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 tumors produced by transplantation into nude mice of human adenoid squamous carcinoma-forming cell line TYS, presumably derived from a minor salivary gland, were treated with a differentiation-inducing agent, vesnarinone, which was given per o.s. daily at a dose of 200 mg/kg for 35 days. They were then examined morphologically and immunohistochemically. The vesnarinone treatment resulted in a significant suppression of tumor growth. In addition, tumor nests indicating keratinocyte and acinar cell differentiation were often observed in the treated tumors, but not in untreated controls. Tissue sections from vesnarinone-treated and untreated TYS tumors were stained with monoclonal antibody (NAb) directed to carbohydrate antigen LeY or proliferating cell nuclear antigen (PCNA) and with rabbit polyclonal antibody to p53. Antibody staining patterns were compared with morphological characteristics of cells as revealed by hematoxylin and eosin staining, and DNA fragmentation patterns as revealed by 3'-OH nick-end labelling techniques. Tissue sections from vesnarinone-treated TYS tumors showed positive reaction with nick-end labelling and were extensively stained strongly by anti-LeY MAb, whereas the untreated tumors showed negative reaction with nick-end labelling and were infrequently stained by anti-LeY MAb. Within LeY-positive areas of tissue sections from the vesnarinone-treated tumors, keratinocyte and acinar cell differentiation as well as DNA fragmentation were frequently observed, although not all LeY-positive cells showed such signs of apoptosis. LeY-positive cells showed consistent negative staining by anti-PCNA MAb and anti-p53 rabbit serum. From these findings, it can be considered that vesnarinone has differentiation and apoptosis-inducing activity against TYS cells grown in athymic nude mouse.
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PMID:Characteristics of antitumor activity of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]- 2(1H)-quinolinone (vesnarinone) against a human adenoid squamous carcinoma-forming cell line grown in athymic nude mice. 775 82

Pre-therapeutic evaluation of p53 gene is very important for treating patients with head and neck cancer. However, the analysis for p53 gene has generally been done by immunohistochemistry, polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and direct sequencing. Functional analysis system for p53 transcriptional activity in mammalian cells is now required. We developed a functional analysis system for p53 transcriptional activity in cancer cells. We used two human head and neck cancer cell lines harboring mutated p53 gene, HSG (Asn30Ser) and TYS (Asp281His), and a human osteosarcoma cell line, Saos-2 as a control. We transfected these cells with luciferase reporter plasmids containing promoter sequence of p53 target genes (p21waf1, BAX, MDM2, p53AIP1 or PUMA). After treating the cells with chemotherapeutic drugs, alteration of the luciferase activity was measured. In HSG cells, none of the target gene promoters was activated by treatment with chemotherapeutic drugs. In TYS cells, p21waf1 promoter was markedly activated by treatment with chemotherapeutic drugs, but Bax and p53AIP1 promoter was not activated. This type of mutated-p53 in TYS cells prevents cell death from DNA damage, and probably accumulates genetic alterations and accelerates the malignant progression of the cells by DNA damaging therapy. Thus, analysis for the diverse function of mutated-p53 may help to determine the therapeutic strategy, especially for chemotherapy and radiation in the individual patients with head and neck cancer.
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PMID:Evaluation of the chemosensitivity of head and neck cancer cells based on the diverse function of mutated-p53. 1252 38