Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's immune system in controlling the devastating course of metastatic renal cell carcinoma. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a 'mixed response', and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.
ObjectiveTo date, only few studies have evaluated the impact of ureteral stenting prior to ureterorenoscopy. This study is to clarify the role of preoperative ureteral stenting in the treatment for ureteral stones.MethodsWe retrospectively reviewed 550 ureterorenoscopies from 1998 to 2008. Patients were classified into two groups depending on whether they had a stent placed before URS. Baseline characteristics of patients and stone properties, stone-free rates, complications, and operation times were compared between both groups. Subanalysis was performed regarding stone localization. We retrospectively reviewed data from patient documentation, X-ray imagery, intravenous urography, and operation reports.ResultsBaseline characteristics of patients were similar in both groups. The majority of patients underwent stent placement before the ureteroscopic stone treatment (88.4%). The mean operation time in the prestented group was longer (43.3 vs. 38.4 min). Stone-free rate of patients with stent was 72.2%, compared to 59.4% without preoperative stenting. The rate of minor complications was 4.7% with stent versus 9.4% without stent, major complications 0.6% versus 1.6%, respectively. Patients with distal ureter stones had similar stone-free rates regardless of a stent placement (90.1% with stent vs. 87.6% without), and no difference in complication rates was observed (3.5% with stent vs. 3.1% without), respectively.ConclusionsStent placement prior to ureteroscopic stone treatment in distal ureter is not reasonable and does not considerably improve stone-free rates.
In the prostate, estrogen receptor B (ERB), the preferred receptor for phytoestrogens, has features of a tumor suppressor. To investigate the mechanisms underlying the beneficial effects on prostate cancer of histone deacetylase inhibitor valproic acid (VPA) and phytoestrogen tectorigenin, we analyzed the expression of ERB after tectorigenin or VPA treatment. For further functional analysis, we knocked down ERB expression by RNA interference. LNCaP prostate cancer cells were treated with 5 mmol/L VPA or 100 Mmol/L tectorigenin and transfected with small interfering RNA (siRNA) against ERB. Control transfections were done with luciferase (LUC) siRNA. Expression of ERB was assessed by Western blot. mRNA expression was quantitated by real-time reverse transcription-PCR. Expression of ERB mRNA and protein markedly increased after VPA or tectorigenin treatment. When ERB was knocked down by siRNA, the expression of prostatederived Ets factor, prostate-specific antigen, prostate cancer -specific indicator gene DD3 PCA3 , insulin-like growth factor-1 receptor, the catalytic subunit of the telomerase, and ERA was up-regulated and the tectorigenin effects were abrogated. ERB levels were diminished in prostate cancer and loss of ERB was associated with proliferation. Here, we show that siRNA-mediated knockdown of ERB increases the expression of genes highly relevant to tumor cell proliferation. In addition, we show that one prominent result of treatment with VPA or tectorigenin is the up-regulation of ERB resulting in antiproliferative effects. Thus, these drugs, by restoring the regulatory function of ERB in tumor cells, could become useful in the intervention of prostate cancer. [Mol Cancer Ther 2007;6(10):2626 -33]
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