Oncology reports
-
The urokinase plasminogen activator system, which consists of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and urokinase plasminogen activator receptor (uPAR), plays an important role in tumor invasion and metastasis, and it may be a potential diagnostic biomarker and therapeutic target in cancer. It has been found that the expression of uPA and PAI-1 in ovarian cancer is related to clinical pathologies, while their effects on the biological behavior of tumor cells and their clinical significance are still unknown. In this study, 100 tissue samples (60 samples from malignant tumors, 20 from benign tumors and 20 from controls) and 147 blood samples (49 samples each from patients with malignant tumors, benign tumors and control group, respectively) were analyzed. The positive expression levels of uPA and PAI-1 in the malignant tumor samples and their serum concentrations in the malignant group were all significantly higher than these levels in the benign tumors and controls. ⋯ The Cox model analysis showed that expression of uPA at the transcription level had significant associations with prognosis. In addition, uPA greatly enhanced the abilities of cell invasion, migration and adhesion through its overexpression in SKOV3 cells. Collectively, our results showed that uPA and PAI-1 play important roles in ovarian cancer development; therefore, their expression in tissues and their concentrations in serum would greatly assist the diagnosis and prediction of the prognosis in ovarian cancer.
-
Heat shock protein 90 (HSP90), a molecular chaperone, has provoked great interest as a promising molecular target for cancer treatment, due to its involvement in regulating the conformation, stability and functions of key oncogenic proteins. At present, a variety of chemical compounds targeting HSP90 have been developed and have shown convincing anti-neoplastic activity in various preclinical tumor models. The aim of our study was to evaluate the antitumor effects of a novel HSP90 inhibitor, NVP-AUY922, in esophageal squamous cancer cells (ESCC). ⋯ Furthermore, the enhanced activity of AKT in PTEN-silenced TE-10 was more easily suppressed by NVP-AUY922. Collectively, NVP-AUY922 exhibits a strong antiproliferative effect, revealing its potential as a novel therapeutic alternative to current ESCC treatment. The effect may be improved further by impeding PTEN expression.
-
The anticancer agent, taxol, stabilizes tubulin polymerization, resulting in arrest at the G2/M phase of the cell cycle and apoptotic cell death. However, the molecular mechanism of this growth inhibition and apoptosis is poorly understood. In this study, we used MCF-7 and MDA-MB-231 human breast carcinoma cells which have different estrogen receptor (ER) and tumor suppressor p53 statuses to examine the mechanisms of taxol-induced growth inhibition and apoptosis. ⋯ Western blot analysis using whole cell lysates from MCF-7 and MDA-MB-231 cells treated with taxol demonstrated that taxol treatment inhibited expression of cyclin A and cyclin B1 proteins in a time-dependent manner. The inhibitory effects of taxol on cell growth and apoptosis induced by taxol were also associated with the downregulation of Wee1 kinase expression and a marked induction in the activity of the cyclin-dependent kinase inhibitor, p21WAF/CIP1. Furthermore, taxol elevated p21 promoter activity in both cell lines. These findings suggest that taxol-induced G2/M arrest and apoptosis in human breast carcinoma cells is mediated through the ER- and p53-independent upregulation of p21.
-
We examined the effects of the preferential cyclooxygenase-2 (COX-2) inhibitor celecoxib on tumorigenesis, angiogenesis, apoptosis, vascular endothelial growth factor (VEGF) protein expression and metastasis in HT-29 human colorectal carcinoma cell xenografts in nude mouse rectum. COX-2 mRNA expression was examined in the xenograft and metastatic sites. The antitumor effect of celecoxib in the xenografts was evaluated by measuring the weight of the peri-ano-rectal tumor. ⋯ Celecoxib suppressed VEGF protein expression in the rectal xenograft. These studies demonstrate that celecoxib reduces the growth and metastatic potential of colorectal carcinoma in mice through COX-2 inhibition, anti-angiogenesis and apoptosis induction. The studies using HT-29 human colorectal carcinoma cell xenografts in nude mouse rectum also provide important information that supports that the COX-2 inhibitor celecoxib has a high potential for use as a clinical agent for inhibition of hematological and lymphatic metastases of colorectal cancer.
-
The prognosis of advanced esophageal cancer patients is poor. Trimodality therapy of surgical resection plus neoadjuvant chemoradiotherapy (CRT) has been developed to improve survival through locoregional control, leading to prevention of micrometastasis. We investigated whether or not neoadjuvant CRT led to survival benefits in TNM stage II/III esophageal cancer patients. ⋯ R1, R2), lymph node metastasis (positive vs. negative), and the effect of CRT were proven to be independent prognostic factors for univariate analysis, with resectability and the effect of CRT for multivariate analysis. These data suggest that CRT in stage II/III (non-T4) ESCC patient contributed to tumor shrinkage, leading to higher resectability and longer survival. Neoadjuvant CRT appears to be a promising option for these patients.