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Biomedical subjects

M Yasutomi

Publications and source records attributed to M Yasutomi.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of cephalic neural tube closure by 5-azacytidine in neurulating rat embryos in vitro.

Head-fold stage rat embryos (9.5 days of gestation) were cultured for 48 h in rat serum with or without 0.8 microM 5-azacytidine. Incomplete closure of the cephalic neural tube was observed in 5-azacytidine-treated embryos cultured for 48 h (25-somite stage). Control embryos showed complete fusion of cephalic neural folds at 33 h (16-somite stage) in culture. Drug administration or removal experiments revealed that embryos were sensitive to 5-azacytidine during 6-12 h of culture (three to five somite stages). Electron microscopical studies indicated that the arrangement and fine structure of cephalic neuroepithelial cells were almost the same in control and treated embryos. There was no significant difference in DNA and protein contents between control and treated embryos cultured for 36 h. Immunocytochemical observations using 5-methylcytosine-specific antibody revealed that the staining of neuroepithelial cells in the median part of the transversely sectioned cephalic neural plate, and of mesenchymal cells near the apices of the plate, was suppressed by 5-azacytidine. These results suggest that DNA methylation of these cells plays an important role in closure of the cephalic neural tube.

5-Methylcytosine↗
PubMed1992

Proliferating cell nuclear antigen in breast lesions: correlation of c-erbB-2 oncoprotein and EGF receptor and its clinicopathological significance in breast cancer.

Monoclonal anti-proliferating cell nuclear antigen (PCNA PC10), which is directed against a 36 kDa auxiliary protein for DNA polymerase delta specific for the S-phase of cell cycle, was used to measure tumour cell proliferation in 4 lactating breasts and 98 benign and malignant breast tumours. The percentage of PCNA-positive cells determined by point counting was significantly lower in the lactating breast [mean 3.6%, standard deviation (SD) 0.67, n = 5] than in fibroadenoma and mastopathy (mean 23.7, SD 5.0, n = 2). Primary breast carcinoma showed a PCNA index ranging from 2% to 36% (mean 12.3, SD 9.3, n = 50), whereas in recurrent carcinoma the index was mean 28.5, SD 4.0. A high index was correlated with c-erbB-2 and epidermal growth factor (EGF) receptor membrane reactivity, worsening histological grade, poor survival and disease-free survival. The expression of c-erbB-2 and EGF receptor was associated with poor survival and disease-free survival in primary breast cancer patients.

Breast Neoplasms↗
PubMed1992

Clinical trials of intrasplenic arterial infusion of interleukin-2 (IS-IL-2) to patients with advanced cancer.

We tried a infusion of interleukin-2 (IL-2) of a relatively low dose via an intrasplenic arterial catheter connected to a chronometric infusion (IS-IL-2). Eighteen patients of colorectal cancer with metastases to the liver or lung or of unresectable hepatoma received a 24 hour continuous infusion with low dose recombinant of IL-2 (mainly 8 x 10(5) JRU/day) for 25-40 days. All patients tolerated this protocol of the therapy and the main toxic effects were fever and general fatigue. Such serious toxicity as previously reported by high dose IL-2 therapy was not observed. Data of hepatic and renal functions were normal. IS-IL-2 therapy induced a high incidence of eosinophilia (12/18) and thrombocythemia (12/18). Peripheral natural killer (NK) and LAK activities were augmented in all patients and total white blood cell counts were increased during IS-IL-2 therapy. An increase in IL-2 receptor expression of peripheral blood mononuclear cells and significant rises in numbers of Leu11 (CD16)+, OKM1(CD11)+ and OKIa1(HLA-DR)+ were observed. Of 18 patients 12 were evaluable for their response to therapy. Partial response (PR) was observed in one unresectable hepatoma and 11 demonstrated no change (NC) or progressive disease (PD). Six patients were not evaluable because of additional therapy (3 cases) or decreasing tumor cell markers having no measurable lesions (3 cases). Three patients of colorectal cancer from an unresectable group were presumed to have micrometastases to the liver as suggested by an elevated serum CEA level. After receiving IS-IL-2 therapy they demonstrated a decrease in the serum CEA level for more than 3 years after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Cystic tumors of mediastinum].

Nine of twenty-four mediastinal tumors showed cystic lesions were operated at Kinki University Hospital. These nine mediastinal cysts included 5 of thymic cysts, 3 teratomas and one pericardial cyst. By the preoperative imagings, thymic cysts showed a smooth wall and homogenous content with water density. Teratoma consisted of cystic and solid parts, and the irregular thickness of the wall was found. One of these teratomas was ruptured into the pleural cavity, it has been proposed that digestive enzyme derived from pancreatic tissue with Langerhans island caused autolysis and necrosis with result in rupture. Pericardial cyst located at cardiophrenic angle mostly and which is useful on diagnosis.

Adult↗
PubMed1992

[Establishment and characterization of a human squamous cell carcinoma cell line LK-52 which produce direct activator of coagulant factor X].

Uterus origin squamous cell carcinoma cell line LK-52 was established from surgical specimen of lung metastatic nodule. LK-52 produce poorly differentiated squamous carcinoma in nude mouse, and doubling time in vitro was 38 hours. Chromosome analysis show various abnormality and main mode number was 67 and 68. LK-52 shed active procoagulant substance into culture medium. The culture medium of LK-52 shortening recalcification time of normal human plasma and factor VII or factor IX deficient plasma but not factor X deficient plasma. Procoagulant activity of LK-52 product may induced with direct activation of coagulant factor X. Procoagulant activity which produced by cancer cell may play a important roll in the unbalanced haemostasis of cancer patient.

Adult↗
PubMed1992

Augmentation of human lymphokine-activated killer cell activity in splenic lymphocytes by the combination of low-dose interleukin 2 plus interleukin 3.

The effect of interleukin 3 (IL-3) on lymphokine-activated killer cell (LAK) generation in splenic lymphocytes was examined in patients with gastric cancer or idiopathic thrombocytopenic purpura (ITP). IL-3 alone did not induce any significant LAK activity from splenic lymphocytes. However, IL-3 addition to the culture with low-dose IL-2 significantly augmented the activity of LAK cells. Spleen cells precultured with IL-3 for 2 days and then added to IL-2 became more potent LAK cells than the spleen cells cultured with the same doses of IL-3 plus IL-2. Phenotypic analysis using flow cytometry demonstrated that IL-2 alone increased in cells expressing CD2+, -11+, and -16+ cells, whereas IL-3 plus IL-2 induced the expansion of CD3+ and CD8+ cells in addition to CD2+, -11+, and -16+ cells. These results suggest that IL-3 plus IL-2 phenotypically induces not only natural killer-like LAK cells (CD2+, -11+, and -16+) but T cell-like LAK cells (CD3+ and -8+). We are now investigating the characteristics of immature T cell populations in the spleen responsive to IL-3 using T-cell receptor antibody.

Antigens, CD↗
PubMed1992

[A phase II study of DWA2114R, a new platinum complex for breast cancer].

A multi-institutional phase II study of DWA2114R was conducted in breast cancer. DWA2114R at doses of 800-1,000 mg/m2 was administered by 1-hour intravenous infusion every 3-4 weeks on minimal two cycles. Fifty-two patients entered the study; 34 were eligible, 7 ineligible. Eleven patients were dropped from evaluation due to incomplete observations. There were 1CR, 6PR, 1MR, 12 NC, and 14 PD with an overall response rate of 20.6%. A median duration of responses was 11 weeks. Leukopenia and nausea/vomiting were frequently observed but well tolerated and recovery was quick. It is concluded that DWA2114R is a useful drug in the treatment of breast cancer.

Anorexia↗
PubMed1992

[Comparison of surgical therapy and combined irradiation in rectal cancer--second report. Effect of irradiation and ACNU on the tumor].

As part of a joint study on preoperative radiotherapy for developing an optimal mode of rectal cancer therapy, ACNU sensitization was studied in a total of 120 cases, with the cooperation of 48 facilities participating nationwide. The following results were obtained. Improvement in depth of invasion was more distinct in the combination preoperative therapy-ACNU group than in the preoperative radiotherapy group, with no other significant differences between the two. This finding suggests that dose and administration method could be improved. White blood cells and platelets were reduced in some cases of the ACNU combination group, but these reductions were not serious enough to impede surgical procedures. In addition, no significant difference in complications was noted between the two.

Adenocarcinoma↗
PubMed1991

Plasminogen activator inhibitor 1 in human carcinoma tissues.

The content of PAI-I was measured in carcinoma tissues from the stomach and colorectum divided macroscopically into 3 portions: the central part of the carcinoma, the marginal part of the carcinoma containing some normal mucosa, and the normal mucosa. Among these tissues, the highest levels of PAI-I antigen were found in the central part of the carcinoma. On the other hand, no PAI-I antigen or activity was observed in the normal mucosae. The PAI-I produced in the stomach and colorectal carcinoma tissues showed a non-lytic zone with a molecular weight of 54 kDa by reverse fibrin autography, and this 54-kDa band reacted with anti-PAI-I IgG on an immunoblotted nitrocellulose membrane by the avidin-biotin complex method. The contents of PAI-2 in the carcinoma tissues were not significantly different from those in the normal mucosa of the stomach and colorectum. In both the stomach and colorectal carcinomas, the highest value of u-PA/total PA (sum of u-PA and t-PA) was observed in the central part of the carcinoma, followed by the marginal part of the carcinoma, and was lowest in the normal mucosa. We conclude that increased levels of PAI-I in malignant tissue of the stomach and colorectal tract may serve to modulate extra-cellular proteolysis by u-PA.

Biomarkers, Tumor↗
PubMed1991

Plasminogen activator inhibitor in stomach and colorectal carcinomas.

The content of PAI was measured in carcinoma tissues from the stomach and colorectum divided macroscopically into three portions: the central part of the carcinoma, the marginal part of the carcinoma containing some normal mucosa, and the normal mucosa. The PAI-1 antigen was highest in the central part of the carcinoma. On the other hand, no PAI-1 antigen or activity was observed in the normal mucosa. The PAI-1 in the carcinoma tissues showed a nonlytic zone with a molecular weight of 54 kd by reverse fibrin autography, and this 54 kd band reacted with anti-PAI-1 immunoglobulin G (IgG) on an immunoblotted nitrocellulose membrane. The contents of PAI-2 in the carcinoma tissues were not significantly different from those in the normal mucosa of the stomach and colorectum, respectively. In both the stomach and colorectal carcinomas, the highest value of u-PA/total PA (sum of u-PA and t-PA) was observed in the central part of the carcinoma, followed by the marginal part of the carcinoma, and was lowest in the normal mucosa. We conclude that increased levels of PAI-1 in malignant tissue of the stomach and colorectal tract may serve to modulate extracellular proteolysis by u-PA.

Adult↗
PubMed1991

[The elevation of serum iron level with oral administration of medroxyprogesterone acetate (MPA) in patients with breast cancer].

The elevation of serum iron level was noted in six out of 45 patients with breast cancers who were treated by medroxyprogesterone acetate (MPA) in Kinki University Hospital. Those six patients were not found to be involved in hemolysis and liver dysfunction during the treatment. The level of serum iron was demonstrated 205-338 micrograms/dl in the blood after MPA treatment. This elevation of serum iron level was not related with another anti-cancer agents. There was no observed serious complication with high level of serum iron. This is the first report of the elevation of serum iron level following MPA therapy for the patients with breast cancers.

Aged↗
PubMed1991

[Phase I study of CI-898. CI-898 Study Group].

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).

Adult↗
PubMed1991

[Cooperative study of surgical adjuvant chemotherapy for colorectal cancer (third report): five-year results. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan].

A randomized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal surgical adjuvant chemotherapy for curatively resected colorectal cancer. The schedules for drug administration were different in four districts: ACNU + Futraful (FT) group and FT alone group in the Hokkaido-Shikoku district; the same schedule groups plus untreated group in the Chubu-Kinki district; MMC+FT group, FT alone group in the Tohoku-Kanto district; and ADM+FT group and FT alone group in the Chugoku-Kyushu district. The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study. The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer, but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies. In n2 (+) or a2(s) rectal cancer in particular, combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate, and the rate of local recurrence was significantly lower with ADM+FT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Splenic or hepatic arterial injections of interleukin-2 with chemotherapeutic agents for hepatic metastases].

Splenic or hepatic arterial injections of interleukin-2 (IL-2) with chemotherapeutic agents were performed in colorectal cancer patients with metastasis of the liver. LAK/NK activities in PBL from the patients receiving IL-2 plus cyclophosphamide (CY) splenic infusion were much potent than those of the patients receiving IL-2 alone. Twelve patients were treated with hepatic arterial infusions of IL-2 and mitomycin C (MMC)/5 fluorouracil (5FU). Ten patients were evaluable and remaining 2 cases were not evaluable because of having no measurable lesion; prophylactic infusion for occult metastasis after hepatectomy. Six out of 10 had a complete or partial response (60%), especially all patients receiving 6 months and more (3 cases) had a complete response (100%) and CEA level decreased to normal range. Lymphocyte phenotype study showed notable decrease in CD8+, 16+, 57+ cells and increase in CD4+ cells (elevation of 4/8 ratio) during the therapy. NK activity was closely related to the percentage of CD 16+, 57+ cells in peripheral blood lymphocytes (PBL). These results might be reflected the dramatic accumulation of cytotoxic cells to the liver by the direct activation of hepatic sinusoidal endothelium due to IL-2 perfusion.

Aged↗
PubMed1991

[Does the pelvic nodes dissection for the rectal cancer patients make any contribution to the end-results of surgery?].

Extended pelvic nodes dissection (PND) was adopted to 182 curatively resected rectal cancer patients from 1978 to 1986 at Kinki University Hospital. All patients were diagnosed preoperatively that the depth of cancer invasion were the proper muscular layer or more. Dissected lymph nodes were examined in detail by the clearing method. Pelvic nodes involvement was found in 19 patients or 10.3% out of 182 with PND, and 5-year survival of 19 patients was 26.3%. All over 5-year survival of 182 patients with PND was 69.0% while 62.2% without PND before 1978. There was no significance in the rates of local recurrence between 13.2% with PND and 13.7% without PND. Urinary and sexual dysfunction was increased from 41% and 38% without PND to 66.7% and 88% with PND respectively. It is difficult to evaluate the meaning of PND in the rectal cancer surgery from this non-randomized study. As 80% of the pelvic nodes involvement, however, were found in the cancer with deeper penetration from the muscular layer (a2) and with the location of the middle or lower rectum, PND should be considered only to these two conditions.

Humans↗