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Biomedical subjects

M Sánchez-Chapado

Publications and source records attributed to M Sánchez-Chapado.

At least 19 recordsLinked to original sources
PubMed2006

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up.

Trial 24, one of three ongoing trials in the Early Prostate Cancer programme, is evaluating the efficacy and tolerability of bicalutamide (Casodex) 150 mg following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with early, non-metastatic prostate cancer. At 7 years' median follow-up, addition of bicalutamide significantly improved objective progression-free survival (PFS) for patients with locally advanced disease, reducing the risk of progression by 34% versus standard care alone (hazard ratio 0.66; 95% confidence interval 0.55, 0.79; P<0.001). In localized disease, a significant difference in objective PFS was not found. There was no significant difference in overall survival.

Anilides↗
PubMed2005

Bicalutamide ('Casodex') 150 mg in addition to standard care in patients with nonmetastatic prostate cancer: updated results from a randomised double-blind phase III study (median follow-up 5.1 y) in the early prostate cancer programme.

Trial 24 is one of three placebo-controlled trials within the ongoing bicalutamide ('Casodex') Early Prostate Cancer (EPC) programme evaluating bicalutamide 150 mg/day in addition to radical prostatectomy, radiotherapy or watchful waiting for T1b-4, any N, M0 prostate cancer. In Trial 24, at 5.1 y median follow-up, the addition of bicalutamide significantly (P < 0.0001) improved objective progression-free survival (PFS) and prostate-specific antigen PFS compared with standard care alone. There was no significant difference in overall survival (P = 0.746). In the context of the whole EPC programme, long-term bicalutamide is not appropriate for localised disease, yet provides advantages in delaying disease progression in patients with locally advanced prostate cancer.

Adult↗
PubMed2001

Bicalutamide (Casodex) 150 mg as immediate therapy in patients with localized or locally advanced prostate cancer significantly reduces the risk of disease progression.

OBJECTIVES: To investigate the efficacy and tolerability of bicalutamide (Casodex) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with localized or locally advanced (T1b-T4, any nodal status, M0) prostate cancer. METHODS: This was a multicenter, prospective, randomized, double-blind, placebo-controlled trial in Europe, South Africa, Australia, and Mexico and is part of the Casodex Early Prostate Cancer program. RESULTS: A total of 3603 men were randomized to receive bicalutamide (n = 1798) or placebo (n = 1805). The patient demographics were well balanced between the two groups. Prior therapy of curative intent had been given to 64% of the patients (prostatectomy [44%], radiotherapy [18%], and prostatectomy and radiotherapy [2%]) and 36% had been monitored with watchful waiting. After a median follow-up of 2.6 years and a median exposure to the study drug of 2.2 years, a significant 43% reduction in the risk of objective progression was observed for the bicalutamide group compared with the placebo group (hazard ratio 0.57, 95% confidence interval 0.48 to 0.69, P << 0.0001). The time to prostate-specific antigen doubling was significantly delayed for the bicalutamide group compared with the placebo group (hazard ratio 0.37, 95% confidence interval 0.32 to 0.43, P << 0.001). The survival data were immature, with 7.2% overall mortality. The most frequently reported adverse events with bicalutamide were gynecomastia alone (17.4%), breast pain alone (17.6%), and gynecomastia with breast pain (47.5%). CONCLUSIONS: Bicalutamide 150 mg daily as immediate therapy, alone or as adjuvant to treatment of curative intent, significantly reduced the risk of disease progression in patients with localized or locally advanced prostate cancer. Longer follow-up is underway to assess any benefit in overall survival.

Adult↗
PubMed2001

Effects of the luteinising hormone-releasing hormone (LH-RH) agonist leuprolide on adenylyl cyclase regulation through G-protein coupled receptors in rat ventral prostate.

Luteinising hormone-releasing hormone (LH-RH) agonists are widely used for the therapy of advanced prostate cancer through the suppression of testosterone secretion. Furthermore, recent studies indicate the existence of prostate LH-RH receptors coupled to signalling pathways resulting in direct antiproliferative effects. In order to shed light on the mechanisms through which these compounds inhibit prostate cell growth, we investigated the effects of leuprolide (a LH-RH agonist) treatment of rats compared with the effects of surgical castration on the behaviour of G-protein coupled receptors acting through adenylyl cyclase in the ventral prostate. Important decreases of both plasma testosterone levels and ventral prostate weight were observed 5 weeks after subcutaneous (s.c.) injection of a leuprolide-depot preparation (1.5 mg/kg body weight (b.w.)) or 5 days after bilateral gonadectomy. However, leuprolide treatment increased the number of vasoactive intestinal peptide (VIP) receptors and the ability of this neuropeptide to stimulate adenylyl cyclase activity in prostate membranes, whereas surgical castration decreased both parameters. Moreover, leuprolide resulted in significant increases of prostate alpha(s) and alpha(i1-3) (but not alpha(i1) and beta) G-protein levels, while the four G-protein subunits were overexpressed after gonadectomy. The estimation of alpha(s) and alpha(i) activity by experiments with Gpp[NH]p and forskolin indicated a potentiation of the two arms of adenylyl cyclase regulation in leuprolide-treated rats. Present observations suggest that leuprolide treatment leads to an antimitogenic response by acting mainly through the activation of Gi proteins negatively coupled to adenylyl cyclase.

Adenylyl Cyclases↗
PubMed2001

Morphometric evaluation of the human prostate.

In order to clarify the ageing-related histological changes in the human prostate, a quantitative morphometric analysis was performed. Complete prostates were obtained at autopsy from 281 men (aged 20-84 years) who died in traffic accidents and presented no clinical symptoms of prostatic disease. The prostates were classified as: histologically normal (n=182), with nodular hyperplasia (n=42), with intraepithelial neoplasia (n=40) and carcinomatous with low Gleason grade (n=20). Each prostate was divided into three regions (periurethral, central and peripheral) and the volume of each region, as well as the average volume occupied by stroma and epithelium in each region were quantified. For each parameter, the average values for each age group were compared. In the histologically normal prostates, an increase with ageing in the total volume and the volume occupied by the central region were observed; these increases were mainly caused by an increase in the stromal volume of the central region in men after 30 years of age. No histologically normal prostates were found in men older than 70 years of age. Nodular prostatic hyperplasia was found in men over 30 years of age and a fluctuation in the total volume throughout ageing was observed. Prostates with intraepithelial neoplasia (PIN) and carcinoma were observed in men aged >20 years and the total volume and those of each prostatic region showed multiple variations, except for the eighth decade where a marked increase with regard to that of the previous decades was observed.

Adult↗
PubMed2001

Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate.

Two different estrogen receptors (ER-alpha and ER-beta) have been described, which are differentially involved in regulating the normal function of reproductive tissues. ER-alpha was considered for a long time to be the only estrogen receptor, and it has been detected in the stromal cells of the human prostate but not in the epithelium. To obtain new information about the differential effects of both receptor types, we have investigated their localization in normal prostates, benign prostatic hyperplasia (BPH), and prostatic cancer (PC) by immunohistochemistry, ELISA and Western blot. Epithelial immunostaining was absent in normal prostates and was present in BPH (10% of cells) and PC (80% of cells), whereas about 15% of stromal cells were positively immunostained for ER-alpha in the three types of prostatic specimens studied. Epithelial immunostaining for ER-beta was detected in normal prostates (13% of cells), BPH (30% of cells) and PC (79% of cells), whereas stromal immunostaining for ER-beta was absent in normal and hyperplastic prostates and was present in PC (12% of cells). The complementary presence of both receptor types in the normal prostate (ER-beta in the epithelium and ER-alpha in the stroma) might explain the mechanism of estrogen action in the development of BPH. The increased epithelial immunostaining for both ER-alpha and ER-beta in BPH and PC suggests that the involvement of estrogen receptors in hyperplasia and cancer concerns mainly the epithelium.

Adult↗
PubMed2001

Low expression of Galpha protein subunits in human prostate cancer.

PURPOSE: Because of increasing interest in G protein regulation of cell growth, differentiation and oncogenesis, we studied the functionality and expression of different G protein subunits in human prostate adenocarcinoma. MATERIALS AND METHODS: Surgical prostate specimens from control patients with bladder cancer and patients with prostate cancer were used. The functionality of alphas and alphai G protein subunits was evaluated by studying somatostatin or guanyl-5'-yl-imidotriphosphate regulation of forskolin stimulated adenylyl cyclase activity. The expression of alphas, alphai and beta subunits was studied by reverse transcriptase-polymerase chain reaction and immunoblot analysis. RESULTS: Adenylyl cyclase sensitivity to somatostatin inhibition decreased in prostate cancer. Low guanyl-5'-yl-imidotriphosphate doses inhibited forskolin stimulated adenylyl cyclase, whereas the opposite was true at high concentrations, evidencing the functionality of alphai and alphas, respectively, in normal and cancer tissue samples. Reverse transcriptase-polymerase chain reaction revealed RNA encoding for alphas and alphai1,2,3 subclasses in normal and pathological conditions. However, immunoblot analysis showed that the level of beta subunits was maintained, whereas that of alphas and alphai subunits decreased 30% to 40% after neoplastic transformation. The levels of alphas and alphai1,2 subunits correlated inversely with serum prostate specific antigen in patients with prostate cancer. CONCLUSIONS: The functionality and expression of G protein subunits are selectively modified in human prostate adenocarcinoma. Low alphas and alphai levels in prostate cancer suggest an important regulatory role of G proteins for cell proliferation and neoplastic transformation in the human prostate and they may have prognostic value.

Adenocarcinoma↗
PubMed2000

Effect of flutamide-induced androgen-receptor blockade on adenylate cyclase activation through G-protein coupled receptors in rat prostate.

The effect of the antiandrogen flutamide on the prostatic vasoactive intestinal peptide (VIP) receptor/effector system was studied in rats. Rats were s.c. injected with a daily dose of flutamide (15 mg/kg B.W.) or vehicle for 14 days. Drug treatment resulted in histological evidence of gland involution and increased plasma membrane fluidity as estimated by fluorescence spectroscopy. The number of VIP receptors and the stimulatory effect of VIP on adenylate cyclase activity in prostatic membranes decreased in flutamide-treated rats. However, the pattern of forskolin stimulation of the enzyme activity was not modified by this drug. Androgen-receptor blockade by flutamide also decreased the prostatic levels of alpha(s,) alpha(i1/2), and alpha(i3/0) G-protein subunits, as estimated by an immunological procedure. Whereas apoptotic DNA fragmentation was evidenced in prostate from 3-day castrated animals, a heterogeneous electrophoretic pattern was observed after flutamide treatment. Thus, androgen-receptor blockade by flutamide results in an important impairment of the components of the VIP receptor/effector system in rat prostate as well as in a modification of their coupling extent, which is presumably due to differences observed in plasma membrane fluidity. These results represent a crosstalk in the prostate between two mechanisms of signal transduction involved in cell proliferation.

Adenylyl Cyclases↗
PubMed2000

The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: To assess the effect of the age of patients with benign prostatic hyperplasia (BPH) on the clinical uroselectivity of alfuzosin during general medical practice. PATIENTS AND METHODS: The present national, multicentre, open-labelled, observational study involved 4018 Spanish outpatients with BPH, i.e. showing lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction. The patients received sustained release (SR) alfuzosin, 5 mg twice daily, for 2 months. The primary efficacy criteria were symptomatic improvements, as assessed by the International Prostate Symptom Score (IPSS) and quality of life (QoL) index. Safety was assessed by monitoring cardiovascular data and adverse events. RESULTS: The patients were divided into four age groups, i.e. < 56, 56-65, 66-75 and > 75 years. All groups of patients showed a mean IPSS decrease of 11-12 (55.8-65.4% from baseline) at the end of the study, while the QoL decreased by 2-3 points (55.6-63.6% from baseline). There were no relevant effects of age on the efficacy of the treatment. Moreover, alfuzosin was well tolerated independently of the age of the patient; 1.2% of the patients enrolled withdrew because of adverse events. The qualitative distribution of vasodilatory/nonvasodilatory adverse events was similar in all age groups. The incidence of asymptomatic orthostatic hypotension was low (0.58%) and not affected by the age of the patients. CONCLUSION: This study confirms that the clinical uro-selectivity of SR-alfuzosin, already described in ran-domized controlled studies, is not significantly affected in clinical practice by the age of the patients. This is considered particularly relevant to the characteristics of patients with BPH, as they are mostly elderly men.

Adrenergic alpha-Antagonists↗
PubMed2000

Safety and efficacy of sustained-release alfuzosin on lower urinary tract symptoms suggestive of benign prostatic hyperplasia in 3,095 Spanish patients evaluated during general practice.

OBJECTIVES: This general practitioner-run study assess the security as well as the efficacy and impact on health-related quality of life of a sustained-release (SR) form of alfuzosin in Spanish patients suffering from lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: 3,095 patients with symptomatic BPH were enrolled into a national, multicentric, open, phase IV observational study. The period of active treatment studied (5 mg, twice daily) was 60 days. Safety was assessed by monitoring blood pressure and spontaneous adverse events. Symptoms were assessed using a validated Spanish International Prostate Symptom Score (I-PSS). Impact of symptoms on health-related quality of life was assessed using the quality of life index (L). RESULTS: 101 adverse events were reported in 82 patients (2.6%). 28 adverse events (2.6%) were classified as severe. 49 patients (1.6%) dropped out of the study due to adverse events but only 17 of these patients (0.5%) showed adverse events related to vasodilation. Incidence of postural events (vertigo, postural hypotension/hypotension, headache and dizziness) was low (55 patients, 1.8%) and effects on sexual function were found not significant: no retrograde ejaculation was reported and only 1 patient (0.03%) showed impotence. Blood pressure or heart rate showed no clinically significant changes. All the I-PSS scores decreased significantly during the treatment with alfuzosin, improvement being excellent in 60% of the patients. Symptomatic improvement was associated with a significant improvement in health-related quality of life. CONCLUSIONS: This large study conducted during general practice on Spanish BPH patients confirms the efficacy on LUTS and good safety profile of SR alfuzosin, especially its low incidence of postural symptoms and no deleterious effect on sexual function.

Adrenergic alpha-Antagonists↗
PubMed1999

In vivo proton magnetic resonance spectroscopy of diseased prostate: spectroscopic features of malignant versus benign pathology.

In vivo Proton Magnetic Resonance Spectroscopy appears potentially useful for non-invasive discrimination between benign prostatic hyperplasia (BPH) and prostate carcinoma (PC). Aiming to delimit the range within which spectra from one or the other pathology should occur, and establish extreme spectroscopic features of malignant versus benign prostate disease, we performed endorectal proton MR spectroscopy on 20 patients severely affected of either benign prostatic hyperplasia (BPH) (n = 10) or prostate cancer (PC) (n = 10). They were selected on the basis of the large volume and homogeneity of their lesions, which were histologically confirmed after spectroscopy. Consequently, high-quality short-TE proton spectra with well-resolved metabolite signals, and practically free of volume averaging issues were obtained in all cases. Apart from the typical citrate, creatine, and choline signals of prostate spectra, both BPH and PC spectra showed a peak centered at 3.6 ppm which was assigned to myo-inositol. The intensity of this contribution was found significantly increased in PC cases compared to BPH. Possible relationships between neoplastic transformation and the metabolic pathways in which myo-inositol participates are discussed. Average spectroscopic profiles were calculated for both advanced pathologies, and showed obvious differentiated features. In quantitative terms, the ratio of citrate to choline peak areas as well as that of creatine to myo-inositol appeared as the most convenient to discriminate between advanced PC cases (both ratios below 1.0) and advanced BPH cases (both ratios above 1.0).

Aged↗
PubMed1999

Identification and functional properties of the pituitary adenylate cyclase activating peptide (PAC1) receptor in human benign hyperplastic prostate.

Pituitary adenylate cyclase activating peptide (PACAP) is a novel neuropeptide with regulatory and trophic functions that is related to vasoactive intestinal peptide (VIP). Here we investigate the expression of specific PACAP receptors (PAC1) and common VIP/PACAP receptors (VPAC1 and VPAC2) in the human hyperplastic prostate by immunological methods. The PAC1 receptor corresponded to a 60-KDa protein whereas the already known VPAC1 and VPAC2 receptors possessed molecular masses of 58 and 68 KDa, respectively. The heterogeneity of VIP/PACAP receptors in this tissue was confirmed by radioligand binding studies using [125I]PACAP-27 by means of stoichiometric and pharmacological experiments. At least two classes of PACAP binding sites showing different affinities could be resolved, with Kd values of 0.81 and 51.4 nM, respectively. The order of potency in displacing [125I]PACAP-27 binding was PACAP-27 approximately equal to PACAP-38 > VIP. PACAP-27 and VIP stimulated similarly adenylate cyclase activity, presumably through common VIP/PACAP receptors. The PAC1 receptor was not coupled to activation of either adenylate cyclase, nitric oxide synthase, or phospholipase C. It appears to be a novel subtype of PAC1 receptor because PACAP-27 (but not PACAP-38 or VIP) led to increased phosphoinositide synthesis, an interesting feature because phosphoinositides are involved via receptor mechanisms in the regulation of cell proliferation.

Aged↗
PubMed1999

A lectin histochemistry comparative study in human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma.

The partial oligosaccharide sequences of glycoconjugates and the nature of their glycosidic linkages were investigated in normal human prostate, benign prostatic hyperplasia (BPH) and prostatic carcinoma by means of lectin histochemistry, using light microscopy and Western blot analysis. The labeling pattern of BPH differed from that of normal prostate in having more intense staining with DSA, HPA, UEA-I and AAA, and in showing lesser staining with WGA and SBA. Prostatic carcinoma differed from normal prostates in displaying the more intense labeling with PNA, DSA, SBA, DBA, UEA-I and AAA, and in having lesser labeling with WGA. The main differences in labeling pattern between prostatic carcinoma and BPH were that the latter specimens showed more marked staining with PNA, DSA, DBA, SBA, UEA-I and AAA, and lesser staining with WGA and HPA. The staining patterns of SNA, MAA, ConA, LCA and GNA were similar in all three groups of specimens. For most of the lectins studied, including those showing a similar immunohistochemical staining in the three groups of specimens studied, the Western blot analysis showed differences in the banding pattern among normal, hyperplastic, and carcinomatous prostates. Present results suggest that the glycosylation of proteins was modified in both BPH and prostatic carcinoma. In BPH a strong expression of N-acetylgalactosamine residues occurred, while in prostatic carcinoma an increase of sialic acid, galactose and fucose residues was observed. No changes in mannose residues were detected.

Adult↗
PubMed1998

[Electric stimulation of sacral roots for the treatment of urinary incontinence due to detrusor instability: application of a technique and results in a clinical case].

OBJECTIVE: To describe a case treated with a new technique in our therapeutic algorithm for non-neurogenic vesicourethral dysfunction. METHODS/RESULTS: A 47-year-old female underwent retropubic urethropexy for stress urinary incontinence. She remained incontinent due to detrusor instability to a degree that was socially unacceptable. After conservative treatment had failed, a percutaneous electrode was applied to the sacral nerve root and she received electrical stimulation of 4-6 milliamperes, 15 Hz and 200 microseconds duration for 7 days. Incontinence remitted for as long as 3 months after the electrode had been removed. CONCLUSION: The results achieved with sacral nerve electrical stimulation reported in the literature and our results support the use of this technique in urological clinical practice.

Electric Stimulation Therapy↗
PubMed1998

[Comparison among patients considered candidates for radical prostatectomy in academic institutes in different countries].

OBJECTIVE: Radical prostatectomy is performed in potentially curable prostatic cancers, but surgical indication might somehow depend on the idiosyncrasies of a population. Herein we compare the characteristics of patients undergoing radical prostatectomy in teaching University Hospitals of different countries. METHODS: We conducted a retrospective review on 250 consecutive patients who underwent radical prostatectomy before January 1997 in five teaching University Hospitals in Europe (Spain, Sweden, Switzerland, Turkey) and the United States (Detroit, MI). Clinicopathological data were recorded and compared, and a questionnaire investigated whether patient and physician attitudes towards surgery differed. RESULTS: The number of surgeries per month at each institution ranged from 0.9 to 10 and the proportion of newly diagnosed patients that undergo surgery from 0.14 to 0.36. The Kruskal-Wallis test revealed both median age and preoperative prostate-specific antigen (PSA) levels were different between groups. Similarly, despite standardized surgery and histologic work-up, differences in the detection of extracapsular invasion and the rate of detectable PSA after surgery were observed between institutions. Diagnosis in the Swedish and Swiss groups was more often based on digital rectal examination, while the rest were more confident with transrectal ultrasound. Doctors at some institutions were more inclined to recommend radical surgery, either by not mentioning or disapproving other therapeutic strategies. The proportion of patients who said they would elect surgery again ranged from 72% to 92%, and the proportion of doctors who said they would perform surgery again ranged from 78% to 100%. Patients' and doctors' degree of satisfaction with the decision made were also different. CONCLUSIONS: (i) Candidates for radical prostatectomy in teaching hospitals of several countries are different. Might therefore have practical implications on the design of clinical trials and the interpretation of the results of treatment. (ii) Patient and physician acceptance of surgery varies according to countries and is more established firm in those countries where it is more frequently performed.

Adult↗
PubMed1997

[Upper urinary tract and urethral tumors in patients with bladder carcinoma].

OBJECTIVE: A clinicopathological study was conducted in patients with urothelial tumor of the bladder and urothelial neoplasm of the upper urinary tract or urethra to analyze the histological features, time interval between diagnoses and prognosis of these associated lesions. METHODS: 338 patients were reviewed retrospectively. A descriptive study was performed, including tables on the associated lesions and survival data. RESULTS: 21 cases (6.2%) had two urothelial tumors: carcinoma of the bladder associated with tumor of the upper urinary tract (14 cases) or urethra (7 cases). There is a longer time interval between diagnoses when the extravesical tumor is diagnosed after than when it is diagnosed before the bladder tumor (p < .05). A correlation between the grade, but not stage, of the extravescial and bladder tumors has been observed. We found no statistically significant differences for survival in patients with two tumors or with bladder cancer alone. Although not statistically significant, patients with metachronous extravescial tumor have a better prognosis than those with synchronous extravesical tumor. CONCLUSION: Patients with bladder cancer should be followed for years and screened for extravesical urothelial tumor. The foregoing associated lesion, especially the metachronous extravesical lesion, apparently does not make the prognosis worse.

Adult↗