Atsushi Igarashi

Detection of circulating urothelial cancer cells in the blood using the CellSearch System

Circulating tumor cells (CTCs) have been shown to aid in the therapeutic management of patients. But, only a few attempts have been made at the detection of urothelial cancer cells in the blood. The purpose of this study was to test the hypothesis that CTCs are detected in patients with urothelial cancers using newly developed CellSearch Assay.

INITIAL EXPERIENCE OF THE ENZALUTAMIDE TREATMENT FOR CASTRATION-RESISTANT PROSTATE CANCER

(Objective) Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with castration-resistant prostate cancer (CRPC). We retrospectively evaluated clinical efficacy and safety of enzalutamide in CRPC. (Patients and methods) We reviewed clinical records of 73 patients who had received enzalutamide for the CRPC at Showa University and affiliated 7 hospitals. Enzalutamide was given at a dose of 160 mg/day, but some patients were treated at lower dose because of there age or poor performance status. Prostrate-specific antigen (PSA) response, prior docetaxel use and the previously administered agents were evaluated retrospectively. (Results) The median patients age was 77 years, the median Gleason score was 9 and the median PSA level at baseline was 26.9 ng/ml. The patients who had prior docetaxel use were 29 (39.7%) and the median of total docetaxel dose was 460 mg/body. The median number of total prior treatments (anti-androgens, Estramustine and steroid) was 3. Twenty seven (61.4%) patients with docetaxel-naïve achieved over 50% reduction of PSA level from baseline, but only 7 (24.1%) in patients previously treated with docetaxel. The most common adverse events included fatigue (24.7%), anorexia (24.7%) and the nausea (16.4%). We found a small proportion of responders to enzalutamide experienced a PSA flare. (Conclusion) Our results of the use of Enzaltamide for CRPC were similar with previous reports. PSA flare was found in some patients with CRPC who responded to enzaltamide. It should be noted that this possible PSA flare phenomenon.

Enhancement of IL-2-induced cytotoxicity by interferon-alpha in renal cell carcinoma.

Metastatic renal cell carcinoma (mRCC) treatment consists of molecular targeted agents and cytokines that have fundamentally different mechanisms of action. Clinical responses also differ; complete response is rare with molecular targeted agents but is sometimes achieved with cytokine therapies. Because of the relatively high efficacy of combination therapy with low-dose interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) against mRCC, it is important to reevaluate cytokine therapies in vitro. Here, we show that when IL-2 is administered in combination with IFN-alpha, a stronger cytotoxic effect of PBMCs on RCC cell lines is observed than when IL-2 is administered alone. The upregulation of TNF-related apoptosis-inducing ligand on NK cell by IL-2 and suppression of regulatory T cells (Tregs) by IFN-alpha were recognized at the same time when cytotoxicity of peripheral blood mononuclear cells (PBMCs) was enhanced. IL-2 is known to activate natural killer cell cytotoxicity; however, IL-2 also stimulates Treg expansion, which enhances immunosuppression. On the other hand, IFN-alpha negatively regulates Treg cells, thereby increasing the function of immune effector cells. Our in vitro results may explain, at least in part, the clinical efficacy of combination low-dose IL-2 and IFN-alpha therapy against mRCC.