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)

An interesting multiple tumor case is described in which 4 different kinds of tumors were diagnosed in the same patient at autopsy and histopathologic examination. The tumors were the following: 1) prolactinoma of the anterior pituitary lobe; 2) basal cell carcinoma of the nose; 3) adenocarcinoma of the colon sigmoideum; 4) multiple oncocytomas (oncocytomatosis) in the kidneys. Immunohistochemical investigation for p53 revealed a strong intranuclear positivity in the colonic carcinoma cells as a result of the overexpression of a possible mutant type of the protein. The other 3 tumors were negative with the p53-specific DO-7 antibody, therefore, no point mutation was thought to be present in the p53 gene of the tumor cells. The immunohistochemical and anamnestic data suggested that this is not a hereditary syndrome, and there is no common pathogenesis of these tumors. Its rarity is interesting in our case because of the coincidence of 4 different unrelated tumors and the absence of anamnestic data for familial accumulation or predisposition for multiple tumors.
 ...
PMID:Multiple tumor case: report and analysis of an autopsy case. 926 95

Ultraviolet (UV) radiation is the carcinogenic factor in sunlight; damage to skin cells from repeated exposure can lead to the development of cancer. UV radiation has been mainly implicated as the cause of non-melanoma skin cancer, although some role for UV in malignant melanoma has been suggested. The induction of skin cancer is mainly caused by the accumulation of mutations caused by UV damage. Cellular mechanisms exist to repair the DNA damage, or to induce apoptosis to remove severely damaged cells; however, the additive effects of mutations in genes involved in these mechanisms, or in control of the cell cycle, can lead to abnormal cell proliferation and tumor development. The molecular events in the induction of skin cancer are being actively investigated, and recent research has added to the understanding of the roles of tumor suppressor and oncogenes in skin cancer. UV radiation has been shown to induce the expression of the p53 tumor suppressor gene, and is known to produce "signature" mutations in p53 in human and mouse skin cancers and in the tumor suppressor gene patched in human basal cell carcinoma. The role of UV radiation in suppression of immune surveillance in the skin, which is an important protection against skin tumor development, is also being investigated. The knowledge gained will help to better understand the ways in which skin cancer arises from UV exposure, which will in turn allow development of better methods of treatment and prevention.
 ...
PMID:Mechanisms of induction of skin cancer by UV radiation. 934 91

The p53 tumor suppressor gene is frequently mutated in human cancer, including squamous cell carcinoma and basal cell carcinoma of the skin, but is rarely mutated in skin melanoma. The p53 mutation spectrum provides insight into both the etiology of human cancer and the functional regions of the encoded protein that lead to clonal expansion of the p53 mutant cell.
 ...
PMID:p53: at the crossroads of molecular carcinogenesis and molecular epidemiology. 962 3

We report the histological, immunohistochemical and ultrastructural findings of an exophytic cutaneous tumor composed of a mixture of typical basal cell carcinoma (BCC) and malignant fibrous histiocytoma. Nine previously reported carcinosarcomas of the skin are reviewed. We prefer the term "sarcomatoid carcinoma" for this rare neoplasm. Only the BCC showed a positive immunoreaction to cytokeratin; the sarcomatous component was negative, but it did express vimentin, and, focally, smooth-muscle-specific actin and KP1 (CD68). Both components showed p53 immunostaining.
 ...
PMID:Sarcomatoid carcinoma of the skin: report of a case. 964 Aug 85

Curcumin, a potent antioxidant and chemopreventive agent, has recently been found to be capable of inducing apoptosis in human hepatoma and leukemia cells by way of an elusive mechanism. Here, we demonstrate that curcumin also induces apoptosis in human basal cell carcinoma cells in a dose- and time-dependent manner, as evidenced by internucleosomal DNA fragmentation and morphologic change. In our study, consistent with the occurrence of DNA fragmentation, nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished the p53 increase and apoptosis induced by curcumin, suggesting that either de novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear extracts of cells treated with curcumin displayed distinct patterns of binding between p53 and its consensus binding site. Supportive of these findings, p53 downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we immunoprecipitated extracts from basal cell carcinoma cells with different anti-p53 antibodies, which are known to be specific for wild-type or mutant p53 protein. The results reveal that basal cell carcinoma cells contain exclusively wild-type p53; however, curcumin treatment did not interfere with cell cycling. Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with the curcumin treatment. Finally, treatment of cells with p53 antisense oligonucleotide could effectively prevent curcumin-induced intracellular p53 protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus, our data suggest that the p53-associated signaling pathway is critically involved in curcumin-mediated apoptotic cell death. This evidence also suggests that curcumin may be a potent agent for skin cancer prevention or therapy.
 ...
PMID:Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. 976 49

To investigate the regulation of apoptosis and proliferation in arsenic-induced skin cancers, we examined the expression of bcl-2, p53, and Ki-67 using immunohistochemical staining. Thirty patients with Bowen's disease (BD), ten with basal cell carcinoma (BCC), eight with squamous cell carcinoma (SCC) and eleven of perilesional normal skin (PLN) of the non-sun exposure sites from endemic area were examined. The results showed that: 1) bcl-2 was expressed in all of the BCC homogeneously, in none of the SCC, and in 12/30 of the BD focally or homogeneously; 2) p53 was expressed in all of the arsenical skin cancers with a labelling index of 75 +/- 14% of BD, 50 +/- 17% of BCC, 61 +/- 15% of SCC, and also in all of the perilesional normal skin with a labelling index of 55 +/- 24%; 3) Ki-67 was expressed in all of the skin cancers with labelling index of 58 +/- 17% of BD, 12 +/- 7% of BCC, 47 +/- 21% of SCC, and in 9/11 of PLN with a labelling index of 41 +/- 24%. Expression of bcl-2 in BCC or BD is related to the phenotype of germinative basal cell. The constant expression of bcl-2 i early dysplastic cells of BD and the earliest expression of P53 in the basal cells of perilesional normal skin indicate that the initial step of arsenic-induced carcinogenesis is from the basal germinative cells. There is no mutual relationship between bcl-2, p53 or Ki-67 expression in any type of the arsenical skin cancers, but there is a positive correlation between p53 and Ki-67 expression identified in perilesional normal skin. BD had the highest labelling index of p53 and Ki-67.
 ...
PMID:Expression of bcl-2, p53 and Ki-67 in arsenical skin cancers. 982 Oct 74

Three hundred and sixteen patients with nonmelanocytic skin cancer, including 46 cases of Bowen's disease (BOD), 134 cases of squamous cell carcinoma (SCC), and 136 cases of basal cell carcinoma (BCC), were examined immunohistochemically using monoclonal antibody DO-7 to assess p53 protein accumulation related to sun exposure and ageing, and growth and differentiation of skin cancer and its precursors. The rates of p53 immunostaining of BOD, SCC and BCC were 80.4%, 76.1% and 70.6%, respectively. p53-positive cells were present not only in cancer nests, but also in dysplastic and even morphologically normal epidermis adjoining cancers. Sun exposure was statistically correlated with the p53 immunostaining scores in morphologically normal epidermis of the three skin cancers and in cancer nests of SCC and BCC. The positivity and score of p53 protein often differed significantly among the three types of cancer, especially in regions of dysplasia. Interestingly, differentiation of SCC was correlated with individual p53 scores for dysplasia and cancer nests, especially for dysplasia. BOD, as the precursor of SCC, demonstrated the strongest p53 expression. Furthermore, 12.3% cases with p53 negative cancer nests showed p53-positive reaction in dysplasia and in morphologically normal epidermis. It seems that the accumulation of p53 protein plays a part in precancerous lesions and in the genesis of more highly differentiated types of skin cancer and affects mainly the growth of tumour cells rather than their differentiation. For BCC, however, age was significantly related to p53 expression. Our findings suggest that overexpression of p53 in normal skin and cancer nests of SCC and BCC is significantly related to sun exposure, that the expression of p53 in BCC is an age-dependent process, and that the early accumulation of p53 protein may be a useful predictor for the detection of nonmelanocytic skin cancer.
 ...
PMID:Sun-exposure- and aging-dependent p53 protein accumulation results in growth advantage for tumour cells in carcinogenesis of nonmelanocytic skin cancer. 1019 Feb 97

Oral arsenic exposure increases the risk for a variety of benign and malignant skin lesions, but the molecular mechanism of the carcinogenic effect is poorly understood. Arsenic-related squamous cell carcinomas of the skin can develop either de novo or progress from Bowen's disease lesions. Arsenic-related basal cell carcinomas develop usually in non-sun-exposed areas and are multiple. Because p53 tumor suppressor protein is a protective cellular molecule against environmental carcinogens and mutations in the p53 gene are frequent in nonmelanoma skin cancers, we studied p53 in 23 premalignant or malignant skin lesions from seven patients with a history of arsenic medication. The eighth patient studied (with six lesions) had a long standing exposure to UV radiation. Accumulation of the p53 protein was detected (with a monoclonal DO-7 antibody) in 78% of the lesions from cases with arsenic exposure. Two of the six (30%) arsenic-related premalignant lesions and in addition one UV related carcinoma in situ lesion were clearly and repeatedly positive when p53 exons 5 to 8 were screened by a nonradioactive single-strand conformation polymorphism (SSCP) analysis. Only one of the arsenic-related lesions was confirmed by sequencing to have a mutation (a CC to TT double transition). No indications of mutations were found among the 18 basal cell carcinoma or two squamous cell carcinoma lesions studied. Our results suggest that the frequent accumulation of p53 protein in arsenic-related skin lesions is not due to p53 mutations. which may not be a prerequisite in the development of arsenic-induced skin cancers.
 ...
PMID:Infrequent p53 mutations in arsenic-related skin lesions. 1022 23

Increased expression of p53 has been found in the majority of basal cell carcinomas (BCCs). The pattern and intensity of this staining, as well as staining for proliferation antigens, seems to correlate with behavior of histologic subtypes of BCC. Nevus sebaceus (NS) is considered a hamartoma. Multiple epithelial neoplasms do arise in NS, and, rarely, they show an aggressive biologic behavior. Significant numbers of these neoplasms, however, have areas of basaloid hyperplasia that are often reported as BCC. Although morphologically similar to BCC, the mechanism underlying the development of these areas has not been investigated, so we sought to evaluate the expression of Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, Factor XIIIa, and CD34 in areas showing basaloid hyperplasia, arising in NS. We performed immunohistochemical stains for Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, Factor XIIIa, and CD34 on seven cases of NS with areas of basaloid hyperplasia. All of the eight cases of NS showed diffuse positive membrane staining for Ber-EP4 and negative nuclear staining for p53. Proliferating cell nuclear antigen and Ki-67 staining was only slightly increased in the areas of basaloid hyperplasia, compared with the surrounding epidermis and with areas of the epidermis peripheral to the hamartomatous proliferation, and bcl-2 was only focally positive. Factor XIIIa-positive cells and CD34-positive vascular endothelial cells were increased within the subjacent dermis, a pattern suggestive of follicular differentiation. Our findings suggest that even though areas of basaloid hyperplasia in NS are morphologically similar to BCC, they are induced by different stimulatory and molecular mechanisms. These different mechanisms result in expression of immunohistochemical markers more characteristic of benign follicular tumors than of BCC.
 ...
PMID:Immunohistochemical staining for Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, CD34, and factor XIIIa in nevus sebaceus. 1034 81

Squamous cell carcinoma of the skin and melanoma are the rare progeny of precancerous lesions that usually remain stable or regress. For SCC the sequence appears to include TP53 mutant clones in normal skin; dysplasia; carcinoma in situ; and SCC. When such lesions are contiguous, their TP53 mutations are consistent with a single clonal lineage. The set of TP53 mutations in tumours is more restricted than in precancers, suggesting additional selection. Melanoma lies at the end of a continuum including mole, dysplastic naevus, radial growth melanoma and vertical growth. The genetics of melanoma is less clear. Basal cell carcinomas seem to arise without a precancer and contain mutations in TP53 and PTCH. Childhood sunlight exposure directs the location and frequency of precancers. For melanoma, its effects on intermittently exposed body sites are superimposed on the effect at sites chronically exposed. SCC precancers and tumours, BCC tumours and melanoma cell lines contain UV induced mutations. Sun exposed skin of normal individuals contains thousands of small clones of TP53 mutated cells. Predisposition to sunlight induced precancer is a multigenic trait involving factors such as hair and skin color, DNA repair proficiency and mole type and number. These each contribute a relative risk on the order of two to four. Familial predisposition to dysplastic naevi carries a larger risk. The cell of origin for melanoma is uncontroversial, and the proposed hair follicle origin of BCC is consistent with the presence of stem cells in the bulge region. The origin of SCCs and the arrangement of interfollicular stem cell compartments are less clear. Clonal expansion of the initial mutated cell may also be driven by sunlight. When a mutation confers apoptosis resistance, as TP53 mutations do, subsequent UV exposure will be more likely to kill normal cells than mutants. The latter can expand into a clone, only one cell of which need be mutated again. Immunosuppressant drugs may have the same effect as UV, facilitating the clonal expansion of precancers. In the absence of exogenous influences, mutant clones and precancers tend to regress. There is little evidence that regression of precancers is immunological, though regression of melanoma appears to be. The chemotherapeutic agent 5-FU causes regression of dysplasias by removing initiated cells, perhaps by enhancing apoptosis. In contrast, retinoic acid temporarily suppresses clonal expansion. Most sunscreens are mutagenic, with as yet unknown consequences. Mice develop dysplasias and SCCs after UV irradiation. Initiation and clonal expansion of dysplasias is UV driven, but conversion to SCC and subsequent growth involve spontaneous events. With chemical carcinogens mice develop papillomas that usually regress and thus are precancers. Tumour promotion yields abundant low risk papillomas that contain Hras1 mutations but rarely progress to SCC. High risk papillomas are infrequent but do convert to SCC, particularly if re-treated with mutagens. Conversion to SCC is associated with TP53 mutations. The mechanisms of multiple mutation and clonal expansion observed in human and mouse systems, respectively, are beginning to converge into a coherent understanding of precancerous events in skin.
 ...
PMID:Skin precancer. 1048 24


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