Attila Varga

Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma

PurposeRecently, functional cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (TRPV1) have been described in human prostate and prostate cancer-derived cell lines where the activation of the receptors resulted in inhibition of cellular growth. We, however, lack the description of the expression of these molecules in human prostate cancer (PCC) and in benign prostate hyperplasia (BPH).MethodsTherefore, immunohistochemistry, Western blotting, and quantitative “real-time Q-PCR were performed to define the expressions of CB1 and TRPV1 in healthy and diseased prostate tissues.ResultsCB1 was identified in epithelial and smooth muscle cells types of the human prostate, whereas TRPV1 was exclusively localized to the mucosal cells. We also found that the expression of CB1 and TRPV1 (both at the protein and mRNA levels) were significantly up-regulated in PCC. However, while the increased expression of TRPV1 showed a proper correlation with increasing PCC tumor grades, such phenomenon was not observed with CB1. In addition, we also measured markedly elevated CB1 levels in BPH tissues whilst the expression of TRPV1 was not altered when compared to healthy control prostate.ConclusionsOur findings strongly argue for that (1) the CB1 and TRPV1 molecules as well as their ligands may indeed possess a promising future role in the treatment of PCC; (2) TRPV1 may also serve as a prognostic factor in PCC; and (3) CB1 may act as a potential target molecule in the therapeutic management of BPH.

RasGRP3 Contributes to Formation and Maintenance of the Prostate Cancer Phenotype

RasGRP3 mediates the activation of the Ras signaling pathway that is present in many human cancers. Here, we explored the involvement of RasGRP3 in the formation and maintenance of the prostate cancer phenotype. RasGRP3 expression was elevated in multiple human prostate tumor tissue samples and in the human androgen-independent prostate cancer cell lines PC-3 and DU 145 compared with the androgen-dependent prostate cancer cell line LNCaP. Downregulation of endogenous RasGRP3 in PC-3 and DU 145 cells reduced Ras-GTP formation, inhibited cell proliferation, impeded cell migration, and induced apoptosis. Anchorage-independent growth of the PC-3 cells and tumor formation in mouse xenografts of both cell lines were likewise inhibited. Inhibition of RasGRP3 expression reduced AKT and extracellular signal-regulated kinase 1/2 phosphorylation and sensitized the cells to killing by carboplatin. Conversely, exogenous RasGRP3 elevated Ras-GTP, stimulated proliferation, and provided resistance to phorbol 12-myristate 13-acetate-induced apoptosis in LNCaP cells. RasGRP3-overexpressing LNCaP cells displayed a markedly enhanced rate of xenograft tumor formation in both male and female mice compared with the parental line. Suppression of RasGRP3 expression in these cells inhibited downstream RasGRP3 responses, caused the cells to resume the LNCaP morphology, and suppressed growth, confirming the functional role of RasGRP3 in the altered behavior of these cells. We conclude that RasGRP3 contributes to the malignant phenotype of the prostate cancer cells and may constitute a novel therapeutic target for human prostate cancer.

Renal cell cancer associated with sarcoid-like reaction

An unusual granulomatous reaction within a conventional clear cell renal cancer in a 62 year-old woman is reported. Using immunohistochemical evaluation, cells of the granuloma were CD68 (Kp1), carboxypeptidase M and CD3 positive. No signs of sarcoidosis were found in other organs. According to the few publications that mention cancer associated sarcoid-like reaction, such lesions do not influence the prognosis. Our patient is still well for a 15 months follow-up.

Percutaneous nephrolithotomy in early pregnancy

We report on an 11-weeks pregnant woman, who under went a percutaneous nephrolithotomy without the use of X-rays during the procedure due to 8-mm left upper ureteric stone. In the available literature, we didn’t find any reported case about percutaneous stone removal without the use of X-rays.

Correlation study between sperm concentration, hyaluronic acid-binding capacity and sperm aneuploidy in Hungarian patients.

Infertile men with low sperm concentration and/or less motile spermatozoa have an increased risk of producing aneuploid spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding may reduce genetic risks such as chromosomal rearrangements and numerical aberrations. Fluorescence in-situ hybridization (FISH) has been used to evaluate the presence of aneuploidies. This study examined spermatozoa of 10 oligozoospermic, 9 asthenozoospermic, 9 oligoasthenozoospermic and 17 normozoospermic men by HA binding and FISH. Mean percentage of HA-bound spermatozoa in the normozoospermic group was 81%, which was significantly higher than in the oligozoospermic (P<0.001), asthenozoospermic (P<0.001) and oligoasthenozoospermic (P<0.001) groups. Disomy of sex chromosomes (P=0.014) and chromosome 17 (P=0.0019), diploidy (P=0.03) and estimated numerical chromosome aberrations (P=0.004) were significantly higher in the oligoasthenozoospermic group compared with the other groups. There were statistically significant relationships (P<0.001) between sperm concentration and HA binding (r=0.658), between sperm concentration and estimated numerical chromosome aberrations (r=-0.668) and between HA binding and estimated numerical chromosome aberrations (r=-0.682). HA binding and aneuploidy studies of spermatozoa in individual cases allow prediction of reproductive prognosis and provision of appropriate genetic counselling. Infertile men with normal karyotypes and low sperm concentrations and/or less motile spermatozoa have significantly increased risks of producing aneuploid (diminished mature) spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding, based on a binding between sperm receptors for zona pellucida and HA, may reduce the potential genetic risks such as chromosomal rearrangements and numerical aberrations. In the present study we examined sperm samples of 45 men with different sperm parameters by HA-binding assay and fluorescence in-situ hybridization (FISH). Mean percentage of HA-bound spermatozoa in the normozoospermic group was significantly higher than the oligozoospermic, the asthenozoospermic and the oligoasthenozoospermic groups. Using FISH, disomy of sex chromosomes and chromosome 17, diploidy and estimated numerical chromosome aberration frequencies were significantly higher in the oligoasthenozoospermic group compared with the three other groups. A significant positive correlation was found between the sperm concentration and the HA-binding capacity, and significant negative correlations between the sperm concentration and the estimated numerical chromosomes aberrations as well as between the HA-binding ability and the estimated numerical chromosome aberrations were identified. We conclude that HA-binding assay and sperm aneuploidy study using FISH may help to predict the reproductive ability of selected infertile male patients and to provide appropriate genetic counselling.

Percutaneous Ureterolithotomy: Direct Method for Removal of Impacted Ureteral Stones

PURPOSE We report 52 percutaneous urterolithotomies in 51 patients having large, impacted middle ureteral stones. Direct percutaneous stone removal can be performed as successfully as in cases of renal stones treated with percutaneous nephrolithotomy. METHODS The operation is performed under local anesthesia; therefore, the procedure is quicker and simpler than the laparoscopic or retroperitoneoscopic intervention. All patients became stone free. In two patients (4%), ultrasound disintegration was necessary; in the remaining cases, there was no need for any fragmentation: the stone was removed intact. A retroperitoneal drain was always left at the end of the procedure. With the exception of two cases, the ureter was always stented without closure of the ureteral incision. RESULTS Fever (> or = 38 degrees C) was observed in 15 patients (29%) for 2 days. Retroperitoneal hematoma 5 cm in diameter was seen in one patient. One patient had urine leakage through the retroperitoneal drain in the postoperative period for 18 days. Also, one patient came back 3 days after discharge with urine leakage through the percutaneous retroperitoneal tract. CONCLUSION Direct percutaneous ureterolithotomy is an effective way to remove impacted middle ureteral stones but is advisable only for endourologists with considerable experience.

Meiotic segregation study of a novel t(3;6)(q21;q23) in an infertile man using fluorescence in situ hybridization (FISH)

Male carriers with balanced reciprocal translocations can produce a variable proportion of unbalanced gametes resulting in reproductive failures. The presence of a structural rearrangement may induce an interchromosomal effect. This is characterized by abnormal bivalents not involved in the reorganization thereby yielding non-disjunction, which would present as aneuploid spermatozoa for these chromosomes. In the present case report segregation analysis of the sperm and investigation of interchromosomal effect were carried out using cytogenetic and fluorescence in situ hybridization (FISH) analysis on blood lymphocytes. The karyotype of the patient was 46,XY,t(3;6)(q21;q23). During sperm segregation analysis a total of 2,002 sperms were evaluated, of which 46.8% showed normal/balanced (alternate segregation mode) and 53.2% of sperm showed an abnormal signal pattern. A significant difference in the frequency of the estimated number of chromosome anomalies was observed in the translocation carrier when compared to the normozoospermic group (P < 0.0001) and the oligozoospermic group (P < 0.0001). Meiotic segregation analysis of sperm together with aneuploidy assessment for X, Y, and 17 chromosomes using FISH allows for the determination of a reproductive prognosis in male balanced translocation carriers and can be used for appropriate genetic counseling.

Fertility preservation in cases of laparoscopic treatment of seminal vesicle cysts.

Seminal vesicle cysts can cause sub- or infertility. Minimally invasive techniques have the advantage of preserving the vas deferens by the treatment of symptomatic cases. After reviewing the published articles, only a few of them presented data on fertility before and after surgery. The authors now report the successful treatment of two patients with seminal vesicle cysts, in which laparoscopic cyst removal resolved the symptoms, preserving fertility and erectile function. Due to the rarity of seminal vesicle cysts, preoperative examinations and treatment modalities should focus not only on the relief of symptoms but also on the preservation of fertility and erectile function.

A novel approach to the treatment of benign prostatic hyperplasia

To assess the clinical efficacy and safety of the combined α1‐ and postsynaptic α2‐blocker GYKI‐16084 compared to placebo during a 28‐day active treatment of patients with benign prostatic hyperplasia (BPH).

[Influence of malignant tumors occurring in the reproductive age on spermiogenesis: studies on patients with testicular tumor and lymphoma].

INTRODUCTION The application of chemo- and radiotherapy results in good survival prognosis for young men with malignant tumors, but long-term gonadoxic effect has to be considered. In addition, malignant disease itself has a negative impact on spermiogenesis. AIM The aim of the authors was to examine the spermiogenetic effect of the most common tumors occurring in the reproductive age in men: testicular cancer, Hodgkin disease and non-Hodgkin disease. METHOD Spermiogram of men with testicular cancer (N = 68), Hodgkin disease (N = 37) and non-Hodgkin disease (N = 14) who were referred for sperm cryopreservation were analysed in the Reproductive Andrology Laboratory of the authors. RESULTS Azoospermia was found in 11.8% of all patients (N = 119), while 58.8% of the patients had oligozoospermia even before the treatment. Sperm concentration of men with testicular cancer was significantly lower than those with lymphomas (32.8 M/mL vs. 24.9 M/mL, p = 0.03). There was no difference in sperm concentration between the Hodgkin and non-Hodgkin lymphoma groups. CONCLUSIONS Spermiogenetic defect is more pronounced in men with testicular cancer than those with lymphomas. Cryopreservation before treatment for fertility preservation should be offered for all reproductive aged men with malignant disease, especially for those with testicular cancer.