Antiandrogen monotherapy: Recommendations for the treatment of prostate cancer

Objective: The concept of antiandrogens as monotherapy for the treatment of prostate cancer is discussed. Methods: Both Medline and Current Contents were used to identify studies on antiandrogen monotherapy in prostate cancer. We tried to analyze this database critically to establish whether or not there is evidence for using this monotherapy. Results: In particular, bicalutamide in monotherapy has been compared with castration in large international trials. Results show that antiandrogen monotherapy is inferior to castration in patients with metastatic tumour but the difference in median survival is limited. In locally advanced M0 prostate cancer bicalutamide 150 mg monotherapy seems equivalent to castration in terms of overall survival and time to progression. Analysis of quality of life showed that there is evidence of some benefits from bicalutamide when compared to castration in both sexual interest and physical capacity. Conclusion: Antiandrogens in monotherapy can be effective and well tolerated. However, more research is needed because none of the available compounds have definitively been proven to be equivalent to castration

Interspecific somatic hybrids between Solanum bulbocastanum and S. tuberosum and their haploidization for potato breeding.

Protoplast fusion between incongruent Solanum bulbocastanum and S. tuberosum haploids was accomplished to produce hybrids combining elite traits from both parents. We identified 11 somatic hybrids out of 42 regenerants analyzed through ISSR markers. Some hybrids had loss or gain of fragments compared to the parents, likely due to rearrangements and deletions of chromosome segments after fusion, and/or to somaclonal variation during hybrid regeneration. Increased heterotic vigor for some traits as well as high diversity was observed as the effect of both ploidy and fusion combination. Microsporogenesis analysis indicated the occurrence of multivalent configurations and several meiotic abnormalities, such as chromosomes bridges and various spindle orientations. Since all hybrids were sterile, in vitro anther culture was employed for haploidization as a possible strategy to overcome barriers to hybridizations. Haploids were obtained from all the tetraploid S. bulbocastanum (+) S. tuberosum somatic hybrids tested, although with differences in both the number of embryos per 100 anthers cultured and the number of differentiated green plantlets. This is the first report on the successful production of haploid plants from S. bulbocastanum (+) S. tuberosum hybrids

Quality of Life in Neurogenic Bladder Patients and Improvement after Botulinum Toxin Injection

Various neurogenic conditions may determine an altered function of the bladder and urethral sphincters leading to urinary symptoms. Among these symptoms, loss of urine is considered the most bothersome, and recent literature has proposed that urinary incontinence and poor quality of life should be considered as associated conditions. Urinary incontinence is responsible for reducing the enjoyment of life, including loss of self-confidence and limitation of social activity; it is also associated with anxiety, depression, and deterioration in sexual life, and reduced physical activity. Conservative treatments represent a first-line therapeutic approach to neurogenic urinary disorders, followed by oral medications. However, these treatments often do not provide complete recovery from symptoms, especially from urinary incontinence. Onabotulimun toxin A has proven to be safe and effective for treating neurogenic urinary incontinence and its use is associated with a strong improvement of patients’ quality of life. Furthermore, this treatment lowers the risk of severe complications to the upper urinary tract, reducing the need for hospitalization. Quality of life improvement as well as clinical efficacy must be considered targets of the therapy, and the use of onabotulimun toxin A for treating neurogenic urinary incontinence reaches both these goals

HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis

Establishment of a DNA-free genome editing and protoplast regeneration method in cultivated tomato (Solanum lycopersicum)

Key message We have established a DNA-free genome editing method via ribonucleoprotein-based CRISPR/Cas9 in cultivated tomato and obtained mutant plants regenerated from transfected protoplasts with a high mutation rate. The application of genome editing as a research and breeding method has provided many possibilities to improve traits in many crops in recent years. In cultivated tomato (Solanum lycopersicum), so far only stable Agrobacterium-mediated transformation carrying CRISPR/Cas9 reagents has been established. Shoot regeneration from transfected protoplasts is the major bottleneck in the application of DNA-free genome editing via ribonucleoprotein-based CRISPR/Cas9 method in cultivated tomato. In this study, we report the implementation of a transgene-free breeding method for cultivated tomato by CRISPR/Cas9 technology, including the optimization of protoplast isolation and overcoming the obstacle in shoot regeneration from transfected protoplasts. We have identified that the shoot regeneration medium containing 0.1 mg/L IAA and 0.75 mg/L zeatin was the best hormone combination with a regeneration rate of up to 21.3%. We have successfully obtained regenerated plants with a high mutation rate four months after protoplast isolation and transfection. Out of 110 regenerated M-0 plants obtained, 35 (31.8%) were mutated targeting both SP and SP5G genes simultaneously and the editing efficiency was up to 60% in at least one allele in either SP or SP5G genes

Variation in chromogranin A serum levels during intermittent versus continuous androgen deprivation therapy for prostate adenocarcinoma

OBJECTIVES. It has been hypothesized that continuous androgen-suppression therapy produces hyperactivation of neuroendocrine (NE) cells and an increase in chromogranin A (CgA) in prostate carcinoma (PC). The aim of this study was to verify whether the intermittent administration of androgen deprivation (IAD) reduces the risk of CgA increase in PC cases treated with complete androgen deprivation (CAD). MATERIALS AND METHODS. We analyzed changes in serum CgA levels in patients with PC who successfully responded to the first 24 months of IAD versus continuous CAD therapy. Two different populations were analyzed: Type 1 = pT3pN0M0 prostate cancers with biochemical (PSA) progression after RRP; Type 2 = metastatic PC directly submitted to CAD. Cases in Type I and Type 2 population were randomly assigned to IAD versus continuous CAD therapy. Forty cases each in Type 1 and Type 2 population were included in the analysis. At 1, 3, 6,12,18,24 months of IAD versus continuous therapy, serum levels of CgA compared to PSA levels were analyzed. RESULTS. In population Type 1 and Type 2, in the group of cases continuously treated with CAD (Group 2), there was a significant trend to increase for CgA levels from baseline to 24 months of therapy. On the contrary, no significant variations were found in cases treated with IAD (Group 1). Either in population Type 1 or Type 2, at 12- and 24-month follow-up, mean and median serum levels of CgA were significantly (P < 0.005) lower in Group 1 than in Group 2. CONCLUSIONS. The present study represents the first evidence in the literature that the intermittent administration of CAD therapy significantly reduces the increase in serum CgA levels during CAD therapy. (C) 2003 Wiley-Liss, Inc

Peritonectomy Procedures and HIPEC for Peritoneal Metastasis from Ovarian Cancer

Peritoneal carcinomatosis (PC) is the most impressive and frequent evidence of loco-regional spread of epithelial ovarian cancer (EOC). For most of its natural history, PC remains confined to the peritoneal district, thus representing a target for various combinations of surgery and systemic or loco-regional chemotherapy. PC is observed both in primary settings, i.e. in patients first treated for locally advanced EOC, and in recurrent, previously treated, EOC patients at any FIGO stage. Since 2000s, the use of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with maximum cytoreduction (peritonectomy) has gradually spread in the treatment of PC from ovarian cancer, as well as for gastrointestinal carcinomatosis and primary tumours of the peritoneum. Use of combined peritonectomy + HIPEC in the treatment of ovarian carcinomatosis is the most discussed issue among those concerning peritoneal surface malignancy (PSM). The main criticism concerns the use of HIPEC, since the need for maximal cytoreduction is consolidated and does not raise any doubts. Communities of surgeon and oncologic gynaecologists who believes in the role of HIPEC have started controlled clinical trials aimed at clarifying the role of HIPEC associated to peritonectomy, but these studies are difficult to conduct and time-consuming. At present and pending the results of future prospective trials, the role and limits of application of the procedure are drawn from experiences from three basic study groups: collective reviews, multicentre studies, monocentric case studies produced by high-volume HIPEC centers. A comprehensive literature review and an in-depth analysis of our personal experience, based on the largest monocentric case series (130 cases), have helped to provide an assessment on the role of peritonectomy + HIPEC in about 2000 patients treated for initial and recurrent PC from ovarian cancer. Comparison of the overall results drawn from these studies, indicates that peritonectomy + HIPEC is able to guarantee in these patients better overall survival (OS) and higher progression-free survival (PFS) rates than those derived from traditional treatments, with acceptable morbidity and mortality. Notwithstanding, some specific aspects, including the role of chemoresistance and neoadjuvant and adjuvant treatments, should be clarified by further experience and the results of on-going trials

Premature Ejaculation patients and their partners: arriving at a clinical profile for a real optimization of the treatment.

The aim of the study is to extrapolate clinical features of Premature Ejaculation (PE) patients and female partners of men affected with PE, in order to get a profile that can be of assistance for physicians within the dynamics of a couple, one of which is a PE patient. An observational, non-interventional, cross-sectional epidemiological study entitled IPER (Italian Premature Ejaculation Research) was conducted and included two different cohorts of subjects that were randomly sampled from a patient dataset of selected General Practitioners: 1. IPER-M sub-cohort (1.104 subjects) was made of male subjects in which they were then distinguished patients with or without PE based on the score of the PEDT questionnaire; IPER-F sub-cohort (1.109 subjects) was made of female subjects from an independent sample of women (therefore not the partners of the IPER-M males) in which they then distinguished those partners of a male subject with PE or not. In addition to an identical general questionnaire to explore demographic aspects and habits, each subcohort was then evaluated using validated questionnaires. No differences were noted between PE+/PE- patients in terms of alcohol consumption, smoking habits, physical activity nor stress condition in everyday life, employment, socio-economic class and marital status. While the prevalence of PE proportionally increased with age, excluding the 50-59 and 70-80 years decades, in the IPER-M group an overall statistically significant difference for the mean age between the PE+ and PE- groups (p = 0.002) was detected, but without reaching any difference amongst the different age classes in the IPER-F group. The PE+ patients reported a significantly lower frequency rate of sexual intercourse, worse QoL (p = 0.006 and p < 0.0001, respectively), and increased anxiety status (p < 0.0001 for both subgroups). This study shows that, rather than talking with a patient affected by PE it would be advisable to introduce the concept of couple counseling with the person patient and his partner, because it is only through classification of both partners as one couple and a full understanding of their mutual sexual experience that PE treatment can be optimized and its results measured accurately

La Boheme

Direcció Artística Napoleone AnnovazziEl repartiment el formen Ken Neate, Antonio Cabanes, Jacinto Santamaría, Anna Leonelli, Pedro Clavería, Manuel Ausensi, Antonio Campo, Ana María Olaria i José Torruella; els decorats són realitzats per Ramón BatlleEmpresa: José F. ArquerOrquestra del Gran Teatre del Liceu ; director Angelo QuestaPrograma de La Bohème, òpera en quatre actes de Giacomo Puccini i llibret de Giuseppe Giacosa i Luigi IllicaDe cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents

Explicit and implicit emotional expression in bulimia nervosa in the acute state and after recovery

Expression of emotional state is considered to be a core facet of an individual's emotional competence. Emotional processing in BN has not been often studied and has not been considered from a broad perspective. This study aimed at examining the implicit and explicit emotional expression in BN patients, in the acute state and after recovery. Sixty-three female participants were included: 22 BN, 22 recovered BN (R-BN), and 19 healthy controls (HC). The clinical cases were drawn from consecutive admissions and diagnosed according to DSM-IV-TR diagnostic criteria. Self reported (explicit) emotional expression was measured with State-Trait Anger Expression Inventory-2, State-Trait Anxiety Inventory, and Symptom Check List-90 items-Revised. Emotional facial expression (implicit) was recorded by means of an integrated camera (by detecting Facial Feature Tracking), during a 20 minutes therapeutic video game. In the acute illness explicit emotional expression [anxiety (p<0.001) and anger (p<0.05)] was increased. In the recovered group this was decreased to an intermediate level between the acute illness and healthy controls [anxiety (p<0.001) and anger (p<0.05)]. In the implicit measurement of emotional expression patients with acute BN expressed more joy (p<0.001) and less anger (p<0.001) than both healthy controls and those in the recovered group. These findings suggest that there are differences in the implicit and explicit emotional processing in BN, which is significantly reduced after recovery, suggesting an improvement in emotional regulation