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991.
Yoshioka H Yamamoto S Hanaoka H Iida Y Paudyal P Higuchi T Tominaga H Oriuchi N Nakagawa H Shiba Y Yoshida K Osawa R Katagiri T Tsunoda T Nakamura Y Endo K 《Cancer immunology, immunotherapy : CII》2012,61(8):1211-1220
Purpose
We examined the possible efficacy of the yttrium-90 (90Y)-labeled anti-CDH3/P-cadherin mouse monoclonal antibody (MAb-6) in radioimmunotherapy (RIT) for lung and colorectal cancers that express CDH3/P-cadherin.Experimental design
MAb-6 was established using genetic immunization. The biodistribution of MAb-6 in nude mice with lung and colorectal cancers was examined by administering indium-111(111In)-labeled MAb-6 to mice. The mice were prepared by inoculation of CDH3/P-cadherin-positive (EBC1, H1373, and SW948) and CDH3/P-cadherin-negative (A549 and RKO) tumor cells. Therapeutic effects and toxicity were investigated by administration of 90Y-labeled MAb-6 (90Y-MAb-6) to EBC, H1373, and SW948-inoculated mice.Results
Our in vivo results confirmed the specific binding of MAb-6 to tumor cells after intravenous injections of 111In-labeled MAb-6 to mice with tumors expressing CDH3/P-cadherin. A single intravenous injection of 90Y-MAb-6 (100?μCi) significantly suppressed tumor growth in mice with tumors expressing CDH3/P-cadherin. Furthermore, two injections of 90Y-MAb-6 led to complete tumor regression in H1373-inoculated mice without any detectable toxicity.Conclusions
Our findings demonstrate that CDH3/P-cadherin-targeting RIT with 90Y-MAb-6 is a promising strategy for the treatment for cancers expressing CDH3/P-cadherin. 相似文献992.
Shiori Sekine Yusuke Kanamaru Masato Koike Ayako Nishihara Masahiro Okada Hideyuki Kinoshita Miki Kamiyama Junichi Maruyama Yasuo Uchiyama Naotada Ishihara Kohsuke Takeda Hidenori Ichijo 《The Journal of biological chemistry》2012,287(41):34635-34645
Regulated intramembrane proteolysis is a widely conserved mechanism for controlling diverse biological processes. Considering that proteolysis is irreversible, it must be precisely regulated in a context-dependent manner. Here, we show that phosphoglycerate mutase 5 (PGAM5), a mitochondrial Ser/Thr protein phosphatase, is cleaved in its N-terminal transmembrane domain in response to mitochondrial membrane potential (ΔΨm) loss. This ΔΨm loss-dependent cleavage of PGAM5 was mediated by presenilin-associated rhomboid-like (PARL). PARL is a mitochondrial resident rhomboid serine protease and has recently been reported to mediate the cleavage of PINK1, a mitochondrial Ser/Thr protein kinase, in healthy mitochondria with intact ΔΨm. Intriguingly, we found that PARL dissociated from PINK1 and reciprocally associated with PGAM5 in response to ΔΨm loss. These results suggest that PARL mediates differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria. Our data provide a prototypical example of stress-dependent regulation of PARL-mediated regulated intramembrane proteolysis. 相似文献
993.
Whether exposure to static magnetic fields (SMF) for medical applications poses a therapeutic benefit or a health hazard is at the focus of current debate. As a peripheral nerve model for studies of the SMF effects, we have investigated whether exposure of in vitro frog sciatic nerve fibers to moderate-intensity gradient SMF up to 0.7 T modulates membrane excitation and refractory processes. We measured the changes in the amplitudes of the electrically evoked compound action potentials for three groups: a control group without SMF exposure and two exposed groups with continuous inhomogeneous exposure to maximum flux densities (B(max)) of 0.21 and 0.7 T SMF for 6 h. The values of the nerve conduction velocity of C fibers were significantly reduced by B(max) of 0.7 T SMF during the 4- to 6-h exposure period but not by B(max) of 0.21 T SMF during the entire exposure period of 6 h, relative to the unexposed control. From these findings, we speculate that exposure to moderate-intensity gradient SMF may attenuate pain perception because the C fibers are responsible for pain transmission. Although the mechanistic reasons for this decrease have yet to be clarified, SMF could affect the behavior of some types of ion channels associated with C fibers. 相似文献
994.
Hideyuki Takahashi Tomohiro Imamura Atsuko Miyagi Hirofumi Uchimiya 《Metabolomics : Official journal of the Metabolomic Society》2012,8(1):154-163
Gentians (Gentiana triflora, G. scabra, and hybrids of the two) are mainly cultivated as ornamental flowers in Japan. Because gentians are allogamous plants, their
diversity and heterozygosity have become a major problem. Recently, explants were clonally cultured to maintain genetic purity,
but culture conditions have not been studied systematically, thus the essential nutrients required for gentian culture are
unknown. We therefore investigated the effects of potassium (K) and phosphorus (P) deficiency in culture media. Explants grew
under K or P deficiency conditions, but P deficiency caused the formation of new structures which are similar to overwintering
buds. To elucidate the mechanism behind the gentian response to mineral deficiency, we performed targeted metabolome analyses
using capillary electrophoresis-mass spectrometry. Multivariate analysis using metabolite profiles showed that characteristic
metabolite patterns arise in response to K or P deficiency. Under P deficiency there is a severe decrease in energy metabolites,
which may in turn trigger overwintering bud formation in vitro. These findings may contribute to understanding the horticultural
conditions required by gentians to trigger bud formation, and may provide a new strategy for maintaining genetic purity for
long periods. 相似文献
995.
Lijun Yang Hideyuki Takahashi Taiji Kawakatsu Fumio Takaiwa 《Plant biotechnology journal》2012,10(9):1035-1045
Human IL‐10 (hIL‐10) is a therapeutic treatment candidate for inflammatory allergy and autoimmune diseases. Rice seed‐produced IL‐10 can be effectively delivered directly to gut‐associated lymphoreticular tissue (GALT) via bio‐encapsulation. Previously, the codon‐optimized hIL‐10 gene was expressed in transgenic rice with the signal peptide and endoplasmic reticulum (ER) retention signal (KDEL) at its 5′ and 3′ ends, respectively, under the control of the endosperm‐specific glutelin GluB‐1 promoter. The resulting purified hIL‐10 was biologically active. In this study, the yield of hIL‐10 in transgenic rice seed was improved. This protein accumulated at the intended deposition sites, which had been made vacant through the selective reduction, via RNA interference, of the endogenous seed storage proteins prolamins or glutelins. Upon suppression of prolamins that were sequestered into ER‐derived protein bodies (PB‐I), hIL‐10 accumulation increased approximately 3‐fold as compared to rice seed with no such suppression and reached 219 μg/grain. In contrast, reducing the majority of the glutelins stored in protein‐storage vacuoles (PB‐II) did not significantly affect the accumulation of hIL‐10. Considering that hIL‐10 is synthesized in the ER lumen and subsequently buds off in ER‐derived granules called IL‐10 granules in a manner similar to PB‐Is, these results indicate that increases in the available deposition space for the desired recombinant proteins may be crucial for improvements in yield. Furthermore, efficient dimeric intermolecular formation of hIL‐10 by inhibiting interaction with Cys‐rich prolamins also contributed to the enhanced formation of IL‐10 bodies. Higher yield of hIL‐10 produced in rice seeds is expected to have broad application in the future. 相似文献
996.
997.
This study was a first analysis of paternal genetic diversity for extensive Asian domestic goats using SRY gene sequences. Sequencing comparison of the SRY 3′‐untranslated region among 210 Asian goats revealed four haplotypes (Y1A, Y1B, Y2A and Y2B) derived from four variable sites including a novel substitution detected in this study. In Asian goats, the predominant haplotype was Y1A (62%) and second most common was Y2B (30%). Interestingly, the Y2B was a unique East Asian Y chromosomal variant, which differentiates eastern and western Eurasian goats. The SRY geographic distribution in Myanmar and Cambodia indicated predominant the haplotype Y1A in plains areas and a high frequency of Y2B in mountain areas. The results suggest recent genetic infiltration of modern breeds into South‐East Asian goats and an ancestral SRY Y2B haplotype in Asian native goats. 相似文献
998.
999.
Hideyuki Yamawaki Naoya Tsubaki Masashi Mukohda Muneyoshi Okada Yukio Hara 《Biochemical and biophysical research communications》2010,393(4):668-672
Omentin is a recently identified adipose tissue-derived cytokine and is implicated in obesity-related cardiovascular disorders. In the present study, we tested the hypothesis that omentin could directly affect vascular reactivity of isolated blood vessels. In endothelium-intact rat isolated aorta, pretreatment with omentin (300 ng/ml, 30 min) inhibited noradrenaline (NA; 1 nM-1 μM)-induced concentration-dependent contraction. In NA (100 nM)-pre-contracted aorta, omentin (1-300 ng/ml) directly induced an endothelium-dependent relaxation. While a nitric oxide (NO) synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester (100 μM, 30 min) inhibited the relaxation, a PI3 K/Akt inhibitor, LY294002 (10 μM, 30 min) or a tyrosine kinase inhibitor, genistein (30 μM, 30 min) was ineffective. Omentin (300 ng/ml, 5 min) induced a phosphorylation of endothelial NOS at serine 1177 but not a phosphorylation of Akt at serine 473. Omentin (1-300 ng/ml) also relaxed NA pre-contracted mesenteric artery. Present study for the first time demonstrated that omentin has a vasodilating effect on isolated blood vessels, which is mediated through endothelium-derived NO. 相似文献
1000.