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A yellow resin (gamboge) from Garcinia hanburyi has been widely used as folk medicine due to its antibacterial and antitumor activities. We isolated four α-glucosidase inhibitory compounds from the methanol extract of gamboge. The compounds (1-4) were identified as gambogoic acid (1), moreollic acid (2), gambogic acid (3), and 10-methoxygambogenic acid (4), respectively through spectroscopic data including 2D-NMR and HREIMS. All compounds were examined in the enzyme inhibition assay against α-glucosidase to identify their inhibitory potencies and kinetic behavior. All compounds (1-4) showed enzyme inhibition against α-glucosidase, but the activity was significantly affected by the methoxy group on C-10 of ring A and pentenyl pyran moiety of ring D. For example, compound 1 (IC50 =41.4 μM) bearing pyran ring eight times effective that 4 (IC50 =350.6 μM) having geranyl group itself. Most active compound was found out to be gambogoic acid (1) which was analyzed most abundant metabolite in gamboge by LC-ESI-MS/MS. In kinetic study, compounds 1 and 2 were proved as noncompetitive inhibitors.

Highlights • An optimal bladder volume and filling protocol is proposed. • The current hydration protocol was well-accepted and tolerated., Background and purpose Inconsistent bladder and rectal volumes have been associated with motion uncertainties during prostate radiotherapy. This study investigates the impact of these volumes to determine the optimal bladder volume. Materials and methods 60 patients from two Asian hospitals were recruited prospectively. 1887 daily cone-beam computed tomography (CBCT) images were analysed. Intra-fraction motion of the prostate was monitored real-time using a four-dimension transperineal ultrasound (4D TPUS) Clarity® system. The impact of planned bladder volume, adequacy of daily bladder filling, and rectum volume on mean intra-fraction motion of the prostate was analysed. Patients’ ability to comply with the full bladder hydration protocol and level of frustration was assessed using a questionaire. Acute side effects were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and quality of life (QoL) assessed using the International Prostate Symptom Score (IPSS). Results The mean (SD) bladder and rectum volumes achieved during daily treatment were 139.7 cm3 (82.4 cm3) and 53.3 cm3 (18 cm3) respectively. Mean (SD) percentage change from planned CT volumes in bladder volume was reduced by 8.2% (48.7%) and rectum volume was increased by 12.4% (42.2%). Linear Mixed effect model analysis revealed a reduction in intra-fraction motion in both the Sup/Inf (p = 0.008) and Ant/Post (p = 0.0001) directions when the daily bladder was filled between 82 and 113% (3rd Quartiles) of the planned CT volumes. A reduction in intra-fraction motion of the prostate in the Ant/Post direction (z-plane) (p = 0.03) was observed when the planned bladder volume was greater than 200 ml. Patients complied well with the hydration protocol with minimal frustration (mean (SD) scores of 2.1 (1.4) and 1.8 (1.2) respectively). There was a moderate positive correlation (0.496) between mean bladder volume and IPSS reported post-treatment urinary straining (p = 0.001). Conclusions A planned bladder volume >200 cm3 and daily filling between 82 and 113%, reduced intra-fraction motion of the prostate. The hydration protocol was well tolerated.

Highlights • Investigates the magnitude of intra-fraction prostate motion using real time monitoring. • A motion-time trend analysis was presented. • A duration-dependent margin was recommended. • Larger margins are required around the prostate in the inferior and posterior directions., Background and purpose During radiotherapy, prostate motion changes over time. Quantifying and accounting for this motion is essential. This study aimed to assess intra-fraction prostate motion and derive duration-dependent planning margins for two treatment techniques. Material and methods A four-dimension (4D) transperineal ultrasound Clarity® system was used to track prostate motion. We analysed 1913 fractions from 60 patients undergoing volumetric-modulated arc therapy (VMAT) to the prostate. The mean VMAT treatment duration was 3.4 min. Extended monitoring was conducted weekly to simulate motion during intensity-modulated radiation therapy (IMRT) treatment (an additional seven minutes). A motion-time trend analysis was conducted and the mean intra-fraction motion between VMAT and IMRT treatments compared. Duration-dependent margins were calculated and anisotropic margins for VMAT and IMRT treatments were derived. Results There were statistically significant differences in the mean intra-fraction motion between VMAT and the simulated IMRT duration in the inferior (0.1 mm versus 0.3 mm) and posterior (−0.2 versus −0.4 mm) directions respectively (p ≪ 0.01). An intra-fraction motion trend inferiorly and posteriorly was observed. The recommended minimum anisotropic margins are 1.7 mm/2.7 mm (superior/inferior); 0.8 mm (left/right), 1.7 mm/2.9 mm (anterior/posterior) for VMAT treatments and 2.9 mm/4.3 mm (superior/inferior), 1.5 mm (left/right), 2.8 mm/4.8 mm (anterior/posterior) for IMRT treatments. Smaller anisotropic margins were required for VMAT compared to IMRT (differences ranging from 1.2 to 1.6 mm superiorly/inferiorly, 0.7 mm laterally and 1.1–1.9 mm anteriorly/posteriorly). Conclusions VMAT treatment is preferred over IMRT as prostate motion increases with time. Larger margins should be employed in the inferior and posterior directions for both treatment durations. Duration-dependent margins should be applied in the presence of prolonged imaging and verification time.

1. 4'-(p-Toluenesulfonylamide)-4-hydroxychalcone (TSAHC) is a synthetic sulfonylamino chalcone compound possessing anti-cancer properties. The aim of this study was to elucidate the metabolism of TSAHC in human liver microsomes (HLMs) and to characterize the cytochrome P450 (P450) enzymes that are involved in the metabolism of TSAHC. 2. TSAHC was incubated with HLMs or recombinant P450 isoforms (rP450) in the presence of an nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)-regenerating system. The metabolites were identified and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). P450 isoforms, responsible for TSAHC metabolite formation, were characterized by chemical inhibition and correlation studies in HLMs and enzyme kinetic studies with a panel of rP450 isoforms. 3. Two hydroxyl metabolites, that is M1 and M2, were produced from the human liver microsomal incubations (K(m) and V(max) values were 2.46 µM and 85.1 pmol/min/mg protein for M1 and 9.98 µM and 32.1 pmol/min/mg protein for M2, respectively). The specific P450 isoforms responsible for two hydroxy-TSAHC formations were identified using a combination of chemical inhibition, correlation analysis and metabolism by expressed recombinant P450 isoforms. The known P450 enzyme activities and the rate of TSAHC metabolite formation in the 15 HLMs showed that TSAHC metabolism is correlated with CYP2C and CYP3A activity. The P450 isoform-selective inhibition study in HLMs and the incubation study of cDNA-expressed enzymes also showed that two hydroxyl metabolites M1 and M2 biotransformed from TSAHC are mainly mediated by CYP2C and CYP3A, respectively. These findings suggest that CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 isoforms are major enzymes contributing to TSAHC metabolism.