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Institution

Kumamoto University

EducationKumamoto, Kumamoto, Japan
About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.


Papers
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Journal ArticleDOI
TL;DR: It is indicated that vitamin E treatment improved endothelium-dependent vasodilation and decreased plasma TBARS levels in patients with CSA, and increased oxidative stress may contribute to endothelial dysfunction and anginal attacks in patientswith CSA.

171 citations

Journal ArticleDOI
TL;DR: Evaluation of signal intensity at T2-weighted imaging and degree of contrast enhancement at dynamic enhanced MR imaging provide useful information on the nature of leiomyomas.
Abstract: PURPOSE: To evaluate the role of dynamic enhanced magnetic resonance (MR) imaging in differentiating leiomyomas with high signal intensity at T2-weighted imaging. MATERIALS AND METHODS: Histologic features of 34 uterine leiomyomas that showed hyperintensity on T2-weighted images were compared with those of ordinary hypointense leiomyomas (n = 74). The results of treatment with gonadotropin-releasing hormone analogue were also analyzed in relation to pretreatment signal intensity. RESULTS: Degenerated leiomyomas (n = 13) had higher signal intensity and heterogeneous architecture, but there was considerable overlap in signal intensity with cellular leiomyomas (n = 21). At dynamic enhanced MR imaging, cellular leiomyomas had marked contrast enhancement in the early phase, while degenerated leiomyomas showed slight or irregular enhancement. Cellular leiomyomas were reduced significantly in size after treatment (P = .02). The response in degenerated leiomyomas was minimal. CONCLUSION: Evaluation of signal inte...

171 citations

Journal ArticleDOI
TL;DR: Analysis of the HTLV-I provirus genome showed the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone, and showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription.
Abstract: Background Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome.

171 citations

Journal ArticleDOI
TL;DR: Molecular pathology of CIPA would provide unique opportunities to explore critical roles of the autonomic sympathetic nervous system as well as peripheral sensory nervous system that transmit noxious stimuli in humans.
Abstract: Congenital insensitivity to pain with anhidrosis (CIPA), also referred to as hereditary sensory and autonomic neuropathy type IV (HSAN-IV), is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. The TRKA (NTRK1) gene located on chromosome 1 (1q21-q22), consists of 17 exons and spans at least 23 kb. TRKA encodes the receptor tyrosine kinase (RTK) for nerve growth factor (NGF) and is the gene responsible for CIPA. Defects in NGF signal transduction at the TRKA receptor lead to failure to support survival of sympathetic ganglion neurons and nociceptive sensory neurons derived from the neural crest. Thirty-seven different TRKA mutations, identified in patients in various countries, including nine frameshift, seven nonsense, seven splice, and 14 missense mutations, are distributed in an extracellular domain involved in NGF binding, as well as in the intracellular signal-transduction domain. Extensive analysis of CIPA mutations and associated intragenic polymorphisms should facilitate detection of CIPA mutations and aid in the diagnosis and genetic counseling of this painless but severe genetic disorder with devastating complications. In addition, naturally occurring TRKA missense mutations with loss of function provide considerable insight into the structure-function relationship in the RTK family. Further, molecular pathology of CIPA would provide unique opportunities to explore critical roles of the autonomic sympathetic nervous system as well as peripheral sensory nervous system that transmit noxious stimuli in humans.

170 citations

Journal ArticleDOI
TL;DR: It is demonstrated that inhibition of the guanine-exchange factors SOS1 and SOS2 or the protein tyrosine phosphatase SHP2 can attenuate this adaptive process and that targeting these factors can enhance the sensitivity of KRAS-amplified models to MEK inhibition in both in vitro and in vivo settings.
Abstract: The role of KRAS, when activated through canonical mutations, has been well established in cancer1. Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ovarian adenocarcinomas2-4. KRAS-amplified gastric cancer models show marked overexpression of the KRAS protein and are insensitive to MAPK blockade owing to their capacity to adaptively respond by rapidly increasing KRAS-GTP levels. Here we demonstrate that inhibition of the guanine-exchange factors SOS1 and SOS2 or the protein tyrosine phosphatase SHP2 can attenuate this adaptive process and that targeting these factors, both genetically and pharmacologically, can enhance the sensitivity of KRAS-amplified models to MEK inhibition in both in vitro and in vivo settings. These data demonstrate the relevance of copy-number amplification as a mechanism of KRAS activation, and uncover the therapeutic potential for targeting of these tumors through combined SHP2 and MEK inhibition.

170 citations


Authors

Showing all 19645 results

NameH-indexPapersCitations
Fred H. Gage216967185732
George D. Yancopoulos15849693955
Kenji Kangawa1531117110059
Tasuku Honjo14171288428
Hideo Yagita13794670623
Masashi Yanagisawa13052483631
Kazuwa Nakao128104170812
Kouji Matsushima12459056995
Thomas E. Mallouk12254952593
Toshio Hirano12040155721
Eisuke Nishida11234945918
Hiroaki Shimokawa11194948822
Bernd Bukau11127138446
Kazuo Tsubota105137948991
Toshio Suda10458041069
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202315
202297
20211,701
20201,654
20191,511
20181,330