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21.
Shuhei ENJOJI Ryotaro YABE Nobuyuki FUJIWARA Shunya TSUJI Michael P. VITEK Takuya MIZUNO Takayuki NAKAGAWA Tatsuya USUI Takashi OHAMA Koichi SATO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(11):1451-1456
Canine melanoma is one of the most important diseases in small animal medicine.
Protein phosphatase 2A (PP2A), a well conserved serine/threonine phosphatase, plays a
critical role as a tumor suppressor. SET/I2PP2A is an endogenous inhibitor for PP2A, which
directly binds to PP2A and suppresses its phosphatase activity. Elevated SET protein
levels have been reported to exacerbate human tumor progression. The role of SET in canine
melanoma, however, has not been understood. Here, we investigated the potential
therapeutic role for SET inhibitors in canine melanoma. The expression of SET protein was
observed in 6 canine melanoma cell lines. We used CMeC-1 cells (primary origin) and CMeC-2
cells (metastatic origin) to generate cell lines stably expressing SET-targeting shRNAs.
Knockdown of SET expression in CMeC-2, but not in CMeC-1, leads to decreased cell
proliferation, invasion and colony formation. Phosphorylation level of p70 S6 kinase was
decreased by SET knockdown in CMeC-2, suggesting the involvement of mTOR (mammalian target
of rapamycin)/p70 S6 kinase signaling. The SET inhibitors, OP449 and FTY720, more
effectively killed CMeC-2 than CMeC-1. We observed PP2A activation in CMeC-2 treated with
OP449 and FTY720. These results demonstrated the potential therapeutic application of SET
inhibitors for canine melanoma. 相似文献
22.
Kazumi KISHIDA Mitsuhiro SAKASE Kenta MINAMI Miyuki M. ARAI Reiko SYOJI Namiko KOHAMA Takayuki AKIYAMA Akio OKA Hiroshi HARAYAMA Moriyuki FUKUSHIMA 《The Journal of reproduction and development》2015,61(6):519-524
The purposes of this study were to examine the relationship between male artificial insemination (AI)
fertility and sperm acrosomal conditions assessed by new and conventional staining techniques and to identify
possible reproductive dysfunctions causing low conception rates in AI using frozen-thawed spermatozoa with
poor acrosomal conditions in Japanese Black bulls. We investigated individual differences among bulls in the
results concerning (1) acrosomal conditions of frozen-thawed spermatozoa as assessed by not merely peanut
agglutinin-lectin staining (a conventional staining technique) but also immunostaining of acrosomal
tyrosine-phosphorylated proteins (a new staining technique), (2) routine AI using frozen-thawed spermatozoa as
assessed by pregnancy diagnosis, (3) in vivo fertilization of frozen-thawed spermatozoa and
early development of fertilized eggs as assessed by superovulation/AI-embryo collection tests and (4)
in vitro fertilization of frozen-thawed spermatozoa with oocytes. The percentages of
frozen-thawed spermatozoa with normal acrosomal conditions assessed by the abovementioned staining techniques
were significantly correlated with the conception rates of routine AI, rates of transferable embryos in
superovulation/AI-embryo collection tests and in vitro fertilization rates. These results are
consistent with new suggestions that the distribution of acrosomal tyrosine-phosphorylated proteins as well as
the acrosomal morphology of frozen-thawed spermatozoa are AI fertility-associated markers that are valid for
the prediction of AI results and that low conception rates in AI using frozen-thawed spermatozoa with poor
acrosomal conditions result from reproductive dysfunctions in the processes between sperm insemination into
females and early embryo development, probably failed fertilization of frozen-thawed spermatozoa with
oocytes. 相似文献
23.
Harigaya S Honda T Rong L Miyakoshi T Chen CL 《Journal of agricultural and food chemistry》2007,55(6):2201-2208
Fresh exudates from the lacquer tree, Rhus vernicifera DC, were extracted with acetone and the solution was chromatographed to isolate monomer, dimer, trimer, and oligomer fractions of urushiols. Constituents of the monomeric and dimeric fractions were then identified by two-dimensional (2D) 1H-13C heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond coherence (HMBC) NMR spectroscopic techniques. The results showed that the monomeric fraction contained 3-[8'Z,11'E,13'Z-pentadecatrienyl]catechol (1), 3-[8'Z,11'Z,14'-pentadecatrienyl]catechol (2), and 3-pentadecanyl]catechol (3), which was verified by HPLC analysis. The dimeric fraction contained 8'-(3' ',4' '-dihydroxy-5' '-alkenyl)phenyl-3-[9'E,11'E,13'Z-pentadecatrienyl]catechol (4), 14'-(3' ',4' '-dihydroxy-5' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadecatrienyl]catechol (5), 2-hydroxyl-3- or -6-alkenylphenyl ethyl ether (6), 14'-(3' ',4' '-dihydroxy-2' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadeca-trienyl]catechol (7), 15'-(2' '-hydroxy-3' '- or -6' '-alkenyl)phenyloxy-3-[8'Z,11'Z,13'E)-pentadecatrienyl]catechol (8), 14'-(2' ',3' '-dihydroxy-4' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadecantrienyl]catechol (9), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-4,3'-biphenyl (10), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-4,4'-biphenyl (11), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-5,4'-biphenyl (12), and 1,2,1'-trihydroxy-6,6'-dialkenyldibenzofuran (13) as constituents. In addition, dimeric ethers and peroxides, such as compounds 14 and 15, were produced by autoxidation of monomeric urushiols in atmospheric air. The possible reaction mechanisms for the dehydrogenative polymerization of urushiols by Rhus laccase present in the fresh raw exudates under the atmospheric oxygen are discussed on the basis of structures identified. This is of primary importance because the use of the urushi exudates as coating materials does not involve organic solvents and is an environmentally friendly process. 相似文献
24.
25.
Biotransformation of alpha-terpineol by the common cutworm (Spodoptera litura) larvae was investigated. alpha-Terpineol was mixed in an artificial diet, and the diet was fed to the larvae (fourth-fifth instar) of S. litura. Metabolites were isolated from the frass and analyzed spectroscopically. Main metabolites were 7-hydroxy-alpha-terpineol (p-menth-1-ene-7,8-diol) and oleuropeic acid (8-hydroxy-p-menth-1-en-7-oic acid). Intestinal bacteria from the frass of larvae did not participate in the metabolism of alpha-terpineol. alpha-Terpineol was preferentially oxidized at the C-7 position (allylic methyl group) by S. litura larvae. 相似文献
26.
Molecular dependence of vesicular endocytosis was investigated with capacitance measurements at the calyx of Held terminal in brainstem slices. Intraterminal loading of botulinum toxin E revealed that the rapid capacitance transient implicated as "kiss-and-run" was unrelated to transmitter release. The release-related capacitance change decayed with an endocytotic time constant of 10 to 25 seconds, depending on the magnitude of exocytosis. Presynaptic loading of the nonhydrolyzable guanosine 5'-triphosphate (GTP) analog GTPgS or dynamin-1 proline-rich domain peptide abolished endocytosis. These compounds had no immediate effect on exocytosis, but caused a use-dependent rundown of exocytosis. Thus, the guanosine triphosphatase dynamin-1 is indispensable for vesicle endocytosis at this fast central nervous system (CNS) synapse. 相似文献
27.
Engelman JA Zejnullahu K Mitsudomi T Song Y Hyland C Park JO Lindeman N Gale CM Zhao X Christensen J Kosaka T Holmes AJ Rogers AM Cappuzzo F Mok T Lee C Johnson BE Cantley LC Jänne PA 《Science (New York, N.Y.)》2007,316(5827):1039-1043
The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well. 相似文献
28.
Shimojima M Miyazawa T Ikeda Y McMonagle EL Haining H Akashi H Takeuchi Y Hosie MJ Willett BJ 《Science (New York, N.Y.)》2004,303(5661):1192-1195
Feline immunodeficiency virus (FIV) induces a disease similar to acquired immunodeficiency syndrome (AIDS) in cats, yet in contrast to human immunodeficiency virus (HIV), CD4 is not the viral receptor. We identified a primary receptor for FIV as CD134 (OX40), a T cell activation antigen and costimulatory molecule. CD134 expression promotes viral binding and renders cells permissive for viral entry, productive infection, and syncytium formation. Infection is CXCR4-dependent, analogous to infection with X4 strains of HIV. Thus, despite the evolutionary divergence of the feline and human lentiviruses, both viruses use receptors that target the virus to a subset of cells that are pivotal to the acquired immune response. 相似文献
29.
Keisuke Tomioka Yuuri Hirooka Toshirou Nagai Hiroyuki Sawada Takayuki Aoki Toyozo Sato 《Journal of General Plant Pathology》2011,77(4):266-268
Severe blight of potted seedlings of monkshood caused by Plectosporium tabacinum was found in glasshouses in Kagawa Prefecture in southwest Japan in May 2001. Root rot and browning of stem bases were followed
by wilting and yellowing of leaves, then blighting of leaves, flower buds and stems. A fungus was isolated from diseased plants
and confirmed to cause the disease. The new disease was named “Plectosporium blight of monkshood”. 相似文献
30.
A modified malonaldehyde (MA) assay for antioxidant activity, which involves derivatization and headspace solid-phase microextraction (HS-SPME) was developed and validated. The recovery of MA as 1-methylpyrazole (product of MA and N-methylhydrazine) from a headspace of an aqueous solution containing MA, buffer, surfactant, and cod liver oil using HS-SPME with a PDMS/DVB fiber was 91.3 +/- 3.38%. MA was analyzed by a gas chromatograph with a nitrogen-phosphorus detector, and its detection limit was 0.0103 nmol/mL. The antioxidant activities of natural compounds were determined as the percentage inhibition of MA formed from cod liver oil oxidized by Fenton's reagents in the above aqueous solution. Sesamol inhibited MA formation most (86.1%), followed by eugenol (84.4%), capsaicin (80.7%), ethylvanillin (45.3%), and vanillin (31.6%) at a level of 50 microg/mL. This method did not require any organic solvents and is a simple, fast, and a highly sensitive method for MA determination. 相似文献