The consensus molecular subtypes (CMS) classification is one of the most robust colorectal cancer (CRC) classifications based on comprehensive gene expression profiles. This study aimed to clarify whether the CMS is a predictive factor for therapeutic effects of standard chemotherapies for metastatic CRC (mCRC). We retrospectively enrolled 193 patients with mCRCs, and using comprehensive gene expression data, classified them into 4 subtypes: CMS1–CMS4. The associations between the subtypes and treatment outcomes were analyzed. Regarding first-line chemotherapy, irinotecan (IRI)-based chemotherapy was significantly superior to oxaliplatin (OX)-based chemotherapy for progression-free survival (PFS; hazard ratio [HR] = 0.31, 95% confidence interval [CI] 0.13–0.64) and overall survival (OS; HR = 0.45, 95% CI 0.19–0.99) in CMS4. Regarding the anti-epidermal growth factor receptor (anti-EGFR) therapy, CMS1 showed particularly worse PFS (HR = 2.50, 95% CI 1.31–4.39) and OS (HR = 4.23, 95% CI 1.83–9.04), and CMS2 showed particularly good PFS (HR = 0.67, 95% CI 0.44–1.01) and OS (HR = 0.49, 95% CI 0.27–0.87) compared with the other subtypes. The biological characteristics of CMS may influence the efficacy of chemotherapy. CMS might be a new predictive factor for the efficacy of chemotherapy against mCRCs.

Deviations from the universal genetic code have been reported for several microorganisms. Termination codons are used for coding some amino acids in Paramecium, Mycoplasma or Tetrahymena, and in Escherichia coli, the UGA termination codon is used to code for selenocysteine. In mitochondria, the changes of sense codons to termination codons or to codons encoding other amino acids have also been reported. Here we report another example of divergence from the universal code, this time in a non-spore-forming yeast Candida cylindracea, in which the universal codon for leucine, CUG, is used to code for serine. This conclusion is based on the observations that: (1) the amino-acid composition and the partial amino-acid sequences of an extracellular lipase from this yeast agreed with those deduced from the complementary DNA if CUG was assumed to specify serine; and (2) serine, but not leucine, was incorporated into a polypeptide in a cell-free translation system from this yeast in the presence of a synthetic CUG oligomer.

Background:Gastrointestinal stromal tumours (GISTs) with high-risk features have poor prognosis even if adjuvant treatment is given. Neoadjuvant imatinib may increase the cure rate by shrinking large GISTs and preserve organ function.Methods:We conducted an Asian multinational phase II study for patients with gastric GISTs ≥10 cm. Patients received neoadjuvant imatinib (400 mg/day) for 6–9 months. The primary end point was R0 resection rate.Results:A total of 56 patients were enroled in this study. In the full analysis set of 53 patients, neoadjuvant imatinib for ≥6 months was completed in 46 patients. Grade 3–4 neutropenia and rash occurred in 8% and 9%, respectively, but there were no treatment-related deaths. The response rate by RECIST was 62% (95% CI, 48–75%). The R0 resection rate was 91% (48/53) (95% CI, 79–97%). Preservation of at least half of the stomach was achieved in 42 of 48 patients with R0 resection. At the median follow-up time of 32 months, 2-year overall and progression-free survival rates were 98% and 89%, respectively.Conclusions:Neoadjuvant imatinib treatment for 6–9 months is a promising treatment for large gastric GISTs, allowing a high R0 resection rate with acceptable toxicity.

1 Anisatin, a toxic, insecticidally active component of Sikimi plant, is known to act on the GABA system. In order to elucidate the mechanism of anisatin interaction with the GABA system, wholecell and single-channel patch clamp experiments were performed with rat dorsal root ganglion neurons in primary culture. 2 Repeated co-applications of GABA and anisatin suppressed GABA-induced whole-cell currents with an EC 50 of 1.10 mM. No recovery of currents was observed after washout with anisatin-free solution.3 However, pre-application of anisatin through the bath had no eect on GABA-induced currents. The decay phase of currents was accelerated by anisatin. These results indicate that anisatin suppression of GABA-induced currents requires opening of the channels and is use-dependent. 4 Anisatin suppression of GABA-induced currents was not voltage dependent. 5 Picrotoxinin attenuated anisatin suppression of GABA-induced currents. [ 3 H]-EBOB binding to rat brain membranes was competitively inhibited by anisatin. These data indicated that anisatin bound to the picrotoxinin site. 6 At the single-channel level, anisatin did not alter the open time but prolonged the closed time. The burst duration was reduced and channel openings per burst were decreased indicating that anisatin decreased the probability of openings.

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