Institution
Kumamoto University
Education•Kumamoto, 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.
Topics: Population, Cancer, Cell culture, Stem cell, Cellular differentiation
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Evidence is presented that the purified MukB protein possesses DNA binding activity, and photoaffinity cross‐linking experiments showed that MukB binds to ATP and GTP in the presence of Zn2+.
Abstract: mukB mutants of Escherichia coli are defective in the correct partitioning of replicated chromosomes. This results in the appearance of normal-sized anucleate (chromosome-less) cells during cell proliferation. Based on the nucleotide sequence of the mukB gene, the MukB protein of 177 kDa was predicted to be a filamentous protein with globular domains at the ends, and also having DNA binding and nucleotide binding abilities. Here we present evidence that the purified MukB protein possesses these characteristics. MukB forms a homodimer with a rod-and-hinge structure having a pair of large, C-terminal globular domains at one end and a pair of small, N-terminal globular domains at the opposite end; it tends to bend at a middle hinge site of the rod section. Chromatography in a DNA-cellulose column and the gel retardation assay revealed that MukB possesses DNA binding activity. Photoaffinity cross-linking experiments showed that MukB binds to ATP and GTP in the presence of Zn2+. Throughout the purification steps, acyl carrier protein was co-purified with MukB.
204 citations
••
TL;DR: Subtype-specific genetic lesions can be used to stratify patients within each LGG subtype, enabling better prognostication and management.
Abstract: Background Diffuse lower-grade gliomas (LGGs) are genetically classified into 3 distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific effects of additional genetic lesions on survival are largely unknown. Methods Using Cox proportional hazards regression modeling, we investigated the subtype-specific effects of genetic alterations and clinicopathological factors on survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped for driver mutations and copy number variations associated with LGGs (n = 308). The results were validated using a dataset from 414 LGG cases available from The Cancer Genome Atlas (TCGA). Results In Oligodendroglioma, IDH-mutant and 1p/19q codeleted, NOTCH1 mutations (P = 0.0041) and incomplete resection (P = 0.0019) were significantly associated with shorter survival. In Astrocytoma, IDH-mutant, PIK3R1 mutations (P = 0.0014) and altered retinoblastoma pathway genes (RB1, CDKN2A, and CDK4) (P = 0.013) were independent predictors of poor survival. In IDH-wildtype LGGs, co-occurrence of 7p gain, 10q loss, mutation in the TERT promoter (P = 0.024), and grade III histology (P < 0.0001) independently predicted poor survival. IDH-wildtype LGGs without any of these factors were diagnosed at a younger age (P = 0.042), and were less likely to have genetic lesions characteristic of glioblastoma, in comparison with other IDH-wildtype LGGs, suggesting that they likely represented biologically different subtypes. These results were largely confirmed in the cohort of TCGA. Conclusions Subtype-specific genetic lesions can be used to stratify patients within each LGG subtype. enabling better prognostication and management.
203 citations
••
TL;DR: Nomiyama et al. as discussed by the authors identified a new CC chemokine termed eotaxin-3, which is another functional ligand for CCR3, in the presence of MPIF-2 genes.
203 citations
••
TL;DR: The aims of this study were to determine whether HPV DNA could readily be demonstrated in skin tumors, as well as in perilesional skin, of immunocompetent patients using two polymerase chain reaction primer sets, and the prevalence of infections in normal skin; andThe prevalence of HPV 38 or HPV 38 related viruses in melanoma.
203 citations
••
TL;DR: It is found that targeting the proinflammatory cytokine IL6 enhances tumor-specific Th1 responses and subsequent antitumor effects in tumor-bearing mice, suggesting that IL6 is a rational immunosuppressive target for overcoming the narrow therapeutic window of anti-PD-1/PD-L1 therapy.
Abstract: Recently emerging cancer immunotherapies combine the applications of therapeutics to disrupt the immunosuppressive conditions in tumor-bearing hosts. In this study, we found that targeting the proinflammatory cytokine IL6 enhances tumor-specific Th1 responses and subsequent antitumor effects in tumor-bearing mice. IL6 blockade upregulated expression of the immune checkpoint molecule programmed death-ligand 1 (PD-L1) on melanoma cells. This PD-L1 induction was canceled in IFNγ-deficient mice or CD4+ T cell-depleted mice, suggesting that CD4+ T cell-derived IFNγ is important for PD-L1 induction in tumor-bearing hosts. In some patients with melanoma, however, treatment with the anti-PD-1 antibody nivolumab increased systemic levels of IL6, which was associated with poor clinical responses. This PD-L1 blockade-evoked induction of IL6 was reproducible in melanoma-bearing mice. We found that PD-1/PD-L1 blockade prompted PD-1+ macrophages to produce IL6 in the tumor microenvironment. Depletion of macrophages in melanoma-bearing mice reduced the levels of IL6 during PD-L1 blockade, suggesting macrophages are responsible for the IL6-mediated defective CD4+ Th1 response. Combined blockade of the mutually regulated immunosuppressive activities of IL6 and PD-1/PD-L1 signals enhanced expression of T cell-attracting chemokines and promoted infiltration of IFNγ-producing CD4+ T cells in tumor tissues, exerting a synergistic antitumor effect, whereas PD-L1 blockade alone did not promote Th1 response. Collectively, these findings suggest that IL6 is a rational immunosuppressive target for overcoming the narrow therapeutic window of anti-PD-1/PD-L1 therapy.Significance: These findings advance our understanding of IL6-PD1/PD-L1 cross-talk in the tumor microenvironment and provide clues for targeted interventional therapy that may prove more effective against cancer. Cancer Res; 78(17); 5011-22. ©2018 AACR.
203 citations
Authors
Showing all 19645 results
Name | H-index | Papers | Citations |
---|---|---|---|
Fred H. Gage | 216 | 967 | 185732 |
George D. Yancopoulos | 158 | 496 | 93955 |
Kenji Kangawa | 153 | 1117 | 110059 |
Tasuku Honjo | 141 | 712 | 88428 |
Hideo Yagita | 137 | 946 | 70623 |
Masashi Yanagisawa | 130 | 524 | 83631 |
Kazuwa Nakao | 128 | 1041 | 70812 |
Kouji Matsushima | 124 | 590 | 56995 |
Thomas E. Mallouk | 122 | 549 | 52593 |
Toshio Hirano | 120 | 401 | 55721 |
Eisuke Nishida | 112 | 349 | 45918 |
Hiroaki Shimokawa | 111 | 949 | 48822 |
Bernd Bukau | 111 | 271 | 38446 |
Kazuo Tsubota | 105 | 1379 | 48991 |
Toshio Suda | 104 | 580 | 41069 |