Biomedical subjects

Kazuhiro Yoshida

Publications and source records attributed to Kazuhiro Yoshida.

94 records · Page 6Linked to original sources

PubMedDate not supplied

The ligands of peroxisome proliferator-activated receptor (PPAR) gamma inhibit growth of human esophageal carcinoma cells through induction of apoptosis and cell cycle arrest.

In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the growth-inhibitory effects of Troglitazone and Pioglitazone, selective ligands for PPARgamma, using a series of human esophageal carcinoma cell lines (TE-1, -3, -7, -8, -12 and -13). PPARgamma expression was detected in all six human esophageal carcinoma cell lines. The esophageal carcinoma cell line TE-13 showed marked growth inhibition in response to Troglitazone and Pioglitazone. Flow cytometry performed on TE-13 cells exposed to Troglitazone showed that the cell cycle was arrested at the G1-phase. This result was confirmed by the finding of reduced cyclin D and cyclin E expression by Western blot analysis. DNA ladder formation was also detected, as was the induction of apoptosis-related proteins. Our results suggested that Troglitazone inhibited the growth of human esophageal carcinoma cell lines via G1 arrest and apoptosis and that PPARgamma ligands should be considered as possible target molecules in the treatment of human esophageal carcinomas.

Antineoplastic Agents↗

PubMedDate not supplied

Phase I study of combination therapy with S-1 and docetaxel (TXT) for advanced or recurrent gastric cancer.

BACKGROUND: S-1, an oral fluorouracil antitumor drug, and docetaxel have both been identified as effective agents for the treatment of gastric cancer. The two drugs have incompletely overlapping principal toxicities, which constitute the rationale for evaluating the effects of a combination of S-1 and docetaxel in this phase I study. The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the recommended dose of docetaxel with a fixed dose of S-1 in patients with advanced or recurrent gastric cancer. PATIENTS AND METHODS: The pharmacokinetics of both drugs were evaluated on Day 1 of treatment. Patients with a performance status (PS) of 0 to 2 received docetaxel at the starting dose of 40 mg/m2 by i.v. infusion over 1 hour on Day 1 and S-1 at the fill dose of 80 mg/m2 daily for two weeks every three weeks. Nine patients were treated with increasing dose levels of docetaxel as follows: (docetaxel/S-1, mg/m2): 40/80 (Level 1), 50/80 (Level 2) and 60/80 (Level 3) and all the cases were found to be assessable for drug safety, while 7 were assessable for response. Colony-stimulating factor (CSF) was not used in this study. The adverse effects of the treatment were analyzed according to NCI-CTC version 2, and the response was assessed according to the Japanese Classification of Gastric Cancer, 13th Ed. RESULTS: The MTD was reached at the 50/80 mg/m2 dose level in three patients out of six, who experienced a dose-limiting toxicity (DLT). The DLTs were neutropenia and allergic reactions. No hematological or non-hematological adverse effects (nore severe than Grade 2) were observed in any of the Level 1 patients. However among the Level 2 patients, 50% developed neutropenia (more severe than Grade 2), 33% developed loss of appetite, 17% developed diarrhea, 33% developed stomatitis and 17% developed allergic reactions. On the other hand, partial response was achieved in 5 (71.4%) of the 7 patients with evaluable lesions. The pharmacokinetics of docetaxel were not altered as compared to that in the historical controls by the administration of S-1. These results indicate that the recommended doses of the two drugs in the combination therapy would be 40 mg/m2 for docetaxel and 80 mg/m2 for S-1. CONCLUSION: The drug combination showed a good safety profile, with neutropenia being a common but manageable adverse reaction. Moreover, the responses observed in the study suggest that the drug combination shows a high degree of efficacy in patients with advanced and or recurrent gastric cancer.

Aged↗

PubMedDate not supplied

Experimental study on fluorescent microspheres as a tracer for sentinel node detection.

BACKGROUND: Common tracers for sentinel node navigation surgery are blue dye and technetium-99m-labelled colloids. However, in most esophageal or lung cancer patients, it is impossible to detect the sentinel node among mediastinal nodes by blue dye because of the anthracotic pigmentation of mediastinal nodes. The use of technetium-99m-labelled colloids requires a special facility, while a large hot-spot at the injection site prevents detection of the sentinel node around the primary lesion. To overcome these problems, we investigated the use of fluorescent microspheres (0.1-20 microm in diameter) as tracers in animals and detected fluorescence-positive nodes by a simple ultraviolet light irradiation method. MATERIALS AND METHODS: Two milliliters of fluorescent microspheres 0.1-20 microm in diameter diluted to 2.5% weight per volume was injected via the tail vein of 30 rats; systemic side-effects were examined. One milliliter of 1.0 microm-diameter microspheres dilution was injected on the backs of 30 rats; local side-effects were examined. A microsphere dilution (0.2 ml, 1.0 microm-diameter microspheres) was injected into the footpad of 18 rats; the lymphatic pathway and drainage were examined. Five milliliters of 1.0 microm-diameter fluorescent microspheres was injected endoscopically into the submucosa of the esophagus, stomach and small and large bowels of 6 domestic pigs, and 5 ml was injected into the subadventitia of the esophagus or subserosa of the stomach, and small and large bowels. Fluorescence-positive lymph ducts or nodes were carefully observed under ultraviolet light irradiation. RESULTS: No systemic side-effects were observed in rats. Only mild edema and a mild inflammatory reaction were observed on the backs of rats. Fluorescent microspheres 0.1, 0.5 and 1.0 microm in diameter were detected in lymph ducts or nodes of pigs within 1 hour after injection. CONCLUSION: Sentinel node navigation surgery with the use of fluorescent microspheres might be feasible and advantageous for patients with esophageal or lung cancer, especially in the mediastinum.

Animals↗

PubMedDate not supplied

DNA methylation of CHFR is not a predictor of the response to docetaxel and paclitaxel in advanced and recurrent gastric cancer.

BACKGROUND: Cell cycle checkpoint dysfunction is often associated with sensitivity to chemotherapeutic agents. In this study, the question of whether DNA methylation of CHFR, a mitotic checkpoint gene, can predict the response of advanced and recurrent gastric cancers (GCs) to docetaxel or paclitaxel was examined. MATERIALS AND METHODS: In a retrospective study, 41 patients with GC treated with paclitaxel alone (n=12) or a combination of docetaxel and S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine, potassium oxonate) (n=29) were studied. The DNA methylation status of the CHFR gene was examined by combined bisulfite restriction analysis of DNAs from 41 GC tissues and the methylation status was compared to their sensitivity to chemotherapy. The levels of CHFR mRNA were measured by quantitative reverse transcription-PCR. RESULTS: DNA methylation of CHFR was found in 15 (36.6%) out of the 41 GC samples and the levels of CHFR mRNA were associated with the methylation status of CHFR (p = 0.034). In 41 samples of corresponding non-neoplastic mucosae, no DNA methylation of CHFR was detected. Among 12 patients treated with paclitaxel alone, only 1 (20.0%) of the 5 patients with CHFR methylation had a partial response (PR) to paclitaxel, whereas 3 (42.9%) of the 7 patients without CHFR methylation had a PR to paclitaxel (p = 0.836). In 29 patients treated with a combination of S-1 and docetaxel, there was no clear association between the CHFR methylation status and response to chemotherapy (p = 0.092). CONCLUSION: We conclude that the DNA methylation of CHFR alone cannot predict the response of advanced and recurrent GC to docetaxel or paclitaxel. Both paclitaxel and docetaxel may be effective for treatment of GC even if CHFR is expressed.

Adult↗