<i>Backgrounds.</i> Doxorubicin (DOX) is an effective therapeutic drug for malignant tumors; however, its clinical applications were limited by its side effects, especially the cardiotoxicity caused by ROS-mediated p53 and MAPK signal pathways' activation-induced cell apoptosis.
<i>TP53</i> (tumor protein p53) is a tumor suppressor gene frequently mutated in cancer and implicated in cell-cycle regulation, apoptosis, and angiogenesis.
(1) Is there a relationship between TACC3 expression and clinicopathologic characteristics such as sex, age (< 20 or ≥ 20 years), histologic type (osteoblastic or others), tumor location (femur or others), American Joint Committee on Cancer staging system (AJCC stage IIA or IIB), tumor necrosis percentage after chemotherapy (< 90% or ≥ 90%), p53 expression (low or high), and Ki-67 expression (low or high)?
(2007) suggest that restoring p53 function alone is sufficient to cause regression of several different tumor types in mice and thus might represent a potent therapeutic strategy to treat certain human cancers.Martins et al.
122 breast cancer (dataset B) from Seoul National University Hospital containing 54 TP53 mutation cancer and 68 without mutations were used in this study.
277Y mutations have been described in human tumours, and Ewing tumour cells expressing this mutant from the endogenous p53 locus selectively activate transcription from transfected luciferase reporters regulated by TTT-mutant p53 binding sites. p53 mutants with altered sequence specificity have potential advantages for cancer gene therapy: if used to activate transcription of conditionally toxic genes they would allow tumour-targeting by p53, which acts as a sensor for the malignant state, but place control over cell killing in the hands of the clinician.
3,3'-Spirocyclopentene oxindoles structurally related to Wang's spiropyrrolidine oxindoles have been highlighted as a new class of antiproliferative agents against cancer cell lines with wild-type p53 status (IC<sub>50</sub> up to 0.96 μM on SJSA-1 and 2.9 μM in HCT116 p53-wt).
Cancers of the cardia more frequently contain p53 mutations than do antral and corpus cancers, suggesting that cancers in the proximal and distal stomach evolve through different molecular pathways.
Cancer-specific survival did not differ significantly between patients with K-ras or TP53 or both mutated and nonmutated tumors, respectively (log-rank test: K-ras, P = 0.72 and TP53, P = 0.77; K-ras and TP53, P = 0.8).
Cancer Biol Ther 2(4):416-430; and Microarray Analysis of p53 Target Gene Expression Patterns in the Spleen and Thymus in Response to Ionizing Radiation.Burns TF, et al.Cancer Biol Ther 2(4):431-443.
Cancer gene therapies using ectopic expression of wild-type p53 to force cancer cells through the apoptotic pathway have been tested extensively preclinically and clinically, and genes in various cell lines have been reported to be regulated upon ectopic p53 overexpression.
Cancer therapies that target specific mutant genes are proving to be highly active and trials assessing agents that exploit the p53 system are ongoing.
Cancer development and chemo-resistance are often due to impaired functioning of the p53 tumor suppressor through genetic mutation or sequestration by other proteins.