Longer time to testosterone recovery impacts favorably on outcomes for prostate cancer following androgen deprivation and radiotherapy.

Purpose: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS).

Methods: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT.

Does postoperative irradiation improve survival in early-stage endometrial cancer?

Endometrial cancer is the most common gynecological cancer in developed countries. Postoperative irradiation has been shown to lower locoregional relapses among high-intermediate risk endometrial cancer patients. In addition, vaginal cuff brachytherapy has demonstrated similar control to external beam radiotherapy but with lower toxicity.

Vaginal cuff brachytherapy in endometrial cancer - a technically easy treatment?

Endometrial cancer (EC) is one of the most common gynecological cancers among women in the developed countries. Vaginal cuff is the main location of relapses after a curative surgical procedure and postoperative radiation therapy have proven to diminish it. Nevertheless, these results have not translated into better survival results.

The usefulness of fleet rectal enemas on high-dose-rate intracavitary cervical cancer brachytherapy. A prospective trial.

Purpose: To evaluate the effects of rectal enemas on rectal doses during radical high-dose-rate (HDR) intracavitary cervical brachytherapy (BT).

Material And Methods: Twenty patients suffering from cervical cancer and treated with external beam radiotherapy and HDR-BT were included in a prospective trial. The first brachytherapy fraction was considered the basal status, and patients were instructed to self-administer two rectal cleansing enemas before the second fraction.

Comparison of New Tau PET-Tracer Candidates With [18F]T808 and [18F]T807.

Early clinical results of two tau tracers, [(18)F]T808 and [(18)F]T807, have recently been reported. In the present study, the biodistribution, radiometabolite quantification, and competition-binding studies were performed in order to acquire comparative preclinical data as well as to establish the value of T808 and T807 as benchmark compounds for assessment of binding affinities of eight new/other tau tracers. Biodistribution studies in mice showed high brain uptake and fast washout.

Analysing the integration of MR images acquired in a non-radiotherapy treatment position into the radiotherapy workflow using deformable and rigid registration.

Aim: Our aim was to analyse the feasibility of integrating an MRI acquired in a non-radiotherapy set-up into the prostate cancer radiotherapy workflow.

Material And Methods: The MRIs of 15 prostate cancer patients, acquired with a flat table-top (MRI-flat), and with a curved tabletop (MRI-curve) were analysed. MRIs were rigidly (RIR) and non-rigidly registered (DIR) with CT images.

Effect of rectal enemas on rectal dosimetric parameters during high-dose-rate vaginal cuff brachytherapy: A prospective trial.

Purpose: To evaluate the effects of rectal enemas on rectal doses during postoperative high-dose-rate (HDR) vaginal cuff brachytherapy (VCB).

Patients And Methods: This prospective trial included 59 patients. Two rectal cleansing enemas were self-administered before the second fraction, and fraction 1 was considered the basal status.

Rectal contrast increases rectal dose during vaginal cuff brachytherapy.

Purpose: To evaluate the impact of rectal dose on rectal contrast use during vaginal cuff brachytherapy (VCB).

Methods And Materials: A retrospective review of gynecology patients who received some brachytherapy fractions with and without rectal contrast was carried out. Rectal contrast was instilled at the clinician's discretion to increase rectal visibility.

Dosimetric analysis of rectal filling on rectal doses during vaginal cuff brachytherapy.

Purpose: Several studies have analyzed the effect of bladder filling during vaginal cuff brachytherapy (VCB), but the effect of rectum filling has not been studied. We sought to evaluate the effects of rectal volume on rectal doses during postoperative VCB.

Methods And Materials: Brachytherapy planning CT scans (334 sets) obtained from 92 consecutive patients treated with VCB were resegmented (bladder and rectum) and replanned retrospectively using the same parameters to homogenize data and improve analysis.

Body Mass Index and Doses at Organs at Risk in a Mediterranean Population Treated with Postoperative Vaginal Cuff Brachytherapy.

Purpose: Association between body mass index (BMI) and doses in organs at risk during postoperative vaginal cuff brachytherapy (VCB) treatment has not been evaluated. The aim of this study was to analyse the impact of BMI on the dose delivered to bladder and rectum during high-dose-rate VCB using computed tomography (CT) scans at every fraction.

Materials And Methods: A retrospective analysis of 220 planning CT sets derived from 59 patients was conducted.

Anti-Parkinson effects of a selective alpha2C-adrenoceptor antagonist in the MPTP marmoset model.

Current dopamine replacement therapies, in Parkinson's disease (PD), result in aversive side effects and rapid drug dose escalation over time. Therefore, a non-dopaminergic treatment would be an advantageous supplement to lower the dose of dopamine replacement treatment postponing the occurrence of side effects. The noradrenergic system plays an important role in the facilitation or maintenance of the activity of the nigrostriatal dopamine pathways.

Dose accumulation during vaginal cuff brachytherapy based on rigid/deformable registration vs. single plan addition.

Purpose: To compare dose summation using a single plan (SP) approach for vaginal cuff brachytherapy (VBT) against dose summation after a rigid or deformable registration for each VBT fraction, in women with early stage endometrial cancer receiving postoperative VBT.

Methods And Materials: A retrospective analysis of 19 patients who received VBT as the sole adjuvant treatment was undertaken. For the purposes of the study, every VBT fraction was re-segmented and re-planned under the same conditions.

Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism.

In previous articles we have described the discovery of a new series of tricyclic isoxazolines combining central serotonin (5-HT) reuptake inhibition with alpha(2)-adrenoceptor antagonistic activity. We report now on the synthesis, the in vitro binding potency and the primary in vivo activity of six enantiomers within this series, one of which was selected for further pharmacological evaluation and assigned as R226161. Some additional in vivo studies in rats are described with this compound, which proved to be centrally and orally active as a combined 5-HT reuptake inhibitor and alpha(2)-adrenoceptor antagonist.

Synthesis of 7-amino-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazole derivatives displaying combined alpha2-adrenoceptor antagonistic and 5-HT reuptake inhibiting activities.

Following a program searching for dual 5-HT reuptake inhibitors and alpha(2)-adrenoceptor antagonists started at Johnson & Johnson Pharmaceutical Research & Development, we now report on the synthesis of a series of 7-amino-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazole derivatives, some of which proved to be the most potent alpha(2)-adrenoceptor blockers within this chemical class of tricyclic isoxazolines, while keeping potent 5-HT reuptake inhibiting activity.

Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking activity.

The synthesis and pharmacology of a new series of 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles that combine central serotonin (5-HT) reuptake inhibition with alpha(2)-adrenoceptor blocking activity is described as potential antidepressants. Four compounds were selected for further evaluation, and the combination of both activities was found to be stereoselective, residing mainly in one enantiomer. Reversal of the loss of righting induced by the alpha(2)-agonist medetomidine in rats confirmed the alpha(2)-adrenoceptor blocking activity in vivo and also demonstrated CNS penetration.

Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha2-adrenoceptor antagonistic activities. Part 2: Further exploration on the cinnamyl moiety.

In our previous paper we have described the synthesis of a series of 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, as novel dual 5-HT reuptake inhibitors and alpha2-adrenoceptor antagonists. That investigation led to the identification of the cinnamyl fragment as the most suitable moiety for combined activity. This paper outlines a further optimisation programme, focused on the exploration of the aromatic ring present on the cinnamyl moiety of compounds 1, 2 and 3.

Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha(2)-adrenoceptor antagonistic activities: a novel series of potential antidepressants.

The synthesis of a series of novel 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles as novel dual 5-HT reuptake inhibitors and alpha(2)-adrenoceptor antagonists is described. Their affinity at the three different human alpha(2)-adrenoceptor subtypes and the 5-HT transporter site is reported. The in vivo activity of the compounds was measured in two different assays: (1).

2-(Dimethylaminomethyl)-tetrahydroisoxazolopyridobenzazepine derivatives. Synthesis of a new 5-HT(2C) antagonist with potential anxiolytic properties.

Following the program started at Johnson & Johnson Pharmaceutical Research & Development searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of 2-(dimethylaminomethyl)-2,3,3a,8-tetrahydroisoxazolo[3,2-a]pyrido[3,4-c]-[2]benzazepine and 2-(dimethylaminomethyl)-2,3,3a,8-tetrahydroisoxazolo[3,2-a]pyrido[3,2-c]-[2]benzazepine. A new method for the synthesis of pyridobenzazepines is described as well. The affinities for several receptors as well as the mCPP antagonistic activity of the compounds synthesised are described.

Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives: novel series of PDE4 inhibitors.

This communication describes the synthesis and in vitro PDE4 inhibitory activity of a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The compounds described were also tested in in vivo models to evaluate their anti-inflammatory activity after topical administration as well as their gastro-intestinal side effects. Several compounds proved to be potent PDE4 inhibitors and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side effects than reference compounds but maintained anti-inflammatory activity after topical administration.

Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT(2A/2C) receptor antagonists. Part 2.

Following the programme started at Janssen Research Foundation searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of a series of substituted 2-(Dimethylaminomethyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives. The 5-HT(2A), 5-HT(2C) and H(1) receptor affinities as well as the mCPP antagonistic activity of the compounds synthesised is described.

Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT(2A/2C) receptor antagonists. Part 1.

The synthesis of a series of novel 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives as well as their 5-HT(2A/2C) and H(1) receptor binding affinities are described. The in vivo activity as potential anxiolytics of the synthesised compounds was measured in a mCPP challenge test. One of the compounds, 2a, proved to be a potent 5-HT(2A/2C) receptor antagonist showing as well oral activity and therefore could be considered as a potential anxiolytic/antidepressant agent.