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)

Recent studies have demonstrated that allelic losses at chromosome 17p are associated with the genesis of a wide variety of human cancers. In order to assess whether the rearrangement of chromosome 17p was responsible for the genesis of renal cell carcinoma (RCC), we used restriction fragment length polymorphism analysis of chromosome 17p. We studied 48 RCCs, including 6 metastatic RCCs, from 43 patients with 5 polymorphic probes to loci within or near the p53 gene. Allelic losses at chromosome 17p were detected in only 6 of the 36 informative cases (17%), and no definitive correlation was demonstrated between allelic losses at 17p and the tumor stages. The 6 RCCs with allelic losses at 17p were histopathologically classified as a clear cell type in one, a mixed cell type in one, and granular cell types in the other four cases. Allelic losses at 17p in the clear cell type of RCC were infrequent (6%, 1 of 18), and were not detected even in the metastatic tumor from a highly advanced case. This finding suggests that allelic losses at 17p could be random genetic rearrangements in the case of the clear cell type of RCC. On the other hand, allelic losses at 17p in the granular cell type of RCC were demonstrated with a significantly higher frequency (44%, 4 of 9). We previously reported that allelic losses at 3p were specific to the clear cell type of RCC (Ogawa et al., Cancer Res., 51:949-953, 1991). Examination of the association of allelic losses at 17p with those at 3p revealed that none of 5 informative RCCs with allelic losses at 17p showed allelic losses at 3p. Conversely, 17 of 25 informative RCCs with retention of 17p alleles lost alleles at 3p. Thus, an inverse relationship was demonstrated with statistical significance (P less than 0.01). These data suggest that the types of rearrangement on chromosome 17p and/or chromosome 3p can differentiate between the histopathological subtypes of RCC.
 ...
PMID:Allelic losses at chromosome 17p in human renal cell carcinoma are inversely related to allelic losses at chromosome 3p. 134 14

This article reviews the present understanding of chromosomal aberrations and specific genetic mutations in renal, bladder, and prostate cancers. In kidney tumors, specific emphasis is given to chromosome 3 deletions in renal cell carcinoma and the characterization of the WT1 gene in Wilms' tumor. In all three urological tumors, the presence of mutations in the RAS, P53, and RB genes (all of which often occur in other tumors) is analyzed. The expression and properties of the androgen receptor in prostate cancer are also summarized.
 ...
PMID:The molecular biology of urological tumors. 157 58

Mutation of the p53 gene, which plays an important role in the genesis of diverse human cancers, was investigated in 23 surgical specimens of human renal cell carcinoma using the polymerase chain reaction single-strand conformation polymorphism method of analysis. Only one of the 23 tumors (4.3%) carried a mutated p53 gene, which was present in exons 7-8. Direct DNA sequencing confirmed a point mutation at codon 276 (GCC to CCC) resulting in a substitution of alanine for proline. No specific clinicopathological characteristics were observed in the case with the p53 gene mutation in human renal cell carcinoma. These observations suggest that mutation of the p53 gene is rare and thus does not contribute significantly to the genesis of this tumor.
 ...
PMID:Infrequent mutation of p53 gene in human renal cell carcinoma detected by polymerase chain reaction single-strand conformation polymorphism analysis. 158 82

In animal systems, complete and permanent eradication of tumours can be achieved by adoptive transfer of MHC-restricted T cells, combined with IL2. In certain types of human cancer (melanoma and perhaps renal cell carcinoma), tumour-specific T cells are probably the therapeutically most active cells among LAK or TIL cells. To prove these points, it is necessary to conduct trials with cloned tumour-specific T cells. Other potentially immunogenic tumors are cervical carcinoma, associated with human papilloma virus, and Burkitt's lymphoma, associated with Epstein-Barr virus. Most other human tumours, caused by subtle mutations in proto-oncogenes, are likely to be poorly or non-immunogenic. It is worthwhile trying to overcome this by vaccination with IL2 or IFN gamma-producing tumour cells or by deliberate vaccination with desirable targets for tumour-specific CTL such as the products of point-mutated oncogenes, including ras (Jung and Schleusener, 1991) and p53 (Rodriguez et al., 1990; Halevy et al., 1990), provided the relevant peptides are processed and bound to MHC class I molecules. Other potential targets are breakpoint peptides of translocated oncogene products such as bcr/abl (Van Denderen et al., 1990). In viral systems, it has already been established that peptide vaccination for protective CTL induction is feasible (Aichele et al., 1989; Schulz et al., 1991; Kast et al., 1991).
 ...
PMID:T-cell immunotherapy of cancer. 175 15

The human p53 gene, a putative tumor suppressor gene, has a polymorphism in amino acid residue 72. We recently developed a method of detecting codon 72 polymorphism in this gene by digestion of polymerase chain reaction-amplified DNA using an allele-specific restriction endonuclease. This polymorphism allows the identification of loss of heterozygosity for the coding region of the p53 gene in limited tissue samples in a short time without using radioactive materials. We examined 33 patients with renal cell carcinoma and 29 with bladder cancer; heterozygosity in the p53 gene was lost in 60% (6 of 10 cases) and 73% (8 of 11 cases) of the renal and bladder tumors, respectively. Additionally, the assay's sensitivity could be improved by using DNA extracted from frozen sections of the tumors. Because the proportions of tumor cells and nontumor cells could be assessed by microscopic evaluation of the frozen sections, we were able to minimize contamination from nontumor cells, which occasionally causes false readings of retained heterozygosity. This simple and sensitive method for detecting loss of heterozygosity in the p53 gene makes it possible to rapidly screen a large number of tissue samples and has the potential to be a useful diagnostic tool for a wide variety of human neoplasms.
 ...
PMID:Detection of loss of heterozygosity in the p53 gene in renal cell carcinoma and bladder cancer using the polymerase chain reaction. 200 30

In a recent paper, we described the expression pattern of proto-oncogenes in primary human renal cell carcinoma [12]. To test the possibility of using xenografts as a useful alternative for such studies, we analyzed xenografts of a number of human renal cell carcinomas in nu/nu mice. Xenografts included RC2, RC14, RC21, RC43 and NC65. Northern blot analysis indicated that c-Ras was expressed in all these xenografts. The identity of the ras transcripts in the individual xenografts was further specified as c-Ha-ras, c-Ki-ras or N-ras. Expression of c-myc and the p53 gene was also found in a number of these tumors. Only RC21 failed to express the c-myc or the p53 gene. In all xenografts, a 3.0 kb c-fes/fps mRNA was present. In RC2, RC14, RC21 and RC43, low levels of the 4.8 kb ab 1 transcript were detectable. Transcripts of myb and sis could not be detected in any of the xenografts. The results indicated that the expression pattern of a variety of proto-oncogenes in xenografts of human renal cell carcinomas was similar to that in the primary tumors.
 ...
PMID:Expression of proto-oncogenes in xenografts of human renal cell carcinomas. 332 44

Four new permanent cell lines (RCC-A, -B, -C, and -D) derived from different human renal cell carcinomas of the clear cell type were established in tissue culture. The cell lines displayed characteristic differences in cell size and shape, which allowed individual identification by phase contrast microscopy. Ultrastructurally, the cell lines exhibited varying amounts of cytoplasmatic glycogen and lipid. Immunohistochemistry revealed co-expression of vimentin and cytokeratin in all cell lines. The mean population doubling time ranged from 27 h (RCC-A) to 104 h (RCC-D). RCC-B and -C cells produced slowly growing tumours after heterotransplantation into nude mice, whereas RCC-A and RCC-D cells were non-tumorigenic. The modal chromosome number was either near-diploid (RCC-A, -B, and -C) or near triploid (RCC-D). Clonal abnormalities affecting the short arm of chromosome 3 were seen in all cell lines. Northern blot analysis revealed no expression of the proto-oncogenes c-fos, c-ros, and c-mos, whereas c-Ki-ras expression was observed in all cell lines. Expression of c-myc was observed in RCC-A, RCC-B, and RCC-D cells, whereas c-raf expression could be detected in RCC-B and RCC-D. Tumour suppressor gene p53 mRNA was observed in the cell line RCC-D.
 ...
PMID:Cytomorphological, cytogenetic, and molecular biological characterization of four new human renal carcinoma cell lines of the clear cell type. 751 57

Hormonal treatment of advanced prostatic cancer patients generally results in an initially beneficial response, but the treated patients develop hormonally resistant disease in which no curative therapy is currently available. Recent studies have revealed that interleukin 6 (IL-6) is a growth factor for myeloma, renal cell carcinoma, and certain T-cell lymphomas. Further, IL-6 has been shown to block apoptosis induced by p53, transforming growth factor beta, and certain cancer chemotherapeutic compounds. The objective of the present study was to determine whether IL-6 is a growth factor for two human prostate cancer lines and whether it protects the tumor cells from drug-induced cell death. Two hormone-independent prostate cell lines were used in this study, namely PC-3 and DU145, and these have been shown to be relatively resistant to cis-diamminedichloroplatinum (CDDP), etoposide (VP-16), and adriamycin (ADR). Both cell lines express IL-6 mRNA and secrete IL-6 constitutively. The addition of anti-IL-6 antiserum to the cell lines resulted in a significant inhibition of cell growth up to day 2, and when additional antibody was added at day 2 the inhibition persisted for 4 days. The coaddition of anti-IL-6 antiserum and CDDP or VP-16 resulted in synergy in cytotoxicity in both cell lines, whereas the combination of antibody and ADR or suramin resulted only in additive effects. Sequential treatment revealed that anti-IL-6 antibody was required to achieve synergy, whereas either sequence of pretreatment resulted in synergy with anti-IL-6 and CDDP but not with VP-16. CDDP treatment of tumor cells down-regulated IL-6 mRNA expression and IL-6 secretion. The present findings demonstrate that IL-6 is an autocrine/paracrine growth factor for DU145 and PC-3 prostate lines. Additionally, the secretion of this cytokine protects the tumor cells against the cytotoxic effect of CDDP and VP-16 and its neutralization sensitizes the cells to cytotoxicity. Overall, the studies suggest that agents that can down-regulate or inhibit protective factors in tumors may overcome drug resistance.
 ...
PMID:Endogenous interleukin 6 is a resistance factor for cis-diamminedichloroplatinum and etoposide-mediated cytotoxicity of human prostate carcinoma cell lines. 755 41

Alterations in the p53 tumor suppressor gene appear to be important in the development of many human tumors. The wild-type p53 gene has a polymorphism at codon 72 that presents the arginine (CGC) or proline (CCC) genotype, which recently has been reported to be associated with genetically determined susceptibility to smoking-related lung cancers. To determine whether this p53 genotype influences individual risk of urologic cancer and/or its progression, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to assay the allelic frequencies of this polymorphism in 85 renal cell carcinoma patients, 151 urothelial cancer patients, 33 testicular cancer patients, 28 prostatic cancer patients and 56 patients without neoplastic disease. The allelic distributions of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) in patients with renal cell carcinoma (29.4%, 55.3%, 15.3%), urothelial cancers (45.7%, 39.7%, 14.6%), testicular cancer (45.4%, 48.5%, 6.1%) or prostate cancer (42.9%, 50.0%, 7.1%) did not differ significantly from those in the normal controls. However, Pro/Pro genotype in renal cell carcinoma and urothelial cancer (smoking-related cancers) was more frequent than that in prostate cancer and testicular cancer (smoking-unrelated cancers) with borderline significance (P = 0.0881). There was no particular correlation between frequency of the three genotypes and grade or stage of each type of tumor. The association of genetic predisposition to urologic cancers with p53 gene codon 72 polymorphism is not so clear as the previous study of Japanese lung cancer patients, but this polymorphism may play some role in urothelial cancers and renal cell carcinoma, in which smoking is an epidemiological risk factor.
 ...
PMID:Allelic frequency of p53 gene codon 72 polymorphism in urologic cancers. 755 95

Rats carrying the Eker tumor-susceptibility mutation (Eker rats) are predisposed to developing renal cell carcinoma. Rats heterozygous for the Eker mutation develop spontaneous multiple bilateral renal cell tumors by the age of 1 yr. In a previous study, Eker-mutation carrier and noncarrier rats were exposed to the renal carcinogen dimethylnitrosamine (DMN), and male rats carrying the Eker mutation exhibited a 70-fold increase in the induction of renal adenomas and carcinomas when compared with noncarrier rats. In this study, spontaneous and DMN-induced rat renal cell tumors (adenomas and carcinomas) were analyzed for mutations of the p53 gene by direct sequencing of cDNA polymerase chain reaction products. There were no mutations in p53 cDNA derived from renal tumors from six untreated rats. Mutations were found in one of 15 of the DMN-induced tumors: a transition at codon 140, CCT-->CTT, in a renal adenoma. Additionally, seven cell lines derived from spontaneous renal cell tumors did not contain mutations in p53. The low frequency of p53 mutations (one of 21 renal cell tumors and none of seven cell lines derived from renal cell tumors) indicates that the development of both spontaneous and carcinogen-induced renal tumors involved a non-p53-dependent pathway. As p53 is infrequently mutated in human renal cell carcinomas and in rat renal mesenchymal tumors, it is likely that a tumor suppressor gene or genes other than p53 are involved in the development of renal cancer.
 ...
PMID:p53 status in spontaneous and dimethylnitrosamine-induced renal cell tumors from rats. 772 45


1 2 3 4 5 6 7 8 9 10 Next >>