Determination of urinary 2-thiothiazolidine-4-carboxylic acid by automated high performance liquid chromatography, as an index of carbon disulfide exposure.
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Carbon Disulfide↗
Biomedical subjects
T Taguchi
Publications and source records attributed to T Taguchi.
[Adjuvant chemotherapy for gastric cancer--the third study. First report: central randomization by telephone method and analysis of patients' background factors].
JFMTC conducted the third adjuvant chemotherapy study for gastric cancer patients after curative surgery from 1982 to 1983. Patients were randomly allocated to one of the three arms by telephone method controlled at the headquarters of the foundation. This method resulted in the marked reduction of ineligible cases (253 cases, 6.0% of 4,236 cases), compared with those in the first study (18.3%). Main reasons of ineligibility were the violation of entry criteria due to the misjudgment of noncancer, duplicate cancers and operative curability. Telephone method for random allocation seems to contribute to the improvement in the data quality of a clinical trial.
Antineoplastic Combined Chemotherapy Protocols↗
[Multi-institutional cooperative study of adjuvant immunochemotherapy in gastric cancer--five-year survival rate].
The Gastric Cancer Immunochemotherapy Study Group, constituted of 412 institutions, carried out six independent trials simultaneously from 1978 to 1981. A total of 4,456 cases were subjected to the study, from which 826 cases (18.5%) were excluded due to the violence of entry criteria. Curative gastrectomy, followed by a combination of mitomycin C (MMC), Ftorafur (FT)and Krestin (PSK) produced better postoperative survivals than either combination of MMC and FT, or MMC and PSK (5-year survival rate: 71.7% in MMC + FT + PSK, 64.1% in MMC + PSK, and 58.5% in MMC + FT). In the subset of patients with negative nodes (n(-)), and with involved serosa by histological examination (ps(+)), a combination of FT and PSK after gastrectomy seemed to be more favorable for the post-operative survivals than the single use of either drug. Four drug combinations of MMC, FT, PSK and Picibanil (OK-432) also had a clinical benefit in the group of patients with poorly differentiated adenocarcinoma, compared with chemotherapy alone. These results, though there are biases due to excluding 18.5% of cases, suggest some clinical benefits in the control of cancer relapse after surgery. The conclusion should be confirmed by a further elaborate trial.
Adjuvants, Immunologic↗
[Present status of surgical adjuvant chemotherapy of gastric cancer].
We need to come back to the origin of chemotherapy in the research of post-operative adjuvant chemotherapy for stomach cancer. We need to establish good regimens of adjuvant chemotherapy, which certainly work in advanced stomach cancer. If chemotherapeutic regimens are modified to use them as adjuvant therapies, we should follow the principle rules of chemotherapy. One of measures which we can take is to conduct randomised controlled studies in patients at high risk to compare best possible regimens which are currently available. On these studies, it is recommended that patients are first stratified by prognostic factors, followed by randomization.
Antineoplastic Combined Chemotherapy Protocols↗
[Cooperative study of surgical adjuvant chemotherapy of colorectal carcinoma (second study): a preliminary report. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].
In a prospectively randomized study, the effect of adjuvant chemotherapy with mitomycin C (MMC) and tegafur (FT) on survival and recurrence was analyzed in 2,477 evaluable patients with colon or rectal cancer who underwent macroscopically curative resection. Patients (1,256 with colon cancer, 1,221 with rectal cancer) were divided into the treatment group (group A) and the control group (surgical resection only, group B). In group A, chemotherapy consisted of intravenous administration of MMC (12 mg/m2 on operative day, followed by 6 mg/m2/2 months, 6 times) and oral administration of FT (800 mg/day for one year). No serious adverse effects were observed in the treatment group. There was no significant difference between group A and group B in three-year survival rate. The disease-free interval curve in group A of rectal cancer revealed significantly better results than group B (p = 0.044). There was no difference in the incidence of local recurrence at three years after operation between group A and group B. The incidence of metachronous liver metastases in group A of rectal cancer was significantly lower than in group B (p = 0.036).
Antineoplastic Combined Chemotherapy Protocols↗
[Cooperative study of surgical adjuvant chemotherapy of colorectal carcinoma (second study): 3-year survival after surgery of non-curatively resected patients. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].
A prospective randomized study was carried out to evaluate the efficacy of surgical adjuvant chemotherapy for non-curatively resected colorectal carcinoma patients as a collaborative study at 428 institutes in Japan from Jan., 1984 to Dec., 1985. A total of 1,138 patients were entered in this study. All patients were divided according to disease location (colon or rectum) and received one of two chemotherapeutic regimens after surgery (Regimen C: MMC 12 mg/m2 i.v. at operation day and 6 mg/m2 in every 2 months +UFT 600 mg/day p.o., D: the same dose of MMC + UFT 400 mg/day p.o.) randomly. 556 cases (colon carcinoma regimen C: 148, D: 185 cases, rectal carcinoma regimen C: 94, D: 129 cases) were evaluable at this presentation. Three-year-survival rate of histologically confirmed non-curatively resected colon carcinoma patients was higher in the group receiving regimen C than in regimen D. But no significant difference was found among the other groups.
Antineoplastic Combined Chemotherapy Protocols↗
[Recent progress in multidisciplinary treatment of hepatic cancer].
Fifteen to 20 years ago, the natural history of HCC demonstrated approximately 1.5 months median survival after diagnosis with rare cases of one-year survival. Ten to 15 years ago, one shot intraarterial (IA) injection of mitomycin C (MMC) or doxorubicin (ADR) became the prevailing treatment and prolonged median survival to 3-5 months. Ten years ago, transcatheter arterial embolization was introduced and improved the survival rate dramatically. In the earlier period, TAE was performed with gelatin sponge (GS) plus ADR or MMC and showed shrinkage of HCC in the well-capsulated case. Combined use of Lipiodol (LPD) with anticancer drug and GS in later period showed further progress in antitumor response and survival. The one year survival rate obtained from our 100 cases was 53.8%, and the 2 year one was 36.5%. We speculate that the effective response of LPD plus drug to intrahepatic daughter nodules contributed to this improvement because we clarified the efflux of LPD to peripheral portal vein clinically and experimentally. Since the metastatic liver tumor originating from colon or gastric cancer is usually hypovascular and shows limited response to intra-arterial chemotherapy, a special device is needed for improvement. We introduced an S.C. implanted port for injection route and long-term intermittent IA combination therapy with ADR or MMC and degradable starch microspheres (DSM), which embolise arteries temporarily for 20-30 minutes. These new methods achieved a favorable response rate with better quality of life, and would be expected to prolong the life span of patients with metastatic liver tumor.
Antineoplastic Agents↗
[Clinical significance of measurement of nuclear DNA content in breast cancer].
Nuclear DNA content measured by a cytofluorometric method was investigated to evaluate its clinical significance in 73 cases with breast cancer which had extended radical mastectomy. Many cases of D type (diploid type) which had a prominent peak at the 2c region (control DNA content of lymphocytes) were safe indications for modified radical mastectomy. Bone recurrence was significantly more frequent in D type than in N type (non-diploid type) which did not have a prominent peak at the 2c region. Because D type had high positive rate of hormone receptors, endocrine therapy might be effective for many cases. Local or lung recurrence was more common in cases with N type which had a significant low cumulative survival rate compared with D type and especially N type 4c-3 of which over 4c cells more than 30% had the poorest prognosis. Therefore, multidisciplinary treatment composed of extended operation, radiation and chemotherapy was necessary to improve the prognosis of breast cancer patients with N type 4c-3. It was concluded that the measurement of nuclear DNA content in breast cancer might be useful for decision of therapy suitable for each case based on malignancy grading.
Breast Neoplasms↗
[Mass culture of LAK cells by a hollow-fiber bioreactor system].
We attempted to culture LAK cells by the use of the hollow-fiber bioreactor system, "Acusyst-P". The number of LAK cells increased by 30-40 times. The majority of LAK cells cultured by this hollow fiber system originated in T cell. LAK cells cultured by hollow-fiber system were different from LAK cells statically cultured in their cytotoxicity and change of phenotype. We obtained LAK cells more efficiently and safely which have higher viability and cytotoxicity by the use of hollow-fiber bioreactor system than by static culture.
Cytological Techniques↗
Evaluation of change with time of glomerular morphology in membranoproliferative glomerulonephritis: a serial biopsy study of 33 cases.
The evolution of renal glomerular lesions was examined in biopsies taken from 33 patients with membranoproliferative glomerulonephritis (MPGN). 25 patients had a diffuse form of MPGN in the first biopsy (group A). Twenty-four of them still showed diffuse MPGN in subsequent biopsies, but one patient improved clinically and histologically 19 years after the initial biopsy. Out of 6 patients with focal MPGN in the first biopsy (group B), 4 developed diffuse MPGN, one remained with focal MPGN in the repeat biopsy, and another one was found in remission, as determined by both histological and clinical features. Group C represents two patients who had no histological findings of MPGN on initial biopsy but later showed evidence of a diffuse form of MPGN on subsequent biopsies. Thus, the focal form of MPGN may be found either in the development of diffuse MPGN or in its healing stage, and the prognosis will vary accordingly.
Adolescent↗
[Overview on the behalf of the Society for Arterial Infusion Chemotherapy Research].
Arterial infusion chemotherapy (AIC) is an attempt to provide a suitable route for anticarcinogens which will increase chemotherapeutic efficacy while diminishing side effects. It was tested around 1950, and progress in vascular surgery and arterial imaging resulted in favorable results. In the Seventies, AIC was conjoined with embolization techniques, resulting in the new chemoembolization approach. With the Eighties, the Society for Arterial Infusion Chemotherapy Research was established. It has since figured largely in pursuing the role of intraarterial chemotherapy for the treatment of cancer.
Antineoplastic Agents↗
[Questionnaire results on implantable catheter systems].
Recent advance of intra-arterial chemotherapy can be attributed to improvement of devices, especially implantable catheter systems. In May 1989, a questionnaire was set out through the Japanese Association of Arterial Cancer Chemotherapy to find out the current use of arterial as well as intravenous implantable systems. The results revealed that: 1) Arterial implantable systems were widely used in 1879 patients at 91 institutes, mainly to treat patients with primary and secondary liver cancers. Intravenous systems were used in 88 patients at 17 institutes. 2) Implantable catheter systems were used for long-term intermittent or continuous infusion. 3) Compared with percutaneous catheters, a decrease in infection and occlusion rates and less daily care were noted. 4) Due to the development of implantable systems, 890 out of 1,879 patients on arterial therapy and 60 out of 88 patients on intravenous therapy could switch over to an outpatient basis. 5) Improvement of "quality of life" was found at all but one institute. 6) All questionnaires (except unanswered) requested health insurance reimbursement for totally implantable catheter systems.
Antineoplastic Agents↗
[Evaluation of predictability of in vitro SDI assay in comparison with in vivo nude mouse assay].
Twenty lines of human gastro intestinal and breast cancer xenografts, in which chemosensitivity spectra by the in vivo nude mouse assay had been clarified. were subjected to the in vitro SDI (succinate dehydrogenase inhibition) assay using MTT dye to assess the accuracy of this drug sensitivity test against 4 drugs i.e., mitomycin C (MMC), adriamycin (ADM) 5 fluorouracil (5-FU), and cisplatin (CDDP). After 3 days incubation, the suspension of every tumor cells including small fragments showed a marked decrease of SD activity even when no anticancer drug was added to the assay medium. Among these 4 drugs evaluated MMC exhibited a statistically significant correlation between chemosensitivity values of the in vitro SDI assay and those of the nude mouse assay. However, the other 3 drugs demonstrated no correlation between the values of these two methods. Since the primary cultured fibroblasts revealed, in general, lower sensitivity to these drugs, contamination of fibroblast may decrease the SDI values when materials from solid tumors with rich stroma such as a type of stomach cancer were subjected. It is considered that the prediction of chemosensitivity to every drug will be impossible by a in vitro SDI assay.
Animals↗
[Selective induction of dog esophageal carcinomas by the restricted oral administration of N-ethyl-N-'-nitro-N-nitrosoguanidine with a projecting spout].
In order to establish an effective method to induce selectively experimental dog esophageal carcinoma, we compared the restricted oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) with projecting spout with the ad libitum oral administration of it. Five dogs were given a solution of ENNG at a concentration of 50mg/l with restricted oral administration with projecting spout for 52 weeks. In all of them, elevated type of esophageal lesions were endoscopically observed soon after the cessation of the ENNG administration. Histological examination revealed that besides the multiple squamous cell carcinomas of the esophagus, various degrees of dysplasias were seen. Two dogs had metastasizes to the regional lymph nodes and one dog had metastatic lesions in the lung. Gastric carcinomas were also seen in four dogs. Another five dogs were given ad libitum the same concentration of ENNG solution. Gastric carcinomas were induced in four dogs, but esophageal carcinomas were seen in small lesions in two dogs. The restricted oral administration of ENNG with projecting spout is a reliable method for the selective induction of esophageal carcinoma in dog.
Administration, Oral↗
[Polarographic analysis of tumor tissue oxygen tension after hyperthermia combined with misonidazole].
For the purpose to analyse the influence of a thermosensitizing drug, misonidazole (MIS), on tissue oxygen tension (TpO2), TpO2 in human gastric cancer tissue (H-23) was measured by a polarographic method. MIS, 500 mg/kg, was given i.p. and then the heat treatment was done in a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. A second treatment was performed to develop thermotolerance at the following intervals: 24 hours, 72 hours, 5 days, and 7 days. Tumor doubling time was shortest at 72-hour interval, i.e., the maximal thermotolerance of the tumor developed at 72-hour interval, whereas the tumor doubling time in case of combined use of MIS was shortest at 24-hour interval. TpO2 in the 72-hour interval treatment decreased soon after hyperthermia, and returned to a pre-heated value 3 hours after, whereas in the other 3 treatments the recovery time was 6 to 12 hours. On the other hand, in 24-hour interval of the combined use of MIS, the post-thermal value of TpO2 was about a half of the pre-thermal value and recovered 24 hours after. In the 5- and 7-day interval treatments, TpO2 declined notably and did not return to the pre-thermal value during 24 hours. These data suggest that the thermo-sensitizing effects of MIS were brought about by prolonged and extreme decrease in TpO2.
Adaptation, Physiological↗
Stimulation of cadmium uptake by estradiol in the kidney of male rats treated with cadmium.
The present study was carried out to analyze the sex differences in the retention of Cd in rats treated with a small amount of Cd, and its mechanisms. Cd and Zn concentrations in the kidney and liver of female rats treated with 28 nmol Cd or 1 nmole Zn were significantly higher than those in male rats. Pretreatment with estradiol (1.8 mumol/kg of b.w., twice a day, 6 consecutive days) increased the Cd and Zn concentrations in the kidney of male rats treated with Cd or Zn. Incubation of MDCK cells with 10(-5) M estradiol, 10(-5) M stilboestrol and 10(-5) M progesterone caused a significant increase in Cd uptake. These results suggest that endogenous female sex hormones may play a role in a higher concentration of Cd and Zn in the kidney of female rats than that in male rats. The basal level of metallothionein (MT) in the liver and kidney of control female rats was within the same range as that in the control male rats. Cd and Zn accumulations caused by pretreatment with estradiol in the kidney of male rats treated with Cd or Zn were so low (Cd: 38 ppb, Zn: 1.0 ppb) as to be probably unable to induce the synthesis of MT. An increase in the concentration of Cd in the cultured renal cells occurred 1 hr after treatment with estradiol and Cd. Pretreatment with estradiol alone also resulted in a modification of the concentration of Na and K, which cannot be bound to MT. Together, all of the above findings suggest that estradiol directly increases the accumulation of Cd into the renal cells without inducing the synthesis of MT.
Animals↗
Biosynthesis of 20,20,20-trifluoroleukotriene B4 from 20,20,20-trifluoroarachidonic acid: a metabolically stable analog of leukotriene B4 and its application to a study of stimulation of leukotriene B4 synthesis by immunoglobulin G1,2.
Leukotriene B4 is rapidly metabolized through omega-oxidation, preventing its detection when it is produced under certain biological conditions. To investigate leukotriene B4 production in various physiological conditions, analogs of arachidonic acid which are converted to metabolically stable analogs of leukotriene B4 would be useful. We have synthesized 20,20,20-trifluoroarachidonic acid by the cis-selective Wittig reaction of the C12-C20 fragment with phosphonium salt. 20,20,20-trifluoroarachidonic acid was transformed into 20,20,20-trifluoroleukotriene B4 when incubated with human neutrophils in the presence of the calcium ionophore A23187. The product was identified by uv absorption spectrophotometry, gas chromatography-mass spectrometry, and coelution on high-performance liquid chromatography with 20,20,20-trifluoroleukotriene B4, which was enantioselectively synthesized by the reaction of the fluorine-containing C11-C20 fragment with the C1-C10 phosphonate. The fluorinated leukotriene B4 demonstrated as much chemotactic activity on human neutrophils as natural leukotriene B4 and was metabolically stable when incubated with human neutrophils, probably by blocking omega-oxidation. Also, enzymes catalyzing the transformation of arachidonic acid (AA) into leukotriene B4 did not discriminate the fluorinated precursors from the natural, nonfluorinated AA, thus 20-F3-AA is a valid analog of AA to be used in the study of AA metabolism. When 50 microM of the fluorinated acid was incubated with neutrophils stimulated with heat-aggregated human immunoglobulin G, a significant amount of fluorinated leukotriene B4 (4.3 ng/10(6) cells/40 min, at most) was formed in a dose-dependent manner while little leukotriene B4 was detected with incubation with 50 microM arachidonic acid, probably due to omega-oxidation of the product, leukotriene B4. 20,20,20-Trifluoroarachidonic acid appears to be a useful tool for studying the capacity of leukotriene B4 synthesis in various biological systems while long-lasting 20,20,20-trifluoroleukotriene B4 would serve as an excellent analog of leukotriene B4 in pharmacological studies to understand functions of leukotrienes B4.
Arachidonic Acids↗
Reduction of nitroglycerin and isosorbide dinitrate by hemodialysis in refractory angina pectoris after acute myocardial infarction.
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Angina Pectoris↗