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)

Diffuse astrocytoma WHO grade II is a well-differentiated, slowly growing tumor that has an inherent tendency to progress to anaplastic astrocytoma (WHO grade III) and, eventually, to glioblastoma (WHO grade IV). Little is known about its molecular basis, except for p53 mutations that are found in >60% of cases. In a search for additional genetic alterations, we carried out gene expression profiling of 11 diffuse astrocytomas using cDNA expression arrays. Expression of six genes (TIMP3, c-myc, EGFR, DR-nm23, nm23-H4, and GDNPF) was detected in 64-100% of diffuse astrocytomas, but not in nontumorous brain tissue. Seven genes (AAD14, SPARC, LRP, PDGFR-alpha, 60S ribosomal protein L5, PTN, and hBAP) were found to be up-regulated more than 2-fold in 20-60% of cases, whereas 11 genes (IFI 9-27, protein kinase CLK, TDGF1, BIN1, GAB1, TYRO3, LDH-A, adducin 3, GUK1, CDC10, and KRT8) were down-regulated to less than 50% of normal levels in 64-100% of cases. Semiquantitative conventional reverse transcription-PCR was performed for 11 genes, 9 of which showed an expression profile similar to that obtained with cDNA expression arrays. Immunohistochemical staining for SPARC showed cytoplasmic immunoreactivity of neoplastic cells in all diffuse astrocytomas analyzed. These results indicate significant changes in gene expression in diffuse astrocytomas, but it remains to be shown which of these are causally related to the transformation of glial cells.
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PMID:Gene expression profiling of low-grade diffuse astrocytomas by cDNA arrays. 1115 82

Apoptosis and cell proliferation occur simultaneously in tumour tissue with tumour suppressor gene, p53 being one of the key players in the complex relationship between these two key phenomena. We, as well as several other groups, have earlier demonstrated the association of p53 immunopositivity with increased degree of cell proliferation in astrocytic tumours. Here we have studied the extent of apoptosis in 62 primary human astrocytic tumours [25 Diffuse Astrocytoma (DA), 9 Anaplastic Astrocytoma (AA) and 28 Glioblastoma multiforme (GBM)] in relation to tumour grade, proliferative status and p53 protein expression. Apoptosis was measured by the TUNEL assay while, cell proliferation (MIB-1 index) and p53 protein immunoreactivity were evaluated by immunohistochemical staining using MIB-1 and DO-1 monoclonal antibodies respectively. The apoptotic index (AI) was greater in GBM than in AA or DA, and more in tumours with p53 immunopositivity than in those without. The most striking observation was the strong correlation between Apoptotic index (AI) and proliferation index (PI) in p53 negative GBM (r=0.766, P < 0.005). However this was not observed in p53 +ve GBM or in low grade DA either p53 positive or negative. Taking p53 negativity in IHC as evidence of a functional gene/protein, this extends the link between proliferation and apoptosis, hitherto observed only in cultured cells with functional p53, to a subset of solid tumours.
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PMID:Apoptosis and proliferation: correlation with p53 in astrocytic tumours. 1598 Oct 97

Diffuse astrocytoma (DA), anaplastic astrocytoma (AA), and glioblastoma (GBM) are defined by the World Health Organization (WHO) based on IDH-mutational status. The vast majority of IDH-mutated gliomas (90% of which involve a mutation in IDH1 R132H, which can be assessed by IDH1 immunohistochemistry [IHC]) occur in persons younger than 55 years of age. This raises the question as to the prevalence of IDH-mutant tumors in older persons and whether the gliomas in older patients should be routinely tested. Since January 1, 2014, we have employed a standard screening panel for all gliomas regardless of patient age. From 578 total gliomas tested, 88 were IDH-mutant DA/AA/GBMs and 11 IDH-mutant tumors were in persons age 55 and older. Of the 11 IDH-mutant examples in the older group, 9 were first clinical presentations of the tumor, 4 of which were in persons age 70 or older (oldest, 76 years). We assessed whether the typical profile of nuclear ATRX loss with or without strong nuclear p53 IHC occurred in these and younger patients and found that ATRX/p53 IHC patterns paralleled those in younger patients. We conclude that, although infrequent, IDH IHC is strongly recommended for all ages of adult patients with diffuse gliomas.
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PMID:IDH1-Mutation in Diffuse Gliomas in Persons Age 55 Years and Over. 2811 Feb 98

Radiation-induced sarcomas in the brain are extremely rare, usually occur with an average latency of 9 years, and are associated with poor outcomes. Latency periods shorter than 1 year may indicate a genetic predisposition such as Li-Fraumeni syndrome. A 34-year-old man underwent initial tumor resection and radiation therapy for a World Health Organization (WHO) Grade II Astrocytoma. Within 6 months, the tumor recurred as WHO Grade III and was treated with temozolomide and then bevacizumab. Despite the patient's apparent improving condition, MRI revealed new dural-based lesions 10 months after radiation therapy and identified as high-grade sarcoma. The patient resumed bevacizumab, began NovoTTF treatment for progressing glioma, and ifosfamide/doxorubicin for the sarcoma. Genetic testing revealed no pathogenic mutation in the TP53 gene. Ultimately, treatment was unsuccessful and the patient succumbed to glioma and sarcoma within 2 years of initial diagnosis. This case was unique due to the rapidly progressing glioma and sudden appearance of a high-grade sarcoma. It is unusual to have two separate intracranial primary cancers with each requiring a different chemotherapy regimen. We discuss the difficulty of simultaneously treating with separate chemotherapy regimens. It remains unclear whether the sarcoma was induced by the radiation treatment or a genetic predisposition.
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PMID:Unique Case Report of a Meningeal Sarcoma Arising during Ongoing Treatment for Progressing Intraparenchymal Glioma. 3188 75