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Akira Tokunaga

Publications and source records attributed to Akira Tokunaga.

28 records · Page 2Linked to original sources
PubMed2003

[Pilot study of TS-1 combined with lentinan in patients with unresectable or recurrent advanced gastric cancer].

TS-1, an anticancer, antimetabolis agent, has shown clinically superior antitumor activity against unresectable advanced or recurrent gastric cancer (UARG). A biological response modifier, lentinan (LNT) prolonged the survival period of patients with UARG when combined with tegafur (FT). To assess the efficacy, the safety and prognostic factors of chemo-immunotherapy using TS-1, a FT derivative, and LNT, we conducted a multi-institutional pilot study in patients with UARG. Patients were treated with TS-1 at 80 mg/m2/day (bid) for 4-weeks, and LNT was given at 2 mg/body (i.v.) in a week, followed by a 2-week rest for 4 cycles. Twenty-two patients were entered from 4 institutes and 19 patients were eligible. The median survival time in eligible patients was 400 days. The incidence of hematological toxicity (grade 2 leukopenia), and non-hematological toxicity (grade 3 nausea or fatigue) was 5.3% (1/19) and no grade 4 toxicity was observed. The response ratio was 37.5% in 8 patients who had been administered the planned dose of TS-1. In subset analyses, the survival period of the patients with normal (< 500 micrograms/ml) serum immunosuppressive acidic protein level was significantly (p < 0.0001) better than that of the higher one. The survival period for those patients whose granulocytes/lymphocytes ratio was not more than 2 tended to be better. From the prolonged survival periods, chemo-immunotherapy using TS-1 combined with LNT would seem to have a benefit against UARG, and reduced toxicity. Future clinical trials are warranted to confirm its potency.

Aged↗
PubMed2002

Gene amplification profiling of esophageal squamous cell carcinomas by DNA array CGH.

Gene amplification is one of the basic mechanisms that lead to overexpression of oncogenes. DNA array comparative genomic hybridization (CGH) has great potential for comprehensive analysis of both a relative gene-copy number and altered chromosomal regions in cancers, which enables us to identify new amplified genes and unstable chromosomal loci. We examined the amplification status in 32 esophageal squamous cell carcinomas (ESCCs) and 13 ESCC cell lines on 51 frequently amplified loci in a variety of cancers by both DNA array CGH and Southern blot analyses. The 1p34 locus containing MYCL1, 2p24 (MYCN), 7p12 (EGFR), and 12q14 (MDM2) were amplified in one of the 32 cases (3%), and the 17q12 locus (ERBB2) and 8p11 (FGFR1) in two of the 32 cases (6%), while only the 11q13 locus (Cyclin D1, FGF4, and EMS1) was frequently amplified (28%, 9/32), demonstrating this locus to be a major target in ESCCs. One locus, 8q24 (c-MYC) was found to be amplified only in the cell lines. Eight out of 51 loci (15.7%) were found to be amplified in at least one of the 32 primary ESCCs or the 13 ESCC cell lines, suggesting that chromosomal loci frequently amplified in a type of human cancer may also be amplified in other types of cancers. This paper is the first report of an application of DNA array CGH to ESCCs.

Blotting, Southern↗
PubMed2002

Novel splice variants of amphiphysin I are expressed in retina.

Using RT-PCR-based cDNA cloning, we identified novel splice variants of amphiphysin I, termed amph Ir, that are expressed specifically in retina. In comparison with the prototype amphiphysin I, amph Ir contained two novel insertions (inserts A and B) and one deletion. Insert A is only 9 bp in length but appears to be a determinant for the retina-specific expression. In contrast, insert B is a large domain of 1740 bp and two shorter transcripts with 3'-truncated insert B were also expressed. All the insert sequences were present as unidentified exons in the amphiphysin I gene on human chromosome 7. Western blot analysis of various rat tissues with anti-insert B antibody confirmed the presence and tissue specificity of the variant proteins.

Alternative Splicing↗
PubMed2002

[Surgical treatment of gastric remnant-stump cancer].

The aim of this study was to evaluate the characteristics, and treatment of gastric remnant cancer based on an analysis of the surgical results of Nippon Medical School over the past 18 years. Thirty seven patients (27 males and 10 females, mean age 60 years) underwent surgery for gastric remnant cancer. Patients who had undergone gastrectomy with Billroth II anastomosis for benign disorder underwent re-gastrectomy for the cancer of gastric remnant 20 years after the first gastrectomy. While, patients who had undergone gastrectomy with Billroth I anastomosis for malignant disorder underwent re-gastrectomy within 10 years after the first gastrectomy. Early-type gastric remnant cancers were not observed in the suture line or gastric stump region, while advanced-type cancers were observed in the anastomotic region. Surgical treatment was carried out by the method of total gastrectomy with Roux-en-Y esophago-jejunal anastomosis. The 5 year survival rates were 77%for early cancer and 14%for advanced cancer. Periodic follow-up endoscopies in gastrectomized patients may be useful for the early detection of gastric remnant cancer after operations for gastric cancer.

Adult↗
PubMedDate not supplied

Tacrolimus enhances colon anastomotic healing in rats.

Tacrolimus inhibits T-cell function and neutrophil chemotaxis during inflammation. We hypothesized that tacrolimus would enhance healing of a rat colon anastomosis by reducing the inflammatory response. Fifty-five male Sprague Dawley rats, 230-260 g body weight, underwent identical surgical manipulation consisting of a single-layer, inverted colon anastomosis and the implantation of osmotic pumps subcutaneously in the left flank area. The animals were randomly assigned to receive tacrolimus, at a dose of 0.01, 0.1, or 1.0 mg/kg/day, or only the control solvent solution. The animals were euthanized 4 days after surgery. Colon-bursting pressure (mmHg), anastomotic collagen content ( micro g hydroxyproline/mg wet tissue), and anastomotic type IV collagenase activity (mU/mg protein) were measured. Tacrolimus significantly increased colon-bursting pressure at all doses used (146 +/- 9, 158 +/- 10, 151 +/- 6 mmHg; 0.01, 0.1, and 1.0 mg/kg/day, respectively) vs. control (119 +/- 7 mmHg, p < 0.01). There was no effect on collagen accumulation except at a dose of 0.01 mg/kg/day, which significantly decreased anastomotic collagen content (p < 0.05). Tacrolimus at a dose of 0.01 mg/kg/day increased anastomotic collagenase activity, which was not changed by treatment with the higher doses. Microscopic examination revealed the preservation of the multilayered structure, including the mucosal muscle, a thickened submucosa, and the proper muscle of the anastomotic site in the tacrolimus-treated groups. These data suggest that tacrolimus enhances wound strength during acute anastomotic healing despite a reduction in collagen content.

Anastomosis, Surgical↗
PubMedDate not supplied

Serum levels of vascular endothelial growth factor, basic fibroblast growth factor and endostatin in human metastatic liver tumors.

BACKGROUND/AIMS: Angiogenic factors are related to the malignant potential of tumors. This study aimed to investigate the relationship of serum angiogenic factors to liver metastasis. METHODOLOGY: The serum levels of vascular endothelial growth factor, basic fibroblast growth factor and endostatin were measured using EIA in 25 patients with metastatic liver tumors and were compared with those of 12 cancer patients without metastasis and 15 controls. RESULTS: The serum vascular endothelial growth factor concentration was significantly higher in the liver metastasis group (503 +/- 84 pg/mL) than in the no metastasis group (205 +/- 38 pg/mL) and the control group (201 +/- 26 pg/mL). The three groups had similar serum basic fibroblast growth factor concentrations. There was no significant difference in serum levels of endostatin among the liver metastasis group (18.8 +/- 1.5 ng/mL), the no metastasis group (23.9 +/- 4.9 ng/mL), and the control group (17.1 +/- 1.5 ng/mL). CONCLUSIONS: Angiogenic response is more prominent than anti-angiogenic responses in liver metastasis. These findings support the rationale for anti-angiogenesis therapy such as endostatin therapy in patients with liver metastasis.

Collagen↗
PubMedDate not supplied

Surgical outcome of 483 patients with early gastric cancer: prognosis, postoperative morbidity and mortality, and gastric remnant cancer.

BACKGROUND/AIMS: The aim of this retrospective study was to evaluate the characteristics, treatment, postoperative morbidity, mortality, and prognosis of early gastric cancer patients as well as the incidence of gastric remnant cancer after curative surgery based on an analysis of the surgical results of Nippon Medical School Hospital over the past 10 years (1991-2000). METHODOLOGY: Out of 1057 patients with gastric cancer (all stages), 483 patients (301 males and 182 females; mean age 60.9 years) underwent surgery for early gastric cancer. Early gastric cancer, defined as that invading the m or sm layer regardless of lymph node metastasis, was classified according to the Japanese Classification of Gastric Carcinoma. The survival rate was calculated using the Kaplan-Meier method. RESULTS: The stages of the 483 patients were as follows: stage Ia patients, 443 cases; stage Ib, 29 cases; stage II, 7 cases; and stage IV, 4 cases. The overall 5- and 10-year survival rates were 95.9% and 95.9% for stage Ia, 82.9% and 80.2% for stage Ib, 73.2% and 68.6% for stage II and 0% for stage IV, respectively. No difference was observed in the 5- and 10-year survival rates between patients with D1 and D2 dissections in cases without lymph node metastasis. In patients with n1 positive sm cancer, however, the 5-year survival rate of the patients who underwent D2 dissection was 91.0% while that of those who underwent D1 dissection was 80.0% (P<0.05). The incidences of postoperative morbidity from various cancers included 4.2% from surgical site infections, 1.6% from anastomotic dehiscence, 1.6% from intestinal obstructions, and 3.9% from respiratory and/or heart dysfunction. Three patients (0.6%) died of multiple organ failure. Five patients who had undergone gastrectomy for early gastric cancer were diagnosed as having early cancer in the gastric remnant during a periodic follow-up endoscopy and underwent regastrectomy. CONCLUSIONS: The prognosis of early gastric cancer is usually excellent, and the morbidity and mortality rates are satisfactory. D2 lymph node dissection is necessary in patients with n1 positive sm cancer. Periodic follow-up endoscopies in gastrectomized patients may be useful for the early detection of gastric remnant cancer.

Gastrectomy↗