Anti-cancer drug adriamycin (ADR) treatment induced cell death in <i>p53</i>-wild-type human osteosarcoma U2OS cells, and this was accompanied by a remarkable accumulation of p53 and γH2AX.
Our results suggest that adenovirus-mediated transduction of p53 family members may have utility in gene therapy for OS, particularly in combination with chemotherapeutic agents.
Our results revealed an inactive form of p53 sporadically seen in the samples, a total loss of Rb protein expression, an increased expression of Cdk4, MDM2, c-fos, and c-myc proteins which literature currently reports being the principal alterations found in osteosarcoma.
Recent developments of importance include an improved understanding of the importance of the p53 gene in the pathogenesis of osteosarcoma, the description of preclinical models, the development of improved imaging techniques for determining tumor extent and responsiveness to chemotherapy, and refinements in therapy.
To determine the relation between COPS3 amplification, P53 mutation, and patient outcome in osteosarcoma, tumors from a large cohort of patients with high-grade osteosarcoma and long-term clinical follow-up were examined.
We show that in hamster (Chinese hamster ovary) or human (osteosarcoma 143) cell lines the replication of both Py and papillomavirus origins was efficiently blocked by p53.
At advanced ages, p53 mKO mice began to die prematurely and had an increased incidence of osteosarcoma, precluding analyses of muscle mass and function in very old p53 mKO mice.
We here demonstrate that the cell cycle was arrested in G2/M phase following supplementation with DZQ of human osteosarcoma Saos-2 cells (lacking both p53 and pRb) and HCT116 cells.
Further experiments suggest that trans-chalcone affected Sp1 down-regulation at the transcriptional level, whereas trans-chalcone up-regulated p53 expression at the post-translational level. trans-chalcone and its derivatives could be important in the development of future clinical trials in osteosarcoma.
A polysaccharide from Enterobacter cloacae induces apoptosis of human osteosarcoma cells through the activation of p53 and mitochondrial intrinsic pathway.
Osteosarcoma development is dependent on loss of p53 and potentiated by loss of pRb, revealing a dominance of p53 mutation in the development of osteosarcoma.
This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.
The relationship between P-glycoprotein expression and p53 status was analyzed by immunohistochemistry in 64 primary and 11 metastatic high-grade osteosarcomas.
A similar proportion of localized osteosarcomas had alterations of the p53 gene (55 of 247 specimens; 22.3%) compared with tumors from patients who had metastases at the time of diagnosis (5 of 25 specimens; 20%; P = 0.96).
Some of the genetic changes identified were in tumor suppressor genes previously identified as altered in osteosarcoma: p53 (arginine→histidine at codon 273 [R273H], R→cysteine at codon 723 [R273C], and tyrosine→C at codon 163 [Y163C]) and retinoblastoma 1 (RB1) (glutamic acid→* at codon 137 [E137*]).
Furthermore, Pla2g16 levels were increased upon expression of mutant p53 in both mouse and human osteosarcoma cell lines, indicating that Pla2g16 is a downstream target of the mutant p53 protein.
This study found an association between alterations in the TP53 gene and the synergy score for combination treatment with doxorubicin and an Src kinase inhibitor using human osteosarcoma cell lines (MG63 and U2OS) and human colon cancer cell line.
By utilizing the clinical information in GSE21257, 10 critical genes associated with osteosarcoma prognosis were obtained, including CTP synthase 2 (CTPS2), tumor protein p53 inducible protein 3 (TP53I3) and solute carrier family 1 member 1 (SLC1A1).
Overexpression of RASSF5 markedly suppressed cell proliferation and invasion, and induced cell apoptosis in the OS cell lines with increased expression of MST1, LATS1 and p53 and decreased expression of PCNA and MMP-9.