Results Demographic and clinicopathologic characteristics of the IBET151 patient population Table 1 shows the patient distribution; their demographic, clinicopathological and molecular characteristics; and their correlation with survival. For both treatment groups, there were similar distributions of patient age, gender, ethnicity, tumor stage, tumor location, tumor size, and tumor grade, in terms of deaths due to CRC. The median follow-up period of the complete study population of 112 patients was 9.31 years (range <1 – >20 years). Survival analysis based on treatment Univariate Kaplan-Meier survival analysis demonstrated no significant differences in overall
Inhibitors,research,lifescience,medical survival rates between the surgery-alone and the 5-FU-treated patient groups (log rank, P=0.71) Inhibitors,research,lifescience,medical (data not shown). Bax (G) 8 mutation frequency and its relation to clinicopathologic features We analyzed for the presence of mutations in the (G) 8 tract of the Bax gene in
a human CRC cell line (LoVo) and in 83 CRCs. The LoVo cells displayed a bi-allelic Bax (G) 8 frame-shift mutation; this status was used as a reference in CRCs for Bax mutations (Fig 1). In our analysis, 23 of 83 (28%) CRCs demonstrated biallelic Bax (G) 8 frame-shift mutations. The majority of CRCs with mutations at the G (8) tract also had Inhibitors,research,lifescience,medical low Bax expressing (20 of 23, 87%). CRCs that displayed these mutations were significantly higher for male patients (17 of 23, 74%) and distal tumors (18 of 23, 79%). However, there was Inhibitors,research,lifescience,medical no association between the presence of Bax (G) 8 mutations with age, race/ethnicity, depth
of wall infiltration, tumor grade, tumor stage, lymph node invasion, or presence of distant metastasis (data not shown). Since the number Inhibitors,research,lifescience,medical of CRCs with Bax mutations is small, we have not further analyzed the mutational data to assess correlation between Bax mutations and patient survival in the surgery alone and surgery and 5-FU therapy patient groups separately. Figure 1 Mutational analysis at 94-base-pair region encompassing the (G) 8 tract in the Bax coding sequence in colorectal adenocarcinoma, adjacent benign epithelium and in LoVo cell line. Olopatadine The CRC and corresponding normal tissue demonstrated lack of Bax (G) 8 frame-shift … Bax immunophenotypic expression analysis Immunoreactivity for Bax was observed in the cytoplasm. In most CRCs, the Bax staining pattern was homogenous, ranging from low to high levels. In 11% of CRCs (12 cases), however, there was intratumoral heterogeneity. A low level of Bax expression was observed consistently in benign colonic epithelium, lymphocytes, and endothelial cells (Fig 2A-C). The presence of staining in intra-tumoral lymphocytes was used as an internal positive control. Of the CRCs, 54% (60 of 112) had high levels of Bax expression (22 of the 5-FU treated group and 38 of the surgery-alone group).