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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 631 records · Page 35Linked to original sources
PubMed1991

[Nuclear DNA content in breast cancer in relation to postoperative recurrence].

Nuclear DNA content in breast cancer patients who underwent extended radical mastectomy was investigated to evaluate its possible relation to postoperative recurrence. The most frequent site of the first recurrence in diploid type (D type) cases was the bone and the frequency was significantly higher than that in non-diploid type (N type) cases. On the other hand, the ploidy pattern in all cases associated with local or local lymph node recurrence was N type and the lung was the next frequent site of recurrence in N type case. The frequency of over 4c cells was the highest in the cases of local or local lymph node recurrence being significantly higher than in all cases of distant recurrence or of the bone recurrence. The cumulative disease-free survival rate in patients with D type breast cancer was significantly higher than that in patients with N type. These results suggest that nuclear DNA content provides important information for deciding therapy and the schedule of postoperative follow-up study based on the mode of recurrence.

Breast Neoplasms↗
PubMed1991

[Combination chemotherapy with orally administered UFT and leucovorin (LV)].

We evaluated the efficacy of the combination therapy of UFT with Leucovorin (LV) against mouse colon adenocarcinomas and human colon adenocarcinoma. In vitro studies, it was shown that LV potentiated the cytotoxicity of FUra against 7 out of 9 cell lines used in this experiment. In vivo studies, the antitumor activity of UFT against mice bearing colon 38 adenocarcinoma was increased following administration of LV either before, after or at the time of treatment with UFT. Further studies were performed on the combination effect of UFT and LV against mouse colon 26 adenocarcinoma and human colon adenocarcinoma KM20C. Consequently, the combined treatment of UFT with LV was more effective than UFT alone against two cell lines. Our studies suggest that combination chemotherapy of UFT with LV is a promising approach for the treatment of a human colon cancer in clinical practice.

Adenocarcinoma↗
PubMed1991

[Cross-resistance of HO-221 and various antitumor agents in sublines of mouse leukemia].

HO-221, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2- nitrobenzoyl) urea is a new benzoylphenylurea derivative. The compound exhibits significant antitumor effects against various animal tumors, and was especially effective against the solid tumors implanted subcutaneously. HO-221 inhibits DNA polymerase alpha activity strongly in vitro. In this study, we examined the cross-resistance of HO-221 to various antitumor agents using sublines of mouse leukemia. HO-221 showed antitumor effects in mice bearing L 1210 or P 388 leukemia resistant to 10 antitumor agents, DM (daunomycin), MMC (mitomycin C), CDDP (cisplatin), 5-FU (5-fluorouracil), Ara-C (cytosine arabinoside), MTX (methotrexate), CPA (cyclophosphamide), CQ (carboquone), ADM (adriamycin) and VCR (vincristine), respectively. These antitumor agents were also effective in P 388 leukemia resistant to HO-221 (P 388/HO-221). Furthermore, CDDP- and MMC-resistant sublines showed a collateral sensitivity to HO-221 in vivo. The grow the inhibitory effects were also noted in vitro in ADM-, CDDP- and MMC-resistant cells by HO-221. However, the in vitro experiments didn't show such collateral sensitivity on the resistant sublines. These results suggest that there is no cross-resistance between HO-221 and other known antitumor agents, and that HO-221 seemed to be worth for evaluating clinical usefulness.

Animals↗
PubMed1991

[Cooperative study of surgical adjuvant chemotherapy for colorectal cancer (third report): five-year results. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan].

A randomized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal surgical adjuvant chemotherapy for curatively resected colorectal cancer. The schedules for drug administration were different in four districts: ACNU + Futraful (FT) group and FT alone group in the Hokkaido-Shikoku district; the same schedule groups plus untreated group in the Chubu-Kinki district; MMC+FT group, FT alone group in the Tohoku-Kanto district; and ADM+FT group and FT alone group in the Chugoku-Kyushu district. The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study. The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer, but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies. In n2 (+) or a2(s) rectal cancer in particular, combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate, and the rate of local recurrence was significantly lower with ADM+FT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Preparation, metabolic stability and biological properties of omega-trifluorinated analog of 12-hydroxyeicosatetraenoic acid.

12-Hydroxyeicosatetraenoic acid (HETE) is associated with a variety of inflammatory conditions. For studies on pathophysiological function of 12-HETE, metabolically more stable analogs of 12-HETE would be useful. We biologically synthesized 20,20,20-trifluoro-12-HETE (20-F3-12-HETE) by incubating enantioselectively synthesized 20,20,20-trifluoro-arachidonic acid with human platelets. The product was identified by UV absorption spectrophotometry and gas chromatography-mass spectrometry. When 1 microgram 20-F3-12-HETE was incubated with 5 X 10(6) human neutrophils for 45 min, only 5% of the analog was metabolized while 66% of 12-HETE was metabolized in the same incubation condition. With 2 X 10(7) neutrophils, 37% of the analog was metabolized at the same incubation condition while 87% of 12-HETE was metabolized. Thus, by blocking omega-oxidation of 12-HETE with fluorine atoms, the stability of 12-HETE was greatly increased. This result indicates that the omega-oxidation is a major pathway for 12-HETE metabolism. The analog demonstrated as much chemotactic activity on human neutrophils as 12-HETE, and binding affinity of the analog for 12-HETE receptor in human epidermal cell was equal to that of 12-HETE. An analog of 12-HETE, which has extended metabolic stability without alteration of neutrophil chemotactic activity and binding affinity, would be a useful tool for studies on pathophysiological role of 12-HETE in inflammatory conditions.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

[Antitumor activity of HO-221, a derivative of benzoylphenylurea against human cancer xenografts in nude mice].

HO-221, a derivative of benzoylphenylurea, is a newly developed anticancer drug which was found to show an excellent antitumor effect against transplantable murine tumors by the novel mechanism of action. This study was designed to evaluate the antitumor effect of HO-221 and to establish the optimum regimen, using seven human gastrointestinal and breast cancers xenografted in nude mice. Better antitumor effect of HO-221 by oral administration was observed when it was suspended in larger volume of the vehicle. Moreover, the effect increased by the multiple intermittent administration compared to the single treatment. Best antitumor effect was observed by oral administration of 75 mg/kg (0.1 ml/10 g mouse body weight) repeated twice weekly for a total of eight times or 300 mg/kg (0.2 ml/10 g mouse body weight) repeated once weekly for a total of four times. The antitumor effects of these two regimens were approximately equal except against H-31, the former regimen being more effective. When the tumor growth inhibition rate (IR) over 58% was rated as "effective", the above two regimens were equally effective against 4 of 7 cancers, H-111, H-154, H-143 and H-31. While HO-221 was not effective to a gastric cancer line, H-81, which was most susceptible to the variety of existing anticancer agents, but effective to another gastric cancer line, H-111, which was relatively resistant to conventional cytocidal agents. From the aspect of chemosensitivity spectrum, this drug revealed a rather different pattern compared to other antimetabolites. Although oral administration volume is limited in small animal model, enhancing its antitumor effect may be possible in clinical application by contriving the method of administration. HO-221 is, thus, considered to be a promising drug for further study.

Administration, Oral↗
PubMed1991

[Combination chemotherapy of HO-221, a derivative of benzoylphenylurea with various anticancer agents against human cancer xenografts in nude mice].

Antitumor effect of HO-221, a derivative of benzoylphenylurea, has been previously studied against seven human cancer xenografts in nude mice established and maintained in our laboratory. In this study, the effect of combination chemotherapy was examined with six of the above seven human cancer cell lines. These consisted of four gastric cancers (H-55, H-111, H-81 and H-154), one breast cancer (H-31) and one pancreatic cancer (H-48). HO-221 was used in combination with one of the following widely used anticancer drugs; mitomycin (MMC), adriamycin (ADM), CDDP, VP-16 and 5-fluorouracil (5-FU). When the tumor growth inhibition rate (IR) by combination of two drugs (at 1/2 MTD for each drug) exceeded both of IR obtained separately with single drug at 1/2 MTD, the combination regimen was rated as showing an additive effect. When IR by combination of two drugs at the same dose level exceeded both of IR obtained separately by MTD of each single drug, the regimen was rated as showing a synergistic effect. Histological changes and side-effects were also taken into consideration for the evaluation of the drug. Combination of HO-221 and MMC produced an additive effect against H-55 and H-111, a synergistic effect against H-81. In the treatment of H-31 which was highly susceptible to these drugs, a remarkable effect was shown in both IR and cellular changes even by combination using 1/2 MTD and 1/4 MTD doses. Combination with ADM at 1/2 MTD for both produced an additive effect against H-111 and H-48. Combination at MTD produced a marked antitumor effect against H-111 and a strikingly remarkable combination effect was confirmed. Combination with CDDP produced an additive effect against H-81 and a synergistic effect against H-154. Moreover, the weight loss by this combination regimen was far less than that by single administration of CDDP at MTD. An additive effect was demonstrated by combination with VP-16. Combination with 5-FU produced minimal combination effect. HO-221 was thus found to have a high antitumor effect by combination with various anticancer agents that are at present widely used clinically. HO-221 is expected to be a promising anticancer drug in its clinical application.

Animals↗
PubMed1991

Lung thallium-201 uptake during exercise emission computed tomography.

To test whether the analysis of lung uptake is worth adding to the interpretation of exercise thallium-201 (201TI) emission computed tomography (ECT), a lung/heart ratio of 201TI uptake was measured from an anterior image during ECT in 25 clinically normal (Group 1), 91 angiographically normal (Group 2), and 265 subjects with coronary artery disease (Group 3). The mean +2 s.d. of ratios in Groups 1 and 2 were the same (0.37). In Group 3, 80 subjects (30%) with increased ratios (greater than 0.37) had higher frequencies of prior infarction and multi-vessel disease, more severe left ventricular dysfunction, and 201TI defects than 185 subjects with normal ratios. Subjects with markedly increased ratios (greater than 0.45) had three-vessel disease more frequently than those with slightly or moderately increased ratios (67% versus 14% or 35%). Thus the measurement of lung/heart ratios may provide information regarding the severity of coronary artery disease and should be added to the routine interpretation of exercise ECT.

Aged↗
PubMed1991

[Combined effect of HO-221 with various antitumor agents against L 1210 leukemia].

Combined effect of N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea, HO-221, with various antitumor agents was studied using L 1210 leukemia in vivo and in vitro. Ten anticancer drugs were chosen from alkylating agents, antitumor antibiotics, antimetabolites and plant alkaloids each. The combined effect was assessed by comparing ILS (increase of life span) in the combined group with the sum of ILS of each single agent. Synergistic effect was considered to exist if ILS of the combination-treatment group exceeds the sum of those in 2 single-treatment groups. The two-drug combination of HO-221 with cyclophosphamide (CPA), adriamycin (ADM), mitomycin C (MMC), vindesine (VDS), vincristine (VCR) or etoposide showed remarkable synergistic effects with 60-days survivors. However, the combination chemotherapy with antimetabolites, 5-fluorouracil (5-FU) and methotrexate (MTX) showed competitive effects. Moreover, the synergistic cytocidal effect in vitro by the clonogenic assay was observed in combination of HO-221 with the same drug using in vivo test. The present results indicate that HO-221 seems to be a useful antitumor agent in combination chemotherapy.

Animals↗
PubMed1991

[An early phase II study of CPT-11 in gynecologic cancers. Research Group of CPT-11 in Gynecologic Cancers].

An early Phase II study of CTP-11, a new derivative of Camptothecin, in gynecologic cancers was carried out by a cooperative study group of 9 institutions. Forty-six patients were enrolled, and there were 14 cases of ovarian cancers, 7 of cervical cancer, 6 of uterine body cancers and 1 of endometrial stromal sarcoma which satisfied study criteria. The response rate in ovarian cancers was 21.4%, and in cervical cancers 42.9%, among an overall rate of 21.4%. Three out of 6 patients with objective response had undergone previous chemotherapies including cisplatin, suggesting that CPT-11 was effective for patients with no response or refractory to these therapies. Leukopenia was a major adverse reaction with an incidence of 60.0% (grade 2 or more). Gastrointestinal symptoms such as nausea vomiting, anorexia and diarrhea were frequently observed (grade 2 or more; 13.3-43.3%). These were generally tolerable except in a few cases. Besides these reactions, alopecia was also observed (33.3%), but severe adverse reactions such as nephropathy were not. These results suggested that CPT-11 was effective against ovarian cancer and cervical cancer. The recommended dose regimen for a late phase II study is considered to be 100 mg/m2 once weekly and 150 mg/m2 once every 2 weeks.

Adult↗
PubMed1991

Naftidrofuryl oxalate improves impaired brain glucose metabolism after microsphere-induced cerebral embolism in rats.

The present study was designed to elucidate possible therapeutic effects of naftidrofuryl on the brain glucose metabolism after cerebral ischemia. Cerebral ischemia was induced by injecting 680 microspheres with a diameter of 48 microns into the right internal carotid artery of the rat. After ensuring the onset of symptoms of stroke on the first day after the operation, the rats were treated with intraperitoneal injections of 15 mg/kg naftidrofuryl oxalate twice a day. The behavioral and metabolic changes of operated rats were monitored up to the 5th day after surgery. The symptoms gradually faded away, from the 3rd day on, after microsphere-induced cerebral embolism. Tissue glucose and glycogen greatly increased after cerebral embolism, suggesting embolism-induced inhibition of glycolysis. To elucidate which steps in the glycolytic catabolism are inhibited after cerebral ischemia, biochemical activities of the glycolytic enzymes in the Embden-Meyerhof pathway and tricarboxylic acid cycle were determined on the 3rd day after surgery. Enzyme activities of hexokinase, phosphofructokinase and pyruvate kinase were not inhibited, but rather increased slightly after cerebral embolism. Malate dehydrogenase activity in the brain mitochondria was markedly increased after microsphere-embolism, whereas other enzyme activities in the tricarboxylic acid cycle were never inhibited by the cerebral embolism. Treatment of naftidrofuryl resulted in an appreciable reverse of the brain glucose and glycogen levels and a substantial recovery of altered enzyme activities to normal levels in the Embden-Meyerhof pathway and tricarboxylic acid cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

IgA glomerulonephritis in a patient with renal cell carcinoma.

A case of IgA glomerulonephritis associated with renal cell carcinoma is reported. A 61-year-old male was admitted because of a left renal mass and proteinuria. A diagnosis of renal cell carcinoma was made by computed tomography and angiography. Left radical nephrectomy was performed. Microscopically, the tumor tissue revealed renal cell carcinoma of the clear cell type. Light, immunofluorescent and electron microscopic examinations demonstrated characteristic features of IgA glomerulonephritis. The proteinuria and hematuria disappeared 8 months after removal of the tumor. These findings suggest that the IgA glomerulonephritis in our patient may have been attributable to an immune response against the renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1991

[A case of malignant pericardial mesothelioma detected by gallium-67 scintigraphy].

A case of malignant mesothelioma originated from pericardium was reported. A 76 year-old male who complained of dyspnea showed cardiomegaly (CTR = 68%) and bilateral pleural effusion in chest plain X-ray film. Gallium-67 (67Ga) scintigraphy revealed doughnut-like accumulation on cardiac apical site and mediastinal accumulation. Cytological examination of pericardial effusion revealed class V. Autopsy confirmed diagnosis of malignant pericardial mesothelioma. 67Ga scintigraphy may be useful in diagnosis of malignant pericardial mesothelioma.

Aged↗
PubMed1991

[Evaluation of cardiotoxicity in new anthracycline analog ME 2303. ME 2303 Study Group].

ME 2303 is a new anthracycline analog which differs from adriamycin in the sugar moiety. ME 2303 displays a higher antitumor activity against L 1210 and P 388 Leukemia than adriamycin. To evaluate the cardiotoxicity of ME 2303, ECG tracings (21 patients) and Holter ECGs (9 patients) were recorded before and after the administration of ME 2303 for various malignancies (mean dose 123.8 mg/m2), and some of the electrocardiographic parameters were analyzed. Control ECGs were normal in 17 patients, in 4 patients minor ECG findings like sinus tachycardia (2 patients), low voltage (1 patient) and flattening of the T wave (1 patient) were observed. After treatment, no relevant ECG changes were observed except one case who showed a flat T in pretreatment ECG. In this patient developed ST-T changes were seen after treatment. The basic rhythm was sinus rhythm in all of the cases, and the heart rate showed no significant changes. ME 2303 had no effects on the specialized conduction system. With regard to arrhythmia, no increase in number and severity was observed. In Holter ECG no development of ST-T changes was seen after treatment.

Adult↗
PubMed1990

Regulatory function for murine intraepithelial lymphocytes. Two subsets of CD3+, T cell receptor-1+ intraepithelial lymphocyte T cells abrogate oral tolerance.

The murine intraepithelial lymphocyte (IEL) population is enriched in T cells that express the gamma delta-TCR, however, the biologic function served by these T cells remains obscure. IEL are considered to be major effector cells in mucosal immunity, and we have investigated whether IEL subsets could reverse orally induced systemic unresponsiveness (oral tolerance; OT) and support secondary type responses when adoptively transferred to mice orally tolerized with SRBC. When purified CD3+ IEL from mice orally primed with SRBC were transferred to adoptive hosts and challenged with SRBC, splenic IgM, IgG1, IgG2b, and IgA anti-SRBC plaque-forming cell responses were observed. However, CD3+ IEL from HRBC orally primed mice did not abrogate SRBC induced OT. Further, HRBC-primed CD3+, IEL converted HRBC-specific OT but not SRBC-specific OT. CD3+ IEL could be separated into four subsets based on expression of CD4 and CD8. CD3+, CD4-, 8+ T cells were the major subset (74.5%), with smaller numbers of CD4- and CD8- (double negatives, DN) (7.8%), CD4+, 8- (7.6%) and CD4+, CD8+ (double positives) (10.1%) T cells. Interestingly, both the CD3+, CD8+, and the CD3+, DN IEL subsets abrogated OT, resulting in significant IgM, IgG1, IgG2b, and IgA anti-SRBC plaque-forming cell responses when adoptively transferred to mice with OT. However, neither CD3+, CD4+, CD8-, nor double positive T cells affected OT when studied in this system. The CD3+, CD8+ IEL subset could be further separated into Thy-1+ (16.6%) and Thy-1- (83.4%) cells; adoptive transfer of Thy-1- cells abrogated oral tolerance whereas the Thy-1+ subset was without effect. When the expression of TCR on IEL with this biologic function was determined by use of monoclonal anti-alpha beta TCR (H57.597), TCR2-, CD3+ IEL possessed immunoregulatory function whereas the alpha beta-TCR+ (TCR2+) fraction did not abrogate OT. Immunoprecipitation of membrane fractions obtained from purified CD3+, CD4-, CD8+, Thy-1- IEL with polyclonal anti-delta peptide (Tyr-Ala-Asn-Ser-Phe-Asn-Asn-Glu-Lys-Leu) antibody revealed bands of 45 and 35 kDa, corresponding to the delta- and gamma-chains, respectively. These results suggest that gamma delta-TCR+ IEL possess a regulatory function, namely the restoration of immune responses in a state of oral tolerance. Further, both CD3+, CD4-, CD8+, Thy-1-, and CD3+, DN IEL T cells exhibit this effector contrasuppressor function.

Administration, Oral↗
PubMed1990

Analysis of Th1 and Th2 cells in murine gut-associated tissues. Frequencies of CD4+ and CD8+ T cells that secrete IFN-gamma and IL-5.

After Ag and/or mitogen stimulation, cloned mouse Th1 and Th2 cells produce different cytokines that contribute to induction of particular B cell isotype responses. In this regard, IL-5 produced by Th2 cells has been shown to enhance IgA synthesis in LPS-triggered splenic (SP) B cell or in unstimulated Peyer's patch (PP) B cell cultures. This raises the possibility that Th2 cells may occur in higher frequency in gut-associated tissues, because B cells in these areas are committed to IgA synthesis. We have used an ELISPOT assay to detect individual T cells producing IFN-gamma or IL-5. For the IL-5 assay, the mAb TRFK-5 and biotinylated TRFK-4 were used in coating and detection, respectively, whereas the mAb R4-6A2 and biotinylated XMG 1.2 were similarly used for enumeration of IFN-gamma-specific spot forming cells (SFC). Specificity of each assay was tested by using Con A-activated, cloned Th1 (H66-61) or Th2 (CDC-25) cells, where the Th1 cells only produced IFN-gamma SFC and the Th2 cells only gave IL-5-specific spots. Further, preincubation of biotinylated TRFK-4 or XMG 1.2 with rIL-5 or IFN-gamma, respectively, abrogated the formation of specific spots when tested with Con A-activated SP CD4+ T cells. Both IFN-gamma and IL-5 were produced de novo, because treatment of T cells with cycloheximide inhibited both IFN-gamma and IL-5 SFC. We have assessed the numbers of T cells spontaneously secreting these cytokines in PP and in lamina propria and intraepithelial lymphocyte (LPL and IEL) populations. Moderate levels of IL-5 SFC occurred in the IEL subset, whereas higher levels existed in the LPL population. Although significant numbers of IFN-gamma SFC (Th1-type) were also seen in LPLs, the frequency of IL-5 SFC was always higher (Th1:Th2 in LPL = 1:3). In IELs, equal numbers of IFN-gamma and IL-5 SFC were seen. Interestingly, CD8+ IEL T cells produced these two cytokines. In contrast, T cells freshly isolated from PP, an IgA inductive site, contained smaller numbers of IL-5- or IFN-gamma-secreting cells and SP T cells had essentially no SFC. When PP or SP T cells were stimulated with Con A, significant and approximately equal numbers of IFN-gamma- and IL-5-producing cells appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗