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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell proliferative activity and the overaccumulation of P53 suppressor gene were evaluated in 26 cases of gestational trophoblastic disease and five cases with normal placentae. Formalin-fixed, paraffin-embedded histological sections were used for immunohistochemistry, utilizing the avidin-biotin-peroxidase technique and antibodies to PCNA (proliferative cell nuclear antigen) and to P53 (product of suppressor gene). Positive reactions for PCNA were graded from 1+ to 3+ (1(+)-less than 10% of cells; 2(+)-10-50%; 3(+)-more than 50%). Eight of 10 cases of choriocarcinoma (80%) showed moderate to strong reactivity for PCNA (2+ and 3+). All 9 cases with hydatidiform mole and 6 of 7 cases with partial mole also demonstrated 2+ and 3+ reactions for PCNA. There was minimal or no PCNA staining in the trophoblastic cells of normal placentae. Five of 10 cases with choriocarcinoma (50%) exhibited P53 overaccumulation as did 7 of 9 cases with hydatidiform mole (78%). In hydatidiform moles, P53 staining was limited to the areas of trophoblastic proliferation separate from chorionic villi. None of the partial moles or normal placentae showed P53 overaccumulation. It is concluded that the cell proliferative activity of choriocarcinomas as well as complete and partial hydatidiform moles are comparable. On the other hand, the mutation of P53 suppressor gene, as demonstrated by the overaccumulation of P53 protein, is seen only in true trophoblastic neoplasms, namely, choriocarcinomas and hydatidiform moles.
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PMID:Cell proliferative activity and mutation of P53 suppressor gene in human gestational trophoblastic disease. 790 85

In order to determine the p53 status of gestational trophoblastic neoplasia, 24 cases of molar pregnancies and two choriocarcinoma cell lines (JAR and JEG-3) were evaluated for the presence of mutations. The evaluation involved the whole coding sequence (i.e. exons 2-11) of the p53 gene with polymerase chain reaction (PCR) amplification of genomic DNA, followed by single strand conformation polymorphism (SSCP) and sequencing. Only one case of hydatidiform mole was found to have a missense point mutation (codon 295, CCT-->CTT, i.e. proline to leucine) of the p53 gene. The results suggest that p53 mutation is rarely involved in the pathogenesis of gestational trophoblastic neoplasia.
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PMID:Infrequent mutation in tumor suppressor gene p53 in gestational trophoblastic neoplasia. 795 57

In this study we compared the expression of p53 in six early placentas and eight hydatidiform moles using Northern blotting. A higher expression of p53 in hydatidiform moles as compared to normal placentas of comparable gestational age was observed. Immunohistochemical studies did not detect mutant protein of p53 in the hydatidiform moles. DNA sequencing was performed on four of the hydatidiform moles with increased expression of p53, but no mutations could be detected. The possible role of p53 in the pathogenesis of hydatidiform mole is discussed.
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PMID:Expression of the p53 gene in trophoblastic cells in hydatidiform moles and normal human placentas. 803 77

Ninety-four cases of early abortion have been studied. Five histological groups of lesion have been identified by routine histological techniques on abortion materials, group I corresponding to partial hydatidiform mole. Cytogenetic analyses have revealed chromosome anomalies in near 50% of cases with a prevalence of triploidies followed by trisomies and monosomies. Normal histological findings are more often associated with normal karyotypes and group I with abnormal karyotypes but a specific correlation between histological pattern and cytogenetic anomalies is lacking. Neither some histochemical reactions nor the well preserved immunohistochemical reactivities of beta-hCG, hPL, PLAP, AFP, cytokeratin, vimentin, desmin, factor VIII, CD 68, MIB1 (growth fraction), EGF-R, p53 and c-erbB-2 oncoproteins have disclosed specific chromosome anomalies. They have only allowed a better definition of histological groups. A simple histological evaluation, although extended to immunohistochemical reaction may not substitute the cytogenetic analyses, not even for purposes of preselection.
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PMID:[Correlation of the histological and cytogenetic pictures in placental tissue from early abortion. Does immunohistochemistry have a role?]. 900 96

This study investigates the extent of apoptosis in complete hydatidiform mole (CHM), using an in situ 3'-end DNA labelling (TUNEL) technique on formalin-fixed and paraffin-embedded sections. The sections were also immunostained with antibodies to p53, Bax and Bcl-2 proteins. In 10 normal placenta cases and 15 CHM cases, the apoptotic index was <1 and 2-4 per cent, respectively. The labelled trophoblastic cells possessed pyknotic nuclei and densely eosinophilic cytoplasm which corresponded well to the so-called apoptotic bodies by light and electron microscopy. The p53 positive reaction was restricted to the nuclei of cytotrophoblasts and intermediate trophoblasts, while the syncytiotrophoblasts showed only rare immunolocalization. Strong p53 expression was seen most often in cytotrophoblasts of CHM (>30 per cent of nuclei) which also showed a higher apoptosis index, while cytotrophoblasts in normal placentae were weakly and focally labelled (<10 per cent of nuclei). There were statistical differences between normal and CHM cases (P<0.05). Bcl-2 accumulation, on the other hand, was observed predominantly in syncytiotrophoblasts of normal placentae, and cytotrophoblasts and intermediate trophoblasts did not express Bcl-2 in all cases. Interestingly, syncytiotrophoblasts were found to be negative for Bax protein and positive in cytotrophoblast, which is consistent with the function of the protein in conveying increased apoptosis susceptibility to this cell population. The results show that the level of apoptosis correlates with the histological type of the gestational trophoblasts, and apoptosis index is higher in cytotrophoblasts in CHM. The fact that p53 quantitative expression and an increase in the Bax/Bcl-2 ratio were also observed in CHM suggested that they may contribute partly to the high level of apoptosis.
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PMID:p53, Bax and Bcl-2 expression, and apoptosis in gestational trophoblast of complete hydatidiform mole. 969 56

Using polymerase chain reaction single strand conformational polymorphism (PCR-SSCP) and EB staining technique, paraffin-embeded sections of 20 hydatidiform mole and 4 choriocarcinoma were detected in the exons 5 and 8 of p53 gene. The results showed that mutations of p53 gene were 0/9 in the normal chorionic villi, 6/20 (30%) in hydatidiform mole and 3/4 in choriocarcinoma. This study suggests that mutations of p53 gene may be an important event in human gestational trophoblastic neoplastigenesis and its progression.
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PMID:[Detection of p53 gene mutations in human gestational trophoblastic neoplasia by polymerase chain reaction-single strand conformational polymorphism techniques]. 986 92

In order to understand the involvement of the p53 tumour suppressor gene in the pathogenesis of gestational trophoblastic disease (GTD), we investigated its genetic status, protein expression and its role in apoptosis in samples of complete and partial hydatidiform mole as compared with those of normal placenta. Direct sequencing of polymerase chain reaction (PCR) products of the coding and non-coding regions of the p53 gene demonstrated no mutations in any of the studied samples. Immunohistochemical studies revealed increased expression of the p53 protein predominantly in the nuclei of villous cytotrophoblasts. This over-expression of p53 was found in all samples of complete mole, in 50 per cent of partial mole samples and in about 30 per cent of normal placenta cases, although no significant difference in the staining intensity and pattern was observed. An in situ detection of DNA nicking (TUNEL) staining, demonstrating apoptosis, was also detected predominantly in villous cytotrophoblasts and in stromal areas. The per centage of apoptotic cells in all studied samples, determined by flow cytometry, demonstrated a significant increase in apoptotic cells in samples of complete and partial hydatidiform mole compared with those of normal placenta (P< 0.0003 and P< 0.004, respectively). In conclusion, the current study may provide a possible explanation to the pathogenesis of GTD, probably associated with extensive p53-dependent apoptosis to modulate excessive trophoblastic proliferation.
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PMID:Expression of the p53 gene and apoptosis in gestational trophoblastic disease. 1069 52

Gestational trophoblastic diseases, like the complete hydatidiform mole (CHM), are a group of human interrelated neoplasms whose etiology and progression is poorly understood at the molecular level. We have previously reported the cloning and expression of a new tumor necrosis factor receptor (TNF-R) related transcript, named CHMS-1 that encodes a potential death domain. Here we show that ectopic expression of the putative CHMS-1 death domain specifically induced apoptosis in a dose-dependent manner, in trophoblastic (JEG-3) and non-trophoblastic (COS-7) cells. We also investigated the expression of apoptosis-related molecules such as Bcl-2 and p53 and demonstrated that Bcl-2 is repressed in CHM while p53 is overexpressed in CHM compared with persistent gestational trophoblastic tumors. Altogether, these data indicate that the CHMS-1 death domain is able to trigger apoptosis, thus suggesting that this new entity might be an important inducer of molar regression mechanisms in women.
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PMID:A new death domain associated with gestational trophoblastic diseases induces apoptosis in distinct cell types. 1171 85

Induction of apoptosis is an attractive strategy in cancer therapy but it clinical practice is not yet sufficient in choriocarcinoma. The quinolinone derivative, vesnarinone, is a novel inotropic agent used for treating congestive heart failure and may also have a potential anticancer activity. It induces apoptosis and differentiation in some tumor cell lines. We examined the antitumor effect of vesnarinone in eight cell lines established from human choriocarcinoma and hydatidiform mole using MTT assay and also analyzed the nuclear fragmentation of tumor cells by DNA electrophoresis assay. Vesnarinone inhibited the proliferation of choriocarcinoma cell lines in a dose-dependent manner and induced DNA fragmentation in cells. However, the BM cell line prepared by subcultivation from hydatidiform mole showed no growth suppression or DNA fragmentation in response to vesnarinone. On the other hand, PCR-SSCP analysis and direct DNA sequencing have shown that a human choriocarcinoma cell line, SCH, has a mutant p53 gene at codon 249. When SCH cells were treated with vesnarinone cellular proliferation was significantly inhibited. Vesnarinone suppressed the proliferation of all choriocarcinoma cell lines and induced apoptosis, regardless of the existence of p53 mutation. In addition, it has been found by RT-PCR that expression of c-Myc mRNA is upregulated by treating choriocarcinoma cells with vesnarinone. The finding suggests that vesnarinone might induce expression of c-Myc gene in choriocarcinoma cells, the product of which may be associated with the inhibition of cell growth and induce apoptosis. These results suggest that vesnarinone is a useful reagent for the treatment of choriocarcinoma.
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PMID:Induction of apoptosis in human choriocarcinoma cell lines by treatment with 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (vesnarinone). 1237 38

Seventy-two patients with gestational trophoblastic tumors (GTTs) and 20 first-trimester healthy pregnant women (controls) participated in this study. According to the WHO scoring system, GTTs were subgrouped into 24 hydatiform mole spontaneous regression (HMSR), 18 postmolar high-risk (PMHR) and 16 low- and 14 high-risk cases of choriocarcinoma. Patients with choriocarcinoma were treated with hysterectomy and methotrexate chemotherapy, whereas molar pregnancy was managed by either oxytocin infusion followed by suction evacuation or by hysterectomy. Serum p53 autoantibodies were determined by enzyme-linked immunosorbant assay and serum hCGbeta was determined by radioimmunoassay before and throughout the 12 months after treatment. p53 autoantibodies were not detected in normal pregnancy and cases of HMSR but were detected in all cases of PMHR and choriocarcinoma. Concentrations of p53 autoantibodies were higher in choriocarcinoma than in PMHR cases. Serial measurements of p53 autoantibodies dropped to an undetectable level within 1 and 6 months after treatment in cases of PMHR and low-risk choriocarcinoma, respectively. Decreasing values of p53 autoantibodies in high-risk choriocarcinoma remained higher than the cut-off level of controls. There was a significant positive correlation between p53 autoantibodies and serum hCGbeta concentration in GTTs. In conclusion, detection of p53 autoantibodies has a high potential for the differential diagnosis of GTTs and their serial measurements are clinically useful to monitor disease progression and to assess response to therapy in GTTs.
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PMID:Diagnostic and prognostic significance of circulating tumor suppressor gene p53 autoantibodies in patients with gestational trophoblastic tumors. 1506 19


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