scholarly journals Reactivity of p53 protein in canine transmissible venereal tumor

2010 ◽  
Vol 62 (2) ◽  
pp. 318-323 ◽  
Author(s):  
J.V. Moro ◽  
M. Tinucci-Costa ◽  
A.C.T. Silveira ◽  
D.G. Gerardi ◽  
A.C. Alessi
Keyword(s):  
P53 Protein ◽  
P53 Gene ◽  
Natural Occurrence ◽  
Functional Abnormality ◽  
Immunohistochemical Reaction

The expression of p53 protein was evaluated in canine transmissible venereal tumor (CTVT), as following: natural occurrence (n=8); resistant to chemotherapy (n=4); and allogeneic transplanted in progression (n=8), stable (n=8), and regression (n=8)stages. The collected specimens were submitted to GM1 immunohistochemical reaction. Results showed a mean percentage of immunomarked cells around 18.6% in CTVT of natural occurrence, 23.8% in CTVT resistant to chemotherapy, 22.9% in allogeneic transplanted CTVT in both progression and stable stages, and 35.8% in transplanted CTVT in regression stage. The results suggest that there is a functional abnormality in p53 gene and its products in the studied tumors; although, it is not possible to correlate the percentage of cells marked by p53 and a prognosis.

scholarly journals Inhibition of polyamine synthesis induces p53 gene expression but not apoptosis

1999 ◽  
Vol 276 (4) ◽  
pp. C946-C954 ◽  
Author(s):  
Li Li ◽  
Ji Li ◽  
Jaladanki N. Rao ◽  
Minglin Li ◽  
Barbara L. Bass ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Inhibition ◽  
P53 Protein ◽  
Specific Inhibitor ◽  
P53 Gene ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Polyamine Biosynthesis ◽  
Fetal Bovine ◽  
P53 Mrna

The nuclear phosphoprotein p53 acts as a transcription factor and is involved in growth inhibition and apoptosis. The present study was designed to examine the effect of decreasing cellular polyamines on p53 gene expression and apoptosis in small intestinal epithelial (IEC-6) cells. Cells were grown in DMEM containing 5% dialyzed fetal bovine serum in the presence or absence of α-difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis, for 4, 6, and 12 days. The cellular polyamines putrescine, spermidine, and spermine in DFMO-treated cells decreased dramatically at 4 days and remained depleted thereafter. Polyamine depletion by DFMO was accompanied by a significant increase in expression of the p53 gene. The p53 mRNA levels increased 4 days after exposure to DFMO, and the maximum increases occurred at 6 and 12 days after exposure. Increased levels of p53 mRNA in DFMO-treated cells were paralleled by increases in p53 protein. Polyamines given together with DFMO completely prevented increased expression of the p53 gene. Increased expression of the p53 gene in DFMO-treated cells was associated with a significant increase in G1 phase growth arrest. In contrast, no features of programmmed cell death were identified after polyamine depletion: no internucleosomal DNA fragmentation was observed, and no morphological features of apoptosis were evident in cells exposed to DFMO for 4, 6, and 12 days. These results indicate that 1) decreasing cellular polyamines increases expression of the p53 gene and 2) activation of p53 gene expression after polyamine depletion does not induce apoptosis in intestinal crypt cells. These findings suggest that increased expression of the p53 gene may play an important role in growth inhibition caused by polyamine depletion.

scholarly journals Tumor Eradication by Wild-type p53-specific Cytotoxic T Lymphocytes

1997 ◽  
Vol 186 (5) ◽  
pp. 695-704 ◽  
Author(s):  
Michel P.M. Vierboom ◽  
Hans W. Nijman ◽  
Rienk Offringa ◽  
Ellen I.H. van der Voort ◽  
Thorbald van Hall ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Normal Tissue ◽  
P53 Protein ◽  
P53 Gene ◽  
Wild Type ◽  
Wild Type P53 ◽  
Tumor Outgrowth ◽  
Tumor Eradication

The tumor suppressor protein p53 is overexpressed in close to 50% of all human malignancies. The p53 protein is therefore an attractive target for immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a murine wild-type p53 peptide, presented by the major histocompatibility complex class I molecule H-2Kb, were generated by immunizing p53 gene deficient (p53 −/−) C57BL/6 mice with syngeneic p53-overexpressing tumor cells. Adoptive transfer of these CTLs into tumor-bearing p53 +/+ nude mice caused complete and permanent tumor eradication. Importantly, this occurred in the absence of any demonstrable damage to normal tissue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs persisted for weeks in the absence of immunopathology and were capable of preventing tumor outgrowth. Wild-type p53-specific CTLs can apparently discriminate between p53-overexpressing tumor cells and normal tissue, indicating that widely expressed autologous molecules such as p53 can serve as a target for CTL-mediated immunotherapy of tumors.

scholarly journals Isolation of Disease-relevant p53 for Cryo-Electron Microscopy Analysis

2021 ◽  
Author(s):  
Maria J. Solares ◽  
GM Jonaid ◽  
William Y. Luqiu ◽  
Yanping Liang ◽  
Madison C. Evans ◽  
...  
Keyword(s):  
P53 Protein ◽  
P53 Gene ◽  
Tp53 Gene ◽  
Tumor Suppressor Protein ◽  
Protein Assemblies ◽  
Cryo Electron Microscopy ◽  
Naturally Occurring ◽  
Imaging Protocols ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis

Abstract Tumor suppressor protein TP53 (p53) plays a multi-faceted role in all cells of thehuman body. Sadly, mutations in the TP53 gene are involved in nearly ~50% of tumors,spurring erratic cell growth and disease progression. Until recently, structural informationfor p53 remained incomplete and there are limited studies on native p53 produced inhuman tumors. Here, we present a highly reproducible and effective protocol to extract,enrich, and purify native p53 protein assemblies from cancer cells for downstreamstructural studies. This method does not introduce purification tags into the p53 gene andmaintains naturally occurring modifications. In conjunction with cryo-Electron Microscopytechniques, we determined new structures for p53 monomers (~50 kDa) and tetramers(~200 kDa) at spatial resolutions of ~4.8 Å and ~7 Å, respectively.1 These modelsrevealed new insights for flexible regions of p53 along with biologically-relevantubiquitination sites. Combining biochemical and structural imaging protocols, we aim tobuild a better understanding of native p53’s impact in cancer formation.

Increased p53 Protein Does Not Correlate to p53 Gene Mutations in Microdissected Human Testicular Germ Cell Tumors

1995 ◽  
Vol 154 (2) ◽  
pp. 617-621 ◽  
Author(s):  
Noah S. Schenkman ◽  
Isabell A. Sesterhenn ◽  
Lucille Washington ◽  
Yue Ao Tong ◽  
Christopher M. Weghorst ◽  
...  
Keyword(s):  
Germ Cell ◽  
P53 Protein ◽  
Germ Cell Tumors ◽  
Gene Mutations ◽  
P53 Gene ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
P53 Gene Mutations

High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene

1989 ◽  
Vol 9 (9) ◽  
pp. 3982-3991
Author(s):  
A Lavigueur ◽  
V Maltby ◽  
D Mock ◽  
J Rossant ◽  
T Pawson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Malignant Transformation ◽  
P53 Protein ◽  
P53 Gene ◽  
Cell Types ◽  
Molecular Events ◽  
High Incidence ◽  
Transgenic Lines ◽  
Functional Inactivation

We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or BALB/c mouse liver DNA. Elevated levels of p53 mRNA were detected in several tissues of two transgenic lines tested. Increased levels of p53 protein were also detected in most of the tissues analyzed by Western blotting (immunoblotting). Because both transgenes encoded p53 proteins that were antigenically distinct from wild-type p53, it was possible to demonstrate that overexpression of the p53 protein was mostly, if not entirely, due to the expression of the transgenes. Neoplasms developed in 20% of the transgenic mice, with a high incidence of lung adenocarcinomas, osteosarcomas, and lymphomas. Tissues such as ovaries that expressed the transgene at high levels were not at higher risk of malignant transformation than tissues expressing p53 protein at much lower levels. The long latent period and low penetrance suggest that overexpression of p53 alone is not sufficient to induce malignancies and that additional events are required. These observations provide direct evidence that mutant alleles of the p53 oncogene have oncogenic potential in vivo and that different cell types show intrinsic differences in susceptibility to malignant transformation by p53. Since recent data suggest that p53 may be a recessive oncogene, it is possible that the elevated tumor incidence results from functional inactivation of endogenous p53 by overexpression of the mutant transgene. The high incidence of lung and bone tumors suggests that p53 transgenic mice may provide a useful model to investigate the molecular events that underlie these malignancies in humans.

scholarly journals The Association and Significance of p53 in Gynecologic Cancers: The Potential of Targeted Therapy

2019 ◽  
Vol 20 (21) ◽  
pp. 5482 ◽  
Author(s):  
Mitsuhiro Nakamura ◽  
Takeshi Obata ◽  
Takiko Daikoku ◽  
Hiroshi Fujiwara
Keyword(s):  
Cervical Cancer ◽  
Endometrial Cancer ◽  
Malignant Tumors ◽  
P53 Protein ◽  
P53 Gene ◽  
Phase Iii ◽  
Significant Prognostic Factor ◽  
Double Positive ◽  
P53 Overexpression ◽  
Tp53 Mutations

Dysfunction of p53 is observed in the many malignant tumors. In cervical cancer, p53 is inactivated by degradation through the complex with human papilloma virus (HPV) oncoprotein E6 and E6-associated protein (E6AP), an E3 ubiquitin protein ligase. In endometrial cancer, overexpression of p53 in immunohistochemistry is a significant prognostic factor. A discrepancy between p53 overexpression and TP53 mutations is observed in endometrioid endometrial cancer, indicating that the accumulation of p53 protein can be explained by not only gene mutations but also dysregulation of the factors such as ERβ and MDM2. Furthermore, the double-positive expression of immunoreactive estrogen receptor (ER) β and p53 proteins is closely associated with the incidence of metastasis and/or recurrence. High-grade serous ovarian carcinoma (HGSC) arises from secretary cells in the fallopian tube. The secretary cell outgrowth (SCOUT) with TP53 mutations progresses to HGSC via the p53 signature, serous intraepithelial lesion (STIL), and serous intraepithelial carcinoma (STIC), indicating that TP53 mutation is associated with carcinogenesis of HGSC. Clinical application targeting p53 has been approved for some malignant tumors. Gene therapy by the adenovirus-mediated p53 gene transfer system is performed for head and neck cancer. A clinical phase III trial using MDM2/X inhibitors, idasanutlin (RG7388) combined with cytarabine, is being performed involving relapse/refractory acute myeloid leukemia patients. The use of adenoviruses as live vectors which encode wild-type p53 has given promising results in cervical cancer patients.

p53 Immunoexpression in Carcinomas Arising in Pleomorphic Adenoma

1996 ◽  
Vol 3 (4) ◽  
pp. 257-262 ◽  
Author(s):  
Joaninha Costa Rosa ◽  
Isabel Fonseca ◽  
Ana Félix ◽  
Jorge Soares
Keyword(s):  
Pleomorphic Adenoma ◽  
P53 Protein ◽  
P53 Gene ◽  
Tumor Grade ◽  
Undifferentiated Carcinoma ◽  
Protein Accumulation ◽  
Low Grade ◽  
Histologic Type ◽  
Epithelial Myoepithelial Carcinoma ◽  
Invasive Carcinomas

p53 protein immunoexpression was evaluated in 17 invasive carcinomas arising in pleomorphic adenoma and correlated with the histologic type and tumor grade. Ten tumors had one malignant histologic component: adenocarcinoma NOS (not otherwise specified) (five), undifferentiated carcinoma (two), malignant myoepithelioma (one), epithelial-myoepithelial carcinoma (one), and malignant oncocytoma (one). In the remaining cases, there was a coexistence of areas of adenocarcinoma (seven), adenosquamous (two), epithelial-myoepithelial (two), adenoid cystic (two), undifferentiated carcinoma (one), and low-grade polymorphous adenocarcinoma (one). p53 positivity was found within adenocarcinoma NOS (three) and adenosquamous carcinoma (two) components of four cases. Tumor areas showing low-grade histology, either mono- or bidifferentiated carcinomas, were always negative in this series, in keeping with previous observations on primary neoplasms of the same histologic type. The benign component of the neoplasms was also found to be consistently negative. The results point to a preferential association of the p53 gene dysfunction and its protein accumulation with the malignant transformation of pleomorphic adenomas into salivary adenocarcinomas with features of high-grade malignancy.

p53 protein accumulation and p53 gene mutation in colorectal cancer

2000 ◽  
Vol 6 (4) ◽  
pp. 275-279 ◽  
Author(s):  
Anna Nasierowska-Guttmejer ◽  
Lech Trzeciak ◽  
Marek P. Nowacki ◽  
Jerzy Ostrowski
Keyword(s):  
Colorectal Cancer ◽  
Gene Mutation ◽  
P53 Protein ◽  
P53 Gene ◽  
Protein Accumulation ◽  
P53 Gene Mutation

Phase I Trial of Adenovirus-Mediated p53 Gene Therapy for Recurrent Glioma: Biological and Clinical Results

2003 ◽  
Vol 21 (13) ◽  
pp. 2508-2518 ◽  
Author(s):  
Frederick F. Lang ◽  
Janet M. Bruner ◽  
Gregory N. Fuller ◽  
Kenneth Aldape ◽  
Michael D. Prados ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase I ◽  
Injection Site ◽  
P53 Protein ◽  
Tumor Biology ◽  
P53 Gene ◽  
Maximum Tolerated Dose ◽  
Intratumoral Injection ◽  
En Bloc ◽  
Clinical Toxicity

Purpose: Advances in brain tumor biology indicate that transfer of p53 is an alternative therapy for human gliomas. Consequently, we undertook a phase I clinical trial of p53 gene therapy using an adenovirus vector (Ad-p53, INGN 201). Materials and Methods: To obtain molecular information regarding the transfer and distribution of exogenous p53 into gliomas after intratumoral injection and to determine the toxicity of intracerebrally injected Ad-p53, patients underwent a two-stage approach. In stage 1, Ad-p53 was stereotactically injected intratumorally via an implanted catheter. In stage 2, the tumor-catheter was resected en bloc, and the postresection cavity was treated with Ad-p53. This protocol provided intact Ad-p53–treated biologic specimens that could be analyzed for molecular end points, and because the resection cavity itself was injected with Ad-p53, patients could be observed for clinical toxicity. Results: Of fifteen patients enrolled, twelve underwent both treatment stages. In all patients, exogenous p53 protein was detected within the nuclei of astrocytic tumor cells. Exogenous p53 transactivated p21CIP/WAF and induced apoptosis. However, transfected cells resided on average within 5 mm of the injection site. Clinical toxicity was minimal and a maximum-tolerated dose was not reached. Although anti-adenovirus type 5 (Ad5) titers increased in most patients, there was no evidence of systemic viral dissemination. Conclusion: Intratumoral injection of Ad-p53 allowed for exogenous transfer of the p53 gene and expression of functional p53 protein. However, at the dose and schedule evaluated, transduced cells were only found within a short distance of the injection site. Although toxicity was minimal, widespread distribution of this agent remains a significant goal.

Sign in / Sign up

Export Citation Format

Share Document