We describe strategies to: i) target EGFR, its ligand-independent variant EGFRvIII, and PDGFR on the cell surface, ii) inhibit constitutively activate RAS/MAPK and PI3K/Akt signaling pathways, iii) target TP53 mutant tumors, and iv) block GBM angiogenesis and invasion.
Therefore, p53 mutation may precede invasion in esophageal carcinogenesis, and multifocal esophageal neoplasms may arise from independent clones of transformed cells.
TP53 mutations were associated with extramural venous invasion on baseline MRI (78% vs. 65%, p = 0.04), poor pathological tumour regression (23% vs. 36%, p = 0.05) and a trend toward a worse 5-year progression-free survival (PFS; 60% vs. 74%, HR 1.59, p = 0.06).
Esophageal cells overexpressing epidermal growth factor receptor (EGFR) and TP53 mutation can invade into the extracellular matrix when grown in 3D-organotypic cultures (OTC) and mimic early invasion in esophageal squamous cell carcinoma (ESCC).
We found that two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) exhibited the highest invasion rates through the Matrigel or collagen matrix.
Using the SKBR3 breast cancer and p53-null H1299 lung cancer cells stably expressing the R175Hp53 mutant protein, we demonstrated that GON triggers the appearance of a wild-type-like p53 protein by using conformation-specific antibodies, immunoprecipitation, DNA-binding assays and target gene expression. p53 restoration was associated with a G2/M arrest, senescence, reduced cell migration, invasion and increased cell death.
The three factors (ALDOB down-regulation, HKII overexpression and p53 mutation) not only correlated with tumor progression, but also interacted with one another, leading to a more aggressive HCC with a portal vein invasion and various extent of intrahepatic metastasis by more than four-fold (ps<1x10(-6)) and frequent ETR by more than two-fold (ps<0.0001) compared with HCCs without the events.
There were statistically significant differences in the extent of pathologic biology, differentiation, and invasion between patients with combined p53 mutation and DAPK, p14(ARF), and/or ASC methylation compared to those without (P < 0.05).
In MPP positive tumors, visceral pleural invasion was identified significantly more frequent than in MPP negative tumors, at stage I. Tumors with MPP showed elevated expressions of caspase-3 (94.5%), p53 (60%), and bcl-2 (54.5%).
The p53 gene underwent loss of heterozygosity (LOH) in 4 of 4 informative cases of intestinal-type gastric cancer with mucosal lesions associated with invasion.
Exons 5 through 8 of the p53 gene were amplified in DNAs and the mutations detected in 28 cases (34%) did not correlate with tumor location, histopathologic classification, histologic depth of tumor invasion, lymph node involvement or clinical stage.
In PBK/TOPK-overexpressing GC cells, knockdown of PBK/TOPK inhibited the cell proliferation through the p53 activation in a TP53 mutation-dependent manner and inhibited the migration/invasion through the PTEN upregulation in a TP53 mutation-independent manner.
In the subset of HCCs that has no mutations of p53 and beta-catenin but showed PAP expression, coexpression of REG1A and PAP was associated with more frequent vascular invasion than PAP expression alone (P < 0.005).
Here, we investigated the role of mutant p53 in cell migration and invasion as well as its underlying molecular mechanisms in human ovarian cancer cells.
Establishment of an oral squamous cell carcinoma cell line (NOS-1) exhibiting amplification of the erbB-1 oncogene and point mutation of p53 tumor suppressor gene: its biological characteristics and animal model of local invasion by orthotopic transplantation of the cell line.