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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 667 records · Page 37Linked to original sources
PubMed1990

[Gastrointestinal toxicity induced by anticancer drugs--including new antiemetic drugs].

In a cross-over design of a study of prevention of emesis induced by cancer chemotherapy done in Saitama Cancer Center, the efficacy of oral lorazepam was superior to that of i.v. domperidone. And then, we proceeded a parallel study with use of oral lorazepam and oral domperidone. However, in this situation lorazepam was not superior to domperidone despite accrual of more than 60 patients. Recently, a multi-institutional study has been started in October of 1988 in an evaluation of the efficacy and safety of the new anti-emetic drug of a 5HT3 receptor antagonist, ondansetron. Two methods of its administration were designed. In one study ondansetron was given 2 hr prior to non-platinum chemotherapy as an 2 or 8 mg dose by oral administration, followed by receiving it 6 hr and 12 hr after chemotherapy. In another study, it was given 15 min prior to cisplatin including chemotherapy as an 2 or 8 mg loading dose by i.v. injection over 5 min, followed by continuous infusion at a rate of 0.25 mg/h or 1 mg/h for 24 h, respectively. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24h after administration of chemotherapy and by an assessment of nausea during the same period. This time the major efficacy category was adopted, which is made up of the complete responder and major responder categories of both vomiting and nausea. 19 patients were evaluable for efficacy in the non-platinum group; the major efficacy rates showed 45% in 2 mg-given group and 88% in 8 mg-given group, respectively. 108 patients were evaluable for efficacy in the cisplatin group: the major efficacy rates showed more than 70% in both 2 mg and 8 mg-given group. However, in the patients given more than 75 mg/mg2 of cisplatin, the major efficacy rates were 55% in the 2 mg-given group, compared to 73% in the 8 mg-given group. Ondansetron was well tolerated, with no significant drug-related adverse events.

Adult↗
PubMed1990

[A phase I study of weekly administration of CPT-11 in lung cancer].

A clinical study of weekly administration of CPT-11, a semi-synthetic derivative of Camptothecin, was performed in patients with advanced lung cancer to determine the optimal dose for a weekly single dose schedule. Sixteen out of 19 patients enrolled were evaluable. The starting dose was 50 mg/m2 and gradually escalated to 100, 125 and 150 mg/m2. CPT-11 was given by intravenous infusion for 90 minutes every week. The maximum tolerated dose for this schedule was estimated to be 125 mg/m2. The dose-limiting toxicity was leukopenia with median nadir of 2,900/mm3, median day to nadir of 21, and median day to recovery of 7. Other major toxicity was gastrointestinal upset, but was mild and tolerable. Objective tumor responses were observed in four patients, three with non-small cell carcinoma and one with double cancer (small and non-small cell carcinoma). The responding patients were treated at a dosage of 100 mg/m2 or more. The recommended dose for a phase II study is considered to be 100 mg/m2 iv infusion for a weekly single-dose schedule.

Aged↗
PubMed1990

[Correlations among the renal parenchymal components and renal function with IgA-GN; age related changes].

To clarify and evaluate the changes by aging to renal parenchyma of IgA nephropathy with normal renal function (serum creatinine levels less than or equal to 1.5 mg/dl), we compared morphological findings and renal function in 100 adult patients with IgA nephropathy similarly distributed in each decade of age including over 60 y.o.. The following histological parameters were investigated; glomerular sclerotic index calculated a mean for total glomeruli, tubulointerstitial damage or interstitial volume measured by the point-counting method, luminal narrowing index by intimal thickening of arterioles determined morphometry. Tubulointerstitial damages were significantly correlated to aging with a direct linear worsening. Luminal narrowing of arterioles rapidly worsened with age after 40 y.o. who were frequently associated with chronic hypertension. The patients over 60 y.o. had a significant correlation between luminal narrowing of arterioles and glomerular sclerotic index, though those were statistically no related in patients less than 60 y.o.. Glomerular sclerotic index was significantly related with tubulointerstitial damage at all decades except for thirtieth decade. Serum creatinine level was well correlated with glomerular sclerotic index and tubulointerstitial damage, respectively; increase of those indices may indicate poor prognosis. We concluded that ischemic glomerular sclerosis by mean narrowing of afferent arterioles may appear after 60 y.o., probably due to insufficiency of autoregulation for glomerular circulation. Luminal narrowing of arterioles in patients less than 60 y.o. may not reflect to be a main cause for ischemic damage of glomerulus. Therefore it may not be a indicator for renal prognosis in patients with IgA nephropathy less than 60 y.o.

Adult↗
PubMed1990

[Combination chemotherapy with etoposide, ADM, and CDDP (EAP) for advanced gastric cancer].

EAP therapy has been performed on 50 cases of advanced gastric cancer from January 1988 to September 1989. Adriamycin 20 mg/m2, Cisplatin 40 mg/m2 and Etoposide 100 mg/m2 were administered on day 1 and 7, 2 and 8, and 4, 5 and 6, respectively, with not less than 2 courses every 3 to 4 weeks. Complete success, PR, NC and PD were obtained in 48, 21, 20 and 7 cases, respectively, the rate of effectiveness being 43.8% with a confidence interval 95% of 30-58%. The rate of effectiveness by lesions for evaluation was high (30.4, 100, and 50% for primary lesion, Virchow's lymphnodal metastasis and liver metastasis, respectively). MST was 5.1 months for EAP therapy, which was highly effective but led to no prolonged survival period. Thus, it is thought that good control of leukopenia, a dose limiting factor remains to be examined.

Adult↗
PubMed1990

[Mechanism of antitumor effect of a benzoylphenylurea derivative, HO-221].

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We previously reported HO-221 showed significant antitumor activities against various experimental tumor models, and was especially effective against the solid tumor. In this report we studied the mechanism of action of the compound. The inhibitory activity of HO-221 and 6 kinds of antitumor agents on DNA polymerase alpha was examined in vitro. HO-221 inhibited DNA polymerase alpha activity strongly. From the comparison with IC50 values of individual agents, the inhibitory activity of HO-221 was almost equivalent to aphidicolin and ara-CTP. By double reciprocal plot analysis, the inhibition of HO-221 was found to be non-competitive with the dCTP unlike that of aphidicolin and ara-CTP. Furthermore, HO-221 showed almost no effect on RNA polymerase activity and the protein synthesis. The effect of HO-221 on cell cycle progression of HL-60 cells was examined by flow cytometry analysis. The compound accumulated cells at S phase at a low concentration. The compound showed accumulation of cells in G1, G1-S and G2 + M phases. At higher concentrations, HO-221 increased the G1 phase of tumor cells, stopping the cell cycle progression. Therefore, G1 and S phase accumulation by HO-221 was considered to be correlated with the inhibition of DNA polymerase alpha dependent DNA synthesis. These results suggest that HO-221 is a novel antitumor agent with different mechanism of action from the known antitumor agents.

Animals↗
PubMed1990

[Antitumor effect of a benzoylphenylurea derivative HO-221].

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.

Animals↗
PubMed1990

Comparisons of interval breast cancers with other breast cancers detected through mass screening and in outpatient clinics in Japan.

In a nation-wide collaborative study on mass screening for breast cancer, we collected 152 cases of interval breast cancer diagnosed at 35 hospitals or clinics distributed throughout Japan. The definition of interval breast cancer used in the present study is "breast cancer cases which were diagnosed as having 'no malignant findings' in a previous screening for breast cancer but subsequently diagnosed as 'breast cancer' at a hospital or medical clinic within two years of the previous screening." The clinical stages and prognoses of these interval cancer were analyzed and compared with those of other breast cancers detected through mass screening and in outpatient clinics. In the clinical staging of interval breast cancer, Tis (non infiltrating cancer) accounted for only 2.1%, compared to 8.0% in cases detected through mass screening. At stage I 43.4% were interval breast cancers compared to 32.9% breast cancers detected through mass screening and 25.4% diagnosed in outpatient clinics. The stage differences between interval breast cancers and breast cancers detected through mass screening were not statistically significant. Five-year survival rates were 85.6% for interval breast cancers, 91.7% for breast cancers detected through mass screening and 84.7% for breast cancers diagnosed in outpatient clinics. Ten-year survival rates were 75.9, 80.5 and 78.1%, respectively, suggesting the interval breast cancer cases to show a similar prognosis to that of breast cancer cases diagnosed in outpatient clinics. The differences in five- and 10-year survival rates among the three groups were not statistically significant. From the present study we were not able to confirm the general belief of interval cancer being more aggressive in nature and showing a poorer prognosis than cancer detected through periodic screening. The reasons for this are discussed.

Adult↗
PubMed1990

[Antitumor activities of ME 2303 on human gastrointestinal cancer xenografted to nude mice].

The antitumor activity of ME 2303 was evaluated on 3 human stomach and 3 colon cancers xenografted to nude mice, which were established in our laboratory. The activity was compared with that of doxorubicin in terms of the inhibition of tumor growth and the histopathological changes. The dosage of ME 2303 was 35 or 50 mg/kg and that of doxorubicin was 5 mg/kg. Both drugs were administered intravenously 4 times at 5-day intervals. Thirty-five mg/kg of ME 2303 was effectively inhibited tumor growth against 3 lines, with marked efficacy against 2 lines. On the other hand, 50 mg/kg of ME 2303 was also effective against 4 lines tested (2 each of gastric and colorectal cancers), with marked efficacy against 3. In all, ME 2303 was more effective than doxorubicin except one of stomach cancer. The histopathological findings also revealed that 35 mg/kg of ME 2303 was equal or slightly superior to doxorubicin in efficacy. The side effects of ME 2303 such as weight loss were as mild as those with doxorubicin, except in the female mice administered 30 mg/kg of ME 2303 and no other adverse effect was observed. ME 2303 seems promising for clinical application in human since the increased efficacy in nude mice human xenograft might be found after more adequate modification of the dosage and administration schedule.

Adenocarcinoma↗
PubMed1990

[The persistence and proliferation of tumor-xenografts implanted under the renal capsule of immunocompetent mice, cyclosporin A-treated mice and nude mice].

The subrenal capsule assay for cancer chemotherapy was performed, using tumor-specimens of 19 patients' cancers. Twelve tumor-specimens were implanted simultaneously under the renal space of immunocompetent CDF1 mice, cyclosporin A (CsA) 60 mg/kg treated mice, and BALB/c-nu/nu (nude) mice. The persistence and growth of implanted tumor-xenografts of each mouse, was evaluated, on day 6 and 9 after inoculation. The tumor-xenografts implanted under the renal space of immunocompetent mice, grew larger on days 6 in 9 cases, but histological evaluation showed tumor tissues were in various degree replaced by host reactive tissues. Host reaction in CsA-treated mice or nude mice was suppressed almost completely, but the persistence and proliferation of tumor-xenografts of both mice was varied, depending on the nature of original tumors. The judgment for cancer chemotherapy on our modified SRC assay was almost similar between CsA-treated mice and nude mice, but there were some cases in which macroscopical judgment didn't correspond with histological effect. The DNA synthesis of tumor-xenografts of 7 patients, was examined by using sequential changes of BrdU labeling index (LI) in the renal space of CsA-treated mice. It was showed LI rather indicated the nature of original tumors itself.

Animals↗
PubMed1990

[Enhanced effect of intra-arterial adriamycin administration in combination with degradable starch microspheres on an intra-arterial chemotherapy model of nude rats transplanted of human gastric cancer].

Enhancement of the antitumor effects of adriamycin (ADR) by concomitant use of degradable starch microspheres (DSM) and pharmacokinetics of ADR in combination with DSM was investigated. An intra-arterial chemotherapy model of the nude rats transplanted of human gastric cancer xenografts (H-154) in the hind-limbs was used for this study. Drug was administered through a catheter inserted into the carotid artery with the tip in the common iliac artery. In the pharmacological study, increase of regional uptake of ADR and decrease of systemic distribution of ADR were recognized in some degree. DSM 30 mg/kg, which caused temporary arrest of blood flow in the tumor, had an only weak effect on tumor growth. ADR 3 mg/kg mixed with DSM 30 mg/kg was more effective than ADR 3 mg/kg solution. Furthermore, mixture of ADR 2 mg/kg and DSM 30 mg/kg had a greater effect on tumor growth than ADR 2 mg/kg following DSM 30 mg/kg. It seems that embolization by DSM, retention of ADR in regional tissues and cytotoxic effect of ADR have contributed to such a strong effect of ADR mixed with DSM.

Animals↗
PubMed1990

[Antitumor activity and metabolism of BOF-A2, a new 5-fluorouracil derivative, with human cancers xenografted in nude mice].

Antitumor activity of BOF-A2, a new 5-fluorouracil (5-FU) derivative, was evaluated with human gastric (H-111 and H-81), colorectal (H-143), pancreatic (H-48) and breast (H-31) cancers xenografted in nude mice. Twenty-five consecutive oral administration of BOF-A2 at 17.5 to 30 mg/kg over 4 weeks caused marked inhibition or regression (over 92% of inhibition rate) to the growth of H-81, H-143 and H-31 cancers. Moreover, BOF-A2 effected to both H-111 and H-48 which have low sensitivity to 5-FU and its known derivatives. Throughout the experiments, the mice seemed to tolerate the consecutive administration of BOF-A2 without severe toxicity. When BOF-A2 was given orally, 5-FU levels in the blood of mice was notably durative for a long time as compared to 5-FU and UFT. Furthermore, 5-FU levels in the tumor tissue tended to increase and persist much more than those in the blood. This maintenance and persistence of objective level of 5-FU in the blood would be concluded to produce a high antitumor effect of BOF-A2 against human cancers xenografted in nude mice.

Administration, Oral↗
PubMed1990

[Phase I clinical study of CPT-11. Research group of CPT-11].

CPT-11 is a new derivative of Camptothecin. Phase I clinical study of single administration with CPT-11 was carried out by a cooperative study group. Starting from 50 mg/m2 (n), dose was escalated to 350 mg/m2 (7n). Dose limiting factor was found to be a decrease in WBC counts (especially in neutrophils), and MTD was presumed to be 250 mg/m2 or more. Nadir of WBC counts was observed after about a week, and it took 2-3 weeks for recovery. The decrease in platelet number and hemoglobin content was mild. Other side effects included G-I toxicities, alopecia, etc. However, no toxic effects on the heart, kidney, lung were observed. SN-38, main metabolite of CPT-11, was observed in blood, and excreted rapidly. Anticancer effects were suggested with dose of 165 mg/m2 or more against colon cancer, gastric sarcoma, melanoma and lung cancer. It is suggested that the optimal dose schedule for an early Phase II study is 200 mg/m2 every 3-4 weeks. However, not only leukopenia but also marked G-I toxicities being noted in some cases, care should be taken for those side effects.

Adult↗
PubMed1989

Multifactorial analysis of parameters influencing chemosensitivity of human cancer xenografts in nude mice.

The results of single-agent chemotherapy, with 11 anticancer agents, of 15 human gastro-intestinal and breast cancer lines xenografted into nude mice indicate inherent individuality of chemosensitivity spectrum of each tumor. The following 9 parameters have been measured as factors possibly relevant to chemosensitivity of tumor tissue or tumor-bearing mice: grade of histological differentiation, vascularity, percentage of necrosis, VDT, 3H-thymidine LI, human LDH activity in the cancer tissue, tissue/serum LDH ratio, TdR Pase activity, and serum CEA. These parameters exhibited presumably constant values for each tumor line. Chemosensitivity, i.e., inhibition of tumor growth by a given drug, was used as the dependent variable, and values of the 9 parameters in each cancer as the explanatory variables. Multiple regression analyses with stepwise deletion were performed for each of the 11 drugs. The equations for 8 drugs exhibited coefficients of determination of over 70%, and in particular those for M-83 (a derivative of mitomycin C), nimustine hydrochloride and doxorubicin exceeded 80% by equations with 3-4 parameters. Consequently, the estimated value for each line of effectiveness derived from the equations for these 8 drugs showed remarkable coincidences with the actual values for the inhibition rates of the corresponding drugs.

Animals↗