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Naohito Yoshizaki

Publications and source records attributed to Naohito Yoshizaki.

10 recordsLinked to original sources
PubMed2006

[Clinical administration of oxaliplatin for patients previously treated for refractory advanced or recurrent colorectal cancer].

Oxaliplatin (L-OHP) was administered to 10 patients previously treated for refractory advanced or recurrent colorectal cancer. The number of times each had received previous chemotherapy treatment ranged from 1 to 5 (median 3) for durations of 2.5 to 52.8 (median 11.7) months. At the time, L-OHP was not yet approved for sale in Japan, and could only be imported from overseas for personal use. As this made it very expensive,we used a low L-OHP dose of 100 mg/body. Combinations with 5-FU were administered differently from previous regimens; these included chronotherapy, weekly high-dose, FOLFOX 4, and FOLFOX 6. L-OHP was administered from 1 to 14 times (median 4.5), and the response to treatment was PR in 2 patients and NC in 5. The response rate was 22.2%. Although in NC there was a tendency toward tumor reduction in 2 of the 5 patients, the treatment had to be suspended because of their financial situations. Overall survival from commencement of the first treatment was 3.1 to 58.7 months (median 17.6+) and after starting L-OHP was 0.6 to 17.2 months (median 6.4+). Adverse events included bone marrow suppression in three patients, 3 cases of leukocytopenia (grade 3 in two patients and grade 4 in one), grade 4 thrombocytopenia in one patient,grade 3 sensory disturbance in one patient,and grade 3 anorexia in two patients. All reactions were able to be controlled except for one patient with Grade 4 thrombocytopenia. In summary,treatment with L-OHP as salvage chemotherapy can possibly contribute to prolongation of survival time in cases of refractory advanced colorectal cancer. It is useful to combine L-OHP with high-dose continuous administration of 5-FU,namely FOLFOX regimens.FOLFOX 6 is the most useful of the FOLFOX regimens because it is simple and can be administered on an outpatient basis.

Aged↗
PubMed2005

A phase I/II study of S-1 plus cisplatin in patients with advanced gastric cancer: 2-week S-1 administration regimen.

BACKGROUND: The combination of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine (S-1) and cisplatin (CDDP) is one of the most active chemotherapy regimens for gastric cancer. However, the optimum schedule for this combination has not yet been determined. This study was conducted to establish the maximum tolerated dose (MTD) and the recommended dose of CDDP when combined with 2-week S-1 administration, and to observe the safety and efficacy of the regimen as treatment for patients with advanced gastric cancer. METHODS: S-1 was administered orally at a dose of 80 mg/m2 per day for 2 weeks, followed by a 2-week rest. CDDP was administered intravenously on day 8 of each course; the initial dose of CDDP was 60 mg/m2 and it was increased in 10-mg/m2 increments. Treatment was repeated every 4 weeks unless disease progression was observed. RESULTS: Eleven patients were enrolled. The main toxicities were leucopenia, neutropenia, nausea, and anorexia. These toxicities were not severe, and were reversible and manageable. The MTD for CDDP was established as 80 mg/m2, as 2 of 5 (40%) patients developed dose-limiting toxicity (DLT) at this level. Therefore, the recommended dose of CDDP was determined to be 70 mg/m2. All 11 patients were evaluable for a response: 8 achieved a partial response and 1 had stable disease. The overall response rate was 73%. CONCLUSION: This regimen is considered to be generally well-tolerated and has substantial antitumor activity.

Administration, Oral↗
PubMed2003

Increased expression of angiogenin in hepatocellular carcinoma in correlation with tumor vascularity.

PURPOSE: Neovascularization is known to be one of the major characteristics of human hepatocellular carcinoma (HCC). Angiogenin (ANG), originally discovered in a human colon cancer cell line, is a liver-derived polypeptide that shows strong angiogenic activity in vivo. However, the role of ANG on the development of HCC remains unknown. The present study was designed to examine the implication of ANG in the neovascularization of human HCC. EXPERIMENTAL DESIGN: Forty-one HCC patients who had undergone conventional celiac angiography were used in this study. ANG protein expression and microvessel density (MVD) in HCC specimens obtained by liver biopsy or surgical resection were examined by immunohistochemistry, and the levels were quantified by the KS-400 image analyzing system. ANG mRNA expression in liver tissues was evaluated by in situ hybridization. Serum ANG concentrations were measured by an ELISA. Survival rates were calculated using the Kaplan-Meier method. RESULTS: Immunohistochemistry and in situ hybridization showed greater increments of ANG protein expression and mRNA expression, respectively, in HCC tissues than in the surrounding nontumorous tissues. MVD within tumorous tissues increased according to dedifferentiation of the histological grade of HCC, showing a significant correlation (r = 0.877, P = 0.0009) with ANG expression levels. Mean +/- SD serum ANG levels of healthy subjects and chronic hepatitis (CH) patients were 362.3 +/- 84.1 ng/ml and 331.9 +/- 133.8 ng/ml, respectively, with no significant difference. Serum ANG levels of liver cirrhosis patients (242.4 +/- 126.9 ng/ml) were lower than those of healthy subjects or CH patients and decreased as the fibrosis grade advanced. In HCC patients, despite the cirrhotic background, serum ANG levels increased as the tumor vascularity increased (197.8 +/- 64.9 ng/ml for hypovascular, 326.7 +/- 148.6 ng/ml for hypervascular, and 405.0 +/- 121.3 ng/ml for very hypervascular), in good accordance with histological grading, and significantly decreased (P = 0.015) after successful treatment with transcatheter arterial embolization or percutaneous ethanol injection. HCC patients were conventionally divided into two groups according to the serum level of ANG, those with values higher than the mean level (332.9 +/- 143.8 ng/ml) and those with values lower than the mean,; the 5-year survival rate of the latter group was determined to be significantly higher than that in the former group. CONCLUSIONS: These results suggest that ANG is one of the neovascularization defining factors of HCC. Thus, measuring serum ANG may assist in monitoring the disease, and targeting ANG may provide a new strategy for treating advanced HCC.

Adult↗
PubMed2003

[A case of liver metastasis from gallbladder cancer with marked response to arterial infusion chemotherapy].

The patient was a 68-year-old woman who visited a nearby clinic with a chief complaint of right hypochondrial pain. A mass lesion in the gallbladder was found by ultrasonography. She was referred to our hospital for further examination and was diagnosed with gallbladder cancer. Cholecystectomy and bile duct resection were performed. Six months after the surgery, multiple liver metastases were found. A subcutaneous implant reservoir was placed in the hepatic artery from the right femoral artery. After arterial infusion chemotherapy by 5-FU and CDDP, or 5-FU alone, liver metastasis markedly responded and became undetectable, and therapy was therefore discontinued. The patient has been disease-free without any sign of recurrence for 7 months after CR was achieved. It is suggested that arterial infusion chemotherapy is useful and safe for the treatment of liver metastasis from gallbladder cancer.

Aged↗
PubMed2002

Enhanced expression of type IV collagen-binding protein (p29) in Fyn-transfected murine fibrosarcoma cells.

We investigated the mechanism of the enhancement of metastatic potential induced by transfection of the fyn gene, a member of the src family. We employed two murine fyn cDNA-transfected clones, ML-SN1 and ML-SN2, which were previously established from an ML-01 low-metastatic clone of Meth A sarcoma of BALB / c mice and were proven to have higher metastatic ability than ML-01 and the mock-transfected clone ML-MT-neo (Takayama et al., 1993). Our present investigation revealed that the two transfectants showed higher metastatic ability and higher rates of adherence to type IV collagen than ML-MT-neo. However, no difference was found in in vitro or in vivo growth rates, attachment to laminin or endothelial cells or cell motility through a reconstituted basement membrane. Analysis of surface membrane proteins labeled with (125)I on SDS-PAGE showed that a 29 kD band specifically bound to type IV collagen-coupled beads was more intense in ML-SN2 than in ML-MT-neo. Genistein, a protein tyrosine kinase inhibitor, dramatically reduced protein tyrosine kinase (PTK) activity of ML-SN2 in a dose-dependent fashion, corresponding to the reduction of adhesiveness to type IV collagen. The expression of the type IV collagen-binding protein (p29) of ML-SN2 was also reduced significantly by genistein treatment. These results suggested that the fyn product in Meth A cells augments the expression of a type IV collagen-binding protein through elevation of the PTK activity of the membrane fraction and thus facilitates the metastasis of Meth A.

Animals↗