Publications by authors named "Shizuka Seki"

2 Publications

  • Page 1 of 1

Sapropterin For Phenylketonuria: A Japanese Post-Marketing Surveillance Study.

Pediatr Int 2021 Jul 31. Epub 2021 Jul 31.

Daiichi Sankyo Company Limited, 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan.

Background: To assess the long-term safety and efficacy of sapropterin in a real-world setting in Japanese patients with tetrahydrobiopterin (BH4)-responsive phenylketonuria (PKU).

Methods: This post-marketing surveillance study enrolled all patients in Japan with confirmed BH4-responsive PKU who were administrated sapropterin between July 2008 and October 2017. Patients were observed at least every 3 months during follow-up, with key data collected on treatment exposure/duration, effectiveness according to physician judgement, serum phenylalanine levels, and adverse events.

Results: Of 87 enrolled patients, 85 patients (male, 42.4%; outpatients, 96.5%) were included in the safety and efficacy analysis sets. Treatment started at age <4 years in 43 (50.6%) patients and the most common starting daily dose was 5-10 mg/kg (n=41 [48.2%]) with the overall duration of treatment between 0.2 and 17.2 years. Serum phenylalanine levels according to loading tests reduced from a baseline level of 9.66 mg/dL (range 0.48-36.80 mg/dL) by >30% in 84 patients. Treatment was deemed effective in 79 of 85 patients (92.9%, 95% CI 85.3-97.4). One (1.2%) patient experienced an adverse drug reaction (alanine aminotransferase increased) 50 days after the start of administration, which resolved without complications with continued treatment.

Conclusions: Sapropterin appears well tolerated and highly effective in Japanese patients treated in a real-world setting, including those who start treatment at age <4 years and pregnant women.
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July 2021

Feasibility study of B16 melanoma therapy using oxidized ATP to target purinergic receptor P2X7.

Eur J Pharmacol 2012 Nov 11;695(1-3):20-6. Epub 2012 Sep 11.

Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi Chiba, Japan.

The P2X7 receptor is not only involved in cell proliferation, but also acts as an adenosine 5'-triphosphate (ATP)-gated non-selective channel, and its expression is increased in human melanoma. An irreversible antagonist of P2X7, such as oxidized ATP (oxATP), might block P2X7 receptor-mediated ATP release and proliferative signaling. Therefore, we carried out basic studies to test this idea and to examine the feasibility of using oxATP to treat B16 melanoma. We first found that low-pH conditions (mimicking the hypoxia and acidosis commonly seen in solid tumors) induced P2X7 receptor-mediated ATP release from B16 melanoma cells. Then, we compared the proliferation rates of B16 melanoma wild-type cells and B16 P2X7 receptor-knockdown clone (P2X7-KDC) cells in the presence of P2X7 agonists. The proliferation rate, as well as the ATP release, of agonist-treated P2X7-KDC cells was lower than that of agonist-treated wild-type cells. Next, the effect of P2X7 antagonist oxATP on B16 melanoma cell growth was examined in vitro and in vivo. oxATP significantly decreased B16 melanoma cell proliferation in vitro, and also significantly inhibited tumor growth in B16 melanoma-bearing mice. These data indicate that extracellularly released ATP may serve as an intercellular signaling molecule. We propose that the P2X7 receptor is a promising target for treatment of solid tumors.
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November 2012