Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine.

Cystinuria is a classic heritable aminoaciduria that involves the defective transepithelial transport of cystine and dibasic amino acids in the kidney and intestine. Six missense mutations in the human rBAT gene, which is involved in high-affinity transport of cystine and dibasic amino acids in kidney and intestine, segregate with cystinuria. These mutations account for 30% of the cystinuria chromosomes studied. Homozygosity for the most common mutation (M467T) was detected in three cystinuric siblings. Mutation M467T nearly abolished the amino acid transport activity induced by rBAT in Xenopus oocytes. These results establish rBAT as a cystinuria gene.

Lipido-sterolic extract of Serenoa repens (LSESr, Permixon) treatment affects human prostate cancer cell membrane organization.

The molecular mechanism by which the lipido-sterolic extract of Serenoa repens (LSESr, Permixon) affects prostate cells remains to be fully elucidated. In androgen-independent PC3 prostate cancer cells, the LSESr-induced effects on proliferation and apoptosis were evaluated by counting cells and using a FACScan cytofluorimeter. PC3 cells were stained with JC-1 dye to detect mitochondrial membrane potential. Cell membrane lipid composition was evaluated by thin layer chromatography and gas chromatographic analysis. Akt phosphorylation was analyzed by Western blotting and cellular ultrastructure through electron microscopy. LSESr (12.5 and 25 microg/ml) administration exerted a biphasic action by both inhibiting proliferation and stimulating apoptosis. After 1 h, it caused a marked reduction in the mitochondrial potential, decreased cholesterol content and modified phospholipid composition. A decrease in phosphatidylinositol-4,5-bisphosphate (PIP2) level was coupled with reduced Akt phosphorylation. After 24 h, all of these effects were restored to pre-treatment conditions; however, the saturated (SFA)/unsaturated fatty acid (UFA) ratio increased, mainly due to a significant decrease in omega 6 content. The reduction in cholesterol content could be responsible for both membrane raft disruption and redistribution of signaling complexes, allowing for a decrease of PIP2 levels, reduction of Akt phosphorylation and apoptosis induction. The decrease in omega 6 content appears to be responsible for the prolonged and more consistent increase in the apoptosis rate and inhibition of proliferation observed after 2-3 days of LSESr treatment. In conclusion, LSESr administration results in complex changes in cell membrane organization and fluidity of prostate cancer cells that have progressed to hormone-independent status.

Cancer stem cells in prostate adenocarcinoma: a target for new anticancer strategies.

Prostate cancer (PC) is major common malignancy in males in most industrialized Western countries, where it is the most commonly diagnosed cancer affecting men after middle age (>50 years). Over 90% of PC patients with incurable disease respond to primary treatment, which consists of intervention to lower serum testosterone. However, the duration of response is short (12-33 months) and in almost all patients, is followed by the emergence of a phenotype resistant to androgen deprivation in therapy (known as hormone or androgen-resistant PC). Considerable research efforts have been directed towards the identification of markers associated with the initiation and progression of PC, yet there is little consensus about the target cell within prostate epithelium that is susceptible to malignant transformation. Stem cells may represent a major target for mutations leading to cancer as their longevity assures continued presence during the long latency between carcinogenic agents exposure and cancer development. Therefore in order to allow the development of more effective treatment strategies for PC, a better understanding of the molecular changes that underlie cancer stem cells is required.

A case of human polyomavirus Bk infection in a patient affected by late stage prostate cancer: could viral infection be correlated with cancer progression?

The basic molecular mechanisms regulating prostate cancer (PCA) development and progression are very poorly understood. Different tumor suppressor genes are implicated in PCA. In particular, since the mutation rate of the p53 gene is also low, researchers have speculated that an infectious agent might play an important role in PCA. Polyomaviruses are candidates for this agent. We selected a patient with a diagnosis of PCA and underwent radical prostatectomy, to investigate the presence of polyomavirus BK (BKV) sequences (urine and neoplastic tissues) and the mutation pattern of p53 gene. The results obtained showed the presence of BKV DNA and of p53 gene mutations in exons 6, 8 and 9. We speculate that BKV might contribute to cellular transformation process, triggered possibly by p53 gene mutations.

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.

Regional variations of insulin-like growth factor I (IGF-I), IGF-II, and receptor type I in benign prostatic hyperplasia tissue and their correlation with intraprostatic androgens.

Benign prostatic hyperplasia (BPH) is an androgen-dependent disease; it originates exclusively in the inner prostate, which includes tissue surrounding the urethra. Stromal-epithelial interaction has a pivotal role in the regulation of the development and growth of the prostate, and locally produced peptide growth factors are considered important mediators of this interaction. Insulin-like growth factor I (IGF-I) and IGF-II, acting mainly through type 1 IGF receptor (IGFR1), have mitogenic and antiapoptotic effects on epithelial and stromal prostatic cells. In this study the expression of IGF-I, IGF-II, and IGFR1 messenger ribonucleic acid (mRNA), the immunoreactive content of IGF-I (irIGF-I) and IGF-II (irIGF-II) were determined in periurethral, intermediate, and subcapsular regions of BPH tissue to verify their possible regional variation; a correlation to the tissue levels of dihydrotestosterone (DHT) and 3 alpha-androstanediol (3 alpha Diol) was also determined to verify their possible androgen dependence. Prostates were removed by suprapubic prostatectomy from 14 BPH patients and sectioned in the periurethral, intermediate, and subcapsular regions. Gene expression of IGF-I, IGF-II, and IGFR1 was evaluated by semiquantitative RT-PCR, using beta-actin as a control. irIGF-I was measured by RIA, and irIGF-II was measured by IRMA after acidification and chromatography on Sep-Pak C(18) cartridges. DHT and 3 alpha Diol concentrations were evaluated by RIA after extraction and purification on Celite microcolumns. IGF-II and IGFR1, but not IGF-I, mRNA was higher in the periurethral than in the intermediate (P < 0.05) and subcapsular (P < 0.01) region. Also, prostatic levels of irIGF-II, expressed as picomoles per g tissue, were higher in the periurethral (20.84 +/- 1.84) than in the intermediate (14.81 +/- 2.11; P < 0.05) and subcapsular (10.88 +/- 1.21; P < 0.001) region. No significant differences were found in irIGF-I content. Considering prostatic androgen levels, DHT and 3alphaDiol presented a regional variation, with the highest concentrations in the periurethral region. IGF-II mRNA and irIGF-II levels were positively correlated with both DHT and 3 alpha Diol content. These results demonstrate that in BPH tissue a greater IGF-II activity is present in the periurethral region, the site of origin of BPH. Moreover, we can hypothesize that the tissue androgen content may modulate prostatic production of IGF-II, acting at the transcriptional and probably the posttranscriptional level. Therefore, even though further studies will need to confirm this hypothesis, DHT may increase IGF-II activity, mainly in the periurethral region, which, in turn, induces, through IGFR1, benign proliferation of both epithelial and stromal cells, characteristic of BPH.

Abnormal patterns of colorectal mucin secretion after urinary diversion of different types: histochemical and lectin binding studies.

Clinical and experimental evidence indicates that ureterosigmoidostomy is associated with a high risk for the development of colonic cancer, while there is no reported evidence of increased risk in patients who undergo urinary diversion of other types. In the present study the histochemical and lectin binding characteristics of goblet cell mucin were investigated in biopsy specimens from patients who had undergone ureterosigmoidostomy and from patients who had undergone rectal bladder surgery. Specimens from transitional mucosa surrounding colonic cancers and from normal rectal mucosa were also studied. For histochemical studies the high iron diamine-Alcian blue method was used. FITC-conjugated Dolichus biflorus agglutinin (FITC-DBA) and Arachis hypogaea agglutinin (FITC-PNA) were used for the study of lectin binding characteristics. In contrast to the striking increase in numbers of sialomucin-containing goblet cells found in the patients who had undergone ureterosigmoidostomy, the mucin proved to be histochemically normal in the rectal bladder surgery group. Abnormal lectin binding patterns were observed in colorectal mucosa after urinary diversion of both types, with the abnormalities consisting of dramatic decreases in FITC-DBA labeling (compared with controls) and the appearance of substantial numbers of FITC-PNA-labeled goblet cells. These findings indicate that the pattern of mucin secretion is definitely abnormal in patients who have undergone urinary diversion. Whether this abnormality is an indicator of premalignant changes remains to be established. These data, however, confirm that endoscopic and histologic follow-up studies may be of value in assessing the risk for the development of cancer in these patients.

Antiandrogens: clinical applications.

Antiandrogens, preventing androgen action at target tissue level, are used in the treatment of various androgen-dependent diseases. Pharmacologically these substances have either a steroidal structure, like cyproterone acetate (CPA) and spironolactone (SPL), or a non-steroidal structure, like flutamide (FLU). In women with hyperandrogenism (PCO syndrome, idiopathic hirsutism, acne), clinical benefit may be obtained with CPA, which also displays a progestational activity and an antigonadotropic effect. CPA (25-50 mg/day) is used in combination with ethinyl-estradiol (EE) (20-30 micrograms/day) in reversed sequential regimen. SPL, less effective than CPA may be employed in moderate hirsutism and acne at dosages of 100-200 mg/day. During SPL treatment menstrual irregularities are frequent: in this case an association with oral contraceptives is indicated. SPL + bromocriptine (2.5-5 mg/day) has been experienced with success in PCO syndrome. The pure antiandrogen FLU, inducing progressive increase in LH and testosterone secretion, may be used only in combination with oral contraceptives. In men antiandrogens have been tested in BPH and prostatic carcinoma. In BPH the decrease in nuclear receptors and DHT nuclear content during CPA or FLU may represent the rational base of the medical treatment. An improvement in urinary obstructive manifestation has been observed with CPA alone or associated with tamoxifen (100 mg + 100 mg day). In advanced prostatic carcinoma antiandrogens represent a good alternative to estrogen therapy with less side effects and in combination with surgical or medical castration (LH-RH analogues) achieve a complete androgen blockade. An increase in the percentage of remissions and survival has been reported.

Immunoreactive EGF in human benign prostatic hyperplasia: relationships with androgen and estrogen receptors.

Benign prostatic hyperplasia (BPH) is a sex steroid dependent disease. Estrogens and androgens can modulate in different mammalian tissues epidermal growth factor (EGF) production and/or secretion. In order to clarify the relationships between estrogen and androgen receptor concentrations and those of immunoreactive EGF (irEGF), we have evaluated these parameters in 14 human BPH samples, by means of a dextran-coated charcoal method and radioimmunoassay, respectively. Cytosolic steroid receptors did not seem to correlate with irEGF. A linear significative relationship was evident between nuclear androgen receptor (ARn) levels and endogenous irEGF but not between nuclear estrogen receptors and irEGF: in ARn negative BPH samples, irEGF levels were lower than in ARn positive ones. Therefore, it is possible that androgens act at prostatic tissue level, through their own receptors, by modulating EGF production and/or secretion.

Relationship between epidermal growth factor and its receptor in human benign prostatic hyperplasia.

Human benign prostatic hyperplasia (BPH) samples were analyzed to evaluate the presence of immunoreactive epidermal growth factor (irEGF) and EGF receptor (EGFR). In all BPH samples examined both peptide and its receptor were present. Scatchard analysis of binding data of [125I]EGF showed two classes of binding sites with high and low affinity. Intratissular irEGF concentrations showed a significant inverse linear correlation with EGFR levels. Two groups of samples can be identified: the first showing high irEGF concentrations and low levels of EGF binding sites; the second low irEGF and high concentrations of EGFR. The simultaneous presence of EGF and its receptor in BPH samples indicates that this growth factor may act in an autocrine/paracrine manner in human prostatic tissue. The inverse relationship between EGF and the two sites of EGFR lead one to hypothesize that EGF itself could play a central role in determining receptor cell surface availability.

Acquired cystic kidney disease: the hormonal hypothesis.

Based on the reported sex difference in the incidence of acquired cystic kidney disease (ACKD) in patients with chronic renal failure, it is hypothesized that the hormonal derangement, well documented in male and female uremic patients on long-term dialysis, could be responsible for the pathogenesis of ACKD. The decreased androgen/estrogen ratio, and the increased estrogen value could be responsible for an estrogen receptor mediated effect on the tubular epithelial cell proliferation, an event further potentiated by the action of regulatory peptides like epidermal growth factor (EGF). The epithelial stimulation is more pronounced in men because male tissues are less adapted than female tissues to high estrogen values. Furthermore the androgen reduction, more remarkable in male than female patients, is responsible for an up-regulation of EGF-R. Therefore hormones and growth factors, by means of their own receptor in renal tissue (homologous to the two oncogenes c-erb A and c-erb B), may be responsible for the development of ACKD, and may play an important role in the pathogenesis of multiple adenomas and renal carcinomas reported with high incidence among uremic patients with ACKD.

Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes.

PURPOSE: To investigate the efficacy and tolerability of oral propionyl-L-carnitine (PLC) plus sildenafil in men with erectile dysfunction (ED) and diabetes unresponsive to sildenafil monotherapy. MATERIALS AND METHODS: Patients with medically documented ED of organic or mixed aetiology and diabetes (type 1 and 2) were randomised to receive oral PLC (2 g/day) plus sildenafil (50 mg twice weekly) (20 patients, Group 1) or sildenafil alone (20 patients, Group 2), in a double-blind, fixed-dose study. All patients had been previously treated unsuccessfully with a minimum of eight administrations of sildenafil. Efficacy was evaluated using the International Index of Erectile Function (IIEF) questionnaire: total score, subscores for questions 3 (Q3; achieving an erection) and 4 (Q4; maintaining an erection) and global efficacy question (GEQ: 'Has treatment improved your erections?'). Patients Event Logs were also used. RESULTS: After 24 weeks of treatment, mean scores for IIEF Q3 and Q4 had improved significantly in patients of Group 1 (4.25 +/- 0.63 and 3.95 +/- 1.0) compared with Group 2 (2.9 +/- 0.71 and 2.7 +/- 0.96) (p < 0.01). Moreover, the percentage of patients with improved erections (GEQ 68% vs. 23%) and successful intercourse attempts (76% vs. 34%) was significantly increased in Group 1 compared with Group 2 (p < 0.01). Fourteen (70%) patients in Group 1 and four (20%) in Group 2 reported an increase in mean IIEF EF domain score of > or = 4 (p < 0.01). Treatments were well tolerated and no patient discontinued study medication. Two patients in Group 1 reported mild gastric pain. CONCLUSIONS: Salvage therapy with PLC plus sildenafil was more effective than sildenafil in the treatment of ED in patients with diabetes refractory to sildenafil monotherapy.

Androgen concentrations and their receptors in the periurethral region are higher than those of the subcapsular zone in benign prostatic hyperplasia (BPH).

Benign prostatic hyperplasia (BPH) is an androgen-dependent disease that initially develops in the inner prostate, where the highest concentrations of testosterone (T) and dihydrotestosterone (DHT) are found. In this study, we have evaluated the cytosolic androgen receptors (ARc), the nuclear androgen receptors (ARn), and the concentrations of T, DHT, and 3alpha-androstanediol (3alphaDiol) in BPH tissue to verify the existence of a possible correlation between androgens and their receptor concentrations. Prostatic samples, removed by suprapubic prostatectomy in 15 untreated patients, were sectioned in periurethral, intermediate, and subcapsular zones. Testosterone, DHT, and 3alphaDiol were evaluated by radioimmunoassay after extraction and purification on celite microcolumns, and ARc and ARn were evaluated by means of dextran-coated charcoal method. In total tissue, mean levels of DHT, T, and 3alphaDiol were 2,531+/-308, 260+/-36, and 403+/-35 pg/mg of DNA (mean+/-SE), respectively. Cytosolic androgen receptors, detectable in all cases, were 16+/-2.8 fmol/mg of protein (mean+/-SE), and ARn, detectable in 12 cases, were 108+/-15 fmol/mg of DNA (mean+/-SE). A linear correlation between DHT and 3alphaDiol, T and DHT, and 3alphaDiol and ARn was found. If the different regions are considered, the periurethral zone, site of the primitive BPH nodule, presents the highest levels of androgens and ARn with respect to the other regions. This relative hyperandrogenism may be responsible for the growth-promoting processes of this area, leading to urinary obstruction.

Ultrastructural and immunohistochemical characterization of the tunica albuginea in Peyronie's disease and veno-occlusive dysfunction.

The tunica albuginea and corpus cavernosum from patients with Peyronie's disease (PD), patients with veno-occlusive dysfunction (VOD), and those from normal control subjects were studied by transmission electron microscopy and immunohistochemical staining for type I, III, and V collagens, platelet-derived growth factor (PDGF) AA and BB homodimers, and PDGF alpha and beta receptors. Ultrastructural modifications resembling a fibrotic reaction were detected in the two pathological tunica albuginea, but not in those from control subjects. Ultrastructural data demonstrated a general increase in fibrous and amorphous extracellular matrix material in the pathological tunica albuginea. The amorphous material probably represents glycoproteins and proteoglycans. The fibrous material, representing collagen, appears disorganized in the tissue and does not display the typical and homogeneous diameter, size, and spatial arrangement. Large areas of extracellular and intracytoplasmic, partially degraded, fibers are visible. An increased type I/III collagen ratio was detected by immunohistochemistry in the two pathological tunica albuginea. Moreover, a strong expression of type V collagen, correlated to fibroblasts, was revealed. Fibroblasts from control tissues, on the other hand, were totally negative. Finally, PDGF AA and BB were positive in fibroblasts from pathological tunica albuginea but were negative in control tissues. PDGF beta receptor was positive in pathological and normal tissue fibroblasts. Tunica albuginea from PD and VOD show similar ultrastructural and immunohistochemical alterations, whereas the corpus cavemosum shows no visible modifications.

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.

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.

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.

Interphase cytogenetics and flow cytometry analyses of renal tumours.

Fluorescent in situ hybridization (FISH) can be used to determine chromosome changes in human neoplasia. In our study, we have tested the feasibility of FISH to interphase cells of renal carcinoma to evaluate chromosome aneuploidies. We carried out in parallel in situ hybridization and flow cytometric studies in order to evaluate the possible correlation between numerical chromosome abnormalities and ploidies detected by flow cytometry (FCM). The ploidy of chromosomes 7, 11, 17 and 18 was investigated in three cases of this tumour utilizing specific probes. We found evaluable and comparable results in every case of renal carcinoma analyzed for both FISH and DNA FCM analyses and our results indicate that fluorescent in situ hybridization with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the detection of numerical specific chromosome abnormalities of interphase nuclei of renal carcinoma.

Epidermal growth factor receptor, MUC-1 and MUC-2 in bladder cancer.

The aim of this study was to investigate the immunohistochemical expression of epidermal growth factor receptor (EGFR), mucin-1 (MUC-1) and mucin-2 (MUC-2) proteins in primary bladder carcinomas and to compare EGFR and MUC staining patterns with the histological findings, grade and stage of bladder carcinoma. Fifty-six surgical specimens obtained from superficial and deeply invasive bladder carcinomas were studied. Of the 56 bladder tumors 42 (75%) expressed EGFR, 34 (60.71%) MUC-1 and 15 (26.78%) MUC-2; while 7 tumors (12.5%) coexpressed MUC-1 and MUC-2 proteins. Immunohistochemical scores showed higher levels of EGFR than of MUC-1 (P <0.05) and MUC-2 (P = 0.000) and higher levels of MUC-1 than MUC-2 (P = 0.0010). EGFR and MUC-1 expression was stronger in high-grade tumors (grade 2/3) than in low-grade (grade 1/2) ones (P <0.05) and stronger in muscle invasive tumors (T2-T4) than in superficial (Ta-T1) ones. Linear regression showed a significant (P <0.05) correlation between EGFR and MUC-1 proteins, but no correlation between EGFR and MUC-2 or between MUC-1 and MUC-2. Immunohistochemical expression of EGFR, MUC-1 and MUC-2 increases as primary bladder carcinomas acquire a more aggressive phenotype. Differences in the distribution of EGFR and mucins within the urothelium may be of diagnostic and prognostic value. These antigens may be useful as markers for bladder malignancy.

Chlamydia trachomatis genitourinary infections: laboratory diagnosis and therapeutic aspects. Evaluation of in vitro and in vivo effectiveness of azithromycin.

Chlamydia trachomatis (C.t.) cell culture represents a sensitive method for the diagnosis of chlamydial infection and the only one which makes it possible to determine the susceptibility of an isolate to antibiotics so that an appropriate drug can be selected for individual treatment. In 11 patients, affected by urethroprostatitis and suspected of treatment failure with standard drug regimens, either due to lack of compliance with therapy or antibiotic resistance, C.t. was isolated in McCoy cell culture from urethral swabs, after prostatic massage. The in vitro activity of azithromycin against these isolates and the in vivo efficacy of the drug in the patients treated with a single 1 g dose have been evaluated. All the C.t. strains tested were susceptible to the action of azithromycin (MIC range 0.125-1.0 microgram/ml). Bactericidal values were one dilution higher (MBC range 0.25-2.0 microgram/ml). These in vitro results are consistent with clinical observations as all the patients treated had negative culture at a 4-week follow-up visit.