ABSTRACT
The RIN1 gene, located on chromosome 11q13.2, is a molecule consisting of a coding region of 2352 bp, has a domain on the 3' side that binds to H-Ras protein, and is presumed to be an important molecule in an intracellular signaling pathway. Since the RIN1 molecule belonging to the effector molecules of H-Ras has not been reported in colorectal or other digestive tract cancers to date, we investigated how the RIN1 gene was involved in colorectal cancer. Fifty-two (51.5%) of 101 colorectal cancer specimens strongly expressed the RIN1 gene compared to the adjacent normal colorectal tissue. The 5-year survival rate of patients positive for the expression of the RIN1 gene was significantly poorer at 55% than that (83%) of patients negative for the expression of the RIN1 gene. Also, we confirmed that RIN1 protein was localized chiefly in the cytoplasm of colorectal cancer cell lines, and bound to 14-3-3 protein, but not to Ras protein. These results indicate that the RIN1 gene serves as an important signal transduction system for evaluating the malignancy of colorectal cancer.
Subject(s)
Colorectal Neoplasms/genetics , Intracellular Signaling Peptides and Proteins/genetics , 14-3-3 Proteins/metabolism , Cell Line, Tumor , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Gene Expression , HT29 Cells , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Neoplasm Staging , Protein BindingABSTRACT
Sixteen patients with highly-advanced gastric cancer were administered low-dose TS-1 and CDDP as a first-line treatment, followed by either paclitaxel or CPT-11/CDDP as a second-line treatment. The results of the 2 second-line treatments are reported herein. Overall response rate for the first-line treatment was 55.6%. For the second-line treatments, responses were noted in both the paclitaxel group and the CPT-11/CDDP group. Overall MST was 16.3 months and 1-year survival was 60%. The paclitaxel group, however, showed significantly better prognoses than the CPT-11/CDDP group. Adverse reactions to the first-line treatment were grade 3 leukopenia in 1 patient, with no other reactions over grade 2 observed. No adverse reaction greater than grade 2 was noted during administration of the second-line treatments. These results appear to present ample data that a first-line treatment of low-dose TS-1/CDDP followed by a second-line treatment of paclitaxel at 1/week in the outpatient setting yields improved prognoses and minimal adverse reactions.