Mitomycin-C, 5-fluorouracil, and leucovorin as a salvage therapy in patients with metastatic colorectal adenocarcinoma.

AIM: There is no further treatment option for metastatic colon patients who are refractory to standard chemotherapy and to whom novel biological agents are not available. We evaluated the outcomes of mitomycin-C, 5-fluorouracil (5-FU) and leucovorin in patients with metastatic colon cancer previously treated with oxaliplatin/5-FU/leucovorin and irinotecan/5-FU/leucovorin. METHODS: We retrospectively analyzed 46 patients who had received mitomycin-C/5FU/leucovorin between March 2008 and December 2009. All patients had failed prior first-line and second-line therapy containing oxaliplatin, irinotecan, and 5-FU. RESULTS: The median age of the patients was 57.0 years (range, 34.0-76.0) and their median Eastern Cooperative Oncology Group performance status was 1 (0-2). A complete or partial response was not observed in any patient and stable disease was observed in 19 patients (41.3%). The median duration of follow up was 29 weeks (range 8-87 weeks). Median progression-free survival was 10 weeks (95% CI 8-12) and median overall survival was 38 weeks (95% CI 32-44). Grade 3 and 4 hematological toxicities included neutropenia in five patients (10.8%) and thrombocytopenia in four patients (8.8%). Grade 3 or 4 non-hematologic toxicities included nausea and vomiting in two patients. There were no treatment-related deaths. CONCLUSION: The combination regimen of mitomycin-C/5-FU/leucovorin showed marginal activity and tolerable toxicity profiles in heavily pretreated metastatic colorectal cancer patients.

Development of a cause analysis system for a CPCS trip by using the rule-base deduction method.

A Core Protection Calculator System (CPCS) was developed to initiate a Reactor Trip under the circumstance of certain transients by a Combustion Engineering Company. The major function of the Core Protection Calculator System is to generate contact outputs for the Departure from Nucleate Boiling Ratio (DNBR) Trip and a Local Power Density (LPD) Trip. But in a Core Protection Calculator System, a trip cause cannot be identified, thus only trip signals are transferred to the Plant Protection System (PPS) and only the trip status is displayed. It could take a considerable amount of time and effort for a plant operator to analyze the trip causes of a Core Protection Calculator System. So, a Cause Analysis System for a Core Protection Calculator System (CASCPCS) has been developed by using the rule-base deduction method to assist operators in a Nuclear Power Plant. CASCPCS consists of three major parts. Inference engine has a role of controlling the searching knowledge base, executing the rules and tracking the inference process by using the depth-first searching method. Knowledge base consists of four major parts: rules, data base constants, trip buffer variables and causes. And a user interface is implemented by using menu-driven and window display techniques. The advantage of CASCPCS is that it saves time and effort to diagnose the trip causes of a Core Protection Calculator System, it increases a plant's availability and reliability, and it makes it easy to manage CASCPCS because of using only a cursor control.

Characterization of mutator pathway in younger-age-onset colorectal adenocarcinomas.

The high-frequency microsatellite instability (MSI-H) phenotype, frequently identified in hereditary nonpolyposis colorectal cancer (HNPCC), also accounts for approximately 15% of sporadic colorectal cancers. Microsatellite instability (MSI) occurs from the mutational inactivation of the DNA mismatch repair genes, i.e. hMSH2 and hMLH1 in HNPCC, as well as from epigenetic inactivation of hMLH1 in sporadic colorectal tumors. The mutator pathway including microsatellite instability, hMLH1 promoter methylation, and hMSH2 and hMLH1 mutation patterns were identified in 21 sporadic colorectal adenocarcinoma patients younger than 30 yr excluding HNPCC. More than half of tumors showed MSI, with five MSI-H and six MSI-L (low-frequency microsatellite instability). Three of six MSI-H tumors showed the hMLH1 promoter methylation and did not express the hMLH1 protein. On the other hand, all MSI-L and all MSS (microsatellite stable) tumors expressed both hMSH2 and hMLH1 proteins. Two novel mutations, i.e. a missense mutation in hMLH1 and a splice-site alteration in hMSH2, were identified in two patients respectively. Although mutator pathway was implicated in younger-age-onset colorectal carcinogenesis, many tumors appeared to evolve from different genetic events other than hMSH2 and hMLH1 mutations frequently identified in HNPCC.