Delving into the Latest Updates on Nihon Schering KK with Synapse

Overview

RATIONALE AND OBJECTIVESTo investigate the potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for the differential diagnosis of nonalcoholic steatohepatitis (NASH) and fatty liver (FL).METHODSTwenty-one male rats were divided into 3 groups. Seven rats in the NASH group were fed a choline-deficient diet for 10 weeks, and the 7 rats in the FL group were fed a standard diet also containing 1% (wt/wt) orotic acid for 4 weeks. As a control, 7 rats were fed a standard diet. After the feeding period, all rats were subjected to contrast-enhanced dynamic and delayed MRI with a 2D-FLASH technique. Gd-DTPA (0.1 mmol Gd/kg) and Gd-EOB-DTPA (0.025 mmol Gd/kg) were injected into the tail vein at 24-hour intervals. Signal intensities of the liver were measured for each MR image and the relative enhancement (RE) was calculated. In addition, the time of maximum RE (Tmax) and the half-life of RE (T1/2) in liver were compared. After MRI, the liver was histologically analyzed to evaluate steatosis, hepatitis, and fibrosis.RESULTSDiffuse macrovesicular steatosis and severe fibrosis were observed in the NASH group, whereas diffuse microvesicular steatosis and rare fibrosis were observed in the FL group. Immediately after the Gd-DTPA injection, the RE in the liver of each group temporarily increased, and thereafter, rapid RE reduction was observed. However, a continuous increase and subsequent slow reduction of RE were induced after the Gd-EOB-DTPA injection. Although there was no difference between the Tmax and T1/2 of each group after the Gd-DTPA injection, Tmax and T1/2 of the NASH group were significantly prolonged in comparison with FL and control groups after the Gd-EOB-DTPA injection (P < 0.01).CONCLUSIONSIt was possible to differentiate NASH and FL by evaluating the SI time course on Gd-EOB-DTPA enhanced MRI.

01 Sep 2006·Molecular Cancer TherapeuticsQ2 · MEDICINE

The Rho kinase inhibitor fasudil inhibits tumor progression in human and rat tumor models

Q2 · MEDICINE

Article

Author: Pagila, Rene ; Kamata, Yoichi ; Ohashi, Yasuhiro ; Alicke, Bruno ; Biroc, Sandra L. ; Xuan, Jian-Ai ; Dinter, Harald ; Ying, Han ; Okada, Toshiya ; Li, Wei-wei

AbstractThe ability of cancer cells to undergo invasion and migration is a prerequisite for tumor metastasis. Rho, a Ras-related small GTPase, and the Rho-associated coiled coil–containing protein kinases (Rho kinases, ROCK1 and ROCK2) are key regulators of focal adhesion, actomyosin contraction, and thus cell motility. Inhibitors of this pathway have been shown to inhibit tumor cell motility and metastasis. Here, we show that fasudil [1-(5-isoquinolinesulfonyl)-homopiperazine], an orally available inhibitor of Rho kinases, and its metabolite 1-(hydroxy-5-isoquinoline sulfonyl-homopiperazine) (fasudil-OH) modify tumor cell morphology and inhibit tumor cell migration and anchorage-independent growth. In addition, we show that fasudil inhibited tumor progression in three independent animal models. In the MM1 peritoneal dissemination model, tumor burden and ascites production were reduced by >50% (P < 0.05). In the HT1080 experimental lung metastasis model, fasudil decreased lung nodules by ∼40% (P < 0.05). In the orthotopic breast cancer model with MDA-MB-231, there were 3-fold more tumor-free mice in the fasudil-treated group versus saline control group (P < 0.01). Fasudil has been approved for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms. In patients, fasudil is well tolerated without any serious adverse reactions. Therefore, the concept of Rho kinase inhibition as an antimetastatic therapy for cancer can now be clinically explored. [Mol Cancer Ther 2006;5(9):2158–64]

01 Jan 2006·Magnetic Resonance in Medical SciencesQ4 · MEDICINE

Superparamagnetic Iron Oxide (SPIO) MRI Contrast Agent for Bone Marrow Imaging: Differentiating Bone Metastasis and Osteomyelitis

Q4 · MEDICINE

Article

Author: Norio Nakao ; Naoki Kato ; Noriko Kotoura ; Shinichi Yoshiya ; Yuko Fukuda ; Reiichi Ishikura ; Kumiko Ando ; Natsuko Tsuda

PURPOSEWe explored appropriate scan timing for bone marrow imaging enhanced using superparamagnetic iron oxide (SPIO) and evaluated the usefulness of SPIO in differentiating metastasis and osteomyelitis in patients.METHODSTo determine the adequate scan timing after administration of SPIO, 5 healthy subjects were examined using a 1.5T magnetic resonance (MR) imaging scanner. Sagittal images of their lumbar spines were obtained using short-TI inversion recovery (STIR) sequence before and 3, 6, 9, 24, and 48 hours after intravenous injection of 8 micromol Fe/kg SPIO (ferucarbotran). MR signal intensities (SIs) were evaluated. Based on the results, 12 patients, five with bone metastasis and seven with vertebral osteomyelitis, were examined using the same procedure before and 3 hours after intravenous injection of ferucarbotran at the same dose. SIs of the bone metastases, osteomyelitis, and surrounding normal bone marrow were measured, and relative enhancement (RE) was calculated for each lesion.RESULTSIn the healthy volunteers, maximum reduction in signal was observed 3 to 24 hours (P<0.05) after administration of SPIO; thereafter and up to 48 hours, the SI gradually recovered. In the patients, the RE of the bone metastases was -12.2%, which was significantly higher than that in the osteomyelitis (-35.0%, P<0.001) and normal bone marrow (-46.6%, P<0.0005).CONCLUSIONMaximum suppression of signal intensity in bone marrow was seen 3 hours after injection of ferucarbotran, the point at which ferucarbotran allows differentiation of bone metastasis from ostoemyelitis.

100 Deals associated with Nihon Schering KK

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100 Translational Medicine associated with Nihon Schering KK

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Pipeline

Pipeline Snapshot as of 07 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

MS-654	Arrhythmias, Cardiac More	Discontinued
MS 247 ( TOP )	Neoplasms More	Discontinued
MS-153 ( NMDA receptor )	Ischemic stroke More	Discontinued
MS-3579 ( β-adrenoceptors )	Arrhythmias, Cardiac More	Discontinued
MS-857 ( PDE3 )	Myocardial Ischemia More	Discontinued