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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 487 records · Page 27Linked to original sources
PubMed1994

[A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer].

A late phase II study of CPT-11 for advanced breast cancer was conducted at 27 institutions. Seventy-nine patients were enrolled, 75 were eligible for the study, and 65 were evaluable for efficacy. One complete response and 14 partial responses were obtained, and the response rate was 23%. The response rate of patients with prior endocrine therapy and prior chemotherapy including adriamycin or other anthracycline drugs was 27% (11/41) and 26% (12/46), respectively. The response rate for patients with estrogen receptor-negative tumors and premenopausal patients was 32% (6/19) and 27% (4/15), respectively. Responses were observed not only for soft tissue lesions such as lymph nodes (5/17), but also for distant metastases in the lungs (8/28) and bone (1/18). The major adverse reactions were myelosuppression and gastrointestinal symptoms. The incidence of Grade 2 or higher leukopenia, anemia, nausea/vomiting, anorexia, diarrhea and alopecia was 68%, 31%, 67%, 59%, 37%, and 30%, respectively. These results suggested that CPT-11 was a promising drug for advanced breast cancer.

Adult↗
PubMed1994

[Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group].

A multi-institutional collaborative late phase II study of irinotecan hydrochloride (CPT-11) was performed on patients with advanced gastric cancer. CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion or as 150 mg/m2 fortnightly. Of 81 registered patients, 77 cases were eligible and 60 cases were evaluable for response. The overall response rate for evaluable cases was 23.3% (14/60), and the response rate was 16.1% (9/45) for the patients who had received prior chemotherapy. The primary tumor showed a 4.5% response, while metastatic lesions in the lymph-nodes, lungs, and liver showed response rates of 36.4%, 33.3%, and 17.4%, respectively. The major toxicities (> or = Grade 3) were leukopenia (41.2%), anemia (28.9%), diarrhea (22.4%) and anorexia (19.7%). These toxicities were generally reversible. CPT-11 showed activity against advanced gastric cancer, suggesting that further clinical studies of CPT-11 combined with other active chemotherapy agents are warranted.

Adenocarcinoma↗
PubMed1994

[A late phase II study of CPT-11, irinotecan hydrochloride, in patients with advanced pancreatic cancer. CPT-11 Study Group on Gastrointestinal Cancer].

A late phase II study of CPT-11 was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with advanced pancreatic cancer as a cooperative study of 19 institutions. From February 1990 to June 1992, 61 patients with advanced pancreatic cancer were enrolled in this study. Fifty-seven patients were evaluable for toxicity and 35 for response. CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion (regimen A) or as a 150 mg/m2 every two weeks (regimen B). The response rate was 11.4% (4/35). The primary tumor showed a 10.3% (3/29) response and the liver metastases showed a 10.5% (2/19) response. The major toxicities were myelosuppression and gastrointestinal symptoms. The incidences (> or = Grade 2) of leukopenia, anemia, anorexia, nausea/vomiting, alopecia and diarrhea were 61.4% (35/57), 56.1% (32/57), 70.2% (40/57), 56.1% (32/57), 40.4% (23/57) and 36.8% (21/57), respectively. The incidence of diarrhea was higher with regimen A than with regimen B, but the antitumor activity was no different between the two regimens. These results suggested that CPT-11 has some antitumor activity against advanced pancreatic cancer.

Adult↗
PubMed1994

[Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies].

A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT-11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma.

Adolescent↗
PubMed1994

[An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with advanced breast cancer].

An early phase II study of irinotecan (CPT-11) in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group of 15 institutes in Japan. CPT-11 was administered by intravenous drip-infusion. The administration schedules were 100 mg/m2 weekly (regimen A), 150 mg/m2 biweekly (regimen B), and 200 mg/m2 every 3-4 weeks (regimen C). There were 4 partial responses (PRs), 12 cases with no changes (1 minor response) and 9 cases of progressive diseases with a response rate of 16% (4/25). One out of 7 patients on regimen A and 3 patients out of 15 patients on regimen C achieved PR with a response rate of 14% and 20%, respectively. In three out of 4 PRs, prior chemotherapy, endocrinotherapy or radiotherapy had failed. Major adverse reactions were leukopenia 28/33 (85%), neutropenia 19/25 (76%), anemia 15/33 (46%), nausea/vomiting 28/33 (85%), anorexia 25/33 (76%), diarrhea 22/33 (67%) and alopecia 20/33 (61%). The incidence of leukopenia and thrombocytopenia seemed to be higher in regimen C than regimen A, and diarrhea was also more severe in regimen C than regimen A. The recovery of leukopenia was delayed in some patients on regimen C. The results suggested that CPT-11 was effective against advanced or recurrent breast cancer. The recommended administration schedule for a late phase II study was thought to be 100 mg/m2 weekly, considering efficacy and safety.

Adult↗
PubMed1994

[Phase I clinical study on new vinca alkaloid derivative, KW-2307 (vinorelbine). KW-2307 Study Group].

Phase I study on a new vinca alkaloid derivative, KW-2307(vinorelbine), was conducted by multiple institutions in 40 patients with a variety of malignant tumors. KW-2307 was given intravenously by single administration or by weekly repeated for 4 weeks (hereinafter as the repeated administration). The initial dose, 10 mg/m2(ln), was escalated to 35 mg/m2(3.5n) in single administration and to 30 mg/m2(3n) in the repeated administration. A total of 35 cases were eligible for evaluation, consisting of 18 cases in single administration group and 17 in the repeated group. Both of single and repeated administration caused leukopenia dose-dependently, and the dose limiting toxicity (DLT) was judged as leukopenia. The maximum tolerated dose (MTD) was 30 mg/m2 in single administration and 25 mg/m2 in the repeated administration provided that administration is made weekly for 4 consecutive weeks. As subjective and objective adverse effects, general fatigue, anorexia, constipation, phlebitis etc. were observed, but all of these symptoms were relatively mild and recoverable. Peripheral neuropathy were found in two cases and judged as Grade 1. In this phase I study, a tendency of the decrease in tumor size was seen in 3 cases; 2 of non-small cell lung cancer and 1 of breast cancer. The pharmacokinetics of KW-2307 in blood after single administration showed a triphasic disappearance pattern with half-life of about 20 to 60 hrs. The data of pharmacokinetics after repeated administration revealed no accumulation of this agent. The recommended dose for early phase II study was supposed to be 20 to 25 mg/m2/week.

Adult↗
PubMed1994

[Cytokines].

The development of our understanding of the cytokines which began with a collection of barely believable activities in supernatants and extracts from various cell types and has now yielded a well-defined series of molecules with key roles in the control of immunity, infection, differentiation, embryogenesis, and growth is a remarkable and continuing story. Our current, incomplete, understanding of the cytokine network is based on the following observations; 1) Most cytokines are produced by more than one cell type. 2) Different cytokines interact with distinct receptors but can produce markedly overlapping biological effects. Some structurally different cytokines (e.g., IL-1 alpha and IL-1 beta) interact with a single receptor and therefore have identical effects. 3) Most cytokines have multiple biological actions. These actions are dependent on cell type and functional state and are modified by the other mediators to which a cell is simultaneously exposed. 4) A single agent (e.g., lipopolysaccharide or viruses) can induce several different cytokines within the same cell, suggesting the cytokine interaction is important. 5) Cytokines interact within the cytokine network by; (1) stimulating the production of other cytokines; (2) transmodulation of receptors for other cytokines; (3) enhancing or inhibiting the biological activity of other cytokines.

Cytokines↗
PubMed1993

Influence of physiological concentration of progesterone on CD(4+)- and CD(8+)-activated lymphocytes with interleukin 2 and autologous plasma: difference between healthy donors and patients bearing malignant tumors.

The influence of progesterone at the physiological concentration on normal donor and malignant patient peripheral blood lymphocytes incubated with interleukin 2 (IL-2) was investigated. Analysis of the phenotypes of IL-2-activated lymphocytes revealed that there was a difference in the positive rates of CD4+ and CD8+ cells between normal donors and patients with malignancies. Activated lymphocytes of normal adults older than 35 years of age consisted of 60-100% of CD4+ cells and 0-30% of CD8+ cells. Donors younger than 35 years of age showed a positive rate of CD4+ cells, ranging from 0-100%, while CD8+ cells were between 0-60%. However, in patients with malignancies both CD4+ and CD(8+)-activated lymphocytes diffused from 0-100%. Activated lymphocytes of most patients were CD8+ cell dominant, which reversed the CD4+/CD8+ ratio. Almost all patients at clinical stage IV showed a deviation of the positive rates of CD4+ and CD8+ cells from the normal range. It is an open question whether the prognosis of the patients with normal positive rates of CD(4+)- and CD(8+)-activated lymphocytes is favorable or not.

Adult↗
PubMed1993

Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma.

Detailed cytogenetic analyses were carried out on primary tumor specimens and cell lines from 23 patients with pleural malignant mesothelioma (MM). Clonal abnormalities were identified in 20 of 23 MM. In 3 cases, karyotypic data were compiled from harvests of both short-term cultures (1-3 days), and primary cultures grown on murine feeder layers for several weeks. The karyotypes obtained with these 2 different culture methods were very similar, although polyploid versions of abnormal clones were found only in the long-term cultures. In addition, while short-term cultures from 9 tumor biopsies usually exhibited near-diploid clones, cell lines derived from 11 tumors tended to have higher ploidies. Each of the cytogenetically abnormal MM displayed multiple clonal alterations. The 2 most frequent changes were chromosomal losses of specific regions in 1p (17 cases) and 9p (16 cases). The shortest regions of overlap of these losses were at 1p21-p22 and 9p21-p22, respectively. Other common abnormalities included losses of 3p21 (13 cases) and 6q15-q21 (9 cases), and numerical losses of chromosomes 14, 16, 18, and 22 (each observed in 10-13 tumors). In many of the MM examined, most or all of these recurrent changes occurred in combination, suggesting the involvement of a pathogenetic cascade in this cancer. The pattern of recurrent chromosomal losses suggests that these regions represent the locations of tumor suppressor genes whose loss/inactivation may have a pivotal role in MM tumorigenesis.

Adult↗
PubMed1993

Synapse formation in dissociated cell cultures of embryonic chick cerebral neurons.

The development of synapses was confirmed in the primary cultures of dissociated cerebral cortex neurons from chick embryos. Whole-cell patch clamp recording applied to dissociated neurons from 6- to 12-day-old embryos revealed that these neurons form functional synapses. In these cultures, both excitatory and inhibitory postsynaptic responses were observed. Synaptogenesis in our cultures seemed to be in proportion to the embryonic equivalent days, which are the sum of the days in incubation and culture.

Animals↗
PubMed1993

Characterization of a Cl(-)-channel from rabbit transverse tubules in the planar lipid bilayer system.

A Cl(-)-channel of the transverse tubule(TT) was incorporated into artificial planar lipid bilayers and its properties were investigated. The channel was found to have the following properties. (1) The single-channel conductance is 40 pS in choline-Cl solution. (2) The rate of gating of the channel does not depend on the membrane voltage. (3) The channel is blocked by stilbene derivatives (DIDS and SITS), which are known as inhibitors of voltage-dependent Cl(-)-channels of the Torpedo electric organ, from both sides of the membrane. (4) An inhibitor of voltage-dependent Cl(-)-channels of skeletal muscle, 9-anthracene carboxylic acid(9-AC), inhibits Cl(-)-current from the cis-side to which the TT vesicles were added.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

Structural studies of a novel type of tetraantennary sialoglycan unit in a carbohydrate-rich glycopeptide isolated from the fertilized eggs of Indian Medaka fish, Oryzias melastigma.

A novel carbohydrate-rich sialoglycopolyprotein of apparent molecular mass approximately 7000 Da was isolated from the fertilized eggs of the Medaka fish species, Oryzias melastigma. The glycoprotein was identified as a member of the L-hyosophorin family because it exhibited the following several distinctive features of L-hyosophorin molecules: (a) it contains a high proportion of carbohydrate (90% by weight), and (b) the amino acid sequence of the apopeptide was identical with that of the Oryzias latipes L-hyosophorin which has previously been demonstrated to be derived from a high molecular weight form of hyosophorin, i.e. H-hyosophorin, present in the cortical vesicles of unfertilized eggs. The apoprotein of H-hyosophorin is composed of tandem repeats of the L-hyosophorin apopeptide, i.e. it is a polyprotein. The structure of the carbohydrate portion of purified L-hyosophorin of O. melastigma was studied by composition and methylation analysis, selective chemical (periodate-Smith degradation; hydrazinolysis-nitrous acid deamination), and enzymatic (endo-beta-galactosidase; peptide:N-glycanase) degradation, together with instrumental methods (fast atom bombardment-mass spectrometry and 1H NMR). O. melastigma L-hyosophorin was found to contain two types of large, branched tetraantennary glycan units capped with sialic acids. The two glycans differ with respect to the branching pattern of the trimannosyl core (x = 4 or 6 in Eq. A). [formula: see text] The possible physiological significance of the hyosophorin family is discussed in the light of their unique structural features.

Animals↗
PubMed1993

Universal mapping probes and the origin of human chromosome 3.

Universal mapping probes (UMPs) are defined as short segments of human DNA that are useful for physical and genetic mapping in a wide variety of mammals. The most useful UMPs contain a conserved DNA sequence immediately adjoined to a highly polymorphic CA repeat. The conserved region determines physical gene location, whereas the CA repeat facilitates genetic mapping. Both the CA repeat and its neighboring sequence are highly conserved in evolution. This permits molecular, cytogenetic, and genetic mapping of UMPs throughout mammalia. UMPs are significant because they make genetic information cumulative among well-studied species and because they transfer such information from "map rich" organisms to those that are "map poor." As a demonstration of the utility of UMPs, comparative maps between human chromosome 3 (HSA3) and the rat genome have been constructed. HSA3 is defined by at least 12 syntenic clusters located on seven different rat chromosomes. These data, together with previous comparative mapping information between human, mouse, and bovine genomes, allow us to propose a distinct evolutionary pathway that connects HSA3 with the chromosomes of rodents, artiodactyls, and primates. The model predicts a parsimonious phylogenetic tree, is readily testable, and will be of considerable use for determining the pathways of mammalian evolution.

Animals↗