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)

The status of the p53 gene in SEWA-AS12-ADH (S-ADH) cells, a subline of the mouse sarcoma cell line SEWA, was examined. Immunoprecipitation with wild-type (wt) or mutant P53-specific monoclonal antibodies (mAb) showed that both wt and mutant P53 were produced. Sequence analysis of the p53 cDNA and genomic DNA revealed a single nucleotide (nt) substitution at a splice donor site at the beginning of intron 7. As a result of this mutation, an alternative splice site 15 nt further 3' in intron 7 is used. The P53 protein translated from this aberrantly spliced mRNA carries an Arg258-->Ser substitution, followed by an insertion of 5 extra amino acids. This is the first example of a splice-site mutation in the mouse p53 gene.
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PMID:A splice donor site mutation results in the insertion of five extra amino acids into P53 from SEWA mouse sarcoma cells. 755 34

Despite modern therapy, one third to one half of patients who get breast cancer will eventually die from it. This disconcerting circumstance has focused attention on prevention, and preventing breast cancer will require a much better understanding of the biological abnormalities underlying its development and progression. Many studies into the mechanisms of invasive breast cancer evolution have evaluated presumed precursor lesions (e.g. proliferative disease without atypia, atypical ductal hyperplasia, and ductal carcinoma in-situ) for genetic alterations known to occur in fully developed invasive carcinomas. This approach has shed some light on events which may be important in early malignant transformation, including the observations that overexpression of the c-erbB-2 oncogene and mutations of the p53 tumor suppressor gene are present in significant subsets of DCIS, but not PDWA or ADH. Although this approach is limited by our incomplete knowledge of cancer genetics, there is still a great deal to learn about breast cancer evolution by evaluating cancer-associated genes in potential precursor lesions using established techniques such as immunohistochemistry and in situ hybridization.
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PMID:Immunohistochemical studies of early breast cancer evolution. 781 82

Early breast neoplasia may be defined in many ways. Any non-invasive or invasive but nonmetastatic breast cancer qualifies as early neoplasia in the sense that they are non-lethal. Before we can prevent lethal breast cancer, we must gain a better understanding of the biological abnormalities underlying its development and progression. Many studies into the mechanisms of breast cancer evolution have evaluated potential precursor lesions (e.g., proliferative disease without atypia [PDWA], atypical ductal hyperplasia [ADH], and ductal carcinoma in situ [DCIS]) for genetic alterations known to occur in fully developed invasive carcinomas. This approach has shed some light on events which may be important in early malignant transformation, including the observations that overexpression of the c-erbB-2 oncogene and mutations of the p53 tumor suppressor gene are present in significant subsets of DCIS, but not PDWA or ADH. This approach is limited by our incomplete knowledge of cancer genetics. However, there is more to learn by evaluating known cancer-associated genes in potential precursor lesions using established techniques such as immunohistochemistry and in situ hybridization. Until recently, technology could not detect unknown genetic abnormalities in microscopic lesions such as PDWA, ADH, or DCIS. Now, PCR-based techniques have the theoretical ability to detect novel tumor promoter and suppressor genes in clinical samples of these very small lesions. For example, suppressor-type genes may be detected using comprehensive mapping probes to identify loss of heterozygosity in PCR-amplified DNA extracted from a few hundred cells microdissected from either fresh or archival tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biomarkers in early breast neoplasia. 800 90

The expression of c-erbB-2 oncogene and p53 tumor suppressor gene was studied in methacarn-fixed, paraffin-embedded biopsy specimens from 58 benign breast lesions and 129 sporadic breast carcinomas, using the supersensitive monoclonal antibodies CB 11 and BP 53-12-1 and the biotin-streptAvidin-amplified methodology. None of the benign lesions studied, which included 36 fibrocystic lesions with mild or florid epithelial hyperplasia, 12 fibrocystic lesions with ADH or ALH and 10 fibroadenomas, demonstrated membrane staining for c-erbB-2 or nuclear immunoreactivity for p53. Overall, 48.06% of primary breast carcinomas showed membrane expression of c-erbB-2, while 28.68% were p53 positive. Those showing p53 immunoreactivity displayed a nuclear and/or cytoplasmic staining type. A significant correlation was seen between c-erbB-2 and p53 expression (r = 0.213, p < 0.05), as well as between c-erbB-2 status and PSNA score (r = 0.221, p < 0.05). In addition, c-erbB-2 and p53, separately or in combination, correlated significantly with the prognostic index. In conclusion, immunohistochemistry of c-erbB-2 and p53 immunohistochemistry allows a better definition of intraductal proliferative lesions and assists in the differentiation between ADH and DCIS. It provides additional clues with regard to the biologic behavior of invasive ductal carcinomas (NOS and medullary).
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PMID:Expression of c-erbB-2 oncogene and p53 tumor suppressor gene in benign and malignant breast tissue: correlation with proliferative activity and prognostic index. 922 49

When does proliferating breast epithelium turn malignant? Single parameter analyses have not answered this question. We have tried to answer this through an analysis of immunohistochemical staining patterns in the following morphologically defined breast lesions: atypical ductal hyperplasia (ADH, 23 cases), papilloma (12 cases), ductal cancer in situ (DCIS, 28 cases), and mammographically detected small primary cancers (34 cases). The seven antibodies used were c-neu, bcl-2, p53, p21, CD44, MIB 1, and FAS. Staining patterns were compared within groups and between groups of lesions. Interesting differences in staining patterns were seen between invasive ductal cancer and invasive lobular cancer: invasive lobular cancer was less p53-positive and more CD44-positive than invasive ductal cancer. We found no common pattern in the different proliferating epithelia to show when they become malignant.
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PMID:Expression patterns of biologic markers in small breast cancers and preneoplastic breast lesions. 1473 79

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; LA-419, lacosamide, landiolol, lanthanum carbonate, lidocaine/prilocaine, liposomal cisplatin, lutropin alfa; Matuzumab, MBP(82-98), mecasermin, MGCD-0103, MMR-V, morphine hydrochloride, mycophenolic acid sodium salt; Natalizumab, NCX-4016, neridronic acid, nesiritide, nilotinib, NSC-330507; O6-benzylguanine, olanzapine/fluoxetine hydrochloride, omalizumab; Panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pemetrexed disodium, perospirone hydrochloride, pexelizumab, phorbol 12-myristate 13-acetate, pneumococcal 7-valent conjugate vaccine, posaconazole, pramiconazole, prasugrel, pregabalin, prilocaine; rAAV-GAD65, raclopride, rasagiline mesilate, retapamulin, rosuvastatin calcium, rotigotine, rufinamide; SarCNU, SB-743921, SHL-749, sirolimus-eluting stent, sitaxsentan sodium, sorafenib; TachoSil, tadalafil, talampanel, Taxus, tegaserod maleate, telithromycin, telmisartan/hydrochlorothiazide, temsirolimus, tenatoprazole, teriflunomide, tetrathiomolybdate, ticilimumab, timcodar dimesilate, tipifarnib, tirapazamine, TPI, tramiprosate, trifluridine/TPI, trimethoprim; Ularitide, Urocortin 2; Valdecoxib, valganciclovir hydrochloride, valproate magnesium, valspodar, vardenafil hydrochloride hydrate, vitespen, vofopitant hydrochloride, volociximab, vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, zotarolimus, zotarolimus-eluting stent.
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PMID:Gateways to clinical trials. 1713 34

The purpose of this report is to review the relationship between genetic polymorphisms involved in carcinogen metabolism, alcohol metabolism and cell-cycle control with the risk of head and neck cancer. The review was performed on available studies on genetic polymorphisms and head and neck cancer (HNC) published in PubMed up to September 2011. 246 primary articles and 7 meta-analyses were published. Among these, a statistically significant association was reported for glutathione S-transferases (GSTM1), glutathione S-transferases (GSTT1) and human microsomal epoxide hydrolase (EPHX1) genes. An increased risk for HNC was also associated reported for P53 codon 72 Pro/Pro, ALDH2 and three variants of the ADH gene: ADH1B (rs1229984), ADH7 (rs1573496) and ADH1C (rs698).
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PMID:A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes, cell cycle control and alcohol metabolism. 2250 60

The changes in DNA methylation status in cancer cells are characterized by hypermethylation of promoter CpG islands and diffuse genomic hypomethylation. Alu and long interspersed nucleotide element-1 (LINE-1) are non-coding genomic repetitive sequences and methylation of these elements can be used as a surrogate marker for genome-wide methylation status. This study was designed to evaluate the changes of Alu and LINE-1 hypomethylation during breast cancer progression from normal to pre-invasive lesions and invasive breast cancer (IBC), and their relationship with characteristics of IBC. We analyzed the methylation status of Alu and LINE-1 in 145 cases of breast samples including normal breast tissue, atypical ductal hyperplasia/flat epithelial atypia (ADH/FEA), ductal carcinoma in situ (DCIS) and IBC, and another set of 129 cases of IBC by pyrosequencing. Alu methylation showed no significant changes during multistep progression of breast cancer, although it tended to decrease during the transition from DCIS to IBC. In contrast, LINE-1 methylation significantly decreased from normal to ADH/FEA, while it was similar in ADH/FEA, DCIS and IBC. In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status, and LINE-1 hypomethylation was associated with negative ER status, ERBB2 (HER2) amplification and p53 overexpression. Alu and LINE-1 methylation status was significantly different between breast cancer subtypes, and the HER2 enriched subtype had lowest methylation levels. In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients. Our findings suggest that LINE-1 hypomethylation is an early event and Alu hypomethylation is probably a late event during breast cancer progression, and prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype.
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PMID:Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer. 2497 11

The aim of this paper was to explore the pharmacological mechanism of Baitouweng Decoction in the treatment of ulcerative colitis(UC) by network pharmacology and to preliminarily verify the related targets by animal experiments. Cytoscape software was used to construct "ingredient-target-disease" network through TCMSP, GeneCards and Uniprot databases. The protein interaction network was constructed using STRING database, and the core targets were speculated. The GO and KEGG enrichment analysis was conducted using R software. Autodock Vina software was used for molecular docking of ingredients and core targets. UC mice induced by dextran sodium sulfate(DSS) were treated by Baitouweng Decoction. The pathological changes of colon tissues were observed by HE staining, and the expression levels of related genes were analyzed by immunohistochemistry.The results showed that 26 active ingre-dients and 30 core targets were found in Baitouweng Decoction through network pharmacology. GO enrichment analysis showed that these genes mainly affected nuclear receptor activity, transcription factor activity, steroid hormone receptor activity, ubiquitin-like protein ligase binding, protein heterodimerization activity, transcription cofactor binding and other biological processes. KEGG enrichment analysis showed that P53 signaling pathway, EGFR signaling pathway, TNF signaling pathway, PI3 K-AKT signaling pathway and some cancer-related pathways were enriched. Molecular docking showed that EGFR, PPARG, CASP3, NOS3, caspase-9, CCND1, ADH, IL6 and NFKB1 were better docked with active ingredients. The experiments verified that Baitouweng Decoction could improve the colon pathology of mice, and EGFR is one of the related targets. Our study suggested that Baitouweng Decoction could treat UC through multiple targets and pathways, which provided a theoretical basis for future research.
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PMID:[Network pharmacological analysis and preliminary validation of mechanisms of Baitouweng Decoction in treatment of ulcerative colitis]. 3248 64