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Biomedical subjects

M Pavone-Macaluso

Publications and source records attributed to M Pavone-Macaluso.

At least 19 recordsLinked to original sources

Soluble and nuclear type I and II androgen-binding sites in benign hyperplasia and cancer of the human prostate.

This paper presents an approach for the assessment of the androgen receptor (AR) status in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues. Evaluation of AR was carried out in both soluble and nuclear fractions by a standard competition method, using tritiated mibolerone as radioligand. Based on our experience with breast and endometrial cancer, this approach focused on both type I (high affinity, low capacity) and type II (reduced affinity, higher capacity) binding sites, aiming mainly at establishing a putative "functional" receptor mechanism, i.e., the presence of type I AR in both cytosol and nucleus. Ancillary studies were carried out to exclude a potential overestimation of the AR content by interference with other steroid receptors, namely, progesterone (PgR) or glucocorticoid (GcR) receptors. Results showed that the interaction by PgR or GcR upon AR measurement was not relevant. The distribution of AR, namely the percent of positivity either in a single or in both cell compartments, was not significantly different in BPH (N = 32) or PCa (N = 24) tissues. For type I binding, the percent of positivity in both soluble and nuclear fractions (i.e., the "functional" AR status) was very close to that observed for other endocrine-related tumors, like breast cancer. Concentrations of type I AR appeared significantly higher in PCa than in BPH tissues; this was true for both soluble and nuclear fractions. In contrast, no significant difference was found in type II AR concentrations in either cell fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

The flexible cystoscope.

We have been using the flexible cystoscope since 1987. Detailed information is given concerning the technique of flexible cystoscopy, its indications, advantages and disadvantages. A comparison is made with the results obtained using the rigid cystoscope in an initial series of 100 patients, yielding false negative results in only 8% of cases during the learning period. The flexible scope can be successfully employed for Neodymium YAG laser coagulation of superficial bladder tumours. The conclusion is reached that once the urologist has learned how to use it, he will consider the flexible cystoscope as a fundamental tool in his diagnostic armamentarium and false negative results will decrease almost to zero, especially if additional investigations, namely cytology, are routinely adopted.

Cystoscopes

A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response.

From 1986 to 1990 the European Organization for Research and Treatment of Cancer--Genitourinary Group conducted a phase 2 trial of neoadjuvant chemotherapy in patients with stage T3-4N0-XM0 transitional cell carcinoma of the bladder. The objectives were to evaluate the clinical response in relation to the pathological response, and to measure the side effects of chemotherapy. Of 171 patients entered 136 were fully evaluable: 18% had clinical complete remissions, 36% had clinical partial remissions, 39% had no clinical remissions and 10% had unknown response. A selected subgroup of 76 patients underwent cystectomy after 2 or 4 courses of chemotherapy: 2 were not evaluable for pathological response because of preoperative radiotherapy after neoadjuvant chemotherapy, 16 had a pathological complete remission, 7 had a pathological partial remission and 51 had no pathological remission. Comparison of the clinical response or T category only after 2 courses of chemotherapy with the pathological response after 2 or 4 courses of chemotherapy showed that in a number of patients the disease status could be downstaged to pathological complete or partial remission by additional courses of chemotherapy. If the discrepancies between clinical and pathological responses, or between T and P categories, induced by further downstaging after additional chemotherapy were left out, it was shown that clinical complete and partial remissions were a heterogeneous group but nonresponders could be delineated with a 100% accuracy by clinical response evaluation and transurethral resection biopsy only. Furthermore it seems important to establish the number of chemotherapy courses to induce a maximal response of the primary tumor.

Adult

A pilot study comparing different dose levels and administration schedules of interferon-alpha 2b combined with epirubicin for prevention of recurrence in bladder cancer.

A pilot study in 62 patients has been carried out to evaluate the combination of epirubicin and interferon (IFN)-alpha 2b using different doses and schedules of intravesical administration in the prevention of recurrence of bladder cancer. Preliminary results show greater prophylactic efficacy not only when higher doses of epirubicin and IFN-alpha 2b are used but also when a larger interval between instillation of the compounds was used.

Administration, Intravesical

Intravesical therapy of superficial bladder transitional cell carcinoma with tumor necrosis factor-alpha: preliminary report of a phase I-II study.

A phase I-II trial of intravesical immunotherapy with tumor necrosis factor (TNF)-alpha in 24 patients affected by superficial bladder tumors is herein presented. Of these, 11 patients were submitted, at weekly intervals, after complete TUR, to 8 instillations of TNF-alpha at increasing doses from 50 to 600 micrograms. Tolerability was excellent, even at the highest dose. In a second group of 13 patients with a histologically proved papillary marker lesion, TNF-alpha was instilled at weekly intervals at the dose of 500 micrograms for 8 weeks. Three complete responses (23%) were obtained.

Administration, Intravesical

Study of cellular DNA content by flow cytometry in primary bladder carcinomas. Significance of monoclonal and multiclonal varieties of DNA aneuploidy.

A prospective study of cellular DNA content by flow cytometry was performed on a nonconsecutive series of 67 patients undergoing diagnostic and/or therapeutic transurethral resection for primary urothelial bladder carcinoma. DNA-aneuploidy was present in 82% of the cases (55/67), while multiclonality was found in 45% of the DNA-aneuploid cases (25/55). DNA-ploidy was much more strictly correlated with histological grading (p less than 0.005) than with papillary or non-papillary growth pattern (p less than 0.05) or T staging (p less than 0.05). Of 26 patients with a minimum follow-up of 24 months, 100% (6/6) of cases with DNA-diploid neoplasias showed no signs of disease relapse, versus 10% (2/20) of those with DNA-aneuploid neoplasias (p less than 0.001). Furthermore, tumoral progression occurred in 10 of 20 cases (50%) with aneuploid DNA content. In this latter group of 10 cases a multiclonal DNA-aneuploid pattern was found, with a significant difference (p less than 0.001).

Aged

[Current therapies of benign prostatic hypertrophy. Can the new medical treatments replace endoscopic resection?].

There has been a renewed interest in benign prostatic hypertrophy over the last two years due to the development of new therapeutic modalities. A recent consensus conference was organized by the World Health Organization (WHO) in Paris in July 1991, at which conventional treatment by transurethral resection was compared with new methods. An updated review is made of the basic concepts concerning BPH and the indications, technique and results of the various treatments: drug treatment by alpha-blockers, hormones, other instrumental treatments: cryotherapy, bladder neck incision, metal stent, hyperthermia. Transurethral resection will be studied in detail: technique, results. The respective indications for these various modalities are discussed.

Adrenergic alpha-Antagonists

The role of epipodophyllotoxin derivatives in bladder cancer.

Past and present experiences with podophyllin derivatives in bladder cancer are described. A preliminary study of teniposide was conducted in 1975 at the Institute of Urology, University of Palermo, in patients with advanced or superficial bladder cancer. In 18 patients with advanced bladder cancer, teniposide was administered intravenously (IV), followed in seven patients by peptichemio or doxorubicin. One complete response (CR) and four partial responses (PRs) were achieved. In 24 patients with superficial tumors, teniposide at a dose of 50 mg dissolved in 30 mL normal saline was administered intravesically as ablative therapy or as prophylaxis following transurethral resection (TUR). Of 12 patients in the ablative therapy group, two CRs and two PRs were achieved. Only 2 patients of 12 in the prophylaxis group relapsed within 6 months. In five cases, teniposide was administered in combination with peptichemio. In recent years, the Urological Group of the European Organization for the Research and Treatment of Cancer (EORTC) has performed a phase II study in which teniposide was used in combination with cisplatin given IV in the treatment of advanced bladder cancer. The EORTC group has also performed a randomized study to compare intravesical teniposide versus thiotepa versus no treatment other than initial resection. A brief report on both studies is given. In December 1987, a study was initiated to evaluate intravesical etoposide use in the prophylaxis of recurrences of superficial transitional cell carcinoma of the bladder. Intravesical etoposide (200 mg dissolved in 50 mL saline solution) was administered at weekly intervals for the first month after TUR and then monthly for 11 months. Of 38 evaluable patients, 20 had recurrences at a mean follow-up of 14 months. No systemic toxicity was noted.

Combined Modality Therapy

[Concentration of aztreonam in plasma, urine, and seminal fluid of patients with chronic prostatitis].

The authors consider the concentration of antibacterial drugs in the seminal fluid as a reliable experimental model for the study of pharmacokinetics in chronic prostatitis (c.p.). The study was conducted on 32 subjects, 20 of whom were affected by c.p. and 12 were normal controls. All subjects were treated with aztreonam at a dosage of 1 g.i.m. The assay was performed 1 hour after the injection, on seminal fluid, urine and serum samples. No difference was observed between normal subjects and patients with c.p. with regard to serum and urinary levels of the drug. There was a trend towards a higher concentration of the drug in the seminal fluid of patients with c.p. when compared to normal subjects, with mean values of 1.8 and 0.9 mcg/ml respectively. This difference was not statistically significant. Furthermore, the drug concentration of the drug in semen was below the sensitivity limits of the assay in 43% of normal subjects and in 10% of patients with c.p. In the latter group of patients the mean values of aztreonam concentration exceeded the minimal inhibitory concentrations for most aetiological agents causing c.p. In conclusion, it is suggested that aztreonam is likely to be effective in acute prostatitis, caused by Gram negative strains and may be indicated in selected cases for the treatment of c.p.

Adult

Androgen receptor assays in specimens of prostatic tissue obtained by transurethral resection and transvesical adenomectomy.

The main goal of this study was to ascertain whether routine transurethral resection (TUR) of prostate may provide useful material for the evaluation of androgen receptor (AR) status. At the same time, either intracellular distribution of binding affinity and capacity of receptor molecules were particularly taken into account. Based on our previous findings in breast and endometrial cancer, we suggest that a "functional" receptor status may correspond to the presence of type I (high affinity, low capacity) AR in both soluble and nuclear fractions. However, the precise significance of type II (lower affinity, higher capacity) binding sites remains to be clarified. Ten samples of large prostatic adenomas, obtained by transvesical adenomectomy (TVA), were compared with ten parallel specimens obtained by an in vitro TUR, whereby a pure cutting current was used. The AR assay was carried out with a standard competition method using tritiated mibolerone as the radioligand and Scatchard analysis for data processing. No significant difference between the TUR and TVA groups emerged concerning type I AR content of soluble, nuclear or soluble together with nuclear fractions; this was also true when the results were expressed either as fmol/ml homogenate or as fmol/mg DNA. Similarly, concentrations of type II AR in TVA and TUR samples did not differ significantly in either cell compartment, although they were widely scattered, especially in the soluble fraction. In the light of our findings, it is suggested that TUR specimens represent suitable material for receptor studies, provided that only cutting current is employed and that the use of coagulation current, to control bleeding from the prostatic bed, is confined to the final step of the TUR procedure.

Electrocoagulation

Recombinant alpha interferon in metastatic renal cell carcinoma. A cooperative phase II study.

A total of 61 evaluable patients with advanced renal cell carcinoma have been treated with 3 x 10(6) IU per square meter of body surface with recombinant alpha 2b interferon three times a week within a Cooperative Phase II Study. Toxic death for terminal renal failure occurred in 1 patient (1.63%), and toxicities greater than WHO grade 2 were present in 10 cases (16%). The overall response rate after six months of treatment was 13.1% (partial response 4, minor response 4). Two complete responses were obtained at nine and fifteen months (3.3%). Long-lasting stabilization of disease was 13.1 percent.

Adult

Natural beta-interferon and androgen receptors in prostatic cancer cells.

Both PC-3 and DU-145 cell lines are androgen-insensitive, but, in our experience, they contain androgen receptors (AR). Treatment of these cells with natural beta-interferon at a concentration of 1,000 IU/ml of culture medium determines an increase of AR (evaluated by a whole-cell assay), statistically significant with respect to control. Androgen unresponsiveness of our cells could be due to an AR level which is lower than that present in hormone-sensitive prostatic cancer cell lines, such as LNCaP cells. For this reason, interferon-promoted AR increase merits further investigation, even if other defects in receptor mechanism, responsible for hormone insensitivity, cannot be excluded.

Cell Line

Symptomatology and diagnosis of benign prostatic hyperplasia.

The symptoms of benign prostatic hyperplasia are well known. Diagnosis rests on digital palpation of the enlarged prostate. Objective parameters are laboratory tests, imaging techniques, endoscopy, and urodynamic investigations. Laboratory tests include urinalysis and serum creatinine measurement. Markers are not reliable and the determination of acid phosphatase and prostate-specific antigen is not recommended routinely for patients with prostatism. Imaging techniques are usually restricted to a complete echographic investigation of the entire urinary tract. Endoscopic manipulations are seldom necessary. Uroflow measurements are customarily performed, but the need for a complete urodynamic investigation is still open to debate.

Humans

Prostatitis, prostatosis and prostalgia. Psychogenic or organic disease?

The term 'chronic prostatitis syndrome' (C.P.S) encompasses chronic bacterial prostatitis, chlamydia or ureaplasma-associated disease, chronic 'abacterial' prostatitis, and patients with prostatosis or prostatosis or prostalgia. Interesting observations emerged from the evaluation of the clinical material indicating that the patients with abacterial prostatitis and those with prostatosis or prostaglia group have frequent sperm abnormalities and ultrasonographic changes suggesting a more complex pathogenesis than mere congestion and neurosis. Treatment in 144 evaluable patients treated with a long-acting sulphur-trimethoprim combination was almost uniformly well tolerated; Chlamydia was eradicated in all 10 treated patients and 77.4% of patients with bacterial C.P.S. were rendered free of bacteria. Sperm abnormalities were almost invariably resistant to the treatment. Only 44.4% of patients showed a partial improvement, limited to one or more parameters. Results did not differ significantly in the various subgroup. An overall evaluation of results showed that disappearance of every presenting symptom and sign was obtained in 24.3% and a significant improvement in another 25% of patients, including those in the prostatosis-prostalgia group. These results suggest that antibacterial treatment may be followed by favourable clinical results even in patients in whom no bacteria or other aetiological agents could be isolated.

Adult