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Biomedical subjects

M Matsutani

Publications and source records attributed to M Matsutani.

At least 127 records · Page 7Linked to original sources

[Effects of anticancer drugs on multicellular spheroid of 9L rat brain tumor].

The effects of the anticancer drugs Nimustine (ACNU), Aclacinomycin A (ACR), Adriamycin (ADM), Bleomycin (BLM), Cisplatin (CDDP), and 5-Fluorouracil (5-FU) on the multicellular spheroid of a chemically-induced 9L rat glioma was studied. The multicellular spheroid in which cells grow in vitro as three-dimensional aggregates represents a biological model, which is intermediate between monolayer cells in vitro and solid tumors. Spheroids were initiated in bacteriological grade petri dishes seeded with 10(6) 9L rat glioma cells, cultured for four days and thereafter transferred and further developed in a spinner flask. Spheroids of 200-400 micron diameter were sorted and exposed for 24 hours to 5-FU and one hour for other drugs. After treatment both cytotoxic effect and growth delay were analyzed. Following disaggregation using collagenase, pronase and DNAase, cytotoxic effect on multicellular spheroids was measured by colony forming assay and were compared with those effects on 9L monolayer culture cells in the exponential growth. For growth delay assay, multicellular spheroids were individually transferred to 16 mm well containing 0.4 ml agarose base and 2 ml culture medium. Spheroid size was measured twice a week and growth curves were drawn. The growth delay was determined as the treated group vs. control differences in time required to a size four times that of the initial volume. For cells both in the monolayer culture and the multicellular spheroid, the dose response curve for ADM, BLM and 5-FU was "biphasic" and that for ACNU, ACR and CDDP "shoulder-threshold" type.(ABSTRACT TRUNCATED AT 250 WORDS)

Aclarubicin↗

Cellular immunity and complement levels in hosts with brain tumours.

As a major defence mechanism against cancer, host immunological surveillance is composed of a cellular immunity as well as humoral immunity including antibody and a complement system. In the course of the progress of brain tumours alone, serum complement level (CH 50) as a humoral immunological factor and the tuberculin skin reactivity as an index of cellular immune activity, were serially measured in brain tumour patients. One hundred and fifty-seven cases of brain tumours, including 75 cases of glioma, 25 benign tumours, and 42 metastatic tumours, were examined. Most cases of benign tumour belong to stage I oder II, in which both tuberculin reaction and complement are active. Many cases of glioblastoma and metastatic tumour belong to stage III; that is, they show negative tuberculin reaction and increased complement activity. The relation of immunological response to the tumour size and the clinical severity in patients with gliomas is revealed by the fact that complement titres rise in accordance with the degree of progress of the tumour and a negative tendency in the tuberculin reaction runs parallel to this. All cases of glioma, even in the terminal stages, remain in stage III. On the other hand, cases of metastatic tumour progress to stage IV and V, in which the tuberculin reaction is negative and complement titres decrease. The combined results of elevated complement level and depressed status of tuberculin reaction in patients with gliomas may be explained by the concept that complement activity rises to compensate for depressed cell-mediated immunity, in order to preserve the activity of the biophylaxis mechanism against cancer.

Adult↗

Pineocytoma. Observation of an autopsy case by electron microscopy and cell markers.

An autopsy case of a 69-year-old female with pineocytoma was reported. The tumor showed neuronal differentiations, which were confirmed not only by light microscopy and electron microscopy, but also by a cell marker of neuron-specific enolase. In addition, existence of astrocytes in the tumor which distributed sparsely was ascertained by electron microscopy and cell markers such as S-100 protein and glial fibrillary acidic protein.

Aged↗

[Immunochemotherapy of human gliomas transplanted into nude mice].

In the first part of this paper, various chemotherapies were performed against oligodendrogliomas subcutaneously transplanted in to nude mice. Vincristine (VCR), adriamycin, and 1000 rads irradiation were effective against this tumors. Concerning these two drugs, dose response effect was observed. And the effect of 1 mg/kg injection of VCR roughly corresponded to that of five weekly injections of 0.2 mg/kg. In the second part of this experiment, single or combined effects of VCR and immunotherapeutic agents including OK-432 (OK), PSK, and recombinant leucocytic interferon (IFN) were examined. Two glioma lines including oligodendroglioma and glioblastoma were used. Following results were obtained from this experiment: 1) Effect of OK and VCR against oligodendrogliomas were as follows: control less than OK local injection (Local) less than OK intraperitoneal injection (IP); VCR; OK (IP X 2) less than VCR + OK(IP) less than VCR + OK (IP X 2). Effects of OK and VCR were expressed in order of their effects against glioblastomas: control less than VCR less than OK (IP); OK(IP X 2); OK(Local) less than VCR + OK (IP); VCR + OK (IP X 2). Effects of PSK and VCR against glioblastomas were as follows: control; PSK (Local) less than VCR less than VCR + PSK (Local) less than VCR + PSK (IP). Effects of IFN and VCR against oligodendrogliomas were as follows: control; IFN (IP) less than VCR less than IFN (Local) less than VCR + IFN (IP); VCR + IFN (Local). Effects of IFN and VCR against glioblastomas were as follows: control less than IFN (IP) less than VCR; IFN (Local); VCR + IFN (IP).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy].

We studied the effects of increased-dose radiation therapy in terms of survival time and improvement in the quality of life in 50 glioblastoma patients with minimal residual tumors. 1) Intraoperative radiotherapy ( IOR , 1,000-2,000 rad) was applied in 13 cases; the 2-year survival was 41.6%. However, in 9 patients who had undergone macroscopic total removal the 2-year survival rate was 68.6%. 2) Wide resection with necrotomy after conventional external irradiation was used in 9 cases and conformation irradiation was added; their 2-year survival was 44.4%. 3) In 22 patients who received only conventional irradiation following surgery, the 2-year survival was 7.5%.

Adult↗

Localization of concanavalin A binding sites in human pituitary adenoma cells as revealed by HRP-labelling method.

Intracellular lectin (Con A)-binding sites of human pituitary adenoma were examined by electron microscopy using the horseradish-peroxidase (HRP)-labelling technique. In this study were used 16 cases of human pituitary adenomas operated on in our clinics between 1977 and 1981: they concluded 4 each of PRL-, GH-, ACTH-producing and hormonal non-functioning adenomas. In parallel with the detection of lectin-binding sites, basal levels of their secreting hormones were determined by the radioimmunoassay technique, and their producing hormones were characterized light microscopically by the immunocytochemical HRP-labelling technique. In the present study, for hormonal functioning adenoma cells, mature or large granules of each specific type of adenoma cells had no definite Con A-binding sites. On the other hand, immature or small secretory granules of RPL- or GH-producing adenoma cells showed a positive reaction with Con A. ACTH-producing adenomas so far examined revealed no definite binding sites. Some variable results were obtained concerning non-functioning adenomas. Lectins have been and will be very useful in the detection of different subtypes of adenomas in each specific group.

Adenoma↗

Microsurgery of teratoma and germinoma involving the diencephalon and the brain stem.

The authors encountered 95 cases of germinoma (two-cell pattern pinealoma) and teratoma involving the third ventricle and the pineal region from 1962 to 1980. Germinoma is radiosensitive. However, removal (extensive or total) of the tumour followed by postoperative irradiation showed better results than simple radiotherapy. In the recent 62 cases, 5-year and 10-year survival rates were 80.2% and 69.3% respectively (in children under 15 years, both were 86.9%). Teratoma is not radiosensitive and requires operation. For operating on a pineal germinoma, either an infratentorial supracerebellar approach or an occipital transtentorial approach is indicated. A teratoma, however, is sometimes too large for these approaches, when exposed, and therefore, the author prefers the transcallosal approach (for huge tumours the frontal transcallosal approach). Technical details will be reported and discussed.

Adolescent↗

Effects of human fibroblast interferon on human gliomas transplanted into nude mice.

Daily intratumor injection of human fibroblast interferon (HuIFN-beta) resulted in significant growth inhibition of human gliomas transplanted into nude mice. Light and electron microscope examinations were conducted to estimate the efficacy of HuIFN-beta. A 29-day daily treatment with HuIFN-beta induced complete regression of oligodendroglioma KG-1--a slowly growing tumor line positive for S-100 protein and negative for glial fibrillary acidic protein (GFAP)--in 9 out of 10 mice receiving 6 X 10(5) IU and 6 out of 9 given 1 X 10(5) IU. In mice with glioblastoma multiforme TMIMS-583, which showed more rapid growth and was positive for GFAP, dose-dependent growth inhibition was observed during 23 days of HuIFN-beta administration. Pathological changes of TMIMS-583 induced by HuIFN-beta were characterized by a decrease of the metaphase tumor cells, by enhanced degeneration of tumor cells with stromal reaction and round cell infiltrates, and by prominence of multinuclear giant cells containing glial filaments. Tumor weights were well correlated with the number of tumor cells in the metaphase (r = 0.89).

Adult↗

[Effects of phenobarbital on the metabolism of ACNU in vivo].

The nitrosourea compounds are often used in the treatment of patients with malignant brain tumors in combination with anticonvulsants, such as phenobarbital (PB). Since PB can induce hepatic microsomal enzyme--P 450 and degrade nitrosoureas in vivo, the effect of PB on tumoricidal activity in relation to toxicity of 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl]-1-(2-chloroethyl)-1-nitrosourea (ACNU) was studied using a rat brain tumor model. To determine toxicity, CD-Fisher rats were treated for 4 days with 19 and 38 mg/kg/day of PB (i.m), 0.4 and 0.7 g/kg/day of sodium valproate--SV (p.o), or 3 days with 50 mg/kg of phenytoin (i.v) prior to an administration of 47 mg/kg of ACNU (i.p). The mortality rate by the toxicity within 14 days after administration of ACNU was calculated in each group. The toxicity of ACNU was markedly reduced in PB pretreated rats compared with those without pretreatment or treated with SV or phenytoin. The tumoricidal activity of ACNU was evaluated in CD-Fisher rats with RG 12 brain tumors. Rats received 20 mg/kg ACNU after pretreatment with 19 mg/kg/day of PB (i.m) or 0.2 g/kg/day of SV (p.o) for 4 days. The mean survival days and the percentage increase in life span (%ILS) were compared in each group. Pretreatment with PB significantly reduced the tumoricidal activity of ACNU as compared with control without pretreatment (p less than 0.001) or pretreatment with SV (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Second-look operations and chemotherapy for malignant tumors of the brain].

Second-look operations for glioblastomas, one of the most malignant types of brain tumor, were performed after the administration of chemotherapeutic treatments of general-VM 26 plus ACNU, local-MTX, or interferon-beta in each of ten, two, and three cases, respectively. Patients who had received the treatments were divided into two groups, living and deceased, as of August 1982. Therapeutic evaluation was performed with clinical parameters. Among the cases of CR, one (a 14-year-old female) had undergone surgery four times in the four years following onset, and no trace of tumor shadow appeared on the CT grams that were taken one month after the last surgery. Her performance was evaluated as almost 100% (ECOG). In cases of local administration, one case, which had been treated with IFN-beta, demonstrated an apparent decrease in the growth fraction and a pronounced decrease in tumor progression potency. Cell kinetic analyses were also performed, and cell cycle time and growth fraction were estimated by computer with the aid of flow cytometry. Efficacious chemotherapy yielded a decreased value of the growth fraction and an increase in cell cycle time. The decreased value of the growth fraction demonstrates especially well the effectiveness of a chemotherapeutic regimen. The cell kinetic analyses aided in the rational establishment of a chemotherapeutic regimen. Second-look operations for malignant brain tumors will enable more effective refinements in chemotherapeutic regimens and more successful results.

Adolescent↗

Phase I-II trials of poly(ICLC) in malignant brain tumor patients.

Poly(ICLC) preparation, containing poly-L-lysine and poly(I) . poly(C) at a weight ratio of 1:2, was given intravenously at a dose of 0.05 to 0.2 mg/kg to 7 patients with malignant brain tumor. Poly(ICLC) induced significant serum interferon (more than 100 reference units/ml) in all patients. The highest interferon titer induced was 875 reference units/ml. Severe side effect was not observed except fever. Hypotension, leukopenia and elevation of liver enzyme levels were observed as side effects in a few cases.

Adult↗

[Effect of interferon inducer (poly ICLC) in the treatment of malignant brain tumor (author's transl)].

Interferon inducing activity, antitumor activity and toxicity of poly ICLC (poly IC stabilized with poly L-Lysine and carboxymethyl cellulose) in rodents were studied. SD strain rats were injected intravenously with poly IC or poly ICLC. Interferon in rat plasma was assayed by a plaque reduction method using stomatitis virus. The peak level of plasma interferon of the poly ICLC injection rat was as high as that of poly IC injection rat, and in the former, high level of plasma interferon persisted for 4-12 hours. Next, brain tumor-bearing rats were treated intravenously with poly ICLC and observed for death daily. Weekly treatment with 1 mg/kg of poly ICLC increased the mean survival time although no antitumor effect was observed with poly IC. The LD 50 value of poly IC was 33.5 mg/kg, and that of poly ICLC was 18.6 mg/kg and as to poly ICLC administration, no remarkable side effect was recognized below the dose of 1.5 mg/kg. In clinical trials, poly ICLC was given intravenously at the dose of 0.05-0.2 mg/kg to 9 patients with malignant brain tumor. (6 patients were glioblastoma, 1 was astrocytoma, and 2 were ependymoma.) In 2 patients, poly ICLC was administered once, in 2 patients twice, in 2 patients 3 times, and in 3 patients more than 5 times. The interval of each administration was 7 days. Poly ICLC induced high level of serum interferon (more than 100 reference unit/ml) in all patients and over 100 unit/ml of interferon was maintained for 24 hours. The highest interferon titer induced was 875 unit/ml. The most frequently encountered toxic reaction was fever, which occurred in all cases. The mean peak temperature elevation was 1.9 degrees C, which usually occurred 4-8 hours after drug administration. Modest hypotention was detected in one case. Leucopenia was detected in 3 cases. These abnormalities were all modest, and improved in a few days. As to the effect of poly ICLC, neurological improvement was recognized in 3 cases, and in one of them, remission on CT scan was also recognized.

Adult↗