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Purpose The aim of this study was to compare early prostate-specific antigen (PSA) decline patterns and PSA nadirs between low-dose-rate seed prostate brachytherapy (LDR-PB) and different fractionations of external beam radiotherapy (EBRT) and their predictive importance for biochemical failure (bF). Methods and Materials Patients with D'Amico low- or intermediate-risk prostate cancer who underwent a single-modality treatment without androgen deprivation were included in this study. Three different treatment groups were compared: (1) normofractionation EBRT up to 70.2–79.2 Gy/1.8–2.0 Gy, (2) LDR-PB, and (3) EBRT with hypofractionation 60 Gy/3 Gy daily or 5–7.25 Gy once a week over 9–5 weeks, to a total dose of 45–36.25 Gy, respectively. The log-rank test, Cox regression analysis, and nonparametric tests were used. Results We analyzed 892 patients: the median followup for patients without bF was 84 months (interquartile range 60–102 months), with 12% of patients experiencing bF. The PSA decline within the first 15 months was generally exponential. LDR-PB showed a faster early exponential decline compared with EBRT treatments, but whether decline was fast or slow had no influence on recurrence. The only factors that were positive predictive factors in univariate and multivariate analyses were the time to nadir >48 months (median), PSA nadir Conclusions Although there are significant differences in early exponential PSA decline between different treatments, only the PSA nadir and longer time to nadir were predictive factors for bF.

In the course of a primary screening of 614 microbial actinomycete extracts for the discovery of tyrosinase inhibitors, the EtOAc extract of the fermentation broth of the strain Streptomyces sp. CA-129531 isolated from a Martinique sample, exhibited in cell free and cell-based assays the most promising activity (IC50 value of 63 μg/mL). Scaled-up production in a bioreactor led to the isolation of one new trichostatic acid analogue, namely trichostatic acid B (1), along with six known trichostatin derivatives (2–7), four diketopiperazines (8–11), two butyrolactones (12–13) and one hydroxamic acid siderophore (14). Among them, trichostatin A (4) showed a Ki value of 6.1 μM and six times stronger anti-tyrosinase activity (IC50 2.18 μΜ) than kojic acid (IC50 14.07 μΜ) used as a positive control. Deoxytrichostatin A (6) displayed also strong inhibitory activity against tyrosinase (IC50 19.18 μΜ). Trichostatin A production in bioreactor started together with the exponential phase of growth (day 4) and the maximum concentration was reached at day 9 (2.67 ± 0.13 μg/mL). Despite the cytotoxicity of some individual components, the EtOAc extract showed no cytotoxic effect on HepG2, A2058, A549, MCF-7 and MIA PaCa-2 cell lines, (IC50 >2.84 mg/mL) and against BG fibroblasts at the concentrations where the whitening effect was exerted, reassuring its safety and great tyrosinase inhibitory potential.

Purpose Because of the low alpha/beta value of prostate cancer, a therapeutic gain may be possible with a hypofractionated radiation scheme, and this gain may be further increased with the adjunct of hormone therapy. A Phase II study was undertaken to study the toxicity of such a treatment. Methods and Materials Forty-two patients with intermediate-risk prostate cancer were recruited for this study. Neoadjuvant and concomitant hormone therapy consisted of one injection of leuprolide acetate (4-month preparation) and 1 month of oral nonsteroidal, anti-androgen medication starting on the day of the injection. Radiation treatment was started 8 weeks after the injection and patients received 57 Gy in 19 fractions. Results Median follow-up was 46 months. The treatment was well tolerated and no interruptions occurred. The majority (59%) had Grade 0 or 1 acute genitourinary (GU) toxicity, whereas 36% had Grade 2 and 5% had Grade 3 acute GU toxicity. Only Grade 1 or 2 gastrointestinal toxicity was seen. All chronic toxicity was of Grade 1 or 2 except for 3 patients (8%) with Grade 3 toxicity. Sixty-eight percent (68%) of patients had no long-term side effects from the treatment. At time of analysis, 79% showed no sign of treatment failure. Conclusions Hypofractionated radiation with neoadjuvant and concomitant hormone therapy is well tolerated with no significant short- or long-term morbidity. Control for this risk group is good, and comparative Phase III studies should be undertaken to determine whether this treatment is superior to new evolving treatments.

Acute intracerebroventricular (i.c.v.) administration of bombesin (BN) reduces meal intake in fasted rats. The overall objective of the present study was to determine the behavioral and other ingestive effects of prolonged central administration of BN. In the first experiment, we characterized the effects of 8-day sustained central administration of BN (0, 0.01, 0.05, 0.1 and 5 micrograms/0.5 microliter/h) or its antagonist (BIM-26226; 0, 0.005, 0.05, 0.5 and 5.0 micrograms/0.5 microliter/h), in free feeding rats. Each dose was delivered over 48 h, in an ascending sequence. At the higher doses, the BN-exposed rats consumed significantly less food whereas those exposed to the BN antagonist ingested significantly more food than the controls (saline exposed), during the dark phase. Due to the limited 48-h exposure to these higher doses, we further investigated the effects of more sustained BN exposure. Thus BN was infused over a 7-day period, at a rate of 0.25 microgram BN/0.5 microliter/h. In this latter study, we determined the effects of sustained BN exposure on a) daily spontaneous ingestive pattern, b) the rat's ingestive and other behavioral responses to a subsequent acute BN (i.c.v.) challenge and, c) BN receptor binding profile in various brain regions. Over the initial 2 days of chronic infusion, BN significantly suppressed spontaneous ingestion, and this effect dissipated by 72 h. Upon acute challenge with bolus injection of BN (0.25 microgram; i.c.v.), both chronically BN-treated and control rats responded by decreased feeding and enhanced grooming behaviors. In terms of effects at the receptor level, chronic BN exposure resulted in significant down-regulation (reduced BN/GRP receptor density) at the PVN and the hippocampal dentate gyrus. These findings represent the first demonstration of concomitant behavioral and receptor based changes consequent to sustained exposure to BN. These data suggest that tolerance to feeding suppressant effects of BN develops gradually, which in part may be mediated by down-regulation of BN/GRP receptors at specific brain loci. Our results also suggest that despite the development of tolerance to the chronic or sustained effects of BN exposure, animals still respond robustly to acute fluctuations in peptide levels.

Introduction Les myelites dites « atypiques » de sclerose en plaques (SEP), c.-a-d. etendues ou pseudovasculaires, sont des entites rares pouvant orienter vers d’autres pathologies. Objectifs L’objectif de cette etude est de colliger des cas de myelites aigues atypiques de SEP et de mieux caracteriser cette population. Patients et methodes Cette etude est observationnelle, retrospective, multicentrique, et inclut les cas incidents vus entre 2012 et 2015. Neuf patients ont ete inclus a Strasbourg, Nice et Montpellier. Nous avons recueilli les caracteristiques demographiques, cliniques et radiologiques de la myelite, les resultats biologiques de la ponction lombaire, l’atteinte cerebrale, les therapeutiques instaurees et le suivi clinique. Resultats L’âge moyen est de 42 ans, le sex-ratio femme/homme est de 3:1. Il s’agit de la premiere poussee pour 8 des 9 patients et tous ont une synthese intrathecale d’immunoglobuline. Radiologiquement, on retrouve 6 myelites transverses, et 7 myelites etendues longitudinalement. L’EDSS median est a 4,5 [1–8] pendant la poussee, a 3 [0–6,5] a 6 mois et a 3,5 [0–7] apres un suivi moyen de 4 ± 10 ans. Trois patients ont presente une deuxieme poussee uniquement sous forme de myelite. Discussion Le faible effectif de notre cohorte est lie a la rarete de cette manifestation clinique dans la SEP. Les myelites etendues constituent l’essentiel de notre cohorte. Il semble ressortir une predominance feminine, un âge de debut plus eleve que dans les poussees typiques de SEP, et une recuperation meilleure que dans la NMO ou les maladies de systeme. Conclusion Les myelites atypiques sont peu frequentes dans la SEP et semblent etre une entite a part ayant un tropisme medullaire a la fois lors de la premiere poussee et lors des recurrences.