Irinotecan Hydrochloride (CPT-11) in Dialysis Patients with Gastrointestinal Cancer

We investigated changes in drug disposition and toxicities with CPT-11 in 15 dialysis patients with gastrointestinal cancers to clarify whether CPT-11 could be administered safely in such patients. For comparison, the same parameters were also investigated in 10 cancer patients not undergoing dialysis. Items investigated included (1) plasma concentrations of SN-38, SN-38G and CPT-11 at 0, 1, 12, 24, 36, 48 and 72h after administration, together with a comparison of mean AUC values for 3 dose levels of CPT-11 (50, 60 and 70mg/m2) in dialysis patients and controls;and (2) occurrence of adverse events. Several findings emerged from this study:(1) No significant difference was observed in the AUC for SN-38 or CPT-11 between the dialysis and control groups;(2) The AUC for SN-38G at each dose was significantly higher in dialysis patients;and (3) Grade 1-4 leucopenia was observed in 11 of the dialysis patients. One patient developed grade 4 leucopenia and died due to sepsis. Anorexia, diarrhea, nausea, alopecia and interstitial pneumonia occurred in 6 dialysis patients. We found changes in drug dispositions of CPT-11, SN-38 and SN-38G in dialysis patients, suggesting that hepatic excretion, especially that of SN-38G, was increased. No significant difference in occurrence of adverse events was observed between the 2 groups. This indicates that CPT-11 can be administered safely in patients on dialysis.</p

Two types of antigorite serpentinite controlling heterogeneous slow-slip behaviours of slab-mantle interface

It is known that plate boundaries in subduction zones show heterogeneous slip nature with strongly coupled seismogenic zones and various types of episodic tremor and slip (ETS) zones. In order to examine the petrological controls on the large-scale structure, we compared recent geophysical observations in the Shikoku area, southwest Japan with petrological models of the hanging wall mantle wedge. As a result, we found a close relationship between mineral assemblages in the mantle wedge and the characteristics of slow slip behaviour recorded in the Shikoku area: Short-term ETSs take place in the antigorite + olivine stability field and silent long-term slow slip events (SSEs) take place in the antigorite+brucite stability field. Based on observations of natural antigorite serpentinites, we propose a model that the dominant serpentinization reaction in the mantle wedge changes with increasing depth resulting in variable extents of pore fluid pressures along slip planes. The serpentinization reaction in the antigorite+brucite stability field (olivine + H2O → antigorite + brucite) proceeds at the expense of water. This is consistent with moderately elevated pore pressures inferred for long-term SSEs. The existence of weak brucite enhances the development of shear zones oblique to the main foliation. The resultant anastomosing network provides fluid pathways that may help reduce pore pressures on slip planes. In contrast, progress of the serpentinization reaction in the antigorite + olivine stability field (olivine + H2O + SiO2 → antigorite) results in a large amount of residual water that contributes to further increase pore fluid pressures on slip planes of short-term SSEs. Our results imply that understanding of serpentinization reactions and their contributions to fluid networks in mantle wedge is important in constructing quantitative 3-D models for strain evolutions along plate boundaries. © 2014 Elsevier B.V

Percutaneous Transluminal Angioscopy During Coronary Intervention

To investigate the feasibility of angioscopic-guided percutaneous transluminal coronary angioplasty and to elucidate the mechanism of efficacy of coronary stenting for acute myocardial infarction, we performed coronary angioscopy in 102 patients with stable angina or acute myocardial infarction. Thrombi and intimal flaps were observed in most patients after coronary angioplasty. Large intimal splits were seen in one third of patients. Stents were inserted in 10 patients who were revealed to have a large flap or protruding split to the inner lumen. Thrombolytic agents were administered in 2 patients with large thrombi. Additional treatments were required in 32% of patients. No acute myocardial infarction or unstable angina occurred in patients during hospitalization. Thus, angioscopy of the coronary lumen enables clinicians to determine the most appropriate and least risky coronary intervention strategy. In patients with acute myocardial infarction, angioscopy revealed occlusive or protruding thrombi in 34 of 35 patients. The protruding thrombi disappeared after stenting. The frequency of large intimal flaps increased after predilatation with balloon, but these disappeared after stenting. The present angioscopic study demonstrates that the coronary stent compresses the occlusive or protruding thrombi and covers the ruptured thrombogenic plaque Consequently, smooth-surfaced and wide vessel lumen are obtained

An Arabidopsis SBP-domain fragment with a disrupted C-terminal zinc-binding site retains its tertiary structure

AbstractSQUAMOSA promoter-binding proteins (SBPs) form a major family of plant-specific transcription factors, mainly related to flower development. SBPs share a highly conserved DNA-binding domain of ∼80 amino acids (SBP domain), which contains two non-interleaved zinc-binding sites formed by eight conserved Cys or His residues. In the present study, an Arabidopsis SPL12 SBP-domain fragment that lacks a Cys residue involved in the C-terminal zinc-binding pocket was found to retain a folded structure, even though only a single Zn2+ ion binds to the fragment. Solution structure of this fragment determined by NMR is very similar to the previously determined structures of the full SBP domains of Arabidopsis SPL4 and SPL7. Considering the previous observations that chelating all the Zn2+ ions of SBPs resulted in the complete unfolding of the structure and that a mutation of the Cys residue equivalent to that described above impaired the DNA-binding activity, we propose that the Zn2+ ion at the N-terminal site is necessary to maintain the overall tertiary structure, while the Zn2+ ion at the C-terminal site is necessary for the DNA binding, mainly by guiding the basic C-terminal loop to correctly fit into the DNA groove

Complete Response Using Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma with Multiple Lymph Node and Bone Metastases: A Case Report

Hepatocellular carcinoma（HCC）is the sixth most commonly diagnosed cancer worldwide. Sorafenib is an oral multikinase inhibitor used in the palliative treatment of advanced HCC. However, there were no reported cases of complete response（CR）from two previous large phaseⅢ clinical trials. Here, we report a case of CR in a patient with advanced HCC with multiple lymph node and bone metastases, treated with sorafenib monotherapy for 8 months. To our knowledge, this is the first evidence showing CR following sorafenib monotherapy for HCC with bone metastasis