Biomedical subjects

M Niimoto

Publications and source records attributed to M Niimoto.

At least 55 records · Page 3Linked to original sources

PubMed1988

[A cooperative study of surgical adjuvant chemotherapy of colorectal cancer (second report): 3-year survival rate. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].

To evaluate the efficacy of surgical adjuvant chemotherapy for patients with curatively resected colorectal cancer (excluding m and sm cancer), a randomized controlled study was performed from January 1982 to October 1983. The schedules for drug administration were different in four districts, and four randomly assigned protocols were studied using tegafur (FT), ACNU, MMC and ADM. A total of 4,906 cases from 491 institutions were entered and 4,206 cases were varied for the study. There were no significant differences in 3-year survival rate in each district protocol. According to Dukes C for rectal cancer patients, ADM + FT group was higher than the FT only group in 3-year survival rate (p = 0.092) and had a significantly longer survival than FT only group in 3-year disease-free rate (p = 0.011). The rate of local recidivation in colon cancer resected curatively was higher in ACNU + FT group than in FT only group (p less than 0.05). A tendency for decreased liver metastasis was observed in FT group compared with the control group, and liver metastasis of ADM + FT group was lower than that of FT only group. No serious adverse effects were observed in any protocol.

Antineoplastic Combined Chemotherapy Protocols↗

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↗

PubMed1988

[Hoarseness after removing a cervical schwannoma--a case report].

A 54-year-old man complained of asymptomatic lump in the right parotid gland region. The lump was well movable and had no fixation to the adjacent tissue. The lump was surgically extirpated and histological sections of the lump revealed benign schwannoma. In view of postoperative evidence of hoarseness, it was thought the tumor might be arose from the cervical vagal nerve. The hoarseness has been observed for one year after operation without any improvement. A statistic study on the hoarseness after removing the cervical tumor was done by sending out questionnaires to the members of the council of the Japan Surgical Society. Of 270, 180 replies were obtained and 67.2% of the members answered that they did not have any knowledge about the hoarseness after removing the cervical tumor.

Cranial Nerve Diseases↗

PubMed1987

Clinical studies on a new screening assay for anticancer agents using nude mice and isotopic evaluation.

A new screening assay for anticancer agents was established using an in vivo nude mouse model. Assessment of the chemosensitivity of individual human tumors was determined by [3H]thymidine incorporation by the treated tumors. Three hundred and thirty tumors derived from cancer patients were transplanted into nude mice s.c. and treated with anticancer agents. Mitomycin C, 5-fluorouracil, cyclophosphamide, and doxorubicin were used in the present studies. In 270 of 330 cancers, chemosensitivity was evaluated by this method (evaluable rate, 81.8%). The rate of positive sensitivity against all tumors was 21.9% in mitomycin C, 12.2% in 5-fluorouracil, 27.4% in cyclophosphamide, and 23.6% in doxorubicin, respectively. The tumor sensitivity to anticancer agents varied according to the type of cancer. Retrospective and prospective clinical studies were performed to determine the usefulness of the nude mouse-isotope assay for the prediction of tumor sensitivity. The 24-month survival rates of 24 gastric cancer patients treated with tumor-sensitive agents was significantly higher than that of 28 patients treated with tumor-resistant agents. The end results after chemotherapy in far-advanced and inoperable terminal cases of gastrointestinal cancers was also investigated, prospectively. Out of 19 cases, the 50% survival time of 11 patients treated with tumor-sensitive agents was longer than that of eight patients treated with tumor-resistant agents. From prospective correlative studies carried out on 25 patients, this assay correlated with clinical responses (overall agreement, 76.0%; P less than 0.05) with specific agreements of sensitivity and resistance of 37.5 and 94.1%, respectively. From these results, it seems reasonable to conclude that nude mouse-isotope assay is a screening assay to identify appropriate agents for the treatment of patients with cancer. However, there is still a need to develop a better protocol in this assay, especially for antimetabolites, and to continue research in order to find more sufficient assays to predict clinical sensitivity to anticancer agents.

Animals↗

PubMed1987

Antitumor effects of recombinant human tumor necrosis factor against human tumor xenografts transplanted into nude mice.

Antitumor activities of recombinant human tumor necrosis factor (rH-TNF) against human tumor xenografts in nude mice were studied. Thirteen human tumor xenografts serially transplanted into nude mice were used for experiments; five gastric, two breast, two gallbladder, one colon and one esophageal carcinoma, one liposarcoma and one squamous carcinoma of the neck. They were inoculated into the subcutaneous tissue of BALB/c nu/nu nude mice and the treatment was started when the estimated tumor weight reached 100-300 mg. rH-TNF was administered intratumorally at schedule of qd X 5 or q3d X 5. rH-TNF showed a marked antitumor activity against various human tumors. The hemorrhagic necrosis was observed in all types of the human tumor xenografts (100 per cent), and the complete regression of the tumor was noted in 4 of 11 tumors (36.4 per cent). On the contrary, intraperitoneal rH-TNF exhibited little antitumor effect. The additive effect in the combination of TNF and Mitomycin C was observed against two Mitomycin C resistant gastric tumors.

Animals↗

PubMed1987

Experimental studies on the combined effects of alpha and gamma interferons against human tumor xenografts transplanted into nude mice.

The antitumor activities, resulting from the combined treatment of leukocyte interferon (IFN-alpha), with recombinant human immune interferon (IFN-gamma), against human tumor xenografts in nude mice, were studied. Nine human tumor xenografts, (7 from gastric carcinoma, 1 from gallbladder carcinoma and 1 from breast carcinoma), were serially transplanted into nude mice for the purpose of this experiment. Each human tumor xenograft was inoculated subcutaneously into BALB/c nu/nu nude mice and treatment was started after the estimated tumor had reached 100-300 mg. IFN was administered intramuscularly at a schedule of qd X 14. Treatment with either IFN-alpha or IFN-gamma alone, did not produce any antitumor effect against the various human tumor xenografts, however the combination of IFN-alpha with IFN-gamma resulted in achieving significant antitumor effects against the various human tumors. Inhibition of tumor growth was observed in 7 of the 9 tumors (77.8 per cent), and regression of the tumor was noted in 5 of the 9 tumors (55.6 per cent).

Adenocarcinoma↗

PubMed1987

Mitomycin C plus carmofur (HCFU) adjuvant chemotherapy for noncuratively resected cases of colorectal carcinoma (interim report).

In order to examine the efficacy of adjuvant chemotherapy employing Mitomycin C (MMC) and carmofur (HCFU) for patients with noncuratively resected colorectal carcinoma, a cooperative study was performed by 54 institutions in the Kyushu and Chugoku areas in Japan. The prospective randomized controlled study consisted of two groups, one receiving only MMC and the other receiving MMC as well as HCFU. Out of an original total of 200, 170 cases were evaluable. Concerning the 30-month survival rate, a better result was observed in the MMC + HCFU group than in the MMC only group (Z-test: p less than 0.05). Significantly better survival rates were obtained in those cases with disseminating peritoneal metastasis, hepatic metastasis and Stage V cancer in the MMC + HCFU group as when compared with the MMC only group (generalized Wilcoxon test: p less than 0.05). No significant side effects due to the combined administration of HCFU were recognized. The combined administration of MMC and HCFU were recognized. The combined administration of MMC and HCFU was suggested to be a safe and effective adjuvant chemotherapy in noncuratively resected cases of colorectal carcinoma.

Aged↗

PubMed1987

Effect of oxygen tension on the antitumor activity of mitomycin C assayed by human tumor clonogenic assay.

The effects of oxygen tensions on the antitumor activity of mitomycin-C (MMC) were surveyed using the human tumor clonogenic assay technique. Six human tumor xenografts (4 gastric cancers, and 2 colon cancers) were used in this study. Tumor cells were continuously exposed to MMC during the experimental period at various oxygen tensions, such as 2 per cent, which is considered to be hypoxic oxygen tension, 5 per cent which is considered as the physiological oxygen tension, and 20 per cent which is the conventional in vitro culture condition. The antitumor activities of MMC on the 6 human tumor xenografts increased when the oxygen tension was lowered from 20 per cent to 5 per cent. However, no further increases of the antitumor activities of MMC were observed by lowering the oxygen tension from 5 to 2 per cent. Additionally, the in vitro antitumor activities of MMC at various oxygen tensions were compared with the in vivo chemosensitivities evaluated in nude mice. In five of the 6 human tumor xenografts, in vitro chemosensitivities assayed at 2 or 5 per cent oxygen tension were concordant with in vivo chemosensitivities, although in vitro chemosensitivities assayed at 20 per cent were concordant with in vivo chemosensitivities in 3 of the 6 tested tumors.

Animals↗

PubMed1987

Comparative study on nude mice isotope assay (NM-IA) and subrenal capsule assay (SRCA) sensitivity tests of anticancer agents.

A comparative study on nude mice isotope assay (NM-IA) and subrenal capsule assay (SRCA) was done to evaluate the usefulness of in vivo assays for predicting individual tumor sensitivity against anticancer agents. Sixty-one fresh tumor specimens collected at surgery, under sterile conditions, were examined. Mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM), adriamycin (ADM) and cis-DDPlatinum (CDDP) were used in both assays. In NM-IA, the tumor sensitivity was determined by the amount of 3H-thymidine incorporated into the tumor which had been implanted into subcutaneous spaces of BALB/c nude mice. In the SRCA, the relative increase in weight of the tumor implanted into the subrenal capsular space of ddY mice was determined and measurements made to evaluate the chemosensitivity. Evaluability rates of the trials were 86.9 per cent with both assays and the response rates were 35.8 per cent in NM-IA and 34.0 per cent in SRCA, respectively. Against MMC, 5-FU, CPM, ADM and CDDP, overall consistency rates between the two assays were 77.8 per cent, 88.6 per cent, 72.7 per cent, 81.8 per cent and 68.2 per cent, respectively. In 8 of these 53 evaluated assays, correlations between the results of assays and clinical effects were examined and overall predictive accuracy rates were 87.5 per cent with both assays. Significant differences between these two in vivo chemosensitivity tests were not evident.

Animals↗

PubMed1987

Comparative studies on in vitro human tumor clonogenic assay (HTCA) and in vivo nude mouse-isotope assay (NM-IA).

Comparative studies between the in vitro human tumor clonogenic assay (HTCA) and nude mouse-isotope assay (NM-IA), in which the final evaluation was made with 3H-thymidine incorporations of tumor cells transplanted into nude mice, were performed simultaneously on 60 fresh human tumors. Tissues used included 27 gastric cancers, 10 breast cancers, 7 colorectal cancers, 4 gallbladder cancers, 4 sarcomas, 3 lymphomas, and 5 other tumors. Mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM) and adriamycin (ADM) were tested. The overall evaluable rate was 66.7 per cent in HTCA and 83.3 per cent in NM-IA, respectively. When the per cent survival in HTCA and the per cent inhibition in NM-IA less than 50 per cent was defined as drug sensitive, the drug sensitive rates of MMC, 5-FU, CPM, and ADM were 23.1, 16.7, 11.8, and 27.8 per cent in HTCA and 17.6, 18.4, 22.4, and 25.5 per cent in NM-IA, respectively. Although statistically significant correlations between the results of HTCA and those of NM-IA were obtained for MMC and ADM, no correlation was observed for 5-FU and CPM. The overall predictive accuracy rate of clinical response was 83.3 per cent (true positive rate 50 per cent and true negative rate 92.9 per cent) in HTCA and 76.0 per cent (true positive rate 37.5 per cent and true negative rate 93.8 per cent) in NM-IA, respectively.

Animals↗

PubMed1987

Antitumor activities of KW-2152, a new isoquinon agent, against human tumor xenografts transplanted into nude mice.

The antitumor activities of KW-2152, a new isoquinon derivative, were examined in thirteen human tumor xenografts, transplanted into nude mice. KW-2152 was administered intravenously at a schedule of q4d X 3, in daily doses of 7.3 mg/kg and 3.6 mg/kg, and q2d X 6 with a daily doses of 7.3 mg/kg, respectively. KW-2152 displayed significant antitumor activities against the human tumor xenografts in 3 out of 13 strains (23.1 per cent) at the schedule of q4d X 3, with a daily dose of 7.3 mg/kg. Depending on the schedule of administration, tumor activity was observed in 8 out of 13 strains (61.5 per cent) at a schedule of q2d X 6, with a daily dose of 7.3 mg/kg. SH-2 and SH-9 gastric tumors were sensitive to KW-2152 and growth was completely inhibited with the schedule of q4d X 3, and a daily dose of 7.3 mg/kg. Thus, KW-2152 seems to have a wide antitumor spectrum, and the possible antitumor effects for clinical use, warrant attention.

Animals↗

PubMed1987

Intestinal metaplasia of the stomach confined to the fundic gland area. Report of two cases.

Two patients with intestinal metaplasia of the stomach, whose distribution was exclusively confined to the fundic gland area, are presented herein. The first, a 51-year-old male, had been treated for pernicious anemia for 14 years when he was found to have gastric cancer. His serum gastrin level was quite high, whereas his gastric acid output was markedly low. The polypoid cancer in the fornix of the stomach, which had been removed endoscopically, revealed tubular adenocarcinoma with its invasion limited to the mucosa. The resected stomach showed no residual carcinoma but had numerous minute foci of intestinal metaplasia, diffusely distributed but exclusively confined to the fundic gland area, by macroscopic observation using the leucine aminopeptidase-alkaline phosphatase double staining method. The intestinal metaplasias were all of the complete type, and the parietal and chief cells were almost completely lost. The second patient, a 76-year-old male without pernicious anemia, underwent total gastrectomy for two polypoid cancers in the body of the stomach. The resected specimens, in addition to two hyperplastic polyps in the transitional area, showed the same distribution of intestinal metaplasia as seen in the first patient.

Adenocarcinoma↗

PubMed1987

[A case of recurrence of gastric cancer with an abdominal wall tumor responding to intratumoral OK-432 administration].

Intratumoral administration of 5 K.E. OK-423 was given every other day for a patient with an abdominal wall recurrence of gastric cancer. After a total dose of 465 K.E. the abdominal tumor turned necrotic and its demarcation was monitored. Finally, the tumor separated and fell from the abdominal wall. Histologically, marked infiltration of neutrophils, lymphocytes, and macrophages were observed in the cancerous tissue. Clinically, local pain lessened and the serum CEA level decreased. PPD and PHA skin tests were markedly stimulated. A long term small-dose intratumoral administration of OK-432 seemed to be effective for a local recurrence of gastric cancer.

Abdominal Muscles↗

PubMed1987

[In vivo chemosensitivity test for UFT and FT-207. I--Subrenal capsule assay].

A chemosensitivity test for UFT and FT-207, which are used in long-term administration clinically, was investigated for prediction of clinical response. Five transplantation-established human tumor xenograft systems were examined using subrenal capsule assay. Both anticancer agents showed antiproliferative effects according to the total administered dose. Two of 5 tumors were determined to be sensitive to UFT using microscopic measurements following intragastric administration of 1/2 of the LD50 value, while they were shown to be resistant to 5-FU. In these two cases, prolongation of life span by long-term administration of UFT was shown clinically. All these experiments could be performed on condition that the loss of body weight in mice was less than 20%. These results suggest that in the 4-day subrenal capsule assay, clinical responses to long-term administration of UFT or FT-207 are predictable using intragastric high-dose administration which does not induce more than 20% body weight loss in experimental mice.

Adenocarcinoma↗

PubMed1987

[In vivo chemosensitivity test for UFT and FT-207. II. Chemosensitivity test on human tumor xenografts transplanted in nude mice].

The present study was designed to predict the clinical effect of UFT and FT-207 in short-term administration using a nude mouse-xenograft system. Five human tumor xenografts transplanted into nude mice were used. UFT and FT-207 were administered with the LD10 doses orally for seven consecutive days. Tumor size was measured on day 7, 14 and 21 after the administrations. No significant differences in antiproliferative effects were observed between the measurements of tumor size made on day 7 and day 21. UFT inhibited significantly the tumor growth of CH-I established from colon cancer in which the prolongation of life span has been obtained by clinical long-term administration of UFT. These results suggest that this chemosensitivity test system using nude mice is useful for prediction of clinical response at 7 days after final administration of UFT and FT-207.

Adenocarcinoma↗