Mayo regimen plus three different second-line chemotherapy regimens in sequential therapy in patients with advanced colorectal cancer (ACRC).

As the number of active drugs for colorectal cancer increases, we continually revisit the question of how best to integrate them. We investigated whether sequential chemotherapy consisting of only bolus plus infusional 5-fluorouracil/folinic acid could be comparable, concerning overall survival, to sequential chemotherapy consisting of bolus 5-fluorouracil/folinic acid plus "new-generation" drugs like CPT-11 or oxaliplatin. Patients with histologically verified locally advanced disease and/or metastatic colorectal adenocarcinoma, without possibility for surgical resection, were eligible for the study. The treatments were: Cohort A--Mayo Clinic Regimen (MCR) in first line, "de Gramont" regimen in second line; Cohort B--MCR in first line, CPT-11 (350mg/m2) in second line; Cohort C--MCR in first line, oxaliplatin (85mg/m2) plus "de Gramont" regimen in second line. A total of 89 patients received first plus second line chemotherapy and all of them were analyzed for survival. Number of patients/cohort: A-32 B-27; C-30. The median survival time of the patients was 15, 11, and 17 months for the patients in cohorts A, B, and C, respectively. Survival of the patients in cohort C was significantly better than survival of the patients in cohort B (log-rank test, p=0.04). There was not a significant difference in overall survival between the cohorts A vs. C (log-rank test, p=0.52) and B vs. C (log-rank test, p=0.27). It is conceivable that infusional HD 5-FU could serve as a basis for first and second-line protocols in which other drugs are added to this regimen. Infusional 5-FU plus oxaliplatin in sequential pattern of application after bolus 5-FU has the best overall survival in comparison to other cohorts. CPT-11 applied as a single drug, was not effective enough in comparison to other treatment options.

An altered body plan is conferred on Arabidopsis plants carrying dominant alleles of two genes.

In this paper, we describe a late-flowering ecotype of Arabidopsis, Sy-0, in which the axillary meristems maintain a prolonged vegetative phase, even though the primary shoot apical meristem has already converted to reproductive development. This novel heterochronic shift in the development of axillary meristems results in the formation of aerial rosettes of leaves at the nodes of the primary shoot axis. We present evidence that the aerial-rosette phenotype arises due to the interaction between dominant alleles of two genes: ART, aerial rosette gene (on chromosome 5) and EAR, enhancer of aerial rosette (on chromosome 4): EAR has been tentatively identified as a new allele of the FRI locus. The possible role of these two genes in the conversion of shoot apical meristems to reproductive development is discussed.