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Biomedical subjects

O Nakamura

Publications and source records attributed to O Nakamura.

At least 109 records · Page 6Linked to original sources
PubMed1986

Interactions of human fibroblast interferon with chemotherapeutic agents and radiation against human gliomas in nude mice.

The growth inhibitory effects of the combination of beta-interferon (beta-IFN) and conventional anticancer drugs such as adriamycin (ADM) and ACNU were evaluated in nude mice receiving subcutaneous transplants of human glioblastoma. Next, the anticancer and radiation sensitizing effects of beta-IFN on human glioblastoma was also evaluated in nude mice model. After three weeks of combined treatment, tumour reduction rates (treated/control values) were evaluated by the Battelle's method. In conclusion, the growth inhibitory effect of IFN was most enhanced when IFN was administered following radiotherapy. Furthermore, the combined effect was enhanced in proportion to the dose of radiation.

Animals↗
PubMed1986

[Flow cytometric analysis of the effect of cAMP on the cell cycle of the 9 L rat glioma in vitro].

Perturbed cell kinetics in 9 L rat brain tumor treated with dibutyryl cyclic AMP (DBcAMP) and theophylline were studied. The methods include a procedure for simultaneous flow cytometric measurements of cellular DNA and amount of bromodeoxyuridine (BrdU) incorporated into cellular DNA and a procedure for flow cytometric measurements of cellular DNA and RNA. Propidium iodide and monoclonal antibody against BrdU were used as a fluorescent probe for total cellular DNA and for BrdU incorporated into cellular DNA, respectively. For analysis of cellular DNA and RNA, acridine orange staining was also applied. The results were as following; cells in S and G2 phase at the time of drug administration (1 mM, each) can undergo mitosis even though a considerable prolongation of G2 phase was apparent. However, cells in G1 at the time of drug administration were arrested in that phase, whereas those cells in S or G2 were able to complete one mitosis before becoming arrest in the G1 phase. These results have been inferred from the study by autographic method with 3H-thymidine. However, using these new methods, these were clearly demonstrated and furthermore, flow cytometric analysis with acridine orange revealed that DBcAMP induced 9 L cells into resting position (G0 cells).

Animals↗
PubMed1985

Immunohistochemical studies with a monoclonal antibody on the distribution of phosphophoryn in predentin and dentin.

A monoclonal antibody was raised against phosphophoryn, a unique noncollagenous phosphoprotein in dentin. Mouse myeloma NS-I cells were fused with spleen cells obtained from BALB/c mice immunized with phosphophoryn from fetal calf tooth germs. Mice inoculated with the hybridoma produced ascites fluid containing the antibody and this reacted only with a band of phosphophoryn transblotted from polyacrylamide gel. Immunohistochemical studies with the antibody showed that phosphophoryn was present in odontoblasts, odontoblastic processes and dentin, but not in the matrix of predentin, and that the phosphophoryn content of the dentin layer was high at and around the predentin-dentin junction and gradually decreased toward the enamel layer. The area corresponding to mantle dentin was not stained with the antibody.

Animals↗
PubMed1985

[Antineoplastic effect of Hu-IFN-beta and other anticancer drugs on malignant brain tumors in athymic nude mice].

We have been studying the therapeutic effect of anticancer drugs such as ACNU and vincristine in human glioma-bearing nude mice models and this time, the effect of interferon was also evaluated. Since 1980, the phase 1, 2 clinical trials on Hu-Interferon (IFN) have been studied in the neurosurgical field and the effect is now regarded to be not as pronounced as previously expected. It is difficult to compare the effect of IFN with other anticancer drugs in an in-vivo study, because of the species specificity of IFN, and only a few studies have so far been reported. With respect to evaluating the therapeutic effect of IFN, the nude mouse model is thought to be useful. The anticancer activity of beta-IFN in nude mice, receiving subcutaneous transplants of human brain tumors (6 strains) was compared with that of conventional anticancer drugs. After 3 weeks of treatment with ACNU, vincristine, bleomycin, mitomycin C, alpha-IFN, beta-IFN, poly ICLC, the tumor reduction rates were evaluated by Battelle's method. Although in 2 out of 6 glioma strains, the tumor reduction rate (treated/control values) treated with beta-IFN was evaluated as effective, the effectiveness of beta-IFN was inferior to that of ACNU and vincristine. Therefore, further studies are indicated to evaluate the efficiency of the drug at higher dosage levels and to determine its tolerance dose. The combined modality treatment such as chemotherapy and radiation are issues that are still to be settled by further studies.

Animals↗
PubMed1985

[Cerebral blood flow measured by Xenon enhanced CT in brain tumors].

In the management of malignant brain tumors, it is important to know the extent and viability of tumors. However, an ordinary CT scan with iodine enhancement has only a limited ability to distinguish the tumor from surrounding normal tissue. Since the blood flow in tumor tissue was found to be relatively high in a previous experimental report, we have investigated the blood flow in a tumor and the surrounding brain. The Xenon enhanced CT method has several advantages over the conventional isotope method and enables us to evaluate rCBF with the same resolving power as with the CT scan. We evaluated rCBF in 15 brain tumor cases and obtained the following results. Mean rCBF value of the tumor is a little lower than that of gray matter and higher than that of surrounding edema. Our Xe-CT method enables us to distinguish the demarcation between the tumor area and the surrounding edematous area and offers useful information for determining the extent of resection in surgery. Mean lambda value of the tumor which is not obtainable in vivo by radionuclide scanning, was 1.02 +/- 0.06 for gliomas and 0.72 +/- 0.09 for metastatic tumors. rCBF value and lambda value are important elements to know the uptake rate of anticancer drugs into the brain tumors. And to evaluate these value in each brain tumor is useful in the selection of chemotherapeutic agents.

Adult↗
PubMed1985

[Prognosis of metastatic brain tumor from lung cancer with special reference to its stages].

An overview of treatment of brain metastasis from lung cancer in National Cancer Center is presented with respect to T and N categories in TNM classification. To know the rate of brain metastasis, CT scan on brain was performed for all the patients with lung cancer hospitalized for surgical treatment and revealed that 3 of 87 patients had brain metastasis without any neurological signs and symptoms. On the other hand, 105 out of 320 (32.8%) lung cancer patients who had taken CT scan for some reason from 1975-1983 in this hospital had shown the brain metastasis. Therefore, it should be memorized that only 3.4% was detected to have brain metastasis from the patients without any neurological signs and symptoms. Two hundred sixty-one patients with metastatic brain tumor from lung cancer were treated in 1963-1983 at National Cancer Center in Japan. Of these, 205 patients were evaluated for the median survival and the average survival according to various therapeutic modalities. Of this 205 patients, 123 had no operation with or without other treatment--chemotherapy or radiotherapy showed median survival of 3-5 months (range 2-25 months). Eighty-two had operation on brain metastasis with or without chemotherapy showed median survival of 6-11 months (range 2-112 months). Correlation between survival time and T and N categories in TNM classification at the diagnosis of lung cancer was studied and no remarkable difference was noted either in T or N categories in the average survival time and percent number of cases survived equal or more than 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1985

[Diffuse bone marrow metastasis of an anaplastic oligodendroglioma].

The authors report a case of anaplastic oligodendroglioma, in which multiple bone metastases developed about 6 years after the first craniotomy. A 32-year-old woman was admitted because of an apathetic state. CT scan and angiography suggested right frontal glioma. On August 15, 1977, a right frontal lobectomy was performed and histological sections showed anaplastic oligodendroglioma. Postoperative course was uneventful and she was discharged after chemoradiotherapy. In January, 1982, CT scan suggested recurrence of the right frontal tumor. On February 8, 1982, the second craniotomy was performed and this time, local radiation therapy by the afterloading technique (192Ir seed assembly) was given after the operation. In March, 1983, she began to complain of low back pains and multiple bone metastases were found by bone X-Ps and scintigrams. Biopsy of bone metastases was performed and at the same time, the whole body was surveyed for malignant tumors. But no primary cancer other than the right frontal brain tumor was found. In spite of therapy such as IFN, her condition gradually deteriorated and she died in December, 1983. Histological bone biopsy sections showed anaplastic oligodendroglioma much like the histology of the first operation. As the progress of curative means has increased, so has also the number of long-time survivors of malignant brain tumors. And in proportion to the increase in long-time survivors, cases of extracranial metastases may also increase. The etiology, diagnosis and therapy of extracranial metastases from the literature was also studied.

Adult↗
PubMed1984

Increased activities of liver cathepsins T and D in carbon tetrachloride-treated rats.

Changes in activities of a new proteinase cathepsin T as well as some other lysosomal acid proteinases and hydrolases were examined in liver homogenate from rats treated with a single hepatotoxic dose of carbon tetrachloride. The most striking changes were several-fold increases of liver cathepsin T and D activities over their levels in untreated rats 3 days after administration of the agent to rats. Increase of cathepsin T was greater than that of cathepsin D at all doses of the hepatotoxin examined. The activities of N alpha-benzoyl-DL-arginine 2-naphthylamide hydrolase, acid phosphatase, beta-galactosidase and beta-glucuronidase in poisoned rat liver were unchanged or only slightly increased. Cathepsin T and D activities were less enhanced in mitochondrial lysosomal fractions than in the homogenate, and were greatly elevated in the supernatant fractions of liver from the treated rats. As judged from the molecular weights, the elevated activities of cathepsins T and D in the treated rat liver could be attributable to the two cathepsins themselves and not to other proteinases. Administration to rats of other hepatotoxic agents, thioacetamide and dimethylnitrosamine, also induced the elevation of the two cathepsin activities in liver, but on partial hepatectomy the activities of liver cathepsins T and D did not show such marked increases. Nonparenchymal liver cell fractions were responsible for almost all the increased activities of liver cathepsins T and D. It is possible that cathepsins T and D play a role in the heterolytic breakdown of hepatocyte molecules following CCl4 poisoning.

Animals↗
PubMed1984

Intensive chemotherapy with autologous bone marrow rescue for recurrent malignant gliomas.

Eight patients, four male and four female, were treated with high dose chemotherapy followed by bone marrow transplantation. In the first two patients, high dose ACNU was used for the treatment without combination with other drugs. This showed severe side effects such as intratumorous bleeding on the 18th day of treatment in the first case and pulmonary fibrosis on the 35th day of treatment in the second case. Considering these results, we considered another treatment schedule which consisted of high dose ADM (100 mg/m2), VCR (1.5 mg/m2), CDDP (80 mg/m2 X 4) and Ex (800 mg/m2) within seven days. Six patients were treated with this schedule and the results indicated that two patients had a partial response (more than 50% reduction of tumour size measured by CT scan), one had a complete remission (no tumour detected by CT scan), two showed no change and one, progression of the lesion. The patients recovered from the suppression of bone marrow function after the bone marrow transplantation as indicated. Granulocytes and platelets in blood began to increase from 10 to 14 days after the transplantation and became normal within three weeks after this. Serial measurements of S-GOT and alkaline phosphatase revealed reversible elevation, if any, within four weeks of the treatment. The number of our cases is still small, but results showed that autologous bone marrow transplantation made high dose chemotherapy possible. The necessity for consideration of the blood-brain barrier for this treatment is also discussed.

Adult↗
PubMed1984

[Synchronization chemoradiotherapy for malignant gliomas].

Cellular synchronization chemoradiotherapy was performed in 122 patients with glioblastoma and malignant astrocytoma (GrIII) registered between April 1977 and August 1982. The study was a non-randomized clinical phase II trial. The chemotherapeutic agents employed as synchronizers during the irradiation were VM26 (epipodophyllotoxin) and vincristine (VCR) as plant alkaloids and ACNU as a nitrosourea. Either VM26 or VCR was administered on D1, D2 and D3 at the dosage of 1 mg/kg (0.025 mg/kg-VCR) body weight. ACNU was administered on D2 and D3 at the dosage of 1 mg/kg body weight. The duration of the chemotherapy was eight to fourteen days at the initial induction stage and almost eight weeks at the maintenance stage. Thus, two synchronization arms of VM26 + ACNU and VCR + ACNU were employed. The regimen-VM 26 + ACNU + Radiation (Rad) could yield the initial induction of CR + PR-30%, NC-50%, and PG-15% in 58 cases. Long-term survival, calculated by the cumulative survival rate, was as follows: one year, 58%; two years, 42%; three years, 32%; four years, 30%, and five years, 25%. The regimen VCR + ACNU + Rad could yield the initial induction of CR + PR-28%, NC-49%, and PG-23% in 64 cases. The cumulative survival rate was calculated as follows: one year, 55%; two years, 42%; three years, 27%; four years, 22%, and five years, 22%. As a control, particularly for the survival rate, the data of the All-Japan Registry were revised to correspond to our study population. The survival rate of simple radiation cases thus revised was as follows: one year, 43%; two years, 23%; three years, 11%; four years, 7%, and five years, 5%. The comparison between VM 26 plus ACNU and VCR plus ACNU yielded a higher initial induction response of 35% for the former (vs. 28% for the latter), although it is difficult to make a judgement on the excellence of the regimen involving VM 26 plus ACNU, because this trial was clinical phase II. On the other hand, compared with the data from the All-Japan Registry, each regimen of cellular synchronization radiation therapy could achieve statistically more excellent responses both in the initial induction and the long-term survival (p less than 0.01). Thus, cellular synchronization radiation therapy is a hopeful therapeutic method for malignant glioma, with less side effects and statistically confirmed higher responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

[Flow cytometric study of enhanced effect of anti-cancer drugs induced by nicardipine hydrochloride].

Flow cytometric analysis was used to study the effect of a calcium influx blocker, nicardipine hydrochloride, on the cytotoxicity of anti-cancer drugs in tumor cells. The parameters used for this study were DNA- and protein-cell distribution histograms. Cells and drugs used for this study were C6 cells from CD Fisher rat glioma and VCR, ADM and ACNU, respectively. The growth inhibitory effect estimated by concentration at ID50 on C6 cells was indicated as follows; VCR showed an 89-fold enhancement, while ACNU showed little enhancement following addition of nicardipine hydrochloride. DNA and protein histograms obtained by flow cytometry revealed almost the same effects as cells which were studied using high concentration of VCR without nicardipine hydrochloride. For the other drugs, ADM showed a small enhancement on histograms, while with ACNU, little enhancement was noted as well as the inhibitory effect of each drug described above. The results indicate that nicardipine hydrochloride greatly affects the cell cytotoxicity of VCR but not so much with ADM and ACNU. From these results, it appears that this drug enhances the action of anti-cancer drugs not only by merely blocking the efflux of drugs from cells but also by other mechanisms which remain to be clarified.

Animals↗
PubMed1983

Ionic dependence and transmission of epidermal action potentials in a newt embryo.

The ionic dependency and transmission of epidermal action potentials have been examined from tailbud to hatching stages of newt embryos. Previously we have reported that the epidermal action potential is composed of a fast- and slow-action component; only the slow-action component, however, is transmitted to other cells. We address in this report the mechanism by which these responses are mediated. The slow-action potential is not produced in Na+-free saline, tricaine saline, or following the application of TTX, and thus appears to be Na+ dependent. The fast-action potential on the other hand is blocked by application of Co2+ and verapamil saline and thus appears to be Ca2+ dependent. The slow-action potentials appear to be chemically transmitted since they are transmitted even to those cells which are electrically uncoupled at low intracellular pH (NaHCO3 + HCl, pH 6.2). Furthermore 1 microM curare and atropine are inhibitory to transmission of the slow potential. Epidermal cells of the newt embryo are sensitive to acetylcholine (ACh) applied by hydrostatic ejection through a micropipet. The latter observation further suggests that propagation of the slow-action potential is, in part, a chemical event.

Action Potentials↗
PubMed1983

Glucagon degradation in fraction of big plasma glucagon in rats treated with carbon tetrachloride.

When whole plasma obtained from rats given carbon tetrachloride was applied to a column of Bio Gel P-30, P-150 or P-300, a large molecular form of immunoreactive glucagon (IRG), so called "big plasma glucagon" (BPG), was eluted in the void volume. Glucagon degrading activity, measured under the same conditions as for radioimmunoassay of IRG, was eluted in parallel with IRG. Since standard assay mixture containing aprotinin was used for the measurement of IRG, this degradation of glucagon might be due to an enzyme(s) other than serine proteinases. p-Hydroxymercuribenzoate depressed glucagon degradation and IRG in the BPG fractions to 20% and 30% of the control values, respectively. Other inhibitors of thiol proteinases, such as N-ethylmaleimide and leupeptin, also decreased the values for both glucagon degradation and IRG to a similar extent. However, phenylmethylsulfonyl fluoride and pepstatin had little or no effect on these values. On filtration of plasma from carbon tetrachloride-treated rats on a column of Bio Gel A-1.5m, IRG peaks between 600k and 1,200k daltons were obtained and glucagon degrading activity was again eluted with IRG. When p-chloromercuriphenyl sulfonate and N-ethylmaleimide were added to the elution buffer and assay mixtures, the glucagon degrading activity was almost completely inhibited and the values for IRG between 600k and 1,200k daltons were decreased to less than 10% of those of the control. These results indicate that more than 90% of the IRG in the fractions of BPG obtained from carbon tetrachloride-treated rats could be accounted for entirely by the degradation of immunoreactive 125I-glucagon by plasma proteinases, probably thiol proteinases. Thus we conclude that some proteinases are still active in the radioimmunoassay system of glucagon which is widely used at present, and lead apparently higher glucagon values owing to degradation of 125I-glucagon.

Animals↗
PubMed1983

[Glioblastoma and fibrosarcoma in the brain with metaplastic bone formation--a case report].

The authors report a case in which left deep temporal fibrosarcoma with calcified area developed about 6 months after radiation therapy for left temporal astrocytoma. A 37 year-old woman was admitted to our clinic because of headache and visual deterioration. CT scan and angiography suggested left deep temporal glioma and on August 5, 1980, partial resection was performed. Histological sections showed astrocytoma G 2. Postoperative course was uneventful and she left the hospital after radiation therapy of 50 Gy. On March, 1981, right hemiparesis was noticed and progressed rapidly. CT scan suggested left temporal tumor recurred. On March 30, 1981, second operation was performed and this time, histological sections showed glioblastoma. After operation, beta-Interferon (IFN) was given intratumorally via Ommaya's reservoir (3 X 10(6) IU, daily). But in spite of IFN therapy, tumor became larger and she died on June 30, 1981. Autopsy revealed coexistence of glioblastoma and fibrosarcoma with metaplastic bone formation. A brief discussion concerning the problem of cerebral mixed tumors follows the description of the case.

Adult↗
PubMed1983

[Effect of human fibroblast interferon on malignant brain tumors].

Since 1980, phase 1 and 2 clinical trials of Hu-IFN-beta have been done in the field of neurosurgery. In the present study, (1) the results of in vivo experiments of Hu-IFN-beta are reported and (2) the effectiveness of Hu-IFN-beta in patients with malignant brain tumors is also evaluated. (1) The antitumor activities of beta-IFN and poly ICLC in nude mice receiving subcutaneous transplants of human brain tumors (2 strains) were compared with those of conventional anticancer drugs. After 3 weeks of treatment with ACNU, vincristine, bleomycin, mitomycin C, beta-IFN and poly ICLC, tumor reduction rates were evaluated by the method of Battelle. The effectiveness of beta-IFN and poly ICLC was slightly inferior to that of ACNU and vincristine, although tumor reduction rates (treated/control values) of 43% and 39% were respectively obtained with beta-IFN and poly ICLC against one strain of glioblastoma. (2) Clinically, 7 patients with malignant brain tumors were given beta-IFN (4 by intratumor administration and 3 by intravenous injection) in a dose of 3 X 10(6) to 9 X 10(6) IU/day for 2 to 6 months to study the efficiency and side effects of IFN treatment. One of four patients given IFN intratumorally showed a reduction in tumor size (partial response) by CT scan; the three patients injected IFN intravenously were unchanged. There were no noteworthy side effects in the cases treated intratumorally except for fever occurring in one patient. In the patients treated intravenously, however, fever, general malaise, leukopenia and thrombocytopenia were noted.

Adolescent↗
PubMed1983

[An evaluation of decompressive laminectomy in metastatic spinal cord tumors].

The results of consecutive cases of decompressive laminectomy for spinal cord compression from spinal metastatic tumor were reviewed. In a series of 65 patients undergoing decompressive laminectomy, the postoperative survival was 8.3 months with 60 patients. Twenty-three per cent of the group was able to ambulate for at least some period postoperatively. Paralysis had developed with great rapidity in the half of the patients who were unable to walk prior to operation. For early diagnosis and effective removal of these lesions this treatment should be taken before when signs of cord compression are evident, and especially before the patient loses his ability to walk.

Adolescent↗
PubMed1982

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↗