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1. Updated design of the CMB polarization experiment satellite LiteBIRD

Author

Sugai, H., Ade, P. A. R., Akiba, Y., Alonso, D., Arnold, K., Aumont, J., Austermann, J., Baccigalupi, C., Banday, A. J., Banerji, R., Barreiro, R. B., Basak, S., Beall, J., Beckman, S., Bersanelli, M., Borrill, J., Boulanger, F., Brown, M. L., Bucher, M., Buzzelli, A., Calabrese, E., Casas, F. J., Challinor, A., Chan, V., Chinone, Y., Cliche, J. -F., Columbro, F., Cukierman, A., Curtis, D., Danto, P., de Bernardis, P., de Haan, T., De Petris, M., Dickinson, C., Dobbs, M., Dotani, T., Duband, L., Ducout, A., Duff, S., Duivenvoorden, A., Duval, J. -M., Ebisawa, K., Elleflot, T., Enokida, H., Eriksen, H. K., Errard, J., Essinger-Hileman, T., Finelli, F., Flauger, R., Franceschet, C., Fuskeland, U., Ganga, K., Gao, J. -R., Génova-Santos, R., Ghigna, T., Gomez, A., Gradziel, M. L., Grain, J., Grupp, F., Gruppuso, A., Gudmundsson, J. E., Halverson, N. W., Hargrave, P., Hasebe, T., Hasegawa, M., Hattori, M., Hazumi, M., Henrot-Versille, S., Herranz, D., Hill, C., Hilton, G., Hirota, Y., Hivon, E., Hlozek, R., Hoang, D. -T., Hubmayr, J., Ichiki, K., Iida, T., Imada, H., Ishimura, K., Ishino, H., Jaehnig, G. C., Jones, M., Kaga, T., Kashima, S., Kataoka, Y., Katayama, N., Kawasaki, T., Keskitalo, R., Kibayashi, A., Kikuchi, T., Kimura, K., Kisner, T., Kobayashi, Y., Kogiso, N., Kogut, A., Kohri, K., Komatsu, E., Komatsu, K., Konishi, K., Krachmalnicoff, N., Kuo, C. L., Kurinsky, N., Kushino, A., Kuwata-Gonokami, M., Lamagna, L., Lattanzi, M., Lee, A. T., Linder, E., Maffei, B., Maino, D., Maki, M., Mangilli, A., Martínez-González, E., Masi, S., Mathon, R., Matsumura, T., Mennella, A., Migliaccio, M., Minami, Y., Mistuda, K., Molinari, D., Montier, L., Morgante, G., Mot, B., Murata, Y., Murphy, J. A., Nagai, M., Nagata, R., Nakamura, S., Namikawa, T., Natoli, P., Nerva, S., Nishibori, T., Nishino, H., Nomura, Y., Noviello, F., O'Sullivan, C., Ochi, H., Ogawa, H., Ohsaki, H., Ohta, I., Okada, N., Pagano, L., Paiella, A., Paoletti, D., Patanchon, G., Piacentini, F., Pisano, G., Polenta, G., Poletti, D., Prouvé, T., Puglisi, G., Rambaud, D., Raum, C., Realini, S., Remazeilles, M., Roudil, G., Rubiño-Martín, J. A., Russell, M., Sakurai, H., Sakurai, Y., Sandri, M., Savini, G., Scott, D., Sekimoto, Y., Sherwin, B. D., Shinozaki, K., Shiraishi, M., Shirron, P., Signorelli, G., Smecher, G., Spizzi, P., Stever, S. L., Stompor, R., Sugiyama, S., Suzuki, A., Suzuki, J., Switzer, E., Takaku, R., Takakura, H., Takakura, S., Takeda, Y., Taylor, A., Taylor, E., Terao, Y., Thompson, K. L., Thorne, B., Tomasi, M., Tomida, H., Trappe, N., Tristram, M., Tsuji, M., Tsujimoto, M., Tucker, C., Ullom, J., Uozumi, S., Utsunomiya, S., Van Lanen, J., Vermeulen, G., Vielva, P., Villa, F., Vissers, M., Vittorio, N., Voisin, F., Walker, I., Watanabe, N., Wehus, I., Weller, J., Westbrook, B., Winter, B., Wollack, E., Yamamoto, R., Yamasaki, N. Y., Yanagisawa, M., Yoshida, T., Yumoto, J., Zannoni, M., and Zonca, A.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Recent developments of transition-edge sensors (TESs), based on extensive experience in ground-based experiments, have been making the sensor techniques mature enough for their application on future satellite CMB polarization experiments. LiteBIRD is in the most advanced phase among such future satellites, targeting its launch in Japanese Fiscal Year 2027 (2027FY) with JAXA's H3 rocket. It will accommodate more than 4000 TESs in focal planes of reflective low-frequency and refractive medium-and-high-frequency telescopes in order to detect a signature imprinted on the cosmic microwave background (CMB) by the primordial gravitational waves predicted in cosmic inflation. The total wide frequency coverage between 34GHz and 448GHz enables us to extract such weak spiral polarization patterns through the precise subtraction of our Galaxy's foreground emission by using spectral differences among CMB and foreground signals. Telescopes are cooled down to 5Kelvin for suppressing thermal noise and contain polarization modulators with transmissive half-wave plates at individual apertures for separating sky polarization signals from artificial polarization and for mitigating from instrumental 1/f noise. Passive cooling by using V-grooves supports active cooling with mechanical coolers as well as adiabatic demagnetization refrigerators. Sky observations from the second Sun-Earth Lagrangian point, L2, are planned for three years. An international collaboration between Japan, USA, Canada, and Europe is sharing various roles. In May 2019, the Institute of Space and Astronautical Science (ISAS), JAXA selected LiteBIRD as the strategic large mission No. 2., Comment: Journal of Low Temperature Physics, in press

Published
2020
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2. Updated Design of the CMB Polarization Experiment Satellite LiteBIRD

Author

Sugai, H, Ade, PAR, Akiba, Y, Alonso, D, Arnold, K, Aumont, J, Austermann, J, Baccigalupi, C, Banday, AJ, Banerji, R, Barreiro, RB, Basak, S, Beall, J, Beckman, S, Bersanelli, M, Borrill, J, Boulanger, F, Brown, ML, Bucher, M, Buzzelli, A, Calabrese, E, Casas, FJ, Challinor, A, Chan, V, Chinone, Y, Cliche, J-F, Columbro, F, Cukierman, A, Curtis, D, Danto, P, de Bernardis, P, de Haan, T, De Petris, M, Dickinson, C, Dobbs, M, Dotani, T, Duband, L, Ducout, A, Duff, S, Duivenvoorden, A, Duval, J-M, Ebisawa, K, Elleflot, T, Enokida, H, Eriksen, HK, Errard, J, Essinger-Hileman, T, Finelli, F, Flauger, R, Franceschet, C, Fuskeland, U, Ganga, K, Gao, J-R, Génova-Santos, R, Ghigna, T, Gomez, A, Gradziel, ML, Grain, J, Grupp, F, Gruppuso, A, Gudmundsson, JE, Halverson, NW, Hargrave, P, Hasebe, T, Hasegawa, M, Hattori, M, Hazumi, M, Henrot-Versille, S, Herranz, D, Hill, C, Hilton, G, Hirota, Y, Hivon, E, Hlozek, R, Hoang, D-T, Hubmayr, J, Ichiki, K, Iida, T, Imada, H, Ishimura, K, Ishino, H, Jaehnig, GC, Jones, M, Kaga, T, Kashima, S, Kataoka, Y, Katayama, N, Kawasaki, T, Keskitalo, R, Kibayashi, A, Kikuchi, T, Kimura, K, Kisner, T, Kobayashi, Y, Kogiso, N, Kogut, A, Kohri, K, Komatsu, E, Komatsu, K, and Konishi, K

Subjects
Physical Sciences, Classical Physics, Condensed Matter Physics, Satellite, Cosmic microwave background, Polarization, Inflation, Primordial gravitational wave, astro-ph.IM, Mathematical Physics, General Physics, Classical physics, Condensed matter physics
Abstract

Recent developments of transition-edge sensors (TESs), based on extensive experience in ground-based experiments, have been making the sensor techniques mature enough for their application on future satellite cosmic microwave background (CMB) polarization experiments. LiteBIRD is in the most advanced phase among such future satellites, targeting its launch in Japanese Fiscal Year 2027 (2027FY) with JAXA’s H3 rocket. It will accommodate more than 4000 TESs in focal planes of reflective low-frequency and refractive medium-and-high-frequency telescopes in order to detect a signature imprinted on the CMB by the primordial gravitational waves predicted in cosmic inflation. The total wide frequency coverage between 34 and 448 GHz enables us to extract such weak spiral polarization patterns through the precise subtraction of our Galaxy’s foreground emission by using spectral differences among CMB and foreground signals. Telescopes are cooled down to 5 K for suppressing thermal noise and contain polarization modulators with transmissive half-wave plates at individual apertures for separating sky polarization signals from artificial polarization and for mitigating from instrumental 1/f noise. Passive cooling by using V-grooves supports active cooling with mechanical coolers as well as adiabatic demagnetization refrigerators. Sky observations from the second Sun–Earth Lagrangian point, L2, are planned for 3 years. An international collaboration between Japan, the USA, Canada, and Europe is sharing various roles. In May 2019, the Institute of Space and Astronautical Science, JAXA, selected LiteBIRD as the strategic large mission No. 2.

Published
2020

3. Genistein Inhibits Prostate Cancer Cell Growth by Targeting miR-34a and Oncogenic HOTAIR

Author

Dahiya, Rajvir, Chiyomaru, T, Yamamura, S, Fukuhara, S, Yoshino, H, Kinoshita, T, Majid, S, Saini, S, Chang, I, Tanaka, Y, and Enokida, H

Abstract

Objective:Genistein is a soy isoflavone that has antitumor activity both in vitro and in vivo. It has been shown that genistein inhibits many type of cancers including prostate cancer (PCa) by regulating several cell signaling pathways and microRNAs (miRNA

Published
2013

4. Superoxide dismutase analog (Tempol: 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) treatment restores erectile function in diabetes-induced impotence

Author

Kawakami, T, Urakami, S, Hirata, H, Tanaka, Y, Nakajima, K, Enokida, H, Shiina, H, Ogishima, T, Tokizane, T, Kawamoto, K, Miura, K, Ishii, N, and Dahiya, R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biotechnology, Urologic Diseases, Diabetes, Metabolic and endocrine, Animals, Antioxidants, Cyclic N-Oxides, Diabetes Complications, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Endothelium, Vascular, Erectile Dysfunction, Immunohistochemistry, Male, Muscle, Smooth, Nitric Oxide Synthase Type II, Penile Erection, RNA, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Spin Labels, Superoxide Dismutase, oxidative stress, nitric oxide, superoxide, diabetes, erectile dysfunction, Psychology, Obstetrics & Reproductive Medicine, Clinical sciences, Clinical and health psychology
Abstract

We hypothesized that the administration of the superoxide dismutase (SOD) mimetic Tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) may reverse diabetes-induced erectile dysfunction. To test this hypothesis, reactive oxygen species-related genes (SOD1, SOD2, GP x 1, CAT, NOS2, NOS3) were tested, erectile functional studies and immunohistochemical analysis were carried out in diabetic rats treated with or without Tempol. Thirty Sprague-Dawley (3-4 months old) rats were divided into three groups (n=10 each), 20 with diabetes (diabetic control and Tempol treatment) and 10 healthy controls. At 12 weeks after the induction of diabetes by streptozotocin and Tempol treatment, all groups underwent in vivo cavernous nerve stimulation. Rat crura were harvested and the expression of antioxidative defense enzymes were examined by semi-quantitative reverse transcriptase PCR (RT-PCR). To confirm the RT-PCR results, we carried out immunohistochemistry (IHC) for catalase (CAT) and iNOS (NOS2). Nitration of tyrosine groups in proteins was also examined by IHC. Mean intracavernous pressure in the diabetic group was significantly lower than in the healthy controls (P

Published
2009

6. LiteBIRD: An All-Sky Cosmic Microwave Background Probe of Inflation

Author

Lee, Adrian T, Ade, P. A. R, Akiba, Y, Alonso, D, Arnold, K, Aumont, J, Austermann, J, Baccigalupi, C, Banday, A. J, Banerji, R, Barreiro, R. B, Basak, S, Beall, J, Beckman, S, Bersanelli, M, Borrill, J, Boulanger, F, Brown, M. L, Bucher, M, Buzzelli, A, Calabrese, E, Casas, F. J, Challinor, A, Chan, V, Chinone, Y, Cliche, J.-F, Columbro, F, Cukierman, A, Curtis, D, Danto, P, de Bernardis, P, de Haan, T, De Petris, M, Dickinson, C, Dobbs, M, Dotani, T, Duband, L, Ducout, A, Du, S, Duivenvoorden, A, Duval, J.-M, Ebisawa, K, Elleflot, T, Enokida, H, Eriksen, H. K, Errard, J, Essinger-Hileman, T, Finelli, F, Flauger, R, Franceschet, C, Fuskeland, U, Ganga, K, Gao, J.-R, Genovo-Santos, R, Ghigna, T, Gomez, A, Gradziel, M. L, Grain, J, Grupp, F, Gruppuso, A, Gudmundsson, J. E, Halverson, N. W, Hargrave, P, Hasebe, T, Hasegawa, M, Hattori, M, Hazumi, M, Henrot-Versille, S, Herranz, D, Hill, C, Hilton, G, Hirota, Y, Hivon, E, Hlozek, R, Hoang, D.-T, Hubmayr, J, Ichiki, K, Iida, T, Imada, H, Ishimura, K, Ishino, H, Jaehnig, G. C, Jones, M, Kaga, T, Kashima, S, Kataoka, Y, Katayama, N, Kawasaki, T, Keskitalo, R, Kibayashi, A, Kikuchi, T, Kimura, K, Kisner, T, Kobayashi, Y, Kogiso, N, Kogut, A, Kohri, K, Komatsu, E, Komatsu, K, Konishi, K, Krachmalnico, N, Kuo, C. L, Kurinsky, N, Kushino, A, Kuwata-Gonokami, M, Lamagna, L, Lattanzi, M, Lee, A. T, Linder, E, Maffei, B, Maino, D, Maki, M, Mangilli, A, Martinez-Gonzalez, E, Masi, S, Mathon, R, Matsumura, T, Mennella, A, Migliaccio, M, Minami, Y, Mistuda, K, Molinari, D, Montier, L, Morgante, G, Mot, B, Murata, Y, Murphy, J. A, Nagai, M, Nagata, R, Nakamura, S, Namikawa, T, Natoli, P, Nerval, S, Nishibori, T, Nishino, H, Nomura, Y, Noviello, F, O'Sullivan, C, Ochi, H, Ogawa, H, Ohsaki, H, Ohta, I, Okada, N, Pagano, L, Paiella, A, Paoletti, D, Patanchon, G, Piacentini, F, Pisano, G, Polenta, G, Poletti, D, Prouve, T, Puglisi, G, Rambaud, D, Raum, C, Realini, S, Remazeilles, M, Roudil, G, Rubino-Martin, J. A, Russell, M, Sakurai, H, Sakurai, Y, Sandri, M, Savini, G, Scott, D, Sekimoto, Y, Sherwin, B. D, Shinozaki, K, Shiraishi, M, Shirron, P, Signorelli, G, Smecher, G, Spizzi, P, Stever, S. L, Stompor, R, Sugai, H, Sugiyama, S, Suzuki, A, Suzuki, J, Switzer, E, Takaku, R, Takakura, H, Takakura, S, Takeda, Y, Taylor, A, Taylor, E, Terao, Y, Thompson, K. L, Thorne, B, Tomasi, M, Tomida, H, Trappe, N, Tristram, M, Tsuji, M, Tsujimoto, M, Tucker, C, Ullom, J, Uozumi, S, Utsunomiya, S, Van Lanen, J, Vermeulen, G, Vielva, P, Villa, F, Vissers, M, Vittorio, N, Voisin, F, Walker, I, Watanabe, N, Wehus, I, Weller, J, Westbrook, B, Winter, B, Wollack, E, Yamamoto, R, Yamasaki, N. Y, Yanagisawa, M, Yoshida, T, Yumoto, J, Zannoni, M, and Zonca, A

Subjects
Astrophysics
Abstract

The LiteBIRD mission will map polarized fluctuations in the cosmic microwave background (CMB) to search for the signature of gravitational waves from inflation, potentially opening a window on the Universe a fraction of a second after the Big Bang. CMB measurements from space give access to the largest angular scales and the full frequency range to constrain Galactic foregrounds, and LiteBIRD has been designed to take best advantage of the unique window of space. LiteBIRD will have a powerful ability to separate Galactic foreground emission from the CMB due to its 15 frequency bands spaced between 40 and 402 GHz and sensitive 100-mK bolometers. LiteBIRD will provide stringent control of systematic errors due to the benign thermal environment at the second Lagrange point, L2, 20-K rapidly rotating half-wave plates on each telescope, and the ability to crosscheck its results by measuring both the reionization and recombination peaks in the B-mode power spectrum. LiteBIRD would be the next step in the series of CMB space missions, COBE, WMAP, and Planck, each of which has given landmark scientific discoveries.

Published
2019

7. 136MO Efficacy and safety of pembrolizumab (pembro) monotherapy in East Asian patients (pts) with urothelial carcinoma (UC) in KEYNOTE-045 or KEYNOTE-052

Author

Lee, J-L., primary, Keam, B., additional, Kanesvaran, R., additional, Yamamoto, Y., additional, Su, W-P., additional, Chiang, P-H., additional, Lin, C-C., additional, Sassa, N., additional, Nishimura, K., additional, Fujimoto, K., additional, Chang, P.M-H., additional, Kim, M., additional, Fukasawa, S., additional, Yokoyama, M., additional, Enokida, H., additional, Xu, J., additional, Homet Moreno, B., additional, Imai, K., additional, Nishiyama, H., additional, and Rha, S.Y., additional

Published
2022
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11. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial

Author

Powles, T. van der Heijden, M.S. Castellano, D. Galsky, M.D. Loriot, Y. Petrylak, D.P. Ogawa, O. Park, S.H. Lee, J.-L. De Giorgi, U. Bögemann, M. Bamias, A. Eigl, B.J. Gurney, H. Mukherjee, S.D. Fradet, Y. Skoneczna, I. Tsiatas, M. Novikov, A. Suárez, C. Fay, A.P. Duran, I. Necchi, A. Wildsmith, S. He, P. Angra, N. Gupta, A.K. Levin, W. Bellmunt, J. van der Heijden, M.S. Lee, J.L. Eigl, B.J. Mukherjee, S.D. Suarez, C. Westgeest, H. Flechon, A. Ou, Y.-C. Park, I. Matveev, V. Pérez-Valderrama, B. Cheng, S. Frank, S. Anido, U. Hamzaj, A. Retz, M. Sridhar, S. Scagliotti, G.V. Voortman, J. Alekseev, B. Alyasova, A. Komyakov, B. Dumez, H. Pavic, M. Kimura, G. Mizokami, A. Osanto, S. Arranz, J.A. Piersma, D. Shin, S.J. Karyakin, O. Delgado, I. Gonzalez, J.L. Pang, S.-T. Tran, A. Lipatov, O. Su, W.-P. Flaig, T. Alva, A. Park Kyong, H. Kopyltsov, E. Almagro, E. Domenech, M. Chang, Y.-H. Sautois, B. Ravaux, A. Aravantinos, G. Georgoulias, V. Mulder, S. Kim, Y.J. Kater, F. Chevreau, C. Tagawa, S. Zalewski, P. Joly, F. Hatiboglu, G. Gianni, L. Morelli, F. Tambaro, R. Hashimoto, Y. Nosov, A. Font, A. Rodriguez-Vida, A.M. Jones, R. Vasudev, N. Srinivas, S. Zhang, J. Gil, T. Finch, D. Grimm, M.-O. Su, Y.-L. Chowdhury, S. Hocking, C. Plas, E. North, S. Jensen, N.V. Theodore, C. Imkamp, F. Peer, A. Kobayashi, T. Sakai, H. Sassa, N. Yoshimura, K. Aarts, M. Ferreira Castro, A. Topuzov, M. Rodriguez, J.F. Vazquez, F.J. Tsai, Y.-C. Crabb, S. Hussain, S. Bendell, J. Gross-Goupil, M. Gwenaelle, G. Berger, R. Statsenko, G. Evans, L. Drakaki, A. Somer, B. Davis, I. Lynam, J. Borges, G. Dettino, A. Fay, A.P. Martins, G. Zucca, L.E. Agerbaek, M. Kalofonos, H. Rosenbaum, E. Enokida, H. Kikukawa, H. Nishimura, K. Tamada, S. Uemura, M. Lopez, Y. Gietema, J. Slojewski, M. Fernandes, I. Smolin, A. Mazhar, D. Kalebasty, A.R. Carthon, B. Loidl, W. Franke, F. Girotto, G. Alimohamed, N. Macfarlane, R. Pappot, H. Niegisch, G. Mavroudis, D. Sella, A. Porta, C. Ebara, S. Nakamura, M. Obara, W. Okuno, N. Shinohara, N. Sugimoto, M. Suzuki, A. Tokuda, N. Uemura, H. Yamaguchi, A. Ramirez, F. Rozanowski, P. Wiechno, P. Keam, B. Kislov, N. Plaksin, D. Cicin, I. Kumar, S. Galsky, M.D. Petrylak, D.P. Rosales, J. Vaishampayan, U. Culine, S. Papandreou, C. Nara, T. Erman, M. Kreiger, L. Janoski, J. Rosa, D. Siqueira, M. Canil, C. Sengelov, L. Tourani, J.-M. Arai, G. Hashine, K. Kawakita, M. Nakaigawa, N. Nomi, H. Shiina, H. Suzuki, H. Yonese, J. Kuri, R. Macedo, E. Rivera, S. Villalobos Prieto, A. Polakiewicz-Gilowska, A. Zaucha, R. Lopes, F. Ponomarev, R. Pomerantz, M. Shariat, S. Luk, C. Lesniewski-Kmak, K.

Abstract

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (

Published
2020

12. LiteBIRD: an all-sky cosmic microwave background probe of inflation

Author

Adrian, Lee, Ade, P. A. R., Akiba, Y., Alonso, D., Arnold, K., Aumont, J., Austermann, J., Baccigalupi, C., Banday, A. J., Banerji, R., Barreiro, R. B., Basak, S., Beall, J., Beckman, S., Bersanelli, M., Borrill, J., Boulanger, F., Brown, M. L., Bucher, M., Buzzelli, A., Calabrese, E., Casas, F. J., Challinor, A., Chan, V., Chinone, Y., Cliche, J. -F, Fabio Columbro, Cukierman, A., Curtis, D., Danto, P., Paolo de Bernardis, Haan, T., Marco De Petris, Dickinson, C., Dobbs, M., Dotani, T., Duband, L., Ducout, A., Duff, S., Duivenvoorden, A., Duval, J. -M, Ebisawa, K., Elleflot, T., Enokida, H., Eriksen, H. K., Errard, J., Essinger-Hileman, T., Finelli, F., Flauger, R., Franceschet, C., Fuskeland, U., Ganga, K., Gao, J. -R, Genova-Santos, R., Ghigna, T., Gomez, A., Gradziel, M. L., Grain, J., Grupp, F., Gruppuso, A., Gudmundsson, J. E., Halverson, N. W., Hargrave, P., Hasebe, T., Hasegawa, M., Hattori, M., Hazumi, M., Henrot-Versille, S., Herranz, D., Hill, C., Hilton, G., Hirota, Y., Hivon, E., Hložek, R., Hoang, D. -T, Hubmayr, J., Ichiki, K., Iida, T., Imada, H., Ishimura, K., Ishino, H., Jaehnig, G. C., Jones, M., Kaga, T., Kashima, S., Kataoka, Y., Katayama, N., Kawasaki, T., Keskitalo, R., Kibayashi, A., Kikuchi, T., Kimura, K., Kisner, T., Kobayashi, Y., Kogiso, N., Kogut, A., Kohri, K., Komatsu, E., Komatsu, K., Konishi, K., Krachmalnicoff, N., Kuo, C. L., Kurinsky, N., Kushino, A., Kuwata-Gonokami, M., Lamagna, Luca, Lattanzi, M., Lee, A. T., Linder, E., Maffei, B., Maino, D., Maki, M., Mangilli, A., Martínez-Gonzalez, E., Silvia Masi, Mathon, R., Matsumura, T., Mennella, A., Migliaccio, M., Minami, Y., Mistuda, K., Molinari, D., Montier, L., Morgante, G., Mot, B., Murata, Y., Murphy, J. A., Nagai, M., Nagata, R., Nakamura, S., Namikawa, T., Natoli, P., Nerval, S., Nishibori, T., Nishino, H., Nomura, Y., Noviello, F., O Sullivan, C., Ochi, H., Ogawa, H., Ohsaki, H., Ohta, I., Okada, N., Pagano, L., Alessandro Paiella, Paoletti, D., Patanchon, G., Francesco Piacentini, Giampaolo Pisano, Polenta, G., Poletti, D., Prouvé, T., Puglisi, G., Rambaud, D., Raum, C., Realini, S., Remazeilles, M., Roudil, G., Rubiño-Martın, J. A., Russell, M., Sakurai, H., Sakurai, Y., Sandri, M., Savini, G., Scott, D., Sekimoto, Y., Sherwin, B. D., Shinozaki, K., Shiraishi, M., Shirron, P., Signorelli, G., Smecher, G., Spizzi, P., Stever, S. L., Stompor, R., Sugai, H., Sugiyama, S., Suzuki, A., Suzuki, J., Switzer, E., Takaku, R., Takakura, H., Takakura, S., Takeda, Y., Taylor, A., Taylor, E., Terao, Y., Thompson, K. L., Thorne, B., Tomasi, M., Tomida, H., Trappe, N., Tristram, M., Tsuji, M., Tsujimoto, M., Tucker, C., Ullom, J., Uozumi, S., Utsunomiya, S., Lanen, J., Vermeulen, G., Vielva, P., Villa, F., Vissers, M., Vittorio, N., Voisin, F., Walker, I., Watanabe, N., Wehus, I., Weller, J., Westbrook, B., Winter, B., Wollack, E., Yamamoto, R., Yamasaki, N. Y., Yanagisawa, M., Yoshida, T., Yumoto, J., Zannoni, M., and Zonca, A.

Subjects
Settore FIS/02, Settore FIS/05
Published
2019

35. Taxol resistance and its reversal by synthetic isoprenoids in human bladder cancer cell line

Author

Imazono Y, Kishiye T, Masayuki Nakagawa, Enokida H, Gotanda T, Nishiyama K, Tachiwada T, Suzuki S, H. Kubo, and Inomata K

Subjects
Vinca, Paclitaxel, Cell Survival, Urology, Immunoblotting, Structure-Activity Relationship, Western blot, Cell Line, Tumor, medicine, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, P-glycoprotein, biology, medicine.diagnostic_test, Chemistry, Terpenes, organic chemicals, biology.organism_classification, Molecular biology, Antineoplastic Agents, Phytogenic, Terpenoid, Multiple drug resistance, Mechanism of action, Urinary Bladder Neoplasms, Cell culture, Drug Resistance, Neoplasm, biology.protein, Efflux, medicine.symptom
Abstract

PURPOSE We investigated the mechanism of action of reversal agents for taxol-resistance in bladder cancers. MATERIALS AND METHODS We isolated a taxol-resistant cell line (KK47/TX30) from a human KK47 bladder cancer cell line (KK47/WT). We characterized KK47/TX30 cells and screened reversal agents for taxol-resistance. RESULTS KK47/TX30 cells exhibited approximately 700-fold resistance to taxol and cross-resistance to Vinca alkaloids and topoisomerase II inhibitors. Western blot analysis demonstrated P-glycoprotein (P-gp) overexpression in taxol-resistant cells. Drug accumulation and efflux studies showed that the decreased taxol accumulation in the resistant cell line was due to enhanced taxol efflux. We synthesized 31 isoprenoids based on the structure of N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB), which could completely reverse multidrug resistance (MDR) as shown previously. Among those examined, trans-N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-1,2-diaminocyclohexane (N-5228) could completely reverse taxol-resistance in KK47/TX30 cells. Results of a structure-activity relationship study of isoprenoids suggested that the following structural features were important for overcoming taxol-resistance: (1) a basic structure of 8 to 10 isoprene units, (2) a cyclohexane ring or benzene ring within the framework, (3) two cationic sites in close proximity to each other, and (4) a benzyl group with 3,4-dimethoxy functionalities with moderate electron-donation. CONCLUSIONS Taxol-resistance was primarily mediated by P-gp overexpression in KK47/TX30 cells. One of the synthetic isoprenoids, N-5228 could completely reverse taxol-resistance in KK47/TX30 cells.

Published
2003

36. Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer.

Author

Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N, Fuse M, Ichikawa T, Naya Y, Nakagawa M, Seki N, Kojima, S, Chiyomaru, T, Kawakami, K, Yoshino, H, Enokida, H, Nohata, N, Fuse, M, Ichikawa, T, and Naya, Y

Abstract

Background: Our recent analyses of miRNA expression signatures showed that miR-1 and miR-133a were significantly reduced in several types of cancer. Interestingly, miR-1 and miR-133a are located on the same chromosomal locus in the human genome. We examined the functional significance of miR-1 and miR-133a in prostate cancer (PCa) cells and identified the novel molecular targets regulated by both miR-1 and miR-133a.Methods and Results: The expression levels of miR-1 and miR-133a were significantly downregulated in PCa compared with non-PCa tissues. Restoration of miR-1 or miR-133a in PC3 and DU145 cells revealed significant inhibition of proliferation, migration, and invasion. Molecular target identification by genome-wide gene expression analysis and luciferase reporter assay showed that purine nucleoside phosphorylase (PNP) was directly regulated by both miRNAs. Silencing of the PNP gene inhibited proliferation, migration, and invasion in both PC3 and DU145 cells. Immunohistochemistry detected positive staining of PNP in PCa specimens.Conclusions: Downregulation of miR-1 and miR-133a was a frequent event in PCa and both function as tumour suppressors. The PNP is a novel target gene of both miRNAs and potentially functions as an oncogene. Therefore, identification of novel molecular networks regulated by miRNAs may provide new insights into the underlying causes of PCa oncogenesis. [ABSTRACT FROM AUTHOR]

Published
2012
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47. Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma

Author

Nohata, N, primary, Hanazawa, T, additional, Kikkawa, N, additional, Sakurai, D, additional, Fujimura, L, additional, Chiyomaru, T, additional, Kawakami, K, additional, Yoshino, H, additional, Enokida, H, additional, Nakagawa, M, additional, Katayama, A, additional, Harabuchi, Y, additional, Okamoto, Y, additional, and Seki, N, additional

Published
2011
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