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Biomedical subjects

T Yagyu

Publications and source records attributed to T Yagyu.

47 records · Page 3Linked to original sources

[Intra-arterial infusion chemotherapy for recurrent breast cancer via an implantable system].

Intra-arterial infusion chemotherapy via implantable port catheter has been applied in 14 patients suffering from recurrent breast cancer. The regimen consisted of at least 2 cycles of epirubicin (1 cycle: 150 mg) and subsequent maintenance infusion (30 mg/2 weeks). The results were as follows: 1) The response rate (CR+PR) was 50%: 42.9% CR, 7.1% PR, 14.3% MR, and the median duration of response was 6 months. 2) Intractable pain, severe lymphedema and infection were reduced in 42.9% (6/14). 3) Leucopenia was the dose-limiting factor, and it appeared with an incidence of 78.8%. Catheter or portal trouble was observed in 28.6% of the patients. Despite the existence of several unanswered questions, intra-arterial infusion chemotherapy via implantable system is promising with regard to therapeutic effect and quality of life.

Adult↗

Use of fibrinogen to enhance the antitumor effect of OK-432. A new approach to immunotherapy for colorectal carcinoma.

OK-432 (5 KE), an immunomodulatory agent prepared from an attenuated strain of Streptococcus pyogenes, was dissolved in 1 ml of aprotinin (1000 KIE) and mixed with 80 mg of fibrinogen containing Factor XIII. A single intratumoral injection of the mixture was performed preoperatively under endoscopy in 20 patients with colorectal carcinoma. Postoperative histopathologic examinations revealed the formation of fibrin fibers at the site of injection and marked infiltration of inflammatory cells into the tumor stroma on the day after injection; the formation of granulomas containing many giant cells after 4 to 7 days; and extensive regression of tumor tissue after 14 days. This study suggests that the high concentration of exogenous fibrinogen gelatinized enough to trap OK-432 in tumor stroma and that OK-432 induced granulomatous hypersensitivity to degenerate tumor stroma, thereby causing regression of the tumors.

Adenocarcinoma↗

Establishment of cytotoxic CD4+ T cell clones from cancer patients treated by local immunotherapy.

We have previously reported that the antitumor effect of OK-432, a Streptococcal preparation, is markedly augmented when injected intratumorally together with fibrinogen (Cancer, 69: 636-642, 1992). In order to elucidate the mechanism of the antitumor effects, we established T cell clones from regional lymph nodes of colorectal cancer patients who received this local immunotherapy. By culture of lymph node lymphocytes, in the presence of IL-2 and OK-432, 4 clones of T cells were established from 4 patients treated by local immunotherapy. These clones had a helper T cell phenotype (CD3+, CD4+, CD8-, CD56-, WT31+) and were successfully maintained for several months. The cells strongly expressed CD25 when stimulated with OK-432 and exhibited a high level of cytotoxic activity in part explained by the increased expression of ICAM-1 and LFA-1, and the release of TNF beta. These results suggest that the CD4+ T cells play a role in the antitumor mechanism of local immunotherapy.

CD4-Positive T-Lymphocytes↗

A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient reactive to a sulfated glycolipid.

A human monoclonal antibody, BMMK-33G, was established by a fusion of human B-lymphoblastoid cells, HO-323, with lymphocytes of axillary lymph nodes obtained from a breast cancer patient. High-performance thin-layer chromatography (HPTLC)-immunostaining and enzyme-linked immunosorbent assay (ELISA) revealed that BMMK-33G was interestingly directed to enough sulfatide (Galactosylceramid-I2-sulfate), which is one of the sulfate ester containing glycolipids. By immunohistochemical staining, BMMK-33G intensely reacted to breast cancer, pancreatic cancer and gastric cancer. It also reacted to many normal human tissues including mammary glands, but these stainings were weaker than those for cancer. This report describes BMMK-33G, a human monoclonal antibody against sulfatide which may be very useful for studying not only tumor immunology but also autoimmune diseases.

Antibodies, Monoclonal↗

Use of a local immunotherapy as an adjunctive tool for the generation of human monoclonal antibodies from regional lymph nodes of colonic cancer patients.

Human hybridomas were generated through the fusion of the human B-lymphoblastoid cell line HO-323 with the regional lymph node lymphocytes of colonic cancer patients who had received a local immunotherapy. A total of 353 hybridomas were obtained from 4 patients and 116 of these were found to secrete greater than or equal to 100 ng/ml human immunoglobulin. The efficiency was remarkably high as compared with that from patients without the local immunotherapy. Further immunohistological examination showed that 5 hybridomas secreted IgM which selectively reacted with colonic cancers. The results indicate that local immunotherapy could be an adjunctive tool for the generation of highly potent human hybridomas through augmenting the host's immunity.

Antibodies, Monoclonal↗

[Intratumoral injection of OK-432 in conjunction with fibrinogen greatly enhances antitumor effect on colorectal carcinomas].

We found that antitumor effect of OK-432, a lyophylized preparation of an attenuated strain of streptococcus pyogenes, on colorectal carcinoma was greatly augmented when it was injected intratumorally in conjunction with fibrinogen. Twenty cases of colorectal cancer received intratumoral injection of 5 KE of OK-432 mixed with 80mg of fibrinogen including factor-XIII and 1ml of aprotinin at the time of endoscopic examination. Changes in the shape of the tumors were observed endoscopically within a few days after injection, and in most cases, decrease in the height of tumor margin was noted. Histopathological findings on surgically resected specimens revealed that the fine meshwork of fibrin was formed at the injected site soon after the injection, and a marked infiltration of inflammatory cells including neutrophils, plasma cells, macrophages, eosinophils and lymphocytes. Such granulomatous changes developed over 7 days after injection, and the degradation of tumors were observed. By 14 days after the injection, tumor tissues were largely replaced with granulomas, and shrinkage of tissues were observed. These findings indicated that fibrinogen including factor-XIII and aprotinin has a potential ability to augment the immunoreaction induced by biological response modifiers, and intratumoral injection of OK-432 in conjunction with fibrinogen solution was superior to intratumoral injection of OK-432 alone as the local immunotherapy of colorectal cancer.

Aprotinin↗

Activation of mammalian target of rapamycin in postmenopausal ovarian endometriosis.

The purpose of this study was to determine whether Akt and mammalian target of rapamycin (mTOR), downstream targets of phosphatidylinositol 3-kinase, are activated in endometriosis and ovarian cancer specimens. We measured total and phosphorylated levels of Akt and mTOR from 17 frozen ovarian cancers and 15 benign endometriosis specimens (nine from premenopausal women and six from postmenopausal women) by quantitation of signals from western blots using antibodies against these proteins. Elevated phospho-Akt was detected in ovarian cancer versus endometriosis specimens from premenopausal women and endometriosis specimens from postmenopausal women (2.3 +/- 0.45 versus 0.10 +/- 0.06 and 0.17 +/- 0.11; P < 0.05) when the western blot signal of activated kinase was normalized to total kinase levels. Elevated phospho-mTOR was detected in ovarian cancer and postmenopausal endometriosis versus premenopausal endometriosis (0.52 +/- 0.19 and 0.46 +/- 0.29 versus 0.13 +/- 0.08; P < 0.05). Expression of total kinases (normalized to beta-actin) was higher in carcinoma versus endometriosis specimens. Elevation of the active mTOR was specifically detected in postmenopausal endometriosis.

Adult↗

Global dimensional complexity of multichannel EEG in mild Alzheimer's disease and age-matched cohorts.

Multichannel EEG as sequence of momentary brain field maps constitutes a trajectory through K-dimensional state space (K = number of channels); the complexity of this trajectory is assessed by the nonlinear measure of global correlation dimension (Global Dimensional Complexity, GDC) with the number of electrodes as embedding dimension. We analyzed eyes-closed EEG of three age-matched subject groups: mild Alzheimer's disease (AD; n = 21), mild cognitive impairment (29) and subjective memory complaint (29). Kruskal-Wallis statistics showed an overall effect between groups. AD patients differed significantly (GDC = 4.56) from mild cognitive impairments (GDC = 4.98) and from subjective memory complaints (GDC = 4.93). GDC also had significant positive correlations with mental condition and performance (MMSE and WAIS-R scores). Thus, the dynamics of brain state development over time in mild AD differs from that in mild cognitive impairment and in subjective memory complaint cases.

Aged↗