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)

Basal cell carcinoma (BCC) generally has an indolent course but a subgroup of BCCs tends to grow aggressively into deep tissues and even metastasize. Although studies have shown a positive correlation between mutations in the tumor suppressor gene p53 and aggressive behavior in epithelial tumors, the results for BCC are conflicting. We aimed to determine whether there is any relationship between p53 expression in BCC and histopathologic subtype of the tumor.Thirty-three formalin-fixed BCC tissue samples were examined at Hazrat-e Rasool University Hospital, Tehran, Iran, from March 2003 to April 2004. Tumors were categorized as aggressive (infiltrative or morpheic) and non-aggressive (nodular or superficial) based on histopathological examination of hematoxylin and eosin sections. p53 expression was demonstrated by immunohistochemical staining using the monoclonal anti-p53 antibody (PAb240) and results were reported using a semiquantitative score. Expression of p53 was compared between aggressive and non-aggressive tumors. All of the 11 aggressive tumors exhibited nuclear staining in more than 50% of the tumor cells. In the 22 non-aggressive tumors, less than 50% of cells showed positive staining. p53 immunoreactivity was significantly higher in aggressive BCCs than non-aggressive ones (x(2) test; p < 0.01). No correlation was found between p53 expression and the age of the patient or site of the tumor. History of childhood radiotherapy correlated positively with higher levels of p53 expression. We conclude that expression of p53 might be used as a marker to predict the aggressiveness of BCCs.
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PMID:Expression of p53 in aggressive and non-aggressive histologic variants of basal cell carcinoma. 1710 76

The class III histone deacetylase (HDAC), SIRT1, is a mammalian homologue of the Saccharomyces cerevisiae chromatin-silencing factor Sir2 that regulates longevity. SIRT1 regulates cell survival via deacetylation of p53 and forkhead transcription factors, and overexpression of SIRT1 is reported to be essential for cell growth and survival in some kinds of cancer. To elucidate the role of SIRT1 in human skin carcinogenesis, we have examined SIRT1 protein expression in 20 cases each of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), and actinic keratosis (AK) by immunohistochemical analysis. Overexpression of SIRT1 is frequently observed in all kinds of non-melanoma skin cancers included in this study. In particular, strong expression was observed in all cases of BD. In addition, no obvious difference between AK and SCC was observed in the expression of SIRT1, suggesting that overexpression of SIRT1 may have some relevance to the early stage of skin carcinogenesis. We suppose that SIRT1 could be one of the critical targets for future therapy with the aim of inhibiting cell proliferation and promoting apoptosis in non-melanoma skin cancers.
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PMID:Strong expression of a longevity-related protein, SIRT1, in Bowen's disease. 1718 Jun 56

The p63 gene, a member of the p53 family, is an epithelial marker expressed in embryonic ectoderm, breast myoepithelium, prostate, oral epithelium, epidermis, and urothelium. The DeltaN-p63 isoforms of p63, which are believed to behave as oncogenes, are expressed in squamous cell carcinoma, basal cell carcinoma, and transitional cell carcinoma. Only a few authors have looked for p63 expression in thymomas and normal thymus. We, therefore, thought of undergoing such a search by taking advantage of our archival material. We studied 66 cases of thymoma (1 type A, 8 type AB, 12 type B1, 19 type B2, 12 type B3, and 14 type C/thymic carcinoma) and 10 specimens of normal human thymus arranged in tissue microarrays. All thymomas (including thymic carcinomas) were positive for p63 regardless of type. Most of the epithelial cells of the normal thymus were also positive for this marker.
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PMID:Expression of p63 in thymomas and normal thymus. 1727 40

The most frequently mutated tumor suppressor gene found in human cancer is p53. In a normal situation, p53 is activated upon the induction of DNA damage to either arrest the cell cycle or else induce apoptosis. However, when mutated, p53 is no longer able to properly accomplish these functions. Our aim was to investigate p53 protein alteration in cases of basal cell carcinoma (BCC) and compare it with the control group. We investigated P53 gene expression in 41 cases of basal cell carcinoma and 20 patients with benign skin disease as control group. The alteration of p53 protein was investigated by immunohistochemistry method. The Data were analyzed using SPSS package, T and Chi-Square tests.Twenty eight out of 41 basal cell carcinoma and 3 out of 20 control were p53-mutated, and there was a statistically significant difference in cases of BCC in comparison with controls (x2 test; p= 0.0001).Taken together, showing alteration of p53 protein, our findings could add to the knowledge that might contribute to the self-maintenance of cancer cells and development of basal cell carcinoma.
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PMID:Immunohistochemistry assessment of p53 protein in Basal cell carcinoma. 1730 41

A very common polymorphism of p53, that of codon 72, codes either for a proline (P72) or an arginine (R72). The two alleles differ in their biological properties: P72 is a stronger inducer of p21, while R72 induces 5-10 times more apoptosis. It is not known, however, whether this polymorphism influences genome stability. The influence of p53 codon 72 polymorphism on cancer risk has been studied for different types of cancer with mixed and inconsistent results. With respect to sporadic non-melanoma skin cancer (NMSC), there are few studies, with small sample sizes, and none in a Latinoamerican population. These studies have found no association between p53 genotype at codon 72 and NMSC. We analyzed whether p53 codon 72 genotype influences genomic stability and the sensitivity of cells to UVB. We also carried out a case-control study of NMSC in a Mexican population which included 204 BCC cases, 42 SCC cases, and 238 controls. There was no association between p53 genotype and basal levels of DNA damage, oxidative DNA damage sensitivity, or DNA repair capacity. R72 dominantly increased the in vitro sensitivity of cells to UVB-induced apoptosis. There was no significant association either between p53 genotype and basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or both combined.
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PMID:p53 codon 72 polymorphism, DNA damage and repair, and risk of non-melanoma skin cancer. 1740 27

Basal cell carcinoma and squamous cell carcinoma, collectively termed non-melanoma skin cancers are the most common malignant tumors in humans. Basal cell carcinoma grows slowly and metastatic spread is very rare. Squamous cell carcinoma is characterized by infiltrative, destructive growth and metastasis. Long-term exposure of skin to UV light has a great impact on development of these epidermal malignancies. UV light induces cascade of events like well known DNA damage of keratinocytes as well as still completely undetermined influence on apoptotic process through expression of proapoptotic and antiapoptotic molecules. The major role in development of skin cancer is given to proapoptotic p53 molecule or tumor suppressor gene which mutation due to UV exposure leads to resistance of DNA-damaged cell to apoptosis. Other proapoptotic molecules such as Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are strongly expressed in basal cell carcinoma and squamous cell carcinoma that could be explained by the ability of tumor to escape the attack of immune system.
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PMID:Epidermal malignant tumors: pathogenesis, influence of UV light and apoptosis. 1746 58

The 2004 WHO classification of lung tumours recognised basaloid carcinoma as a variant of squamous and large cell carcinoma. We report a unique case of primary pulmonary adenocarcinoma with a basaloid component. An 82-year-old man underwent pulmonary lobectomy for a 2.8 cm tumour. The patient is disease-free 13 months after diagnosis. Histologically, an invasive carcinoma having a glandular and a solid component was observed. The former was an adenocarcinoma with mucus containing spaces lined by columnar mucinous cells and basaloid cells. The solid component was an organoid proliferation of basaloid-type cells, as in cutaneous basal cell carcinoma. Basaloid cells, but not mucinous cells, were immunoreactive for high molecular weight cytokeratins (CK), CK 7 and, focally, for TTF-1. High Ki67 index, p53 and EGFR expression were also found. This tumour is unique in several respects: (1) The solid areas resemble a conventional basaloid carcinoma, except for the presence of small mucin-containing spaces. (2) The mucinous adenocarcinoma areas contain two layers of columnar and basaloid cells. (3) Both components are neoplastic based on cell morphology, invasive properties and phenotypic profile. These findings indicate that a basaloid variant of adenocarcinoma is also existing in the spectrum of basaloid carcinomas of the lung.
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PMID:Basaloid adenocarcinoma. A new variant of pulmonary adenocarcinoma. 1761 55

Skin undergoes self-renewal throughout life. Terminally differentiated keratinocytes, namely the corneocytes, are continually shed from the surface of the skin, whereas immature cells produce progeny that proceed through the differentiation process. Notch signaling controls a number of cellular processes including cell fate decision, proliferation, differentiation and survival/apoptosis. Hence, Notch and its ligands are expressed in multiple tissues including the skin, where they are abundantly expressed in the epidermis. Notch activation results in the promotion of growth arrest and the onset of differentiation, therefore suggesting that specific Notch activation may regulate skin homeostasis by balancing these processes, i.e. Notch signaling functions as a molecular switch that controls the transition of cells between skin layers during the epidermal differentiation process. Recent advances in the study of Notch signaling have confirmed that there is cross-talk between the Notch signaling pathway and a variety of other signaling molecules including Sonic hedgehog (Shh), beta-catenin and the p53 family member, p63. The absence of Notch activity allows Wnt and Shh signaling to persist in a tissue where they are normally repressed. In addition, Notch counteracts the action of p63 to maintain immature cell characteristics. However, aberrant Notch signaling results in the development of psoriasis and skin cancers such as squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Future efforts to further define how Notch controls cell proliferation and differentiation may lead to the application of Notch in new therapies for various skin diseases.
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PMID:Notch signaling: its role in epidermal homeostasis and in the pathogenesis of skin diseases. 1762 39

Imiquimod is an immune response modifier currently used as a topical treatment of genital warts, basal cell carcinoma, cutaneous metastasis of malignant melanoma, and vascular tumors. We developed more efficient killers from the same family of compounds that can induce apoptosis without the prominent pro-inflammatory response associated with imiquimod. Among these new products, tk;4EAPB0203, a member of the imidazo[1,2-a]quinoxalines, exhibits an important cytotoxic activity in vitro. HTLV-I-associated adult T-cell leukemia (ATL) and HTLV-I-negative peripheral T-cell lymphomas are associated with poor prognosis. Using potentially achievable concentrations of EAPB0203, we demonstrate inhibition of cell proliferation, G2/M cell- cycle arrest, and induction of apoptosis in HTLV-I-transformed and HTLV-I-negative malignant T cells and fresh ATL cells, whereas normal resting or activated T lymphocytes were resistant. EAPB0203 treatment significantly down-regulated the antiapoptotic proteins c-IAP-1 and Bcl-XL and resulted in a significant loss of mitochondrial membrane potential, cytoplasmic release of cytochrome c, and caspase-dependent apoptosis. Moreover, in HTLV-I-transformed cells only, EAPB0203 treatment stabilized p21 and p53 proteins but had no effect on NF-kappaB activation. These results support a potential therapeutic role for EAPB0203 in ATL and HTLV-I-negative T-cell lymphomas, either as a systemic or topical therapy for skin lesions.
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PMID:EAPB0203, a member of the imidazoquinoxaline family, inhibits growth and induces caspase-dependent apoptosis in T-cell lymphomas and HTLV-I-associated adult T-cell leukemia/lymphoma. 1821 50

Exposition of the skin with solar ultraviolet radiation (UV) is the main cause of skin cancer development. The consistently increasing incidences of melanocytic and nonmelanocytic skin tumors are believed to be at least in part associated with recreational sun exposure. Epidemiological data indicate that excessive or cumulative sunlight exposition takes place years and decades before the resulting malignancies arise. The most important defense mechanisms that protect human skin against UV radiation involve melanin synthesis and active repair mechanisms. DNA is the major target of direct or indirect UV-induced cellular damage. Low pigmentation capacity in white Caucasians and rare congenital defects in DNA repair are mainly responsible for protection failures. The important function of nucleotide excision DNA repair (NER) to protect against skin cancer becomes obvious by the rare genetic disease xeroderma pigmentosum, in which diverse NER genes are mutated. In animal models, it has been demonstrated that UVB is more effective to induce skin cancer than UVA. UV-induced DNA photoproducts are able to cause specific mutations (UV-signature) in susceptible genes for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In SCC development, UV-signature mutations in the p513 tumor suppressor gene are the most common event, as precancerous lesions reveal approximately 80% and SCCs > 90% UV-specific p53 mutations. Mutations in Hedgehog pathway related genes, especially PTCH1, are well known to represent the most significant pathogenic event in BCC. However, specific UV-induced mutations can be found only in approximately 50% of sporadic BCCs. Thus, cumulative UVB radiation can not be considered to be the single etiologic risk factor for BCC development. During the last decades, experimental animal models, including genetically engineered mice, the Xiphophorus hybrid fish, the south american oppossum and human skin xenografts, have further elucidated the important role of the DNA repair system in the multi-step process of UV-induced melanomagenesis. An increasing body of evidence now indicates that nucleotide excision repair is not the only DNA repair pathway that is involved in UV-induced tumorigenesis of melanoma and nonmelanoma skin cancer. An interesting new perspective in DNA damage and repair research lies in the participation of mammalian mismatch repair (MMR) in UV damage correction. As MMR enzyme hMSH2 displays a p53 target gene, is induced by UVB radiation and is involved in NER pathways, studies have now been initiated to elucidate the physiological and pathophysiological role of MMR in malignant melanoma and nonmelanoma skin cancer development.
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PMID:UV damage and DNA repair in malignant melanoma and nonmelanoma skin cancer. 1834 55


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