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1.
J Endocrinol Invest ; 43(9): 1347, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32504459

RESUMEN

Unfortunately, the 5th author name has been publisehd incorrectly in the original publication. The complete correct name is given below.

2.
Andrology ; 8(2): 427-433, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31433119

RESUMEN

BACKGROUND: Type 5 phosphodiesterase (PDE5) expression in the normal and pathological prostate is controversial. OBJECTIVES: This study aimed at identifying the cell type/s, if any, expressing PDE5 in human healthy or pathological prostate sections in order to further validate the rationale of PDE5 inhibitor (PDE5i) treatment of benign prostatic hyperplasia (BPH) and their safety in the treatment of erectile dysfunction following prostate cancer (PCa) surgery. MATERIALS AND METHODS: By immunohistochemical analysis, we studied PDE5 expression in tissue microarrays containing sections obtained from healthy, BPH, and PCa samples. RESULTS: Our results showed that PDE5 is barely expressed in the epithelial or stromal compartment of normal human prostates, but it is highly expressed in the stromal compartment of BPH sections. We also found that a low but significant number of PCa samples (22%) expressed PDE5 in the epithelial cancer cells but not in stromal cells and that such expression was not correlated with the tumor aggressiveness, according to their Gleason score. DISCUSSION AND CONCLUSION: PDE5 overexpression in the stromal compartment of BPH samples supports the rationale of PDE5 as a target in lower urinary tract symptoms of BPH. PDE5 expression in a significant percentage of PCa samples but the lack of correlation with the Gleason score suggests that this enzyme is not correlated with tumor aggressiveness; however, a role of PDE5 in the minimal residual disease of PCa cannot be excluded.


Asunto(s)
Adenocarcinoma/enzimología , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/biosíntesis , Próstata/enzimología , Hiperplasia Prostática/enzimología , Neoplasias de la Próstata/enzimología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/análisis , Humanos , Masculino , Persona de Mediana Edad , Próstata/patología , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología , Adulto Joven
3.
Eur Rev Med Pharmacol Sci ; 23(6): 2669-2680, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30964194

RESUMEN

OBJECTIVE: Endothelial dysfunction (ED) predisposes to venous thrombosis (VT) and post-thrombotic syndrome (PTS), a long-term VT-related complication. Sulodexide (SDX) is a highly purified glycosaminoglycan with antithrombotic, pro-fibrinolytic and anti-inflammatory activity used in the treatment of chronic venous disease (CVD), including patients with PTS. SDX has recently obtained clinical evidence in the "extension therapy" after initial-standard anticoagulant treatment for the secondary prevention of recurrent deep vein thrombosis (DVT). Herein, we investigated how SDX counteracts ED. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used. Metabolic and non metabolic-induced ED was induced by treating with methylglyoxal (MGO) or irradiation (IR), respectively. Bafilomycin A1 was used to inhibit autophagy. The production of reactive oxygen species (ROS), tetrazolium bromide (MTT) assay for cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for cell apoptosis, Real-time PCR and Western blot analysis for gene and protein expression were used. RESULTS: SDX protected HUVEC from MGO- or IR-induced apoptosis by counteracting the activation of the intrinsic and extrinsic caspase cascades. The cytoprotective effects of SDX resulted from a reduction in a) ROS production, b) neo-synthesis and release of pro-inflammatory cytokines (TNFα, IL1, IL6, IL8), c) DNA damage induced by MGO or IR. These effects were reduced when autophagy was inhibited. CONCLUSIONS: Data herein collected indicate the ability of SDX to counteract ED induced by metabolic or non-metabolic stresses by involving the intracellular autophagy pathway. Our experience significantly increases the knowledge of the mechanisms of action of SDX against ED and supports the use of SDX in the treatment of CVD, PTS and in the secondary prevention of recurrent DVT.


Asunto(s)
Glicosaminoglicanos/farmacología , Células Endoteliales de la Vena Umbilical Humana/citología , Piruvaldehído/efectos adversos , Rayos X/efectos adversos , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Citocinas/genética , Citocinas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de la radiación , Humanos , Modelos Biológicos , Especies Reactivas de Oxígeno/metabolismo
4.
J Endocrinol Invest ; 42(2): 183-197, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29790086

RESUMEN

PURPOSE: Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in childhood, rarely affects adults, preferring male. RMS expresses the receptor for androgen (AR) and responds to androgen; however, the molecular action of androgens on RMS is unknown. METHODS: Herein, testosterone (T) effects were tested in embryonal (ERMS) and alveolar (ARMS) RMS cell lines, by performing luciferase reporter assay, RT-PCR, and western blotting experiments. RNA interference experiments or bicalutamide treatment was performed to assess the specific role of AR. Radiation treatment was delivered to characterise the effects of T treatment on RMS intrinsic radioresistance. RESULTS: Our study showed that RMS cells respond to sub-physiological levels of T stimulation, finally promoting AR-dependent genomic and non-genomic effects, such as the transcriptional regulation of several oncogenes, the phosphorylation-mediated post-transductional modifications of AR and the activation of ERK, p38 and AKT signal transduction pathway mediators that, by physically complexing or not with AR, participate in regulating its transcriptional activity and the expression of T-targeted genes. T chronic daily treatment, performed as for the hormone circadian rhythm, did not significantly affect RMS cell growth, but improved RMS clonogenic and radioresistant potential and increased AR mRNA both in ERMS and ARMS. AR protein accumulation was evident in ERMS, this further developing an intrinsic T-independent AR activity. CONCLUSIONS: Our results suggest that androgens sustain and improve RMS transformed and radioresistant phenotype, and therefore, their therapeutic application should be avoided in RMS post puberal patients.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Receptores Androgénicos/metabolismo , Rabdomiosarcoma/metabolismo , Transducción de Señal/fisiología , Testosterona/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Rabdomiosarcoma/patología , Transducción de Señal/efectos de los fármacos
6.
Andrology ; 5(5): 863-872, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28787547

RESUMEN

The impact of phosphodiesterase type 5 inhibitor (PDE5I) treatment modality (on-demand vs. daily), PDE5I half-life and time from surgery to PDE5I prescription on the achievement of drug-assisted erectile function (EF) recovery is uncertain. We systematically reviewed published randomized clinical trials (RCTs). We performed meta-analyses of data on 2317 men treated with PDE5Is after nerve-sparing radical prostatectomy (NSRP). A PubMed and SCOPUS search was performed for trials published from 1 January 1969 to 30 June 2016. PDE5Is are effective in achieving drug-assisted recovery of erectile function (EF). From a statistical standpoint, these studies were subjected to Trial Sequential Analysis to determine whether the pooled data were adequately powered to verify the study outcomes. On-demand treatment with PDE5Is was significantly better than daily treatment in recovering drug-assisted EF. This effect was maintained even when the drugs were stratified according with half-life. Although not based on head-to-head trials, Avanafil used on-demand was the most effective PDE5I in recovering drug-assisted EF. Whereas tadalafil was equally effective when used both on-demand and daily, vardenafil significantly improved drug-assisted EF recovery only when used on-demand. The start of PDE5I treatment six months or more after surgery compared to treatment started earlier did not negatively affect the rate of drug-assisted EF recovery or the possibility to have successful intercourse based on the Sexual Encounter Profile question-3 (SEP-3). Current trials do not support the hypothesis that PDE5I use recovers drug-unassisted EF, although chronic low-dose tadalafil administration may help to preserve erectile tissue integrity. Potential shortcomings in the trials design may partially explain these disappointing results and several questions concerning the recovery of drug-unassisted EF remain unanswered. Thus, there is a need for well-designed new RCTs requiring changes in the timing of PDE5I administration as well as in the dose and the treatment duration.


Asunto(s)
Erección Peniana , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Prostatectomía , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/etiología , Humanos , Masculino , Erección Peniana/efectos de los fármacos , Prostatectomía/efectos adversos , Prostatectomía/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
J Endocrinol Invest ; 40(2): 227-233, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27667822

RESUMEN

PURPOSE: The aim of this study was to investigate homophobic attitudes in three European countries: Italy, Albania, and Ukraine. One thousand and forty-eight students were recruited in Italian (n = 766), Albanian (n = 180), and Ukrainian (n = 102) university centers. METHODS: A socio-demographic questionnaire and Homophobia Scale (HS) were administered by our staff. RESULTS: Cross-cultural and significant differences among Italian, Albanian, and Ukrainian students were found on the Homophobia Scale (HS; Italy: mean = 22.26 ± 16.73; Albania: mean = 38.15 ± 17.28; Ukraine: mean = 59.18 ± 16.23). The analysis of socio-demographic characteristics revealed that the male gender emerged as main predictor of homophobic attitude in all the three countries, although also a conservative political orientation and the religious belief predict higher homophobia levels in Italy and Albania, particularly. CONCLUSIONS: This study revealed that in these European countries assessed, attitudes toward homosexuality are different. Ukrainians display higher levels of homophobia than Albanians and Italians, confirming the central role of cultural differences in homophobic attitudes. Nevertheless, some socio-demographic aspects such as identification as male have a similar influence on homophobic attitudes in all assessed populations.


Asunto(s)
Actitud , Comparación Transcultural , Demografía , Homosexualidad/psicología , Percepción Social , Estudiantes/psicología , Adolescente , Adulto , Características Culturales , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Masculino , Encuestas y Cuestionarios , Universidades , Adulto Joven
8.
Andrology ; 4(5): 921-6, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27214119

RESUMEN

To the best of our knowledge, no psychometric tools have been specifically developed to measure if premature ejaculation (PE) is related to low sexual pleasure in terms of perception of orgasmic intensity. Hence, the aim of this study was to evaluate if men with PE suffer from a low perception of orgasmic intensity using a new tool, the 'Orgasmometer', to quantitatively measure the intensity of orgasmic pleasure. Among 329 subjects attending our andrological unit for suspected PE, 257 men fulfilled the inclusion criteria. Of these, 156 (60.7%; 156/257) were affected by PE (PE group) and 101 (39.3%; 101/257) did not have any sexual dysfunction (Control group). Men were requested to fill out the Premature Ejaculation Diagnostic Tool (PEDT) and the Orgasmometer, a new visual tool recording orgasm intensity on a Likert scale. Interestingly, MANCOVA analysis revealed a statistically significant difference between the two groups (p = 0.044) in the subjective perception of orgasm intensity with the PE group scoring lower on the Orgasmometer (mean 5.8; 95% CI 5.191-6.409) than the Control group (mean 7.95; 95% CI 7.033-8.87). In addition, multiple linear regression revealed an inverse correlation between the PEDT and the Orgasmometer scores (p < 0.0001). Hence, higher PEDT scores were associated with a lower subjective perception of orgasmic intensity. The Orgasmometer was well understood, had good test-retest reliability and a high AUC in differentiating between men with high and low orgasmic pleasure intensity. The ROC curve analysis showed that a cut-off ≤6 had 87.7% sensitivity (95% CI 79.6-92.6), 95% specificity (95% CI 88.7-98.4), 95.3% positive predictive value (PPV) and 86.4% negative predictive value (NPV). Men affected by premature ejaculation perceived significantly lower orgasmic intensity than sexually healthy men. The Orgasmometer is an easy-to-perform, user-friendly tool for measuring orgasmic intensity.


Asunto(s)
Orgasmo/fisiología , Placer/fisiología , Eyaculación Prematura/psicología , Conducta Sexual/psicología , Adulto , Eyaculación/fisiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Eyaculación Prematura/fisiopatología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Conducta Sexual/fisiología , Encuestas y Cuestionarios
9.
Radiat Res ; 185(4): 411-22, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27104757

RESUMEN

We have previously reported that the MEK/ERK pathway sustains in vitro and in vivo transformed phenotype and radioresistance of embryonal rhabdomyosarcoma (ERMS) cell lines. Furthermore, we found that aberrant MEK/ERK signaling activation promotes c-Myc oncoprotein accumulation. In this study, the role of c-Myc in sustaining the ERMS transformed and radioresistant phenotype is characterized. RD and TE671 cell lines conditionally expressing MadMyc chimera protein, c-Myc-dominant negative and shRNA directed to c-Myc were used. Targeting c-Myc counteracted in vitro ERMS adherence and in suspension, growth motility and the expression of pro-angiogenic factors. c-Myc depletion decreased MMP-9, MMP-2, u-PA gelatinolytic activity, neural cell adhesion molecule sialylation status, HIF-1α, VEGF and increased TSP-1 protein expression levels. Rapid but not sustained targeting c-Myc radiosensitized ERMS cells by radiation-induced apoptosis, DNA damage and impairing the expression of DNA repair proteins RAD51 and DNA-PKcs, thereby silencing affected ERMS radioresistance. c-Myc sustains ERMS transformed phenotype and radioresistance by protecting cancer cells from radiation-induced apoptosis and DNA damage, while promoting radiation-induced DNA repair. This data suggest that c-Myc targeting can be tested as a promising treatment in cancer therapy.


Asunto(s)
Transformación Celular Neoplásica , Fenotipo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Tolerancia a Radiación , Rabdomiosarcoma Embrionario/patología , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Movimiento Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Roturas del ADN de Doble Cadena/efectos de la radiación , Reparación del ADN/efectos de la radiación , Silenciador del Gen , Humanos , Invasividad Neoplásica , Neovascularización Patológica , Proteínas Proto-Oncogénicas c-myc/deficiencia , Proteínas Proto-Oncogénicas c-myc/genética , ARN Interferente Pequeño/genética
10.
J Endocrinol Invest ; 39(4): 411-22, 2016 04.
Artículo en Inglés | MEDLINE | ID: mdl-26335302

RESUMEN

PURPOSE: Radiotherapy toxicity is related to oxidative stress-mediated endothelial dysfunction. Here, we investigated on radioprotective properties of Vitamin D (Vit.D) on human endothelial cells (HUVEC). METHODS: HUVEC, pre-treated with Vit.D, were exposed to ionizing radiation (IR): ROS production, cellular viability, apoptosis, senescence and western blot for protein detection were performed. The role of MAPKs pathway was investigated by using U0126 (10 µM) MEKs/ERKs-, SB203580 (2.5 µM) p38-inhibitor or by over/expressing MKK6 p38-upstream activator. RESULTS: Vit.D reduced IR-induced ROS production protecting proliferating and quiescent HUVEC from cellular apoptosis or senescence, respectively, by regulating MAPKs pathways. In proliferating HUVEC, Vit.D prevented IR-induced apoptosis by activating ERKs while in quiescent HUVEC counteracted IR-induced senescence by inhibiting the p38-IR-induced activation. MEKs&ERKs inhibition in proliferating or MKK6/mediated p38 activation in quiescent HUVEC, respectively, reverted anti-apoptotic or anti-senescent Vit.D properties. SirT1 protein expression levels were up-regulated by Vit.D. ERKs inhibition blocked Vit.D-induced SirT1 protein up-regulation in proliferating cells. In quiescent HUVEC cells, p38 inhibition counteracted the IR-induced SirT1 protein down-regulation, while MKK6 transfection abrogated the Vit.D positive effects on SirT1 protein levels after irradiation. SirT1 inhibition by sirtinol blocked the Vit.D radioprotective effects. CONCLUSION: Vit.D protects HUVEC from IR induced/oxidative stress by positively regulating the MAPKs/SirT1 axis.


Asunto(s)
Apoptosis/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sirtuina 1/metabolismo , Vitamina D/farmacología , Vitaminas/farmacología , Apoptosis/efectos de la radiación , Western Blotting , Ciclo Celular/efectos de los fármacos , Ciclo Celular/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Células Cultivadas , Senescencia Celular/efectos de la radiación , Endotelio Vascular/patología , Endotelio Vascular/efectos de la radiación , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/patología , Células Endoteliales de la Vena Umbilical Humana/efectos de la radiación , Humanos , Estrés Oxidativo/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo
11.
Eur J Surg Oncol ; 41(8): 1054-8, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25956212

RESUMEN

PURPOSE: This study was planned to clarify the optimal treatment for squamous cell carcinoma of the rectum, an histological entity extremely rare. METHODS: Ten patients with histologically proven squamous cell carcinoma of the rectum were treated with concomitant radiochemotherapy. Radiation therapy was delivered with a 3Dconformational multiple field technique to a dose ranging from 45 to 76.5 Gy, with 6-15 MV energy photons. Chemotherapy consisted of an antimetabolite drug in association with mitomycin C or oxaliplatin. Overall survival and disease free survival were considered in months from the end of the concomitant treatment. RESULTS: All patients completed programmed radiochemotherapy treatment but two patients were excluded to the analysis. Six patients (75%) presented negative biopsy 6 months after the end of radiochemotherapy. Seven patients (87.5%) showed a tumour regression after initial treatment. Only 1 patient underwent salvage surgery. Considering a mean follow-up of 41.75 months, 7 patients are still disease free survivors. Only 1 patient developed local recurrence at 6 months and he died 14 months after abdomino-perineal resection. CONCLUSION: Primary radio chemotherapy, with a curative intent, could be considered the treatment modality of choice for squamous carcinoma of the rectum.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias del Recto/terapia , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias del Recto/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia
12.
J Endocrinol Invest ; 38(9): 999-1005, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25894866

RESUMEN

PURPOSE: The assessment of sexual function is fundamental to the Assisted Reproductive Technology (ART). Nevertheless, it is still not a common clinical routine among infertility centres. The aim of this survey is to describe the main aspects of sexological screening that are considered in Italian centres of ART. METHODS: After the consensus of the Italian Society of Andrology and Sexual Medicine (SIAMS), a mailing list of reproductive medicine centres was created. Then, we sent a questionnaire concerning the essential characteristics of sexological screening. The respondents to compilers of the questionnaire sent back the information from their centres, and an analysis of absolute frequencies and percentages was performed. RESULTS: First, 16 centres completed and returned the questionnaire, while 5 ignored the invitation. The main findings concerned the wide use consideration of vardenafil 10 mg (68.7%; 11/16) for the treatment of erectile dysfunction in comorbidity with reproductive problems, the diffuse administration of International Index of Erectile Function (68.2%; 11/16) and Structured Interview for the Erectile Dysfunction (50%; 8/16) as psychometric tools and lesser use of Female Sexual Function Index (31.2%; 5/16) for the evaluation of female sexuality in the infertile couple. CONCLUSIONS: To conclude, we noticed a major focus on male sexuality and the eventual treatment or evaluation of sexual dysfunction compared to female sexuality. This aspect highlights an important issue for clinical practice to strongly consider and eventually reinforce. In this regard, improvement of the assessment and treatment of possible female sexual problems in reproductive medicine seems necessary.


Asunto(s)
Infertilidad/terapia , Técnicas Reproductivas Asistidas , Disfunciones Sexuales Fisiológicas/diagnóstico , Adulto , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico
13.
Int J Impot Res ; 27(3): 81-5, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25119586

RESUMEN

The aim of this study was to investigate attachment styles in a group of women and men with sexual dysfunction. We recruited 44 subjects (21 women and 23 men) with sexual dysfunction and 41 subjects (21 women and 20 men) with healthy sexual function as the control group. Validated instruments for the evaluation of male and female sexual dysfunctions (M/F SD) and a psychometric tool specifically designed to investigate attachment style were administered. In women, significant differences were found between subjects with sexual dysfunction and healthy controls. The scales indicating an insecure attachment showed: discomfort with closeness (FSD = 42.85 ± 11.55 vs CTRL = 37.38 ± 8.54; P < 0.01), relationship as secondary (FSD = 26.76 ± 2.60 vs CTRL = 18.42 ± 7.99; P < 0.01), and need for approval (FSD=26.38 ± 3.61 vs CTRL = 20.76 ± 7.36; P < 0.01). Healthy women also had significantly higher scores in secure attachment (confidence: FSD = 24.57 ± 3.89 vs CTRL = 33.42 ± 5.74; P < 0.01). Men with sexual dysfunctions differed from healthy men in confidence (MSD = 30 ± 6.33 vs CTRL = 36.05 ± 5.26; P < 0.01) and in discomfort with closeness (MSD = 39.08 ± 8 vs CTRL = 34.25 ± 7.54; P < 0.05). These results suggest that particular aspects related to insecure attachment have a determinant role in people with sexual dysfunctions. It is therefore fundamental to identify the attachment styles and relational patterns in patients receiving counselling and psychological treatments focussed on sexual problems.


Asunto(s)
Apego a Objetos , Disfunciones Sexuales Fisiológicas/psicología , Disfunciones Sexuales Psicológicas/psicología , Sexualidad/fisiología , Sexualidad/psicología , Adulto , Estudios de Casos y Controles , Dispareunia/fisiopatología , Dispareunia/psicología , Disfunción Eréctil/fisiopatología , Disfunción Eréctil/psicología , Femenino , Humanos , Masculino , Matrimonio , Persona de Mediana Edad , Pruebas Neuropsicológicas , Disfunciones Sexuales Fisiológicas/fisiopatología , Disfunciones Sexuales Psicológicas/fisiopatología , Factores Socioeconómicos , Encuestas y Cuestionarios , Vaginismo/fisiopatología , Vaginismo/psicología
14.
Biomed Res Int ; 2014: 909623, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24971356

RESUMEN

Different options are available as second-line treatment of metastatic castrate-resistant prostate cancer: cabazitaxel, abiraterone, and enzalutamide. Phase III studies evaluating cabazitaxel and the two hormonal agents have been shown to significantly prolong overall survival compared to mitoxantrone and placebo, respectively. Several studies have also demonstrated feasibility and activity of docetaxel rechallenge in case of a sufficient progression-free interval (3-6 months), good performance status, and previous acceptable safety profile, thus providing an additional treatment option in clinical practice. Clinical and biological parameters should be considered to tailor II line treatment. In clinical practice, we can primarily evaluate patients' fitness according to age, performance status, symptomatic disease, comorbidities, and expected safety profile of each drug. Different prognostic/predictive factors may be considered, such as presence of bone-limited or visceral metastases, length of androgen deprivation therapy (ADT) before chemotherapy, time to progression after docetaxel, Gleason score, PSA doubling time, and serum testosterone, even if their clinical relevance is still debated. This review will discuss current options of innovative drugs sequencing and selection according to bioclinical parameters.


Asunto(s)
Toma de Decisiones , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/secundario , Docetaxel , Humanos , Masculino , Pronóstico , Taxoides/administración & dosificación , Taxoides/uso terapéutico
15.
Int J Impot Res ; 26(2): 51-4, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24048013

RESUMEN

Devotism, defined as sexual attraction toward disabilities, has not undergone extensive study. To verify whether devotees have characteristics suggestive of a paraphilic behavior, an ad hoc internet questionnaire was developed to study a population of 209 subjects enrolled from online devotee communities. With respect to the sexual preference, we observe a first population comprising subjects sexually attracted by disability per se and considers it as an erotic object. In the absence of disability, this group is also unable to become sexually aroused and experiences discomfort due to their condition. The second subpopulation comprises subjects attracted by specific characteristics of people with disabilities such as adaptability, fortitude, courage and ability to overcome obstacles. This group experiences low levels of discomfort for their sexual preference. Further studies will be necessary to confirm these data.


Asunto(s)
Personas con Discapacidad , Trastornos Parafílicos/psicología , Femenino , Humanos , Internet , Masculino
16.
Int J Impot Res ; 25(3): 113-6, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23466663

RESUMEN

The aim of this study was to measure the prevalence of alexithymia and emotional dysregulation in women with vaginismus not associated with other organic or psychopathological disorders. The study involved the psychometric assessment of 41 patients with vaginismus and 100 healthy women, all of childbearing age. Alexithymia was evaluated by TAS-20 (Toronto Alexithymia Scale). Sexual function was assessed by FSFI (Female Sexual Function Index). In patients with vaginismus, the primary diagnosis of dyspareunia was excluded and an expert psychologist evaluated patients and controls according to DSM IV (Diagnostic and Statistical Manual of Mental Disorders: 4th edition) criteria to exclude mental disorders. Over half (51.1%) of the patients with vaginismus were classified as alexithymic or borderline (alexithymic trend), compared with just 18% of the control group. In addition, there was a significant difference in the TAS-20 total scores between the two groups (P<0.0001). In terms of relative risk, women suffering from vaginismus thus have a 3.8 times higher probability of showing alexithymia than do healthy women. Vaginismus is a complex syndrome and alexithymia is far from being its only characteristic. However, we found a significant correlation between vaginismus and alexithymia. In theory, alexithymia could thus be a risk factor for vaginismus, although future studies are required to demonstrate any chain of causation between these two conditions.


Asunto(s)
Síntomas Afectivos/complicaciones , Vaginismo/psicología , Adulto , Síntomas Afectivos/clasificación , Síntomas Afectivos/epidemiología , Escolaridad , Femenino , Humanos , Vaginismo/fisiopatología
17.
J Cardiovasc Transl Res ; 6(2): 221-31, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23247634

RESUMEN

Endothelium homeostasis alterations govern the pathogenesis of cardiovascular diseases. Several studies show that vitamins anti-oxidant proprieties rescue the endothelial functions adversely affected by oxidative stress in several diseases. We investigated the vitamin D anti-oxidant potential in human endothelial cells exposed to H2O2 oxidative stress. Vitamin D protected endothelial cells against H2O2 oxidative stress counteracting the superoxide anion generation, the apoptosis and blocking the extrinsic caspase cascade by positively controlling phospho-active ERKs level. MEKs/ERKs inhibitor U0126 reverted the vitamin D anti-oxidant effects. Characterizing the vitamin D downstream effector, we found that vitamin D up-regulated SirT-1 and reverted the SirT-1 down-regulation induced by H2O2. ERKs activation by vitamin D strictly correlated with SirT-1 protein accumulation since both MEKs/ERKs inhibition and ERK1/2 silencing decreased SIRT-1. SirT-1 inhibition by Sirtinol reverted the vitamin D anti-oxidant effects. Thus, vitamin D significantly reduced the endothelial malfunction and damage caused by oxidative stress, through the activation of MEKs/ERKs/SirT-1 axis.


Asunto(s)
Antioxidantes/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Quinasas Quinasa Quinasa PAM/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sirtuina 1/metabolismo , Vitamina D/farmacología , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Células Cultivadas , Citoprotección , Relación Dosis-Respuesta a Droga , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/genética , Inhibidores de Histona Desacetilasas/farmacología , Células Endoteliales de la Vena Umbilical Humana/enzimología , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Interferencia de ARN , Transducción de Señal/efectos de los fármacos , Sirtuina 1/antagonistas & inhibidores , Superóxidos/metabolismo , Factores de Tiempo , Transfección
18.
Eur Radiol ; 21(9): 2004-10, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21533865

RESUMEN

OBJECTIVES: To determine whether Radiofrequency Ablation (RFA) followed by Radiotherapy (RT) (RFA-RT) produces better palliation in terms of pain than RT alone in patients with osteolytic bone metastases. METHODS: Patients with solitary bone metastases and a pain score of least 5 or more on the VAS scale were selected. Fifteen patients were treated with RFA-RT (20 Gy delivered in 5 fractions of 4 Gy over 1 week) and were compared with a matched group (30 subjects) treated by RT. RESULTS: A complete response in terms of pain relief at 12 weeks was documented in 16.6% (5/30) and 53.3% (8/15) of the subjects treated by RT or RFA-RT, respectively (p = 0.027). The overall response rate at 12 weeks was 93.3% (14 patients) in the group treated by RFA-RT and 59.9% (18 patients) in the group treated by RT (p = 0.048). Although recurrent pain was documented more frequently after RT (26.6%) than after RFA-RT (6.7%) the difference did not reach statistical significance. The morbidity related to RT did not significantly differ when this treatment was associated with RFA. CONCLUSIONS: Our results suggest that RFA-RT is safe and more effective than RT. The findings described here should serve as a framework around which to design future clinical trials.


Asunto(s)
Neoplasias Óseas/radioterapia , Neoplasias Óseas/cirugía , Ablación por Catéter/métodos , Cuidados Paliativos , Radioterapia/métodos , Anciano , Neoplasias Óseas/mortalidad , Neoplasias Óseas/secundario , Distribución de Chi-Cuadrado , Estudios de Cohortes , Terapia Combinada , Intervalos de Confianza , Estudios de Factibilidad , Femenino , Humanos , Masculino , Osteólisis/radioterapia , Osteólisis/cirugía , Manejo del Dolor/métodos , Dimensión del Dolor , Dolor Intratable/radioterapia , Dolor Intratable/cirugía , Pronóstico , Medición de Riesgo , Estadísticas no Paramétricas , Análisis de Supervivencia
20.
Oncol Rep ; 24(5): 1383-8, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20878134

RESUMEN

The hypothesis being tested in this study is that hypofractionated radiotherapy is well tolerated and not lower in terms of oncological outcome than conventional radiotherapy. Forty patients with histologically proven glottic cancer were included in the analysis. Twenty-two were treated by hypofractionated radiotherapy (3D-HFRT) (25 fractions of 2.4 Gy delivered daily to a total dose of 60 Gy). This group was retrospectively compared to 18 subjects who met the same inclusion criteria and who were treated with conventional radiotherapy (3D-CRT) (33 fractions of 2 Gy delivered daily to a total dose of 66 Gy). One year after RT treatment in 10 patients (5 in the arm-1 and 5 in the arm-2) mild dysphonia persisted. The other patients achieved a complete recovery of the overall quality of voice with no significant difference documented between the two groups. At 3 years the local control rate was 100% for the patients treated with hypofractionated radiotherapy and 96% for the patients treated with conventional regimen. The statistical analysis did not show any significant difference in local control between the two groups (p=0.45). No significant acute and late toxicity was documented in both groups. Subjects with early glottic cancer seem to experience comparable levels of morbidity irrespective whether they were treated by hypofractionated or conventional conformal therapy without any worsening of the tumor local control. Thus, we provide clinical evidence to justify trends already emerging toward hypofractionated regimens in early glottic cancer.


Asunto(s)
Disfonía/etiología , Glotis/patología , Neoplasias Laríngeas/fisiopatología , Neoplasias Laríngeas/radioterapia , Pliegues Vocales/efectos de la radiación , Anciano , Anciano de 80 o más Años , Fraccionamiento de la Dosis de Radiación , Femenino , Glotis/efectos de la radiación , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Pliegues Vocales/fisiopatología , Calidad de la Voz/efectos de la radiación
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