Biomedical subjects

Tetsuya Hamaguchi

Publications and source records attributed to Tetsuya Hamaguchi.

23 records · Page 2Linked to original sources

PubMed2002

Pharmaceutical and biomedical differences between micellar doxorubicin (NK911) and liposomal doxorubicin (Doxil).

The stability and biological behavior of an in vitro system of doxorubicin (DXR) entrapped in NK911, polymer micelles, was examined and compared with those of DXR entrapped in Doxil, polyethylene-glycol-conjugated liposomes. The fluorescence of DXR inside micelles or liposomes in an aqueous solution is known to be strongly quenched by the outer shells of the micellar or liposomal formation. Thus, by measuring the fluorescence intensity of DXR released from NK911 or Doxil, we could determine the stability of the micellar or liposomal DXR formation. Furthermore, NK911 was found to be less stable than Doxil in saline solution. In drug distribution experiments using an in vitro solid tumor model, when spheroids formed from two human colonic cancer lines, HT-29 and WiDr, and a human stomach cancer line, MKN28, were exposed to NK911, DXR was distributed throughout the spheroids, including their center. On the other hand, when the spheroids were exposed to Doxil, DXR was distributed only to the surface of the spheroids. It has been suggested that Doxil can deliver DXR to a solid tumor more efficiently than NK911 via the EPR (enhanced permeability and retention) effect, because Doxil may be more stable in plasma than NK911. On the other hand, DXR packed in NK911 may be distributed by diffusion to cancer cells distant from the tumor vessel, because NK911 can leak out of the tumor vessel and may be able to release free DXR more easily than Doxil. It has been suggested that drug carrier systems such as liposomes and micelles should be selected appropriately bearing in mind the characteristics of the tumor vasculature and the tumor interstitium.

Doxorubicin↗

PubMed2002

Three novel single nucleotide polymorphisms in UGT1A10.

Three novel single nucleotide polymorphisms (SNPs) were found in the UDP-glucuronosyltransferase (UGT) 1A10 gene from 24 Japanese patients with various cancers who were administered the anti-tumor drug, irinotecan (CPT-11). The detected SNPs were as follows: 1) SNP, MPJ6_U1A003; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CAGATGCCATGAC/TTTTCAAGGAGAG-3'. 2) SNP, MPJ6_U1A004; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CCTAGAAATAGCC/TTCTGAAATTCTC-3'. 3) SNP, MPJ6_U1A030; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-GGTTGTAGTCATG/ACCAGAGGTGAGT-3' All the three SNPs were located in exon 1 and their frequencies were all 0.021. Among these SNPs, MPJ6_U1A003 and U1A030 resulted in amino acid alterations, T202I and M59I, respectively. The third SNP, MPJ6_U1A004, introduced a synonymous amino acid change (A231A).

Journal Article↗

PubMedDate not supplied

Rapid emergence of mammary preneoplastic and malignant lesions in human c-Ha-ras proto-oncogene transgenic rats: possible application for screening of chemopreventive agents.

For comparison of mammary gland whole mounts with examination of 2 histologic sections of mammary gland, 56 Hras128 rats were intravenously injected with 50 mg/kg body weight of N-methyl-N-nitrosourea at 50 days of age and then sacrificed at days 5, 10, 15, 20, 25, and 56. Comparison of detection sensitivity between the whole mounts and histologic sections revealed no lesions apparent in whole mounts on day 10, although intraductal proliferation was clearly detected in histologic sections in 44% of treated rats. Proliferative lesions were first detected in whole mounts at a 44% incidence on day 15, while intraductal proliferations and atypical hyperplasias were apparent in the sections at 89% and 44% incidences, respectively. On day 20, atypical hyperplasias and small adenocarcinomas in histologic sections were found in almost all animals. In conclusion, examination of 2 histologic sections from mammary tissues was found to be practical for detection of small malignant lesions as early as 15 days after MNU injection, and suppressive effects of soy isoflavones were clearly evident within 20 days after carcinogen exposure. These results suggest that this model has practical utility for short-term screening of chemopreventive agents for mammary carcinogenesis.

Adenocarcinoma↗

PubMedDate not supplied

Long-term survivor of gastric small cell carcinoma.

We describe the long-term survival of a patient following the diagnosis of primary gastric small cell carcinoma. In January 2000, a 73-year-old male was found to have advanced gastric small cell carcinoma directly invading his liver. He received combination chemotherapy with cisplatin and irinotecan as first-line chemotherapy, then cisplatin and etoposide as second-line chemotherapy. He had a complete response after four cycles of second-line chemotherapy. In March 2001, the tumor recurred in the stomach and the patient underwent a total gastrectomy. He has survived free of disease for more than 2 years after the first diagnosis.

Aged↗

PubMedDate not supplied

Small cell carcinoma of the esophagus. Analysis of 14 cases and literature review.

BACKGROUND/AIMS: The aims of this study are to retrospectively analyze data on the epidemiology, clinical characteristics, and treatment outcomes of 14 cases of small cell carcinoma of the esophagus. METHODOLOGY: Patient records were reviewed for data on demographics, presenting symptoms, diagnosis, disease stage, type of treatment and outcome. RESULTS: Between January 1990 and December 2001, 14 patients with small cell carcinoma of the esophagus were treated at the National Cancer Center Hospital, representing 0.8% of all esophageal carcinomas diagnosed during this period. Eleven patients presented with extensive disease at the time of diagnosis, while three patients were noted to have limited disease. Nine patients received combination chemotherapy with or without radiotherapy. Three of these patients achieved a complete response to first-line treatment and two of them have survived more than two years. Five patients underwent esophagectomy as an initial treatment with curative intent. All of these patients developed early relapse after esophagectomy, and only one patient has survived more than two years. The overall median survival was 7.7 months (range: 0.6-89.1 months) for all 14 patients. CONCLUSIONS: Although curative esophagectomy may be effective as a primary treatment in some patients, systemic chemotherapy with or without concurrent radiotherapy should be considered as an important treatment option for small cell carcinoma of the esophagus.

Adult↗