Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan.

Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone.

High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination.

Our previously reported phase I clinical trial with the allogeneic gene-modified tumor cell line RCC-26/CD80/IL-2 showed that vaccination was well tolerated and feasible in metastatic renal cell carcinoma (RCC) patients. Substantial disease stabilization was observed in most patients despite a high tumor burden at study entry. To investigate alterations in immune responses that might contribute to this effect, we performed an extended immune monitoring that included analysis of reactivity against multiple antigens, cytokine/chemokine changes in serum and determination of the frequencies of immune suppressor cell populations, including natural regulatory T cells (nTregs) and myeloid-derived suppressor cell subsets (MDSCs).

High DGK-α and disabled MAPK pathways cause dysfunction of human tumor-infiltrating CD8+ T cells that is reversible by pharmacologic intervention.

CD8(+) tumor-infiltrating T cells (CD8-TILs) are found in many types of tumors including human renal cell carcinoma. However, tumor rejection rarely occurs, suggesting limited functional activity in the tumor microenvironment. In this study, we document that CD8-TILs are unresponsive to CD3 stimulation, showing neither lytic activity, nor lytic granule exocytosis, nor IFN-γ production.

[Metastatic renal cell cancer in Germany in 2010. Impact of different target therapies].

Background: Since 2006 in Germany six different target drugs for therapy in metastatic renal cell cancer (mRCC) have been used. Comparative studies for the application with the same indication are absent, and the order of potential sequential therapy is up to now unclear. The aim of the study was to collect data on therapy decisions in Germany regarding mRCC in the age of "targeted therapy".

A clinical phase I/II trial with the monoclonal antibody cG250 (RENCAREX®) and interferon-alpha-2a in metastatic renal cell carcinoma patients.

Purpose: To evaluate the efficacy and safety of WX-G250, a chimeric monoclonal antibody that binds to carboxy anhydrase IX, combined with low-dose interferon-alpha (LD-IFNα) in patients with progressive metastatic renal cell carcinoma (mRCC).

Patients And Methods: Thirty-one patients, nephrectomized for the primary tumor, clear cell progressive mRCC, were enrolled to receive weekly infusions of WX-G250 (20 mg i.v.

Survival benefit of radical prostatectomy in lymph node-positive patients with prostate cancer.

Background: Positive lymph node (LN) status is considered a systemic disease state. In prostate cancer, LN-positive diagnosis during pelvic LN dissection (PLND) potentially leads to the abandonment of radical prostatectomy (RP).

Objective: To compare the overall survival (OS) and relative survival (RS; as an estimate for cancer-specific survival) in LN-positive patients with or without RP.

[Impact of immunotherapy in metastatic kidney cancer in Germany after introduction of new target therapy--results of a telephone survey of the German Society of Immuno- and Targeted Therapy (DGFIT)].

Introduction: Until recently, the standard therapy for metastatic renal cell carcinoma (mRCC) in Germany consisted of interleukin-2 (IL-2), interferon-alfa (IFN) as single agents or in combination, with or without chemotherapy. Since 2005, new drugs (target drugs) in the therapy for mRCC are available. The aim of this study was to analyse the current therapy standard in Germany.

Phase 1 trial of allogeneic gene-modified tumor cell vaccine RCC-26/CD80/IL-2 in patients with metastatic renal cell carcinoma.

Preclinical studies showed that the allogeneic tumor cell line RCC-26 displayed natural immunogenic potential that was enhanced through expression of CD80 costimulatory molecules and secretion of interleukin-2. Here we report the study of RCC-26/CD80/IL-2 cells in a phase 1 vaccine trial of renal cell carcinoma patients with metastatic disease (mRCC). Fifteen patients of the HLA-A*0201 allotype, with at least one metastatic lesion, were included.

Prognostic relevance of disseminated tumour cells in bone marrow of patients with transitional cell carcinoma.

Objective: This prospective study is the first immunocytochemical investigation of the frequency and prognostic value of CK+ tumour cells in the bone marrow of patients with transitional cell carcinoma (TCC).

Methods: Bone marrow aspirates from 228 TCC patients were taken preoperatively. Cytospins were made and stained by immunocytochemistry using the monoclonal antibodies CK2 and A45-B/B3.

Efficacy and safety of TachoSil as haemostatic treatment versus standard suturing in kidney tumour resection: a randomised prospective study.

Objective: Elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) has gained general acceptance as an alternative to radical nephrectomy. To achieve haemostasis without risk of local ischaemia and necrosis of kidney parenchyma after standard haemostatic suturing, we investigated TachoSil's efficacy and safety as atraumatic haemostatic treatment after kidney tumour resection.

Methods: A total of 185 patients scheduled for NSS for small, superficial kidney tumours were included in an open, randomised, prospective, multicentre, parallel-group trial.

A phase I study with adecatumumab, a human antibody directed against epithelial cell adhesion molecule, in hormone refractory prostate cancer patients.

Aim Of The Study: Adecatumumab (also known as MT201) is a human recombinant IgG1 monoclonal antibody binding with low affinity to epithelial cell adhesion molecule (EpCAM). To explore safety, pharmacokinetics and pharmacodynamics of adecatumumab, a phase I trial in patients with hormone refractory prostate cancer (HRPC) was performed.

Methods: Twenty patients were treated with two adecatumumab infusions on days 0 and 14 in cohorts with doses of ten up to 262 mg/m2.

Frequency and prognostic relevance of disseminated tumor cells in bone marrow of patients with metastatic renal cell carcinoma.

Background: The prognostic relevance of disseminated cytokeratin-positive (CK+) tumor cells in the bone marrow of patients with different types of carcinoma has been demonstrated in several studies. In this prospective study, the frequency and prognostic value of CK+ tumor cells was investigated in the bone marrow of 55 consecutive patients with metastatic renal cell carcinoma (M1 RCC) in comparison with 256 M0 RCC patients from a previous study.

Methods: Aspiration of bone marrow from the anterior iliac crest was performed immediately before tumor resection in RCC patients.

Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells.

Initial vaccine developments for renal cell carcinoma (RCC) have concentrated on cell-based approaches in which tumor cells themselves provide mixtures of unknown tumor-associated antigens as immunizing agents. Antigens derived from autologous tumors can direct responses to molecular composites characteristic of individual tumors, whereas antigens derived from allogeneic tumor cells must be commonly shared by RCC. Three types of cell-based vaccine for RCC have been investigated: isolated tumor cell suspensions, gene modified tumor cells and dendritic cells (DCs) expressing RCC-associated antigens.

Influence of CD80, interleukin-2, and interleukin-7 expression in human renal cell carcinoma on the expansion, function, and survival of tumor-specific CTLs.

Purpose: A renal cell carcinoma (RCC) line, RCC-26, has been identified as a suitable candidate for development of an allogeneic tumor cell vaccine based on its expression of a variety of tumor-associated antigens (TAA). To improve immunogenicity, RCC-26 cells were genetically engineered to express CD80 alone or in combination with interleukin (IL)-2 or IL-7. The effect of these modifications on proliferation, function, and survival of autologous and allogeneic tumor-specific CTLs was assessed.

Local recurrence in patients after radical cystectomy and orthotopic ileal neobladder: impact on function.

Whether an orthotopic bladder substitute should be constructed in patients with locally advanced or lymph node positive bladder cancer remains a subject of debate. These patients are at risk that local recurrence may impair reservoir function in orthotopic neobladders. We retrospectively assessed reservoir function in 68 consecutive patients with locally advanced bladder cancer.

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

Purpose: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma.

Patients And Methods: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine.

Detection and prognostic value of cytokeratin positive tumor cells in bone marrow of patients with renal cell carcinoma.

Purpose: Several investigations indicate the prognostic value of disseminated cytokeratin positive tumor cells in bone marrow of patients with carcinoma of different origin. In this study we evaluated the prognostic significance of epithelial cells in bone marrow of patients with renal cell carcinoma (RCC).

Materials And Methods: Aspiration of bone marrow was performed preoperatively in 335 patients with RCC between 1990 and 1998.

[Surgical treatment of pulmonary metastases from renal cancer].

Based on a large single-center follow-up database, we evaluated the long-term results after curative resection of pulmonary metastases from renal cancer. During a 20-year period, 105 patients underwent a total of 150 resections with curative intention. Hospital mortality was 0.

Application of Photofrin II as a specific radiosensitising agent in patients with bladder cancer--a report of two cases.

Background: The effect of ionizing radiation on tumour tissues can be optimised by adding radiosensitising agents to enhance tumour inactivation. Photofrin II has been approved as a photosensitising agent for the photodynamic therapy (PDT) of selected solid tumours. At present, no chemical modifier has been found to act as a selective radiosensitiser.

Disseminated tumor cells in bone marrow of patients with transitional cell carcinoma: immunocytochemical detection and correlation with established prognostic indicators.

Purpose: Previous investigations have demonstrated the prognostic value of disseminated cytokeratin positive cells in bone marrow of patients with breast, gastric, colon and prostate cancer. We evaluated the potential of an immunocytochemical assay, using a monoclonal antibody against cytokeratin 18 (CK 18), for the detection of disseminated tumor cells in bone marrow aspirates of patients with transitional cell carcinoma.

Materials And Methods: Bone marrow aspiration was performed preoperatively on 128 patients with transitional cell carcinoma of various stages and on 27 controls with nonmalignant disease.

Isolation of circulating cancer cells from whole blood by immunomagnetic cell enrichment and unenriched immunocytochemistry in vitro.

Purpose: We improved tumor cell detection compared with currently available immunocytochemical methods by immunomagnetic cell enrichment.

Materials And Methods: Two methods of immunomagnetic enrichment using antibody coated magnetic beads were tested and compared with unenriched immunocytochemistry, including positive selection of epithelial cells with the antiepithelial antibody BER-EP4 and depletion of mononuclear cells with the anti-leukocyte antibody CD45. Various numbers of tumor cells from the 4 tissue culture cell lines DU 145, RT-4, KTCTL-2 and KTCTL-30 obtained from urological tumors were added to whole blood and mononuclear cells were isolated by density centrifugation.

[Telerobotic surgery between Baltimore and Munich].

The rapid development of laparoscopy in urology necessitates the training of specialists to guarantee the high standard of patient care. The real-time data communication of medical information between physicians in different locations is known as telemedicine. Telementoring describes the assistance of an experienced surgeon, while telerobotics requires the use of robots.