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)

In order to clarify the significance of mutation of the p53 tumor suppressor gene in the genesis and development of human hepatocellular carcinoma (HCC) in an aflatoxin B1 low-exposure area, the spectrum, i.e., incidence, type, and site, of p53 gene mutations was examined in 169 tissue samples resected mainly from Japanese patients using single-strand conformation polymorphism analysis and direct sequencing. Forty-nine tumors (29%) showed a p53 mutation (39 point mutations and 10 frameshifts). The point mutations comprised 18 transitions, only 4 of which occurred at CpG sites, and 21 transversions. Two evolutionarily conserved domains, IV and V, contained 65% of all mutations and codon 249 was the most frequent mutation site (7/49). The spectrum of p53 mutation did not differ among HCCs in relation to the type of hepatitis virus infection, sex, age, and background liver disease of patients, tumor size, or presence of metastasis, but incidence and site were significantly associated with the degree of differentiation of cancer cells. In poorly differentiated HCC, p53 mutation was frequent (54%) and clustered on domains IV and V, whereas in well or moderately differentiated HCC, the mutation was less frequent (21%) and equally distributed on domains II to V. Restriction fragment length polymorphism analysis revealed loss of heterozygosity on chromosome 17p in 55 (69%) of 80 informative cases and in 34 (95%) of 36 cases with p53 mutation. Therefore, p53 gene mutation is suggested to occur independently of the type of viral infection or status of preexisting liver disease and to occur preferentially in moderately and poorly differentiated HCCs in association with or after loss of another p53 allele as a late event of HCC progression.
Cancer Res 1992 Nov 15
PMID:p53 gene mutation spectrum in hepatocellular carcinoma. 133 Feb 91

Mutant p53 has been found in a wide variety of human malignancies including carcinomas of the lung, breast and colon. Because of the controversial mutational rate of the p53 gene in hepatocellular carcinoma, a large series of liver tumors from white patients with different risk factors was examined immunohistochemically for expression of the p53 mutant to assess its prevalence and the relationships between p53 overexpression and clinicopathological data. Nine of 58 specimens were found to have detectable evidence of p53 gene mutation by virtue of the immunohistochemical detection of mutant p53 protein. The p53 mutation was more frequent in patients with serological hepatitis B and C markers than in patients without these markers (p = 0.046). The prevalence of p53-positive tumors was also significantly higher in the group of tumors with invaded portal branches than in the group without (p = 0.02). Our results showed that p53-positive hepatocellular carcinoma is a rare finding in patients exposed to a low dietary aflatoxin intake and that p53 mutation seems to occur at a late stage of the tumoral process and could contribute to an aggressive tumoral phenotype.
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PMID:Overexpression of p53: a rare event in a large series of white patients with hepatocellular carcinoma. 133 Aug 67

Recent developments in the field of oncogenes and growth stimulatory factors have provided limited but essential models in neuro-oncology. The observation in gliomas of platelet growth factor (PDGF)-like immunoreactivity fits with the autocrine secretion model, rising the possibility for the growth factor independence of the cancer cells. The discovery of the tumor suppressor genes, for which loss of function mutations are oncogenic as in the RB gene of the retinoblastoma and p53 gene, has introduced a new concept of oncogenesis which could be useful even in the cure of the neoplasms. Several oncogenes are amplified and/or expressed in brain tumors, some associated with polymorphism leading to abnormal protein products. Therefore, corresponding functions, such as production of deficient epidermal growth factor receptor (EGFR) encoded by erb-B, are impaired. Abnormal chromosomal patterns have been recognized in brain tumors and found mainly in chromosomes 7 and 22 on which oncogenes erb-B and sis are located, respectively. Location of proto-oncogenes, which are normally expressed in the brain, indicate that they share common distribution patterns mainly involving the cerebellum, hippocampus and olfactory bulbs. These proto-oncogenes may be regulated by physiological and pathological events. The concept of oncogene involvement in brain tumors must be extended to include the other factors such as G-proteins, growth factor receptors, membrane-associated and cytoplasmic protein kinases, which are all responsible for the control of the cell growth and their response to external signals including chemotherapeutic drigs.
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PMID:Oncogenes: cause or consequence in the development of glial tumors. 133 37

One of the major debates in hepatocellular carcinogenesis at present is whether the hepatitis-B and -C viruses are directly carcinogenic or exert their effect indirectly by causing chronic necro-inflammatory hepatic disease, which in turn is responsible for malignant transformation of hepatocytes. This debate has been fueled by the observation that hepatitis C virus is a single-stranded RNA virus with no precedent for inducing cancer but with a marked propensity to cause chronic necro-inflammatory hepatic disease and by the findings in Chisari's transgenic mouse model, which suggest that severe and prolonged hepatocellular injury per se induces a proliferative response that progresses to tumour formation. Recent reports of a guanine to thymine mutation of the third base of codon 249 of the tumour suppressor gene, p53, in 50% of patients with hepatocellular carcinoma in regions of high aflatoxin exposure, and mutagenic experiments showing that aflatoxin B1 binds particularly to guanine residues in G-C-rich domains and that codon 249 is a preferred target have suggested a mechanism whereby aflatoxin might induce malignant transformation.
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PMID:Tumours of the liver. 133 85

The products of the two major suppressor genes p53 and Rb interact with the oncogene products of the DNA tumour viruses. These viral-host protein interactions mimic and interfere with the normal interactions of p53 and Rb with host proteins. The Rb gene product is frequently mutated in human cancers such that it no longer binds to viral or host proteins. In contrast we find that this is not the case with p53 as some, but not all, mutant p53 proteins still bind to the SV40 T antigen. In particular the hot spot mutation found in most Chinese and African cases of hepatocellular carcinoma (HCC) retains T binding activity. The simple subdivision of different p53 mutations revealed by this analysis may have diagnostic and prognostic consequences.
Eur J Cancer 1992
PMID:Diversity of human p53 mutants revealed by complex formation to SV40 T antigen. 133 35

The presence of mutations in the p53 gene was examined in ovarian cancers by a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. The primers were designed to amplify exons 5 through 9 that contain phylogenetically conserved domains of the p53 gene. Mutations were detected in 5 out of 10 cases, one of which contained a deletion in the second allele. A single base substitution was detected in 4 cases at codons 162, 175, 205 and 273 and a single base insertion in one case within codon 315. A high frequency of p53 mutations in ovarian cancers and lack of mutation in 6 benign ovarian tumors and 2 normal ovaries suggested that the mutation of the p53 gene was associated with the genesis and/or progression of ovarian cancer. In 1 of 7 endometrial cancers, two mutations at codons 239 and 254 were detected.
Jpn J Cancer Res 1992 Oct
PMID:Detection of p53 gene mutations in human ovarian and endometrial cancers by polymerase chain reaction-single strand conformation polymorphism analysis. 133 65

In this study we analysed by immunohistochemistry the expression of p53 protein in 14 malignant fibrous histocytomas (MFHs), 22 other types of sarcoma (eight leiomyosarcomas, four rhabdomyosarcomas, four liposarcomas, two fibrosarcomas, two chondrosarcomas, one malignant schwannoma, and one dermatofibrosarcoma protuberans), and 25 non-malignant mesenchymal lesions (eight dermatofibromas, four cases of nodular fasciitis, three leiomyomas, three fibromatoses, two epithelioid.leiomyomas, two neurofibromas, one schwannoma, one myositis ossificans, and one giant cell tumour of tendon sheath). Four MFHs and nine other types of sarcoma (four leiomyosarcomas, two chondrosarcomas, one liposarcoma, one fibrosarcoma, and one dermatofibrosarcoma protuberans) showed nuclear positivity for p53. Of the benign soft tissue lesions, p53 positivity was observed in two fibromatoses, one nodular fasciitis, and one dermatofibroma. The number of p53-positive cells in these benign lesions was considerably smaller than that in most of the p53-positive sarcomas. The p53 positivity in MFHs and other types of sarcoma indicates that p53 gene alterations may play a part in the neoplastic transformation of these tumours. The occurrence of p53 positivity in benign mesenchymal lesions suggests that sometimes p53 protein may accumulate in cells without an associated malignancy. Because of this, p53 immunoreactivity cannot, by itself, be used as a criterion of malignancy. According to our results, p53 positivity in over 1 per cent of tumour cells in mesenchymal lesions favours malignancy.
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PMID:p53 immunohistochemistry in malignant fibrous histiocytomas and other mesenchymal tumours. 133 24

Fifteen primary non-small-cell lung carcinomas (8 adenocarcinomas and 7 squamous-cell carcinomas) were analyzed by multiparameter flow cytometry for their expression of p53 and c-myc proteins. In addition, the fraction of cells staining with the proliferation-associated antibody Ki-67 and DNA ploidy was determined. These 4 biological markers were analyzed in parallel samples from a single-cell suspension made from fresh, frozen biopsies. Thus, the internal relationship between these markers within each tumor-cell population was established. Three different anti-p53 antibodies were used: PAb 421, PAb 1801 and PAb 240. All 15 tumors were p53-positive with the antibodies PAb 1801 and PAb 240, whereas only 9 were positive as judged by the antibody PAb 421. This indicates that the choice of p53 antibody is not irrelevant. Ten tumors were c-myc-positive; 7 of these were adenocarcinomas. The c-myc-positive tumors had a significantly higher level of p53 expression, judged by PAb 1801 and PAb 240, than c-myc-negative tumors. For PAb 421, there was no difference. We did not find any correlation between Ki-67 staining and expression of p53 and c-myc proteins, either with DNA ploidy, S-phase fraction or histological type. Our study indicates that there might be an association between accumulation of p53 protein and c-myc over-expression in non-small-cell lung cancer, and that this in particular might apply to adenocarcinomas. Furthermore, we show that multiparameter flow cytometry is a powerful tool in the study of the relationship between different markers in a cell population.
Int J Cancer 1992 Dec 02
PMID:Quantitation of biological tumor markers (p53, c-myc, Ki-67 and DNA ploidy) by multiparameter flow cytometry in non-small-cell lung cancer. 133 53

Using the polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis, we have examined the highly conserved regions of the p53 gene in 58 biopsy samples of head and neck tumors. Mutations were found in 13/58 (23%) tumor specimens, but not in 6 normal tissues. Ten of 13 mutations were due to single base changes and the remaining 3 were 1- or 8-base deletion mutants. These mutations were clustered in exons 5 and 7 and resulted in amino acid changes. Our results seem to indicate that mutations in the p53 gene contribute to a significant number of cases of the head and neck tumors including 20% of nasopharyngeal carcinoma biopsies. The relationship of Epstein-Barr virus or human papillomavirus and p53 gene mutations in this group of cancers was also analyzed and discussed.
Cancer Lett 1992 Dec 24
PMID:Detection of mutations in the p53 gene in human head and neck carcinomas by single strand conformation polymorphism analysis. 133 31

The clinical and pathological significance of mutation of the p53 tumor-suppressor gene was examined in 108 cases of primary uterine cancers using single-strand conformation polymorphism and direct DNA sequencing analyses. Mutation of the p53 gene was detected in 19 (31%) of 62 cases of cancer of the uterine corpus and was more frequent in groups at an advanced clinical stage and/or with aggressive histology. Among four adenocarcinomas arising in the lowest portion of the uterine corpus, three showed integration of human papillomavirus (HPV) types 16 and/or 18 DNA, and two of them also showed p53 mutation. In cancer of the uterine cervix, p53 mutations were rare; 7% (3/46) in total, 3% (1/30) of cases with integration of HPV types 16 and/or 18 DNA and 13% (2/16) of cases without HPV DNA integration. Three mutations were detected among two cases at clinical stage IV and two cases of undifferentiated cervical carcinoma. Immunohistochemically, all five cases of uterine cancer which showed diffuse (> 50% of cancer cells) nuclear staining of p53 protein also carried the p53 mutation. Therefore, p53 alterations were suggested to be involved in the development of uterine cancers showing aggressive biological behavior. Although a high incidence of HPV DNA integration and a low incidence of p53 mutation were confirmed in cancer of the uterine cervix, there was no inverse association between integration of HPV types 16 and/or 18 DNA and p53 mutation.
Jpn J Cancer Res 1992 Nov
PMID:Frequent occurrence of p53 gene mutations in uterine cancers at advanced clinical stage and with aggressive histological phenotypes. 133 92


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