Increased Expression and Altered Cellular Localization of Fibroblast Growth Factor Receptor-Like 1 (FGFRL1) Are Associated with Prostate Cancer Progression.

Fibroblast growth factor receptors (FGFRs) 1-4 are involved in prostate cancer (PCa) regulation, but the role of FGFR-like 1 (FGFRL1) in PCa is unclear. FGFRL1 expression was studied by qRT-PCR and immunohistochemistry of patient tissue microarrays (TMAs) and correlated with clinical patient data. The effects of FGFRL1 knockdown (KD) in PC3M were studied in in vitro culture models and in mouse xenograft tumors.

Benefit of Adjuvant Chemotherapy and Pelvic Lymph Node Dissection in pT3 and Node Positive Bladder Cancer Patients Treated with Radical Cystectomy.

Benefits of adjuvant chemotherapy (AC) and extent of pelvic lymph node dissection (PLND) in radical cystectomy (RC) are debated. Results from randomized trials are still expected. To analyze the effects of AC and PLND in two academic centers with opposite policies regarding their use.

Increased expression of fibroblast growth factor 13 in prostate cancer is associated with shortened time to biochemical recurrence after radical prostatectomy.

Fibroblast growth factor homologous factors (FHFs) belong to the fibroblast growth factor (FGF) superfamily, which plays an important role in prostate cancer (PCa). Mining of public database suggests that FGF13 (FHF2) mRNA expression is altered in over 30% of PCa cases. This study examined the FGF13 expression pattern in human PCa specimens and evaluated its potential as a biomarker for patient outcome after radical prostatectomy (RP).

Cancer-associated changes in the expression of TMPRSS2-ERG, PCA3, and SPINK1 in histologically benign tissue from cancerous vs noncancerous prostatectomy specimens.

Objective: To investigate whether messenger ribonucleic acid (mRNA) expression of TMPRSS2-ERG fusion gene, a suggested prostate cancer (PCa) biomarker, was specific to cancerous lesions alone and to study the expression of SPINK1 and PCA3 mRNAs in the same cohort to also explore the proposed mutual exclusivity of TMPRSS2-ERG and SPINK1 expression.

Methods: Levels of 2 TMPRSS2-ERG transcripts, PCA3, and SPINK1 mRNAs were measured with highly standardized reverse transcription quantitative polymerase chain reaction assays in cystoprostatectomy specimens from 19 patients with invasive bladder cancer and 174 radical prostatectomy (RP) samples (88 histologically benign prostate [HBP] tissues and 86 from cancerous lesions) from 87 patients with clinically localized PCa.

Results: Expression of TMPRSS2-ERG transcripts was detected in 45 of 88 (51%) HBP tissues from RP specimens and more frequently (57 of 86, 66%) found in cancerous lesions.

Association of transcript levels of 10 established or candidate-biomarker gene targets with cancerous versus non-cancerous prostate tissue from radical prostatectomy specimens.

Objectives: The benefits of PSA (prostate specific antigen)-testing in prostate cancer remain controversial with a consequential need for validation of additional biomarkers. We used highly standardized reverse-transcription (RT)-PCR assays to compare transcript levels of 10 candidate cancer marker genes - BMP6, FGF-8b, KLK2, KLK3, KLK4, KLK15, MSMB, PCA3, PSCA and Trpm8 - in carefully ascertained non-cancerous versus cancerous prostate tissue from patients with clinically localized prostate cancer treated by radical prostatectomy.

Design And Methods: Total RNA was isolated from fresh frozen prostate tissue procured immediately after resection from two separate areas in each of 87 radical prostatectomy specimens.

[Update on current care guidelines: benign prostatic hyperplasia].

Most benign prostatic hyperplasia (BPH) patients can be diagnosed and treated in primary care. Evaluation requires a medical history and a symptom score (DAN-PSS or IPSS) and a careful physical examination including a digital rectal examination. Careful follow-up and medical therapy are the usual first-line management options in uncomplicated BPH.

Does patient age affect survival after radical cystectomy?

Unlabelled: What's known on the subject? and What does the study add? Elderly patients have more years to compound comorbidities and it has previously been shown that comorbidity is an important predictor of overall survival in patients with bladder cancer, including those treated with radical cystectomy (RC). Other studies have also demonstrated higher stage at diagnosis, higher rate of upstaging on final pathology and a longer delay to definitive therapy for older patients. Because of these findings, elderly patients are being offered RC less often than younger patients.

Improved detection of localized prostate cancer using co-registered MRI and 11C-acetate PET/CT.

Objectives: We aimed to study the ability of contrast enhanced MRI at 1.5 T and 11C-acetate PET/CT, both individually and using fused data, to detect localized prostate cancer.

Methods: Thirty-six men with untreated prostate cancer and negative for metastatic disease on pelvic CT and bone scan were prospectively enrolled.

Immunoassay for the discrimination of free prostate-specific antigen (fPSA) forms with internal cleavages at Lys(₁₄₅) or Lys(₁₄₆) from fPSA without internal cleavages at Lys(₁₄₅) or Lys(₁₄₆).

Total levels of circulating prostate-specific antigen (tPSA) are strongly associated with prostate cancer (PCa) risk and outcome but benign prostate disease is the most frequent cause of a moderately elevated PSA level. Free PSA (fPSA) forms are independently associated with PCa risk and contribute modest diagnostic enhancements above and beyond tPSA alone. We developed an immunoassay for fPSA subfractions containing internal cleavages at Lys(145) or Lys(146) (fPSA-N).

[Treatment of benign prostatic hyperplasia].

Due to the changing population structure, the proportion of aged men has increased, whereby there is an increasing need for the treatment of prostatic hyperplasia. Most men can be treated with medication within the primary health care. Although the disease is mostly mild in nature and merely lowering the quality of life, it may cause severe complications in the urinary tract, if left untreated.

Intact and internally cleaved free prostate-specific antigen in patients with prostate cancer with different pathologic stages and grades.

Objectives: To measure the concentration levels of free prostate-specific antigen (PSA) isoforms in patients with prostate cancer selected for curative treatment using radical prostatectomy and to study the association between the isoforms and the pathologic cancer stage and grade.

Methods: Preoperative plasma samples were obtained from 309 consecutive patients scheduled to undergo radical prostatectomy at Turku University Hospital. The pathologic TNM stage, Gleason score, and World Health Organization grade of the tumors were recorded.

Functional imaging of localized prostate cancer aggressiveness using 11C-acetate PET/CT and 1H-MR spectroscopy.

Unlabelled: We assessed the ability of (11)C-acetate PET/CT, MRI, and proton MR spectroscopy ((1)H-MRS) to image localized prostate cancer and detect its aggressiveness, using qualitative and quantitative approaches.

Methods: Twenty-one patients with untreated localized prostate cancer, diagnosed using transrectal ultrasound-guided biopsy, were prospectively enrolled. Cancer laterality was based on the percentage of cancer and the highest Gleason score determined from biopsies.

N-terminal truncation of Stat5a/b circumvents PIAS3-mediated transcriptional inhibition of Stat5 in prostate cancer cells.

Transcription factor Stat5a/b is critical for prostate cancer cell survival and for prostate xenograft tumor growth. In addition, the Stat5a/b signaling pathway may contribute to progression of organ-confined prostate cancer to castration-resistant and/or metastatic disease. Expression of nuclear Stat5a/b is clustered to high grade human prostate cancers, and nuclear Stat5a/b in primary prostate cancer predicts early disease recurrence after initial treatment.

Twenty-year experience of radical cystectomy for bladder cancer in a medium-volume centre.

Objective: To evaluate long-term survival after radical cystectomy (RC) for bladder cancer (BC) and to define risk factors for BC-specific death.

Material And Methods: Patients having RC for BC with curative intent in Turku University Hospital 1986-2005 were assessed. Survival results were recorded and 10 risk factors for BC-specific death were analysed.

Risk factors for mortality and morbidity related to radical cystectomy.

Objectives: To evaluate the risk factors for mortality and morbidity related to radical cystectomy (RC) in a medium-sized academic centre, and to analyse the rate and trends of perioperative morbidity and mortality, as although complications related RC to are lower in modern than historic series, RC is still associated with marked risks.

Patients And Methods: The study included 258 patients undergoing RC for bladder cancer in Turku University Hospital in 1986-2005. Basic patient characteristics and in-hospital, early (from hospital discharge to 3 months) and combined morbidity and mortality were analysed.

Quantitative real-time RT-PCR assay for PCA3.

Objectives: To develop a quantitative, internally standardized real-time RT-PCR assay for prostate cancer antigen 3 (PCA3), a non-translated gene found to be prostate-specific and highly overexpressed in cancer, and examine the role of PCA3 in peripheral blood with a small sample cohort.

Design And Methods: The RT-PCR assay for PCA3 is based on target-specific lanthanide probes. Peripheral blood from 91 prostatic cancer/disorder patients and healthy controls was assayed for PCA3 and prostate-specific antigen (PSA) expression.

Autocrine prolactin promotes prostate cancer cell growth via Janus kinase-2-signal transducer and activator of transcription-5a/b signaling pathway.

The molecular mechanisms that promote progression of localized prostate cancer to hormone-refractory and disseminated disease are poorly understood. Prolactin (Prl) is a local growth factor produced in high-grade prostate cancer, and exogenously added Prl in tissue or explant cultures of normal and malignant prostate is a strong mitogen and survival factor for prostate epithelium. The key signaling proteins that mediate the biological effects of Prl in prostate cancer are Signal Transducer and Activator of Transcription (Stat)-5a/5b via activation of Janus kinase-2.

Novel homogenous time-resolved fluorometric RT-PCR assays for quantification of PSA and hK2 mRNAs in blood.

Objectives: The purpose of this study was to design, validate, and optimize internally standardized real-time quantitative RT-PCR assays and to identify and avoid problems with assay reliability and examine the impact of an exogenous internal standard.

Design And Methods: The model system consisted of internally standardized quantitative real-time RT-PCR assays specific for PSA and hK2 mRNA based on time-resolved fluorometric detection of lanthanide chelates.

Results: Reproducibility was best when large copy numbers (>5000 per milliliter blood) were analyzed.

Intact free prostate-specific antigen and free and total human glandular kallikrein 2. Elimination of assay interference by enzymatic digestion of antibodies to F(ab')2 fragments.

Various blood constituents can interfere with immunoassays, usually by binding the Fc portion of antibodies. Our previously developed assays for intact free prostate-specific antigen (PSA), free human kallikrein 2 (hK2), and total hK2 frequently yielded falsely high results despite including an excess of scavenger antibodies. We investigated whether this interference could be eliminated by replacing monoclonal capture or tracer antibodies with F(ab')2 or recombinant Fab fragments.

Free and total human glandular kallikrein 2 in patients with prostate cancer.

Objectives: The use of prostate-specific antigen (PSA, hK3) results in the overdiagnosis and overtreatment of prostate cancer. Markers are needed that could identify aggressive, fast-growing tumors and help decide which patients would benefit most from aggressive treatment. Human glandular kallikrein 2 (hK2) could be such a marker.

Associations between serum testosterone fall and cognitive function in prostate cancer patients.

Data on the association between cognition and testosterone levels in elderly men are inconclusive. Androgen deprivation therapy is commonly used in the treatment of prostate cancer with the aim of achieving castration levels of serum testosterone. The study group comprised 26 elderly men (mean age 65 years) with newly diagnosed prostate cancer.

Activation of signal transducer and activator of transcription 5 in human prostate cancer is associated with high histological grade.

We have recently identified signal transducer and activator of transcription 5 (Stat5) as a critical survival factor for prostate cancer cells. We now report that activation of Stat5 is associated with high histological grade of human prostate cancer. Specifically, immunohistochemical analysis demonstrated a strong positive correlation with activation of Stat5 and high Gleason score in 114 human prostate cancers.

Development of sensitive immunoassays for free and total human glandular kallikrein 2.

Background: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity.

Methods: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2.

Kinetics of [(11)C]choline uptake in prostate cancer: a PET study.

Carbon-11 choline has recently been introduced as a potential tracer for tumour imaging with positron emission tomography (PET). We evaluated the kinetics of the uptake of [(11)C]choline in prostate cancer and benign prostatic hyperplasia. We also evaluated the association between the uptake of [(11)C]choline and the histological grade of malignancy, Gleason score, volume of the prostate and prostate-specific antigen (PSA).