Trehalose and a calcium chelator for ram semen cryopreservation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Contribuições para a proposta de uma política municipal de pagamento por serviços ambientais: o caso de Botucatu/SP

Environmental services are the ones done by the nature, that supports both the life and the environment. Payments for Environmental Services (PES) are financial transfers by beneficiaries of environmental services for the ones who provide such services due to conservation practices. Botucatu is a city in São Paulo State with a great potential for PES. Therefore, this paper develops a comparative study of PES projects in Federal and State ranges, aiming to analyze, select and propose criteria in order to contribute to the creation of a PES policy for the city.

Prostate biopsy in patients with long-term use of indwelling bladder catheter: What is the rationale?

Objective: Acute urinary retention (AUR) is expected to occur in 2% to 39% men with benign prostatic hyperplasia. To date, no study has elucidated the effect of long-term use of indwelling bladder catheter on serum prostate specific antigen (PSA) levels and on the incidence of prostate cancer (CaP). The aim of the present study is to analyze the incidence of CaP in patients with long-term use of indwelling bladder catheter and determine some practice patterns on this issue. Materials and methods: The study comprised a retrospective analysis of data from 1,651 patients who had undergone transrectal ultrasound (TRUS)-guided prostate biopsy from July 2004 to June 2009. Among these patients, 198 (12%) were using an indwelling bladder catheter during the biopsy for at least 1 month. The incidence of CaP was recorded according to total PSA levels. Other variables such patient age, free/total PSA rate, PSA density, prostate volume, and duration of catheter use was also analyzed. Men with a digital rectal examination suspicious for cancer were not considered for analysis. Results: Median patient age was 71 years (37 to 89 years). Overall, 25% of patients presented a CaP diagnosis. CaP incidence according to the PSA levels was 0%, 18.9%, 24.5%, and 40.6% for patients with PSA <= 4.0, 4.1-10.0, 10.1-20.0, and >20.0 ng/ml, respectively. When prostate volume was analyzed together, we demonstrated that only 1 (2.4%) patient with PSA below 10.0 ng/ml and prostate volume >60 g had CaP. Median total PSA, PSA density, and prostate volume were statistically different between patients with and without CaP. Conclusions: Prostate biopsy should not be indicated for all patients with diagnosis of BPH and AUR who present an elevated PSA level. Patients with PSA below 10.0 ng/ml, and prostate volume >60 g should only undergo biopsy in selected cases. Patients with PSA >20.0 ng/ml and a prostate volume <= 60 g are at higher risk of CaP diagnosis. (C) 2012 Elsevier Inc. All rights reserved.

TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients

Methods. One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination. Results. After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients. Conclusion. This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs. Trial Registration: ClinicalTrials.gov, ext-link-type="uri" xlink:href="www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.clinicaltrials.gov, NCT01151644.

Surrogate endpoints for prostate cancer-specific mortality after radiotherapy and androgen suppression therapy in men with localised or locally advanced prostate cancer: an analysis of two randomised trials

Background Androgen suppression therapy and radiotherapy are used to treat locally advanced prostate cancer. 3 years of androgen suppression confers a small survival benefit compared with 6 months of therapy in this setting, but is associated with more toxic effects. Early identification of men in whom radiotherapy and 6 months of androgen suppression is insufficient for cure is important. Thus, we assessed whether prostate-specific antigen (PSA) values can act as an early surrogate for prostate cancer-specific mortality (PCSM). Methods We systematically reviewed randomised controlled trials that showed improved overall and prostate cancer-specific survival with radiotherapy and 6 months of androgen suppression compared with radio therapy alone and measured lowest PSA concentrations (PSA nadir) and those immediately after treatment (PSA end). We assessed a cohort of 734 men with localised or locally advanced prostate cancer from two eligible trials in the USA and Australasia that randomly allocated participants between Feb 2, 1996, and Dec 27, 2001. We used Prentice criteria to assess whether reported PSA nadir or PSA end concentrations of more than 0.5 ng/mL were surrogates for PCSM. Findings Men treated with radiotherapy and 6 months of androgen suppression in both trials were significantly less likely to have PSA end and PSA nadir values of more than 0.5 ng/mL than were those treated with radiotherapy alone (p<0.0001). Presence of candidate surrogates (ie, PSA end and PSA nadir values >0.5 ng/mL) alone and when assessed in conjunction with the randomised treatment group increased risk of PCSM in the US trial (PSA nadir p=0.0016; PSA end p=0.017) and Australasian trial (PSA nadir p<0.0001; PSA end p=0.0012). In both trials, the randomised treatment group was no longer associated with PCSM (p >= 0.20) when the candidate surrogates were included in the model. Therefore, both PSA metrics satisfied Prentice criteria for surrogacy. Interpretation After radiotherapy and 6 months of androgen suppression, men with PSA end values exceeding 0.5 ng/mL should be considered for long-term androgen suppression and those with localised or locally advanced prostate cancer with PSA nadir values exceeding 0.5 ng/mL should be considered for inclusion in randomised trials investigating the use of drugs that have extended survival in castration-resistant metastatic prostate cancer.

miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer

Background: Prognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line. Materials and methods: To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR). Results: The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025). Conclusions: Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.

Underexpression of MMP-2 and its Regulators, TIMP2, MT1-MMP and IL-8, is Associated with Prostate Cancer

Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (>= 7) over-expressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.

GREB1 tissue expression is associated with organ-confined prostate cancer

Objective: By reason of its heterogeneous behavior, it is difficult to determine the prognosis of many prostate cancer cases. Patients with the same clinicopathologic conditions may present varying clinical findings and rates of progression. We determined the role of new genes as potential molecular markers for prostate cancer prognosis. Materials and methods: We performed a microarray analysis of two pools of patients with prostate cancer divided according to their clinicopathologic characteristics. After that, we validated these results by testing the genes with most different expressions between the two pools using the quantitative real time polymerase chain reaction method. We analyzed gene expression in 33 patients with localized prostate cancer according to prostate specific antigen (PSA), pathologic stage, Gleason score, and biochemical recurrence. For statistical analysis we used the Mann-Whitney Test. Results: The microarray analysis revealed that 4,147 genes presented a different expression between the two pools. Among them, 3 genes, TMEFF2, GREB1, and THIL,, were at least 13-times overexpressed, and 1 gene, IGH3, which was at least 5times under-expressed in pool 1 (good prognosis) compared with pool 2 (bad prognosis), were selected for analysis. After the validation tests, GREB1 was significantly more overexpressed among patients with stage T2 compared with T3 (P = 0.020). The expressions of other 3 genes did not present significant differences according to the clinicopatholoOcal variables. Conclusions: Tissue expression of GREB1 is associated with organ-confined prostate cancer and may constitute a gene associated with a favorable prognosis. (C) 2012 Elsevier Inc. All rights reserved.

Biochemical control of prostate cancer with iodine-125 brachytherapy alone: experience from a single institution

Brachytherapy is an adequate option as monotherapy for localised prostate cancer. The objective of this study was to evaluate and compare biochemical failure free survival (BFFS) after low-dose-rate brachytherapy (LDRB) alone for patients with prostate cancer using ASTRO and Phoenix criteria, and detect prognostic factors. Data on 220 patients treated between 1998 and 2002 with LDRB were retrospectively analysed. Neoadjuvant hormone therapy was used in 74 (33.6%) patients. Median follow-up was 53.5 months (24-116). Five year BFFS was 83.0% and 83.7% using, respectively, the ASTRO and Phoenix criteria. Low -and intermediate-risk patients presented, respectively, 86.7% and 77.8% 5-year BFFS using the ASTRO definition (p=0.069), and 88.5% and 78.6% considering the Phoenix criteria (p=0.016). Bounce was observed in 66 (30%) patients. Multivariate analysis detected PSA at diagnosis < 10 ng/ml and less than 50% positive biopsy fragments as favourable prognostic factors, regarding BF using both criteria. For the Phoenix criteria, also Gleason score < 7 and low-risk group were identified as independent favourable prognostic factors. LDRB alone should be considered mostly for low-risk patients. PSA level was a strong independent prognostic factor. We support the use of the Phoenix criteria for detection of BF in patients submitted to LDRB alone.

Botulinum Neurotoxin Type A for the Treatment of Benign Prostatic Hyperplasia: Randomized Study Comparing Two Doses

Purpose. To assess the efficacy and safety of intraprostatic injection of two botulinum neurotoxin type A (BoNT-A) doses for the treatment of benign prostatic hyperplasia (BPH). Materials and Methods. Men with symptomatic BPH who failed medical treatment were randomized to receive 100 U or 200 U of BoNT-A into the prostate. The International Prostatic Symptom Score (IPSS), maximum flow rate (Q(max)), post-void residual volume (PVR), PSA levels and prostate volume before injection and after 3 and 6 months were evaluated. Adverse events were compared between the groups. Results. Thirty four patients were evaluated, including 17 in the BoNT-A 100 U group and 17 in the BoNT-A 200 U group. Baseline characteristics were similar in both groups. Both doses produced significant improvements in IPSS, Q(max) and PVR after 3 and 6 months and both doses promoted comparable effects. Prostate volume was affected by 200 U BoNT-A injection only after 6 months of treatment. PSA levels were significantly affected in the 100 U group only after 6 months of treatment. In the 200 U group, PSA levels were significantly decreased after 3 and 6 months. The complication rate was similar in both groups. Conclusions. Efficacy and safety of both BoNT-A doses are similar for BPH treatment in the short term followup.

Are we able to correctly identify prostate cancer patients who could be adequately treated by focal therapy?

Introduction and Objective: Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. Material and methods: A total of 599 patients who underwent transrectal ultrasound, (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only I biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level < 10 ng/ml, Gleason score < 7 and clinical stage T1c, T2a-b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. Results: Fifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a-b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason >= 7, and 25% were staged pT3. Conclusion: Although focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated. (c) 2012 Elsevier Inc. All rights reserved.

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

OBJECTIVE: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). MATERIALS AND METHODS: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. RESULTS: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (> 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). CONCLUSION: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.

Effects of environmental complexity on neurogenesis in the hippocampal dentate gyrus

Introduction. Postnatal neurogenesis in the hippocampal dentate gyrus, can be modulated by numerous determinants, such as hormones, transmitters and stress. Among the factors positively interfering with neurogenesis, the complexity of the environment appears to play a particularly striking role. Adult mice reared in an enriched environment produce more neurons and exhibit better performance in hippocampus-specific learning tasks. While the effects of complex environments on hippocampal neurogenesis are well documented, there is a lack of information on the effects of living under socio-sensory deprivation conditions. Due to the immaturity of rats and mice at birth, studies dealing with the effects of environmental enrichment on hippocampal neurogenesis were carried out in adult animals, i.e. during a period of relatively low rate of neurogenesis. The impact of environment is likely to be more dramatic during the first postnatal weeks, because at this time granule cell production is remarkably higher than at later phases of development. The aim of the present research was to clarify whether and to what extent isolated or enriched rearing conditions affect hippocampal neurogenesis during the early postnatal period, a time window characterized by a high rate of precursor proliferation and to elucidate the mechanisms underlying these effects. The experimental model chosen for this research was the guinea pig, a precocious rodent, which, at 4-5 days of age can be independent from maternal care. Experimental design. Animals were assigned to a standard (control), an isolated, or an enriched environment a few days after birth (P5-P6). On P14-P17 animals received one daily bromodeoxyuridine (BrdU) injection, to label dividing cells, and were sacrificed either on P18, to evaluate cell proliferation or on P45, to evaluate cell survival and differentiation. Methods. Brain sections were processed for BrdU immunhistochemistry, to quantify the new born and surviving cells. The phenotype of the surviving cells was examined by means of confocal microscopy and immunofluorescent double-labeling for BrdU and either a marker of neurons (NeuN) or a marker of astrocytes (GFAP). Apoptotic cell death was examined with the TUNEL method. Serial sections were processed for immunohistochemistry for i) vimentin, a marker of radial glial cells, ii) BDNF (brain-derived neurotrofic factor), a neurotrophin involved in neuron proliferation/survival, iii) PSA-NCAM (the polysialylated form of the neural cell adhesion molecule), a molecule associated with neuronal migration. Total granule cell number in the dentate gyrus was evaluated by stereological methods, in Nissl-stained sections. Results. Effects of isolation. In P18 isolated animals we found a reduced cell proliferation (-35%) compared to controls and a lower expression of BDNF. Though in absolute terms P45 isolated animals had less surviving cells than controls, they showed no differences in survival rate and phenotype percent distribution compared to controls. Evaluation of the absolute number of surviving cells of each phenotype showed that isolated animals had a reduced number of cells with neuronal phenotype than controls. Looking at the location of the new neurons, we found that while in control animals 76% of them had migrated to the granule cell layer, in isolated animals only 55% of the new neurons had reached this layer. Examination of radial glia cells of P18 and P45 animals by vimentin immunohistochemistry showed that in isolated animals radial glia cells were reduced in density and had less and shorter processes. Granule cell count revealed that isolated animals had less granule cells than controls (-32% at P18 and -42% at P45). Effects of enrichment. In P18 enriched animals there was an increase in cell proliferation (+26%) compared to controls and a higher expression of BDNF. Though in both groups there was a decline in the number of BrdU-positive cells by P45, enriched animals had more surviving cells (+63) and a higher survival rate than controls. No differences were found between control and enriched animals in phenotype percent distribution. Evaluation of the absolute number of cells of each phenotype showed that enriched animals had a larger number of cells of each phenotype than controls. Looking at the location of cells of each phenotype we found that enriched animals had more new neurons in the granule cell layer and more astrocytes and cells with undetermined phenotype in the hilus. Enriched animals had a higher expression of PSA-NCAM in the granule cell layer and hilus Vimentin immunohistochemistry showed that in enriched animals radial glia cells were more numerous and had more processes.. Granule cell count revealed that enriched animals had more granule cells than controls (+37% at P18 and +31% at P45). Discussion. Results show that isolation rearing reduces hippocampal cell proliferation but does not affect cell survival, while enriched rearing increases both cell proliferation and cell survival. Changes in the expression of BDNF are likely to contribute to he effects of environment on precursor cell proliferation. The reduction and increase in final number of granule neurons in isolated and enriched animals, respectively, are attributable to the effects of environment on cell proliferation and survival and not to changes in the differentiation program. As radial glia cells play a pivotal role in neuron guidance to the granule cell layer, the reduced number of radial glia cells in isolated animals and the increased number in enriched animals suggests that the size of radial glia population may change dynamically, in order to match changes in neuron production. The high PSA-NCAM expression in enriched animals may concur to favor the survival of the new neurons by facilitating their migration to the granule cell layer. Conclusions. By using a precocious rodent we could demonstrate that isolated/enriched rearing conditions, at a time window during which intense granule cell proliferation takes place, lead to a notable decrease/increase of total granule cell number. The time-course and magnitude of postnatal granule cell production in guinea pigs are more similar to the human and non-human primate condition than in rats and mice. Translation of current data to humans would imply that exposure of children to environments poor/rich of stimuli may have a notably large impact on dentate neurogenesis and, very likely, on hippocampus dependent memory functions.

Enabling Techniques and Algorithms for Integrated Communication and Navigation Satellite Systems

This thesis presents the outcomes of my Ph.D. course in telecommunications engineering. The focus of my research has been on Global Navigation Satellite Systems (GNSS) and in particular on the design of aiding schemes operating both at position and physical level and the evaluation of their feasibility and advantages. Assistance techniques at the position level are considered to enhance receiver availability in challenging scenarios where satellite visibility is limited. Novel positioning techniques relying on peer-to-peer interaction and exchange of information are thus introduced. More specifically two different techniques are proposed: the Pseudorange Sharing Algorithm (PSA), based on the exchange of GNSS data, that allows to obtain coarse positioning where the user has scarce satellite visibility, and the Hybrid approach, which also permits to improve the accuracy of the positioning solution. At the physical level, aiding schemes are investigated to improve the receiver’s ability to synchronize with satellite signals. An innovative code acquisition strategy for dual-band receivers, the Cross-Band Aiding (CBA) technique, is introduced to speed-up initial synchronization by exploiting the exchange of time references between the two bands. In addition vector configurations for code tracking are analyzed and their feedback generation process thoroughly investigated.

Small Molecules as Modulators of Different Targets Involved in Tumor Progression

Tumor is a lesion that may be formed by an abnormal growth of neoplastic cells. Many factors increase the risk of cancer and different targets are involved in tumor progression. Within this thesis, we have addressed two different biological targets, independently connected with tumor formation, e.g. Hsp90 and androgen receptor. The ATP-dependent chaperone Hsp90 is responsible for the conformational maturation and the renaturation of proteins. “Client” proteins are associated with the cancer hallmarks, as cell proliferation and tumor progression. Consequently, Hsp90 has evolved into promising anticancer target. Over the past decade, radicicol has been identified as potential anticancer agent targeting Hsp90, but it is not active in vivo. With that aim of obtaining radicicol-related derivatives, we developed the design and synthesis of new chalcones analogs. Chalcones, which are abundant in edible plants, own a diverse array of pharmacological activities and are considered a versatile scaffold for drug design. Antiproliferative assays and western blot analysis on the new compounds showed that some of those display an interesting cytotoxic effect and the ability to modulate Hsp90 client proteins expression. Androgen Receptor (AR) hypersensitivity plays crucial role in prostate cancer, which progression is stimulated by androgens. The therapy consists in a combination of surgical or chemical castration, along with antiandrogens treatment. Casodex® (bicalutamide), is the most widespread antiandrogen used in clinic. However, hormonal therapy is time-limited since many patients develop resistance. Commercially available antiandrogens show a common scaffold, e.g. two substituted aromatic rings linked by a linear or a cyclic spacer. With the aim of obtaining novel pure AR antagonists, we developed a new synthetic methodology, which allowed us to introduce, as linker between two suitably chosen aromatic rings, a triazole moiety. Preliminary data suggest that the herein reported new molecules generally decrease PSA expression, thus confirming their potential AR antagonistic activity.