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)

Mutations of the P53 gene, strictly associated with the carcinogenesis are a commonly observed in neoplastic cells. The aim of this study was the immunohistochemical evaluation of P53 protein expression in colorectal carcinomas and analysis of its relationship to chosen anatomo-clinical and morphological parameters of the tumours. The study used the material obtained during surgical treatment of 74 colorectal carcinomas. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the antihuman P53 protein monoclonal antibody. The immunolocalization of P53 protein was performed using the Labelled Streptavidin Biotin (LSAB) method. The P53 protein expression was semiquantitatively assessed in neoplastic cells and the reaction present in more than 25% of tumour cells was accepted as the threshold of positivity. No correlation was found between P53 protein expression and tumour histologic type and site, and age and sex of patients. However, P53 protein expression in primary and metastatic tumours was found statistically significantly correlated.
 ...
PMID:Study of P53 protein expression in colorectal cancer. 1137 3

The aim of this study was the immunohistochemical evaluation of p53 protein expression in localized prostate cancer (Pca) following radical prostatectomy and analysis of its relationship to chosen anatomo-clinical and morphological parameters of the tumours. The present investigation included material from 28 randomly selected patients undergoing radical prostatectomy. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the anti-human p53 protein monoclonal antibody. The immunolocalization of p53 protein was performed using the Labelled Streptavidyn Biotin (LSAB) method. The p53 protein expression was semiquantitatively assessed in neoplastic cells and the reaction present in more then 25% of tumour cells was accepted as the threshold of positivity. No correlation was found between p53 protein expression and Gleason score, pT stage, lymph node metastases, seminal vesicles invasion, positive or negative surgical resection margins, age of patients. However, p53 protein expression and capsular penetration was found statistically significantly correlated.
 ...
PMID:Study of p53 protein expression in prostate cancer. 1182 Jun 5

Both L-arginine supplementation and deprivation influence cell proliferation. The effect of high doses on tumours is determined by the optical configuration: L-arginine is stimulatory, D-arginine inhibitory. Arginine-rich hexapeptides inhibited tumour growth. Deprivation of L-arginine from cell cultures enhanced apoptosis. The pro-apoptotic action of NO synthase inhibitors, like NG-monomethyl-L-arginine, is manifested through inhibition of the arginase pathway. NG-hydroxymethyl-L-arginines caused apoptosis in cell cultures and inhibited the growth of various transplantable mouse tumours. These diverse biological activities become manifest through formaldehyde (HCHO) because guanidine group of L-arginine in free and bound form can react rapidly with endogenous HCHO, forming NG-hydroxymethylated derivatives. L-arginine is a HCHO capturer, carrier and donor molecule in biological systems. The role of formaldehyde generated during metabolism of NG-methylated and hydroxymethylated arginines in cell proliferation and death can be shown. The supposedly anti-apoptotic homozygous Arg 72-p53 genotype may increase susceptibility of some cancers. The diverse biological effects of L-arginine and its methylated derivatives call for further careful studies on their possible application in chemoprevention and cancer therapy.
 ...
PMID:Role of arginine and its methylated derivatives in cancer biology and treatment. 1198 27

p53 suppressor gene mutations are a well known step which occurs in the late stages of the complex tumourigenesis of colorectal cancer. A deregulation of p53 protein function may be associated with increased neovascularization and aggressive tumour growth. In vitro studies have shown that these genetic alterations cause a loss of wild-type p53-induced anti-angiogenetic control and could possibly induce expression of the neoangiogenic vascular endothelial growth factor (VEGF). Therefore, this in vivo study was performed to assess p53 mutations, i.e. hot spots in exons 4-9, in primary colorectal cancers and in corresponding liver metastases in order to test whether there is an association between p53 mutated tumours with increased microvessel density (MVD) and VEGF overexpression. Twenty-two tissue samples taken from primary colorectal cancers and the corresponding liver metastases were immediately snap-frozen in liquid nitrogen and fixed in formaldehyde. After DNA extraction exons 4-9 were amplified and directly sequenced. Cryostat sections were stained immunohistochemically using antibodies against VEGF, CD34, and p53 protein. A modified semiquantitative Weidner score and interactive computerized image analysis was used to assess MVD. Overexpression of immunohistochemically detected p53 protein was found in 7 of the 11 primary tumours and liver metastases (64%). Sequencing showed 3 out of 11 primary tumours (27%) and 5 out of 11 liver metastases (46%) to have p53 point or frameshift mutations; these samples tested immunohistochemically positive for p53 protein. Two p53 mutations in samples of liver metastases were not detectable in the corresponding primaries. We detected one frameshift mutation in exon 4 that has not yet been described in the literature. Tumour samples with p53 mutations and increased VEGF immunoreactivity were associated with higher MVD (p<0.01 and p<0.05, respectively). However, there was no association detected immunohistochemically between p53 and MVD as well as p53 mutations and VEGF overexpression. Our data demonstrate specific genetic alterations in the coding regions of p53 suppressor gene in both primary colorectal cancers and corresponding liver metastases, these alterations are associated with an increase in MVD, but not in VEGF overexpression. In addition, a novel frameshift mutation in both colorectal cancer and metastasis is described.
 ...
PMID:Association of p53 mutations, microvessel density and neoangiogenesis in pairs of colorectal cancers and corresponding liver metastases. 1211 17

The retinoblastoma (RB) gene product has been shown to restrict cell proliferation, promote cell differentiation, and inhibit apoptosis. Loss of RB function can induce both p53-dependent apoptosis and p53-independent apoptosis; little is known about the mechanisms of RB-regulated p53-independent apoptosis. Here we show that RB specifically activates transcription of the survival gene bcl-2 in epithelial cells but not in NIH 3T3 mesenchymal cells. This transcriptional activity is mediated by the transcription factor AP-2. By monitoring protein-DNA interactions in living cells using formaldehyde cross-linking and chromatin immunoprecipitation, we show that endogenous RB and AP-2 both bind to the same bcl-2 promoter sequence. In addition, we demonstrate that RB and AP-2 also bind to the E-cadherin gene promoter in vivo, consistent with regulation of this promoter by both AP-2 and RB in epithelial cells. This study provides evidence that RB activates bcl-2 and E-cadherin by binding directly to the respective promoter sequences and not indirectly by repressing an inhibitor. This recruitment is mediated by a transcription factor, in this case AP-2. For the first time, our results suggest a direct molecular mechanism by which RB might inhibit apoptosis independently of p53. The results are discussed in a context where RB and Bcl-2 contribute under nonpathological conditions to the maintenance of cell viability in association with a differentiated phenotype, contributing to the tumor suppressor function of RB and playing important roles in normal development.
 ...
PMID:The retinoblastoma protein binds the promoter of the survival gene bcl-2 and regulates its transcription in epithelial cells through transcription factor AP-2. 1239 Nov 56

Previous studies described a family of anticancer histone deacetylase inhibitor prodrugs of formula Me(CH(2))(2)COOCH(R)OR(1), which upon intracellular hydrolysis release acids and aldehydes. This study examines the mechanisms by which the prodrugs affect tumor cells and the contribution of the released aldehyde (formaldehyde or acetaldehyde) and acids to their anticancer activity. Type I prodrugs release 2 equiv of a carboxylic acid and 1 equiv of an aldehyde, and of Type II release 2 equiv of acids and 2 equiv of an aldehyde. SAR studied inhibition of proliferation, induction of differentiation and apoptosis, histone acetylation, and gene expression. Formaldehyde, measured intracellularly, was the dominant factor affecting proliferation and cell death. Among the released acids, butyric acid elicited the greatest antiproliferative activity, but the nature of the acid had minor impact on proliferation. In HL-60 cells, formaldehyde-releasing prodrugs significantly increased apoptosis. The prodrugs affected to a similar extent the wild-type HL-60 and MES-SA cell lines and their multidrug-resistant HL-60/MX2 and MES-Dx5 subclones. In a cell-free histone deacetylase (HDAC) inhibition-assay only butyric acid inhibited HDAC activity. The butyric acid and formaldehyde induced cell differentiation and increased p53 and p21 levels, suggesting that both affect cancer cells, the acid by inhibiting HDAC and the aldehyde by an as yet unknown mechanism.
 ...
PMID:The role of intracellularly released formaldehyde and butyric acid in the anticancer activity of acyloxyalkyl esters. 1571 72

Histone deacetylase 2 (HDAC2) is one of the histone-modifying enzymes that regulate gene expression by remodeling chromatin structure. Along with HDAC1, HDAC2 is found in the Sin3 and NuRD multiprotein complexes, which are recruited to promoters by DNA-binding proteins. In this study, we show that the majority of HDAC2 in human breast cancer cells is not phosphorylated. However, the minor population of HDAC2, preferentially cross-linked to DNA by cisplatin, is mono-, di-, or tri-phosphorylated. Furthermore, HDAC2 phosphorylation is required for formation of Sin3 and NuRD complexes and recruitment to promoters by transcription factors including p53, Rb, YY1, NF-kappaB, Sp1, and Sp3. Unmodified HDAC2 requires linker DNA to associate with chromatin but is not cross-linked to DNA by formaldehyde. We provide evidence that unmodified HDAC2 is associated with the coding region of transcribed genes, whereas phosphorylated HDAC2 is primarily recruited to promoters.
 ...
PMID:Differential distribution of unmodified and phosphorylated histone deacetylase 2 in chromatin. 1782 54

Primary pure small cell carcinoma of the urinary bladder is an extremely rare and highly aggressive tumor with an average five-year survival rate of less than 10% as cited by multiple case reports. It accounts for about 0.5-1% of all bladder tumors. We present the case of a 44-years-old man, smoker (10 cigarettes/day) hospitalized in the Department of Urology, from the "Prof. dr. Th. Burghele" Hospital, Bucharest, for one month intermittent hematuria. Ultrasonography showed a sessile tumoral mass, sized 37/30mm. Transurethral resection of the tumor mass was performed and tissue fragments were sent to the pathologic lab to establish the histologic type, the degree of differentiation and invasion. Fragments of the tumor were fixed in 10% formaldehyde, paraffin embedded and processed as standard technique; the sections were stained with HE, VG and immunohistochemically with: CROMO, EMA, NSE, CD56, NK1, p53 and betaHCG. The microscopic examination reveled a tumor proliferation composed of two distinct components: extensive small cells areas and foci of typical low grade (G2) papillary urothelial carcinoma. The small cell are uniformly, round, with increased nucleo-cytoplasmic ratio, eosinophyl cytoplasm, hyperchromatic nuclei, finely granular chromatin and inconspicuous nucleoli. Immunohistochemical stains showed diffuse positive staining of the small cell component for CROMO, EMA, NSE, CD56, NK1 and urothelial carcinoma component stained focally for betaHCG. The rate of cell proliferation was increased (p53 - 80% positive reaction). Conclusions. A diagnosis of small cell carcinoma coexisting with low-grade urothelial carcinoma was established. Because of aggressive behavior and distinct treatment, the pathologist should watch out for the presence of small cell carcinoma component.
 ...
PMID:Small cell carcinoma of the urinary bladder--a new case report. 1791 2

In a mouse model, in vitro fertilization or extended embryo culture leads to the increased expression of TRP53 in susceptible embryos. Ablation of the TRP53 gene improved embryo viability indicating that increased expression of TRP53 is a cause of the reduction of embryo viability resulting from in vitro fertilization or embryo culture. This study investigates the status of TRP53 expression in human embryos produced by intracytoplasmic sperm injection. Following fertilization, embryos were cultured for 96 h and then cryopreserved. Immediately upon thawing they were fixed in formaldehyde and subjected to immunostaining for TRP53. Staining was visualized by confocal microscopy. Negative controls were incubated with isotype control immunoglobulin and showed negligible staining. All embryos showed TRP53 staining above negative controls. TRP53 staining was heterogenous within and between embryos. An embryo that showed retarded development showed high levels of TRP53 expression. A blastocyst that had a collapsed blastocoel also showed high levels of TRP53 compared to morphologically normal blastocysts. Most TRP53 staining was in the region of the nucleus. Morphologically normal blastocysts tended to show little nuclear accumulation of stain. However, some cells within these embryos had high levels of nuclear TRP53 expression. The results show that embryos have varying sensitivity to the stresses of production and culture in vitro, and this resulted in variable expressivity of TRP53.
 ...
PMID:Variable expressivity of the tumour suppressor protein TRP53 in cryopreserved human blastocysts. 1793 78

p53 is the most frequently altered tumor-suppressor gene in skin cancer. In normal tissues the p53 protein (wild type) has a very short half-life and it is not detectable immunohistochemically. In contrast, the mutant p53 protein has an extended half-life in tumor cells and can be detected by immunohistochemical methods. p53 is widely used as an indicator of tumor aggression and progression. Fixation methods especially formaldehyde based fixation may mask the immunohistochemical detection of p53 protein but antigen retrieval methods enhance the inmmunohistochemical detection of p53 protein by remodification of protein structure. This study was designed to evaluate the efficacy of different fixatives, of microwaving and microwave pretreatment method to retrieve p53 immunoreactivity in paraffin-embedded non-lesioned (adjacent normal tissue) human skin samples or pathological human skin samples diagnosed as basal cell carcinoma. The samples were fixed at RT and/or in microwave oven either in neutral buffered formalin or alcohol for different time periods. For antigen retrieval, the sections were irradiated in a microwave oven for 5 cycles in 10 mM citrate buffer (pH 6.00). In this study the effects of six different fixation methods on the immunohistochemical staining have been investigated in basal cell tumor specimens. The application of antigen retrieval method was also examined and compared. Optimal results were obtained using samples fixed in alcohol either at room temperature (24 h) or in microwave oven.
 ...
PMID:Immunohistochemical detection of p53 protein in basal cell skin cancer after microwave-assisted antigen retrieval. 1909 7


<< Previous 1 2 3 4 Next >>