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Biomedical subjects

O Abe

Publications and source records attributed to O Abe.

At least 199 records · Page 11Linked to original sources
PubMed1986

Differential inhibitory properties of dog and human alpha 1-proteinase inhibitors.

Dog alpha 1-proteinase inhibitor (alpha 1-PI) was found to be an effective inhibitor of bovine chymotrypsin and also of porcine pancreatic elastase as in the case of human inhibitor. The dog inhibitor inactivated both proteinases at a molar ratio of 1:1. However, compared to the human inhibitor, dog alpha 1-PI was a relatively poor inhibitor of bovine trypsin. The association rate constants (kass) of the interactions of dog alpha 1-PI with bovine chymotrypsin and with porcine elastase were determined to be 6.9 +/- 0.3 X 10(6) M-1 s-1 and 6.4 +/- 0.1 X 10(5) M-1 s-1, respectively. These values are 1.3- and 2.7-fold higher than the corresponding values for the human inhibitor. On the other hand, kass for the dog inhibitor with bovine trypsin (2.6 +/- 0.3 X 10(4)M-1 s-1) was found to be about 5 times smaller than that of the human inhibitor.

Amino Acid Sequence↗
PubMed1986

[Combination cancer chemotherapy of human gastric and colon carcinomas in nude mice--sequential cancer chemotherapy involving mitomycin C and tegafur].

Three human tumor xenografts serially transplanted into nude mice were used for an experimental combination cancer chemotherapy consisting of mitomycin C (MMC) and tegafur (FT-207). The strains used for the experiments were two gastric (St-4 and St-15) and one colon (Co-3) carcinomas. The minimal effective doses of MMC were administered i. p. 24h after the s. c. tumor inoculations followed by 60 mg/kg of FT-207 in the three different modalities i. p. These were (A) daily administration of FT-207, (B) FT-207 only, 24h after MMC treatment and (C) FT-207 only, 5 days after MMC treatment. The antitumor effect assessed by the tumor weight at the end of the experiment was found to be (A) divided by (B) greater than (C), whereas the total administration doses of FT-207 were (A) greater than (B) = (C). As this result suggested the significance of FT-207 given 24h after MMC, flow cytometric analysis of St-15 tumor was conducted 24 and 48 h after the MMC treatment. It was observed that the incidence of 2n cells was depressed and the amount of 4n cells increased by MMC, indicating the recruitment of tumor cells into the proliferating phase. Because these recruited cells were thought to be sensitive to FT-207, it was supposed that the antitumor effect was elevated when FT-207 was given 24h after MMC. This semi-synchronized combination cancer chemotherapy involving MMC and FT-207 might therefore be useful for clinical application.

Adenocarcinoma↗
PubMed1986

Cell kinetics and chemosensitivity of human carcinomas serially transplanted into nude mice.

Six human carcinoma xenografts serially transplanted into nude mice were used for the study of chemosensitivity and cell kinetics. Three gastric carcinomas (St-4, St-40 and H-111), two colon carcinomas (Co-3 and Co-4) and one breast carcinoma (MX-1) were inoculated into the subcutaneous tissue of BALB/cA nude mice. The maximum tolerable doses of mitomycin C (MMC), adriamycin (ADM), cyclophosphamide (CPA) and 5-fluorouracil (5-FU) were administered when the tumor weights reached 100-300 mg. The response rates of the tumor to these drugs were found to be 3/6 for MMC, 2/6 for 5-FU and 1/6 for ADM and CPA. Percent labeled mitosis curves obtained from 3H-thymidine pulse labeling were analyzed by the method of Quastler and Sherman. It was found that the antitumor effect of MMC was closely correlated with the growth fractions of the tumors (r = -0.98, P less than 0.001), and it appeared that the tumor cells were more sensitive to MMC in the resting stages during the proliferating phase than in the other cell cycle phases. Cell kinetics is considered to be an important factor in determining chemosensitivity, and the system of human tumor xenografts-nude mice seems to be a suitable experimental model for investigating the correlation between cell kinetics and chemosensitivity in vivo.

Animals↗
PubMed1986

[Phase II study of epirubicin on breast cancer: a cooperative group study].

A phase II multicenter clinical study of epirubicin, a new anthracycline anticancer agent, was carried out in 46 patients with advanced breast cancer. The treatment schedule consisted of either 60 mg/m2 every three weeks or 40 to 50 mg/m2 on day 1 and day 8 every four weeks. Objective responses were observed in 23.7% of 38 evaluable patients (1 CR and 8 PR). Response rates according to previous chemotherapy were 50.0% (4/8) in previously non-treated patients and 36.4% (4/11) in patients previously treated with non-anthracyclines. The major adverse effect was bone-marrow suppression; leukopenia was observed in 82.1% of patients, anemia in 53.8% and thrombocytopenia in 20.0%. Other toxicities frequently observed were anorexia (55.0%), nausea-vomiting (55.0%) and alopecia (66.7%), but these seemed to be milder than those produced by doxorubicin.

Adult↗
PubMed1986

[Clinical study of clonogenic assays--with reference to adjuvant cancer chemotherapy after operation].

One hundred surgical specimens were used for the clonogenic assay to determine the chemosensitivity in vitro and the results were compared with the antitumor effect of the adjuvant cancer chemotherapy after operation. The clonogenic assay was performed according to the method of Salmon et al. The dissociated tumor cells were contacted with drugs in a concentration of 1 microgram/ml for 1 hr. (mitomycin C; MMC) or 2-3 wks. (5-fluorouracil; 5-FU). Fifty percent or more inhibitory rate of the colonies were evaluated as positive. The clinical antitumor effects were assessed by the tumor reduction in non-curatively operated cases and by the survival period after the operation in curatively operated cases. Overall evaluable cases were 52 of 100 cases with a median cloning efficiency rate of 0.1%. The efficacy rates of the drugs in vitro were found to be 21.3% for MMC and 31.8% for 5-FU. The histological differentiations, Stages, pretreatments and cloning efficiency rates were observed to have few influence on the chemosensitivity. Nineteen non-curatively operated cases were eligible for the comparison between in vitro and in vivo, showing 40% true positive, 100% true negative and 84.2% predictable rates. In curatively operated cases, whereas 2 of 14 cases have died of cancer in not adapted adjuvant cancer chemotherapy group, no cancer deaths were encountered in 7 cases whose adjuvant cancer chemotherapy was evaluated as effective in the clonogenic assay. From these findings, it was concluded that in vitro clonogenic assay might be useful to select a suitable adjuvant cancer chemotherapy in curatively operated cases as well as cases with advanced carcinomas.

Antineoplastic Agents↗
PubMed1986

[A randomized controlled study of (2'' R)-4'-O-tetrahydropyranyladriamycin and adriamycin in combination with cyclophosphamide and 5-fluorouracil in the treatment of advanced and recurrent breast cancer].

A comparative study of two combination chemotherapy regimens including (2'' R)-4'-O-Tetrahydropyranyladriamycin (THP) or Adriamycin (ADR) was performed to evaluate its efficacy and safety in advanced and recurrent breast cancer. In this study 64 patients were evaluated, and the response rate was 35.1% (13 of 37 patients) in group A (combination chemotherapy of THP, 5-Fluorouracil and cyclophosphamide), and 29.6% (8 of 27 patients) in group B (ADR, 5-Fluorouracil and cyclophosphamide). There was no statistically significant difference between the response rates of the two groups. As for safety, that of group A was significantly superior to group B for alopecia while that of group A tended to be lower than group B for anorexia. From the above results, THP in combination with cyclophosphamide and 5-Fluorouracil is comparable to ADR in efficacy and can be regarded as having better safety than ADR for the treatment of breast cancer.

Anorexia↗
PubMed1986

[Detection of DU-PAN-2 antigen (pancreatic cancer-associated antigen) in sera of patients with cancer of the digestive tract].

DU-PAN-2 is an antigen detected by a monoclonal antibody to pancreatic adenocarcinoma. In order to determine the clinical usefulness of DU-PAN-2 for diagnosis and monitoring in cancer patients, the DU-PAN-2 level (EIA, less than or equal to 300 U/ml) was measured in 238 patients with cancer of the digestive tract including 47 with pancreatic cancer, and in 57 with benign abdominal disease. The positive rate and maximum level for pancreatic cancer were 48.9% and 85,960 U/ml, respectively. However, DU-PAN-2 levels were also relatively high in hepatobiliary cancers. For stage II pancreatic cancer, the positive rate and maximum level of DU-PAN-2 were only 22.2% and 661 U/ml, respectively. On the other hand, these values were 0% and 196 U/ml (pancreatic cyst) in 15 benign pancreatic diseases. In postoperative monitoring of up to 35 months in 17 resected patients with pancreatic cancer, the DU-PAN-2 level decreased on resection of the tumor and increased on recurrence. This study suggested that DU-PAN-2 seems promising as a means for differentiating pancreatic cancer from benign pancreatic disease and for detecting the recurrence of pancreatic cancer. However, differentiation between pancreatic and hepatobiliary cancers appears difficult.

Antigens, Neoplasm↗
PubMed1986

[Phase II study of THP (2''R)-4'-0-tetrahydropyranyladriamycin) in breast cancer].

In a phase II study of THP, fifty-six patients with advanced or recurrent breast cancer were evaluated, and a response rate of 23.2% including 1.8% with complete response and 21.4% with partial response, was obtained. Response rates of THP varied according to the location of metastasis and the highest rate was shown to be 38.5% in patients with soft tissue metastasis. The median dose for inducing response was 100 mg with a range from 60 mg to 160 mg. Toxicities such as leukopenia and gastrointestinal disorders were observed during THP treatment. The favorable response to THP was close to that of adriamycin, but it was noteworthy that a lower frequency of alopecia occurred.

Adult↗
PubMed1986

[Phase II study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with solid tumors. Multi-Institutional Cooperative Study].

A Phase II Study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with various solid tumors was carried out by 44 cooperative study institutions. Seven hundred fifty-six patients administered the drug intravenously were entered into this study. Of these, 499 patients were evaluated for objective responses. THP was given mainly at a dose of 40 to 60 mg/body every 3 to 4 weeks or 20 to 30 mg/body once a week. Response rates were 18.8% for head and neck cancer, 13.1% for stomach cancer, 21.4% for breast cancer, 22.2% for bladder cancer, 30% for renal pelvic and urinary tract tumor, 26.8% for ovarian cancer and 24.2% for uterine cancer. Overall response rate was 15.4% including 10 complete responses and 67 partial responses. Adverse reactions were similar to those previously reported in the phase I study, including gastrointestinal toxicities and myelosuppression. Alopecia and stomatitis, which are major side effects of other anthracyclines, were rather mild. Incidence of ECG changes was 2.8% and no congestive heart failure was observed.

Adult↗
PubMed1985

A phase III trial of oral high-dose medroxyprogesterone acetate (MPA) versus mepitiostane in advanced postmenopausal breast cancer.

A randomized controlled trial was performed to compare the therapeutic results of oral high-dose medroxyprogesterone acetate (HD-MPA) versus mepitiostane (MS) in the treatment of postmenopausal breast cancer. MPA was given at three doses of 400 mg orally daily to 47 patients and produced objective responses in 19 cases (40.4%). An objective response was seen in 14 of the 40 control patients given MS at two doses of 10 mg orally daily (35.0%). Among patients with bone metastases, 6 of 19 (31.6%) for HD-MPA and 2 of 13 (15.4%) for MS showed objective responses. The other merits of HD-MPA suggested in the study were improvement in performance status, increase in appetite, and myeloprotective effect.

Adult↗
PubMed1985

New fluorogenic substrate for esterase activity of alpha-chymotrypsin and related enzymes.

A new fluorogenic substrate, benzyloxycarbonyl-L-phenylalanine 4-methylcoumaryl-7-ester, has been developed for determination of the esterase activity of alpha-chymotrypsin and related enzymes. Synthesis of the substrate was achieved simply by the carbodiimide condensation of benzyloxycarbonyl-L-phenylalanine and 7-hydroxy-4-methylcoumarin in a 86% yield. The esterase activity was measured by increase of the fluorescence intensity at excitation and emission wavelengths of 325 and 465 nm, respectively. An initial rate of hydrolysis was linear over a 100-fold range of the enzyme concentration. As little as 2 ng of alpha-chymotrypsin could be detected in the standard assay. A typical enzyme assay, stability of the substrate, kinetic parameters, and specific activity have been reported.

Chymotrypsin↗
PubMed1985

Carbohydrate antigen defined by a monoclonal antibody raised against a gastric cancer xenograft.

A monoclonal antibody, ST-4-39, was obtained by using a human gastric cancer xenograft, St-4, as an immunogen. Immunization was achieved by transferring immunocompetent mouse spleen cells into a nude mouse bearing St-4. Hybridomas were produced with the spleen cells of the mouse after rejection of the tumor and screened for immunohistochemical reactivity with cancers and normal tissues on formalin-fixed paraffin sections. ST-4-39 immunohistochemically reacted with various cancers including gastric, colorectal and pancreatic cancers as well as some normal tissues. ST-4-39 and NS 19-9 differed in immunohistochemical reactivity, although they reacted with some cancers and a few normal tissues in common. PBS extracts of normal and cancer tissues were examined for antigen reactive with ST-4-39 by sandwich enzyme immunoassay. Extractable antigen was detected in adenocarcinomas of colon, stomach and lung, while it was detected only in salivary gland and trachea among normal tissues examined. Gel filtration analysis of the antigen indicated a molecular weight of greater than or equal to 1 X 10(6), and the antigenic determinant was suggested to be a carbohydrate chain with terminal sialic acid by studies using periodic acid, neuraminidase and pronase treatments. Furthermore, the ST-4-39 antigen affinity-purified from two gastric cancer strains was shown to contain multiple carbohydrate determinants including sialyl-Lewisa and sialyl-Lewisx, suggesting the antigen to be a mucin.

Animals↗
PubMed1985

[Phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with malignant cancer--a multi-institutional cooperative study].

A phase II study of oral 5'-deoxy-5-fluorouridine (5'-DFUR) was conducted on a multi-institutional basis. Six hundred and ninety-two cases were entered into this study and evaluated by the extramural review committee. In 437 evaluable cases the response rate was 16.0%, 13 CR and 57 PR. The response rate of gastric cancer was 14.3%, 1 CR and 19 PR out of 140 evaluable cases, that of colorectal cancer was 9.2%, 1 CR and 6 PR out of 76 evaluable cases, and that of breast cancer was 35.9%, 11 CR and 26 PR out of 103 evaluable cases. The response rate was high with a long-lasting efficacy in breast cancer. Although the number of cases was small, PR was observed in 3 cases of head & neck, and in 1 case each of esophagus, gall-bladder and thyroid cancer. The optimal daily dosage was considered to be 800-1,200 mg/body/day. The tumor began to decrease in size within 8 weeks of treatment in most of the responded cases. Side effects were observed in 44.4% of 513 cases. Diarrhea occurred with the highest rate (26.3%), but this was controllable.

Anorexia↗
PubMed1985

[A comparative study of 5'-DFUR and tegafur in recurrent breast cancer].

UNLABELLED: A comparative study was performed to evaluate the efficacy and safety of 5'-DFUR and tegafur in recurrent breast cancer. The oral daily dosage of 5'-DFUR was 1,200 mg and that of tegafur was 800 mg, both drugs being administered every day for more than 4 weeks. RESULTS: Cases evaluable for anti-tumor effect were 50 with 5'-DFUR and 38 with tegafur. The response rate was 28.0% (14/50) with 5'-DFUR while that with tegafur was 15.8% (6/38). In the cases with no prior fluorinated pyrimidine therapy, 5'-DFUR was significantly superior to tegafur in the response rate. Effective cases determined within 8 weeks numbered 9 out of 50 cases with 5'-DFUR, showing a tendency to be more than those of tegafur, 1 out of 38 cases. This indicates that the appearance of response for 5'-DFUR seems to be faster. The duration of PR tended to be longer with 5'-DFUR than with tegafur. As for the safety, there was no difference between the two groups except for a high incidence of diarrhea in 5'-DFUR. 5'-DFUR tended to be superior to tegafur in its usefulness judged from the angles of efficacy and safety. From the above results, 5'-DFUR can be regarded as having a better efficacy than tegafur for the treatment of recurrent breast cancer, with a fast-appearing anti-tumor effect and a long durability for continuous treatment.

Administration, Oral↗