TP53 in Biology and Treatment of Osteosarcoma

Synoradzki, Kamil; Bartnik, Ewa; Czarnecka, Anna M.; Fiedorowicz, Michał; Firlej, Wiktoria; Brodziak, Anna; Stasinska, Agnieszka; Rutkowski, Piotr; Grieb, Paweł

doi:10.3390/cancers13174284

Cited by 32 publications

(31 citation statements)

References 209 publications

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“…Expression of mutated p53 has been associated with poor prognosis and response to chemotherapy in many human malignancies ( 20 , 21 ). p53 mutations are also frequently detected in OS and have been suggested as possible targets of novel therapies ( 22 ). p53 has been also found to be overexpressed in a significant subset of OS of the jaws ( 9 , 16 , 23 , 24 ) Specifically, p53 positivity was detected in 88% and 52% of the jaw OS cases reported by Lopes et al .…”

Section: Discussionmentioning

confidence: 99%

Juvenile trabecular ossifying fibroma: Immunohistochemical expression of MDM2, CDK4 and p53 compared to conventional ossifying fibroma

Nikitakis¹,

Georgaki²,

Merkourea³

et al. 2022

J Clin Exp Dent

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Background Juvenile ossifying fibroma (JOF) is an uncommon benign fibro-osseous lesion of the craniofacial skeleton; compared to conventional ossifying fibroma (OF), JOF is characterized by local aggressiveness and propensity for recurrence. The biologic basis for this different biologic behavior between JOF and OF remains elusive. The aim of this study was to evaluate the immunohistochemical expression of MDM2, CDK4 and p53, molecules associated with bone oncogenesis, in the trabecular variant of JOF. Material and Methods The study material consisted of five cases of trabecular JOF, affecting three male and two female patients with a mean age of 11.8 years. Three cases arose in the maxilla and two in the mandible. All cases were initially treated by enucleation; two cases recurred necessitating more aggressive treatment. Immunohistochemical study of MDM2, CDK4 and p53 was performed in all cases, as well as in five control cases of conventional OF. Results CDK4 positivity was noted in all JOF cases; the staining pattern was diffuse and strong in 4 cases and focal and weak in one case. In contrast, 4 out of 5 cases of OF were weakly and focally CDK4 positive, the remaining one being negative. Immunostaining for MDM2 was observed in 3 JOF cases; all OF were MDM2 negative. All cases of OF and JOF were negative for p53, except for one focally positive JOF case. Conclusions CDK4 and MDM2 expression in the trabecular variant of JOF is higher compared to conventional OF. In contrast, p53 expression is almost universally negative in JOF and OF. Despite some overlapping features, differential expression patterns of proteins involved in bone oncogenesis can elucidate the pathogenesis and may facilitate accurate diagnosis and prediction of behavior of bone tumors in the craniofacial region. Key words: Juvenile ossifying fibroma, trabecular variant, conventional ossifying fibroma, MDM2, CDK4, p53.

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Section: Discussionmentioning

confidence: 99%

Juvenile trabecular ossifying fibroma: Immunohistochemical expression of MDM2, CDK4 and p53 compared to conventional ossifying fibroma

Nikitakis¹,

Georgaki²,

Merkourea³

et al. 2022

J Clin Exp Dent

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“…The change further emphasized that the assessment of bone tumors should be more thorough and personalized. We reviewed previous studies on prognostic-related molecular markers and found that the vascular endothelial growth factor (VEGF) and p53 mutation were two important biomarkers related to the evaluation of the biological aggressiveness of osteosarcoma and GCTB (3,(8)(9)(10)(11)(12)(13)(14)(15). Angiogenesis occurs in numerous biological processes, which is essential for the growth of tumors and metastases.…”

Section: Introductionmentioning

confidence: 99%

A Multiparametric Method Based on Clinical and CT-Based Radiomics to Predict the Expression of p53 and VEGF in Patients With Spinal Giant Cell Tumor of Bone

Wang

Zhang

et al. 2022

Front. Oncol.

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PurposeThis project aimed to assess the significance of vascular endothelial growth factor (VEGF) and p53 for predicting progression-free survival (PFS) in patients with spinal giant cell tumor of bone (GCTB) and to construct models for predicting these two biomarkers based on clinical and computer tomography (CT) radiomics to identify high-risk patients for improving treatment.Material and MethodsA retrospective study was performed from April 2009 to January 2019. A total of 80 patients with spinal GCTB who underwent surgery in our institution were identified. VEGF and p53 expression and clinical and general imaging information were collected. Multivariate Cox regression models were used to verify the prognostic factors. The radiomics features were extracted from the regions of interest (ROIs) in preoperative CT, and then important features were selected by the SVM to build classification models, evaluated by 10-fold crossvalidation. The clinical variables were processed using the same method to build a conventional model for comparison.ResultsThe immunohistochemistry of 80 patients was obtained: 49 with high-VEGF and 31 with low-VEGF, 68 with wild-type p53, and 12 with mutant p53. p53 and VEGF were independent prognostic factors affecting PFS found in multivariate Cox regression analysis. For VEGF, the Spinal Instability Neoplastic Score (SINS) was greater in the high than low groups, p < 0.001. For p53, SINS (p = 0.030) and Enneking stage (p = 0.017) were higher in mutant than wild-type groups. The VEGF radiomics model built using 3 features achieved an area under the curve (AUC) of 0.88, and the p53 radiomics model built using 4 features had an AUC of 0.79. The conventional model built using SINS, and the Enneking stage had a slightly lower AUC of 0.81 for VEGF and 0.72 for p53.Conclusionp53 and VEGF are associated with prognosis in patients with spinal GCTB, and the radiomics analysis based on preoperative CT provides a feasible method for the evaluation of these two biomarkers, which may aid in choosing better management strategies.

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“…It can be activated through various stresses, including DNA damage, oncogene expression, hypoxia, and replication stress, as well as cellular metabolic changes. Once activated, p53 can trigger apoptosis, cell cycle arrest, or senescence to suppress tumor progression by activating its target genes [15,16]. CDKN1A is the critical induced gene in p53-mediated cellular senescence.…”

Section: Introductionmentioning

confidence: 99%

Different Cell Responses to Hinokitiol Treatment Result in Senescence or Apoptosis in Human Osteosarcoma Cell Lines

Yang

Chen

Chuang

et al. 2022

IJMS

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Hinokitiol is a tropolone-related compound isolated from the heartwood of cupressaceous plants. It is known to exhibit various biological functions including antibacterial, antifungal, and antioxidant activities. In the study, we investigated the antitumor activities of hinokitiol against human osteosarcoma cells. The results revealed that hinokitiol treatment inhibited cell viability of human osteosarcoma U-2 OS and MG-63 cells in the MTT assay. Further study revealed that hinokitiol exposure caused cell cycle arrest at the S phase and a DNA damage response with the induction of γ-H2AX foci in both osteosarcoma cell lines. In U-2 OS cells with wild-type tumor suppressor p53, we found that hinokitiol exposure induced p53 expression and cellular senescence, and knockdown of p53 suppressed the senescence. However, in MG-63 cells with mutated p53, a high percentage of cells underwent apoptosis with cleaved-PARP expression and Annexin V staining after hinokitiol treatment. In addition, up-regulated autophagy was observed both in hinokitiol-exposed U-2 OS and MG-63 cells. As the autophagy was suppressed through the autophagy inhibitor chloroquine, hinokitiol-induced senescence in U-2 OS cells was significantly enhanced accompanying more abundant p53 expression. In MG-63 cells, co-treatment of chloroquine increased hinokitiol-induced apoptosis and decreased cell viability of the treated cells. Our data revealed that hinokitiol treatment could result in different cell responses, senescence or apoptosis in osteosarcoma cell lines, and suppression of autophagy could promote these effects. We hypothesize that the analysis of p53 status and co-administration of autophagy inhibitors might provide more precise and efficacious therapies in hinokitiol-related trials for treating osteosarcoma.

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TP53 in Biology and Treatment of Osteosarcoma

Cited by 32 publications

References 209 publications

Juvenile trabecular ossifying fibroma: Immunohistochemical expression of MDM2, CDK4 and p53 compared to conventional ossifying fibroma

Juvenile trabecular ossifying fibroma: Immunohistochemical expression of MDM2, CDK4 and p53 compared to conventional ossifying fibroma

A Multiparametric Method Based on Clinical and CT-Based Radiomics to Predict the Expression of p53 and VEGF in Patients With Spinal Giant Cell Tumor of Bone

Different Cell Responses to Hinokitiol Treatment Result in Senescence or Apoptosis in Human Osteosarcoma Cell Lines

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