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Biomedical subjects

Y Shibamoto

Publications and source records attributed to Y Shibamoto.

At least 127 records · Page 7Linked to original sources
PubMed1991

Incorporation of cortical bone autografts following intraoperative extracorporeal irradiation in rabbits.

In an experimental study using 60 rabbits, a cortical bone segment of the unilateral tibial diaphysis was resected, irradiated extracorporeally, and reimplanted immediately as an autograft. The subsequent process of graft incorporation was examined over a 26-week period by roentgenography, histology, and histomorphometry. The irradiation doses were 0 (control), 50, 100, and 200 Gy. Roentgenographic and histologic examinations revealed that cortical bone autografts irradiated at 50 to 200 Gy were incorporated in the same manner as non-irradiated controls. By histomorphometry, the mean unresorbed fraction of the grafts at 6 weeks post-implantation was estimated to be 88.4% for the control group and 89.4% for the 200 Gy group. That of 26 weeks postimplantation was 17.5% for the control and 28.5%, 26.1%, and 27.8% for the 50, 100, and 200 Gy groups, respectively. Cumulative new bone formation showed a similar but inverse pattern of difference between the control and irradiated groups at 26 weeks. However, these differences were not statistically significant and were considered to be slight when compared with the overall similarity of the process. The total cross-sectional area of cortical bone at 26 weeks was similar to that of the contralateral side in all groups. In none of the adopted evaluation methods was any difference detected among the three irradiated groups with different doses. The results of this study suggest that extracorporeal irradiation of autografts at the specified doses impairs possible cellular contribution of the grafted marrow to the incorporation process, but does not interfere with the contribution of the matrices. The results provide useful information concerning the method of limb salvage surgery using intraoperatively-irradiated autografts.

Animals↗
PubMed1991

In vivo radiosensitizing activity of a new fluorinated hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation.

Since most clinical radiotherapy is given as multiple small irradiation fractions, the present study was undertaken to test the in vivo radiosensitizing activity of a new hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation. Radiosensitizing activity was measured by a growth delay assay using a transplanted mammary tumor in C3H/He mice, and by an in vivo-in vitro assay using the SCC VII tumor. KU-2285 was injected intraperitoneally 30 min before irradiation in all experiments. The in vivo-in vitro assay using SCC VII tumors showed that 12.5 micrograms/g of KU-2285 sensitized the tumors to irradiation (5 Gy/fr x 5 fr/48 hr or 6 Gy/fr x 3 fr/48 hr). KU-2285 also sensitized the transplanted mammary tumors to fractionated irradiation. We concluded that KU-2285 was able to sensitize two different murine tumors when given in combination with radiation dose fractionation.

Animals↗
PubMed1991

Evaluation of a new 2-nitroimidazole nucleoside analogue, RK-28 as a radiosensitizer for clinical use.

The experimental data previously reported on RK-28, a hypoxic cell sensitizer which is now being tested in a phase I clinical trial, are confusing. Some data indicate superiority of RK-28 over misonidazole (MISO), whereas others do not. This paper presents our experimental data on the efficacy, toxicity, and pharmacokinetics of RK-28, in comparison with those of MISO, and also summarizes the data of other investigators. In our experiments, RK-28 had a 1.5-2.5 times higher sensitizing activity in vitro on EMT6 and SCCVII cells than MISO, and the difference was larger when the pre-irradiation incubation time was longer. The latter was considered to be due to the time-dependent cellular uptake and reactivity of RK-28 with non-protein sulphydryls. In vivo, RK-28 was almost as efficient as or slightly inferior to MISO against SCCVII and EMT6 tumours when assayed with an in vivo/in vitro assay and a growth delay time assay. The LD50/7 by a single injection of RK-28 was half that of MISO, but when 60% of LD50/7 was injected into mice every day, the total dose that could be given was higher for RK-28 than for MISO. Pharmacokinetic studies using mice, rats, rabbits, and a dog showed that RK-28 was rapidly eliminated from the blood and various tissues. From our results it was concluded that the possible success of the clinical trial of RK-28 depends on its low cumulative toxicity.

Animals↗
PubMed1991

Changes in bone after high-dose irradiation. Biomechanics and histomorphology.

We studied the effects of high-dose irradiation on the mechanical properties and morphology of cortical bone in rabbits for 52 weeks after a single dose of 50 Gy of electron-beam to the tibia. After four weeks, the bending strength of the irradiated bone was unchanged, but at 12 weeks, the strength had decreased significantly. At 24 weeks after irradiation mean strength was less than half of controls but by 52 weeks there was a tendency toward recovery. Similar, synchronous changes of damage and recovery were seen in cortical porosity, haematopoietic cells in the bone marrow and endosteal new bone formation.

Animals↗
PubMed1991

Tumor radiosensitivity prediction by the cytokinesis-block micronucleus assay.

An in vivo to in vitro cytokinesis-block micronucleus assay technique using cytochalasin B (Cyt-B) was established in xenografted human and murine tumors, and the correlation between radiosensitivity measured by this assay and that measured by a colony-forming assay was investigated. Tumors were irradiated in situ, excised immediately, and disaggregated to single cells that were plated for the micronucleus and colony-forming assays. Some of the tumor cells were irradiated in vitro rather than in vivo. For the micronucleus assay, Cyt-B (0.5-3 micrograms/ml) was added to dishes soon after plating or in vitro irradiation and the cells were subsequently fixed and stained at intervals (12-144 h). The micronucleus frequency in binucleate cells was evaluated under conditions of maximum yield of the binucleate cells. The micronucleus frequency after irradiation was quite variable depending on the tumor type and the average number of micronuclei per single binucleate cell after 4 Gy ranged from 0.2 to 1.4. The results of in vitro irradiation were not significantly different from those of in vivo irradiation for all tumors. A good correlation was found between the radiosensitivity determined by the micronucleus assay and that found with the colony-forming assay in six human tumors (r = 0.94 approximately 0.98) but not in four murine tumors because of one exceptional tumor. When this tumor was excluded, a correlation was also found for the remaining nine tumors (r = 0.62 approximately 0.96). These results indicated that the cytokinesis-block micronucleus assay has some promise as a rapid predictive assay of radiosensitivity.

Animals↗
PubMed1990

Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic vincristine-doxorubicin-cyclophosphamide-prednisolone chemotherapy.

Thirty patients with histologically proven primary intracranial non-Hodgkin's lymphoma were treated at Kyoto University. Ten of them were treated prospectively with a radiation-chemotherapy protocol. All but four specimens were recently reexamined and classified according to the Working Formulation system. The predominant histologic types were diffuse large cell type, large cell immunoblastic type, and diffuse mixed small and large cell type, seen in 38%, 21%, and 21% of cases, respectively. Before 1980, 16 patients were treated with postoperative radiation without definite chemotherapy, and only one has survived more than 5 years. Local recurrence was the most common cause of failure. In 1981, the authors started a protocol in which four to six courses of systemic chemotherapy with vincristine, doxorubicin, cyclophosphamide, and prednisolone (VEPA) was given after whole brain radiation (30-40 Gy) with a local boost up to 50 to 60 Gy. Eight patients completed this protocol, and all of them are alive at 16 to 100 months after diagnosis, with three patients surviving more than 5 years. Only one patient developed recurrence. On the other hand, six patients who did not complete or receive chemotherapy after 1981 are dead or alive with recurrence. Correlation between the Working Formulation subtype and prognosis was not clear because of the variety of treatment. Two patients receiving chemotherapy developed brain necrosis, which was fatal in one case, and the other two patients treated with the protocol are in a poor state without signs of recurrence. Chemotherapy may enhance the radiation effect on normal brain tissue as well as tumor. Combination of radiotherapy and chemotherapy can improve the survival rate, but the optimal dosage needs to be investigated further.

Adolescent↗
PubMed1990

KIH-802, an acetohydroxamic acid derivative of 2-nitroimidazole, as a new potent hypoxic cell radiosensitizer: radiosensitizing activity, acute toxicity, and pharmacokinetics.

The radiosensitizing activity, acute toxicity, and pharmacokinetics of a new hypoxic cell radiosensitizer, potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802), were compared with those of misonidazole (MISO) and etanidazole (SR-2508). The radiosensitizing activity of KIH-802 was slightly higher than that of MISO and SR-2508 in vitro and was similar to or slightly higher than that of MISO or SR-2508 in vivo. The acute toxicity of KIH-802 was slightly higher than that of MISO. The concentrations of KIH-802 in the brains and peripheral nerves of mice were as low as those of SR-2508 and lower than those of MISO.

Animals↗
PubMed1990

Intracerebral malignant lymphoma with fluctuating regression and spatial evolution.

Seven patients with histologically proven primary intracerebral malignant lymphoma, characterized by a fluctuating nature with both transient regression and spatial evolution of the tumors without contiguity to the initial lesion, are presented. Although the overall outcome was unfavorable, two cases had a long-term survival of 3 years or more and one of them showed a good quality of life. Correlation among characteristic clinical presentations, computed tomography scans, and prognostic factors after management with surgery, radiation, and chemotherapy, including steroids, is discussed.

Aged↗
PubMed1990

Supratentorial malignant glioma: an analysis of radiation therapy in 178 cases.

To analyze treatment results of supratentorial malignant gliomas in the megavoltage era, all the histologic specimens were reviewed and glioblastoma multiforme (GBM) was distinguished from anaplastic astrocytoma (AA) by the presence of necrosis. Among those who had completed radiotherapy and who had been followed for at least one year, 135 GBM and 43 AA patients were found. The median survival time (MST) after operation was 12 months for GBM and 18 months for AA. The 5-year survival rate was 0.9% for GBM and 18% for AA. The size of radiation field had little influence on survival time; MST was 12 months for GBM patients treated with a local field covering tumor plus less than 2 cm margin, 12 months for those treated with a generous field (2 cm or more margin), and 13 months for those treated to whole brain. Also for AA, whole brain radiation did not prolong survival. Initial relapse of GBM and AA developed within the irradiated volume in 86% of the cases treated with a generous field. Whole brain radiation seemed useless for the treatment of malignant gliomas. Survival time appeared to be dose-dependent; MST was 10, 13, and 16 months for GBM patients who received 45-57, 57-63, and 63-72 Gy, respectively. Extensive surgical resection was associated with a better prognosis in GBM. AA patients 60 years old or older had a poorer prognosis than younger patients, but age was not a significant prognostic factor for GBM. Chemotherapy appeared to prolong survival slightly without improving long-term survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Effect of recombinant human granulocyte colony-stimulating factor on granulocytopenia in mice induced by irradiation.

We report the effect of human granulocyte colony-stimulating factor (hG-CSF) on the recovery from granulocytopenia induced by irradiation. Female 9-week old C3H/He mice were used. The irradiation schedule was as follows: Group 1 and 2 received whole-body irradiation of 1 Gy and 5 Gy, respectively, on day 0; Group 3 and 4 received whole-body irradiation of 0.5 and 1.0 Gy, respectively, for 5 consecutive days; Group 5 received upper hemibody irradiation of 3 Gy for 5 consecutive days. Daily subcutaneous injections of G-CSF (3 x 10(5) Unit/mouse) or 0.3 ml of saline to each group were started from the day after the first irradiation and continued for 18 days. Mice were sampled randomly from each group, and the total number of leukocytes, erythrocytes of peripheral blood, nucleated cells in femur, and spleen weight were counted and measured, respectively, on day 0, 3, 5, 7, 9, 12, and 18. The leukocyte counts decreased with an increase in radiation doses. In Group 1 and 2 mice, G-CSF enhanced the leukocyte count more than saline. In Group 3 mice, the recovery of leukocytopenia was facilitated by G-CSF, but in Group 4 mice, G-CSF had no effect on the leukocyte count decrease or on leukocytopenia recovery. In Group 5 mice, G-CSF greatly affected leukocytopenia recovery. Increase in spleen weight paralleled the peripheral leukocyte count. Daily administration of recombinant hG-CSF accelerated the granulocytopenia recovery which was induced by irradiation, and it may be a useful therapeutic agent for treating myelosuppressive cases.

Agranulocytosis↗
PubMed1990

High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer.

Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5-year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases.

Adult↗
PubMed1990

Pharmacokinetics of 2-nitroimidazole hypoxic cell radiosensitizers in rodent peripheral nervous tissue.

The concentrations of seven 2-nitroimidazoles--including misonidazole, etanidazole (SR-2508), pimonidazole (Ro 03-8799), desmethylmisonidazole (Ro 05-9963), RK28, RP170, and KU2285--were measured in the sciatic nerves of C3H/He mice using reverse-phase high-performance liquid chromatography. Drug exposure to the peripheral nervous system was highest for misonidazole, followed by desmethylmisonidazole, etanidazole, pimonidazole and RK28. The lower drug exposure of pimonidazole and RK28 seemed to be related to their lower hydrophilicity. The apparent biological half-lives of the compounds in the peripheral nerves were correlated to their hydrophilicity: the more hydrophilic the compound, the longer the apparent biological half-life in the peripheral nervous tissue of the mice. Measurement of drug exposure in the rodent peripheral nervous system, rather than in the brain, was a better indicator for estimating the occurrence of clinical peripheral neuropathy by 2-nitroimidazoles.

Animals↗
PubMed1990

Combined effect of radiation and YM-881 (SMANCS) on murine tumors and bone marrow.

The combined effect of radiation and YM-881 (SMANCS) was studied in vitro and in vivo. When 0.25 microgram/ml of YM-881 was simultaneously combined with radiation, during and after irradiation for 30 min in total, Dq decreased from 3.3 Gy to 1.4 Gy without changing D0 in the dose-survival curve of exponentially growing SCC VII tumor cells. Five or ten times administrations of 0.1 mg/kg YM-881 at an interval of 24 h did not inhibit tumor growth. However, administration of 0.1 mg/kg YM-881 just before every irradiation which was repeated five times at an interval of 24 h yielded dose modifying factors (DMFs) of 1.8-1.2 when the tumor response to treatment was evaluated by the time for the tumors to regrow to three times the original volume. Administration of YM-881 ten times just before every irradiation yielded DMFs of 1.3-1.2. Adverse effects of the combination on bone marrow were examined by spleen colony assay. After five injections of 0.1 mg/kg YM-881, the mean number of CFU-S per femur decreased to 77% of the pretreatment level, but this was not significant statistically (0.1 greater than p greater than 0.05). The slope of radiation response curve for CFU-S per femur was not affected by the combination.

Animals↗
PubMed1990

[Radiographic staging procedures and radiotherapy of malignant lymphoma].

Radiographic studies play an important role in the clinical staging of malignant lymphoma (ML). Conventional procedures are plain chest X-ray, lymphangiography, gastrointestinal series, and 67Ga scintigraphy. Gastro-intestinal series is essential in non-Hodgkin's lymphoma (NHL) of Waldeyer's ring and thyroid. 67Ga scintigraphy is a non-invasive procedure useful in the screening of ML. Recently marked improvements have been made in the diagnostic modalities. CT scan and NMR have made it very easy to diagnose ML of the central nervous system and detect the extension of tumors at all sites. In some cases with Hodgkin's disease (HD), staging laparotomy is necessary, but not in cases with NHL. If tumors are localized, subtotal or total nodal irradiation is performed for patients with HD, and generous involved field is employed for NHL with or without combined chemotherapy at our department. Good local control is obtained except for NHL of the central nervous system at a total dose of 40-50 Gy. NHL is prone to relapse outside the radiation field. Therefore we consider that combined chemotherapy is indicated for NHL such as T-cell lymphomas, those with high grade histology classified according to the Working Formulation, and with involvement of lymph nodes larger than 6 cm in diameter.

Combined Modality Therapy↗
PubMed1990

Treatment of murine SCC VII tumors with localized hyperthermia and temperature-sensitive liposomes containing cisplatin.

The release of cisplatin (CDDP) encapsulated in temperature-sensitive unilamellar liposomes to murine SCC VII carcinoma by localized hyperthermia and the effects of the treatment on tumor growth were studied. A transition temperature of the temperature-sensitive liposomes containing cisplatin (LIP-CDDP) was 41 degrees C. Twenty-four hours after injection of LIP-CDDP, the heated tumors (42 degrees C, 60 min) contained 3.3 times more CDDP than the unheated tumors receiving free CDDP. Although the uptake of liposome-associated CDDP by liver was approximately threefold greater at 1.5 h after injection than uptake of free CDDP, it decreased about 50% over a 24-h period. No difference in uptake of the two forms of CDDP by kidney was observed. The combination of LIP-CDDP and localized heating at 42 or 43 degrees C was more effective relative to the amount of CDDP in delaying tumor growth than that of free CDDP and hyperthermia. Treatment with LIP-CDDP plus local heating resulted in a dose-modifying factor of 5.3 when compared with free CDDP and no hyperthermia. The dose-modifying factor was 2.8 when treatment with LIP-CDDP and heat was compared with treatment with free CDDP and heat. Thus CDDP could be released selectively from the temperature-sensitive liposomes by heat and resulted in both a greater uptake of the drug and a delay in tumor growth.

Animals↗
PubMed1989

[Results of radiation therapy for medulloblastoma].

Results of radiation therapy for cerebellar medulloblastoma at Kyoto University Hospital were reviewed. Between 1962 and 1988, 30 patients with histologically-proven medulloblastoma completed radiotherapy. Before 1971, the treatment volume was either the posterior fossa only or posterior fossa plus spinal axis, but after 1972, it was extended to include the entire neuraxis. The mean dose was 48 Gy to the posterior fossa, 36 Gy to the whole brain, and 25 Gy to the spinal axis. The 5-year survival rate and 5-year relapse-free survival rate estimated by the Kaplan-Meier's method were 36% and 37%, respectively, for total cases, but were as high as 79% and 80%, respectively, for the recent 10 patients. This improvement in the treatment results appeared to be due to extensive tumor resection and improved radiotherapy technique, and not to the use of chemotherapy. The prognosis was significantly better in patients treated with craniospinal irradiation than in those otherwise treated. There was a trend towards better survival in patients who received 50 Gy or more to the posterior fossa or 24 Gy or more to the spinal axis, compared to the patients who received lower doses to each site. No significant morbidity of radiotherapy was seen. Four of the six surviving patients who were treated below age 12 have a mental retardation and/or a short stature, but one patient treated at age 5 has a normal growth and a good intelligence. From these analysis, it is recommended to irradiate craniospinal axis and posterior fossa up to 25-35 Gy and 50-55 Gy, respectively.

Adolescent↗