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)

Multifocal alveolar hyperplasia associated with pulmonary lymphangioleiomyomatosis is reported in a 21-year-old woman with tuberous sclerosis. Beside the cystic lesions of lymphangioleiomyomatosis, the tomography showed nodules up to 8 mm in both upper lobes. A proliferation of type II pneumonocytes and Clara cells lining the alveolar walls in an adenoma-like pattern was observed. Nuclear atypia, mitoses and necrosis were not observed, providing evidence against multicentric bronchioloalveolar carcinoma or micronodular atypical alveolar adenomatous hyperplasia. Whereas the lymphangioleiomyomatosis lesions showed strong positivity for HMB45 and expressed oestrogen and progesterone receptors, the alveolar hyperplasia was negative for these markers as it was for carcinoembryonic antigen, p53 and MIB1 antibodies. Multifocal alveolar hyperplasia in tuberous sclerosis is probably a benign hamartomatous lesion in our case without progression on a 2-year follow-up. Its histogenesis is unknown, but is possibly related to chromosome instability.
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PMID:Multifocal alveolar hyperplasia associated with lymphangioleiomyomatosis in tuberous sclerosis. 920 62

In this study, immunoglobulin variable (Ig V) region genes, c-myc re-arrangement and sequence and p53 status were analyzed in clones derived from a Burkitt's lymphoma cell line (LAM) in which it was previously demonstrated that Epstein-Barr virus (EBV) infection occurred late during lymphomagenesis. Such evidence was based on the finding that 2 groups of cellular clones, characterized by the same c-myc re-arrangement but different EBV-fused termini, were obtained from the LAM cell line. The Ig V gene sequences were identical for the 2 groups of clones with different EBV-fused termini. The Ig variable heavy (V(H)) gene sequence displayed a substantial accumulation of point mutations (but no intra-clonal diversification), whereas the productive Ig V lambda (V(lambda)) gene sequence was virtually unmutated. Studies on the Ig V kappa (V(kappa)) locus suggested a receptor revision event (with a switch from kappa to lambda chain production) prior to EBV infection. Likewise, it was determined that the mutations observed in both p53 alleles and in the re-arranged c-myc gene occurred before EBV infection. Based on these findings, we present a model for the various steps of lymphomagenesis. It is proposed that stimulation by an antigen or a superantigen initially favored the clonal expansion and accumulation of other cytogenetic changes, including those involved in receptor editing. These events occurred prior to or during the germinal center (GC) phase of B-cell maturation. Thereafter, possibly upon exit of the cells from the GC, EBV infection occurred, further promoting lymphomagenesis.
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PMID:Analysis of stepwise genetic changes in an AIDS-related Burkitt's lymphoma. 1107 43

We report a peculiar case of multifocal micronodular pneumocyte hyperplasia (MMPH) occurring in a 43-year-old man with tuberous sclerosis. Computed tomography of the chest demonstrated multiple micronodules, measuring up to 5 mm in size, present bilaterally in the lung fields, with no cystic change. Histologically, a proliferation of type II pneumocytes without the typical nulclear atypia lined the thickened alveolar septa in an adenomatoid pattern. Proliferation of immature smooth muscle cells suggestive of LAM was not observed. The characteristic findings of the positive immunohistochemical stains for cytokeratin and surfactant apoprotein A and B, and negative stains for HMB-45, alpha-1 smooth muscle actin, desmin, p53 and carcinoembryonic antigen confirmed the presence of alveolar lining cells in each MMPH lesion. Since the MMPH was observed in a male and did not appear to possess malignant potential, the MMPH appears to be a hamartomatous proliferation occurring in a male with tuberous sclerosis that is separate from lymphangiomyomatosis (LAM) which is related to estrogen and progesterone receptors.
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PMID:Multifocal micronodular pneumocyte hyperplasia in a man with tuberous sclerosis. 1594 95

Perivascular epithelioid cell tumor (PEComa) is rare entity and has been described only recently. By immunohistochemistry and genetics it belongs to the family of tumours which comprises angiomyolipoma, clear cell "sugar" tumor of lung, lymphangioleiomyomatosis and clear cell myomelanotic tumor of ligamentum falciforme/teres hepatis. We describe an unusual case of hepatic PEComa arising in a 55-year-old woman with previous history of glioblastoma. Histologically the tumor grew in expansive way, and was composed of clear and eosinophilic epithelioid cels, without vascular or lipomatous component characteristic of angiomyolipoma. There was mild nuclear pleomorphism, sporadic mitotic activity and haemorrhage without necrosis. On immunohistochemistry, the tumor was HMB-45+50, Melan-A and smooth muscle actin positive. Tyrosinase, S-100 protein, cytokeratin coctail, EMA, vimentin, muscle specific actin, CD10, TTF-1, hepatocyte, desmin and cyclin D1 were negative. Sporadic nuclear p53 positivity was seen. The main differential diagnosis of hepatic PEComa includes clear cell variant of liver cell adenoma and hepatocellular carcinoma, metastases of various clear cell carcinomas and metastasis of malignant melanoma. In respect of uncertain biologic potential of PEComa, long term follow up is indicated.
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PMID:[Perivascular epithelioid cell tumor (PEComa) of the liver: a case report and review of the literature]. 1737 Apr 72

Lantadenes are pentacyclic triterpenoids isolated from leaves of Lantana camara L. and have antitumor activity. Lantadene A (LA) and methyl ester of LA (LAM) were earlier studied in the author's lab for their chemopreventive effect on 7,12-dimethylbenz(a)anthracene (DMBA) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced squamous cell carcinoma incidence in Swiss albino mice. The present study was specially designed to initiate the involvement of the molecular targets in chemopreventive activity of these compounds. Skin lesions were induced by twice-weekly topical application of DMBA (100 nmol/100 microl of acetone) for 2 weeks followed by TPA (1.7 nmol/100 microl of acetone) on depilated back of mice for 20 weeks. LA and LAM were administered orally at a dose of 50 mg/kg body weight twice weekly, 1 week before DMBA application and continued for 20 weeks thereafter. A significant decrease in the incidence of number of lesions in mice was obtained in LA/LAM treated groups as compared to DMBA/TPA alone. Significant increase in the protein levels of c-jun, p65, and p53 by ELISA were observed in DMBA/TPA treated mice tumors whereas less expression was observed in LA and LAM treated tumors. Further immunohistochemical localization of transcription factors was studied which also showed less localization of c-jun, p65, and p53 in LA and LAM treated tumors as compared to localization in DMBA/TPA treated tumors. It can be inferred that LA and LAM chemopreventive activity may be linked to the deregulation of above molecular targets which warrants further studies in that direction.
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PMID:Chemopreventive activity of lantadenes on two-stage carcinogenesis model in Swiss albino mice: AP-1 (c-jun), NFkappaB (p65) and P53 expression by ELISA and immunohistochemical localization. 1842 23

We report a peculiar case of multifocal micronodular pneumocyte hyperplasia (MMPH) in a 54-year-old woman with tuberous sclerosis complex (TSC) diagnosed during antituberculous treatment. Findings were initially detected by chest computed tomography (CT) to check for complication of pulmonary tuberculosis. Chest CT demonstrated multiple small nodules with ground-glass opacity, measuring up to 5 mm diameter, presenting in the bilateral lung fields, without cystic change. Because the differentiation from multiple atypical adenomatous hyperplasia (AAH) was necessary, we finally performed a diagnosis of MMPH based on specimens obtained by video-assisted thoracoscopic surgery. Histologically, type II pneumocytes without nuclear atypia lined the thickened alveolar septa and proliferated papillary structures. There was no proliferation of immature smooth muscle cells suggestive of lymphangioleiomyomatosis. Although immunohistochemical stains for cytokeratin and surfactant apoprotein A and B were positive for alveolar lining cells in each MMPH lesion, those for HMB-45, alpha-smooth muscle actin, p53 and carcinoembryonic antigen were negative. We must consider MMPH as part of the differential diagnosis along with multiple AAH when multiple small nodules with ground-glass opacity were observed on chest CT in patients with TSC.
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PMID:Multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis: differentiation from multiple atypical adenomatous hyperplasia. 1853 95

A 41-year-old woman carrying a germline tuberous sclerosis complex 2 (TSC2) mutation, whose regular medical follow-up for tuberous sclerosis complex and tuberous sclerosis complex-associated lymphangioleiomyomatosis had continued for 2 years, had uterine angiosarcoma concomitant with uterine lymphangioleiomyomatosis. Immunohistochemically, the uterine angiosarcoma cells showed an extremely skewed lymphatic differentiation; they were diffusely immunopositive for CD31 but negative for other vascular endothelial markers including factor VIII and CD34 yet strongly immunopositive for lymphatic endothelial markers including D2-40 and Prox-1. Loss of heterozygosity analysis demonstrated that not only lymphangioleiomyomatosis and renal angiomyolipoma but also the uterine angiosarcoma had loss of heterozygosity on TSC2. Furthermore, direct sequencing revealed a TP53 mutation in the uterine angiosarcoma. Collectively, the findings suggest that combined dysfunction of the p53 and TSC2 tumor suppressor proteins may contribute to the development of uterine angiosarcoma in this rare clinical setting.
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PMID:Uterine angiosarcoma associated with lymphangioleiomyomatosis in a patient with tuberous sclerosis complex: an autopsy case report with immunohistochemical and genetic analysis. 2274 2

We discovered that 90.3% of patients with angiomyolipomas, lymphangioleiomyomatosis (LAM), and tuberous sclerosis complex (TSC) carry the arginine variant of codon 72 (R72) of TP53 and that R72 increases the risk for angiomyolipoma. R72 transactivates NOTCH1 and NODAL better than the proline variant of codon 72 (P72); therefore, the expression of NOTCH1 and NODAL is increased in angiomyolipoma cells that carry R72. The loss of Tp53 and Tsc1 within nestin-expressing cells in mice resulted in the development of renal cell carcinomas (RCC) with high Notch1 and Nodal expression, suggesting that similar downstream mechanisms contribute to tumorigenesis as a result of p53 loss in mice and p53 polymorphism in humans. The loss of murine Tp53 or expression of human R72 contributes to tumorigenesis via enhancing epithelial-to-mesenchymal transition and motility of tumor cells through the Notch and Nodal pathways. IMPLICATIONS: This work revealed unexpected contributions of the p53 polymorphism to the pathogenesis of TSC and established signaling alterations caused by this polymorphism as a target for therapy. We found that the codon 72 TP53 polymorphism contributes to TSC-associated tumorigenesis via Notch and Nodal signaling.
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PMID:The Codon 72 TP53 Polymorphism Contributes to TSC Tumorigenesis through the Notch-Nodal Axis. 3108 7

We previously reported the benefit of lomustine addition to conventional chemotherapy in older acute myeloid leukemias with nonadverse chromosomal aberrations in the LAM-SA 2007 randomized clinical trial (NCT00590837). A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients being treated with lomustine in combination with idarubicin and cytarabine and 167 without lomustine, identified 1088 mutations with an average of 3.3 mutations per patient. NPM1, FLT3, and DNMT3A were the most frequently mutated genes. A putative therapeutic target was identified in 178 patients (54%). Among five molecular classifications analyzed, the ELN2017 risk classification has the stronger association with the clinical evolution. Patients not treated with lomustine have an expected survival prognosis in agreement with this classification regarding the overall and event-free survivals. In strong contrast, lomustine erased the ELN2017 classification prognosis. The benefit of lomustine in nonadverse chromosomal aberrations was restricted to patients with RUNX1, ASXL1, TP53, and FLT3-ITDhigh/NPM1WT mutations in contrast to the intermediate and favorable ELN2017 patients. This post-hoc analysis identified a subgroup of fit elderly AML patients with intermediate cytogenetics and molecular markers who may benefit from lomustine addition to intensive chemotherapy.
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PMID:Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study. 3294 50