Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-two oral squamous cell carcinomas (SCCs) were analysed for p53 mutations and human papillomavirus (HPV) infection to examine the prevalency of these factors and correlation with apoptotic index (AI; number of apoptotic cells per 100 tumour cells) of the tumour tissue. In polymerase chain reaction (PCR)-Southern blot analysis, HPV DNAs were detected from 22 out of 42 SCCs (52%) with predominance of HPV-16 (68%). p53 mutations in exons 5-8, screened by nested PCR-single-strand conformation polymorphism (PCR-SSCP) analysis, were observed in 16 of 42 tumours (38%). The state of the p53 gene did not show any correlation with HPV infection. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) method was used for detection of apoptotic cells. The mean AI was 2.35, ranging from 0.31 to 6.63. SCCs associated with p53 mutation had significantly lower AI than those without p53 mutation (P < 0.01), whereas no difference in AI was found between SCCs with and without HPV infection. The results of this study confirmed that HPV infection and/or p53 mutations are implicated, but are not mutually exclusive events, in carcinogenesis of oral SCC and also showed that decrease in apoptosis is more closely related to p53 mutation than HPV infection.
 ...
PMID:p53 mutations and human papillomavirus DNA in oral squamous cell carcinoma: correlation with apoptosis. 970 82

The incidence of primary lymphomas of the central nervous system (CNS) has significantly increased over the last years. However, the pathogenesis of this serious and fatal disease is still largely unknown. The aim of the present study was to investigate whether impairment of apoptosis is involved in the pathogenesis of primary CNS lymphomas. A series of 35 primary CNS lymphomas was investigated for the presence of apoptotic cells and the expression of apoptosis-inhibiting and proapoptotic gene products of the bcl family by application of the terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) technique and immunohistochemistry. The majority (23/35) of the tumors contained no or less than 10% of apoptotic cells. All tumors were MIB-1 positive, and 53% of them showed a high proliferative activity with more than 20% MIB-1-positive cells. The bcl-2 gene was expressed in 54% of the tumors (19/35), whereas bcl-x and bax gene products were present in only a low fraction of these lymphomas (4/35). In contrast, bak and the tumor suppressor gene p53 product were not detectable. These findings indicate that apoptosis is inhibited in the majority of this series of primary CNS lymphomas. Since there was no statistical correlation between the degree of apoptosis and the expression of proteins of the bcl gene family, other apoptosis-inhibiting factors may be involved in the pathogenesis of primary CNS lymphomas.
 ...
PMID:Apoptosis and apoptosis-related gene products in primary non-Hodgkin's lymphoma of the central nervous system. 970 31

1. The possible mechanisms of the antiproliferative and apoptotic effects of curcumin (diferuloylmethane), a polyphenol in the spice turmeric, on vascular smooth muscle cells were studied in rat aortic smooth muscle cell line (A7r5). 2. The proliferative response was determined from the uptake of [3H]-thymidine. Curcumin (10(-6)-10(-4) M) inhibited serum-stimulated [3H]-thymidine incorporation of both A7r5 cells and rabbit cultured vascular smooth muscle cells in a concentration-dependent manner. Cell viability, as determined by the trypan blue dye exclusion method, was unaffected by curcumin at the concentration range 10(-6) to 10(-5) M in A7r5 cells. However, the number of viable cells after 10(-4) M curcumin treatment was less than the basal value (2 x 10(5) cells). 3. To analyse the various stages of the cell cycle, [3H]-thymidine incorporation into DNA was determined every 3 h. After stimulation with foetal calf serum, quiescent A7r5 cells started DNA synthesis in 9 to 12 h (G1/S phase), then reached a maximum at 15 to 18 h (S phase). Curcumin (10(-6)-10(-4) M) added during either the G1/S phase or S phase significantly inhibited [3H]-thymidine incorporation. 4. Following curcumin (10(-6)-10(-4) M) treatment, cell cycle analysis utilizing flow cytometry of propidium iodide stained cells revealed a G0/G1 arrest and a reduction in the percentage of cells in S phase. Curcumin at 10(-4) M also induced cell apoptosis. It is suggested that curcumin arrested cell proliferation and induced cell apoptosis, and hence reduced the [3H]-thymidine incorporation. 5. The apoptotic effect of 10(-4) M curcumin was also demonstrated by haematoxylin-eosin staining, TdT-mediated dUTP nick end labelling (TUNEL), and DNA laddering. Curcumin (10(-4) M) induced cell shrinkage, chromatin condensation, and DNA fragmentation. 6. The membranous protein tyrosine kinase activity stimulated by serum in A7r5 cells was significantly reduced by curcumin at the concentration range 10(-5) to 10(-4) M. On the other hand, the cytosolic protein kinase C activity stimulated by phorbol ester was reduced by 10(-4) M curcumin, but unaffected by lower concentrations (10(-6)-10(-5) M). 7. The levels of c-myc, p53 and bcl-2 mRNA were analysed using a reverse transcription-polymerase chain reaction (RT-PCR) technique. The level of c-myc mRNA was significantly reduced by curcumin (10(-5)-10(-4) M) treatment. And, the level of bcl-2 mRNA was significantly reduced by 10(-4) M curcumin. However, the alteration of the p53 mRNA level by curcumin (10(-5)-10(-4) M) treatment did not achieve significance. The effects of curcumin on the levels of c-myc and bcl-2 mRNA were then confirmed by Northern blotting. 8. Our results demonstrate that curcumin inhibited cell proliferation, arrested the cell cycle progression and induced cell apoptosis in vascular smooth muscle cells. Curcumin may be useful as a template for the development of drugs to prevent the pathological changes of atherosclerosis and post-angioplasty restenosis. Our results suggest that the antiproliferative effect of curcumin may partly be mediated through inhibition of protein tyrosine kinase activity and c-myc mRNA expression. And, the apoptotic effect may partly be mediated through inhibition of protein tyrosine kinase activity, protein kinase C activity, c-myc mRNA expression and bcl-2 mRNA expression.
 ...
PMID:Effect of curcumin on cell cycle progression and apoptosis in vascular smooth muscle cells. 972 Jul 70

The effect of pre-operative radio-chemotherapy (RCT) has been examined in a total of 15 oral squamous cell carcinomas (SCCs), in terms of apoptosis (cell loss) and proliferation. All the patients received pre-operative radiation at a dosage of 30 or 40 Gy, as well as anticancer agents including tagaful (FT), 5-fluorouracil (5-FU), bleomycin (BLM) and peplomycin (PEP). Surgical specimens were obtained before and after RCT, and serial sections were prepared for immunohistochemistry for p53 oncoprotein and Ki-67 antigen, as well as for terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). TUNEL indices (TI; percentage of TUNEL-positive cells in the tumor cells) before and after RCT were 1.2+/-1.1 and 4.7+/-2.9 in the nine well-differentiated oral SCCs, and 1.0+/-0.7 and 3.9+/-2.1 in the six poorly differentiated SCCs, respectively. Similarly, Ki-67 indices (KI; percentage of Ki-67 antigen-positive cells in tumor cells) before and after RCT were 31.1+/-14.2 and 15.8+/-11.1 in the former, and 37.1+/-7.8 and 8.7+/- 13.4 in the latter, respectively. Thus, pre-operative RCT enhanced apoptotic cell death and abated proliferative activity significantly (P<0.05), regardless of histological differentiation. Enhancement of apoptosis was more prominent in the group treated with FT or 5-FU than with BLM or PEP. Oral SCC with >20% of nuclear p53-positive tumor cells was noted in six cases. Enhanced TI and abadement of KI did not differ among the p53-positive and -negative tumors.
 ...
PMID:Pre-operative radio-chemotherapy enhances apoptotic cell death in oral squamous cell carcinoma. 973 27

We investigated the effects of ultraviolet B (UVB) irradiation on pig epidermal sunburn cell (apoptotic cell) formation. Expression of p53 tumor suppressor gene product, p21 (WAF1/CIP1), and proliferating cell nuclear antigen (PCNA) was also determined immunohistochemically. Apoptotic cells appeared at 12 h and reached a peak at 48 h following 2 MED-UVB irradiation. The formation of sunburn cells was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) method. p53-positive cells, and p21-positive cells appeared at 6 h, and 12 h, respectively, following the UVB-irradiation. The peak of p53-positive cells was observed at 24 h, and that of p21-positive cells was at 48 h. No expression of TUNEL-, p53-, or p21-positive cells was detected in non-irradiated epidermis. The increase in PCNA-positive cells was observed at 24 h and reached its peak at 96 h following the UVB-irradiation. Flow cytometric analyses indicated a decrease in S-phase cells at 24 h, that was followed by their increase at 96 h. Cells in G2/M phase were also considerably decreased at 6 h and 48 h following the UVB-irradiation, and was followed by their increase thereafter. The [3H]thymidine uptake and mitotic counts remained low up until 48 h, and then both parameters increased reaching their peaks at 72 96 h. Effects of UVB irradiation were also determined in tape stripping-induced hyperproliferative epidermis. The numbers of UVB-induced apoptotic cells and PCNA positive cells were markedly enhanced in the tape stripping-treated epidermis, while the numbers of p53- and p21-positive cells were not significantly altered. No induction of apoptosis, p53, or p21 was observed by tape stripping alone. Our results indicate that UVB irradiation induces G1 arrest, prolonged S, and G2/M block of epidermal keratinocytes as well as apoptosis. These processes provide a G1 check point and the elimination of possibly hazardous cells carrying DNA damage, respectively. Our results also indicate that the UVB-induced apoptotic process is enhanced in hyperproliferative skin condition suggesting that apoptosis is closely associated with cell cycle progression.
 ...
PMID:Epidermal cell kinetics of pig skin in vivo following UVB irradiation: apoptosis induced by UVB is enhanced in hyperproliferative skin condition. 974 61

Atherosclerosis is a fibroproliferative disease of the arterial intima. It was recently found that wild-type p53 (wt p53) accumulates in human atherosclerotic tissue. Wt p53 is a cell cycle regulator involved in DNA repair, DNA synthesis, cell differentiation, and apoptosis and might therefore make an important contribution to the cellularity of atherosclerotic plaques. The product of the MDM2 gene is a nuclear protein which forms a complex with p53, thereby inhibiting the negative regulatory effects of wt p53 on cell cycle progression. In order to address a potential role of the interaction of p53 with MDM2 for the regulation of cellularity in atherosclerotic tissue, 22 carotid atheromatous plaques from patients undergoing endarterectomy were studied to determine the presence of p53 immunoreactivity (IR), MDM2 IR, cell proliferation as evidenced by MIB1/Ki-67 IR and DNA fragmentation by in situ terminal transferase-mediated dUTP 3' end labelling (TUNEL), as a marker for apoptosis. p53 IR localized to areas with evidence of chronic inflammation (22/22) and was observed in virtually all cell types in 68.79 +/- 7.51 per cent of the nuclei. p53 staining in the control tissue from human internal mammary arteries was present in 0.2 +/- 0.29 per cent of the cells (P < or = 0.002). MDM2 IR was present in all cases (22/22) in macrophages and smooth muscle cells (SMCs) in 60.53 +/- 8.32 per cent of the nuclei (controls: 0.8 +/- 0.65 per cent, P < or = 0.002) and co-localized with p53 IR as shown by examination of adjacent sections and by double immunofluorescence labelling. Importantly, co-immunoprecipitation and western blot analysis revealed that p53 and MDM2 were physically associated, indicating that MDM2-p53 complex formation takes place in vivo in human atherosclerotic tissue. Positive TUNEL staining and MIB1/Ki-67 IR present in 3.01 +/- 1.27 per cent of the nuclei (controls: 0 per cent, P < or = 0.002) localized to the same plaque compartments as p53 IR and MDM2 IR. Thus, the fate of cells with p53 accumulation may depend on the interaction and the stoichiometry of the p53 and MDM2 proteins. Cells were indeed found with strong p53 accumulation and nuclear morphology typical for apoptosis and there were a few MIB1/Ki-67-positive cells with co-expression of MDM2, indicating a possible role for MDM2 in reversing the negative regulatory effects of p53 for cell cycle progression. The nuclear co-localization of p53 IR with MDM2 IR and the co-immunoprecipitation assay indicate the presence of p53-MDM2 complex formation in vivo in human atherosclerotic tissue. The destiny of individual p53 and MDM2-co-expressing cells either to undergo p53-dependent apoptosis or to re-enter the cycle of cell proliferation may depend on the relative ratios of the two proteins. p53 and MDM2 may therefore play an important role in regulating cellularity and inflammatory activity in human atherosclerotic plaques.
 ...
PMID:Co-expression of p53 and MDM2 in human atherosclerosis: implications for the regulation of cellularity of atherosclerotic lesions. 977 85

Human ovarian cancer cell lines with different p53 status were investigated for p53-dependency of cell cycle arrest upon treatment with cytostatic drugs. For this purpose commonly used anti-cancer drugs and a novel anti-cancer drug, gemcitabine, were applied. Cell cycle arrest was dependent on the drug dose used, as observed for all anti-cancer drugs applied, but not related to functional p53. With the exception of the etoposide-effected G2/M arrest at high concentrations, which seems to depend on functional p53, since it did not occur in cells with inactive p53. Only in cells with wt p53 and quasi-wild-type, p53 accumulated in the nucleus upon drug treatment with all anti-cancer agents applied. The level of accumulation was drug dose-dependent for each drug tested. The accumulated p53 was biochemically active, as measured in a transient transfection assay upon treatment with gemcitabine, cisplatin, etoposide, and Taxol. Activity was dependent on the drug dose applied and proportional to the level of accumulated p53, except for Taxol-induced p53 accumulation which correlated inversely with p53 biochemical activity. Apoptosis was estimated by in situ end labeling by biotinylated dUTP with the terminal deoxyribonucleotidyl transferase assay. Apoptosis occured after arrest at the various phases of the cell cycle in all cell lines tested, depending on the drug and the drug dose used. Nevertheless, cells with wt p53 exhibited the highest fraction of apoptotic cells.
 ...
PMID:Cell cycle arrest in ovarian cancer cell lines does not depend on p53 status upon treatment with cytostatic drugs. 977 93

Keloids are the result of a dysregulated wound-healing process and are characterized by formation of excess scar tissue that proliferates beyond the boundaries of the inciting wound. In this study, we investigated the expression of key proteins involved in regulating apoptosis in keloids. Twenty archival paraffin-embedded keloid samples were randomly selected for an immunoperoxidase assay with antibodies against fas, p53, bcl-2, and bcl-x proteins using the target antigen-retrieval technique. Apoptosis was assessed in keloids and normal skin and in keloid and normal fibroblasts by the TdT-mediated dUTP nick-end labeling (tunel) assay on tissue sections, fibroblast cultures, and by flow cytometry for cell suspensions. We found that 18 of 20 keloids expressed p53 protein; bcl-2 was expressed by keloid fibroblasts in 19 of 20 keloids, and all specimens had prominent fas expression throughout the tissue. The distribution of these three antigens was regional within each lesion and followed a consistent pattern of p53 and bcl-2 expression colocalized to the hypercellular, peripheral areas of each keloid in a perinuclear pattern (p < .001). In contrast, an inverse distribution of fas expression was shown, with staining being more diffuse across the cell surfaces and limited to the central, more hypocellular regions in16 of 17 keloids (p < .001). There was no specific staining pattern in these keloids with antihuman bcl-x. In vitro studies on cultured keloid fibroblasts (derived from six patients) revealed maintenance of the p53+, bcl-2+ phenotype up to passage 10. Neither neonatal nor normal adult skin fibroblasts expressed either antigen but could be induced to express p53 by exposure to adriamycin. Keloid lesions and keloid fibroblasts were found to have lower rates of apoptosis than normal controls. Keloid fibroblasts displayed enhanced apoptosis rates in response to hydrocortisone, gamma interferon, and hypoxia treatment as compared with normal adult fibroblasts. Focal dysregulation of p53 combined with upregulation of bcl-2 may help produce a combination of increased cell proliferation and decreased cell death in the younger, hypercellular areas of the keloid. This phenotype is reversed in the older areas of the keloid and may prevent malignant degeneration, thus favoring normal apoptosis as evidenced by prominent fas expression.
 ...
PMID:p53 and apoptosis alterations in keloids and keloid fibroblasts. 977 48

Recent evidence has emphasized the importance of programmed cell death or apoptosis in the maintenance of tissue homeostasis and pathogenesis of tumors. This study, analyzed in breast cancer, investigates the significance of apoptosis in relation to the expression of p53 and bcl-2 proteins, tissue proliferation defined by Ki-67 expression, hormone receptors and tumor grade. The extent of apoptosis was defined by morphological criteria and the TUNEL (Tdt-mediated dUTP biotin nick end labelling) assay. Immunocytochemistry was performed for p53, bcl-2, estrogen receptor, progesterone receptor and Ki-67 expression. Mutant p53 protein was detected using a mutant specific ELISA. Immunoreactivity of p53 significantly correlated with the presence of mutant p53 protein detected by ELISA (r = 0.654, p = 0.00001). An inverse correlation was observed between bcl-2 expression and the extent of apoptosis (r = -0.33369, p = 0.01912). The extent of apoptosis directly correlated with p53 protein accumulation (r = 0.485, p = 0.00041), Ki-67 immunoreactivity (r = 0.435, p = 0.001), histopathological grade (r = 0.492, p = 0.0003), tumor size (r = 0.326, p = 0.023) and lymph node status (r = 0.287, p = 0.047). A direct correlation was also observed between p53 expression and Ki-67 immunoreactivity (r = 0.623, p = 0.0002). There was no statistically significant association between estrogen and progesterone receptor status and apoptosis. In addition, the TNM stage of the disease correlated with immunoreactivity of p53 (r = 0.572, p = 0.00012) and Ki-67 (r = 0.3744, p = 0.00818). Bcl-2, by inhibiting apoptosis, may cause a shift in tissue kinetics towards the preservation of genetically aberrant cells, thereby facilitating tumor progression. These results imply that rapidly proliferating tumors appear to have a high "cell turnover state" in which there may be an increased chance of apoptosis amongst the proliferating cells. The ability of apoptosis to also occur in the presence of mutant p53 protein suggests the existence of at least two p53-dependent apoptotic pathways, one requiring activation of specific target genes and the other independent of it.
 ...
PMID:Spontaneous programmed cell death in infiltrating duct carcinoma: association with p53, BCL-2, hormone receptors and tumor proliferation. 977 89

Apoptosis is a key phenomenon in the regulation of the life span of terminally differentiated leukocytes. Human gingiva represents an established model to study immune responses to bacterial infection. In this investigation, we used the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) technique to evaluate presence and topographic location of apoptosis-associated DNA damage in human gingival biopsies along with the expression of the p53 and Bcl-2 apoptosis-regulating proteins. Qualitative data analysis showed high densities of cells expressing DNA damage and p53 both within the epithelial attachment to the tooth and in the perivascular infiltrate (infiltrated connective tissue [ICT]) immediately underlying the site of chronic bacterial aggression. Topographic consistency between DNA damage- and p53-positive cells was consistently observed. Quantitative analysis of the ICT showed mean densities of DNA damage- and p53-positive cells of 345 +/- 278 and 403 +/- 182 cells/mm2, respectively. Numerical consistency was confirmed by multivariate regression analysis: densities of DNA damage-positive cells were significantly predicted by densities of p53-positive cells (P = 0. 001, r2 = 0.84). In the ICT, cells displaying biotinylated DNA nicks were 3.8% +/- 2.7% of total cellularity, while p53- and Bcl-2-positive cells represented 4.4% +/- 1.7% and 15.4% +/- 6.7% of total cells, respectively. It is suggested that p53 expression associated with DNA damage is a prevalent phenomenon in chronically inflamed human gingiva, and that apoptosis may be a relevant process for the maintenance of local immune homeostasis at sites of chronic bacterial challenge in vivo.
 ...
PMID:In situ detection of apoptosis at sites of chronic bacterially induced inflammation in human gingiva. 978 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>