Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

We report the case of a 42-year-old male patient who was diagnosed with a large tumor of the right thoracic aperture 30 months after unrelated hematopoietic stem cell transplantation (HSCT) for accelerated phase of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML). Biopsy revealed an immature lymphoid neoplasia with blastic tumor cell morphology and immunoreactivity for CD34, CD79a, CD43, and CD30 as well as slight positivity for TdT and CD20. Bcr-Abl rearrangement was found in interphase tumor cell nuclei by fluorescence in situ hybridization (FISH). Furthermore, a translocation t(14;18)(q32;q21) was amplified by polymerase chain reaction (PCR). Bone marrow (BM) examination showed regular hematopoiesis including a negative FISH analysis for Bcr-Abl and complete donor chimerism. Nested PCR from peripheral blood (PB), but not conventional PCR, was positive for the b3a2 Bcr-Abl transcript. Neither radiation nor intensive chemotherapy was capable of achieving a tumor remission, and the patient died from progressive disease 6 months later. Postmortem examinations showed a shift of immunophenotype with appearance of myeloperoxidase-positive tumor cells and loss of lymphoid antigens. In addition, there were characteristic cytogenetic findings of multiple Ph chromosomes and a clonal loss of P53 tumor suppressor gene. The latter was already deleted before HSCT. We conclude that lymphoid neoplasia occurring in our patient should be interpreted as an extramedullary, very immature blast crisis of CML expressing lymphoid differentiation markers rather than a true de novo NHL.
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PMID:Extramedullary blast crisis of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation mimicking aggressive, translocation t(14;18)-positive B-cell lymphoma. 1257 66

To investigate the effects of wt-p53 gene on proliferation and differentiation of K562 cells and to explore the feasibility of wt-p53 in leukemia gene therapy, pC53-SN(3), containing wt-p53 cDNA, and temperature-sensitive p53 mutant pN53cG(Val135) which behaved like wt-p53 at 32.5 degrees C, were introduced into p53-null K562 cells respectively by lipofectin mediated DNA transfection. In the presence of G418, K-SN(3) and K-pN53cG clones expressing P53 protein were selected. The effects of exogenous wt-p53 gene on the proliferation and differentiation of K562 cells were studied by detection of cell growth curves, leukemic colony formation, cell cycle analysis and DNA fragmentation, TdT-mediated dUTP nick end labeling (TUNEL) and benzidine staining. The results showed: (1) The level of p53 mRNA in K-SN(3) cells was lower than that in K-pN53cG cells by RT-PCR. (2) K-SN(3) and K-pN53cG(32.5 degrees C) cells proliferated more slowly than the control K562 cells, and their colony formation was obviously suppressed. The cells in G(0)/G(1) phase increased, and the cells in S phase decreased. These features were more obvious in K-pN53cG(32.5 degrees C). (3) K-pN53cG(32.5 degrees C) showed the feature of apoptosis and K-SN(3) showed the characteristics of erythroid lineage differentiation. It was indicated that exogenous of wt-p53 was capable of inhibiting the proliferation of K562 cells and inducing apoptosis of the cells at higher p53 level and interestingly, inducing the cells differentiation on erythroid lineage at lower p53 level.
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PMID:[Effects of Exogenous Wild-Type p53 Gene on K562 Cells] 1257 16

Cardiac myocytes undergo apoptosis under condition of ischemia. Little is known, however, about the molecular pathways that mediate this response. We show that serum deprivation and hypoxia, components of ischemia in vivo, resulted in apoptosis of rat ventricular myoblast cells H9c2. Hypoxia alone did not induce significant apoptosis for at least 48 h, but largely increased the proapoptotic action of serum deprivation. H9c2 cells apoptosis is evidenced by an increase in terminal (TdT)-mediated dUTP nick end-labeling-positive nuclei and by activation of caspases 3, 6, 7 and 9, and loss of mitochondrial functions. In this model of simulated ischemia, represented by serum deprivation plus hypoxia, cardiomyoblasts apoptosis was associated with a p53-independent Bax accumulation and with a down-regulation of Bcl-xL, whereas the levels of cIAP-1, cIAP-2 and X-IAP proteins did not change. Phorbol-12-myristate-13-acetate significantly reduced the induction of apoptosis, inhibiting caspase 3 cleavage, Bax accumulation, Bcl-xL down-regulation as well as restoring cell viability.
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PMID:H9c2 cardiac myoblasts undergo apoptosis in a model of ischemia consisting of serum deprivation and hypoxia: inhibition by PMA. 1258 43

The aim of this study was to determine the histologic and cellular characteristics of 2 cell types, mononuclear cells (Mos) and multinuclear giant cells (GCs), that predominantly constitute pigmented villonodular synovitis (PVS). Synovial tissues examined in this study were obtained from 10 patients with PVS. Five methods were used for cell analysis: (1) enzyme-histochemistry for tartrate-resistant acid phosphatase (TRAP); (2) immunohistochemistry using antibodies for CD68, macrophage colony-stimulating factor (M-CSF), MIB-1, p53, p21, p16, and cathepsin-L (cath L); (3) TdT-mediated deoxyuridine triphosphate-biotin terminal end labeling (TUNEL) as a measure of apoptosis; (4) fluorescence-based polymerase chain reaction single-strand conformation polymorphism analyses (FPCR-SSCP) to detect p53 gene mutations; and (5) in situ hybridization using gene-specific oligoprobes for matrix metalloproteinase (MMP)-2, MMP-9, receptor activator of nuclear factor kappaB ligand (RANKL), and calcitonin receptor (CTR). Both Mos and GCs were shown to express the macrophage/histiocyte marker CD68. In GCs, TRAP and CTR, both of which are known as characteristic phenotype markers of osteoclasts, were expressed. M-CSF and RANKL, which are together essential for osteoclast differentiation, were expressed in both Mos and GCs. Mos were shown to express MIB-1, but GCs were not. Although proliferation-suppressor proteins p53, p21, and p16 were expressed in both Mos and GCs, little apoptotic phenomenon of lining Mos was detected by TUNEL. In our study, p53 gene mutations for exons 5, 7, and 8 in PVS synovial tissues were not detected by FPCR-SSCP analysis. Furthermore, both types of cells demonstrated the proteolytic enzymes MMP-2 and MMP-9 mRNA, and cath L protein. These results suggest that PVS has a hyperplastic property consisting of the CD68-positive monocytic cell lineage with differentiation of osteoclastic giant cells from monocyte and probably controlled against proliferation by wild-type p53, p21, and p16.
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PMID:Cell characterization of mononuclear and giant cells constituting pigmented villonodular synovitis. 1260 68

The etiology and pathogenesis of Hodgkin lymphoma (HL) are not yet known. There are implications of genes involved in programmed cell death (apoptosis), and there have been repeated suggestions of an association with Epstein-Barr virus (EBV). The aim of this study was to investigate the protein expression patterns of key cell cycle-related genes, together with evidence of apoptosis and EBV status, in relation to clinical stage in HLs. A double immunohistochemical and in situ hybridization technique was used to detect the expression of bcl-2, p53, retinoblastoma (Rb), p21, Ki67 (MIB 1), and topoisomerase IIalpha (TopoIIalpha), together with latent membrane protein-1 and EBER for EBV status and TdT-mediated dUTP-FITC nick end-labeling (TUNEL) as a measure of apoptosis, on tissue microarray sections of 62 cases of classic HL (35 NS, 17 MC, 8 LR, and 2 LD). A panel of phenotypic markers was used to facilitate recognition of Hodgkin and Reed-Sternberg (H-RS) cells: CD3, CD20, CD30, CD15, and EMA. The H-RS cells of 62 classic Hodgkin lymphomas were bcl-2-positive in 35 cases (56.45%), p53-positive in 14 (22.58%), and positive for both EBV latent membrane protein-1 and EBER in 37 (59.68%); there was complete concordance of results for EBV by both procedures. No correlation was found between expression of bcl-2, p53, or EBV markers in H-RS cells and clinical stage (P > 0.05). Expression of Rb, Ki67, p21, and TopoIIalpha did, however, show significant differences with clinical stage. Expression of Rb and p21 in CD30-positive H-RS cells decreased with more advanced stage (P < 0.001). In contrast, Ki67 and ToPoIIalpha expression increased with later stage (P < 0.01). No correlation was found between expression of any of these markers in H-RS cells and the subtypes of nodular sclerosis HL, mixed cellularity HL, and LRHL (P > 0.05). TUNEL was found in the nonneoplastic cellular background in all cases and in H-RS cells in only 10 of 62 cases (16.12%) (8 nodular sclerosis HL, 1 mixed cellularity HL, and 1 LRHL). There was a significant correlation between high expression of bcl-2 and a low score by TUNEL (P < 0.05). These data are consistent with the notion that overexpression of bcl-2 may be linked to blockage of apoptosis-mediated death of H-RS cells in classic HL. Abnormal expression of p53-related protein may not play a major role in HL, because it is present in H-RS cells in only a minority of cases. Increased expression of Ki67 and TopoIIalpha by H-RS cells is significantly associated with advanced stage and may indicate aggressive disease. Adverse clinical outcome in HL also is associated with loss of Rb and p21 protein expression, consistent with the possible roles of Rb and p21 in inhibition of the growth of H-RS cells. Within the limitations of the methods used, almost two thirds of cases of HL provide evidence of an association with EBV. The tissue microarray technique is valuable not only for examination of large numbers of cases of a disease by a complex panel of markers but also potentially as a control for staining quality in immunohistochemistry and in situ hybridization.
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PMID:Apoptosis and cell cycle-related genes and proteins in classical Hodgkin lymphoma: application of tissue microarray technique. 1296 46

The accumulation of p53 protein, which is considered to be caused by a p53 gene mutation, is closely associated with poor prognosis in patients with certain types of carcinomas. The progression of esophageal squamous cell carcinoma (ESCC) is also suspected to depend on p53 gene status. We analyzed the relationship between p53 and p21 protein accumulation in ESCC, and simultaneously analyzed the frequency of apoptosis. Formalin-fixed paraffin-embedded sections were taken from 46 patients who underwent esophagectomy for ESCC. These sections were examined by immunostaining with monoclonal antibodies PAb1801 and EA10 to determine p53 and p21 protein accumulation, respectively. We also analyzed the frequency of apoptosis by TdT-mediated dUTP-biotin nick end-labeling (TUNEL). For estimation of the proportion of stained cells, we used computer analysis with NIH image analysis software. p21 protein accumulation showed an almost inverse distribution to that of p53 protein. In areas where both p53 and p21 proteins were accumulated, few apoptotic cells were observed. Particularly in cases of mucosal tumors, p53 protein was prominently accumulated in the lower layer of the tumor, whereas p21 protein accumulation was confined to the upper layer. Our results suggest that progression of esophageal squamous cell carcinoma is controlled by a p53-dependent pathway.
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PMID:p53 expression and p21 expression are mutually exclusive in esophageal squamous cell carcinoma. 1465 3

The present study focused on the effects of simulated microgravity on the human follicular thyroid carcinoma cell line ML-1. Cultured on a three-dimensional clinostat ML- 1 cells formed three-dimensional multicellular tumor spheroids (MCTS: 0.3 +/= 0.01mm in diameter). Furthermore, ML-1 cells grown on the clinostat showed elevated amounts of the apoptosis-associated Fas protein, of p53 and of bax, but reduced quantities of bcl-2. In addition, signs of apoptosis as assessed by TdT-mediated DUTP digoxigenin nick end labeling, DAPI staining, DNA laddering and 85-kDa apoptosis-related DNA fragments became detectable. The latter ones resulted from enhanced 116-kDa poly(ADP-ribose)polymerase activity. Electron microscopy revealed all morphological signs of apoptosis. Caspase 3 was clearly upregulated. In conclusion, our experiments show that conditions of simulated microgravity induce early programmed cell death and use different pathways of apoptosis.
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PMID:Simulated microgravity induces programmed cell death in human thyroid carcinoma cells. 1500 88

The peritoneal mesothelial cell is a critical component of the peritoneal membrane. The intraperitoneal use of several antibiotics to treat bacterial peritonitis is current clinical practice. Our previous study showed that cephalothin (CPL) and cefotaxime (CFT) have cytotoxic effects on human peritoneal mesothelial cells (HPMC), however, the exact mechanism of cytotoxicity has not been elucidated. In the present study, flow cytometry, TdT-mediated dUTP nick-end labelling (TUNEL) staining and electron microscopy were used to detect the apoptosis of HPMCs. Immunofluorescent staining was used to evaluate the cytochrome c distribution pattern. Western blotting was used to assess apoptotic signalling proteins. We found that CPL (0.5 mg/mL) and CFT (1 mg/mL) induced apoptosis of HPMCs, whereas cefazolin (0.5 mg/mL) and ceftriaxone (0.5 mg/mL) failed to induce apoptosis of HPMCs. While the DNA content of CFT- or CPL-treated cells was reduced, as determined by flow cytometry, cefazolin and ceftriaxone had no such effect. The CFT- or CPL-treated cells displayed the features of apoptosis both under the electron microscope and by using TUNEL staining. However, cefazolin and ceftriaxone produced the same result as the medium controls. Furthermore, CFT and CPL increased the expression of Bax and p53, and caused the translocation of cytochrome c from the mitochondria to the cytoplasm. The HPMC treated by CFT but not by CPL induced the cleavage of procaspase-3 to form active caspase-3. In conclusion, cefotaxime and cephalothin induce apoptosis of HPMCs in vitro. Signal transduction may be through the mitochondrial pathway.
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PMID:Antibiotics induce apoptosis of human peritoneal mesothelial cells. 1501 31

A preliminary clinical experience suggested tazarotene, a new acetylenic retinoid, as an effective alternative topical treatment of basal cell carcinomas (BCC). The mechanisms of action of this synthetic retinoid, however, have not been yet clarified. In this work we assessed the in vivo effects of daily application of tazarotene for 24 wk, on 30 small superficial and nodular BCC, and the in vitro effects of tazarotene on immortalized basal and squamous tumor epidermal cells. Cellular proliferation, apoptosis and changes in expression of retinol and retinoic acid receptors (RAR), p53, bcl-2, and bax were studied by immunohistochemistry, western blotting and PCR. Overall, 76.7% of treated tumors showed >50% regression. Complete healing was observed in 46.7% of all treated BCC, without recurrences at 2-y observation. Regression was associated with reduced proliferation and increased apoptosis, demonstrated by Ki-67- and TdT-mediated dUTP-biotin nick-end labelling-positive nuclear staining, and with enhanced RAR-beta and bax expression, with RAR-alpha and -gamma expression unchanged. In vitro, tazarotene induced a concentration-dependent increase of RAR-beta and bax associated with a greater rate of apoptosis and growth inhibition in basaloid tumor cells compared with squamous tumor cells. Our studies provide convincing evidence that tazarotene induces BCC regression possibly by synergistic RAR-beta-dependent anti-proliferative and pro-apoptotic pathways.
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PMID:Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene. 1510 95

Eicosapentaenoic acid (EPA) has been demonstrated to induce apoptosis and cell cycle arrest in various cancer cell lines in vitro. In this study, we investigated the anti-tumor effects of EPA on hepatoma cell lines and the mechanisms responsible for induced cell death. Three hepatoma cell lines tested had different p53 status: HepG2 with a wild-type p53; Hep3B, of which the endogenous p53 was deleted; and Huh7 with its p53 mutated. MTT assay showed reduced viability of HepG2 cells after exposure to EPA, and the cytotoxicity of EPA was time and dose dependent. However, EPA had no effect on the viability and cell death in the two other hepatoma cell lines containing dysfunctional p53. DNA fragmentation analysis and TUNEL (terminal deoxynucleotidyl transferase [TdT]-mediated deoxyuridine diphosphate [dUTP] nick end labeling) staining showed a typical pattern of DNA laddering and DNA breaks staining, respectively, in wild-type p53-containing HepG2 cells after EPA treatment. We also observed that EPA induced transient nuclear accumulation of P53 protein that subsequently up-regulated the expression of Fas messenger RNA and protein in HepG2 cells. In contrast, these findings were not observed in Hep3B and Huh7 cells exposed to EPA. Most notably, EPA-induced apoptosis in HepG2 cells could be reduced almost completely by treatment with FasL antisense oligonucleotides. We conclude that EPA inhibits the growth of HepG2 cells and mediates its effect, at least in part, via the Fas-mediated apoptosis. It appears that the effects of EPA on hepatoma cells are determined by the status of p53 and that wild-type p53 is a prerequisite for the anticancer effect of EPA.
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PMID:Eicosapentaenoic acid induces Fas-mediated apoptosis through a p53-dependent pathway in hepatoma cells. 1528 29


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