Biomedical subjects

T Saeki

Publications and source records attributed to T Saeki.

At least 181 records · Page 10Linked to original sources

PubMed1989

The histological assessment and evaluation of a 4 day subrenal capsule assay by the percentage inhibition of DNA/protein.

A four day subrenal capsule assay was investigated in order to determine its ability to clinically predict tumor chemosensitivity. To establish more objective and accurate evaluation criteria, a histological assessment and measurement of the DNA and protein content of excised tumor implants was conducted in ddY mice. The histological studies provided qualitative results concerning the percentage of cancer cells in the xenograft, the number of mitoses, the amount of necrosis, and the extent of lymphocytic infiltration. The DNA content was measured by a modified version of the Schmidt-Thannhauser-Schneider method and the protein content was estimated using the Bio-Rad protein assay. The percentage of cancer cells in the xenograft correlated poorly with the relative increase in tumor size, weight and the percentage inhibition of DNA/protein (per cent DNA/protein), however, the per cent DNA/protein correlated well with the clinical effects in 85.7 per cent of the tumors studied. Moreover, the histological assessment information was only consistent with those results obtained for per cent DNA/protein in the control group.

Animals↗

PubMed1989

Chemosensitivity tests in colorectal cancer patients.

In order to assess the usefulness of chemosensitivity tests in the treatment of colorectal cancer, 71 tumor specimens were tested for chemosensitivity in the following assays: nude mouse isotope assay (NMIA), subrenal capsule assay (SRCA), human tumor clonogenic assay (HTCA) and adenosine triphosphate inhibition assay (ATPA). The agents examined were: mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM), adriamycin (ADM) and cis-diamminedichloroplatinum (CDDP). The evaluability rates were 90.8, 93.9 and 92.3 per cent in NMIA, SRCA and ATPA, respectively, but only 42.9 per cent in HTCA. The tumor response rates were 50.8, 45.2, 16.7 and 33.3 per cent in NMIA, SRCA, HTCA and ATPA, respectively. Individual drug sensitivity rates differed among all 4 assays, ranging from 0 to 33.3 per cent. In the arbitrary judgment of the 4 assays, the most sensitive agent was CDDP, followed by CPM, ADM, 5-FU and MMC. In the prospective study, predictive accuracy rates of the clinical responses were 81.3, 66.7, 100, 100 and 76.5 per cent in NMIA, SRCA, HTCA, ATPA and the arbitrary judgment, respectively. A significant correlation between the survival time and the results of SRCA was detected retrospectively. These results suggested that colorectal cancer might not be completely resistant to anticancer agents, and that chemosensitivity tests might be useful in the individual therapy of colorectal cancer patients.

Antineoplastic Agents↗

PubMed1989

Transforming growth factors in human breast cancer.

Transforming growth factors alpha and beta (TGF alpha and TGF beta) are two growth factors which are frequently associated with a number of human breast cancer cell lines and with primary human breast carcinomas. Expression of TGF alpha protein and specific TGF alpha mRNA transcripts (4.8 and 1.6 kb) can be induced by estrogens in estrogen-responsive breast cancer cells, suggesting that the mitogenic effects of estrogen may in part be mediated through this potential autocrine growth factor. In contrast, anti-estrogens such as tamoxifen can increase the secreted levels of TGF beta, which is a potent growth-inhibitor for some human breast cancer cell lines. Anti-estrogens generally decrease TGF alpha production. TGF alpha mRNA expression has been detected in approximately 40-70% of primary human breast tumors, while expression of a 2.6 kb TGF beta mRNA transcript can be detected in 70-80% of breast tumors. Interference with (e.g. TGF alpha) or augmentation of (e.g. TGF beta) the effects of these two growth factors may have some potential clinical applications in the treatment of breast cancer.

Breast Neoplasms↗

PubMed1989

[Comparative study on the anticancer activities of KW2149 and mitomycin C against human tumor xenografts using subrenal capsule assay].

The anticancer activity of KW2149, a new derivative of mitomycin C (MMC), was investigated against 5 human tumor xenografts derived from digestive organs using 4-day subrenal capsule assay (SRCA). Normal immunocompetent mice were used in this assay. For the comparative study, KW 2149 and MMC were administered intraperitoneally for 3 days after implantation, and the anticancer activity and the weight loss of mice were evaluated. The total doses were determined as 1/2, 1/3 and 1/4 of LD50 value of each anticancer agent. The anticancer activities of the two drugs were almost the same with no significant difference in 3 xenografts. Thus, it may be suggested the difference of the anticancer spectrum between the two drugs. The anticancer activity of KW2149 indicated higher correlation with the administered doses as compared with MMC. The toxicity of KW2149 was almost the same as MMC according to the weight loss of mice.

Animals↗

PubMed1989

[Experimental study of normal liver regeneration in hepatic arterial infusion with degradable starch microspheres (DSM)].

Influence of hepatic arterial infusion with degradable starch microspheres (DSM) or with anti-cancer drug or with both for normal liver regeneration in rat was determined by histological and microautoradiographical examination and liquid scintilation before or after 70% hepatectomy. DSM was seen in interlobular artery in early phase after hepatic arterial infusion, but disappeared into the central vein by degrees for 2 hours later. Adriamycin (ADM) in serum was detected for a long time after hepatic arterial infusion with DSM + ADM. In the heart muscle, a significantly lower concentration of ADM was seen in the DSM + ADM group than in the ADM only group. In the case of hepatic arterial infusion with DSM only after hepatectomy, there was no influence on normal liver regeneration. No significant difference was seen between hepatic arterial infusion and intravenous infusion with ADM only. However, in the case of hepatic arterial infusion with DSM + ADM after hepatectomy, a significant difference was seen in the inhibition of liver regeneration from any other groups.

Animals↗

PubMed1989

[Combination chemotherapy of CPM-MTX-5-FU in non-resectable and recurrent cancer patients].

Fifty-two non-resectable and recurrent cancer patients with prior treatment, were entered in this study; 1 esophageal, 33 gastric, 1 duodenal, 4 colorectal, 2 pancreatic, 2 bile duct, and 9 breast cancer. The protocol of this therapy was as follows: On day 1, 500 mg/body cyclophosphamide (CPM) was administered by drip infusion, and on day 2, 200 mg/m2 methotrexate (MTX) was infused intravenously for 30 min; immediately after, 500 mg/body 5-fluorouracil (5-FU) was injected by bolus infusion for 5-10 min. On day 3, 24 hours after MTX administration, leucovorin rescue was added. This combination chemotherapy was repeated every two weeks. As a result, 35 of 52 patients were evaluable and the response rate (CR + PR) was investigated; 2/21 (9.5%) for gastric, 2/7 (28.6%) for breast, and 0% for miscellaneous. As complications for side effect, general fatigue, anorexia, nausea, vomiting and stomatitis were observed symptomatically, and leukopenia and thrombocytopenia were recognized in laboratory data as dose limiting factors.

Anorexia↗

PubMed1989

[Evaluation and problems of second-look operations in resectable gastric cancer].

During the period from June 1973 to December 1985, one thousand and ninety-seven patients with primary gastric cancer have been operated on in our Dept. of Surgery. Of the 1097 gastric cancer patients, 59 were reoperated and evaluated for chemotherapeutic effects. The cases were 21/548 (3.83%) for absolute curatively resection, 16/202 (7.92%) for relative curatively resection, 9/64 (14.0%) for relatively noncurative resection and 13/283 (4.59%) for absolutely noncurative resection, respectively, The median survival period from primary gastrectomy to second look operation was less than 2 years, and the prognoses were not very good. The factors of relaparotomy were peritoneal dissemination 44/59 (78.6%), invasion to contiguous structures, lymph node metastases and liver metastasis. Those with local recurrence or remnant stomach cancer could be resected in 5 cases, and one patient was well more than 2 years following surgery. The reoperation procedures were reconstruction of artificial anus, intestinal anastomosis or intestinal fistula. Some 7 of 59 patients were found to be entirely beyond surgical aid at the second look operation and were administered large-dose OK-432 or ADM patch method. These methods are suggested for their usefulness for peritoneal dissemination.

Antineoplastic Agents↗

PubMed1989

[Comparison of succinic dehydrogenase inhibition test with adenosine triphosphate inhibition assay for human solid tumors as in vitro chemosensitivity tests].

In order to determine the most effective anticancer agents for individual human tumor, succinic dehydrogenase inhibition test (SDI-T) and adenosine triphosphate inhibition assay (ATP-A) as in vitro chemosensitivity tests were performed. Fifty tumors and 57 tumors derived from cancer patients surgically methods were examined by SDI-T and ATP-A respectively. As the results, the evaluable rate was 70% by SDI-T and 94.7% by ATP-A, respectively. With SDI-T, the positive rate against all tumors was 51.4% in mitomycin-C (MMC), 42.9% in adriamycin (ADM), 20.0% in 5-fluorouracil (5-FU), 54.3% in cis-diamminedichloroplatinum (CDDP). On the other hand, with ATP-A, that was 20.4% in MMC, 29.5% in ADM, 20.6% in 5-FU, 20.4% in CDDP, respectively. Retrospective and prospective clinical trials were also carried out to determine the usefulness of both assays. With SDI-T, overall predictive accuracy rate was 57.1% while with ATP-A that was 88.9%. Furthermore, the rates of sensitivity for the same tumors using SDI-T and ATP-A were compared. The rate of the same sensitive cases in both assays were 30% with MMC, 70% with 5-FU, 42.1% with ADM, 36.8% with CDDP, respectively. In conclusion, it is suggested that ATP-A was more useful than SDI-T as in vitro chemosensitivity test to determine the most adequate drug for cancer patients.

Adenosine Triphosphate↗

PubMed1989

In vivo effects of vitamin E on peritoneal macrophages and T-kininogen level in rats.

In order to clarify the modulating effect on macrophages by vitamin E, we investigated the in vivo effects of vitamin E on the peritoneal macrophages and T-kininogen level in rats. Peritoneal injections of vitamin E for 6 successive days resulted in a significant increase of leucocytes, mostly consisting of macrophages, in the peritoneal cavity. Namely, in the case of 5 mg vitamin E per rat (400 g body weight), the number of leucocytes in the peritoneal cavity and T-kininogen level in plasma showed 171.57 +/- 15.96 X 10(6) per rat and 1372 +/- 364 micrograms/ml, whereas the placebo vehicle was 28.54 +/- 8.24 X 10(6) and 315 +/- 130, respectively. Macrophages, in which alpha-tocopherol contained approximately 158.2 ng/10(6) cells after exogenous vitamin E treatment, showed less acid phosphatase activity and less O2- generation than that treated with placebo vehicle. In contrast, the acid phosphatase activity of cellfree peritoneal exudate fluid with vitamin E increased approximately two to three-fold as compared to the placebo vehicle. From these results, we discussed the relationship between in vivo effects of vitamin E on peritoneal macrophages and T-kininogen induction.

Acid Phosphatase↗

PubMed1988

Combined effects of UFT with other anticancer agents using in vivo chemosensitivity tests.

In order to estimate the combined effects of UFT with other anticancer agents, a nude mouse experimental system (NMES), and a subrenal capsule assay (SRCA) were investigated. Three human tumor xenografts were serially transplanted into nude mice and examined. These were; EH-1 established from esophageal cancer, SH-6 from gastric cancer and CH-3 from colon cancer. The antiproliferative effects were estimated in accordance with the NCI therapeutic protocol. Significant antiproliferative effects were obtained only in NMES and a positive relationship was observed between the two assays (p less than 0.05). In the groups which were treated with a single agent, positive tumor responses were observed against mitomycin C in SH-6, against cis-DD platinum in SH-6 and EH-1, and against adriamycin in EH-1, respectively. On this study the synergistic, additive and subadditive effects were defined as the positive combined effects. The combination of MMC and UFT produced positive combined effects for all xenografts in both assays.

Animals↗

PubMed1988

The indications of chemosensitivity tests against various anticancer agents.

In order to determine the indications of chemosensitivity tests against various anticancer agents, clinical trials of 4 different assays, namely; nude mouse isotope assay (NMIA), subrenal capsule assay (SRCA), human tumor clonogenic assay (HTCA) and adenosine triphosphate inhibition assay (ATPA), were performed on 391 patients. Analysis of the correlation between assay results and clinical effects presented the possibility of determining the indications as follows; (1) The positive clinical response of mitomycin C (MMC) should be predicted by ATPA; (2) The clinical tumor resistance against MMC should be predicted by SRCA; (3) Concerning 5-fluorouracil (5-FU) the chemosensitivity test (ATPA) should only be used for the detection of tumor resistance in the assay; (4) The poor results of this study indicated the difficulty of correctly estimating the effects of cyclophosphamide (CPM); (5) The perfect prediction of clinical effects in this trial indicated that cis-DDPlatinum (CDDP) should be estimated by SRCA; (6) The positive clinical tumor response against adriamycin (ADM) should be predicted by SRCA, while the negative one should be predicted by HTCA; and (7) ATPA showed good potential for estimating not only time dependent drugs such as 5-FU, but also cytotoxic drugs.

Adenosine Triphosphate↗

PubMed1988

The antiproliferative effects of fluoropyrimidine derivatives against human tumor xenografts in a subrenal capsule assay.

The antiproliferative effects of the fluoropyrimidine derivatives, 5-fluorouracil (5-FU), 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur), UFT, 1-hexylcarbamoyl-5-fluorouracil (HCFU), and 5'-deoxy-5-fluorouracil (5'DFUR), were investigated in a 4 day subrenal capsule assay. The antiproliferative effects against two human tumor xenografts established in athymic mice were examined after treatment with three different doses of each anticancer agent, and the adequate dose of each anticancer agent in this experimental system was estimated as: 473 mg/kg for Tegafur, 433 mg/kg for UFT, 50 mg/kg for HCFU and 185 mg/kg for 5'DFUR, respectively. A comparative study of the antiproliferative effects of fluoropyrimidine derivatives was carried out against 7 xenografts. According to our criteria of positive tumor response, the effective rates were: 1 of 7 (14.3 per cent) by 5-FU, 2 of 7 (28.6 per cent) by Tegafur, 2 of 7 (28.6 per cent) by UFT, 1 of 6 (16.7 per cent) by HCFU, and 1 of 4 (25.0 per cent) by 5'DFUR, respectively. Although no statistical differences were demonstrated between the agents, the utility of a chemosensitivity test before clinical use was suggested.

Animals↗

PubMed1988

[Multidisciplinary treatment of unresectable liver cancer].

From January 1984 to December 1987, 63 unresectable liver cancers (22 hepatocellular carcinoma and 41 metastatic liver cancer) were treated with multidisciplinary therapy: partial resection of liver, hepatic arterial infusion, coagulation therapy using microwave tissue coagulator and intratumoral injection of the liver. The median survival period was 5-7 months, and the clinical response rate was 21.6% in these therapies, but there was no statistically significant difference between the treatments. Recently, we usually use degradable starch microspheres (DSM) with anticancer agents in hepatic arterial infusion. Adriamycin + DSM was administered for hepatocellular carcinoma, and Mitomycin C + DSM was used for metastatic liver cancer. The regimens were used for 12 cases, 6 of hepatocellular carcinoma and 6 of metastatic liver cancer, with a response rate of 50%, respectively. We also undertook chemosensitivity tests for liver cancer. The coincidence of clinical response with results of chemosensitivity tests was above 50%. In future, we shall use the most effective anticancer agents for individual tumors with DSM in arterial infusion.

Adult↗

PubMed1988

[Prospective randomized controlled study of bestatin in gastric cancer surgery].

The effectiveness of bestatin combined with mitomycin C and tegafur as an adjuvant to surgery for gastric cancer was investigated in a prospective randomized controlled study. All patients underwent curative gastrectomy during the period from November 1980 to April 1984. Five-year survival rate revealed no significant difference between groups with or without bestatin. The effectiveness of bestatin was suggested in postoperative peritoneal recurrence in cases with positive histological invasion into the veins of the stomach wall.

Adjuvants, Immunologic↗

PubMed1988

[Combined effects of interferon alpha-A/D with fluoropyrimidine derivatives in the subrenal capsule assay].

The combined effects of interferon alpha-A/D (IFN alpha-A/D) with 5-fluorouracil and fluoropyrimidine derivatives such as 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), UFT, 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 5'-deoxy-5-fluorouracil (5'-DFUR), were examined by 4-day subrenal capsule assay. Four human tumor xenografts serially transplanted in athymic mice, H-111, SH-10 established from gastric cancers, CH-4 and CH-5 from colon cancers, were used. In this experiment, the adequate dose of each agent was estimated as 50 mg/kg for 5-FU, 473 mg/kg for tegafur, 433 mg/kg for UFT, 50 mg/kg for HCFU, 185 mg/kg for 5'-DFUR and 1 x 10(5) IU for IFN alpha-A/D, respectively. When synergistic, additive and subadditive effects were defined as positive combined effects, all combinations produced positive combined effects against H-111 and CH-5, while negative ones were observed for all combinations against CH-4. The combinations of 5-FU, HCFU and 5'-DFUR with IFN alpha-A/D produced synergistic effects against SH-10. These results indicate that the combination therapy of 5-FU and fluoropyrimidine derivatives with IFN alpha-A/D would be useful.

Animals↗

PubMed1988

[Fundamental and clinical studies of intra-arterial chemotherapy combined with degradable starch microspheres (DSM)].

Degradable starch microspheres (DSM, Pharmacia) are specially formulated cross-linked starch microspheres about 45 microns in diameter. The microspheres are degraded by serum amylase and become progressively smaller with t1/2 for complete dissolution between 20 and 30 min. in vitro (in normal serum). In vivo, DSM-occluded microcirculation was observed in lobular artery of liver and disappeared 60 minutes after administration; then PAS-positive debris, which was suspected to be degraded DSM, was found in intrahepatic tissues. We also carried out comparative studies on regrowth liver in rats as an index of 3H-thymidine incorporation to determine the influence for surgical operation. DSM + adriamycin (ADM) was injected into intrahepatic artery at 2 and 5 days before partial liver resection. In DSM + ADM group, regrowth of liver tissue was inhibited with injection 2 days before, while injection 5 days before had no influence. Since the usefulness of DSM combined with anticancer agents had been indicated by the experimental results mentioned above, we carried out a clinical study (phage II). Chemoembolization therapy was undertaken in combination with DSM in 6 patients each with primary and metastatic liver cancers. Six cases were evaluated as Partial Response (PR). Recently, we performed clinical trials to investigate the combination with noradrenaline, too. Noradrenaline was suggested to enhance the effect of DSM.

Adult↗

PubMed1988

[Anticancer activities of a new mitomycin derivative KW 2149, against human tumors xenografted into nude mice].

Anticancer activity of KW 2149, a new derivative of mitomycin C (MMC), was investigated using 4 human tumors xenografted into nude mice. The basic methodology was essentially the same with NCI's therapeutic protocol. For the comparative study, KW 2149 or MMC was administered intraperitoneally at a schedule of q4d X 3. Daily doses were determined as a 1/3, 1/4 and 1/5 of LD50 value of each anticancer agent (7.5 mg/kg, 5.6 mg/kg and 4.5 mg/kg for KW 2149, and 2.7 mg/kg, 2.1 mg/kg and 1.7 mg/kg for MMC). Anticancer activity of KW 2149 seemed to be dependent on the doses. Comparing with MMC, KW 2149 produced higher response rates at the doses of 1/3 and 1/4 of LD50 and was less toxic judging from the decrease of the body weight. This study may indicate an utility of KW 2149, as a new anticancer agents, or suggest the difference of anticancer activities between these two agents.

Adenocarcinoma↗

PubMed1988

[Inhibition of thymidylate synthetase and antiproliferative effect by 1-hexylcarbamoyl-5-fluorouracil].

In order to estimate tumor chemosensitivity of fluoropyrimidine derivative, inhibition of thymidylate synthetase (TS) was investigated using a nude mouse experimental system. Four human tumors xenografted in nude mice; H-111, SH-8 and SH-10, each established from gastric cancer, and EH-1 from esophageal cancer, were used. When the transplanted tumor volumes reached to approximately 200 mm3, 1-hexylcarbamoyl-5-fluorouracil (HCFU) was given for 5 days. Tumors was removed for the measurement of total and free TS at 0 hr, 6 hrs and 24 hrs after the last administrations. Simultaneously, the anti-proliferative effects were investigated according to the therapeutic protocol of NCI. No positive correlation between the inhibition rate of TS and the anti-proliferative effects was observed, although the absolute values of free TS were similar to the tumor inhibition rates. The measurement of total TS provided a highest concentration in SH-8, while extremely low in EH-1. On the analysis of free TS, a significant increase of the concentration was observed at 24 hrs after the last administration compared with at 6 hrs in SH-8. These results indicate that free TS had a potentiality as a new parameter for predicting tumor chemosensitivity of fluoropyrimidine derivative and the analysis of TS should be affected strongly by the characteristics of enzymic activity of examined tumor.

Animals↗