TP53-Deficient Angiosarcoma Expression Profiling in Rat Model

Smyczyńska, Urszula; Strzemecki, Damian; Czarnecka, Anna M.; Fendler, Wojciech; Fiedorowicz, Michał; Wełniak-Kamińska, Marlena; Guzowska, Magdalena; Synoradzki, Kamil; Cheda, Łukasz; Rogulski, Z.; Grieb, Paweł

doi:10.3390/cancers12061525

Cited by 4 publications

(4 citation statements)

References 43 publications

(59 reference statements)

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“…Heterozygous rats Tp53C273X/+ (Wistar background) predominantly develop osteosarcomas [67]. The tumors developed in this model were characterized by elevated 18F-FDG (fluorodeoxyglucose) uptake in comparison to adjacent tissues, so they are clearly visible in positron emission tomography scans [68].…”

Section: Diamond-blackfan Anemiamentioning

confidence: 99%

Molecular Biology of Osteosarcoma

Czarnecka

Synoradzki

Firlej

et al. 2020

Cancers

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Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are responsible for syndromes that predispose to osteosarcomas including Li Fraumeni syndrome, retinoblastoma syndrome, Werner syndrome, Bloom syndrome or Diamond–Blackfan anemia. TP53 is the most frequently altered gene in osteosarcoma. Among other genes mutated in more than 10% of OS cases, c-Myc plays a role in OS development and promotes cell invasion by activating MEK–ERK pathways. Several genomic studies showed frequent alterations in the RB gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in NOTCH1, FOS, NF2, WIF1, BRCA2, APC, PTCH1 and PRKAR1A genes. Some miRNAs such as miR-21, -34a, -143, -148a, -195a, -199a-3p and -382 regulate the pathogenic activity of MAPK and PI3K/Akt-signaling pathways in osteosarcoma. CD133+ osteosarcoma cells have been shown to exhibit stem-like gene expression and can be tumor-initiating cells and play a role in metastasis and development of drug resistance. Although currently osteosarcoma treatment is based on adriamycin chemoregimens and surgery, there are several potential targeted therapies in development. First of all, activity and safety of cabozantinib in osteosarcoma were studied, as well as sorafenib and pazopanib. Finally, novel bifunctional molecules, of potential imaging and osteosarcoma targeting applications may be used in the future.

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Section: Diamond-blackfan Anemiamentioning

confidence: 99%

Molecular Biology of Osteosarcoma

Czarnecka

Synoradzki

Firlej

et al. 2020

Cancers

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227

186

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“…Homozygotes develop mostly angiosarcomas, while heterozygotes develop OSs and less frequently angiosarcomas and B-cell lymphomas [ 139 ]. Metabolically active tumors are present in various locations, including the brain, head and neck, abdomen, and extremities [ 143 , 144 ]. Another Tp53 knockout rat generated on the Sprague Dawley background also develops mostly sarcomas.…”

Section: Animal Modelsmentioning

confidence: 99%

TP53 in Biology and Treatment of Osteosarcoma

Synoradzki

Bartnik

Czarnecka

et al. 2021

Cancers

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The TP53 gene is mutated in 50% of human tumors. Oncogenic functions of mutant TP53 maintain tumor cell proliferation and tumor growth also in osteosarcomas. We collected data on TP53 mutations in patients to indicate which are more common and describe their role in in vitro and animal models. We also describe animal models with TP53 dysfunction, which provide a good platform for testing the potential therapeutic approaches. Finally, we have indicated a whole range of pharmacological compounds that modulate the action of p53, stabilize its mutated versions or lead to its degradation, cause silencing or, on the contrary, induce the expression of its functional version in genetic therapy. Although many of the described therapies are at the preclinical testing stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future.

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“…Sarcomas, encompassing soft-tissue sarcomas (STS) and bone sarcomas, are a heterogeneous group of malignancies arising from mesenchymal tissues ( 1 ). They are rare tumors that comprise approximately 1% of adult malignancies, and nearly 15% of pediatric malignancies ( 2 , 3 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of GINS1 as a potential prognostic biomarker for sarcoma using bioinformatic analysis

Zhao¹,

He²,

Ma³

2023

Transl Cancer Res

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Background The GINS complex is related to cancer development, invasion, and poor prognosis in multiple tumors. In the study, we attempted to investigate the prognostic value of GINS1 in sarcoma patients. Methods We analyzed GINS1 expression using Tumor IMmune Estimation Resource (TIMER) 2.0, Gene Expression Omnibus (GEO; GSE21122, GSE39262, and GSE21050), and The Cancer Genome Atlas (TCGA) databases. The prognostic value of GINS1 was explored using the survival and survminer packages of R. Genetic alteration analysis was investigated using cBioPortal. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) R script was used for the immunocyte infiltration analysis. MicroRNAs (miRNAs) targeting GINS1 were predicted using GEO (GSE69470) and MicroRNA Target Prediction Database (miRDB). Results We found that GINS1 was overexpressed in sarcoma, especially in metastatic samples, and was associated with a worse prognosis. High GINS1 expression was a poor prognostic indicator for sarcoma patients. Moreover, GINS1 alteration was associated with worse survival of sarcoma patients. Immune infiltration analysis indicated that GINS1 expression was correlated with the infiltration of M0 and M2 macrophages in sarcoma. Finally, the miRNA hsa-miR-376a-3p was identified to potentially regulate GINS1 in sarcoma. Conclusions These results indicate that GINS1 may be a promising prognostic biomarker and therapeutic target for sarcoma.

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TP53-Deficient Angiosarcoma Expression Profiling in Rat Model

Cited by 4 publications

References 43 publications

Molecular Biology of Osteosarcoma

Molecular Biology of Osteosarcoma

TP53 in Biology and Treatment of Osteosarcoma

Identification of GINS1 as a potential prognostic biomarker for sarcoma using bioinformatic analysis

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