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)

Publicly available human genomic sequence data provide an unprecedented opportunity for researchers to decode the functionality of human genome. Such information is extremely valuable in cancer prevention diagnosis and treatment. Cancer Genome Anatomy Project (CGAP) and Gene Expression Omnibus (GEO) are two bioinformatic infrastructures for studying functional genomics. The goal of this study is to explore the feasibility of incorporating the Internet-available bioinformatic databases to discover human breast cancer-related genes. Several tools including the Gene Finder, Virtual Northern (vNorthern) and SAGE digital gene expression displayer (DGED) were used to analyze differential gene expression between benign and malignant breast tissues. A pilot study was performed using both EST and SAGE vNorthern to analyze the expression of a panel of known genes, including high abundance genes beta-actin and G3PDH, low abundance genes BRCA1 and p53, tissue-specific genes CEA and PSA and two breast cancer-related genes Her2/neu and MUC1. We found a high expression of beta-actin and G3PDH and a low expression of BRCA1 and p53 across different types of tissues as well as a tissue-specific expression of CEA in colon and PSA in prostate. A further analysis of 30 known breast cancer-related genes in breast cancer tissues by vNorthern demonstrated a high expression of oncogenes and low expression of tumor suppressor genes. An open-end analysis of two pools of breast cancer and benign breast tissue libraries by SAGE DGED produced 53 differentially expressed genes according to the screening criteria of a >five-fold difference and p<0.01. Further analysis by EST vNorthern and virtual microarray analysis reduced the candidate genes to six, with four down-regulated genes, ANXA1, CAV1, KRT5 and MMP7, and two up-regulated genes, ERBB2 and G1P3 in breast cancer. These findings were validated by a real-time RT-PCR analysis in eight paired human breast cancer tissue samples. We conclude that the combined multiple high throughput analyses is an effective data mining strategy in cancer gene identification. This approach may improve the usage of public available genomic data through strategic data mining of high throughput analysis.
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PMID:In silico identification of breast cancer genes by combined multiple high throughput analyses. 1564 32

OK-PSA, an active component of OK-432, induces anti-tumor immunity via Toll-like receptor (TLR) 4/MD-2 complex. In the current study, we evaluated the effect of the OK-PSA on human head and neck cancer cell lines. Twelve cancer cell lines including 7 squamous cell carcinoma (SCC) cell lines and 5 salivary gland cancer (SGC) cell lines were examined. The quantitative real-time PCR analysis revealed that TLR4 mRNA was expressed in all 12 cell lines, and that MD-2 mRNA was expressed in 5 cell lines. OK-PSA stimulation resulted in the activation of NF-kappaB in the 4 SCC cell lines which express both TLR4 and MD-2 genes, and in 5 SGC cell lines which express at least TLR4 gene independently of MD-2 expression. In these OK-PSA-responsive cell lines, OK-PSA activated caspase-1, caspase-3 and caspase-8, and induced apoptosis. OK-PSA-induced apoptosis were observed even in a SGC cell line in which p53 is mutated and its function is impaired. These findings strongly suggest that OK-PSA induces apoptosis by the activation of caspases through p53-independent pathway via TLR4 signaling in head and neck cancer cells.
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PMID:[Induction of apoptosis in human head and neck cancer cell lines by an active component of OK-432 through p53-independent pathway via toll-like receptor (TLR) 4 signaling]. 1631 69

This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous "take rate" in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation.
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PMID:Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo. 1672 21

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking.
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PMID:Prognostic factors in prostate cancer. 1675 47

Prostate carcinoma, one of the most frequent male malignancies, is in certain stages of its development significantly influenced by androgens. Therefore, we carried out a retrospective study on a set of 130 patients with nongeneralized, localized prostate carcinoma (stage T1-T2, PSA up to 25 ng/ml). We determined immunohistochemically the expression of proliferation markers PCNA and Ki67, Bax, p53, Bcl-2, p21waf1, p27kiP1 and compared them with the expression of the androgen receptor (AR). Multivariation statistical analysis of the results using the chi-square test with Pearson's correction and variability analysis using the SPSS 8.0 software program showed a strong correlation of the PCNA and Ki67 proliferation markers with the expression of hormonal dependence and apoptosis markers. The expression of PCNA correlated strongly with p27 kip1 and Bax, while the expression of Ki67 correlated most strongly with p27 kip1 and Bcl-2. The expression of p27 kip1 correlated with the expression of androgen receptor, PCNA, Ki67 as well as Bcl-2. None of the observed markers correlated significantly with Gleason's score. We did not find substantial significant relation between the observed markers and the expression of p53 and p21 waf1. The results indicate a significant role of the expression of p27 kip1 protein in regulating proliferative activity and hormonal responsiveness in the initial stage of prostate carcinoma.
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PMID:[Proliferative and apoptotic markers in prostate carcinoma in relation to androgen receptor]. 1695 59

Oncolytic viruses infect, replicate in, and eventually lyse tumor cells but spare normal ones. In addition to direct lysis, a result of viral replicative cycle, viruses also mediate tumor cell destruction by inducing nonspecific and specific antitumor immunity. Some viruses express proteins that are cytotoxic to tumor cells. Viruses recognized as oncolytic agents can therefore be divided into three categories: 1/ naturally occurring viruses (e.g. Newcastle disease virus, vesicular stomatitis virus, autonomous parvoviruses, some measles virus strains, reovirus) that selectively replicate in tumor cells, in some instances owing to their relative resistance to interferon action; 2/ virus mutants in which some genes essential for replication in normal cells but evitable in cancer cells have been deleted (e.g.adenovirus ONYX 015 that replicates only in cells with defected p53 or herpes virus G207 which exacts the presence of ribonucleotide reductase); 3/ virus mutants modified by the introduction of tissue-specific transcriptional elements that drive viral genes (e.g.adenovirus CV706 that has PSA restricted expression of E1A and E1B and adenovirus adMycTK that binds selectively on myc protein). Reovirus is prevalent in the human population but not associated with any known human disease. Studies have shown that reovirus multiplicate preferentially in tumor cells with activated gene of ras family or ras-signaling pathway while sparing normal cells. Activated ras or its pathway could be found in as many as 60-80% of human malignancies. In our studies we used cell lines that demonstrably express activated ras. We showed the cytopathic effect of reovirus (serotype 3 strain Dearing) on medulloblastoma cell lines and compared it with its acting on normal human fibroblasts. Oncolytics Biotech Inc. is currently guiding three Phase I or Phase I/II Reolysin studies, and has completed two clinical studies and concluded enrolment in a third one.
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PMID:Reovirus - possible therapy of cancer. 1716 12

5-Methyltetrahydrofolate, (R)-flurbiprofen; Ad5CMV-p53, adalimumab, alefacept, alemtuzumab, Alequel, alicaforsen sodium, almotriptan, anakinra, aprepitant, aripiprazole, armodafinil; Bevacizumab, bortezomib, bosentan; Canfosfamide hydrochloride, ciclesonide, clofarabine, Cypher; Darbepoetin alfa, diclofenac potassium, drotrecogin alfa (activated), duloxetine hydrochloride; Eel calcitonin, eletriptan, eplerenone, everolimus, ezetimibe; Frovatriptan; Gefitinib, gamma-hydroxybutyrate sodium; HKI-272, HYB-165; Ibutamoren mesylate, imatinib mesylate, interleukin-21, ixabepilone; KRN-951; L-Arginine hydrochloride, levodopa/carbidopa/entacapone; Micafungin sodium, motexafin gadolinium, mycophenolic acid sodium salt; Nesiritide; Peginterferon alfa-2a, pitavastatin calcium, pralatrexate, pregabalin, pVAX/L523S-Ad.L523S; Rasagiline mesylate, recombinant human nerve growth factor, regadenoson, rF-PSA, rimonabant, rizatriptan, rofecoxib, rosuvastatin calcium, rV-B7.1, rV-PSA; Sipuleucel-T, sirolimus-eluting stent, solifenacin succinate, sorafenib, sunitinib malate; Talactoferrin alfa, Taxus, tegaserod maleate, teriparatide, tipifarnib; Valdecoxib, vandetanib, vatalanib succinate; WT1-peptide vaccine; Xaliproden hydrochloride. (c) 2006 Prous Science. All rights reserved.
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PMID:Gateways to clinical trials. 1720 Jul 30

We report 2 patients with conventional prostatic adenocarcinoma who developed sarcomatoid carcinoma of probable prostatic origin 6 and 2.5 years after radiation treatment (seed implantation and external beam). Our cases had histologic features consistent with those cases previously reported in the literature. The tumors consisted of spindle cells with large hyperchromatic nuclei and a pattern mimicking a sarcoma. Immunohistochemical studies showed the tumors to be weakly positive for EMA, CK7, and vimentin. Ki67 staining showed positivity in more than 50% of tumor cells. The tumors also stained diffusely positive for p53 and p63. PSA and PAP were negative. Clinically, the sarcomatoid carcinomas appeared to be of prostatic origin. The pathogenesis of the tumors is still uncertain but most likely represent a radiation-induced dedifferentiation of prostatic adenocarcinoma.
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PMID:Sarcomatoid carcinoma after radiation treatment of prostatic adenocarcinoma. 1832 77

Dendritic cells play a pivotal role in immune induction. Dendritic cells perform antigen uptake, processing and presentation to T cells only when they are matured and in the functional state. In the development of a vaccine, it is of utmost importance to consider how to make dendritic cells' functions immunologically adequate. In this paper, we report the development of a series of antitumor DNA vaccines with similar structural framework, in which a gene encoding tumor-associated antigenic peptide is ligated upstream to the gene coding secondary lymphoid-tissue chemokine and downstream to the gene encoding the Fc portion of IgG (named chemotactic-antigen DNA vaccine [CADV]). CCR7(+) T, B, natural killer and dendritic cells can be attracted by secondary lymphoid-tissue chemokine, and Fc facilitates antigen uptake via Fc receptors expressed on dendritic cells. In a series of experiments in mice vaccinated by CADV with such tumor-associated antigenic specificities as HPV-16 E7, PSA-PSM-PAP, HER-2/neu, p53 and hTERT, CADV can attract immune cells to the vaccine inoculation site, remarkably inhibit tumor growth and extend survival time in tumor-bearing mice. The antitumor effect is more efficacious than that in mice treated with SLC-Ag or Ag-Fc hybrid gene. Tumor-associated antigenic-specific cytotoxic T lymphocytes can be induced by in vitro experiment in a human system. When combined with measures blocking the negative immune feedback circuits, the therapeutic effect of the vaccine can be further enhanced. Large-scale production of CADV is possible for clinical application.
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PMID:Novel chemotactic-antigen DNA vaccine against cancer. 1840 41

Accurate prognostic parameters in prostate biopsies are needed to better counsel individual patients with prostate cancer. We evaluated the prognostic impact of morphologic and immunohistochemical parameters in preoperative prostate cancer biopsies. A consecutive series of prostate biopsies of 279 men (72% with clinical stage T1c and 23% with T2) who subsequently underwent radical prostatectomy was prospectively analysed for Gleason score, number and percentage of positive cores (NPC, PPC), total percentage of biopsy tissue with tumour (TPT), maximum tumour percentage per core (MTP), and expression of Ki67, Bcl-2 and p53. All biopsy features were significantly associated with at least one feature of the radical prostatectomy specimen. pT stage was independently predicted by PSA, seminal vesicle invasion by Ki67 LI, positive margins by PSA and MTP, large tumour diameter by PSA and PPC, and Gleason score by biopsy Gleason score, MTP, and Ki67 LI, respectively. Biopsy Gleason score, NPC (1 vs. >1), TPT (<7 vs. >or=7%), and Ki67 LI (<10 vs. >or=10%) were significant predictors of biochemical recurrence after radical prostatectomy (p < 0.01, each). KI67 LI was the only independent prognostic factor in case of a low TPT (<7%) or low Gleason score (<7), the hazard ratio being 6.76 and 6.44, respectively. In summary, preoperative Gleason score, NPC, TPT and Ki67 LI significantly predict the risk of recurrence after radical prostatectomy, and Ki67 is an independent prognosticator in biopsies with low-volume or low-grade prostate cancer. Analysis of Ki67 LI in these biopsies may help to better identify patients with clinically insignificant prostate cancer.
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PMID:Tumour growth fraction measured by immunohistochemical staining of Ki67 is an independent prognostic factor in preoperative prostate biopsies with small-volume or low-grade prostate cancer. 1911 60


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