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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 775 records · Page 43Linked to original sources
PubMed1987

Blood vascular architecture of the rat parathyroid glands: a scanning electron microscopic study of corrosion casts.

Blood vascular beds of the rat parathyroid glands were reproduced with a methacrylate casting medium and observed with a scanning electron microscope. The rat possesses only a single pair (one left and the other right) of parathyroid glands. Each gland was found to contain a rich capillary network which was completely isolated from the capillary plexus of the thyroid gland. Each parathyroid gland received some small afferent arteries from the superior thyroid artery and emitted a thick efferent vein continuous with the superior thyroid vein. The capillary network of the parathyroid gland consisted of freely anastomosing capillaries. The afferent arteries were divided in the superficial and deep layers of the gland. The thick efferent vein arose in the deep layer of the gland. Some small or accessory efferent veins arose in the superficial layers of the gland. These also drained into the superior thyroid vein.

Animals↗
PubMed1987

Palmar interosseous muscle of the human thumb.

The adductor pollicis muscle was studied in fifty hands of Japanese adult cadavers of both sexes. The radial portion of the oblique head of the adductor pollicis muscle has carpal and metacarpal origins and an insertion into the wing tendon of the extensor apparatus. This portion was located dorsal to the palmar metacarpophalangeal articular nerve and superficial palmar metacarpal artery. Thus, the radial portion of the oblique head of the adductor pollicis muscle (more strictly, the slips dorsal to the palmar-penetrating twig of the ulnar nerve) is similar to the palmar interosseous muscles, except that its slips cannot be clearly distinguished from each other.

Female↗
PubMed1987

[Evaluation by multiple regression analysis of factors influencing the chemosensitivity of human tumors xenografted into nude mice].

The chemosensitivity of human cancer lines is thought to be expressed as a result of contributions by various interacting factors. Multiple regression analyses were performed in order to clarify the weighting of factors responsible for the chemosensitivity of 15 human cancers xenografted into nude mice. Inhibition rates of 11 anticancer agents predetermined for each line of human cancer were used as the criterion variables. As the explanatory variables, 9 parameters characteristic of each cancer or cancer-bearing mouse were selected as follows; grade of differentiation, vascularity, percentage necrosis, volume doubling time, labeling index, LDH activity, tissue/serum LDH ratio, thymidine phosphorylase activity and serum CEA. By applying this analysis with stepwise deletion, the estimated multiple regression equations for drug sensitivity were clarified for each drug. Although all equations were composed of different factors and their partial repression coefficients varied from drug to drug, those among analogous drugs such as FT-207 and UFT, or MMC and M-83 had similar factors. The equations for M-83, ACNU and ADR consisted of a number of parameters with a sufficiently high coefficient of determination of over 80%. Even in cases of MXT that showed no significant factor upon simple correlation analysis, an equation with 7 factors revealed a coefficient of determination of 0.83. The estimated values of effectiveness for these drugs showed remarkable coincidence with each actual value. For some drugs, the in vivo mode of action was inferred through this analysis.

Animals↗
PubMed1987

[Combination chemotherapy with 3 or 4 drugs on human breast and gastrointestinal cancer xenografts in nude mice (II)].

Because of the limited effects of single-agent chemotherapy for solid tumors, combination therapy was employed in an attempt to enhance the clinical effects. Following our former report in which the combination effects of mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) were clarified, combined applications of 4 drugs, vindesine (VDS), methotrexate (MTX), cisplatin (CDDP) and 5'-DFUR against 3 lines of human breast cancer (H-62, H-31, H-71), and one line each of gastric cancer (H-55) and colon cancer (H-110) xenografted into nude mice were evaluated in comparison with CAF (cyclophosphamide, adriamycin and 5-FU) therapy which is commonly used for breast cancer. Treatment was initiated in groups of 7 mice each when the mean tumor volume of subcutaneous tumors had reached about 100mm3, and the therapeutic effect was evaluated in terms of the inhibition rate (I.R.). A synergistic effect is said to exist when the combination therapy is superior to each single drug therapy at the maximal tolerated dose. Combination therapy with 3 drugs (VDS, CDDP and 5'-DFUR) or 4 drugs (VDS, CDDP, MTX and 5'-DFUR) achieved an I.R. of over 98%, i.e., a marked effect with tumor shrinkage, in 3 lines of tumors (H-55, H-31 and H-62). Moreover, remarkable effects were shown even in the other 2 lines which were insensitive to every single-agent therapy, the I.R. values being 85.7% (H-71) and 78.5% (H-110). A synergistic effect was obtained in 3 of the 5 lines examined. These combination therapies were histologically superior to therapies employing each single-drug therapy or CAF therapy. The side effects for combination of these 3 or 4 drugs evaluated by body weight loss were transient and equivalent to maximal dose of VDS or CDDP. Clinically, it is thought that these combined therapies of 3 or 4 drugs will bring about a considerable response in practice.

Animals↗
PubMed1987

[Effects of alternating chemotherapy with 2 non-cross-resistant drug combinations on human alimentary and breast cancer xenografts in nude mice].

Despite the recent advances made in the development of anticancer drugs, any single chemotherapy treatment has only limited effects on cancers of the stomach, colon and breast, so that the combined use of multiple drugs is necessary for the treatment of solid tumors. In our previous studies with human gastrointestinal and breast cancers xenografted into nude mice, combination therapy with mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) [I] or cisplatin (CDDP), vindesine (VDS) and 5'-DFUR [II] produced higher response rates than single-agent therapy with any one of these drugs. In the present study, the effectiveness of alternating chemotherapy with the combination regimens I and II was evaluated using 3 lines of cancer xenografts with special emphasis on relapse-free survival. Even in untreated controls, different influences of these cancers on the host as well as differences in their growth rates resulted in delayed tumor death in breast cancer (H-31) compared with pancreas (H-48) and colon (H-110) cancers. Four cycles of the regimen I drug combination failed to prolong life due to toxic side effects in every cancer line. In H-48 cancer, although regimen I alternated with regimen II achieved an inhibition rate (IR) of 96% with tumor shrinkage, 2 of 7 mice died of toxicity. In H-110 cancer, which is only sensitive to VDS, 4 cycles of regimen II alone produced an IR of 83.5%, which was slightly superior to alternating chemotherapy. In H-31 cancer, which retains considerable sensitivity to CDDP, MMC and 5'-DFUR, mice treated with alternating chemotherapy starting from regimen I for a total of 5 cycles attained a maximal IR of over 99% including disappearance of the tumor in 6 of 7 mice during the treatment course, and at the end of the experiment (20th week), all had survived with one in a relapse-free state, compared with the control group which had only 2 survivors. Thus, cyclic delivery of two non-cross-resistant drug combinations with optimal treatment doses and timing prevented toxic effects and induced long-term survival without relapse. Also, this appears to be the first study that has evaluated the effects of cancer chemotherapy in a human solid tumor-nude mouse system according to survival rate.

Animals↗
PubMed1987

[5'-DFUR (doxifluridine)].

5'-DFUR is converted to 5-FU by pyrimidine nucleoside phosphorylase. The activity of this enzyme is higher in tissue tissue than in most normal tissues, leading to a significantly higher conversion to 5-FU and 5-FU concentration in the tumor tissue than in normal tissue and serum. This activation mechanism provides this compound with high tumor selective toxicity. Based on these characteristics, 5'-DFUR has shown significant antitumor activity with less toxicity and immunosuppressive activity in experimental models. In the clinical study, 5'-DFUR has shown antitumor activity in gastric, colo-rectum and breast cancer. Especially in breast cancer, high response was observed including CR cases and also suggested a fast onset of action and long duration of efficacy. In the safety, major adverse reaction was diarrhea but it was controllable. Bone marrow suppression and CNS toxicity were very mild. 5'-DFUR can be a good candidate for the combination regimen and surgical adjuvant chemotherapy.

Animals↗
PubMed1987

Effects of phospholipases C on membrane-bound enzymes of yeast.

Alkaline phosphatase was released from protoplasts of the yeast Saccharomyces cerevisiae without cell lysis not only by phosphatidylinositol (PI)-specific phospholipase C but also by phosphatidylcholine (PC)-hydrolyzing phospholipase C. Activities of mitochondrial enzymes such as succinate dehydrogenase, antimycin-sensitive NADH-cytochrome c reductase, and oligomycin-sensitive ATPase were decreased by the action of PC-hydrolyzing phospholipase C. Hydrolysis of microsomal PC or PI did not cause any decrease in the activities of NADPH-cytochrome c reductase and antimycin-insensitive NADPH-cytochrome c reductase. In the requirement of phospholipids, the properties of yeast mitochondrial enzymes were very close to those of mammalian mitochondrial enzymes, whereas those of yeast microsomal enzymes were completely different from those of mammalian microsomal enzymes.

Adenosine Triphosphatases↗
PubMed1987

[Oily chemoembolization of hepatoma].

Since 1983 we have performed transcatheter oily chemoembolization (TOCE) using adriamycin (40-100 mg), Lipiodol (5-20 ml) and Gelfoam in the treatment of 100 cases with unresectable hepatocellular carcinoma. Adriamycin was dissolved in a fluid equal in specific gravity to Lipiodol and the adriamycin solution was mixed with 3 volumes of Lipiodol, making an adriamycin-in-oil emulsion (AOE). After TOCE, the blood concentration of adriamycin was obviously lower than that after one-shot injection because of the slow release of adriamycin from the AOE. Also, in cases of hepatic resection after TOCE, there was a clear difference in the adriamycin concentration between the tumor and the normal hepatic tissue. The cumulative survival rates for the 100 patients treated by TOCE were: 6 months 81.9%, 1 year 53.8% and 2 years 36.5%. Thus, improvement was found in comparison with the cumulative survival rates for 104 patients who underwent hepatic embolization without Lipiodol, which were 6 months 67.4%, 1 year 45.2% and 2 years 16.3%. AOE retained in the tumor as microemboli brings about the slow-releasing effect of adriamycin. Furthermore, by adding the effect of Gelfoam embolization, TOCE has a strong antitumor effect.

Carcinoma, Hepatocellular↗
PubMed1987

[Chemoembolization].

Chemoembolization is a technique by which the blood flow in the artery feeding a tumor is arrested and, at the same time, an antitumor agent is delivered in a high concentration to the target site in anticipation of a synergistic antitumor effect. Usually, this is a transcatheter technique. The embolic materials used to arrest the blood flow include gelatin sponge, Lipiodol, microcapsule, albumin microsphere, degradable starch microsphere and the like. Since the gelatin sponge and Lipiodol are available on the market, transcatheter oily chemoembolization (TOCE) using these two materials was performed in cases of hepatic tumor. In many cases of TOCE, adriamycin was used as an adriamycin solution Lipiodol mixture (adriamycin-in-oil emulsion). The cumulative survival rates for 100 patients with unresectable hepatoma treated by TOCE were 53.8% for one year and 36.5% for two years. Thus, improvement was observed in comparison with the cumulative survival rates of 104 patients who underwent hepatic embolization without Lipiodol (1 year, 45.2%, 2 years, 16.3%). Adriamycin-in-oil emulsion retained in the tumor as microemboli brings about the slow-releasing effect of adriamycin. The effect was demonstrated in the blood and tissue concentrations of adriamycin following TOCE.

Aged↗
PubMed1987

[Cooperative study of surgical adjuvant chemotherapy of colorectal cancer (first report): Investigation of background factors and adverse effects. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].

In order to evaluate the efficacy of surgical adjuvant chemotherapy in patients undergoing gross curative resection for colorectal cancer (excluding m and sm cancer), a randomized controlled study was conducted from January, 1982 to October, 1983. Four hundred and ninety-one institutions participated in this study. The schedules for drug administration differed according to each district. In the Hokkaido and Shikoku districts, the patients were divided into the following two groups, one was a combination of ACNU and Futraful (FT) and the other was FT only. In the Chubu and Kinki districts, three groups were studied, namely those receiving a combination of ACNU and FT, those receiving FT only and those given no adjuvant chemotherapy. In the Tohoku and Kanto districts, a combination of MMC and FT and administration of FT only were studied. In the Chugoku and Kyushu districts, the patients were divided into a combination of ADM and FT, and FT only group. Among the 3,926 registered cases, 3,421 cases were valid for the study. As to the background factors, there were no significant differences among the groups in each district. There were no significant differences in one-year survival rates and one-year disease-free rates. No serious adverse effects were observed in any of the groups.

Alopecia↗
PubMed1987

[A model for the sensitivity determination of anticancer agents against human cancer using nude mice].

Human tumors transplanted into nude BALB/c-nu mice have been used to test the sensitivity of the tumors to various anticancer agents. Three cancer cell lines from the stomach and one from the colon were transplanted into nude mice to establish a standard assay method for selection of effective drugs on individual tumors using the criteria of the Japanese Association of Sensitivity Determination for Carcinostatic Agents. From the LD values of anticancer drugs in nude mice, the appropriate doses of drugs were 6 mg/kg of MMC X 1(i.p.), 50 mg/kg of 5-FU q4d X 3 (i.p.), 120 mg/kg of CPA (i.p.), 30 mg/kg of ACNU (i.p.) 8 mg/kg of CDDP (i.p.) and 8 mg/kg of ADM (i.v.). At 3 weeks after initial treatment, the inhibition rate (IR) of the tumor was calculated from the formula IR = (1-T/C) X 100%, where T is the mean tumor weight of the treated group and C is the mean weight of the untreated group at that time. The tumors respond well to the anticancer agents when IR is more than 58%.

Adenocarcinoma↗
PubMed1987

[A multi-institutional study on postoperative adjuvant immunochemotherapy of gastric cancer (II)].

A multi-institutional cooperative study of postoperative immunochemotherapy for gastric cancer was studied using PSK and/or OK-432 combined with Tegafur (FT) and/or MMC. A total of 3,630 gastrectomized patients from 412 institutions were entered into the study using 6 randomly assigned protocols. Unbiased background cases were analyzed by 4-year or 5-year survival rates (SVR) for each protocol. The efficacy of combined PSK with FT was noticed in all cases of curative operation macroscopically and in n(-) X ps(+) cases (4-y SVR). The combination of MMC, FT and PSK produced better survival than MMC with FT or PSK administration in all cases of macroscopic curative operation (5-y SVR) and in non-curative operation (4-y SVR). The combination of MMC, FT, PSK and OK-432 was effective for poorly differentiated cancer (4-y SVR). Immunochemotherapy with MMC, FT, PSK and OK-432 was more effective in patients with preoperative positive PPD skin test than in those with negative PPD skin test. These results suggested that adjuvant immunochemotherapy using PSK and/or OK-432 combined with MMC and FT is effective for the improved survival of gastrectomized patients with gastric cancer.

Biological Products↗
PubMed1987

[Subrenal capsule assay for chemosensitivity testing].

The subrenal capsule (SRC) assay for cancer chemotherapy was tested according to Bogden's methodology. Of 37 patients providing tumor tissue for assay, 29 cases were considered suitable for evaluable assays. Fourteen patients had clinically evaluable diseases and 10 cases were evaluable for SRC assays. Correspondence between sensitive assay and clinical sensitivity was seen in 2 cases, and that between resistant assay and clinical resistance was seen in 4 cases. Discordance between sensitive assay and clinical resistance was seen in 4 cases. In histological studies, cancer tissues implanted in the subrenal space in immunocompetent mice did not show marked proliferation and were replaced by prominent leukocyte infiltration and fibrosis on day 6 after inoculation. The degree of leukocyte infiltration in the xenografts in the mice administered some anti-cancer drugs was slight in comparison with that in untreated control mice, which showed a remarkable trend in xenografts treated with 5-fluorouracil and cyclophosphamide, respectively. Our study suggests that there are many problems involved in the SRC assay methodology of Bogden, and that careful examination of this aspect will be required.

Animals↗
PubMed1987

[Advances in mitomycin studies--clinical studies: progress over 10 years].

Novel clinical trials with mitomycin C (MMC) have been more frequently reported in Europe and the States than in Japan. It was considered useful for the future development of clinical studies to summarize the results presented mainly in these latest reports. In this paper, clinico-pharmacological results, results by single and combined therapies, results by intraarterial infusion, researches of derivatives and trials of local chemotherapy using the drug delivery system are summarized, and reports on hemolytic-uremic syndrome, which is said to be possibly caused by MMC, are introduced briefly. Such reports have recently been published also in Japan. On the whole, it can be concluded that, though MMC has still held the place as the most extensively applicable antineoplastic agent, it cannot be used by any other methods than the middle-dose intermittent administration for preventing side effects. More detailed studies on mechanisms of its therapeutic actions and adverse effects are needed for further investigations on effective application of MMC and for finding out useful derivatives. It is desirable that these investigations will be more actively conducted in Japan.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Recent advanced studies on mitomycins, antitumor activity and mode of action].

Mitomycin C (MMC) showed a wide antitumor spectrum with regression of various tumors and the optimal schedule of a single or intermittent administration against human tumor cells xenografted to nude mice, confirming the early reports obtained in rodent tumor system. The sensitivity of various human tumors xenografted to nude mice has been tested to antitumor agents to establish the system which could select the clinically active drugs. The effectiveness of MMC against human stomach cancers xenografted to nude mice clearly correlated to the clinical effect of MMC against gastric cancer. The covalent cross-link adducts between MMC and DNA were isolated in the bioreductive system of NADPH-cytochrome C reductase and NADPH, and the major monoadduct was determined as N2-(2'' beta 7'-diaminomitosen-1''-alpha yl)-2'-deoxyguanine. Importantly, bisadduct was isolated, and the structure was determined by spectroscopic method. DNA-DNA cross-link formation was shown by alkaline elution in cells treated with MMC. The activation of MMC has been characterized by the two electron transfer process, however, the one electron transfer process was proposed by electrochemical analysis. MMC was effective against hypoxic cells. Several cell lines resistant to MMC were isolated, and some MMC derivatives showed in vivo and in vitro anti-tumor activity against these resistant cells.

Animals↗