl-2-Associated X Protein/metabolism*
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Myocardium/metabolism*
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Myocardial Infarction/drug therapy*
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Apoptosis
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MicroRNAs/metabolism*
10.Diagnostic p53 expression in gastric endoscopic mucosal resection.
Jeong Hee CHO ; Im Hwan ROE ; Young Joo JIN
Journal of Korean Medical Science 1999;14(4):412-416
Endoscopic mucosal resection (EMR) has been standardized for the treatment of intestinal type of intramucosal gastric carcinomas, and careful histological examination of the resected specimen is important for further treatment. To evaluate the diagnostic utility of p53 expression in gastric EMR samples, using immunohistochemical staining, we examined 24 gastric carcinomas (22 intestinal types and two diffuse types) and 20 adenomas removed by EMR. Intestinal type of adenocarcinomas revealed strong p53 expression in 13 cases (59%), weak in four cases (18%), and negative in five cases (23%). Resection margins of 11 carcinomas were involved in the carcinoma cells, which showed the same p53 expression pattern with main carcinoma cells. Squeezed carcinoma cells, remaining in resection margins, were definitely identified by strong p53 expression in seven cases of which the main tumor strongly expressed p53. Microscopic in situ carcinoma could be easily detected in p53 immunostaining. Multifocal involvement and submucosal invasion of carcinomas could be demarcated easily and definitely by strong p53 expression of carcinoma cells. All adenomas showed diffuse weak p53 expression. The difference of p53 expression (p< 0.001) could be used as a differential diagnosis between adenomas and carcinomas. According to these results, we propose that for careful histological examination in hospital diagnosis, both histological evaluation and p53 immunostaining are important diagnostic parameters in EMR samples of the intestinal type of gastric carcinomas.
Adenocarcinoma/surgery
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Adenocarcinoma/pathology
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Adenoma/surgery*
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Adenoma/pathology*
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Endoscopy*
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Gastric Mucosa/metabolism
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Gastric Mucosa/chemistry
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Human
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Immunoenzyme Techniques
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Protein p53/diagnostic use*
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Protein p53/biosynthesis
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Protein p53/analysis
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Stomach Neoplasms/surgery*
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Stomach Neoplasms/pathology*
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Tumor Markers, Biological