The transcription factor ETS-1 is induced in endothelial cells (ECs) by angiogenic growth factors and the specific elimination of synthesis antisense oligodeoxynucleotide inhibited angiogenesis vitro (Iwasaka et al., 1996, J Cell Physiol 169:522–531). To understand precise role angiogenesis, we established both high low expression EC lines compared properties these cell with those parental murine line, MSS-31. Although rate was almost identical for each invasiveness markedly enhanced reduced...

Therapeutic angiogenesis is thought to be beneficial for serious ischemic diseases. This investigation was designed establish a simple and practical procedure applicable therapeutic angiogenesis.When cultured skeletal muscle cells were electrically stimulated at voltage that did not cause their contraction, vascular endothelial growth factor (VEGF) mRNA augmented an optimal-frequency stimulation. increase of VEGF derived primarily from transcriptional activation. Electrical stimulation...

Ets-1, a transcription factor, is induced in endothelial cells (ECs) during angiogenesis. Here, we investigated the expression of Ets-1 reendothelialization. When confluent monolayer human umbilical vein cell line, ECV304, was denuded, ECV304 at wound edge expressed Ets-1. An immunohistochemical analysis revealed that accumulated migrating and returned to basal level when reendothelialization accomplished. This induction could be reproduced vivo denudation rat aortic endothelium by balloon...

Transforming growth factor-β (TGF-β) is normally secreted in a latent form, and plasmin-mediated proteolytic cleavage of latency-associated peptide (LAP), component TGF-β complex that makes the inactive, activates TGF-β. In present study, we investigated possible involvement calpain, one cysteine proteases, activation When recombinant was incubated with calpain (1–10 u/ml) test tube, cleaved LAP released mature from complex. applied to cultured bovine capillary endothelial (BCE) cells, low...

Abstract —The platelet-derived growth factor (PDGF) ligands and their receptors have been implicated as critical regulators of the formation arterial lesions after tissue injury. SU9518 (3[5-{5-bromo-2-oxo-1,2-dihydroindol-3-ylidenemethyl}-2,4-dimethyl-1 H -pyrrol-3-yl]propionic acid) is a novel synthetic indolinone that potently selectively inhibits cellular PDGF receptor kinase receptor–induced cell proliferation. Inhibition phosphorylation in cell-based assays occurs within 5 minutes drug...

Recently, alpha(1)-adrenoceptors (alpha(1)-ARs) have been reported to play a prominent role in the growth of variety cells; however, little is known about prostate and subtype-specific effects on cell proliferation. We examined alpha(1d)-AR effect subtype-selective alpha(1)-AR antagonist, naftopidil, which has relatively higher affinity for alpha(1d)-AR, vitro vivo.First, we naftopidil proliferation PrEC, PrSC, PrSMC using WST-1 assay. Second, performed real-time RT-PCR quantify each subtype...

Abstract Background: FGFs (fibroblast growth factors) and their receptors (FGFRs) play crucial roles in regulation of cell proliferation, survival, migration differentiation. The FGFRs are comprised four subtypes (FGFR1∼4) gene abnormalities such as amplification, translocation mutations have been reported multiple cancers including breast, bladder, lung, gastric, endometrial myeloma. We identified a highly potent selective irreversible FGFR inhibitor, TAS-1201) which inhibits all 4 FGFR. In...

A bstract : Angiogenesis is a complex phenomenon that requires at least migration, proliferation, and tubular morphogenesis of endothelial cells (ECs). Some genes are expressed in ECs during these processes, therefore the regulation gene expression critical. Increasing evidence suggests Ets family transcription factors plays an important role angiogenesis. We observed Ets‐1, prototype factors, promoted angiogenesis by inducing matrix metalloproteinases integrin β3 ECs, elimination...

No AccessJournal of UrologyInvestigative Urology1 Oct 2011Up-Regulation α1a and α1d-Adrenoceptors in the Prostate by Administration Subtype Selective α1-Adrenoceptor Antagonist Tamsulosin Patients With Benign Prostatic Hyperplasia Yoshiyuki Kojima, Shoichi Sasaki, Yasue Kubota, Makoto Imura, Nobuyuki Oda, Mamoru Kiniwa, Yutaro Hayashi, Kenjiro Kohri KojimaYoshiyuki Kojima More articles this author , SasakiShoichi Sasaki KubotaYasue Kubota ImuraMakoto Imura OdaNobuyuki Oda KiniwaMamoru Kiniwa...

Approximately 25–40% of patients with lung cancer show bone metastasis. Bone modifying agents reduce skeletal-related events (SREs), but they do not significantly improve overall survival. Therefore, novel therapeutic approaches are urgently required. In this study, we investigated the anti-tumor effect TAS-115, a VEGFRs and HGF receptor (MET)-targeted kinase inhibitor, in tumor-induced disease model. A549-Luc-BM1 cells, an osteo-tropic clone luciferase-transfected A549 human adenocarcinoma...

Histological observations of clinical benign prostatic hyperplasia specimens show that tissue is mainly composed stromal components, smooth muscle and fibrous tissue, so-called hyperplasia. However, little understood regarding the pathogenesis this due to no suitable model elucidate pathology We created a novel accompanied by clinically relevant hyperplasia.The urogenital sinus isolated from male rat 20-day embryos was implanted into pubertal ventral prostates. Two 8 weeks after operation...

Abstract We generated a series of monochain HLA class I knock-in (KI) mouse strains, in which chimeric molecule (α1/α2 domain HLA-A*0201, HLA-A*0301, HLA-A*2402, or HLA-A*3101 and α3 H-2Db) was covalently linked with 15 aa to human β2-microglobulin (β2m) introduced into the endogenous β2m locus. In homozygous KI mice, gene disruption resulted loss H-2 molecules reduction peripheral CD8+ T cell population that partially restored by expression. A dosage-dependent expression HLA, similar PBMCs,...

Transforming growth factor-beta (TGF-beta) is secreted in a latent form; thus, activation critical for the control of TGF-beta action. Latent exists complex which mature noncovalently linked to latency associated peptide (LAP) and binding protein (LTBP) complex. We have shown that efficiently activated heterotypic cultures endothelial cells (ECs) smooth muscle (SMCs). Under those conditions, LAP plays an important role targeting surface SMCs, plasmin calpain target it ECs activation. Here,...

1. To search an appropriate evaluation methodology for the intestinal first-pass metabolism of new drug candidates, grapefruit juice (GFJ)- and vehicle (tap water)-pretreated mice or rats were orally administered midazolam (MDZ) triazolam (TRZ), blood levels parent compounds their metabolites measured by liquid chromatography/MS/MS. A significant effect GFJ to elevate was observed only TRZ in mice.2. In vitro experiments using mouse, rat human hepatic microsomal fractions demonstrated that...

The purpose of this study was to determine the efficacy and possible mechanism action a recently synthesized drug, TAS-301 [3-bis (4-methoxyphenyl)methylene-2-indolinone], on intimal formation in comparison with those tranilast, clinical which reported earlier. Rat carotid arteries were injured using balloon catheter. Neointimal thickening, measured 14 days after injury, reduced by oral administration dose-dependent fashion (3-100 mg/kg), effect at dose 100 mg/kg significantly greater than...

Summary— The pharmacological properties of TH‐142177 (N‐n‐butyl‐N‐[2′‐(1‐H‐tetrazole‐5‐yl)biphenyl‐4‐yl]‐methyl‐(N‐carboxymethyl‐benzylamino)‐acetamide), a novel antagonist the angiotensin II (AII) AT 1 receptor, were studied in vitro and vivo, compared to those losartan. In rat isolated aorta, produced parallel shifts right concentration‐response curves for AII‐induced contractions without affecting maximal response (pA 2 = 9.07). inhibitory potency aorta was about three times greater than...

Abstract Die durch Aminierung der Pyrazole (I) mit Hydroxylamin‐O‐sulfonsäure (II) zugänglichen N‐Amino‐Derivate (III) liefern bei Oxidation Blei(IV)‐acetat unter Ringerweiterung die 1,2,3‐Triazine (IV).

You have accessJournal of Urology1 Apr 2009PROSTATE GROWTH INHIBITION BY SUBTYPE-SELECTIVE ALPHA1-ADRENOCEPTOR ANTAGONIST NAFTOPIDIL IN BENIGN PROSTATIC HYPERPLASIA Yoshiyuki Kojima, Shoichi Sasaki, Nobuyuki Oda, Masa Hayase, Yasue Kubota, Yutaro Hayashi, Mamoru Kiniwa, and Kenjiro Kohri KojimaYoshiyuki Kojima More articles by this author , SasakiShoichi Sasaki OdaNobuyuki Oda HayaseMasa Hayase KubotaYasue Kubota HayashiYutaro Hayashi KiniwaMamoru Kiniwa KohriKenjiro View All Author...

The purpose of this study was to determine the efficacy and possible mechanism action a recently synthesized drug, TAS-301 [3-bis(4-methoxyphenyl)methylene-2-indolinone], on stenosis after balloon overstretch injury porcine arteries. We measured diameter vessels by angiography conducted histological analysis. oral administration kept dilated angiographic luminal injured segment 4 weeks reduced calculated ratio in dose-dependent manner, significantly reducing it at doses 30 100 mg/kg....

You have accessJournal of UrologyDiscussed Poster, Tuesday, May 11, 2004, 8:00 am - 12:00 pm1 Apr 20041338: Desirable Therapeutic Approach on Benign Prostate Hyperplasia; Proposal from Anti-Androgen Therapy Novel Stromal Hyperplasia Model Nobuyuki Oda, Motomu Watanabe, Fukumitsu Sakakibara, Fumitaka Mori, Mamoru Kiniwa, and Kazuhisa Miyoshi OdaNobuyuki Oda More articles by this author , WatanabeMotomu Watanabe SakakibaraFukumitsu Sakakibara MoriFumitaka Mori KiniwaMamoru Kiniwa...