PubMed Health⌕ Search

Biomedical subjects

F Fujita

Publications and source records attributed to F Fujita.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Antitumor activity of LY 188011, a new deoxycytidine analog, against human cancers xenografted into nude mice].

LY 188011 (gemcitabine hydrochloride) was evaluated for its antitumor effect in fifteen human tumors xenografted in nude mice from seven gastric, two colorectal, two breast, two lung and two liver cancer lines, in the latter four of which the results were compared with those obtained with mitomycin C. LY 188011 significantly reduced the volume of tumor xenografts in seven lines, including drug-resistant colorectal and lung cancer lines. The antitumor effect of LY 188011 was further confirmed by pathological observation. Moreover, LY 188011 has shown to be significantly more potent in two lung cancer models than mitomycin C. Administration of LY 188011 induced less side effect; early loss of body weight was observed in four lines out of fifteen tested. These data suggest that LY 188011 seemed to be an excellent candidate in clinical trials for the treatment of cancer.

Animals↗
PubMed1993

[Antitumor activity of combination treatment of BOF-A2 with CDDP against human lung cancers xenografted in nude mice].

CDDP, commonly used in cancer chemotherapy, behaves as not only effector but also modulator of 5-FU when combined with 5-FU and the derivatives. Therefore, the antitumor activity of combination treatment of BOF-A2, a new 5-fluorouracil derivative, with CDDP was evaluated with two human lung cancers (H-74 and LC-376) xenografted in nude mice. BOF-A2 was orally administered at 30 mg/kg (MTD) or 15 mg/kg (1/2 MTD) 3 times a week totally twelve times, and CDDP was administrated interperitoneally at 5 mg/kg (MTD) or 2.5 mg/kg (1/2 MTD) once a week totally 4 times. The antitumor effect of combination of two drugs at the 1/2 MTD was effective to H-74 and markedly effective to LC-376, and the effect was more remarkable than each drug administered individually at the 1/2 MTD, and the combination effect was additive. The effect by the combination was not synergistic but showed a similar activity compared with single drug given individually at the MTD. Moreover, the side effect of combination of the 1/2 MTD was less than group given MTD of CDDP in terms of body weight loss. These data suggests a clinical usefulness of combination BOF-A2 with CDDP against lung cancer.

Adenocarcinoma, Papillary↗
PubMed1993

[Antitumor activity of BOF-A2, a new 5-fluorouracil derivative, against human cancers xenografted in nude mice by intermittent administration].

Antitumor effects of BOF-A2 given intermittently was evaluated with human gastric (H-111, H-83), colorectal (H-110, H-143) and lung (H-74, LC-376) cancers xenografted in nude mice and compared with those by continuous administration. BOF-A2 was orally given 3 or 4 times per week at 30 or 35 mg/kg over 4 weeks. This drug was effective to 5 strains except H-110 (IR > or = 58%), remarkably effective to H-81 and H-143 (IR > or = 80%) and caused tumor regression in mice bearing H-81 especially. Moreover, the drug was effective to H-74 which is rather insensitive to 5-FU and its known derivatives. When the drug was given orally to nude mice xenografted LC-376, 5-FU levels in the tumor tissue was notably durative for a long time as compared to UFT. It would be concluded that BOF-A2 was much effective to insensitive tumor to fluorinated pyrimidines or other anticancer, because of persistence of high levels of 5-FU in the tumor tissue. On the other hand, diarrhea which is caused by other fluorinated pyrimidines or consecutive administration of BOF-A2, was mild by the intermittent administration of BOF-A2.

Administration, Oral↗
PubMed1993

[Accordance of the chemosensitivity between clinical specimens and their xenografts in nude mice by SDI test and the value of in vivo chemosensitivity test using nude mice].

We assessed the sensitivity to anticancer drugs by SDI (succinate dehydrogenase inhibition) test with 11 clinical specimens obtained from operated patients. The results were compared with those of xenografted specimen in nude mice, using the adjuvant part of the specimens assayed. Chemosensitivity of clinical specimens against 3 drugs is mitomycin (MMC), adriamycin (ADM) and cisplatin (CDDP), showed a good accordance (73%) with those of xenografted tumors. The drug sensitivity was considered to be one of the features of original tumors and to be well preserved in the xenografts in nude mice. We also studied in vivo experimental chemotherapy on 19 tumor lines in nude mice to compare the chemosensitivity with clinical response to the same chemotherapy observed in each donor patient. A close correlation (83% on responder, 100% on non-responder and the overall predicting accuracy rate were 95%) was shown, suggesting in vivo nude mouse assay having an excellent predictability for clinical results.

Adult↗
PubMed1992

Airflow study of pathologic larynges using a constant temperature anemometer: further experience.

Phonatory airflow was recorded in 361 laryngeal disease patients and 59 normal subjects by using a constant temperature anemometer to measure Isshiki's proposed parameter, the AC/DC percentage. The pathologic groups displayed AC/DC percentage values smaller than those of the normal group. The value differentials observed among the various diseases suggest that the AC/DC percentage may reflect the vibrational capacity of the vocal cords.

Female↗
PubMed1991

Gender differences in negative affect and well-being: the case for emotional intensity.

Affect intensity (AI) may reconcile 2 seemingly paradoxical findings: Women report more negative affect than men but equal happiness as men. AI describes people's varying response intensity to identical emotional stimuli. A college sample of 66 women and 34 men was assessed on both positive and negative affect using 4 measurement methods: self-report, peer report, daily report, and memory performance. A principal-components analysis revealed an affect balance component and an AI component. Multimeasure affect balance and AI scores were created, and t tests were computed that showed women to be as happy as and more intense than men. Gender accounted for less than 1% of the variance in happiness but over 13% in AI. Thus, depression findings of more negative affect in women do not conflict with well-being findings of equal happiness across gender. Generally, women's more intense positive emotions balance their higher negative affect.

Adult↗
PubMed1991

[Predictability of preclinical evaluation of anticancer drugs by human gastrointestinal cancer--nude mouse panel].

We evaluated the predictability to clinical response of experimental effects of various anticancer agents on human cancer--nude mouse panel established in our department. The human cancer lines used were 12 gastric, 4 colorectal, 3 breast, 2 pancreatic cancers and 1 melanoma xenografted into BALB/c athymic nude mice under SPF conditions. Seven mice each with equivalent mean volume of sc inoculated tumor (about 100 mm3) were subjected to the treatment and control groups. Experimental treatment was conducted daily 25 times for antimetabolites, and intermittently 5 times once or twice a week for other drugs. Dosage of each drug adopted was maximal tolerated dose predetermined for the treatment schedule. Four weeks after the initiation of treatment, the therapeutic effect of each experiment was evaluated by the tumor growth inhibition rate (IR) based on the comparison of mean tumor weight between the 2 groups. When the IR was greater than 58%, the drug was evaluated as effective. The clinical response rate of each drug was referred from the result of the phase II study. Direct comparison of effects on 16 experimental chemotherapies in xenografts with responses to the corresponding clinical therapy of each donor patient revealed a fairly high accordance rate (94%). To elucidate the value of human cancer--nude mouse panel as the preclinical secondary screening, the response rates of 8 anticancer drugs treated to 15 cancer xenografts were compared with the cumulative clinical data available in each drug. Generally, the response rates of the human cancer xenografts to the drugs showed fairly good correlations with the cumulative clinical response rates of the corresponding drugs to the same organs. Using this panel, preclinical examinations of 6 new agents under development, including 254 S and other 2 CDDP derivatives, were performed in expectation the positive correlation with further clinical data.

Animals↗
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↗
PubMed1990

[Relationship between antitumor activity and the inhibition of thymidylate synthase after oral administration of UFT in nude mice bearing human tumor].

We studied the relationship between antitumor efficacy of UFT, which is a most widely used drug among fluorinated pyrimidines recently, and its effect on the content and the inhibition rate of thymidylate synthase (TS) in 15 human tumor xenografts derived from stomach, colon, breast and pancreatic cancer patients. There was a linear relationship between the content of TS and tumor mass doubling time (MDT). It may be shown that TS content reflects the growth rate of tumor cells. It should be stressed that tumor growth inhibition rate (TGIR), induced by UFT, correlated well with the inhibition of TS (TSI), particularly in the stomach and breast cancer. These results demonstrate that the measurement of inhibition rate of TS is important for the prediction and evaluation of clinical efficacy of UFT.

Administration, Oral↗
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

[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↗
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↗
PubMed1989

[Synthesis of thieno[2,3-d]pyrimidine derivatives and their antifungal activities].

4-Chlorothieno[2,3-d]pyrimidines were prepared by the chlorination of 4-oxo-3,4-dihydrothieno[2,3-d]pyrimidines with phosphoryl chloride. 4-Oxo-3,4,5,6,7,8-hexahydro[1]-benzo- and 4-oxo-6-phenylthieno[2,3-d]pyrimidine were synthesized by the cyclization of 2-acylaminothiophene-3-carboxamide derivatives with base. 2-Methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine was prepared by the treatment of 2-methyl-4-trichloromethylthieno-[2,3-d]pyrimidine with sodium hydroxide in aqueous methanol. A series of 4-alkylamino- and 4-arylaminothieno[2,3-d]pyrimidines were synthesized by the nucleophilic substitution of 4-chlorothieno[2,3-d]pyrimidines with various amines. These compounds were evaluated for antifungal activity against Piricularia oryzae. The preventive effects on Rice blast, Sheath blight, and Cucumber powdery mildew were also determined by pot tests.

Drug Resistance, Microbial↗
PubMed1989

[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↗