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INTRODUCTION AND OBJECTIVE:Recent evidence suggests that human leukocyte antigen class I (HLA-I) genotypes influence cancer response to checkpoint blockade immunotherapy. In this study, we assessed...

INTRODUCTION AND OBJECTIVE:Selection of patients for cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) is challenging. We evaluated the utility of the scoring system of Regis...

INTRODUCTION AND OBJECTIVES:CHOKAI and STONE are clinical scoring systems for predicting the presence ureteral stones. The former system consists of seven categories: sex, timing, age, nausea/vomit...

INTRODUCTION AND OBJECTIVES:The eukaryotic initiation factor 4E (eIF4E) is a 5′-cap component binding to mRNA. It is regulated by two pathways; mTOR/4EBP1/eIF4E and MNK/eIF4E pathway. The mTOR/4EBP...

INTRODUCTION AND OBJECTIVES: Renal dysfunction is frequent side effect of VEGFR-inhibitors, especially sunitinib. We investigated the association of renal function change during VEGFR-inhibitors administration and antitumor efficacy in patients with metastatic renal cell carcinoma (mRCC). METHODS: Retrospective data were collected for mRCC patients received VEGF-targeted therapy between January 2005 and October 2011. We investigated renal adverse events and clinically significant increased serum creatinine level in patients who received VEGF targeted therapy. GFR was estimated with the Modification of Diet in Renal Disease (MDRD) formula. RESULTS: Ninety three patients with mRCC who received sunitinib (n 46), sorafenib (n 38), axitnib (n 9) were included in this analysis. During administration, gradual and significant increase of serum creatinine was observed in 34 (73.9 %) sunitinib recipients compared with sorafenib (15.2 %) or axitinib (33.3 %) recipients (p 0.041). Significant decrease of estimated GFR (eGFR) compared to baseline correlated with increase of serum creatinine level developed in ‘on’ period of 6 sunitinib administration cycle (p 0.013). No significant change was observed in serum creatinine level and eGFR in patients received other VEGF-targeted agents. Decrease of eGFR in the first ‘on’ period was associated with less frequent tumor response to sunitinib and a short time to disease progression (p 0.028 and 0.042). CONCLUSIONS: Our data suggest that nephrotoxicity developed in a high percentage of patients on sunitinib compared for sorafenib and axitinib in mRCC patients. In patients with mRCC, sunitinib-associated renal function impairment in the first ‘on’ period may be an efficacy biomarker.

assay, matrigel invasion assay and XTT assay, respectively. RESULTS: We found that chromosome 8q24.3 loci was considerably amplified in the 5 UC cell lines. LY6K was the most amplified gene (6.14-fold) among the genes on 8q24.3 by the CGH array as well as the most up-regulated gene (2.84-fold) on 8q24.3 by the cDNA microarray using clinical UCs. Real-time RT-PCR reveals that LY6K mRNA expression was significantly higher in clinical UCs than in NBEs (77.7 ± 19.1 vs. 2.4 ± 0.6, p < 0.0001). Wound healing assays demonstrated a significant wound healing acceleration in the LY6K transfectant compared to control and wild-type T24 cells (% of wound closure; 100 ± 2.3, 64.2 ± 5.8, and 67.4 ± 4.4, respectively, p < 0.0001). Matrigel invasion assay also showed a significant invasion acceleration in LY6K transfectant compared to the counterparts (cell counts; 99.3 ± 10.2, 43.5 ± 4.9, and 42.8 ± 3.4, respectively, p = 0.0249). No significant difference was observed in cell proliferation between the cells. CONCLUSIONS: Our data imply that LY6K might be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for UC treatment.

253 SMAC-N7 PEPTIDE WAS MORE POTENT THAN XIAP GENE TARGETING IN SENSITIZING RENAL CANCER CELLS TO APOPTOTIC STIMULI Tomoyuki Kato*, Sei Naito, Hisashi Kawazoe, Tomohiro Shibasaki, Yuko Nakano, Takuya Yamanobe, Akira Kajinuma, Akinori Muto, Bilim Vladimir, Akira Nagaoka, Yoshihiko Tomita. Yamagata, Japan. INTRODUCTION AND OBJECTIVE: Renal cell carcinoma (RCC) is known to be resistant to chemoand radiotherapy due to a high apoptotic threshold. Inducing apoptosis in RCC cells leads to tumor regression and a molecule responsible for avoiding apoptosis can be a biomarker of molecular target therapy. In this study we tried to manipulate function of the strong anti-apoptotic molecule, XIAP, using RNAi and a peptide mimicking its inhibitory molecule, the second mitochondriaderived activator of caspase (Smac), releasing from mitochondria when a cell is exposed to apoptotic stimuli. METHODS: The surgical specimens from 34 patients who underwent surgery for RCC from January to December 2005 at the Yamagata University Hospital were subjected to immunohistochemical staining with anti-Smac and XIAP antibodies. Staining score was calculcuated by staining intensity multiplied by percent of positive cells, range 0-300. Caki1 RCC cell line with high levels of XIAP was transfected with XIAP targeting shRNA vector and stable clones were generated. The cell permeable peptide Smac-N7 was applied to in vitro treatment of the Caki1. Detection of apoptosis was performed by Hoechst 33342 and Giemsa staining and cell viability was checked by MTS assay. RESULTS: Smac was found in all tumors with staining scores varying from 200 to 300 and staining intensity was weaker than in normal kidneys. XIAP expression levels increased from pT1 (mean score 164.4±108.2) to pT2(195.0±83.3) and pT3(266.7±57.7), as well as from grade 1 (75.0± 98.7) to grade 2 (201.2 ± 93.6) (p