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Biomedical subjects

F Di Silverio

Publications and source records attributed to F Di Silverio.

At least 127 records · Page 7Linked to original sources

Hormonal pattern in prostatic carcinoma following orchidectomy: 5-year follow-up.

Clinical and hormonal findings have been collected from 14 patients affected by carcinoma of the prostate observed over a 5-year period following orchidectomy. Plasma testosterone decreased significantly after surgery (62 ng +/- 21 SD/100 ml), remaining below 100 ng/100 ml even in cases showing only a partial regression or increase of the tumour. Gonadotropin FSH increased 1 year after orchidectomy to 28 mIU +/- 5/ml and remained constantly elevated up to the 5th year, whilst LH increased progressively up to the 5th year (30 mIU +/- 12/ml). Finally, plasma cortisol increased progressively up to 23.2 microng +/- 17.4/100 ml at the 5th year post-orchidectomy, especially in those cases showing partial regression or increase of the tumoral mass, indicating an adrenal hyperfunction which is probably responsible for increased production of weak androgens that can be transformed in the prostate into more active compounds. These results suggest therefore that after orchidectomy, cortisol and adrenal androgen determination may be of value in detecting the potential activation of prostatic adenocarcinoma.

Adenocarcinoma↗

Biosynthesis and metabolism of androgenic hormones in cancer of the prostate.

The conversion of dehydroepiandrosterone sulfate into testosterone, delta4-androstenedione, and dihydrotestosterone has been measured in minced prostatic adenocarcinoma tissue from three untreated patients, two patients treated with diethylstilbestrol, and one treated with cyproterone acetate. The results obtained show that in both treated and untreated patients the dehydroepiandrosterone sulfate is actively transformed into dehydroepiandrosterone. The subsequent conversion into testosterone and dihydrotestosterone is less evident and inconstant in untreated patients and is inhibited in patients treated with diethylstilbestrol or cyproterone acetate. No formation of delta4-androstenedione was demonstrated in either treated or untreated patients.

Adenocarcinoma↗

Insulin-like growth factor-I and -II in human benign prostatic hyperplasia: relationship with binding proteins 2 and 3 and androgens.

In prostatic tissue, androgen action may be mediated by growth factors such as insulin-like growth factor-I (IGF-I) and II (IGF-II), which are mitogenic for prostatic cells and modulate the stroma-epithelium interaction. IGF-binding proteins (IGFBPs) have an autocrine and/or paracrine role in regulating the local actions of the IGFs. In this study, testosterone, dihydrotestosterone (DHT), 3 alpha androstanediol (3 alpha diol), IGF-I, IGF-II, IGFBP2, and IGFBP3 concentrations were evaluated in human benign prostatic hyperplasia (BPH) tissue. Samples of prostate tissue were removed by suprapubic prostatectomy from twelve BPH patients. Androgen tissue levels were determined by radioimmunoassay after purification on celite microcolumns. IGF-I, IGFBP2, and IGFBP3 were measured by radioimmunoassay, and IGF-II by immunoradio metric assay, after acidification and chromatography on Sep-pak C18 Cartridges for IGF-I and IGF-II. Androgen concentrations, expressed in ng/g tissue (mean +/- SE), were 0.51 +/- 0.05 for testosterone, 5.3 +/- 0.16 for DHT, and 1.1 +/- 0.07 for 3 alpha diol. IGF-I, IGF-II, IGFBP2, and IGFBP3 levels were 24 +/- 3.7, 121 +/- 14 ng/g tissue and 0.44 +/- 0.05 and 1.2 +/- 0.17 micrograms/g tissue, respectively. No correlation between IGF-I, androgens, and IGFBPs was found. IGF-II was positively correlated with DHT (r = 0.78; p = 0.003) and 3 alpha diol (r = 0.66; p = 0.021) but not with IGFBPs. These data suggest that in BPH, DHT modulates the IGF system by increasing IGF-II without modifying IGFBPs. Therefore, the stroma-epithelium interaction, which plays an important role in prostatic growth, may be regulated by DHT through IGF-II.

Aged↗

Variation of chromogranin A serum levels after radical retropubic prostatectomy for prostate adenocarcinoma.

This study evaluated perioperative and postoperative variations in serum CgA levels induced by radical retropubic prostatectomy (RRP) and their relationship with serum PSA levels in prostate cancer patients. Thirty consecutive patients with clinically localized adenocarcinoma of the prostate undergoing RRP were prospectively analyzed. Serum levels of CgA and total PSA were analyzed in each case preoperatively (time 0), at removal of the prostate (time 1), 1 h after the end of RRP (time 2) and then at regular postoperative intervals till 12 weeks (time 14). During the postoperative period no adjuvant therapies were performed and none of the 30 cases showed biochemical (PSA > 0.2 ng/mL) and/or clinical progression. Mean preoperative serum levels of CgA were 57 +/- 14 ng/mL. Immediately after the surgical removal of the prostate gland (time 1), in all 30 cases there was a significant (time 0-time 1: p = .001) increase in serum PSA, but a nonsignificant modification in serum CgA levels (60 +/- 15 ng/mL). After time 1, serum PSA levels progressively decreased to below the detection limit of 0.2 ng/mL. On the contrary, at time 2, serum CgA levels were postoperatively increased (time 2 = 145 +/- 47) and they remained significantly higher than preoperative values (time 0) till the 21-day postoperative interval (time 11). Moreover, at the last control (time 14) mean and median CgA levels were very similar to those shown preoperatively (time 14: 58 +/- 18 ng/mL). In patients with untreated clinically localized adenocarcinoma of the prostate submitted to RRP, surgical and postoperative stress, more than surgical manipulation of the prostate gland, could produce a significant increase in serum CgA levels maintained for a longer period when compared to the increase in serum PSA levels.

Adenocarcinoma↗

Prostate--specific G protein couple receptor genes and STAG1/PMEPA1 in peripheral blood from patients with prostatic cancer.

We investigated whether prostate - specific G protein couple receptor genes and STAG1/PMEPA1 gene expression in peripheral- blood could be useful as a diagnostic or prognostic marker of prostate cancer. Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect PSGR and STAG1/PMEPA1 mRNA in peripheral blood (PB) from 11 patients with treated prostate cancer (CaP), 11 with newly-diagnosed untreated CaP and 20 with benign prostatic hyperplasia (BPH) (controls). RT-PCR amplified PSGR in 8 of 11 untreated and in 9 of 11 treated patients with CaP and in 16 of 20 with BPH; whereas it amplified PMEPA1 in 1 of 11 untreated and in 7 of 11 treated patients with CaP and in 4 of 20 with BPH. In our control tissues and cell lines nearly all the prostatic and non- prostatic tissues and cell lines expressed PSGR mRNA, whereas only one prostatic neoplastic tissue and the androgen-responsive (LNCaP) and androgen non-responsive (PC3) prostatic cell lines expressed PMEPA1. These findings suggest that the investigated genes are poorly specific and probably of little use as diagnostic or prognostic markers in peripheral blood for monitoring prostate cancer progression and recurrence.

Base Sequence↗

Effects of triptorelin, a gonadotropin-releasing hormone agonist, on the human prostatic cell lines PC3 and LNCaP.

Some analogues of gonadotropin-releasing hormone (GnRH) influence the in vitro proliferation of cultured human cells by complex interactions that are only partially understood. This study explored the effect of Triptorelin, a GnRH agonist, on the LNCaP and PC3 prostatic cell lines, which are, respectively, responsive and unresponsive to androgen stimulation. The toxicity and cell cycle modifications induced by the drug were investigated by FACScan analysis; the effect on cell proliferation in different culture conditions was determined by counting in a Burker chamber; and the expression of binding sites for 125I-Triptorelin was revealed by displacement experiments. PC3 cell growth was completely unaffected by Triptorelin. The drug caused a double stimulatory-inhibitory action on the growth of actively proliferating LNCaP cells, depending upon the dose and environment. A significant inhibitory effect on proliferation, ranging from 25% to 65% compared with controls, was observed at a high dose (10(-4) M) according to the culture conditions; and a proliferative effect (42% compared with controls) was observed at a lower dose (10(-7) M) only in fetal bovine serum-supplemented medium. Displacement experiments revealed the expression of moderately high affinity and low affinity binding sites in LNCaP cells (Kd = 2.6 x 10(-8) and 7.7 x 10(-6) M) but only low affinity binding sites in PC3 cells (Kd = 2.7 x 10(-6) M), which suggests that the expression of binding sites with different affinity could be associated with a biological response to the drug. Proliferation studies in the presence of Cetrorelix, a GnRH antagonist, confirmed the different sensitivity of the 2 cell lines to GnRH analogues and showed that the proliferative effect of Triptorelin on LNCaP cells can be inhibited by the antagonist. Data confirm the cell specificity of Triptorelin's action and the peculiarity of its effects on prostatic cell proliferation in our experimental conditions.

Cell Cycle↗

Heat shock protein-90, IL-6 and IL-10 in bladder cancer.

The progression of transitional-cell carcinomas of the bladder is associated with changes in general and local immune status. To understand the factors involved in the progression of transitional cell carcinoma and in the maintenance of an efficient anti-tumoural response, in this study we investigated by immunohistochemistry expression of HSP-90, IL-6 and IL-10 proteins in 56 surgical specimens obtained from superficial and deeply invasive bladder carcinomas. Of the 56 bladder carcinoma 52 (92.9%) expressed HSP-90, 48 (85.7%) IL-6 and 45 (80.3%) IL-10. High-grade and muscle-invasive tumours contained significantly higher levels of HSP-90 and IL-6 antibodies than low-grade and superficial tumours (p < 0.05). Linear regression showed a significant correlation between HSP-90 and IL-10 (p = 0.022) but not between HSP-90 and IL-6, or IL-6 and IL-10 expression. The variable quantities of HSP-90, IL-6 and IL-10 in the high-grade bladder carcinomas studied suggest that these proteins have independent functional roles and may be the immunogenic targets for an anti-tumoural response.

Aged↗