Purpose: Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carcinogenesis. We aimed to determine whether Cox-2 expression in itself can predict outcome of colorectal cancer patient after surgery. In addition, the expression of Cox-1 was also evaluated.Experimental Design: Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox-2 and Cox-1 expressions. The specimens were graded based on the intensity and extent of staining; then, the correlations between Cox-2 and Cox-1 expressions with clinicopathologic parameters and survival time were analyzed.Results: Expression of Cox-2 was positive in 70.8% of primary tumor, 92.0% of lymph node metastases, 100.0% of hepatic metastases, and was significantly associated with tumor size, depth of invasion, lymph node metastasis, vessels invasion, stage and recurrence. In contrast, Cox-1 was positive in 42.7% of primary tumor, 84.0% of lymph node metastases, 37.5% hepatic metastases, and was associated with only tumor size. Patients with Cox-2-positive tumors had a significant shorter survival time than those with negative tumors did (P ‫؍‬ 0.0006 by log-rank test); and, in a multivariate analysis, Cox-2 was an independent prognostic factor (P ‫؍‬ 0.0103; relative risk 4.114; 95% confidence interval, 1.397-12.120). Cox-1 status had no statistically effect on patient survival time.Conclusions: Elevated Cox-2 expression, but not that of Cox-1, was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients.

Purpose: Ashwagandha is regarded as a wonder shrub of India and is commonly used in Ayurvedic medicine and health tonics that claim its variety of health-promoting effects. Surprisingly, these claims are not well supported by adequate studies, and the molecular mechanisms of its action remain largely unexplored to date. We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha. Experimental Design: Selective tumor-inhibitory activity of the leaf extract (i-Extract) was identified by in vivo tumor formation assays in nude mice and by in vitro growth assays of normal and human transformed cells. To investigate the cellular targets of i-Extract, we adopted a gene silencing approach using a selected small hairpin RNA library and found that p53 is required for the killing activity of i-Extract. Results: By molecular analysis of p53 function in normal and a variety of tumor cells, we found that it is selectively activated in tumor cells, causing either their growth arrest or apoptosis. By fractionation, purification, and structural analysis of the i-Extract constituents, we have identified its p53-activating tumor-inhibiting factor as withanone. Conclusion: We provide the first molecular evidence that the leaf extract of ashwagandha selectively kills tumor cells and, thus, is a natural source for safe anticancer medicine.

The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.

The PI3K-AKT pathway is activated in a variety of human cancers, resulting in disturbance of cell growth, proliferation and survival. Among the factors affecting the pathway, the K-Ras mutation and PIK3CA mutation are the most common oncogenic alterations in colorectal cancer. We hypothesized that these two mutations are important in activation of the PI3K pathway and colorectal carcinogenesis. In this study, we aimed to examine the influence of PIK3CA mutation and K-Ras mutation on AKT activation, and to clarify whether PIK3CA mutation, K-Ras mutation and p-AKT expression may be used as parameters for predicting prognosis in colorectal cancer. Tissue samples from 158 colorectal cancer patients who underwent surgical resection were examined. The sequences of exon 1 of K-Ras and exons 9 and 20 of PIK3CA were determined by direct sequencing using genomic DNA extracted from paraffin-embedded blocks. Activation status of AKT was evaluated by immunohistochemical staining using phospho-specific AKT antibody (Ser473). Correlation between these factors and clinicopathologic findings/patient survival were examined. As a result, PIK3CA mutation was significantly associated with shorter relapse-free survival (RFS) in stage II/III patients (p 5 0.0216) and shorter disease-specific survival in all patients (p 5 0.0357). In the multivariate analysis, PIK3CA mutation was the only independent and significant prognostic factor for RFS in stage II/III patients (p 5 0.0433, HR 2.478). This study revealed the prognostic value of PIK3CA mutation in colorectal cancer patients. Patients with PIK3CA mutation should be followed up carefully. Moreover, our result suggests that inhibition of PIK3CA mutant may be a new molecular target therapy. ' 2007 Wiley-Liss, Inc.