[Benefit of a pretreatment planning library-based adaptive radiotherapy for cervix carcinoma?]. / Bénéfice de la radiothérapie adaptative par bibliothèque de plans de traitement pour les cancers du col utérin ?

PURPOSE: In case of intensity-modulated radiotherapy (IMRT) for locally advanced cervix carcinoma, the objectives were to quantify the difference between the planned and the delivered doses by a standard irradiation, and to estimate the dosimetric benefit of a pretreatment planning library-based adaptive radiotherapy. MATERIAL AND METHODS: Ten patients with locally advanced cervix carcinoma had three planning CTs corresponding to three bladder volumes: empty, intermediate (vi) and full. On each CT, two IMRT plans were generated to deliver 45 Gy to the planning target volume (PTV), with two different margins: clinical target volume (CTV)+10mm and CTV+15 mm. Using bi-weekly CBCTs, three scenarios of treatment have been simulated and compared: standard IMRT (one vi planning) with 10 and 15 mm margins and adaptive radiotherapy with 10mm margin. The cumulated dose in the organs at risk was estimated by elastic registration. RESULT: In case of standard IMRT, the cumulated dose was significantly different than the planning dose, with an under-dose of the CTV and the bladder, and an over-dose of the rectum and the peritoneal cavity. For 54% of the fractions, the adaptive radiotherapy planning was not based on vi. Considering the cumulated dose and compared to IMRT with 10-mm margin, adaptive radiotherapy increased the dose to the CTV (1.4 Gy for D98%) and decreased slightly the dose to the rectum and the peritoneal cavity. Compared to a standard IMRT with 15 mm margin, adaptive radiotherapy decreased significantly the dose to the rectum (20% for V40), the bladder (13% for V40) and the peritoneal cavity (2% for V35). CONCLUSION: A pretreatment planning library-based adaptive radiotherapy in cervix carcinoma decreases the dose to the organs at risk and increases the dose to the CTV.

Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: effects of 5-HT and RS67333 on isoforms A and B.

Serotonin 4 receptors (5-HT4Rs) are particularly abundant within the limbic system, where they constitute potential targets for the development of novel, rapid acting antidepressants. However, the population of limbic 5-HT4Rs is not homogenous, comprising various isoforms of which 5-HT4(a) and 5-HT4(b) are among the most abundant variants. Sequence divergence at their C-termini is predictive of specificity in isoform signalling and regulation, but the differences, if any, remain ill-defined. The present study compared isoforms 5-HT4(a) and 5-HT4(b) in their ability to undergo endocytic regulation following exposure to 5-HT and to the putatively fast acting antidepressant RS67333. Both ligands differed in their ability to induce internalization of either isoform, 5-HT being more effective than RS67333 in HEK293 cells and in neurons. In contrast, trafficking induced by 5-HT was isoform-specific. In particular, while PKC, GRK2 and betaarrestin were necessary for 5-HT4(a)R internalization, sequestration of 5-HT4(b)Rs required PKC but not GRK2 and relied significantly less on betaarrestin. After endocytosis, isoform (b) appeared scattered throughout the intracellular compartment and efficiently recycled to the membrane upon agonist removal. Isoform (a) accumulated in the perinuclear compartment and displayed little recycling. Isoform-specific subcellular distribution was present in HEK293 cells and in neurons. In neurons, where internalization by RS67333 was more pronounced than in HEK293 cells, receptors internalized by this ligand followed the same distribution pattern as observed with 5-HT. These results point to isoform-related differences in the way that 5-HTRs respond to different ligands. Such diversity should be taken into account when developing therapeutic agents that target 5-HT4Rs.

Sesquiterpene hydrocarbons with trifarane backbone in the liverwort Trocholejeunea sandvicensis.

The hydrocarbon fraction of the liverwort Trocholejeunea sandvicensis was investigated. Four new sesquiterpene hydrocarbons including the trifaranes (-)-trifara-9,14-diene (6) and (-)-3,7-di-epi-3,7-trifara-9,14-diene (7), as well as (+)-sandvicene (8), a sesquiterpene with uncommon skeleton, and the rearranged trifarane sesquiterpene (+)-neotrifaradiene (9) were isolated and their structure elucidated. A biogenetic pathway for the four compounds is proposed, with nerolidol as their common precursor.

Actinidic acid, a new triterpene phytoalexin from unripe kiwi fruit.

Seven phytoalexins (1-7), including a new compound, were isolated from the peel of unripe kiwi fruit (Actinidia deliciosa cv. Golden King) that had been wounded and inoculated with Colletotrichum musae. The new phytoalexin (1) was identified as 2alpha,3beta,23-trihydroxy-12,20(30)-ursadien-28-oic acid, and named actinidic acid. Phytoalexins 2-6 are known triterpenes but have not previously been described as phytoalexins. Phytoalexin 7 is the same triterpene as the phytoalexin of nectarine fruit.

Triterpene phytoalexins from strawberry fruit.

Strawberry cv. Houkouwase is resistant to infection by Colletotrichum fragariae. The formation of antifungal compounds was observed in unripe fruit which had been wounded and inoculated with conidia of C. musae. Three antifungal compounds were isolated and identified as euscaphic acid, tormentic acid and myrianthic acid. Myrianthic acid inhibited the growth of C. musae at 3 microg, and euscaphic and tormentic acids showed inhibitory effects at 100 microg. A quantitative analysis of their contents showed that the triterpenes increased in wounded fruit, and in wounded and inoculated fruit, but not in non-treated fruit. These findings indicate that unripe fruit of Houkouwase produced the triterpenes as phytoalexins. The triterpene phytoalexins seem to be involved in the resistance of strawberry to the fungus.

Microbial transformation of dehydropinguisenol by Aspergillus sp.

Two metabolites were obtained by microbial transformation of a furanosesquiterpene alcohol, dehydropinguisenol, using Aspergillus niger and Aspergillus cellulosae. Their structures were established as 10-oxo-lejeuneapinguisenol and lejeuneapinguisenol on the basis of their spectroscopic data. The latter compound was obtained after 4 and 9 days of incubation with A. cellulosae at 30 degrees C and 25 degrees C, respectively. Aspergillus niger produced both metabolites after 3 and 5 days incubation at 30 degrees C, respectively. A possible pathway for the formation of these compounds is discussed here together with their antimicrobial activity against A. niger and A. cellulosae.

Highly oxygenated sesquiterpenes from the liverwort Trocholejeunea sandvicensis.

Four pinguisane type sesquiterpenes were isolated from the liverwort Trocholejeunea scandvicensis, together with three aromatic compounds. The structures of the cited compounds were established on the basis of spectroscopic means. The first two compounds were new sesquiterpenes, while the other compounds were previously isolated from other liverworts and lichen sp., respectively. The stereochemistry for lejeuneapinguisanolide was determined by X-ray analysis, a possible biosynthetic pathway to it was postulated. The other new sesquiterpene is lejeuneapinguisenone.

Danielone, a phytoalexin from papaya fruit.

A new phytoalexin was induced and isolated from papaya fruit slices treated with copper salts; its structure was established as 3',5'-dimethoxy-4'-hydroxy-(2-hydroxy)acetophenone. This compound showed high antifungal activity against Colletotrichum gloesporioides, a pathogenic fungus of papaya.