297 research outputs found
Gap Structures of A-15 Alloys from the Superconducting and Normal-State Break-Junction Tunnelling
Hepatocyte growth factor and Met in tumor biology and therapeutic approach with NK4
金沢大学がん研究所分子標的がん医療研究開発センターHepatocyte growth factor (HGF) and Met/HGF receptor tyrosine kinase play a role in the progression to invasive and metastatic cancers. A variety of cancer cells secrete molecules that enhance HGF expression in stromal fibroblasts, while fibroblast-derived HGF, in turn, is a potent stimulator of the invasion of cancer cells. In addition to the ligand-dependent activation, Met receptor activation is negatively regulated by cell-cell contact and Ser985 phosphorylation in the juxtamembrane of Met. The loss of intercellular junctions may facilitate an escape from the cell-cell contact-dependent suppression of Met-signaling. Significance of juxtamembrane mutations found in human cancers is assumed to be a loss-of-function in the negative regulation of Met. In attempts to block the malignant behavior of cancers, NK4 was isolated as a competitive antagonist against HGF-Met signaling. Independently on its HGF-antagonist action, NK4 inhibited angiogenesis induced by vascular endothelial cell growth factor and basic fibroblast growth factor, as well as HGF. In experimental models of distinct types of cancers, NK4 inhibited Met activation and this was associated with inhibition of tumor invasion and metastasis. NK4 inhibited tumor angiogenesis, thereby suppressing angiogenesis-dependent tumor growth. Cancer treatment with NK4 suppresses malignant tumors to be "static" in both tumor growth and spreading. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA
Hepatocyte growth factor twenty years on: Much more than a growth factor
金沢大学がん研究所Liver regeneration depends on the proliferation of mature hepatocytes. In the 1980s, the method for the cultivation of mature hepatocytes provided an opportunity for the discovery of hepatocyte growth factor (HGF) as a protein that is structurally and functionally different from other growth factors. In 1991, the scatter factor, tumor cytotoxic factor, and 3-D epithelial morphogen were identified as HGF, and Met tyrosine kinase was identified as the receptor for HGF. Thus, the connection of apparently unrelated research projects rapidly enriched the research on HGF in different fields. The HGF-Met pathway plays important roles in the embryonic development of the liver and the placenta, in the migration of myogenic precursor cells, and in epithelial morphogenesis. The use of tissue-specific knockout mice demonstrated that in mature tissues the HGF-Met pathway plays a critical role in tissue protection and regeneration, and in providing less susceptibility to chronic inflammation and fibrosis. In various injury and disease models, HGF promotes cell survival, regeneration of tissues, and suppresses and improves chronic inflammation and fibrosis. Drug development using HGF has been challenging, but extensive preclinical studies to address its therapeutic effects have provided significant results sufficient for the development of HGF as a biological drug in the regeneration-based therapy of diseases. Clinical trials using recombinant human HGF protein, or HGF genes, are in progress for the treatment of diseases. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Tunneling spectra of break junctions involving Nb₃Sn
The electronic gap structure of Nb3Sn was measured by the break-junction (BJ) tunneling technique. The superconducting
gap values are estimated to be in the range 2∆ = 4–5.5 meV at T = 4.2 K as follows from the observed
distinct conductance peaks. In addition to the superconducting gap structure, we observed reproducible
hump-like structures at the biases of about ± 20 and ± 50 mV. Such a coexistence of gap and hump structures resembles
the situation found in the high-Tc copper-oxide superconductors. Above the superconducting critical
temperature Tc ~ 18 K, the humps appear as the only gap-like structures. Their possible origin is discussed in
connection to the structural phase transition occurring in Nb₃Sn
Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer
Table S2. Change in NK population in PBL
Metastases of soft tissue sarcoma to the liver: A Historical Cohort Study from a Hospital-based Cancer Registry
Background: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. Methods: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis. Results: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%. Conclusions: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment.ArticleCancer medicine 17(17) : 6159-6165(2020)journal articl
Dense Molecular Clumps associated with the LMC Supergiant Shells LMC 4 \& LMC 5
We investigate the effects of Supergiant Shells (SGSs) and their interaction
on dense molecular clumps by observing the Large Magellanic Cloud (LMC) star
forming regions N48 and N49, which are located between two SGSs, LMC 4 and LMC
5. CO (=3-2, 1-0) and CO (=1-0) observations with the ASTE
and Mopra telescopes have been carried out towards these regions. A clumpy
distribution of dense molecular clumps is revealed with 7 pc spatial
resolution. Large velocity gradient analysis shows that the molecular hydrogen
densities () of the clumps are distributed from low to high
density (- cm) and their kinetic temperatures () are typically high (greater than K). These clumps seem to be in the
early stages of star formation, as also indicated from the distribution of
H, young stellar object candidates, and IR emission. We found that the
N48 region is located in the high column density HI envelope at the interface
of the two SGSs and the star formation is relatively evolved, whereas the N49
region is associated with LMC 5 alone and the star formation is quiet. The
clumps in the N48 region typically show high and ,
which are as dense and warm as the clumps in LMC massive cluster-forming areas
(30 Dor, N159). These results suggest that the large-scale structure of the
SGSs, especially the interaction of two SGSs, works efficiently on the
formation of dense molecular clumps and stars.Comment: 26 pages, 7 tables, 16 figure
Dense Clumps in Giant Molecular Clouds in the Large Magellanic Cloud: Density and Temperature Derived from CO() Observations
In order to precisely determine temperature and density of molecular gas in
the Large Magellanic Cloud, we made observations of optically thin
CO() transition by using the ASTE 10m telescope toward 9 peaks
where CO() clumps were previously detected with the same
telescope. The molecular clumps include those in giant molecular cloud (GMC)
Types I (with no signs of massive star formation), II (with HII regions only),
and III (with HII regions and young star clusters). We detected
CO() emission toward all the peaks and found that their
intensities are 3 -- 12 times lower than those of CO(). We
determined the intensity ratios of CO() to CO(),
, and CO() to CO(),
, at 45\arcsec resolution. These ratios were used for
radiative transfer calculations in order to estimate temperature and density of
the clumps. The parameters of these clumps range kinetic temperature
= 15 -- 200 K, and molecular hydrogen gas density
= 8 -- 7 cm. We confirmed
that the higher density clumps show higher kinetic temperature and that the
lower density clumps lower kinetic temperature at a better accuracy than in the
previous work. The kinetic temperature and density increase generally from a
Type I GMC to a Type III GMC. We interpret that this difference reflects an
evolutionary trend of star formation in molecular clumps. The
and kinetic temperature of the clumps are well correlated
with H flux, suggesting that the heating of molecular gas
= -- cm can be explained by stellar FUV
photons.Comment: 39 pages, 7 figures, 4 tables. Accepted for publication in The
Astronomical Journa
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Recombinant human thrombomodulin inhibits neutrophil extracellular trap formation in vitro
The aim of this study was to investigate the effects of recombinant human-soluble thrombomodulin (rTM) on lipopolysaccharide (LPS)-induced, platelet-dependent neutrophil extracellular trap (NET) formation (NETosis). Human peripheral blood neutrophils and platelets were co-incubated with or without LPS (0.2 μg/ml) in the presence and absence of rTM (2 μg/ml). NETosis was confirmed by immunostaining and confocal microscopy. In the absence of platelets, LPS did not induce NETosis in the neutrophils. NETosis, however, was induced by LPS when neutrophils were co-cultured with platelets (64 % of neutrophils). Notably, rTM was able to fully inhibit NETosis in neutrophils cultured with platelets and in the presence of LPS. rTM did not induce NETosis in this co-culture system (p < 0.01 versus LPS in the absence of rTM). These results show that rTM can suppress LPS-induced platelet-dependent NETosis in vitro
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