Structure–function studies of ultrahigh molecular weight isoprenes provide key insights into their biosynthesis

Some plant trans-1,4-prenyltransferases (TPTs) produce ultrahigh molecular weight trans-1,4-polyisoprene (TPI) with a molecular weight of over 1.0 million. Although plant-derived TPI has been utilized in various industries, its biosynthesis and physiological function(s) are unclear. Here, we identified three novel Eucommia ulmoides TPT isoforms—EuTPT1, 3, and 5, which synthesized TPI in vitro without other components. Crystal structure analysis of EuTPT3 revealed a dimeric architecture with a central hydrophobic tunnel. Mutation of Cys94 and Ala95 on the central hydrophobic tunnel no longer synthesizd TPI, indicating that Cys94 and Ala95 were essential for forming the dimeric architecture of ultralong-chain TPTs and TPI biosynthesis. A spatiotemporal analysis of the physiological function of TPI in E. ulmoides suggested that it is involved in seed development and maturation. Thus, our analysis provides functional and mechanistic insights into TPI biosynthesis and uncovers biological roles of TPI in plants

Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin

The influence of duodenally-delivered Shakuyakukanzoto (Shao Yao Gan Cao Tang) on duodenal peristalsis during endoscopic retrograde cholangiopancreatography: a randomised controlled trial

Abstract Background Anti-cholinergic agents may be used to inhibit duodenal peristalsis, but they may have adverse effects. Shakuyakukanzoto ( Shao Yao Gan Cao Tang ) has an anti-spasmodic effect and has been used before for oesophagogastroduodenoscopy and colonoscopy. This randomised clinical trial aimed to evaluate the inhibitory effect of Shakuyakukanzoto on duodenal peristalsis, and its usefulness when administered into the duodenum just before endoscopic retrograde cholangiopancreatography (ERCP). Methods Participants were recruited between June 2008 and December 2010. All were aged\ua0\u226518\ua0years and provided written informed consent. Exclusion criteria were: acute pancreatitis, a history of ischemic heart disease, prostatic hypertrophy or glaucoma, and altered/postsurgical upper gastrointestinal anatomy. The recruited participants were randomly assigned to the Shakuyakukanzoto group and control group. Shakuyakukanzoto 100\ua0mg/mL solution or placebo (warm water) was administered directly as a spray into the duodenum during endoscopy. Efficacy was evaluated by observing the extent of duodenal peristalsis and assessing the difficulty of cannulating the common bile duct, the required time (RT) from administration to inhibition of duodenal peristalsis and the stop duration time (DT, the duration for which peristalsis was inhibited). Side effects were evaluated by measuring serum potassium concentration after ERCP. Results Of 28 participants, 15 were assigned to the Shakuyakukanzoto group and 13 to the control group. Duodenal peristalsis was inhibited in eight of the 10 eligible participants (80.0%) in the Shakuyakukanzoto group and none (0%) of the nine eligible participants in the control group ( P \ua0=\ua00.026). In the Shakuyakukanzoto group, mean RT (\ub1standard deviation) was 76.0\ua0\ub1\ua023.9\ua0s and DT was 11.3\ua0\ub1\ua04.2\ua0min. No adverse effects were observed in the Shakuyakukanzoto group during or after ERCP. Conclusion Duodenal peristalsis can be inhibited by spraying Shakuyakukanzoto solution directly into the duodenum. Trial registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN00001146

Evaluation of the field-in-field technique with lung blocks for breast tangential radiotherapy

Several studies have reported the advantages of the field-in-field (FIF) technique in breast radiotherapy, including dose reduction in the lungs by using lung field blocks. We evaluated the FIF technique with lung blocks for breast tangential radiotherapy. Sixteen patients underwent free breathing (FB) computed tomography (CT), followed by two CT procedures performed during breath hold after light inhalation (IN) and light exhalation (EX). Three radiotherapy plans were created using the FIF technique based on the FB-CT images: one without lung blocks (LB0) and two with lung blocks whose monitor units (MUs) were 5 (LB5) and 10 (LB10), respectively. These plans were copied to the IN-CT and EX-CT images. V20Gy, V30Gy, and V40Gy of the ipsilateral lung and V100%, V95%, and the mean dose (Dmean) to the planning target volume (PTV) were analyzed. The extent of changes in these parameters on the IN-plan and EX-plan compared with the FB-plan was evaluated. V20Gy, V30Gy, and V40Gy were significantly smaller for FB-LB5 and FB-LB10 than for FB-LB0; similar results were obtained for the IN-plan and EX-plan. V100%, V95%, and Dmean were also significant smaller for FB-LB5 and FB-LB10 than for FB-LB0. The extent of changes in V20Gy, V30Gy, and V40Gy on the IN-plan and EX-plan compared with the FB-plan was not statistically significant. Lung blocks were useful for dose reduction in the lung and a simultaneous PTV decrease. This technique should not be applied in the general population