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)

Immunogenic tumor antigens have been sought through a variety of paradigms for several past decades. Recent developments in antigen presentation have radically changed the prism through which we view these enigmatic antigens. This article discusses the small but growing treasure chest of these antigens--stress-induced proteins, the P1AB antigen of the P815 mastocytoma, the p53 tumor suppressor protein, the gp95/p97 antigen of human melanoma, mucins and others.
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PMID:Protein tumor antigens. 175 84

We have examined the immune response to full-length wild-type human p53 presented by a recombinant canarypox vector (ALVAC) and by plasmid DNA. For the ALVAC recombinant, intravenous, but not subcutaneous, intramuscular or intradermal administration, induced CD8+ CTLs that lysed tumor cells transfected with human mutant p53. Intrasplenic administration also induced CTLs. Biodistribution studies showed that intravenously injected ALVAC localized primarily in the lung, liver and spleen, whereas intramuscularly injected virus remained predominantly at the injection site. Intradermal and intramuscular immunization with naked plasmid DNA encoding human wild-type p53 also induced a specific CTL response. DNA immunization induced complete protection against challenge with a mouse embryo fibroblast transfected with human mutant p53 and partial, but significant, protection against a transfected mastocytoma. The ALVAC recombinant induced partial protection in both models. These results suggest that recombinant ALVAC and DNA might be interesting presentation platforms for p53 to be tested in clinical studies.
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PMID:The mode of presentation and route of administration are critical for the induction of immune responses to p53 and antitumor immunity. 960 32

Four case reports of mesenchymal neoplasms showing chromosomal abnormalities are presented. In a case of hemangiopericytoma trisomy 2 and centric fusion 19;21 were present. In a mastocytoma a deleted chromosome 35 was seen. A homogeneously staining region (HSR) on chromosome 1 was detected in a histiocytoma. Trisomy 5 and monosomy 31 were observed in a case of granulocytic sarcoma (chloroma). The lack of mutations in exons 1 and 2 of oncogenes N-ras, K-ras, and H-ras and exons 5, 6, 7, and 8 of tumor suppressor gene p53 in these four patients and in a larger series of investigated dogs (25 hemangiopericytomas, 12 mastocytomas, and 8 histiocytomas) is highlighted.
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PMID:Cytogenetic, ras, and p53: studies in cases of canine neoplasms (hemangiopericytoma, mastocytoma, histiocytoma, chloroma). 998 18

This report describes a case of a canine cutaneous grade I mast cell tumour which developed within a lipoma in the right axillar region of an 8-year-old male Boxer. Immunohistologically, the neoplastic mast cells were positive for serotonin, CD45 vimentin and p53, and negative for lysozyme, CD3 and CD79a expression. The proliferation index of the mast cell tumour based on the Ki-67 antigen was 6.1%. Between the benign neoplastic lipocytes and mastocytoma tumour cells intratumoural microvessels were detected by immunohistochemical staining using CD31 and claudin-5 as markers for vascular endothelium.
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PMID:Cutaneous mast cell tumour within a lipoma in a boxer. 1958 39

Mast cell tumor (MCT) is the most common skin malignancy of domestic dogs and presents with a widely variable clinical behavior. Although activating KIT mutations are present in approximately 20% of canine MCTs, molecular etiology is largely unknown for the majority of this cancer. Characterization of genomic alterations in canine MCTs may identify genomic regions and/or genes responsible for their development and progression, facilitating the discovery of new therapeutic targets and improved clinical management of this heterogeneous cancer. We performed genome-wide DNA copy number analysis of 109 primary MCTs derived from three popular canine breeds (the Boxer, Labrador Retriever, and Pug) as well as nontarget breeds using oligonucleotide array comparative genomic hybridization (oaCGH). We demonstrated a stepwise accumulation of numerical DNA copy number aberrations (CNAs) as tumor grade increases. DNA sequencing analysis revealed that KIT mutations were found less frequently in the Pug tumors and were strongly associated with high histological grade. Tumors with KIT mutations showed genome-wide aberrant copy number profiles, with frequent CNAs involving genes in the p53 and RB pathways, whereas CNAs were very limited in tumors with wild-type KIT. We evaluated the presence of four CNAs to predict aggressive tumor phenotypes. This approach predicted aggressive tumors with a sensitivity of 78-94% and specificity of 88-93%, when using oaCGH and droplet digital PCR platforms. Further investigation of genome regions identified in this study may lead to the development of a molecular tool for classification and prognosis, as well as identification of therapeutic target molecules.
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PMID:Genomic profiling of canine mast cell tumors identifies DNA copy number aberrations associated with KIT mutations and high histological grade. 2805 43

Cobalt manganese ferrite nanoparticles have application potential in the biomedical field, however there is limited information concerning the biological response. The aim of this work was to investigate the cytotoxic potential of cobalt-manganese ferrite nanoparticles in canine mastocytoma tumor cells (C2) and adipose-derived mesenchymal stromal stem cells (ASCs) cultured under a static magnetic field (MF). In this study, we investigated the viability and proliferation rate of ASC and C2 cells cultured with Co0.2Mn0.8Fe2O4 nanoparticles under 0.5T MF. We observed cells morphology and measured intracellular ROS generation. Thermal observations were used to characterize the thermotrophic cell behavior in different condition and RNA level of heat shock proteins and apoptotic genes was measured. Nanoparticles reduced cell viability, caused cell damage, i.e., through the formation of reactive oxygen species (ROS) and increased transcriptional level of apoptotic genes (Bcl-2, Bax, p53, p21). In addition, we have found that C2 mastocytoma cells cultured with metal oxide nanoparticles under MF exhibited unexpected biological responses, including thermotolerance and apoptotic response induced by the expression of heat shock proteins and ROS produced under a MF. Our results suggest that stimulation using MF and Co0.2Mn0.8Fe2O4 nanoparticles is involved in mechanisms associated with controlling cell proliferative potential signaling events. We can state that significant differences between normal and cancer cells in response to nanoparticles and MF are apparent. Our results show that nanoparticles and MF elevate the temperature in vitro in tumor cells, thereby increasing the expression of ROS as well as heat shock proteins.
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PMID:The Effect of Co0.2Mn0.8Fe2O4 Ferrite Nanoparticles on the C2 Canine Mastocytoma Cell Line and Adipose-Derived Mesenchymal Stromal Stem Cells (ASCs) Cultured Under a Static Magnetic Field: Possible Implications in the Treatment of Dog Mastocytoma. 2858 34

Mastocytosis is a disorder resulting from an abnormal mast cell (MC) accumulation in tissues that is often associated with the D816V mutation in KIT, the tyrosine kinase receptor for stem cell factor. Therapies available to treat aggressive presentations of mastocytosis are limited, thus exploration of novel pharmacological targets that reduce MC burden is desirable. Since increased generation of the lipid mediator sphingosine-1-phosphate (S1P) by sphingosine kinase (SPHK) has been linked to oncogenesis, we studied the involvement of the two SPHK isoforms (SPHK1 and SPHK2) in the regulation of neoplastic human MC growth. While SPHK2 inhibition prevented entry into the cell cycle in normal and neoplastic human MCs with minimal effect on cell survival, SPHK1 inhibition caused cell cycle arrest in G2/M and apoptosis, particularly in D816V-KIT MCs. This was mediated via activation of the DNA damage response (DDR) cascade, including phosphorylation of the checkpoint kinase 2 (CHK2), CHK2-mediated M-phase inducer phosphatase 3 depletion, and p53 activation. Combination treatment of SPHK inhibitors with KIT inhibitors showed greater growth inhibition of D816V-KIT MCs than either inhibitor alone. Furthermore, inhibition of SPHK isoforms reduced the number of malignant bone marrow MCs from patients with mastocytosis and the growth of D816V-KIT MCs in a xenograft mouse model. Our results reveal a role for SPHK isoforms in the regulation of growth and survival in normal and neoplastic MCs and suggest a regulatory function for SPHK1 in the DDR in MCs with KIT mutations. The findings also suggest that targeting the SPHK/S1P axis may provide an alternative to tyrosine kinase inhibitors, alone or in combination, for the treatment of aggressive mastocytosis and other hematological malignancies associated with the D816V-KIT mutation.
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PMID:Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of Neoplastic Mast Cells With D816V-KIT. 2964 55