[A critical assessment of phytotherapy for prostate cancer]. / Eine kritische Bewertung der Phytotherapie des Prostatakarzinoms.

Prostate cancer patients increasingly use complementary and alternative medicines to support the body's immune system in addition to conventional treatment to minimize morbidity associated with conventional treatment, to enhance the quality of life, and ultimately in the hope to cure cancer when conventional treatment fails. As there is a large variety of phytomedicines promoted as potential treatment for prostate cancer, the aim of this review was to differentiate between preventive and therapeutic approaches and evaluate which phytochemicals might be suited for therapy of prostate cancer. Therefore, preclinical in vitro and in vivo data as well as clinical trials with phytosubstances such as genistein, lycopene, epigallocatechin gallate, resveratrol, and mistletoe were assessed. The presented data show that at present there is no clinical evidence that phytochemicals might have a therapeutic use in prostate cancer in relation to reduction of tumor progression or improved survival. The question about an improved immune function or quality of life remains open. Potentially the use of phytochemicals could play a role in a preventive setting.

Soy isoflavone genistein in prevention and treatment of prostate cancer.

Dietary habits and incidence of prostate cancer (PCa) are very different in several parts of the world. Among the differences between Eastern and Western diets is the greater intake of soy in the Eastern cultures. This might be one factor contributing to a lower incidence of PCa in Asian men. Many studies using PCa cells and animal studies of chemical carcinogenesis have shown that a wide range of dietary compounds have cancer chemopreventive potential. Therefore, the interest in nutrition-based approaches for prevention and treatment of PCa is increasing. We reviewed all experimental preclinical in vitro and in vivo data as well as clinical trials performed with soy isoflavone genistein for prevention and treatment of PCa. The preclinical data for genistein presented in this review show a remarkable efficacy against PCa cells in vitro with molecular targets ranging from cell cycle regulation to induction of apoptosis. In addition, seemingly well-conducted animal experiments support the belief that genistein might have a clinical activity in human cancer therapy. However, it is difficult to make definite statements or conclusions on clinical efficacy of genistein because of the great variability and differences of the study designs, small patient numbers, short treatment duration and lack of a standardized drug formulation. Although some results from these genistein studies seem encouraging, reliable or long-term data on tumor recurrence, disease progression and survival are unknown. The presented data potentially allow recommending patients the use of genistein as in soy products in a preventive setting. However, at present there is no convincing clinical proof or evidence that genistein might be useful in PCa therapy.

New agents for treatment of advanced transitional cell carcinoma.

The prognosis for any patient with progressive or recurrent invasive transitional cell carcinoma remains poor. In this context, the focus of clinical research in these invasive cancers concentrates on identifying systemic treatment options and new agents in order to improve survival of patients. Cisplatin-based chemotherapy is standard treatment of patients with metastatic urothelial cancer; however, despite regimens as the cisplatin-gemcitabine combination, the overall response rates vary between 40% and 65%, with complete response in 15%-25% with survivals up to 16 months. This survival is frequently achieved with severe and life-threatening side effects. None the less, almost all responding patients relapse within the first year; therefore, the need for development of new and tolerable agents is urgent. This review highlights some new active chemotherapeutic as new platinum compounds (oxaliplatin, lobaplatin), gallium nitrate, ifosfamide, the antifolates piritrexim and pemetrexed (Alimta, LY231514), vinflunine and molecular targeting agents such as farnesyltransferase inhibitors (lonafarnib, R115777, SCH66336), ribozyme (RPI.4610), histone deacetylase inhibitor (CI-994) and monoclonal antibodies (epidermal growth factor receptor, Her 2/neu).

Superselective embolization of arterial bleeding as a late complication 3 months after nephron sparing surgery for renal cell carcinoma.

To our knowledge, this is the first case of an arterial bleeding as a late complication 3 months after nephron sparing surgery of renal cell cancer, presumably originating from an arteriocalyceal fistula. Superselective embolization of the feeding arterial branch was chosen for treatment of the hemorrhage and proved successful. The high efficacy of superselective embolization as a minimally invasive procedure in this and other cases of bleeding Vessels should be the preferred method instead of open surgery.

Preclinical evaluation of a radiosensitizing effect of gemcitabine in p53 mutant and p53 wild type bladder cancer cells.

OBJECTIVES: Despite clinical use, the radiosensitizing effect of gemcitabine (2'2'-difluorodeoxycytidine) in human transitional cell carcinoma (TCC) has not been shown to date. We investigated gemcitabine as a radiosensitizer for human TCC cells. METHODS: Monolayer cultures of RT112 (G1, p53 wild type), RT4 (G1-G2, p53 wild type), T24 (G3, p53, mutant type), and SUP (G4, p53 mutant type) cells were incubated in medium with gemcitabine. Electron beam radiation was applied alone, simultaneous, or 3, 6, 12, and 24 hours after gemcitabine. Jurkat leukemia cells were used as controls for radiation toxicity. Cell survival was determined 6, 12, 24, 48, and 72 hours after radiation by microculture tetrazolium assay. DNA damage was evaluated by flow cytometric assessment of poly(ADP-ribose) polymerase, and apoptosis was determined by terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling and flow cytometric assessment after annexin-V and propidium iodide labeling. RESULTS: In all TCC cell lines, radiation alone caused only little and insignificant growth inhibitory effects at 10 Gy. Gemcitabine alone had a dose-dependent cytotoxic and apoptosis inducing effect on all TCC cell lines independent of p53 status. Assays combining radiation with gemcitabine in different dose and time schedules demonstrated no radiosensitizing effect in TCC cells. CONCLUSIONS: Gemcitabine is effective in TCC cell lines independent of p53 status. A radiosensitizing effect could not be demonstrated. Again, p53 status was not predictive of the radioresponse in the bladder cancer cell lines. Clinical studies with gemcitabine and radiotherapy might nevertheless yield different results but should be performed with utmost caution.

Gemcitabine monotherapy as second-line treatment in cisplatin-refractory transitional cell carcinoma - prognostic factors for response and improvement of quality of life.

OBJECTIVES: i) To evaluate objective response, toxicity, and quality of life (QoL) of gemcitabine monotherapy as second-line treatment in patients with cisplatin-refractory, metastatic transitional cell carcinoma (TCC). ii) To assess prognostic parameters for response to treatment and for improvement of QoL parameters. PATIENTS AND METHODS: 30 patients were prospectively enrolled in this open-label, nonrandomized multicenter phase II trial. Patients received up to 6 courses of gemcitabine monotherapy (1,250 mg/m(2) on day 1 and 8 of a 21-day course). 28 of 30 patients were available for response evaluation. RESULTS: Objective response (OR) was seen in 3/28 (11%) of patients (2 complete remissions, 1 partial remission). The mean time to progression (TTP) was 4.9 +/- 3.5 months and mean disease-specific survival time was 8.7 +/- 4.7 months. 13 of 28 patients did not progress (OR + 10 stable diseases), and TTP (8.0 +/- 2.7 months, p < 0.001) as well as survival time (10.2 +/- 3.8 months, p < 0.05) differed significantly from those who showed progressive disease within 18 weeks of treatment. Pain values significantly improved in the group of responders from 4.3 +/- 1.9 to 5.8 +/- 1.3 points (p < 0.05). Response to cisplatin pretreatment was the best prognosticator for the response to gemcitabine. CONCLUSIONS: Gemcitabine monotherapy as second-line treatment is justified in patients with metastatic TCC who are refractory to cisplatin treatment. Patients with initially OR to cisplatin benefit most from second-line treatment. QoL remains stable during treatment, and pain improves especially in patients with bone metastases.

Soluble Fas and Fas-ligand in bladder cancer in vitro and in vivo.

Circulating soluble Fas (sFas) and expression of Fas-ligand on cancer cells are mechanisms of immune escape. The aim of the present study was to investigate expression and production of Fas and Fas-ligand on bladder cancer cell lines of different grade as a basic mechanism of their secretion in vivo. sFas and sFas-ligand serum levels of patients with different stage of bladder cancer were examined to determine the possible clinical use of these molecules as tumor markers. Bladder cancer cell lines RT4 (G1), RT112 (G1), T24 (G3) and SUP (G4) were analyzed by flowcytometry for Fas and Fas-ligand expression. To determine if the Fas-ligand gene is transcribed in these bladder cancer cell lines, RT-PCR was performed on mRNA extracted from these cell lines. Production of sFas and sFas-ligand was examined in cell culture supernatants of the cancer cells as well as in the serum of 62 patients with bladder cancer by a specific ELISA test. We demonstrate that Fas is expressed in similar levels on all human bladder carcinoma cell lines. In T24 (G3) and SUP (G4) cell lines we were able to detect the Fas-ligand protein, whereas no Fas-ligand protein could be found in RT4 and RT112 (G1) cells. Fas-ligand mRNA was expressed in all bladder cancer cell lines. Furthermore, all bladder cancer cell lines produce sFas but no sFas-ligand in spite of mRNA expression. The range of sFas levels in the serum of all patients with bladder cancer was large and did not show a correlation to the histopathological stage of bladder cancer. Although there is in vitro evidence that sFas and Fas-ligand play a role in bladder cancer, no correlation between the sFas and s Fas-ligand serum levels and the histopathological stage of bladder cancer could be found. Therefore, serum sFas and sFas-ligand have to date limited clinical relevance.