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)

The novel early response gene p22/PRG1 is linked to cell cycle entry and the induction of proliferation in various cell types although its exact function is still unknown. The p22/PRG1 promoter region contains a 20 bp sequence matching the consensus binding motif for the tumor suppressor protein p53. Gel shift assays demonstrated that p53 specifically binds to an oligonucleotide derived from the p53 binding site of the p22/PRG1 promoter. Chloramphenicol acetyltransferase (CAT) reporter gene assays confirmed that this site confers p53-dependent transcriptional activity to the p22/PRG1 promoter. In Hela cells, p22/PRG1 promoter constructs induced CAT expression only when cotransfected with an expression plasmid for wild-type, but not for mutant p53. Similarly, CAT expression was inducible at the permissive (31 degrees C) but not at the non-permissive temperature (39 degrees C) in the rat embryo fibroblast-derived cell line clone-6 that expresses a temperature-sensitive mutant p53. Conversion of this mutant p53 to a functional p53 at the permissive temperature was accompanied by a significant increase of endogenous p22/PRG1 mRNA level in this cell line. Gamma-irradiation of rat splenocytes or doxorubicin-treatment of Hela cells increased p53 levels followed by transcriptional activation of p22/PRG1 and p21/Waf1 in parallel. Our data demonstrate that p22/PRG1 transcription is induced by p53 during p53-dependent cell cycle arrest and apoptosis. Therefore, p22/PRG1 represents a novel target for transcriptional activation by p53.
 ...
PMID:The proliferation-associated early response gene p22/PRG1 is a novel p53 target gene. 962 14

Seventy-three cases of malignant, atypical, and multicentric granular cell tumors of soft tissue were studied to clarify criteria for malignancy and prognostic factors. Six histologic criteria were assessed: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (> 2 mitoses/10 high-power fields at 200x magnification), high nuclear to cytoplasmic (N:C) ratio, and pleomorphism. Neoplasms that met three or more of these criteria were classified as histologically malignant; those that met one or two criteria were classified as atypical; and those that displayed only focal pleomorphism but fulfilled none of the other criteria were classified as benign. Hence, 46 cases were classified as histologically malignant, 21 as atypical (3 were multicentric), and 6 as benign (all were multicentric). The patients with benign multicentric and atypical granular cell tumors had no metastases and there were no tumor deaths. In contrast, 11 of 28 patients (39%) with malignant granular cell tumor with follow-up information died of disease at a median interval of 3 years; 8 of 28 (29%) were alive with disease, and 9/28 (32%) were disease free (median intervals, 2 and 7 years, respectively). There were local recurrences in 9 of 28 malignant cases (32%) and metastases in 14 of 28 (50%) (median intervals, each 2 years). Forty-eight cases were studied immunohistochemically; 100% expressed vimentin, 98% S-100 protein, 98% neuron-specific enolase, 69% CD57, and 65% CD68. Alpha-smooth muscle actin, desmin, epithelial membrane antigen (EMA), cytokeratins (with CAM 5.2 and KL-1), chromogranin, and HMB45 were not detected. The proliferative index with Ki67 (MIB 1) was 10-50% in 14 of 25 malignant tumors (56%), and immunostaining for p53 was detected in 50% or more of tumor cells in 17 of 25 (68%); both of these factors were statistically significant with regard to the histologic classification as benign, atypical, or malignant. Ultrastructural examination of 13 benign, atypical, and malignant granular cell tumors showed engorgement of the cytoplasm with complex granules and lysosomes, as well as Schwannian features. By flow cytometric DNA analysis, two of six malignant tumors were aneuploid, two were hyperdiploid, and two were diploid. One atypical tumor was aneuploid and all 11 benign tumors were either diploid (9 cases) or hyperdiploid (2 cases). Statistically significant adverse prognostic factors with regard to survival included local recurrence, metastasis, larger tumor size, older patient age, histologic classification as malignant, presence of necrosis, increased mitotic activity, spindling of tumor cells, vesicular nuclei with large nucleoli, and Ki67 values greater [corrected] than 10%. This study defines clinical and morphologic criteria for malignancy in granular cell tumors and shows that malignant granular cell tumor is a high-grade sarcoma with a high rate of metastases and a short survival.
 ...
PMID:Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation. 966 41

A new cell line, FR-car, has been established from a biopsy of a low-grade human cervical squamous intraepithelial lesion (SIL). We confirmed the epithelial origin of the cells by keratin staining using polykeratin, AE1/AE3 and CAM 5.2 antibodies. Sixty percent to 80% of the cultured cells stained positive for proliferative cell nuclear antigen (PCNA) and Ki-67. There was no overexpression of p53. Karyotyping revealed that the cell line was hypodiploid with clonal abnormalities on chromosome 6 and 16. Sections of a biopsy adjacent to the lesion from which the culture was initiated tested positive for human papillomavirus (HPV) 18 DNA by the polymerase chain reaction, but cultured cells tested at several passages were HPV-negative by either type-specific or consensus PCRs. This HPV-negative SIL line may be useful in studies into the cell biology of dysplastic epithelium.
 ...
PMID:Characterization of an HPV-negative cell line (FR-CAR) derived from a cervical squamous intraepithelial lesion. 979 25

A review is presented on the role of conventional and molecular tumour markers (TM) in diagnosis and monitoring of patients with biliopancreatic malignancies. For biliopancreatic malignancy, following CEA as more historical and basic TM of gastrointestinal diseases, the mainstay marker is CA 19-9 as monosialo-ganglioside/glycolipid and sialyl derivative of lacto-N-fucopentaose II (sialyl-Lewis(a), hapten of human Lewis(a) bloodgroup determinant). It is detected in serum of healthy individuals at low concentration < 40 U/ml, with lower and often transitional elevation in benign hepatobiliary diseases and with highest levels in excretory ductal pancreatic adenocarcinoma (s = 70%-95%, sp = 72%-90%), biliary (s = 55%-79%), hepatocellular and cholangiocellular cancer (s = 22%-51%) besides gastric, colorectal and ovarian cancer and occasionally in lung, breast and uterine cancer. Physiologically elevated concentrations in healthy individuals have to be considered in all sorts of secretions (e.g. sputum, saliva, bronchial/gastric secretions, bile juice) of individuals with Lewis(a)-positive secretor status in contrast with low or lacking serum levels of CA 19-9 in patients with Lewis(a-/b-) status (7%-10% of population). In biliopancreatic malignancies, especially pancreatic cancer, CA 19-9 correlates well with clinical course of disease following surgical, chemo- or radiotherapy by a quick normalisation within 2-4 weeks after complete surgery, a transient decrease with successful palliative therapy and an often anticipated increase (lead time up to 6 months) before clinical detection in case of relapse or progressive disease. From CA 19-9 related TM tests some are detecting in addition to sialyl-Lewis(a) (sialyllacto-N-fucopentaose II) also the non-fucosylated precursor sialyl-Lewis(c) (sialyllacto-N-tetraose: CA 50, CA 242, Span-1) solely detected by the DUPAN-2 test and independent of the Lewis(a) secretor status. Some other markers comprise in addition to sialyl-Lewis(a) partially the non-sialylated Lewis(a) antigen (CA 195, CAM 43, CA 494) or are less related (CAM 17.1). The initial phase of screening and early detection is hoped to be better assessed by using molecular markers detecting gene mutations (p53, K-ras), growth factors (EGF, TGF-alpha, TGF-beta, HB-EGF, a/bFGFs, KGF) and growth factor receptor alterations (EGFr, c-erbB2/3/4). From these, K-ras mutations detected in blood, stool and bile juice of patients at risk for pancreatic cancer seem to be more promising than p53 alterations as a more later step in carcinogenesis, although they are neither yet well established nor standardised by reliable assays. In contrast growth factor and growth factor receptor alterations mainly concerning signal transducing systems seem to reflect increased tumour aggressiveness, thus shorter survival and poorer prognosis thereby contributing in the selection of patients for more aggressive therapy.
 ...
PMID:Role of tumour markers, cytogenetics. 1043 9

We reviewed 11 cases of primary thymic neuroendocrine carcinomas with combined features ranging from well-differentiated to poorly differentiated neuroendocrine carcinoma. For 3 asymptomatic patients, tumors were discovered during routine examination. Presentation in the other patients was as follows: Cushing syndrome, 2 patients; chest pain, 3 patients; superior vena cava syndrome, 1 patient; and hypercalcemia and hypophosphatemia, 1 patient. No clinical data were available for the 11th patient. All tumors were located in the anterior mediastinum and treated by surgical excision. The lesions were large and well-circumscribed with areas of hemorrhage and necrosis. They were characterized by areas showing a proliferation of monotonous, round tumor cells adopting a prominent organoid pattern admixed with areas showing sheets of atypical cells with hyperchromatic nuclei, frequent mitoses, and extensive areas of hemorrhage and necrosis. Immunohistochemical studies performed in 6 cases showed strong CAM 5.2 low-molecular-weight cytokeratin positivity in all cases, chromogranin and synaptophysin positivity in 4, Leu-7 in 3, and focal positivity for p53 in 2. Follow-up information for 9 cases showed that all patients died of their tumors between 1 and 4 years after diagnosis. The present cases highlight the heterogeneity of neuroendocrine neoplasms and reinforce the notion that these tumors form part of a continuous spectrum of differentiation.
 ...
PMID:Thymic neuroendocrine carcinomas with combined features ranging from well-differentiated (carcinoid) to small cell carcinoma. A clinicopathologic and immunohistochemical study of 11 cases. 1070 13

Twenty-two cases of oncocytic thymic neuroendocrine carcinomas (carcinoid tumors) are presented. The patients were 17 men and 5 women between the ages of 26 and 84 years (median, 55 years). Nine were asymptomatic, and the tumor was found on routine examination; four patients presented with chest pain, two with weight loss, two with multiple endocrine neoplasia I syndrome, and one with Cushing's syndrome. Surgical resection of the mediastinal tumor was performed in all cases. The lesions were described as soft, light tan to brown, measuring from 3 to 20 cm in greatest diameter. On cut section, the tumors showed a homogeneous surface, soft consistency, and focal areas of hemorrhage. Microscopically, the lesions were characterized by nests or trabeculae of tumor cells that contained abundant granular to densely eosinophilic cytoplasm, with round to oval nuclei and in some areas prominent nucleoli. Mitotic figures ranged from 2 to 10 per 10 high-power fields; foci of comedonecrosis were seen in all cases. Immunohistochemical studies including broad spectrum keratin, CAM 5.2, chromogranin, synaptophysin, Leu-7, and p53 were performed in 12 cases. All of the tumors were strongly positive for CAM 5.2 low-molecular-weight cytokeratin, 11 showed strong positive reaction for Leu-7, 10 for broad-spectrum keratin, 8 for chromogranin, 7 for synaptophysin, and only 1 case showed focal positive staining of the tumor cells for p53. Clinical follow-up of 14 patients showed that 10 were alive between 2 and 11 years, and 4 patients had died of tumor from 4 to 11 years after diagnosis. Patients with good clinical outcome were those whose tumors showed low mitotic activity and minimal nuclear pleomorphism, whereas those who had died of their tumors were those whose tumors were characterized by marked nuclear atypia and higher mitotic rates. Oncocytic thymic carcinoids should be added to the differential diagnosis of anterior mediastinal neoplasms characterized by a monotonous population of tumor cells with prominent oncocytic features.
 ...
PMID:Primary neuroendocrine carcinoma (thymic carcinoid) of the thymus with prominent oncocytic features: a clinicopathologic study of 22 cases. 1082 19

We report the case of a 24-year-old woman with nodular hidradenocarcinoma on the scalp. While histopathology of the tumor showed a circumscribed, lobulated intradermal mass with prominent squamous differentiation, the immunohistochemical study with antibodies to cytokeratins, CAM 5.2 and 19, epithelial membrane antigen, carcinoembryonic antigen, S-100 protein and p53 all demonstrated positivity. These findings confirmed that the tumor was of eccrine sweat gland origin and it was thought to be a nodular hidradenocarcinoma differentiating toward the eccrine duct and/or secretory portions. She was treated with a wide local excision and no recurrence was observed 18 months after excision.
 ...
PMID:Nodular hidradenocarcinoma with prominent squamous differentiation: case report and immunohistochemical study. 1095 91

The EB-1 cell line is a stable transfectant of EB, a p53 null colon carcinoma cell line, with an inducible promoter controlling expression of a wild type p53 cDNA. The induced p53 is transcriptionally active and gives rise to apoptosis in these cells. Using this cellular model for presence or absence of the transcription factor p53 and transactivated genes, the Suppression Subtractive Hybridization (SSH) technique permitted the isolation of 17 mRNA candidates (GIPs-Genes induced by p53), whose expression appears to be p53-dependent. Identity has been established for nine of the 17 isolated candidates. These are HGFL/MSP, Zap-70, APOBEC2, Ponsin/SH3P12/CAP/FLAF2, CDCrel2b/H5/Pnutl2, IgG, lats 2, cytokeratin 15 and PIG-3 (quinone oxidoreductase). The latter gene is the only GIP previously demonstrated to be p53 regulated. Of the eight remaining GIPs, six correspond to Unigene clusters. One candidate, GIP #1, is significantly homologous (72% identity) to a chicken zinc finger protein, CTCF, which binds to insulator elements and thus attenuates enhancer cross-talk between physically adjacent promoters. The p53-dependent expression of GIPs was confirmed by dependence of expression upon induction of wt p53 expression in the EB-1 cellular model and by up-regulation following activation of an endogenous wt p53 by treatment with adriamycin. Oncogene (2000) 19, 3978 - 3987.
 ...
PMID:Isolation and characterization of sixteen novel p53 response genes. 1096 54

Even though the tumor suppressor gene p53 is highly important in human cancer, as indicated by the fact that it is mutated in about 50% of cases, up to a few years ago no similar proteins had been identified. Recently, two p53 homologues have been identified, p73 and p63, with high amino acid identity suggesting similar functions. Indeed, like p53, p73 as well (i) can bind mdmX, mdm2, p300/CAF and adenovirus E4-orf6 proteins, (ii) can trigger several promoters including p21, bax, mdm2, gadd45, cyclin G, IGFBP3, 14-3-3 sigma, (iii) is able to trigger cell death, (iv) is involved in the DNA damage response, although through a different pathway. Here we analyze the data present in the literature in search of diverging pathways among the p53, p63, p73 family. Both p63 and p73 present two significant structural peculiarities: the presence of an extended non-conserved C-terminus containing a sterile alpha motive (SAM), typical of developmental proteins, and the presence of number of different splicing isoforms differing in the N-terminus or in the absence of the transactivation domain (delta N forms), acting as dominant negative. The mouse knockout of p63 and p73, unlike the ones for p53, shows developmental abnormalities; p63 and p73 are rarely mutated in human cancers; both genes are regulated in different differentiation models. This strongly suggests the involvement of p63 and p73 in development. A picture is emerging showing a gradient of function among p53, p73, p63 ranging from tumor suppression to development.
 ...
PMID:Evolution of functions within the p53/p63/p73 family. 1119 45

We present a case of mucoepidermoid carcinoma of the anal canal, with special reference to immunohistochemical analysis of the tumor to clarify its histogenesis. A 36-year-old man underwent surgery for mucoepidermoid carcinoma of the anal canal. Immunohistochemical analysis of the resected specimen was performed. Serial sections were stained immunohistochemically by the labeled streptavidin-biotin peroxidase method for various antigens, including epithelial membrane antigen (EMA); carcinoembryonic antigen (CEA); different types of cytokeratins, including CK10 and CAM 5.2; and p53 oncoprotein. The solid component of the tumor cells was immunohistochemically positive for EMA, CEA, and CAM 5.2, but negative for CK10. These staining patterns were different from those of anal squamous epithelium. These results confirm that mucoepidermoid carcinoma of the anus may arise from the anal transitional zone, and that it is biologically different from squamous cell carcinoma of the anus.
 ...
PMID:Mucoepidermoid carcinoma of the anal canal: an immunohistochemical study. 1148 Jul 98


<< Previous 1 2 3 4 5 6 7 Next >>