Cross-talk between ribosome biogenesis, translation, and mTOR in CD133+ 4/CD44+ prostate cancer stem cells.

OBJECTIVE: To investigate the gene expression profile of CSCs and to explore the key pathways and specific molecular signatures involved in the characteristic of CSCs. MATERIALS AND METHODS: CD133+ /CD44+ CSCs and bulk population (non-CSCs) were isolated from DU-145 cells using fluorescence-activated cell sorting (FACS). We used Illumina HumanHT-12 v4 Expression to investigate gene expression profiling of CSCs and non-CSCs. Protein-protein interaction (PPI) network analysis was performed using the STRING database. Biomarkers selected based on gene expression profiling were visually analyzed using immunofluorescence staining method. An image analysis program, ImageJ®, was used for the analysis of fluorescence intensity. RESULTS: In microarray analysis, we found that many ribosomal proteins and translation initiation factors that constitute the mTOR complex were highly expressed. PPI analysis using the 33 genes demonstrated that there was a close interaction between ribosome biogenesis, translation, and mTOR signaling. The fluorescence amount of mTOR and MLST8 were higher in CSCs compared to non-CSCs. CONCLUSIONS: The increase in a number of genes associated with ribosome biogenesis, translation, and mTOR signaling may be important to evaluate prognosis and determine treatment approach for prostate cancer (PCa). A better understanding of the molecular pathways associated with CSCs may be promising to develop targeted therapies to prolong survival in PCa.

Transrectal ultrasound in detecting prostate cancer compared with serum total prostate-specific antigen levels.

We carried out a retrospective study to review the efficiency of grey-scale transrectal ultrasonography (TRUS) in detecting prostate cancer compared with the data in recent published work, including alternative imaging methods of the prostate gland. Our study group consisted of 830 patients who underwent TRUS-guided biopsy of the prostate between May 2000 and June 2004. The relation between abnormal TRUS findings and serum total prostate-specific antigen (tPSA) levels was evaluated in patients with prostate cancer who were divided into three different groups according to serum tPSA levels. Group I included patients with tPSA levels of 4-9.9 ng/mL, group II included tPSA levels of 10-19.9 ng/mL and group III included patients with tPSA levels of 20 ng/mL or more. In general, TRUS detected 185 (64%) of 291 cancers with a specificity of 89%, a PPV of 76% and an accuracy of 80%. TRUS findings enabled the correct identification of 22 (56%) of the 39 cancers in group I, 28 (30%) of the 93 cancers in group II and 135 (85%) of the 159 cancers in group III. In conclusion, TRUS alone has a limited potential to identify prostate cancer, especially in patients with tPSA levels lower than 20 ng/mL. Therefore, increased numbers of systematically placed biopsy cores must be taken or alternative imaging methods are required to direct TRUS-guided biopsy for improving prostate cancer detection.

Women with low libido: correlation of decreased androgen levels with female sexual function index.

The aim of the present study was to investigate a possible correlation between decreased androgen levels and female sexual function index (FSFI) in women with low libido and compare these findings with normal age-matched subjects. In total, 20 premenopausal women with low libido (mean age 36.7; range 24-51 y) and 20 postmenopausal women with low libido (mean age 54; 45-70 y), and 20 premenopausal healthy women (mean age 32.2; range 21-51 y) and 20 postmenopausal healthy women (mean age 53.5; range 48-60 y) as controls were enrolled in the current study. Women with low libido had symptoms for at least 6 months and were in stable relationships. All premenopausal patients had regular menstrual cycles and all postmenopausal patients and controls were on estrogen replacement therapy. None of the patients were taking birth control pills, corticosteroids or had a history of chronic medical illnesses. All completed the FSFI and Beck's Depression Inventory (BDI) questionnaires. Hormones measured included: cortisol; T3, T4 and TSH; estradiol; total and free testosterone; dehydroepiandrosterone sulfate (DHEA-S); sex hormone binding globulin (SHBG). We performed statistical analysis by parametric and nonparametric comparisons and correlations, as appropriate. We found significant differences between the women with low libido and the controls in total testosterone, free testosterone and DHEA-S levels and full-scale FSFI score for both pre- and postmenopausal women (P<0.05). In addition, decreased total testosterone, free testosterone and DHEA-S levels positively correlated with full-scale FSFI score and FSFI-desire, FSFI-arousal, FSFI-lubrication and FSFI-orgasm scores (P<0.05). Our data suggest that women with low libido have lower androgen levels compared to age-matched normal control groups and their decreased androgen levels correlate positively with female sexual function index domains.

Histopathological examination of both ipsilateral and contralateral testes with different obstructive models in prepubertal and adult rats.

OBJECTIVE: To determine the histopathological changes in both the ipsilateral and contralateral testes of prepubertal and adult male rats 60 days after creating different obstructive models. MATERIAL AND METHODS: Thirty-six prepubertal and 32 adult albino male rats were examined in three different obstructive models of the right testis. In group 1 the spermatic cord was ligated, in group 2 the ligation was between the caput epididymis and testis, and in group 3 the vas deferens was ligated. Sixty days after ligation both testes were removed and evaluated for testis diameter, mean seminiferous tubule diameter (MSTD), and degenerative, obstructive and inflammatory changes. RESULTS: The diameter of the obstructed right testis and MSTD were significantly greater in prepubertal rats but there was no apparent difference in adult rats. For obstructive changes, sloughing of germ cells in the prepubertal rats and germ cell absence in adult rats were significantly more common in group 3. The contralateral testis diameter and MSTD of group 3 was significantly greater only in prepubertal rats. Statistically significant values of obstructive change, e.g. sloughing of germ cells and apical vacuolation in Sertoli cells, were apparent in prepubertal rats, but tubular ectasis was the only statistically significant criterion of obstruction in adult rats. CONCLUSION: The testes are more susceptible to obstruction of the vas deferens in prepubertal than in adults rats, resulting in increased hydrostatic pressure and oedema of both the ipsilateral and contralateral testes, which might be caused by collateral circulation and rat testicular microcirculation, with a rhythmic pattern of arteriolar dilatation and constriction (vasomotion). Although the presence of oedema and high hydrostatic pressure was not prominent in adults, formation of spermatic granulomas and absence or sloughing of germ cells in the obstructed and contralateral testes reflect the early effects of vas ligation on spermatogenesis in adulthood.

Comparison of Gleason scores from sextant prostate biopsies and radical prostatectomy specimens.

OBJECTIVES: We compared the Gleason scores obtained from sextant prostate biopsy and radical prostatectomy (RP) specimens in patients with localized prostate cancer. PATIENTS AND METHODS: Sixty-one patients having a clinical diagnosis of localized prostate cancer underwent needle biopsy under transrectal ultrasonography (TRUS) and RP. Grading and staging were assigned based on Gleason scores and the TNM system, respectively. RESULTS: Mean patient age was 65.5 +/- 13.43 years and mean PSA level was 14.69 +/- 3.95. Mean Gleason score for prostate biopsy and RP specimen were 5.85 +/- 0.7 and 6.34 +/- 1.44, respectively. With respect to clinical stage, there were 20 patients in stage 1 and 41 patients in stage 2 prostate cancer. Comparing the Gleason scores, the biopsy score was lower in 26 (42.26%) and higher than RP specimens in 7 (11.84%) cases, and there was agreement between the biopsy and RP specimens in 28 (45.9%) patients. The difference between the two Gleason scores was +/- 1 for 18 patients (29.5%) and +/- 2 or more for 17 patients (27.86%). CONCLUSION: In our study, high Gleason score biopsies with elevated PSA level (>10 ng/ml) were risk factors for extraprostatic extension, and we demonstrated that Gleason scores were significantly correlated with seminal vesicle and lymph node invasion (p < 0.05). The Gleason scores of biopsy and RP specimens agreed with 45.9% of TRUS-guided sextant prostate biopsies, and this ratio was 91.1% in moderately differentiated tumors

Histopathological mapping of open testicular biopsies in patients with unobstructive azoospermia.

OBJECTIVE: To evaluate, in patients with unobstructive azoospermia, the heterogeneity of spermatogenesis within the testes and thus whether there is any region of advanced spermatogenesis. Patients and methods Seventy infertile men (mean age 34 years, SD 5.01) with no varicoceles or testicular atrophy had bilateral open testicular biopsies taken from six different sites. For each biopsy specimen the number of seminiferous tubules and of tubules with sperm maturation were counted (by light microscopy at x 400). The ratio of tubules with active spermatogenesis to the total number was calculated for each biopsy sample. RESULTS: The mean (SD) right and left testicular volumes were 19.82 (7.8) and 18.84 (7.89) mL, respectively; the patients' follicle-stimulating hormone level was 8.34 (1.17) IU/mL. On sextant biopsy spermatozoa were detected in 42 of the 70 patients (60%). The mean (SD) ratio of tubules with spermatozoa was 5.23 (0.8)% for the right and 5.37 (0.76)% for the left testes. There was no statistically significant difference in the ratio of seminiferous tubules positive for spermatozoa at the different biopsy sites in either the right or left testis. Spermatozoa were identified in only one to three biopsy sites in almost half of those with maturation arrest; this ratio increased to 74% in patients diagnosed as having Sertoli-cell-only syndrome with focal spermatogenesis. Conclusion There is no region of the testis that is rich or advanced in spermatogenesis in patients with unobstructive azoospermia. Without multiple testicular biopsy it is possible to miss advanced spermatogenesis in some unobstructed patients. The sextant testis biopsy is a reliable method for detecting the presence and exact location of seminiferous tubules with spermatozoa in patients with unobstructive azoospermia.

Leydig cell tumor of the testis: comparison of histopathological and immunohistochemical features of three azoospermic cases and one malignant case.

Leydig cell tumors of the testis are rare, mostly presenting as a testicular mass or as endocrinological symptoms. Here, three patients who were admitted for investigation of primary infertility and one patient presenting with a testicular mass are reported. The histological features were reviewed and an immunohistochemical study was done using a panel of antibodies against cytokeratin, vimentin, inhibin A, S-100, Ki-67, follicle-stimulating hormone, luteinizing hormone, prolactin, p53, bcl-2, and c-erbB2. The latter case (lost during follow up of metastatic disease) demonstrated massive tumor necrosis, extension through the tunica albuginea, and a high mitotic activity and MIB-1 score. Only this malignant case was bcl-2 positive. Of the two oncogenic markers studied, none of the cases were positive for c-erb2, while p53 was positive in more than 50% of cells in the malignant case and in one case of infertility with a large tumor, hemorrhage, focal necrosis and atypical cytological features. We recommend the evaluation of infertile men for Leydig cell tumors, and we believe that a panel of antibodies, including Ki-67, p53 and bcl-2, used for immunohistochemical analysis could be of diagnostic value in the identification of malignant and borderline cases of Leydig cell tumor.

A comparison of the histopathological findings after open and percutaneous needle testicular biopsy in adult male rats.

OBJECTIVE: To define the histopathological changes occurring as a result of open and percutaneous needle testicular biopsy in adult rats. MATERIALS AND METHODS: Percutaneous needle and open testicular biopsies were taken from 35 male albino rats (120-140 days old). Nine of the rats were killed 10 days after the biopsy, eight after 30 days and the other eight 60 days after the biopsy. A control group of six rats underwent orchidectomy with no preceding testicular biopsy. RESULTS: Significant tubulitis and obstructive findings were detected 10 days after needle biopsy (P < 0.05); epididymo-orchitis was frequent after open biopsy during this period. At 10-30 days after needle biopsy the mean seminiferous tubule diameters were significantly greater than in either the control group or after open biopsy (P < 0.05). The histopathological damage recovered 60 days after open and needle biopsy. CONCLUSION: Although percutaneous, a needle biopsy (as an alternative to open biopsy) causes tubulitis and frequent obstructive findings in the early period; therefore, repeat testicular procedures should be planned after these changes have resolved.

The best management of superficial bladder tumours: comparing TUR alone versus TUR combined with intravesical chemotherapy modalities?

To compare retrospectively the recurrence rates of TUR alone versus different intravesical chemotherapy modalities in superficial bladder cancer cases, 187 patients with stage Ta and T1 bladder tumours were treated with transurethral resection followed by adjuvant intravesical chemotherapy with mitomycin, BCG or epirubicin or by transurethral resection alone. All patients in this study had historically proven transurethrally resectable primary, category Ta and T1 transitional cell carcinoma (TCC) of the bladder. Group I included transurethral resection alone, and the other groups included intravesical mitomycin-C (Group II), BCG (Group III) and epirubicin (Group IV) therapies after transurethral resection. 146 male and 41 female patients (78% male and 22% female patients) in this study were diagnosed as primary TCC bladder tumours. Only 52 of them were stage Ta and 135 of them were stage T1 bladder tumours. Examining the histological grade of the bladder tumours, 88 (47%) of the patients had grade I, 53 (28%) had grade IIa, 30 (16%) had grade IIb and remaining 16 (9%) had grade III bladder cancers. The recurrence rates were 25% for Group I, 23.8% for Group II, 26.2% for Group III and 22.7% for Group IV. These values were given with disregarding the grade and volume of the bladder tumours. For solitary, less than 3 cm low grade tumours (grade I, IIa) recurrence rates were 16% for Group I, 15.4% for Group II, 17.8% for Group III, 17.2% for Group IV (p > 0.05). As a result of this retrospective study, for patients with low grade, stage Ta and T1 tumours TUR alone may be the best treatment modality. Although intravesical chemotherapy is effective in decreasing short-term incidences of tumour recurrence, it has not decreased long-term incidences of tumour recurrence. The high cost and adverse side effects of intravesical chemotherapy should also be taken into consideration in superficial, single, low grade tumours of bladder.