Noboru Yamagata

Publications of Noboru Yamagata

• Tetracycline protects myocardium against ischemic injury.

  Authors: Norio Kagawa, Taka-aki Senbonmatsu, Kumi Satoh, Kazuo Ichihara, Noboru Yamagata, Osamu Hatano, Takako Saito, Viet Q Nguyen, Michael R Waterman, Edward Price, James B Atkinson, Tadashi Inagami

  Frontiers in bioscience : a journal and virtual library. 02/2005; 10:608-19.

  Stress pretreatments protect myocardium from ischemic injury. We hypothesized that tetracycline, an antibiotic, may induce a stress response via the inhibition of mitochondrial translation as itStress pretreatments protect myocardium from ischemic injury. We hypothesized that tetracycline, an antibiotic, may induce a stress response via the inhibition of mitochondrial translation as it induces the cold stress response by translational inhibition in E. coli. If so, tetracycline may protect myocardium from ischemic injury as stress pretreatments do. Thus, we investigated the effects of tetracycline on myocardial ischemia and its association with stress response. In a dog model of acute ischemia, 4mg/kg tetracycline injected 30 min prior to the occlusion improved the functional recovery from stunning of myocardium caused by ischemia. The same dosage of tetracycline dramatically reduced the size of infarct area in murine hearts analyzed by tetrazolium staining. In HeLa cells, tetracycline induced molecules that were increased by cold stress, which suggests that tetracycline may induce a cold stress-like response in mammalian cells. These molecules were also induced by ischemic stress in murine hearts, suggesting that the stress response caused by translational inhibition in mitochondria may be associated with the cardioprotection by tetracycline. Our results suggest that a subclinical dosage of tetracycline may protect heart from ischemic injury. Therefore, tetracycline may be of great use in suppressing the development of infarction caused by myocardial ischemia. This study is also important for providing new insights into the non-antimicrobial effects of tetracycline and its derivatives.

• A training-testing approach to the molecular classification of resected non-small cell lung cancer.

  Authors: Noboru Yamagata, Yu Shyr, Kiyoshi Yanagisawa, Mary Edgerton, Thao P Dang, Adriana Gonzalez, Sorena Nadaf, Paul Larsen, John R Roberts, Jonathan C Nesbitt, Roy Jensen, Shawn Levy, Jason H Moore, John D Minna, David P Carbone

  Clinical cancer research : an official journal of the American Association for Cancer Research. 11/2003; 9(13):4695-704.

  PURPOSE: RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of thesePURPOSE: RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of these subsets casting doubt on their biological significance. EXPERIMENTAL DESIGN: In this study, we used a training-testing approach to test the reliability of cDNA microarray-based classifications of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA microarray. RESULTS: Groups of genes were identified that were able to differentiate primary tumors from normal lung and lung metastases, as well as identify known histological subgroups of NSCLCs. Groups of genes were identified to discriminate sample clusters. A blinded confirmatory set of tumors was correctly classified by using these patterns. Some histologically diagnosed large cell tumors were clearly classified by expression profile analysis as being either adenocarcinoma or squamous cell carcinoma, indicating that this group of tumors may not be genetically homogeneous. High alpha-actinin-4 expression was identified as highly correlated with poor prognosis. CONCLUSIONS: These results demonstrate that gene expression profiling can identify molecular classes of resected NSCLCs that correctly classifies a blinded test cohort, and correlates with and supplements standard histological evaluation.

• Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor.

  Authors: Li Yang, Noboru Yamagata, Rajwardhan Yadav, Suzanne Brandon, Regina L Courtney, Jason D Morrow, Yu Shyr, Mark Boothby, Sebastian Joyce, David P Carbone, Richard M Breyer

  The Journal of clinical investigation. 04/2003; 111(5):727-35.

  Prostaglandin E(2) (PGE(2)), a major COX metabolite, plays important roles in several facets of tumor biology. We characterized the contribution of the PGE(2) EP2 receptor to cancer-associated immuneProstaglandin E(2) (PGE(2)), a major COX metabolite, plays important roles in several facets of tumor biology. We characterized the contribution of the PGE(2) EP2 receptor to cancer-associated immune deficiency using EP2(-/-) mice. EP2(-/-) mice exhibited significantly attenuated tumor growth and longer survival times when challenged with MC26 or Lewis lung carcinoma cell lines as compared with their wild-type littermates. While no differences in T cell function were observed, PGE(2) suppressed differentiation of DCs from wild-type bone marrow progenitors, whereas EP2-null cells were refractory to this effect. Stimulation of cells in mixed lymphocyte reactions by wild-type DCs was suppressed by treatment with PGE(2), while EP2(-/-)-derived DCs were resistant to this effect. In vivo, DCs, CD4(+), and CD8(+) T cells were significantly more abundant in draining lymph nodes of tumor-bearing EP2(-/-) mice than in tumor-bearing wild-type mice, and a significant antitumor cytotoxic T lymphocyte response could be observed only in the EP2(-/-) animals. Our data demonstrate an important role for the EP2 receptor in PGE(2)-induced inhibition of DC differentiation and function and the diminished antitumor cellular immune responses in vivo.

• Effects of genetic blockade of the insulin-like growth factor receptor in human colon cancer cell lines.

  Authors: Yasushi Adachi, Choon-Taek Lee, Keith Coffee, Noboru Yamagata, Joyce E Ohm, Kyung-Ho Park, Mikhail M Dikov, Sorena R Nadaf, Carlos L Arteaga, David P Carbone

  Gastroenterology. 10/2002; 123(4):1191-204.

  BACKGROUND & AIMS: Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for maintenance of growth and tumorigenicity of several tumor types. We have previously shown successfulBACKGROUND & AIMS: Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for maintenance of growth and tumorigenicity of several tumor types. We have previously shown successful therapy in a lung cancer xenograft model using an adenovirus expressing antisense IGF-Ir. In this study, we sought to better dissect the mechanism and develop potentially more effective IGF-Ir-targeted therapeutics by developing and testing tetracycline-regulated and recombinant adenoviruses expressing dominant negative receptors. METHODS: Truncated IGF-I receptors (IGF-Ir/tf; 482 and 950 amino acids long, respectively [IGF-Ir/482st and IGF-Ir/950st]) were cloned into tetracycline-regulated vectors and recombinant adenoviruses and then studied in colorectal cancer cells. We assessed the effect of IGF-Ir/tf on signaling blockade, colony formation, stress response (serum starvation and heat), chemotherapy-induced apoptosis, and in vivo therapeutic efficacy in xenografts. RESULTS: Activation of IGF-Ir/tf expression by withdrawal of tetracycline suppressed tumorigenicity both in vitro and in vivo and up-regulated stressor-induced apoptosis. It effectively blocked both IGF-I- and IGF-II-induced activation of Akt-1. IGF-Ir/tf expression increased chemotherapy-induced apoptosis, and this combination therapy was very effective against tumors in mice. These findings were confirmed in a therapy model against established tumors using adenoviruses expressing IGF-Ir/tf. Moreover, IGF-Ir/482st was more effective than IGF-Ir/950st because of its bystander effect. CONCLUSIONS: Anti-tumor activity of IGF-Ir/tf is mediated through inhibition of Akt-1 and enhances the efficacy of chemotherapy. Adenovirus IGF-Ir/482st may be a useful anticancer therapeutic for colorectal carcinoma.