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)

Anaplastic thyroid carcinoma (ATC) is usually associated with a poor prognosis, with most patients dying within a few months. The mechanism of its carcinogenesis is unclear, and its rapid growth and spread often prevent effective surgical therapy. Thus, chemotherapy is necessary. However, ATC is often resistant to anticancer drugs. Therefore, prediction of chemosensitivity is important in selecting appropriate treatment. In this study, after the establishment of three cell lines (K119, KOA2, and IAA) from patients with ATC, we analyzed them for abnormalities in certain oncogenes (myc, ras, ret, and c-erbB2) and the p53 tumor suppressor gene. Only one of three cell lines (KOA2) had a N-ras mutation [codon 61 CAA(Gln)-->CGA(Arg)] and a p53 gene mutation [exon 6 codon 192 Caa(Gln)-->TAG(stop)]. We also investigated their in vitro drug sensitivity and compared it with clinical chemosensitivity, retrospectively. In vitro drug sensitivity was determined using an adhesive tumor cell culture system. Only the K119 cells were sensitive to adriamycin and cisplatin in vitro. The other two were resistant to them in vitro. These results paralleled the clinical responses. We also evaluated the in vitro drug sensitivity of a poorly differentiated thyroid carcinoma cell line (SMP) and papillary thyroid carcinoma cell lines (NPA). None of the five cell lines expressed the multidrug resistance gene (mdr-1). In conclusion, we established ATC cell lines that are suitable models for characterizing the nature of multidrug resistance and carcinogenesis.
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PMID:Establishment of anaplastic thyroid carcinoma cell lines useful for analysis of chemosensitivity and carcinogenesis. 885 99

Detection of various epitopes of the p53 and MDM-2 proteins, using new antibodies was performed on formalin-fixed and paraffin-embedded tissue samples from breast cancer and compared with results obtained using well-characterized antibodies. The results show that the distribution of positive nuclei and intensity of staining varies significantly depending on the antibody used, as well as on the microwaving procedure. Antibodies DO-14, DO-13 and SMP-14 have very good characteristics and are available for immunohistochemical analysis of p53 and MDM-2. Our results indicate, that immunohistochemical expression of p53 and MDM-2 is a not stable and unitary phenomenon and from this point of view a single antibody is not sufficient for its determination. Since, characteristics of p53 and MDM-2 molecules can vary from one sample to the next, panel antibodies capable of determining a wide range of wide type and mutant conformations must be used.
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PMID:Immunoreactivity of new antibodies anti-p53 and anti-MDM-2 in paraffin embedded tissue samples. 943 95

Inactivation of wild-type p53 during gastric carcinogenesis is usually caused by mutations within exons 5-8 of the p53 gene leading to mutated, usually immunohistochemically detectable p53 proteins. However, functional inactivation of wild-type p53, mimicking mutational inactivation, may also result from binding to overexpressed MDM2 protein. While these two mechanisms of p53 inactivation are considered to be mutually exclusive, no data exist as to whether MDM2 overexpression occurs during gastric carcinogenesis. MDM2 protein overexpression was therefore studied in relation to p53 protein accumulation in gastric carcinogenesis. Forty-five paraffin-embedded gastrectomy specimens from early gastric carcinomas were examined for the presence of chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type was reassessed for all early carcinomas. p53 protein accumulation was examined using the monoclonal antibody DO-7. MDM2 protein overexpression was assessed with the monoclonal antibody SMP-14. Complete absence of nuclear p53 protein accumulation was observed in chronic active gastritis, chronic atrophic gastritis, and intestinal metaplasia, irrespective of the subtype. In gastric dysplasia (one mild, two moderate, one severe), only severe dysplasia was p53-positive. Intestinal-type (n = 20) and diffuse-type early gastric carcinoma (n = 25) were p53-positive in 70 and 52 per cent of the cases, respectively. MDM2 protein overexpression was not observed during gastric carcinogenesis, either in the p53-positive or in the p53-negative cases. In conclusion, it appears that functional inactivation of wild-type p53 by MDM2 protein overexpression plays no role in (early) gastric carcinogenesis.
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PMID:No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis. 987 38

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate hydrate; Satraplatin, Sch-58500, semaxanib, sitaxsentan sodium, SMP-114, SU-6668; Teriparatide, tetrathiomolybdate, tipifarnib, tolvaptan, travoprost, treprostinil sodium; Valdecoxib, valganciclovir hydrochloride, vardenafil hydrochloride hydrate, vatalanib succinate; Ximelagatran; Z-335, ziprasidone hydrochloride, zoledronic acid monohydrate, ZYC-00101.
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PMID:Gateways to clinical trials. 1457 Dec 86