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)

The study of epidemiology and of the carcinogenesis in epidermoid carcinomas of the upper aerodigestive tract shows that their occurrence is not random. Tobacco abuse plays a major role, especially because of benzopyrene, mutagen of the P53 gene, however it is associated with many other potentiating factors: alcohol, metals, hydrocarbures, virus, food, climate, genetic fragility that create genetic lesions at the origin of carcinogenesis. The latter occurs as "field cancerization" with multiple alterations of the mucosa and general attack of the control systems of the differentiation, growth and cell apoptosis which usually protect the cell against the phenomena of carcinogenesis. The P53 protein gene, retinoid receptors as well as the system of detoxifying glutathion S transferase are modified at the very early stage of these diseases, these abnormalities can be logically related to epidemiological data. These data lead us therefore to imagine complementary specific reverting therapies of induced genetic abnormalities, through the reexpression of non mutated gene encoding P53 protein and the use of retinoid. These various modalities are reported hereafter.
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PMID:[Elements of epidemiology and initiation of carcinogenesis in carcinomas of the upper aerodigestive tract. Future therapeutic consequence?]. 1037 57

Squamous cell carcinoma of the head and neck commonly affects patients in their sixth decade and older, particularly those with a prolonged history of alcohol and tobacco abuse. Less frequently, carcinomas occur in young individuals even in the absence of known risk factors. The purpose of this study is to investigate a possible relationship between these tumors and human papilloma virus (HPV). Thirty-three cases of squamous cell carcinoma of the head and neck in young patients under the age of 40 years were studied: 15 oral, 11 tonsillar, and 7 laryngeal. HPV DNA was detected by polymerase chain reaction in 10 tonsillar and 2 laryngeal carcinomas and in none of the oral tumors. Of the 12 HPV-positive tumors, 11 were HPV16 and 1 was HPV31. HPV-positive tumors had a distinct nonkeratinizing basal cell morphology, they stained diffusely and strongly with p16 antibodies, had higher Ki-67 and lower p53 staining scores as compared with the conventional keratinizing HPV negative carcinomas. It is concluded that in young patients high-risk HPV, particularly HPV16, is strongly associated with tonsillar squamous cell carcinoma and some cases of laryngeal, but not oral, tumors. The HPV-positive carcinomas have a distinct histopathologic and immunophenotypic features.
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PMID:Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. 1457 81

Invasive tumors (cancers or malignant lesions) typically develop in the setting in which there is the presence of putative non-invasive lesions and the development of these non-invasive lesions frequently precedes the development of cancers. For some organs, such as the oral cavity, cervix and skin, the respective putative pre-invasive lesions can be observed over time and documented to progress to invasive lesions. However, for less readily observable lesions, such as those of the prostate, the progression of the pre-invasive lesions, e.g., prostatic intraepithelial neoplasia (PIN) and prostatic proliferative inflammatory atrophy (PIA) to prostatic cancer are more difficult to document. Thus, for most organ systems, specific pre-invasive neoplastic lesions have been proposed based upon the apparent observations of one or more of the following: 1) microinvasive disease developing from a pre-invasive neoplastic lesion, 2) the general association of the pre-invasive lesion with invasive lesions, 3) the subsequent development of invasive lesions following diagnosis of the pre-invasive lesion, 4) correlations of the molecular features of the putative pre-invasive lesion with the matching invasive lesions, and 5) reductions in the rate of cancer following removal of the pre-invasive lesion. When there are mixtures of pre-invasive lesions with actual cancers in the same case, some of the above specific associations are more difficult to make. Several terms have been used to describe pre-invasive lesions, many of which are now less useful as our knowledge of these lesions increases. It is now commonly accepted that these lesions are a features of the spectrum of neoplastic development and most are accepted as ``neoplastic lesions'' with associated molecular features, even though they may be reversible even if they have mutations in suppressor genes (e.g., p53) or are associated with viral etiologies (e.g., cervical intraepithelial neoplasia). The overall term, "pre-invasive neoplasia", seems to best describe these putative pre-invasive lesions. Thus, terms such as incipient neoplasia should be abandoned. The term "intra-epithelial neoplasia" with an associated grade, which has been developed for pre-invasive neoplastic lesions of the cervix, i.e. cervical intraepithelial neoplasia (CIN), seems to be a terminology that adds consistency across epithelial organs. Thus, adoption of these terms for the additional organ sites of pancreas (PanIN) and prostate (PIN) seems accepted. Less descriptive terms such as the degrees of dysplasia of the oral cavity and bronchopulmonary system and actinic keratosis and Bowen's disease of the skin might be better designated as oral intraepithelial neoplasia (OIN), pulmonary intraepithelial neoplasia (PulIN) and dermal intraepithelial neoplasia (DIN). The etiology of pre-invasive neoplasia is the etiology of the matching cancers. Some obvious initiating factors include exposure to the whole range of ionizing and non-ionizing radiation, tobacco abuse and a broad range of other carcinogens (e.g., benzene). A frequent initiation factor is the setting of long standing continuing damage, inflammation and repair (LOCDIR) which leads to early molecular features associated with neoplasia after about one year. An excellent example of this is ulcerative colitis (UC) in which dysregulation of microsatellite repair enzymes have been documented one year following diagnosis of UC. While the nomenclature, description, diagnosis and etiology of pre-invasive neoplasia has advanced, approaches to therapy of such lesions have not progressed adequately even though it has been identified that, for example, removal of polyps periodically from the colorectum, DCIS from the breast, and high grade CIN from the cervix, results in a reduction in the development of cancers of the colorectum, breast, and cervix, respectively. With the development of more molecularly targeted therapy with fewer side effects, preventive therapies may be more successfully targeted to pre-invasive neoplastic lesions.
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PMID:The biology of incipient, pre-invasive or intraepithelial neoplasia. 2211 68

Squamous carcinomas of the head and neck area are carcinomas that were traditionally associated with alcohol and tobacco abuse. More recently, a pathogenic relationship of oncogenic human papilloma viruses (HPV) with head and neck cancer of the oropharynx and the base of the tongue has been revealed. Two proteins of HPV, E6 and E7, are involved in neoplastic transformation not only in the head and neck but in other locations, where these epitheliotropic viruses cause carcinomas, such as the uterine cervix and the anal region. The E6 viral protein associates with cellular E3 ubiquitin ligase E6-AP and promotes degradation of tumour suppressor p53 by the proteasome. This molecular event reveals the important role that the ubiquitin-proteasome system (UPS) plays in the pathogenesis of head and neck cancer. The role of this system in head and neck carcinogenesis is not restricted to the destruction of p53 but extends to most, if not all, signaling pathways that regulate carcinogenesis in this location. These roles are reviewed here and implications for treatment are discussed.
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PMID:Ubiquitination and the ubiquitin - proteasome system in the pathogenesis and treatment of squamous head and neck carcinoma. 2402 78