Biomedical subjects

Satoshi Yuki

Publications and source records attributed to Satoshi Yuki.

5 recordsLinked to original sources

PubMed2006

Orally active neurotrophin-enhancing agent protects against dysfunctions of the peripheral nerves in hyperglycemic animals.

Biological substances with neurotrophic activities, such as nerve growth factor (NGF) and monosialoganglioside GM1, have been considered as agents for diabetic peripheral neuropathy. Because recent studies have suggested that decreased availability of these substances might contribute to the pathogenesis of diabetic peripheral neuropathy, some clinical trials of NGF for diabetic peripheral neuropathy have been conducted and have led to mixed conclusions. The major reasons were its limited delivery to the nervous system and adverse effects induced by subcutaneous injection, which was necessary because NGF is a polypeptide. The current study investigates whether an orally active sialic acid derivative, MCC-257, has neuroprotective properties in diabetic peripheral nerves. MCC-257 augmented NGF activity in cultured dorsal root ganglia and PC12 (pheochromocytoma 12) cells. Treatment with MCC-257 elevated NGF levels in the sciatic nerve, accompanied by improvement in nerve conduction velocity in streptozotocin-induced diabetic animals. More importantly, MCC-257 ameliorated small fiber dysfunctions, including thermal hypoalgesia, substance P content, and histopathological innervation in the plantar skin of diabetic animals. Thus, the orally active neurotrophin enhancer provides a new option for the clinical treatment of diabetic peripheral neuropathy.

Administration, Oral↗

PubMed2006

[Irinotecan plus oral S-1 in patients with advanced gastric cancer-biweekly IRIS regimen].

We reported the results of phase I study with CPT-11 and S-1 (IRIS) in advanced gastric cancer (AGC) patients at ASCO 2002. Now I present an outline of this phase I/II trial. A combined treatment of IRIS (CPT-11 + S-1) was given to the AGC patients who had not received prior chemotherapy. S-1 was orally administered twice a day for 14 days, and CPT-11 was administered as a 90-minute intravenous infusion on days 1 and 15. This schedule was repeated every 4 weeks. Fifteen patients were registered in this phase I study and 9 patients were added in this phase II study. Non-hematological toxicities were almost classified as grade 2 or lower, except for grade 3 nausea and grade 3 dermatitis of level 2. These adverse events were manageable by administering anti-emetic drugs and a drug rest. As for hematological toxicities, grade 4 neutropenia occurred with one patient at level 1 and level 2 in phase I. And grade 4 neutropenia occurred with four patients at level 2 in phase II. However, they recovered after the drug rest, and we could continue the administration based on the standard dose modifications. These side effects were tolerable, and the overall response rate was 54.2%. MST of this regimen is 581 days. The IRIS treatment is effective and tolerable for outpatient treatments.

Administration, Oral↗

PubMed2006

[Irinotecan plus oral S-1 in patients with advanced colorectal cancer--biweekly IRIS regimen].

We planned to conduct a phase II clinical study of combination therapy with CPT-11 and S-1. The antitumor effect was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20-75 years. Based on the results of our previous phase I/II study in patients with gastric cancer, the dosage was established in consideration of safety for outpatient therapy. CPT-11 was administered at a dose of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Interim analysis suggested excellent results, with a response rate of 50%. Combination therapy with CPT-11 and S-1 achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer.

Administration, Oral↗

PubMed2004

[Immunological rapid urease test].

Immunological rapid urease test for detection of Helicobacter pylori infection, composed of a solid-phase tip coated with monoclonal antibody against H. pylori's urease and ion-sensitive field transistor (ISFT)-based pH sensor system, was developed. The monoclonal antibody against H. pylori's urease was useful to avoid the contamination of urease activity in other bacteria. Because ISFTT had high ability to detect pH change, the sensitivity and specificity of immunological rapid urease test was significantly improved comparing with that of conventional rapid urease test. The utility of immunological rapid urease test was evaluated in some clinical studies.

Antibodies, Monoclonal↗

PubMed2003

Structure-activity relationship of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone).

This paper describes the discovery of a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone, 1), as a potent antioxidant agent against lipid peroxidation. The structure-activity relationship of edaravone indicated that lipophilic substituents were essential to show its lipid peroxidation-inhibitory activity. In vivo studies revealed that edaravone showed brain-protective activity in a transient ischemia model.

Animals↗