Evidence for benefits and risks of tadalafil as a non-prescription medicine: review and evaluation using the Group Delphi technique to achieve consensus amongst clinical experts.

An evidence-based consensus meeting was held with urologists, a pharmacist and a cardiologist to perform a structured benefit-risk analysis of reclassifying tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor for treatment of erectile dysfunction (ED), to be available without prescription in Germany. As per the Brass process endorsed by regulatory authorities, an evidence-based Brass value tree was developed, which identified the incremental benefits and risks that should be considered above the safety and efficacy evidence required for prescription medicines. During the Group Delphi consensus meeting, the expert panel rated the likelihood and clinical impact of each benefit and risk on a scale of 0 (none) to 3 (high).

Investigating self-reported efficacy of lifestyle medicine approaches to tackle erectile dysfunction: a cross-sectional eSurvey based study.

Background: Erectile dysfunction (ED) is the most common sexual dysfunction in men. Some types of ED are amenable to treatment using lifestyle medicine approaches with or without pharmacotherapy.

Aim: Investigate self-reported efficacy of lifestyle medicine approaches to tackle ED.

Thinking About Pathomechanisms and Current Treatment of Erectile Dysfunction-"The Stanley Beamish Problem." Review, Recommendations, and Proposals.

Introduction: Up to 50% of all men over 50 years of age suffer from erectile dysfunction. Since the late 1990s erectile dysfunction has been treated mostly with phosphodiesterase 5 inhibitors (PDE5I). Over the past 20 years, numerous scientific findings on the development of erectile dysfunction have been collected, which have so far received little attention in the treatment of erectile dysfunction.

Impact of vasectomy on the sexual satisfaction of couples: experience from a specialized clinic.

Introduction: Vasectomy is the simplest, safest, and most effective form of definitive fertility control in men [1]. Vasectomy is used for 10% of contraception worldwide but only for 2% in Germany [2]. The aim of this study was to investigate the impact of vasectomy on the sexual satisfaction of sterilized men and their partners.

Plasmin-clipped beta(2)-glycoprotein-I inhibits endothelial cell growth by down-regulating cyclin A, B and D1 and up-regulating p21 and p27.

beta(2)-Glycoprotein-I (beta(2)gpI), an abundant plasma glycoprotein, functions as a regulator of thrombosis. Previously, we demonstrated that plasmin-clipped beta(2)gpI (cbeta(2)gpI) exerts an anti-angiogenic effect on human umbilical vein endothelial cells (HUVEC). The present study was focused on the molecular background responsible for this phenomenon.

Maspin modulates adhesion of bladder carcinoma cells to vascular endothelium.

Purpose: Maspin belongs to the serpin family and has been shown to suppress tumor growth and metastasis in several tumor types. The role of maspin in bladder carcinoma has not been fully elucidated, and the object of this study was to investigate whether maspin contributes to bladder tumor adhesion to vascular endothelial cells (HUVEC).

Methods: Expression of maspin-coding mRNA was evaluated in a panel of bladder carcinoma cell lines.

Association of intravesical tumor location with metastases to the pelvic lymph nodes in transitional cell cancer of the bladder.

Introduction: In this study, we aimed to determine those clinical and pathologic features that are associated with pelvic lymph node metastasis in patients with transitional cell cancer of the bladder. Unlike previous studies, we particularly focused on intravesical tumor location.

Methods: We included 173 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for muscle-invasive or high-risk superficial bladder cancer.

Expression of angiogenesis inhibitors in human bladder cancer may explain rapid metastatic progression after radical cystectomy.

Angiogenesis is essential for tumor growth and progression. It has been demonstrated that the expression of angiogenesis stimulators (e.g.

An endogenous inhibitor of angiogenesis derived from a transitional cell carcinoma: clipped beta2-glycoprotein-I.

Background: Invasive cell carcinoma of the bladder often develops after complete transurethral excision of superficial transitional cell carcinoma. It has been postulated that primary tumors release angiogenesis-blocking proteins which suppress distant metastases. We have identified an endogenous protein which might be responsible for tumor dormancy.

Combined MRI and MR spectroscopy of the prostate before radical prostatectomy.

Objective: The purpose of this study was to evaluate a routine protocol for combined MR and spectroscopic imaging of the prostate for staging accuracy.

Subjects And Methods: Fifty patients with biopsy-proven prostate carcinoma were examined with our sequence protocol, which consisted of T2-weighted fast spin-echo sequences and a pelvic T1-weighted spin-echo sequence. For spectroscopy, we used a 3D chemical shift imaging (CSI) spin-echo sequence.

Clinical relevance of maspin expression in bladder cancer.

Transitional cell carcinoma (TCC) of the bladder is a solid tumor that induces angiogenesis to maintain nutrition and oxygenation of tumor cells. Maspin, a serpin with tumor suppressing activity, has recently been identified as an inhibitor of angiogenesis. This study examined the impact of maspin expression in the growth pattern of TCC of the bladder.

CXCR4 chemokine receptor mediates prostate tumor cell adhesion through alpha5 and beta3 integrins.

The mechanisms leading to prostate cancer metastasis are not understood completely. Although there is evidence that the CXC chemokine receptor (CXCR) 4 and its ligand CXCL12 may regulate tumor dissemination, their role in prostate cancer is controversial. We examined CXCR4 expression and functionality, and explored CXCL12-triggered adhesion of prostate tumor cells to human endothelium or to extracellular matrix proteins laminin, collagen, and fibronectin.

Endothelial adhesion of synchronized gastric tumor cells changes during cell cycle transit and correlates with the expression level of CD44 splice variants.

Aim: To study adhesion capacity and CD44 expression of human gastric adenocarcinoma MKN45 cells at different stages of a first cell cycle.

Methods: MKN45 cells were synchronized by aphidicolin and assayed for adhesion to an endothelial cell (HUVEC) monolayer. Surface expression of CD44 and CD44 splice variants on MKN45 cells was evaluated by flow cytometry.

Prostate tumor CXC-chemokine profile correlates with cell adhesion to endothelium and extracellular matrix.

Though chemokines of the CXC family are thought to play key roles in neoplastic transformation and tumor invasion, information about CXC chemokines in prostate cancer is sparse. To evaluate the involvement of CXC chemokines in prostate cancer, we analyzed the CXC coding mRNA of both chemokine ligands (CXCL) and chemokine receptors (CXCR), using the prostate carcinoma cell lines PC-3, DU-145 and LNCaP. CXCR proteins were further evaluated by Western blot, CXCR surface expression by flow cytometry and confocal microscopy.

Clinical relevance of serum angiogenic activity in patients with transitional cell carcinoma of the bladder.

Angiogenesis is essential for tumor growth and progression and is mediated by positive and negative regulators of vessel growth. Since angiogenic mediators found in patient serum have been postulated to reflect the angiogenic potential of a malignant tumor, we investigated the angiogenic activity in the serum of patients with transitional cell carcinoma (TCC). The data were correlated to tumor characteristics and the clinical course of the patients.

Gene signatures of progression and metastasis in renal cell cancer.

Purpose: To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC).

Experimental Design: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified.

Controlled and reversible induction of differentiation and activation of adult human hepatocytes by a biphasic culture technique.

Aim: Clinical application of human hepatocytes (HC) is hampered by the progressive loss of growth and differentiation in vitro. The object of the study was to evaluate the effect of a biphasic culture technique on expression and activation of growth factor receptors and differentiation of human adult HC.

Methods: Isolated HC were sequentially cultured in a hormone enriched differentiation medium (DM) containing nicotinamide, insulin, transferrin, selenium, and dexame-thasone or activation medium (AM) containing hepatocyte growth factor (HGF), epidermal growth factor (EGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil.

The most undesirable complication of an effective immunosuppressive therapy is neoplastic tumor recurrence or the development of de novo cancer. Though the immunosuppressive drug, mycophenolate mofetil (MMF), has been introduced into clinical practice, no data dealing with the influence of MMF on tumor cell malignancy are available. We analyzed the adhesion capacity of colon, pancreas and kidney carcinoma cell lines to endothelium, as well as their chemokine profile before and after MMF treatment.

Valproic acid modulates NCAM polysialylation and polysialyltransferase mRNA expression in human tumor cells.

Polysialic acid (PSA) is a dynamically regulated carbohydrate modification of the neural cell adhesion molecule NCAM, which has been linked to cancer development and dissemination. Two enzymes, the polysialyltransferases ST8SiaIV and ST8SiaII, are known to be involved in the polysialylation of NCAM. The antiepileptic drug valproic acid (VPA) is associated with anti-cancer activity.

Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy.

Background: Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment.

Valproic acid induces expression of neutrophil chemoattractants of the CXC chemokine family in endothelial cells.

The branched-chain fatty acid valproate (valproic acid; VPA) displays antitumoral properties by blocking tumor growth, progression and invasion. Recent data have shown that VPA reduces the angiogenic activity of endothelial cells. The object of this study was to investigate whether endothelial modulation might also influence the level of chemotactic mediators.

Uropharmacology: current and future strategies in the treatment of erectile dysfunction and benign prostate hyperplasia.

Because of the increasing percentage of the world male population suffering from erectile dysfunction (ED) and benign prostate syndrome (BPS), there is a need for new and innovative therapeutic approaches. Pharmacotherapy is an avenue presently being followed in the treatment of both these syndromes. A profound change in the therapy of ED has been obtained through use of the selective phosphodiesterase inhibitor sildenafil.

Angiogenesis inhibition by angiostatin, endostatin and TNP-470 prevents cyclophosphamide induced cystitis.

Angiogenesis, the induction of vessel growth is involved in numerous physiological and pathological processes. While the anti-tumor effect of angiogenesis inhibitors has been extensively investigated in malignant tumors, there is very little information on the effect of angiogenesis inhibitors on inflammation induced angiogenesis. In this report, we utilized a murine model of acute chemically induced cystitis to investigate the ability of three different angiogenesis inhibitors, angiostatin, endostatin and TNP-470, to inhibit the angiogenesis stimulated by this injury.

Human cytomegalovirus infection of tumor cells downregulates NCAM (CD56): a novel mechanism for virus-induced tumor invasiveness.

Pathologic data indicate that human cytomegalovirus (HCMV) infection might be associated with the pathogenesis of several human malignancies. However, no definitive evidence of a causal link between HCMV infection and cancer dissemination has been established to date. This study describes the modulation of the invasive behavior of NCAM-expressing tumor cell lines by HCMV.

Phosphorylation of hepatocyte growth factor receptor and epidermal growth factor receptor of human hepatocytes can be maintained in a (3D) collagen sandwich culture system.

In vitro culture models that employ human liver cells could be potent tools for predictive studies on drug toxicity and metabolism in the pharmaceutical industry. However, an adequate receptor responsiveness is necessary to allow intracellular signalling and metabolic activity. We tested the ability of three-dimensionally arranged human hepatocytes to respond to the growth factors hepatocyte growth factor (HGF) or epidermal growth factor (EGF).