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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 883 records · Page 49Linked to original sources

[Chemosensitivity of human gastrointestinal and breast cancer xenografts in nude mice].

Experimental chemotherapies for 15 human cancers xenografted into nude mice were performed using 14 anticancer agents including 6 drugs in clinical use. Treatment with each single agent was performed for every cancer line using the maximum tolerated dose through continuous daily (antimetabolites) or intermittent (cytocidal agents) schedules. Effectiveness of each drug was evaluated by inhibition rate (IR) calculated from mean tumor weights of both treated and untreated groups. Response to a treatment was judged as effective when the IR was higher than 58%. Response rate of each drug was as follows; MMC was 67%, UFT 67%, CPA 47%, FT-207 40%, ACNU 33%, ADR 27%, SOAz 87%, 5'-DFUR 80%, MXT 20%, Leakadine 17%, M-83 17%, CAM 0% and GANU 0%. Generally, the experimental results for each drug on the xenografts was in good accordance with the known clinical effect of each drug on the same type of cancer. On the other hand, individual cancer xenografts showed considerable differences in chemosensitivity. Some tumors were sensitive to a majority of the drugs, whereas some were resistant to many of them. Each cancer line seemed to retain individuality in its spectrum of chemosensitivity irrespective of whether it originated from the same organ or whether it was of similar histologic type. This fact suggests the necessity of selecting drugs effective to the individual tumor when considering a patients chemotherapy regime.

Animals↗

[Chemotherapy for recurrent breast carcinoma].

5-FU and its analogs, Cyclophosphamide (CPA), Methotrexate (MTX), Adriamycin (ADM) and Vincristine (VCR) are among the many different anticancer agents that have proven effective by themselves against progressive recurrent carcinoma of the breast. However, in actual clinical practice, multiple combination therapy with these drugs which are effective singly, has been found to be even more effective. Regimens with CF (CPA + 5-FU), CMF (CPA + MTX + 5-FU), CMFVP (CPA + MTX + 5-FU + VCR + Pred., CAF (CPA + ADM + 5-FU), and AC (ADM + CPA) are well known, but the dosage and administration schedule differ somewhat with the researcher. In any case, a 30 to 50% response rate has been reported on the overall. With recurrent carcinoma of the breast, the primary choice of a chemotherapy regimen involving various agents, the combination with hormone therapy, the conditions as to the location of the recurrence or pre-treatment situation, pose serious problems. CMF, CMFVP or AC are recommended as the regimen of choice, and it is only natural that the agents not used in the preferred regimen be combined in the second choice of treatment. Also, testing with new drugs must be aggressively pursued in many cases.

Antineoplastic Combined Chemotherapy Protocols↗

[Phase I study of recombinant human interferon alpha A (Ro 22-8181) in patients with malignant tumors].

A clinical Phase I study of recombinant human interferon alpha A (Ro 22-8181) was performed in patients with malignant tumors; twenty of them received an American product and seven others a domestic product. Both products were administered in single intramuscularly injected doses of 18, 36, 50, 75 and 100 X 10(6)U. Main side effects included fever and influenza-like symptoms (headache, chill/shivering, general fatigue, lumbago), and digestive symptoms (anorexia, nausea/vomiting). Numbness of fingers or limbs and somnolence were also observed in higher dose groups, but these symptoms all disappeared on the day of administration or by the 3rd day after administration. Abnormal laboratory findings included leukopenia, granulocytopenia, lymphocytopenia, thrombocytopenia and increased GOT/GPT/LDH, but these returned to normal by the 10th day after administration. The peak blood concentration was correlated with the dose, falling to the base line 72 hr after administration. The American product and the domestic product were nearly comparable in the type and incidence of their side effects, and also produced generally comparable blood concentrations. Furthermore, increased anti-IFN-alpha antibody titer was not observed in any of the patients; and the Prick Test proved negative in all of them. No significant changes were observed in any immunological parameters, either.

Adolescent↗

[Microvascular architecture of human gastrointestinal and breast cancer xenografts in nude mice, and its relation to chemosensitivity].

As a tumor factor possibly responsible for chemosensitivity of human cancer xenografts in nude mice, the vascular architecture of tumors growing in mice was investigated in 15 kinds of cancer lines. These consisted of 7 gastric, 3 colorectal, 3 breast and 2 pancreatic cancers. Whole body angiograms of tumor-bearing mice were obtained by perfusing a radiopaque silicone rubber compound (Microfil) through the left ventricle of each mouse. Each cancer retained a characteristic vascular architecture comparable to its histopathological finding. According to the vascularity of the viable part of the tumor, the 15 lines of cancer were classified into 5 groups. Compared with colorectal cancers, stomach cancers had a tendency to decline to a more hypervascular group. There was no apparent relation between vascularity and growth rate, or histological differentiation of the tumors. Among 14 anticancer agents studied, statistically significant correlation between chemosensitivity and vascularity of the 15 cancer lines was observed in 2 drugs, 5'-DFUR and adriamycin. The vascular architecture of the tumors would have some influence in their chemosensitivity through drug accessibility to cancer cells.

Adenocarcinoma↗

[Therapeutic effect of dried ion exchange resin-treated human immunoglobulin (SM-4300) against severe bacterial and/or fungal infections in surgery].

A newly developed human immunoglobulin for intravenous use, SM-4300, purified by cold ethanol precipitation and ion exchange resin, has been studied in the surgery. SM-4300 has been evaluated clinically against inpatients with severe bacterial and/or fungal infections in the combined use with the antibiotics which were resistant to antibiotic therapy. Total number of 13 patients affected with various severe infections were treated with SM-4300. Clinical effects of SM-4300 were excellent in 2 cases, good in 6, fair in 3 and poor in 2. The efficacy rate was summarized as 61.5%. No subjective and objective clinical side effects and abnormal laboratory findings were observed. In conclusion, combination therapy with SM-4300 and antibiotics was considered to be safe and effective against severe bacterial and/or fungal infections in the surgery.

Adolescent↗

Chemical synthesis of (24R)-24,25-dihydroxy[26,27-3H]vitamin D3 of high specific activity.

Chemical synthesis of (24R)-24,25-dihydroxy-[26,27-3H]vitamin D3, and its 24-epimer has been devised that allows introduction of 3H at the terminal step of the synthesis. The epimeric mixture is derivatized as the tris(trimethylsilyl) ethers and resolved by high-performance liquid chromatography. The product has a specific activity of 178 Ci/mmol and is fully active in binding to the rat plasma vitamin D binding protein and in the elevation of serum calcium levels of vitamin D deficient rats. The synthesis begins with the readily available 3 beta-hydroxy-5-cholenic acid methyl ester and involves a Pummerer rearrangement, introduction of the delta 7, irradiation, and isolation of the 26,27-dinor-25-carboxylic acid methyl ester of vitamin D3. This compound is then treated with a Grignard reagent containing 3H (80 +/- 10 Ci/mmol).

24,25-Dihydroxyvitamin D 3↗

[An improved method for plasma methimazole assay and its clinical application].

An improved method for plasma methimazole assay using high performance liquid chromatography is described. The plasma samples were treated with sodium bisulfite and ammonium sulfate prior to extraction with chloroform. This pretreatment of the samples raised the extraction coefficient to 90%, while simple extraction yielded only 55%. The minimal detection limit was 0.02 microgram/ml, and the coefficient of variation at the level of 0.2 and 1.0 microgram/ml was less than 5%. Pharmacokinetics of methimazole was studied after a single oral dose (20 mg/m2) in six subjects including two healthy adults and four thyrotoxic children. Plasma levels of methimazole showed a peak concentration of 1.03 +/- 0.25 microgram/ml approximately one hour after the drug administration. Plasma half-life, area under the curve and distribution volume were 4.56 +/- 0.71 hr, 7.05 +/- 0.95 microgram/ml X hr, and 630 +/- 110 ml/kg respectively.

Adolescent↗

Postoperative adjuvant chemotherapy for gastric carcinoma. Analysis of data on 1805 patients followed for 5 years.

The effectiveness of combination chemotherapy with mitomycin-C (MMC) plus Futraful (N1-(2'-tetrahydrofuryl)-5-fluorouracil) for gastric cancer was investigated in a prospective randomized and controlled study. Two thousand sixty-four Japanese patients in 297 hospitals were entered, and 1805 could be followed. All patients had undergone gastrectomy from May 1975 to July 1976. These patients were grouped into two protocols: protocol I (intermittent intravenous injection of a moderate dose of MMC), and protocol II (bolus intravenous injection of MMC), each of which was allocated to group A (without Futraful) and group B (MMC plus oral administration of Futraful for 3 months). Statistically, this randomized study showed that the 5-year survival rate of patients with advanced cancer was not enhanced. However, with protocol II the Futraful administration seemed to improve the 5-year survival rate for those with Stage III cancer and for those with positive lymph node metastasis plus obvious serosal invasion.

Adult↗

Gd(-) Gifu and Gd(-) Fukuoka. Two new variants of glucose-6-phosphate dehydrogenase found in Japan.

Two new glucose-6-phosphate dehydrogenase (G6PD) variants were discovered in Japan. The first, found in a 9-year-old male, was associated with chronic hemolysis and hemolytic crises after upper respiratory infections. The enzyme activity of the variant was 2.9% of normal. The patient's G6PD showed an increased utilization of substrate analogue, deamino-NADP, and thermal instability. The second variant occurred in a 7-year-old male with drug-induced hemolysis. The main enzymatic characteristics were reduced enzyme activity, being 6.4% of normal, faster-than-normal anodal electrophoretic mobility, slightly high Michaelis constant for glucose-6-phosphate, thermal instability, and biphasic pH optima. Enzymatic properties of these variants allowed each to be distinguished from previously reported variants. The first variant was designated Gd(-)Gifu and the other, Gd(-)Fukuoka.

Child↗

Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer--a randomized controlled trial.

Adjuvant immunochemotherapy using Schizophyllan (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed at random for 326 Japanese patients with resectable gastric cancer. The overall survival rates for 3 years did not differ between the SPG and control groups. In 62 patients with stage I gastric cancer and 67 with stage II, there was little difference in the 3-year survival rates. The survival rates for 100 patients with stage III were enhanced at p = 0.0811 in the SPG group, as compared to the controls. The survival rates in 97 patients with stage IV cancer were much the same. These results warrant further application of this immunopotentiating drug for treating patients with resectable gastric cancer.

Clinical Trials as Topic↗

Tetraphenylboron increases choline permeability through a calcium release channel of isolated sarcoplasmic reticulum.

The lipophilic anion tetraphenylboron (TPB-) but not the lipophilic cation tetraphenylphosphonium (TPP+) increased the choline permeability of isolated sarcoplasmic reticulum (SR). Choline permeability was mainly measured by the stopped flow method by following the change in scattered light intensity. TPB- and TPP+ did not affect the choline permeabilities of liposomes, liver microsomes, or denatured SR vesicles. These phenomena are similar to the Ca2+ release phenomena activated by TPB- reported by Shoshan, MacLennan, and Wood (J. Biol. Chem. 258, 2837 (1983)). These results strongly suggest that TPB- activates a pre-existing channel of SR membrane and choline permeates through the same channel as that for the Ca2+ release. This channel is different from that for the Ca2+-induced Ca2+ release. The former is present in all of the vesicles formed by fragmented SR, while the latter is rich in the heavy fraction of fragmented SR and poor in the light fraction. The channel specificities for permeable ions are different from each other. For example, the latter passes Tris+ but the former does not. The physiological role of this channel is not clear at present.

Animals↗

Thanatophoric dysplasia.

Two autopsy cases of thanatophoric dysplasia in male newborn infant are described. They have markedly short-limbs and narrow thoraxes. Histologically, generalized disruption of endochondral ossification with normal resting cartilage was seen at the epiphyseal region of femur. Differential diagnosis from other 3 types of lethal chondrodysplasia is described and the histogenesis of thanatophoric dysplasia is considered with a survey of the literature.

Achondroplasia↗

A pathological study of fulminant hepatic disease.

Among 4,030 autopsies, 67 cases of fulminant hepatic failure were selected and studied from a pathological viewpoint. No sex difference in incidence was seen and the patients' age ranged very widely from 3 months to 78 years, showing comparatively high risk in the 20 s and 30 s in both sexes. Hepatitis virus was the most common cause, followed by toxic chemicals, shock, etc. Histopathological study revealed severe and extensive hepatic cell necrosis as the most conspicuous and common change of the liver, which was pathomorphologically quite similar to that experimentally produced by focal intravascular coagulation in rabbit. This evidence, as well as pathological findings of the other organs obtained at autopsy and the patients' reported clinical course, including laboratory data, were consistent with our proposal of a pathological disease entity, fulminant liver disease, which corresponds to the clinical symptom-complex known as fulminant hepatic failure. It is suggested that the characteristic feature of acute, severe and extensive hepatic cell necrosis which is seen in such cases is probably a result of an anoxic state caused in most instances by intrahepatic circulatory disturbances. Besides, we consider that fulminant liver disease can be regarded as a group of systemic diseases with the main focus of illness in the liver, rather than a specific disease of a single organ, the liver.

Adolescent↗

[Effects of 5'-deoxy-5-fluorouridine on human gastrointestinal and breast cancers xenografted to nude mice].

As a preclinical secondary screening trial, the efficacy of a new derivative of 5-fluorouracil, 5'-deoxy-5-fluorouridine (5'-DFUR), on 15 human cancers xenografted serially to nude mice of BALB/c background was evaluated in comparison with two other derivatives, tegafur and UFT. Oral administration of 123 mg/kg/day of 5'-DFUR, 25-30 times, produced effective inhibition in 5 out or 7 gastric cancers, 2 out of 3 colorectal cancers, all 3 of breast cancers and 1 out of 2 pancreatic cancers, totalling 11 out of 15 cancer lines (73%) examined. In some cases shrinkage of tumors was noted without any noticeable side effects. Although an increased dose of 185 mg/kg/day of 5'-DFUR resulted in more prominent inhibition on all 9 tumors tested, some animals suffered from severe loss of body weight or diarrhea. Comparative experiments with of equimolac doses of 5'-DFUR(123 mg/kg) and FT-207(100 mg/kg) showed that the inhibition rate of the former was higher than that of the latter in all 8 lines of cancers examined. Six experiments in particular (2 gastric, 1 colorectal, 2 breast and 1 pancreatic cancers), showed that 5'-DFUR statistically sustained more effective suppression. Direct comparisons of 5'-DFUR and UFT were also made in 5 experiments in which 3 cancers were more sensitive to the former drug. Promising results in clinical trials can be expected with the new drug 5'-DFUR for these kinds of cancers.

Adenocarcinoma↗

[Treatment of hepatic tumors by transcatheter chemo-embolization with gelatin sponge].

Transcatheter chemo-embolization is a technique for achieving a marked antitumor effect by embolizing the hepatic artery with a gelatin sponge immediately after infusion of adriamycin 60 mg into the same artery. Chemo-embolization was performed in 212 cases of hepatocellular carcinoma and 23 cases of metastatic liver cancer, a total of 235 patients. Of this population, 19 patients with hepatocellular carcinoma underwent hepatectomy, and in 7 of them, complete necrosis of tumors having thick capsules and less than 4 cm in diameter was confirmed. The cumulative survival rate of patients with unresected hepatocellular carcinoma was 75.6% at 6 months, 52.6% at 1 year, and 20.3% at 2 years. The longest survival time was 3 years and a half, and this patient is now living. As regards metastatic liver cancer, complete necrosis could be achieved in 1 of 2 patients undergoing resection, whereas the cumulative survival rate of unresected cases was 55% at 6 months and 44% at 1 year: only two patients survived for more than 1 year. Technically, the use of a balloon catheter (7F) resulted in the virtual elimination of unsuccessful cases and the prevention of adverse effects due to migration of the gelatin sponge.

Carcinoma, Hepatocellular↗

[Experimental anterior interbody fusion of the cervical spine. Comparative study between autograft and Al2O3 ceramic implantation].

The purpose of this paper is to compare autograft and Al2O3 ceramic implantation as grafting interbody fusion of the cervical spine of rabbits. Fifty six rabbits were used. In 36 rabbits, Al2O3 ceramic spacers were inserted into the level of C4-5. The spacer is hexahedronic in shape, measuring 6 X 4 X 3 mm. In 20 rabbits, autologous bones, same size as the spacer, were inserted under the same procedure. Animals were killed at 2, 4, 8 and 12 weeks after the procedure. Each material was evaluated radiologically, histologically and biomechanically. The main results found in this study were as follows: Radiologically, periodic anteroposterior and lateral X-rays were taken for the duration of 12 weeks after the procedure. Although the animals with Al2O3 ceramics showed extrusion at higher rate as compared with autografts, they didn't show any collapse and local kyphosis in the procedure site except for extrusive cases. Histologically, new bone formation was observed around Al2O3 ceramics at 4 weeks. And it is clear that Al2O3 ceramics have good histocompatibility. Biomechanically, the maximum resistance to bending or the rigidity of each fixed intervertebrae was measured with the Tensiron testing machine. In the resistance, Al2O3 ceramics were inferior to autograft, but almost equal to the normal motion segment. According to these results, Al2O3 ceramics have many advantages, and results as favourable as those obtained by native bone may be obtained with a proper shape of the implant.

Aluminum↗

[The theory and practice of chemotherapy by arterial infusion--the importance of pharmacokinetic research].

Chemotherapy using arterial infusion was employed to introduce an anti-cancer drug directly into the arteries which nourish the tumor, thereby distributing a high concentration of the drug to the tumor, increasing the anti-tumor effect and reducing the amount of the drug in circulation throughout the body, thus mitigating its side effects. However, the uptake of the anti-cancer drug into the tumor and its distribution throughout the body are influenced by a large number of factors: the method or route of administering the anti-cancer drug; rate of infusion; local blood flow; permeability of the blood vessels; structure and affinity of the drug; the metabolism of the drug and the speed of its breakdown and elimination. As long as this kind of pharmacokinetics is involved, the principal merit of the arterial-infusion chemotherapy is that the first time the drug is circulated, a high concentration is distributed to the arteries which feed the tumor. However, there is a great deal as yet unknown about the peculiarities and variability of anti-cancer drugs and the internal organs.

Animals↗