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Biomedical subjects

M Inokuchi

Publications and source records attributed to M Inokuchi.

12 recordsLinked to original sources

Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer.

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m-2 day-1, stepping up to 100 mg m-2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m-2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m-2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m-2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1-13). The incidences of severe (grade 3-4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2-76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.

Administration, Oral↗

Quantitative evaluation of metastases in axillary lymph nodes of breast cancer.

We have established a highly sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metastases in 358 axillary lymph nodes obtained from 23 breast cancers of 22 patients were investigated by conventional haematoxylin and eosin (H&E) staining, immunohistochemical staining and quantitative RT-PCR assay. The detection rates of axillary lymph node metastasis using H&E staining, immunohistochemistry and RT-PCR assay were 4.5, 5.9 and 13.1%, respectively. RT-PCR assay was the most sensitive of these three methods for detecting lymph node metastases. Cytokeratin 19 mRNA expression values of both histologically and immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001), and those of histologically negative, but immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001). Furthermore, metastatic rates of sentinel nodes were higher than the rates of nonsentinel lymph nodes as measured by all three methods. These results indicate that quantitative RT-PCR assay is a sensitive and reliable method for detecting lymph node metastasis. Furthermore, quantification of metastases in sentinel lymph nodes by quantitative RT-PCR assay may be useful to assess the entire axillary burden of breast cancer patients.

Adult↗

Expression of cathepsin B and cystatin C in human breast cancer.

Cathepsin B, which was originally found to be a lysosomal cysteine protease, is also an important matrix protease. In this study, we investigated the expression of cathepsin B and cystatin C, the strongest inhibitor of cathepsin B, and measured the relative amounts of each in human breast cancer tissues. Cystatin C expression relative to cathepsin B expression was found to be decreased. This finding could be associated with the looseness of cancerous interstitial tissue, which might play a role in cancer invasion and metastasis. This report documents the first simultaneous investigation of cathepsin B and cystatin C in breast cancer tissues.

Breast Neoplasms↗

Sotos syndrome with enamel hypoplasia: a case report.

A rare case of Sotos syndrome with enamel hypoplasia is described. Dental abnormalities include enamel hypoplasia, expansion of the pulp cavity, high arched palate, and absence of the bilateral pre-molar teeth of the mandible.

Abnormalities, Multiple↗

Expression of hsp90 and cyclin D1 in human breast cancer.

The integral roles of heat shock proteins (hsps) in the cell cycle and in multistep processes leading to tumorigenesis have been implied. We examined the expression of hsp90alpha, hsp90beta and cyclin D1 in human breast cancer. Levels of mRNAs coding for hsp90alpha and cyclin D1 were significantly higher in cancer tissues than in non-cancer tissues. Moreover, there was a close relationship between the extent of the two mRNA levels, suggesting that increased expression of hsp90alpha, an isoform of the hsp90 family, is associated with the proliferation of human breast cancer. Hsp90beta was expressed in cancer cells, but not associated with cell proliferation.

Breast Neoplasms↗

Genotype configuration in a case of primary gastric lymphoma with T-cell phenotype.

T-cell malignant lymphoma of the gastrointestinal tract is rare. The genotype of gastric T-cell lymphoma remains unclear. The aim of this study was to elucidate the pathogenesis of a case of primary gastric T-cell lymphoma by using cytogenetics and molecular biology. Gastric biopsy specimens and lymphoma cells in the ascites were examined by immunocytology, cytogenetic analysis, and Southern blot analysis. The histological diagnosis of the gastric lymphoma was diffuse large cell type. T-cell markers were positive in immunocytochemistry of the gastric lymphoma cells and in FACS analysis of lymphoma cells in the ascites. All lymphoma cells in the ascites had complex abnormal karyotypes containing t(8;14)(q24;q32). Southern blot analysis revealed rearrangement of the IgH and C-MYC genes of the lymphoma cells in both the stomach and the ascites, but no comigration of the C-MYC with the JH locus could be detected. The TCR-beta and -gamma genes were in their germ-line configurations. In this patient, although the phenotype was T-cell lymphoma, the karyotype t(8;14)(q24;q32) and genotype had the characteristics of B-cell lymphoma. The unique B-cell genotype configuration and the C-MYC activation suggested that the cellular origin of this rare case of malignant lymphoma with a T-cell phenotype was quite immature lymphocytes.

Adult↗

[Anesthesia for funnel chest operation].

The incidence of perioperative complication and days of hospital stay were studied in 56 patients with funnel chest operation under inhalational anesthesia (18 cases), intravenous anesthesia (23 cases) and epidural anesthesia (15 cases). Perioperative complication occurred most frequently in the inhalational group and was followed by intravenous and epidural group. Postoperative hospitalization on an average was 21.4 days in the inhalational group, 21.9 days in the intravenous group and 16.7 days in the epidural group. It is said that postoperative pain leads to splinting of the chest, which can cause atelectasis and/or pneumonia. Severe postoperative pulmonary complication was reduced in the epidural groups. As a result, hospitalization in the epidural group was shorter than in other groups. This study suggests that epidural anesthesia is more advantageous for funnel chest operation because epidural anesthesia has protective action against arrhythmia and postoperative pulmonary complication.

Adolescent↗

[Interstitial vascular reaction of naturally occurring mammary adenocarcinoma in old C3H/HeJ female mice].

Angiogram by soft-X-ray and giant histo-sections were used to investigate the interstitial vascular architectures and correlation between vascular reaction and histologic types of naturally occurring mammary adenocarcinoma in old C3H/HeJ female mice. The tumors were diagnosed as adenocarcinoma B type (Dunn's classification) composed of three different histologic types: solid, comedo, and papillomatous. From the findings of the angiograms, the interstitial vascular architectures of the tumor were classified into three patterns: sinusoidal, hypovascular, and hypervascular. The vascular patterns was characteristic in each histologic type and showed a close correlation with the intensity of tumor proliferation. The fine intratumoral angiographic investigation also made clear that necrosis of tumor cells and tissues seen in the histologic types showing marked proliferation was caused by hypoxia. Application of these methods to investigation of the fine vascular architecture in tumors may useful in research for adenocarcinoma.

Adenocarcinoma↗

Identification of the interplexiform cell in the dace retina by dye-injection method.

The responses of interplexiform cells in the dace retina were recorded intracellularly and identified morphologically. The response pattern closely resembles the response of bipolar cells and amacrine cells (on- and off-types). Morphologically, the perikaryon of most of these cells lies in the amacrine cell layer, and is usually large in size. Distal and proximal processes arise from the soma directly. The distal process ramifies and extends widely in the outer plexiform layer, but does not make contact with receptor terminals. The proximal process branches and extends widely in the inner plexiform layer. The majority of these cells resembles the dopaminergic interplexiform cells, but a few resemble the glycinergic interplexiform cells in the goldfish retina.

Animals↗