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)

Origin of collecting duct carcinomas (CDC) of the kidney is not entirely known, although it is thought that they originate from the distal collecting duct system, whereas clear cell renal cell carcinoma (cRCC) may originate from the proximal tubular epithelium. In cRCC, the von Hippel Lindau gene (vHL) is damaged in almost 100% of cases; the frequency of vHL deletions in CDC is not known. Loss of heterozygosity (LOH) of CDC and cRCC of vHL (3p), p16 (9p), p53 (17p) and the retinoblastoma (RB) gene (13q) was studied to evaluate possible genetic differences between the two. LOH of the vHL was seen in 77.7% of cRCC and in 55% of CDC. P16 was lost in 33% of cRCC and in 50% of CDC. LOH in p53 was observed in 0/8 cases of cRCC compared to 18.7% in CDC. LOH in 13q was seen in 25% of both CDC and cRCC. The high LOH rate of the vHL gene in CDC has not been observed previously. The findings indicate that CDC and cRCC share certain genetic alterations, including frequent deletion of the vHL gene. CDC is not clearly related to cRCC but may be of heterogeneous origin.
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PMID:Collecting duct carcinomas of the kidney: a comparative loss of heterozygosity study with clear cell renal cell carcinoma. 962 47

We report a case of a 62-year-old woman with goblet cell carcinoid of the appendix. She was admitted to our hospital in September 1994 after the discovery of liver tumors. After admission, a tumor in the right kidney and multiple tumors in the liver were found. She was diagnosed with renal cell cancer and metastasis to the liver and underwent excision of the kidney and enucleation of the largest liver tumor. Histological examination revealed that the liver tumor was a metastatic carcinoid tumor. As carcinoid tumors have frequently been found in the appendix, endoscopic examination was performed and a lesion was found in the appendix by colonoscopy. As predicted, the biopsy specimen was a carcinoid tumor, and she underwent an appendectomy. Histologically, the tumor was a goblet cell carcinoid. Goblet cell carcinoid is a rather rare neoplasm that has the histologic features of both carcinoids and adenocarcinoma. Forty-two cases of goblet cell carcinoid of the appendix have been reported thus far in Japan. However, few were diagnosed via endoscopic examination before surgical operation. We also carried out an immunohistochemical study with anti p53 antibody on the goblet cell carcinoid tumor of the appendix. Most tumor cells were strongly positive, while in three benign carcinoid tumors investigated simultaneously they were negative. These findings suggest that goblet cell carcinoid has an aggressive phenotype compared with benign carcinoid tumors.
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PMID:Goblet cell carcinoid of the appendix endoscopically diagnosed and examined with p53 immunostaining. 971 48

The expression of the Wilms tumor suppressor gene WT1 is largely restricted to elements of the developing urogenital system. In the fetal kidney, WT1 transcripts are present at low levels in the condensing mesenchyme and at much higher levels in differentiating glomerular epithelium and are not detected in other mesenchymal-derived epithelial structures such as the proximal and distal tubules. However, WT1 expression is observed in tubule-like elements found in some Wilms tumors. As renal cell carcinoma (RCC) of the clear cell type is one of the most prevalent adult tumors of the kidney, and is thought to originate from the epithelial cells of the proximal tubules, we studied WT1 expression in RCCs. Despite the absence of WT1 in normal primary epithelial cells derived from proximal tubules, RCC tumors and tumor-derived cell lines expressed WT1 RNA. Immunocytochemical analyses of tumor cryosections showed widespread expression throughout the poorly differentiated epithelial components of the tumor. Immunoblots of RCC samples detected a normal size WT I protein and reciprocal antibody immunoprecipitations of RCC cell extracts indicated that WT I interacts with p53 as has been demonstrated for normal human fetal kidney. The aberrant expression of functional WT1 in RCC may represent a reversion to a more de-differentiated phenotype and may contribute to the tumorigenic phenotype by inappropriately activating or repressing genes involved in growth regulation.
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PMID:Constitutive expression of the Wilms tumor suppressor gene (WT1) in renal cell carcinoma. 975 50

p73, a protein that has substantial structural and functional similarity to p53, has recently been identified. It was found to be monoallelically expressed in all cell lines and normal individuals tested. To elucidate its role in cancer development and as a potential imprinted tumor suppressor, we investigated the allele-specific expression of the human p73 gene in 28 cases of renal cell carcinoma and its imprinting status in fetal pancreatic and thymic tissues. Of 12 informative pairs of renal cell carcinoma and matched normal tissues identified by StyI restriction fragment length polymorphism (RFLP) in exon 2, p73 showed monoallelic expression in 11 out of 12 normal tissues but biallelic expression in 8/12 and switched allele expression in 2/12 of the matched corresponding cancers. An imprinting study of the p73 gene in two families using a newly identified exonic BanI RFLP indicated that expression of p73 was limited to the maternal allele in RNA from fetal pancreas and thymus, demonstrating that p73 is imprinted in at least these two tissues. These findings strongly suggest that loss of imprinting or switching of allelic expression of the p73 gene is associated with the development of renal cell carcinoma.
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PMID:Loss of imprinting and allele switching of p73 in renal cell carcinoma. 979 3

An immunohistochemical study was conducted to examine the expression of p53 and bcl-2 proteins in RCC (renal cell carcinoma) with sarcomatoid change in order to determine whether abnormalities in those proteins are associated with an enhanced malignant potential of RCC. Paraffin-embedded tissues from 11 patients with RCC, in which sarcomatoid change was prominent, were stained using anti-p53, bcl-2 and Ki-67 antibodies. Immunoreactivities for these antibodies were compared between the sarcomatoid components and corresponding basic histologic (clear or papillary) components in individual cases. Measurement of the mean nuclear areas of each component was also performed using an image analyzer system. There was no substantial increase in immunoreactivity for p53 or bcl-2 proteins in sarcomatoid components as compared with basic components. In contrast, the percentage of Ki-67-positive cells and the mean nuclear area were significantly larger in sarcomatous components than in basic components. The expression of p53 and bcl-2 proteins was not likely to play a major role in the sarcomatoid change of RCC.
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PMID:Immunohistochemical expression of p53 and bcl-2 proteins is not associated with sarcomatoid change in renal cell carcinoma. 1042 17

We describe 12 patients with a distinctive variant of pleomorphic liposarcoma that histologically shows epithelioid features and focally resembles a solid carcinoma. The tumors occurred in nine men and three women (median age, 63 yr; range, 40-78 yr). Five tumors were in the thigh, two in the chest wall, two in the axilla, and one each in the retroperitoneum, groin, and calf. Most were 15 to 20 cm in maximal diameter. They consisted of sheets of epithelioid-appearing cells with ample, variably eosinophilic cytoplasm, often showing a honeycomb-like pattern of cell borders and little if any collagenous extracellular matrix. Their histologic features often resembled those of renal clear cell carcinoma or adrenal cortical carcinoma, but all showed evidence of adipocytic differentiation, and five also showed focal spindle cell components. One patient whose tumor in the thigh had been originally diagnosed as metastatic renal carcinoma had undergone nephrectomy without a finding of a kidney tumor. All of the cases were positive for vimentin; 6 of 11 cases were positive for S-100 protein, usually focally; 5 of 11 were focally positive for keratins; and all were negative for epithelial membrane antigen, muscle actins, desmin, and CD34. High mitotic activity (mean, 42 mitotic figures per 10 high power fields) and high MIB-1-positive proliferative fraction (>30%) were seen in all of the cases, and nuclear p53 immunoreactivity was detected in five of seven cases. Of the eight patients with complete follow-up, five died of disease (median survival, 6 mo), two died of unrelated causes 10 and 18 years later, and 1 was alive and well 24 years later. The epithelioid variant of pleomorphic liposarcoma is a high-grade tumor that must be distinguished from malignant epithelial tumors, especially in view of the keratin immunoreactivity of some of these neoplasms.
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PMID:Epithelioid variant of pleomorphic liposarcoma: a study of 12 cases of a distinctive variant of high-grade liposarcoma. 1043 Feb 77

2, 5-bis(5-Hydroxymethyl-2-thienyl)furan (NSC 652287), is a representative of a series of thiophene derivatives that exhibit potent and selective antitumor activity against several tumor cell lines in the National Cancer Institute Anticancer Drug Screen. NSC 652287 has noticeable activity for the renal cell lines and produces cures in certain corresponding xenografts. The cellular mechanisms of action of NSC 652287 were therefore investigated in this study in greater detail. The most sensitive renal carcinoma cell line, A498, exhibited cell cycle arrest in G(0)-G(1) and G(2)-M at 10 nM NSC 652287, with increased p53 and p21(WAF1) protein. At higher concentrations, NSC 652287 still induced p53 elevation but with p21(WAF1) reduction and massive apoptosis. These results collectively suggested that NSC 652287 induced DNA damage. Using alkaline elution techniques, we found that NSC 652287 induced both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks. These DNA-protein cross-links (DPC) persisted for at least 12 h after drug removal and their frequency was correlated with cytotoxicity in the renal cell lines studied. The most sensitive cells (A498) produced the highest DPC followed by the cell line with intermediate sensitivity (TK-10). DPC were minimal in the two resistant cell lines, ACHN and UO-31. Nonetheless, a similar degree of DPC occurred at doses imparting equitoxic effects. These results indicate that DNA is a primary target for the novel and potent anticancer thiophene derivative, NSC 652287. NSC 652287 did not cross-link purified DNA or mammalian topoisomerase I suggesting the importance of active metabolite(s) for the cross-linking activity.
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PMID:DNA protein cross-links produced by NSC 652287, a novel thiophene derivative active against human renal cancer cells. 1046 35

We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21(waf1/cip1), and their relationship to clinical and histopathological parameters as well as to clinical outcome. Cyclins A and D1 and cyclin-dependent kinase inhibitor p21 (waf1/cip1) were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21(waf1/cip1) were always nuclear but cyclin A was also expressed in the cytoplasm of the tumour cells. The mean (range) fractions of cyclin A, cyclin D1 and p21(waf1/cip1)-positive tumour cells were 2.2% (range 0-20%), 23.3% (range 0-90%) and 6.8% (range 0-70%) respectively. The expression of cyclin A was related to venous invasion, high nuclear grade, high mitotic rate, high Ki-67 and high PCNA expressions (P < or = 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P < or = 0.05 for all). An inverse correlation was present between p21(waf1/cip1) and cyclin D1 (P = 0.011). Cyclin A predicted survival in the entire study group (P = 0.0014), in T1-4/N0-2/M0 (P = 0.0007) and in T1-2/N0/M0 tumours (P = 0.0007). Cyclin A was also a powerful predictor of disease-free survival in T1-4/N0/M0 (P = 0.0027) tumours (P = 0.0007). Cyclin D1 and p21(waf1/cip1) were not significantly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence of distant metastases (relative risk (RR) 5.16, P < 0.001), T category (RR 2.68, P < 0.001), Ki-67 expression (RR 1.02, P = 0.026) and cyclin A expression (RR 1.12, P = 0.001). The independent predictors in T1-4/N0/M0 tumours were T-category (RR 2.67, P = 0.001) and cyclin A (RR 1.21, P < 0.001), and in T1-2/N0/M0 tumours the only significant predictor was cyclin A (RR 1.19, P = 0.0002). In renal cell carcinoma, cyclin A is a powerful and independent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21(waf1/cip1) have no prognostic value.
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PMID:Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival. 1047 Oct 53

Blood lymphocytes of a HLA-A2 positive breast cancer patient were stimulated with either MCF-7 or MDA-MB-231, i.e., HLA-A2-matched allogeneic breast carcinoma cell lines. Several CD8+ CTL clones with reactivity against the stimulator cells but not against K562 were generated. Reactivity could be blocked with monoclonal antibody (mAb) W6/32, MA2.1, and/or BB7.2, indicating that the clones are HLA-class I and HLA-A2 restricted. The CTL clones generated following stimulation with MCF-7, recognized various other allogeneic HLA-A2+ tumor cell lines, including breast carcinoma, renal cell carcinoma, and melanoma cell lines, but not HLA-A2 tumor cell lines. The CTL clones did not recognize normal HLA-A2+ cells including breast epithelial cells, renal proximal tubular epithelial cells (PTEC), or EBV-transformed B cells including the autologous EBV cell line. In contrast to the CTL clones induced with MCF-7, the reactivity of the clones stimulated with MDA-MB-231, was limited to the stimulator cell MDA-MB-231. Cytotoxicity assays utilizing T2 cells loaded with peptides as target cells indicated that none of the examined CTL-epitopes derived from HER-2/neu, Muc-1, Ep-CAM-1, and p53 were recognized by the CTL clones generated. Our findings underscore that breast cancer is an immunogenic tumor and that HLA-class I-matched allogeneic tumor cells can be used as stimulator cells to generate tumor-specific CTL from peripheral blood of a breast cancer patient with specificity for an antigenic determinant that is broadly expressed on tumor cells from various origins or with specificity limited to the breast cancer stimulator cell.
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PMID:Isolation of broadly reactive, tumor-specific, HLA Class-I restricted CTL from blood lymphocytes of a breast cancer patient. 1062 33

Using fluorescence in situ hybridization (FISH) to interphase nuclei, we examined the replication timing of 1 allele relative to its counterpart in PHA-stimulated peripheral blood lymphocytes of normal subjects and patients suffering from a solid tumor (renal cell carcinoma). In the FISH assay, an unreplicated DNA sequence is identified by a single dot-like hybridization signal, whereas a replicated region gives rise to a duplicated, bipartite signal. Accordingly, lymphocytes of normal individuals show 2 patterns of allelic replication: (i) synchronized replication of allelic counterparts, as exemplified by the biallelically expressed loci TP53 and D21S55; and (ii) non-synchronized replication of allelic partners, as exemplified by the early and late replicating alleles of GABRB3, an imprinted locus subjected to monoallelic expression. However, when present in lymphocytes of the cancer patients, all 3 loci change their replication mode: alleles of TP53 and D21S55 become asynchronous, whereas the early replicating allele of GABRB3 delays replication, leading to relaxation in the imprinted mode of replication. Based on the tight relationship between temporal order of allelic replication and allelic mode of expression, the modified order of allelic replication observed in nonmalignant cells of individuals diagnosed with cancer represents a novel genetic alteration associated with malignancy. This alteration detected by simple cytogenetic means, applied to peripheral blood lymphocytes, offers a potential test for cancer identification. Genes Chromosomes Cancer 27:270-277, 2000.
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PMID:Modification in the inherent mode of allelic replication in lymphocytes of patients suffering from renal cell carcinoma: a novel genetic alteration associated with malignancy. 1067 16


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