Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Point mutations at the tumour suppressor gene p53 are one of the most frequent genetic alterations in squamous cell carcinoma of the head and neck (SCCHN), which lead to the nuclear accumulation and overexpression of inactive p53 protein. The overexpression of mutant p53 protein can induce a specific humoral response in cancer patients. p53 protein was studied in 112 SCCHN. Biopsies and sera samples were collected before initiation of treatment. 74 patients received neoadjuvant chemotherapy (5-fluorouracil-cisplatin-folinic acid). p53 protein expression was evaluated by immunohistochemistry (IHC) on paraffin-embedded sections. The analysis of mutations was assessed by PCR-SSCP of exons 5-10 on DNA from 28 representative cases. Antibodies specific for p53 protein were analysed in sera of 74 patients by an ELISA procedure. Overexpression (> 20% positive cells) of p53 protein was frequent (56%: 63/112) and was correlated with localisation of the primary tumour and tumour stage. p53 mutations were detected in 57% (16/28) of studied cases. The prevalence of p53 antibodies in sera was high (44% 32/74) and among this population, 68% (20/29) had a positive immunophenotype and 67% (6/9) a p53 mutation in the tumour. In addition, the presence of anti-p53 antibodies was slightly associated with complete response to neoadjuvant chemotherapy. If the humoral response seems to be an indicator of the p53 protein status, the detection of anti-p53 antibodies could be a good approach in the early detection of the presence of p53 alterations in SCCHN and recurrent tumours or the appearance of second primary cancer.
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PMID:Implications of p53 alterations and anti-p53 antibody response in head and neck squamous cell carcinomas. 968 69

To date the response rates to biomodulated 5-fluorouracil in patients with metastatic or unresectable colorectal carcinoma have been varied. Potentially responsive patients are difficult to identify and treatment schedules are both expensive and toxic. Thus, any method that could be used to predict patient response would be both clinically and economically valuable. Increased p53 protein levels have previously been shown to correlate with disease progression in a series of colorectal carcinoma patients treated with 5-FU/folinic acid biomodulated chemotherapy. In addition to mutation of the p53 tumour suppressor gene, mutation of the K-ras gene at codon 12 has also been shown to be a frequent occurrence in the step-wise progression from normal colonic mucosa to adenocarcinoma. Oncogenic activity in the ras family has recently been shown to correlate with decreased levels of apoptosis and thus increased resistance to both radiation and certain chemotherapeutic agents. The aim of the present study was therefore to investigate if a correlation existed between mutation of the K-ras gene at codon 12 and disease progression in the series of colorectal carcinoma patients previously evaluated for levels of p53 protein expression. Response to 5-FU/folinic acid was assessed radiologically by CAT scan (WHO criteria) and clinically by Karnofsky performance scale (KPS) 3 months after the initial treatment. The presence of a K-ras gene mutation was assessed with radiolabelled oligonucleotide probes on amplified patient DNA, dot blotted on to a nylon membrane. Fifty-two patients were assessed and 25% were found to possess mutations at codon 12 of their K-ras gene. In contrast to increased levels of p53 protein, K-ras mutation at codon 12 did not correlate with disease progression when assessed either radiologically or clinically.
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PMID:Mutation in the K-ras gene at codon 12 does not correlate with disease progression in colorectal carcinoma patients treated with 5-FU/folinic acid biomodulated chemotherapy. 2154 41