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)

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.
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PMID:Multiple tumor case: report and analysis of an autopsy case. 926 95

It is well known that normal human diploid fibroblasts undergo a significant, p53-dependent arrest in the G1 phase of the cell cycle after exposure to ionizing radiation. The presence and magnitude of a G1 arrest in human tumor cell lines, however, has been controversial, particularly in cells derived from solid tumors and irradiated during exponential growth. To examine this question more precisely, we synchronized cells by mitotic selection and irradiated them in very early G1 prior to any of the described G1 checkpoints. Progression of cells from G1 into the S phase was monitored by autoradiographic measurement of cumulative labeling indices and by flow cytometric analysis. Three different human tumor cell lines confirmed as expressing normal p53 function were examined, i.e., lines derived from an adenocarcinoma of the colon (RKO), a breast cancer (MCF-7), and a squamous cell carcinoma (SCC61). Following irradiation with 4-8 Gy, there was a transient delay in progression from G1 into S phase, lasting approximately 2 h, and in two of the three cell lines (RKO and MCF-7), a small fraction of cells (5-8%) never entered the first S phase. Although there was no evidence for a prolonged G1 arrest, the expected G2 delay was observed in all three cell lines. When irradiated RKO cells were resynchronized at the next mitosis, approximately 30% of the cells did not enter the second S phase. This latter finding is consistent with earlier reports on the kinetics of radiation-induced reproductive failure in mammalian cells. These results indicate that cells derived from human solid tumors that express normal p53 may respond to irradiation quite differently than do normal cells in terms of G1 checkpoint control.
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PMID:Absence of a radiation-induced first-cycle G1-S arrest in p53+ human tumor cells synchronized by mitotic selection. 958 50

This study was conducted to confirm the hypothesis that intestinal microflora are required for the development of adenocarcinoma in the colon of the TCRbeta and p53 double-knockout (TCRbeta-/- p53-/-) mouse. Germ-free TCRbeta-/- p53-/- mice were produced. At 7 weeks of age, the animals were divided into two groups (n = 10/group), and one of these groups was conventionalized. Animals of both groups were subjected to histopathological examination for adenocarcinoma of the colon at 4 months of age. There was no development of adenocarcinoma of the colon among the germ-free mice, whereas in the conventionalized group, adenocarcinomas of the ileocecum and cecum were detected in 70% of animals. These results indicate the usefulness of the TCRbeta-/- p53-/- mouse as a colon cancer animal model that develops spontaneous adenocarcinoma of the colon early in life, and suggest that intestinal microflora play a major role in the development of adenocarcinoma of the colon in this animal model.
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PMID:Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice. 1128 3

Antineoplastons work as molecular switches, which regulate expression of genes p53 and p21 through demethylation of promoter sequences and acetylation of histones. They also inhibit the uptake of growth-critical amino acids, such as 1-glutamine and 1-leucine in neoplastic cells. Phase II trials indicate efficacy of antineoplastons in low-grade glioma, brain stem glioma, high-grade glioma, adenocarcinoma of the colon, and hepatocellular carcinoma. The best results were observed in children with low-grade glioma, where 74% of patients obtained objective response, and in patients with adenocarcinoma of the colon with liver metastases whose survival rate of more than 5 years is 91% versus 39% in controls on chemotherapy. Gene array studies will explain antineoplaston-induced changes in gene expression.
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PMID:The present state of antineoplaston research (1). 1531 59

Colon adenocarcinoma is the third most commonly diagnosed cancer and the second deadliest one. Metabolic reprogramming, described as an emerging hallmark of malignant cells, includes the predominant use of glycolysis to produce energy. Recent studies demonstrated that mitochondrial electron transport chain inhibitor reduced colon cancer tumour growth. Accumulating evidence show that myoferlin, a member of the ferlin family, is highly expressed in several cancer types, where it acts as a tumour promoter and participates in the metabolic rewiring towards oxidative metabolism. In this study, we showed that myoferlin expression in colon cancer lesions is associated with low patient survival and is higher than in non-tumoural adjacent tissue. Human colon cancer cells silenced for myoferlin exhibit a reduced oxidative phosphorylation activity associated with mitochondrial fission leading, ROS accumulation, decreased cell growth, and increased apoptosis. We observed the triggering of a DNA damage response culminating to a cell cycle arrest in wild-type p53 cells. The use of a p53 null cell line or a compound able to restore p53 activity (Prima-1) reverted the effects induced by myoferlin silencing, confirming the involvement of p53. The recent identification of a compound interacting with a myoferlin C2 domain and bearing anticancer potency identifies, together with our demonstration, this protein as a suitable new therapeutic target in colon cancer.
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PMID:Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis. 3085 May 80

BACKGROUND Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high incidence and mortality rates. The interferon regulatory factor (IRF) family is known as a key transcription factor in the IFN signaling pathway and cellular immunity. This research explored the relationship between the IRF family and COAD through use of bioinformatics technology. MATERIAL AND METHODS Using the UALCAN and GEPIA databases, we analyzed the transcription and prognostic value of IRFs in COAD, and GSCALite was used in cancer genomics analysis. TIMER, LinkedOmics, and Metascape were used to assess the potential function of IRFs in COAD. RESULTS The transcription levels of IRF3 were elevated in COAD tissues, while IRF2/4/6 were downregulated compared with normal patients in subgroup analyses of race, age, weight, sex, nodal metastasis, individual cancer stages, TP53 mutation status, and histological subtypes. IRF3 and IRF7 in COAD were significantly associated with a poor prognosis. Drug sensitivity analysis revealed that the expression level of IRF2/4/8 was negatively associated with drug resistance. A significant correlation was found between the IRF family and immune cell infiltration. Moreover, enrichment analysis revealed that the IRFs were associated with response to tumor necrosis factor, transcription misregulation in cancer, and JAK-STAT signaling pathway. We also identified several kinase and miRNA targets of the IRF family in COAD. CONCLUSIONS We identified IRF3 and IRF7 as prognostic biomarkers in COAD, and the IRF family was associated with immune cell infiltration and gene regulation networks, providing additional evidence showing the significant role of the IRF family in COAD.
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PMID:Identification of the Prognostic Value and Clinical Significance of Interferon Regulatory Factors (IRFs) in Colon Adenocarcinoma. 3316 10