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)

Neuroblastoma, a tumor of the sympathetic nervous system, is one of the most common solid malignancies in infants and represents 7% of all cases of childhood cancer outside of the central nervous system. Thirty-five samples of neuroblastoma from 31 patients were obtained from Duke University Medical Center between 1979 and 1991 and studied to determine the relative prognostic value of a number of clinical, histologic, nuclear, and oncogenic features. The features studied were: stage, Shimada classification, DNA ploidy, MIB-1-proliferation index and status for HER-2/neu, p53 and epidermal growth factor receptor (EGFr). Only age (P = .03), HER-2/neu (P = .01), and p53 (P = .02) reached statistical significance as prognostic indicators. The median survival for patients with HER-2/neu expression was 12 months; median survival for patients with no HER-2/neu expression was 138 months. Similarly, the median survival for patients with p53 expression was 12 months; patients with no p53 expression had a median survival was 144 months. The combination of either HER-2/neu or p53 positivity was especially strong as a prognostic indicator (P = .002).
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PMID:Prognostic indicators for neuroblastoma: stage, grade, DNA ploidy, MIB-1-proliferation index, p53, HER-2/neu and EGFr--a survival study. 774 72

Thirty-two cases of neurofibromatosis Type I (NF1) were identified among 6,678 pediatric cancer patients treated at St. Jude Children's Research Hospital over a 29-year period. A total of 35 malignant neoplasms have been diagnosed in these patients. Two of three patients with second malignant neoplasms had colon cancer at the primary or second tumor. Of particular interest are two cases in which both NF1 and malignant peripheral nerve sheath tumors were present in multiple successive generations: a patient with colon cancer and non-Hodgkin lymphoma who has a constitutional abnormality of the p53 gene, and a patient with acute lymphoblastic leukemia with the Philadelphia chromosome and other cytogenetic abnormalities, including the t(8;14). Outcome of patients in the largest subgroup, that of malignant peripheral nerve sheath tumors, was favorable only for those patients having resectable extremity lesions. In contrast, all patients with central nervous system tumors are surviving. These cases reflect the molecular and cytogenetic abnormalities that can be present in NF1 and the variety of tumors that may result in these patients.
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PMID:Neurofibromatosis type I and malignancy: review of 32 pediatric cases treated at a single institution. 825 5

The author reviews current findings regarding inherited cancer predisposition and childhood cancer and proposes development of genetic services for long-term survivors of childhood cancer. Overall, it is suggested that relatively rare germline mutations in the tumor suppressor genes, Rb, p53, and WT1, may have important implications for long-term survivors relevant to familial cancer, second malignant neoplasms, and developmental disorders. Although continued research clearly is needed, planning for genetic services for long-term survivors should begin now.
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PMID:Genetic implications for long-term survivors of childhood cancer. 838 78

The tremendous progress achieved in understanding the molecular basis of cancer, was unfortunately not followed by a mutual improvement in the morbidity and mortality of adult cancer. In contrast, the success rate achieved in paediatric oncology has increased significantly during the past 30 years, and more than two-thirds of the children with cancer can now be cured. p53 has been shown to have a central role on apoptosis in various cells. As apoptosis is a final common pathway for much of our anti cancer therapy, resistance to apoptosis due to a normal activity of p53 is an important mechanism of tumor resistance and treatment failure. Contrary to the findings in most adult tumors, where about 50% of the tumors lack p53 activity, the rate of p53 mutations in childhood cancer is surprisingly low. This may be the key to the much better prognosis of children with cancer. In most adult tumors, multiple genetic events, between five and seven, are usually involved. The oncogenes involved in such tumors usually represent those located upstream of the nuclear transcription factors. In most paediatric tumors, in contrast, the initiating event is the activation of nuclear transcription factors secondary to chromosomal translocations. It can be speculated that multiple events activating various components of the signal transduction machinery are needed for tumorigenesis, and hence the evolution and progression of such tumors is slow. Moreover, if the malignant cell has to accumulate multiple mutations, the chances of crippling the apoptotic mechanism are higher. Genomic instability evidenced by microsatellite variation has been found in colon, pancreas, breast, liver and ovarian adult tumors, and not in paediatric tumors. As multiple somatic mutations are needed for the initiation and progression of the common adult malignancies, inherent genomic instability can dispose to accumulation of multiple mutations. All these molecular interactions are discussed with relevance to the difference between non-curable, mostly adult tumors, and curable, mostly paediatric tumors.
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PMID:Curable and non-curable malignancies: lessons from paediatric cancer. 886 35

Colorectal carcinoma is one of the most common primary malignancies in adults and occurs in older patients after pelvic radiation. It is rare in children and young adults. We report two cases of colonic adenocarcinoma which were second malignant neoplasms following treatment for early childhood malignancies. One child had Wilms' tumor at 9 months of age treated with preoperative radiation and surgery. He developed radiation colitis and multifocal intestinal adenocarcinomas 42 years later and died with abdominal carcinomatosis. The second child had retroperitoneal embryonal rhabdomyosarcoma at age 1 year and was treated with preoperative radiation, surgery, and chemotherapy. At age 2 years he had radiation colitis; at age 11 years he had rectal adenocarcinoma associated with adenomatous polyps, focal adenomatous change and radiation colitis. Immunohistochemical studies revealed p53 positivity in both adenocarcinomas and in adenomas from the second patient, suggesting that p53 mutation was involved in carcinogenesis. The history of high-dose radiation in early childhood and the multifocal lesions suggest the adenocarcinomas in both patients were second malignant neoplasms, with associated reactive and benign neoplastic and premalignant lesions well documented in one case. These two cases document the phenomenon of early onset of adult type tumors in survivors of childhood cancer and emphasize the need for continued clinical evaluation of patients at risk for second malignant neoplasms.
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PMID:Colorectal adenocarcinoma as a second malignant neoplasm following Wilms' tumor and rhabdomyosarcoma. 888 17

We investigated the report of a community cluster of cancers in 33 children, which included two siblings known to have dominantly inherited Li-Fraumeni syndrome and a germline p53 mutation. After defining criteria for inclusion in the cluster, the 12 eligible childhood cancer probands diagnosed between 1980 and 1989 were not excessive (expected, ten cases). The corresponding childhood cancer mortality rates for the community fluctuated between 1950 and 1989 and were not increased overall. However, three additional probands had family histories of childhood cancer that suggested a forme fruste of Li-Fraumeni syndrome. The epidemiological data suggested a geographic cluster of this rare hereditary disorder, but absence of germline p53 mutation in the three other multicase families indicates genetic heterogeneity. Laboratory studies can assist analyses of suspected clusters, although investigations of geographic clusters of hereditary cancers raise complex issues of confidentiality and protection of affected individuals, their families, and the community.
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PMID:Molecular epidemiology study of a suspected community cluster of childhood cancers. 907 19

The use of RT in pediatric cancer has been virtually eliminated in certain diseases (NHL); greatly reduced in some (Wilms' tumor, ALL, neuroblastoma); and refined and modified in others (rhabdomyosarcoma, Ewing's sarcoma). At present, however, it seems clear that RT will continue to be an important modality (particularly in brain tumors) and a much greater understanding of its effects has been achieved and utilized. The knowledge of the occurrence of late effects and SMN in a child cured of cancer is continuing to modify initial treatment strategies: A classic example of such an effort is the common use of lower RT doses and nonalkylator-based chemotherapy in Hodgkin's disease. Further, the use of DNA testing in children may be able to identify the presence of germline RB and p53 mutations, which may identify a child at high risk for SMN, so that appropriate therapeutic modifications may be made. In addition, knowledge of these late consequences in children mandates that they be carefully monitored and closely followed, so that prompt and effective treatment can be administered to give them a better chance for a long and healthy life.
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PMID:Pediatric radiotherapy. An overview. 937 90

Malignant rhabdoid tumor (MRT) is a rare, enigmatic childhood cancer characterized by extreme aggressiveness and resistance to chemotherapy. To understand better the origin of the tumor and the mechanisms by which it develops and resists treatment, five cell lines were established from patients presenting with MRT (two renal and three extrarenal tumors). All of the cell lines display the light microscopic and ultrastructural features, as well as the variable immunohistochemical profile, characteristic of MRT. All are capable of forming tumors in nude mice. Three of the cell lines have detectable abnormalities of chromosome 22: one a t(22, 22) unbalanced translocation and two others a loss of heterozygosity of polymerase chain reaction-based microsatellite markers. Northern blot analysis showed that overexpression of the c-myc message was a consistent characteristic of the five MRTs evaluated. Although mutations of the p53 gene were not detectable by sequence analysis, all of the cell lines showed nuclear accumulation of the p53 protein by an immunocytochemical analysis in a minority of the cells. This result suggests that dysfunction in a p53-dependent apoptotic pathway might play a role in the multiple drug resistance phenotype of these tumors.
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PMID:Establishment and molecular characterization of five cell lines derived from renal and extrarenal malignant rhabdoid tumors. 987 56

The development of second primary solid tumors, especially breast neoplasms, is increased among patients who have survived childhood or adolescent malignancies. With the increased long-term survival of patients with pediatric cancer, questions regarding breast cancer screening in this group have been raised. At this time, there are no established guidelines for breast cancer surveillance in this high-risk population. The objective of this review is to summarize the incidence, list additional risk factors for the development of breast cancer, and discuss the benefits of early detection of second primary breast cancers in pediatric cancer survivors. We have devised an algorithm for breast cancer screening in survivors of childhood malignancy. Implications of treatment with radiation and chemotherapy and the influence on prognosis of genetic abnormalities such as p53 mutations are debated.
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PMID:Screening Childhood Cancer Survivors for Breast Cancer. 1038 54

We report on two patients in whom osteosarcoma occurred as second malignancy of childhood cancer. One patient had a malignant teratoma and the other adrenocortical carcinoma as the primary cancer. The emergence of cancer in cured cases and long-term survival cases of childhood cancer may result in an increase in the number of osteosarcomas seen in adolescence occurring as second malignancy. Anti-cancer drugs in large does were used for the treatment of a malignant teratoma in the former. These anti-cancer drugs may be involved in the occurrence of the second malignancy. In the latter, the patient has the germ-line mutation of p53 tumor suppressor gene, so genetic factors are presumably related to the occurrence of the second malignancy.
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PMID:Two cases of osteosarcoma occurring as second malignancy of childhood cancer. 1069 17


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