Sorafenib decreases proliferation and induces apoptosis of prostate cancer cells by inhibition of the androgen receptor and Akt signaling pathways.

Antihormonal and chemotherapy are standard treatments for nonorgan-confined prostate cancer. The effectivity of these therapies is limited and the development of alternative approaches is necessary. In the present study, we report on the use of the multikinase inhibitor sorafenib in a panel of prostate cancer cell lines and their derivatives which mimic endocrine and chemotherapy resistance.

Single institution experience with the transobturator sling suspension system AdVance® in the treatment of male urinary incontinence: mid-term results.

Purpose: To evaluate the clinical outcome after placement of AdVance® sling in men with stress urinary incontinence after prostate surgery.

Materials And Methods: Incontinence was assessed on basis of number of pad usage. Patients' satisfaction was evaluated using a non-validated patient questionnaire at 12 months post-operatively.

Retrospective multicentre study of carboplatin monotherapy for clinical stage I seminoma.

Objective: • To evaluate, in a retrospective multicentre study, the long-term oncological efficacy and morbidity of using carboplatin as an alternative treatment for patients with clinical stage I seminoma.

Patients And Methods: • Patients with clinical stage I seminoma treated with two cycles of adjuvant single-agent carboplatin (400 mg/m² body surface) from February 1990 until September 2008 were retrospectively identified. • A database was created (including information on patient characteristics, initial tumour staging, tumour marker levels, follow-up, oncological outcome, treatment side effects and long-term side effects), descriptive analyses were performed and the data were compared with those available in the literature.

Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy : A multicenter randomized, double-blind, placebo-controlled trial.

Background: The medical community lacks results from prospective controlled multicenter studies of the diagnostic efficacy of 5-aminolevulinic acid (5-ALA) cystoscopy on tumor recurrence in patients with superficial bladder tumors.

Methods: A prospective randomized, double-blind, placebo-controlled study was conducted in 370 patients with nonmuscle-invasive urinary bladder carcinoma who received either 5-ALA (n = 187) or a placebo (n = 183) intravesically before cystoscopy. Each group underwent cystoscopy under visible white light and under fluorescent light followed by transurethral tumor resection.

SOCS-3 antagonises the proliferative and migratory effects of fibroblast growth factor-2 in prostate cancer by inhibition of p44/p42 MAPK signalling.

Fibroblast growth factor-2 (FGF-2) is highly expressed in prostate cancer. It promotes tumour progression through multiple pathways including those of signal transducers and activators of transcription factor 3 (STAT3), mitogen-activated protein kinases (MAPKs) and Akt. In previous studies, we have reported that STAT3 phosphorylation inversely correlates with suppressor of cytokine signalling-3 (SOCS-3) expression in prostate cancer cells.

Down-regulation of suppressor of cytokine signaling-3 causes prostate cancer cell death through activation of the extrinsic and intrinsic apoptosis pathways.

Suppressor of cytokine signaling-3 (SOCS-3) acts as a negative feedback regulator of the Janus-activated kinase/signal transducers and activators of transcription factors signaling pathway and plays an important role in the development and progression of various cancers. To better understand the role of SOCS-3 in prostate cancer, SOCS-3 expression was down-regulated in DU-145, LNCaP-IL-6+, and PC3 cells by consecutive SOCS-3 small interfering RNA transfections. SOCS-3 mRNA and protein expression as measured by quantitative reverse transcription-PCR and Western blot, respectively, were decreased by approximately 70% to 80% compared with controls.

[Androgens stimulate the expression of SOCS-3 and inhibits their effect on proliferation and secretion].

Purpose: Suppressors of cytokine signalling (SOCS) are induced by interleukins and peptide hormones. These molecules prevent the activation of diverse signalling pathways in benign and malignant cells. In previous studies, we showed that SOCS-3 is expressed in most prostate cancer cell lines and tissue specimens.

Suppressor of cytokine signaling (SOCS)-1 is expressed in human prostate cancer and exerts growth-inhibitory function through down-regulation of cyclins and cyclin-dependent kinases.

Suppressor of cytokine signaling (SOCS) proteins play a pivotal role in the development and progression of various cancers. We have previously shown that SOCS-3 is expressed in prostate cancer, and its expression is inversely correlated with activation of signal transducer and activator of transcription factor 3. We hypothesized that SOCS-1, if expressed in prostate cancer cells, has a growth-regulatory role in this malignancy.

Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor.

It is hypothesized that ligand-independent activation of the androgen receptor is one of the mechanisms implicated in tumour progression. However, supportive evidence is limited to the effect of HER-2/neu that stimulates prostate cancer progression through activation of the androgen receptor. In the present study, we have asked whether the proinflammatory cytokine interleukin-6 (IL-6), which is known to stimulate androgen receptor activity and expression of its downstream target genes, may also induce growth of androgen-sensitive cells.

[Chemotherapy for prostate cancer].

For many years the benefit of chemotherapy in patients with prostate cancer was thought to be limited to palliation of late-stage disease, and thus this treatment option only became involved in patient care towards the end of the disease process, if at all. However, two landmark phase-III trials with docetaxel-based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a survival benefit for patients with hormone refractory prostate cancer (HRPC) thus prompting a change in patterns of care. With raising interest for chemotherapeutic options and clinical trials for new drugs and new indications (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local treatment, and hormone sensitive cancer) under way our goal was to review within the context of a multidisciplinary team the available evidence and explore the standard for the medical treatment of prostate cancer outside of clinical trials.

Oligomeric proanthocyanidin complexes (OPC) exert anti-proliferative and pro-apoptotic effects on prostate cancer cells.

Background: Oligomeric proanthocyanidin complexes (OPC) are extracted from grape seeds or maritime pine bark and have been used for enhancement of capillary stability and lymphatic drainage. Since a role for OPC in cancer prevention was postulated, we asked whether they have an effect on prostate cancer cells.

Methods: Cell proliferation was determined by (3)H-thymidine assay and cell cycle status was analyzed on a flow cytometer.

Mcl-1 is regulated by IL-6 and mediates the survival activity of the cytokine in a model of late stage prostate carcinoma.

The proinflammatory cytokine interleukin-6 (IL-6) has been considered a positive growth factor in late stage prostate cancer (PC) cells and a potential target for therapeutic interference. We studied the effects of inhibition of IL-6 in LNCaP-IL6+ cells, a model system for advanced PC, which produce IL-6. By using the chimeric anti-IL-6 antibody, CNTO 328, we showed that the autocrine IL-6 loop is responsible for decreased sensitivity of LNCaP-IL-6+ cells to die by apoptosis.

Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion.

Suppressors of cytokine signalling (SOCS) are induced by interleukins (ILs) and various peptide hormones and may prevent sustained activation of signalling pathways. We have previously shown that SOCS-3 antagonizes regulation of cellular events by cAMP and is expressed in human prostate cancer. To investigate possible effects of androgen on SOCS-3 protein expression, two prostate cancer cell lines (PC3-AR and LAPC4) were treated with different concentrations of R1881.

Posttraumatic high-flow priapism in children: noninvasive treatment by color Doppler ultrasound-guided perineal compression.

To our knowledge, only 1 case has been reported of high-flow priapism in boys younger than 6 years of age and only a small number of prepubertal boys have had high-flow priapism. Because of this, the diagnostic and therapeutic procedures are still under discussion. We report a case of a 3-year-old boy with posttraumatic high-flow priapism treated by ultrasound-guided compression of the arteriocavernous fistula.

Increased resistance to trail-induced apoptosis in prostate cancer cells selected in the presence of bicalutamide.

Background: Following prolonged treatment with the non-steroidal anti-androgen bicalutamide (Casodex), LNCaP cells have become resistant to this drug. Previously, we found that the bicalutamide-refractory subline LNCaP-Bic acquires a growth advantage and does not respond to androgenic stimulation. In the present study, we have asked whether changes in response to the tumor-selective apoptosis inducer TNF-related apoptosis-inducing ligand (TRAIL) occur in LNCaP-Bic cells.

Androgen deprivation increases p300 expression in prostate cancer cells.

Standard therapy for nonorgan confined prostate cancer aims to block the production or action of androgens. Although initially successful, antiandrogen therapy eventually fails and androgen depletion independent (ADI) disease emerges. Remarkably, ADI prostate cancers still rely on a functional androgen receptor (AR).

Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer.

Interleukin-6, levels of which are elevated in prostate cancer, activates different signal transduction pathways including that of Janus kinases/signal transducer and activator of transcription (STAT)3. However, phosphorylation of STAT3 has been reported to be associated with either stimulatory or inhibitory effects on cellular proliferation. To better understand the mechanisms of STAT3 regulation in benign and malignant prostate, we have investigated the role of suppressor of cytokine signaling (SOCS)-3.

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1.

Levels of the proinflammatory cytokine interleukin-6 (IL-6) are increased in therapy-resistant prostate cancer. IL-6 has been considered a positive growth factor in late-stage prostate cancer cells and a potential target for therapeutic interference. Effects of inhibition of IL-6 on cell survival were studied in LNCaP-IL6+ cells, a model system for advanced prostate cancer, which produce IL-6.

Regulation of growth of prostate cancer cells selected in the presence of interleukin-6 by the anti-interleukin-6 antibody CNTO 328.

Background: Interleukin-6 (IL-6) is a multifunctional regulator of cellular events in prostate cancer. LNCaP-IL-6+ cells selected in the presence of IL-6 were taken for assessment of effects of the chimeric monoclonal anti-IL-6 antibody CNTO 328.

Methods: Cell viability was assessed after treatment with CNTO 328 by the ATP assay.

Metastatic spermatocytic seminoma--an extremely rare disease.

Metastatic spermatocytic seminoma is an extremely rare disease with only one documented case in literature. We present another patient with metastatic disease confirmed by histological work-up after laparoscopic retroperitoneal lymph node dissection (L-RPLND).

The androgen receptor pathway is by-passed in prostate cancer cells generated after prolonged treatment with bicalutamide.

Background: Experimental work in various prostate cancer models revealed that the androgen receptor is frequently upregulated and implicated in tumor progression. However, little attention has been paid to the androgen receptor-signaling pathway in the development of therapy resistance in patients who receive chronic treatment with a non-steroidal anti-androgen.

Methods: We have generated a novel subline, LNCaP-Bic, after prolonged treatment with androgen and bicalutamide in vitro.

Mechanisms of endocrine therapy-responsive and -unresponsive prostate tumours.

Several options for the endocrine treatment of non-organ-confined prostate cancer are available. They include surgical or medical removal of androgenic hormones or administration of non-steroidal anti-androgens. However, tumour progression after a period of remission of the disease inevitably occurs in virtually all patients.

Interleukin-6 regulation of prostate cancer cell growth.

Interleukin-6 (IL-6) is involved in regulation of immune reaction and cell growth and differentiation. It causes multifunctional responses ranging from inhibition of proliferation to promotion of cell survival. IL-6 effects may depend on experimental conditions such as passage numbers and serum composition.

Interleukin-6 and oncostatin M stimulation of proliferation of prostate cancer 22Rv1 cells through the signaling pathways of p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase.

Introduction: Interleukin-6 (IL-6) is a pleiotropic regulator of prostate cancer cell growth. Oncostatin M (OSM), an IL-6-type cytokine, affects the growth of prostate cancers in a paracrine and autocrine manner. In order to understand better the mechanisms controlling proliferation and intracellular signaling by these cytokines in advanced prostate carcinoma, we performed studies in 22Rv1 cells derived from the relapsed xenograft CWR22R.