Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo

金沢大学医学部附属病院泌尿器科Purpose: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. Materials and methods: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n = 6-8). Results: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 μmol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 μmol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%] = growth of TAK-165 treated tumor/average growth of control tumor × 100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. Conclusions: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer

Search for VHE gamma rays from SS433/W50 with the CANGAROO-II telescope

SS433, located at the center of the supernova remnant W50, is a close proximity binary system consisting of a compact star and a normal star. Jets of material are directed outwards from the vicinity of the compact star symmetrically to the east and west

Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC

Purpose: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. Patients and methods: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). Results: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with Conclusions: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870)

Reproducibility and validity of food group intake in a short food frequency questionnaire for the middle-aged Japanese population

Purpose: The purpose of this study was to evaluate the reproducibility and validity of a short food frequency questionnaire (FFQ) for food group intake in Japan, the reproducibility and partial validity of which were previously confirmed for nutrients. Methods: A total of 288 middle-aged healthy volunteers from 11 different areas of Japan provided nonconsecutive 3-day weighed dietary records (DRs) at 3-month intervals over four seasons. We evaluated reproducibility based on the first (FFQ1) and second (FFQ2) questionnaires and their validity against the DRs by comparing the intake of 20 food groups. Spearman’s rank correlation coefficients (SRs) were calculated between energy-adjusted intake from the FFQs and that from the DRs. Results: The intake of 20 food groups estimated from the two FFQs was mostly equivalent. The median energy-adjusted SRs between the FFQ1 and FFQ2 were 0.61 (range 0.38–0.86) for men and 0.66 (0.45–0.84) for women. For validity, the median de-attenuated SRs between DRs and the FFQ1 were 0.51 (0.17–0.76) for men and 0.47 (0.23–0.77) for women. Compared with the DRs, the proportion of cross-classification into exact plus adjacent quintiles with the FFQ1 ranged from 58 to 86% in men and from 57 to 86% in women. According to the robust Z scores and the Bland–Altman plot graphs, the underestimation errors in the FFQ1 tended to be greater in individuals with high mean levels of consumption for meat for men and for other vegetables for both men and women. Conclusion: The FFQ demonstrated high reproducibility and reasonable validity for food group intake. This questionnaire is short and remains appropriate for identifying associations between diet and health/disease among adults in Japan

Detection of Gamma-rays around 1TeV from RX J0852.0-4622 by CANGAROO-II

We have detected gamma-ray emission at the 6sigma level at energies greater than 500GeV from the supernova remnant RX J0852.0-4622 (G266.2-1.2) using the CANGAROO-II Imaging Atmospheric Cherenkov Telescope (IACT). The flux was 0.12 times of that of Crab at 1TeV. The signal centroid is consistent with the peak of the X-ray emission in the north-west rim of the remnant.Comment: 12pages, 4figures, to be published in ApJ

Search for TeV gamma-rays from SN 1987A in 2001

We searched for TeV gamma-rays from the remnant of SN 1987A around 5400 days after the supernova. The observations were carried out in 2001, from November 16 to December 11, using the CANGAROO-II Imaging Atmospheric Cherenkov Telescope. In total, 708 minutes of ON- and 1019 minutes of OFF-source data were obtained under good conditions. The detection threshold was estimated to be 1 TeV, due to the mean zenith angle of 39$^\circ$. The upper limits for the gamma-ray flux were obtained and compared with the previous observations and theoretical models. The observations indicate that the gamma-ray luminosity is lower than $1\times 10^{37}$ erg s$^{-1}$ at $\sim 10$ TeV.Comment: 8 pages, 3 figures, submitted for publication, style file adde

Detection of diffuse TeV gamma-ray emission from the nearby starburst galaxy NGC 253

We report the TeV gamma-ray observations of the nearby normal spiral galaxy NGC 253. At a distance of $\sim$2.5 Mpc, NGC 253 is one of the nearest starburst galaxies. This relative closeness, coupled with the high star formation rate in the galaxy, make it a good candidate TeV gamma-ray source. Observations were carried out in 2000 and 2001 with the CANGAROO-II 10 m imaging atmospheric Cerenkov telescope. TeV gamma-ray emission is detected at the $\sim 11\sigma$ level with a flux of $(7.8 \pm 2.5)\times 10^{-12} {\rm cm}^{-2} {\rm sec}^{-1}$ at energies $>$0.5 TeV. The data indicate that the emission region is broader than the point spread function of our telescope.Comment: 4 pages, double colomn, 3 figures, aa.cl