Biomedical subjects

M Niimoto

Publications and source records attributed to M Niimoto.

At least 37 records · Page 2Linked to original sources

PubMed1989

The discrepancy between immunocytochemical and biochemical assay of estrogen receptor in breast cancer patients treated by endocrine therapy.

Estrogen receptor (ER) expression was investigated by ER-immunocytochemical assay (ICA) and the dextran coated charcoal (DCC) method in 10 recurrent or primary-advanced breast cancer patients treated with endocrine or chemo-endocrine therapy. In 6 of these 10 patients, ER was examined both before and after treatments by the 2 methods. ER contents measured by the DCC method were found to be decreased after treatments, however, no change in the immunoreactivities of ER-ICA was observed. In the remaining 4 patients, the ER of new lesions refractory to endocrine or chemo-endocrine therapy was examined. ER status was determined as negative in 3 of the 4 patients by the DCC method, whereas by ER-ICA, the proportion of ER stained cells was about 70 per cent, those cells being diffusely distributed in the section. A discrepancy between ER-ICA and the DCC method was thus demonstrated in breast cancer patients treated by endocrine therapy.

Adrenalectomy↗

PubMed1989

Epidermal growth factor induces the expression of its receptor gene in human gastric carcinoma cell line TMK-1.

To ascertain the possible autocrine pathway in the growth promotion of gastric carcinomas, a study was made on the effects of exogenous human epidermal growth factor (hEGF) on the expression of mRNA for EGF, transforming growth factor-a (TGF-a), EGF receptor, FOS and MYC genes by TMK-1 cells. Exogenous hEGF increased FOS and MYC mRNA levels 30 min and 1 h after the treatment, respectively. TMK-1 cells accumulated the mRNA for EGF receptor about 7- to 8-fold by 3 h after treatment. Expressions of mRNA for EGF and TGF-a genes were detected, but the amounts of the mRNA of these genes in TMK-1 cells were not altered after the treatment.

Cell Line↗

PubMed1989

[Submucosal injection of lipiodol-bleomycin in esophageal cancer].

Submucosal injection of Lipiodol-bleomycin (BLM) for esophageal cancer is complementary to CT scan in preoperative determination of the depth of the cancerous invasion in the esophageal wall. This procedure was performed not only for diagnosis but also as a preoperative therapy in 109 cases with esophageal cancer in Hiroshima University Hospital. The Lipiodol-BLM suspension was prepared by mixing 45 mg BLM and 5 ml Lipiodol on a clean bench. The mixture was usually injected into the submucosal layer of the esophagus using fiberscopy 12 days before the operation. BLM concentration was measured in the primary tumor, normal esophageal tissue around the tumor and regional lymph nodes in the specimen in 14 cases. As a result, a low level of BLM had been maintained in these tissues for a long time. The concentration of the primary tumor was 4 times higher than that of the normal esophageal tissue. In order to predict the side effects of BLM, such as pulmonary fibrosis, the change in serum BLM level was measured in 12 cases. Serum BLM decreased to an unmeasurable level 24 hours after the injection. Thus, the submucosal injection of lipiodol-BLM for esophageal cancer seems to be promising for a targeting cancer chemotherapy.

Bleomycin↗

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

Involvement of the nipple in early carcinoma of the breast.

Cancerous involvement of the nipple and subareolar tissue (nipple and areolar complex, NAC) was confirmed histopathologically in 24 of 65 patients with gross tumors measuring 2.5 centimeters or less. Erosion of the nipple as a clinical manifestation of involvement of NAC was seen in only two patients. The other 22 were all subclinical. The histologic form of involvement of NAC included intraductal-1 in 19 patients, stromal in one patient, lymphatic in two patients and intraductal-1 as well as stromal in two. Stepcut and serial observation of the whole breast suggested that both intraductal spread and stromal invasion of carcinoma were continuous processes from the underlying tumor. Involvement of NAC was more frequent if the patient was aged 50 years or less and if the proximity of the tumor to the nipple was less than 4 centimeters, regardless of the size of the tumor.

Adult↗

PubMed1989

[Expression of the epidermal growth factor receptor in esophageal cancer].

The level of epidermal growth factor receptor (EGF-R) has been measured by a competitive binding assay in 45 human esophageal cancer tissues. The EGF-R level in the esophageal cancer tissue was found to be significantly higher than in specimens of gastric or colonic cancer. No correlation was observed, however between the EGF-R level and the pathological findings, such as the depth of the tumoral invasion, the degree of lymph node metastasis, and the histologic staging. Even so, the prognosis of the patients with a high level of EGF-R of more than 50 fmol/mg of protein was significantly worse than those with a low level of EGF-R and less than 50 fmol/mg of protein (p less than 0.01). Further, according to an immunohistochemical assay using anti EGF-R monoclonal antibody, EGF-R was focally stained in the basal cells and in the parabasal cells of normal esophageal mucossa, but was diffuse in almost all tumor cells of ane esophageal cancer. Thus, a good relationship with the quantitative level of EGF-R and its immunoreactivities was demonstrated, indications that EGF-R plays an important role in tumor progression and appears to be a useful prognostic factor in cases of esophageal cancer.

Binding, Competitive↗

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↗

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

Immunocytochemical study on the variation in estrogen receptors of primary and nodal metastases of breast cancer.

The variation in estrogen receptors (ER) between primary and regional nodal metastatic lesions was examined by an estrogen receptor immunocytochemical assay (ER-ICA) in 25 mammary carcinoma patients. The ER status was evaluated in terms of the percentage of ER positive stained cells, staining intensity and distribution of those stained cells. The overall ER status was consistent in both sites, however, the percentage of ER positive cells and the staining intensity were not always consistent. A decrease in the percentage of ER positive cells and staining intensity was demonstrated in the nodal metastatic lesions of 4 and 3 cases out of a total 14 ER positive cases, respectively. The mean percentage of ER positive cells in the nodal metastatic lesions was 57 per cent compared with 73 per cent in primary lesions. Thus, a tendency of both the percentage of ER positive cells and the staining intensity to decrease in nodal metastases as when compared with primary lesions in breast cancer was demonstrated.

Antibodies, Monoclonal↗

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

Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years.

In order to evaluate the combination of immunochemotherapy with mitomycin C (MMC), futraful (FT) and PSK, as an adjuvant to surgery for curatively resected gastric cancer, a randomized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan. The MMC + FT + PSK group showed a significant increase in 5 year survival from the other groups (p less than 0.05). Moreover the survival rate was significantly higher in the MMC + FT + PSK group than in the MMC + FT group (p less than 0.01). According to the analysis on stratification, the MMC + FT + PSK group showed the best survival rate in cases with positive lymph node metastases, positive serosal invasion and positive lymph node metastases plus serosal invasion, and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction (p less than 0.01 or p less than 0.05). Thus, the combination of MMC, FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer submitted to curative resection.

Adjuvants, Immunologic↗

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

[Epidermal growth factor receptor in human breast cancer].

For the purpose of demonstrating the relationship between epidermal growth factor receptor (EGFR) content in the tumor and histopathologic characteristics, 45 women with breast cancer who underwent mastectomy were analyzed. EGFR content was measured by competitive binding assay using 125I, while EGFR was detected by immunocytochemical staining. Tumors with more than 1 fmol/mg protein EGFR were defined as positive, and a good correlation between competitive binding assay and staining was observed. Seventeen of them (37.8%) had EGFR-positive tumors. Eight of the 17 EGFR-positive tumors (47.1%) were positive for estrogen receptor (ER), whereas 24 of the 28 EGFR-negative tumors (85.7%) were ER-positive. This inverse relation was statistically significant (chi 2; p less than 0.05). Twelve of the 17 EGFR-positive cases (70.6%) had axillary node involvements, against 11 of the 28 (39.3%) in the EGFR-negative cases. There was no difference in the size of primary tumor between the two groups. These results suggested that EGFR-positive tumors have more malignant potency than EGFR-negative tumors. In 8 cases, EGFR content in metastatic axillary nodes was compared with that in primary tumors. More EGFR content indicated in metastatic axillary nodes than in primary tumors without significant difference.

Antibodies, Monoclonal↗

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↗