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Y Shibamoto

Publications and source records attributed to Y Shibamoto.

At least 145 records · Page 8Linked to original sources
PubMed1989

Variation in tumor response to fluosol-DA (20%).

The effects of Fluosol-DA 20% (FDA) and carbogen (95% O2/5% CO2) on radiosensitivity of the three experimental tumors, SCC VII tumor, RIF-I tumor, and transplanted mammary tumor of C3H/He mouse, subcutaneously inoculated in the leg were examined. The effect of FDA plus carbogen, and carbogen alone on radiosensitivity of SCC VII and RIF-I tumors was tested using the in vivo-in vitro assay. The growth curves were obtained for both SCC VII tumor and transplanted mammary tumor. The effect of the combination of FDA and carbogen was only observed in the transplanted mammary tumor. In the other two tumors, only the effect of inspiring carbogen was observed. We concluded that the effect of FDA on the radiosensitivity of experimental tumors varies with the kind of tumor systems.

Animals↗
PubMed1989

Radiation therapy for brain stem tumor with special reference to CT feature and prognosis correlations.

Seventy-nine patients with tumors of the medulla oblongata, pons, and midbrain treated by radiation therapy between 1962 and 1987 were analyzed. According to histology obtained in 28 cases, 61% were high-grade astrocytomas and 39% were low-grade astrocytomas. The 5- and 10-year survival rates of 71 patients who completed radiotherapy were 17 and 15%, respectively. Various potential prognostic factors were analyzed, and patients with a midbrain tumor, with a low-grade tumor, and without cranial nerve paresis were found to have a better prognosis. Computed tomography (CT) was performed both before and after radiotherapy on 42 patients. The volume of the tumor estimated from the CT image was various, but the tumors could be classified into three types according to the pattern of contrast enhancement (CE). Twenty-three tumors showed no CE, 15 showed a diffuse CE, and 4 showed a ring CE. No-CE tumors were generally hypodense on plain scan and were mostly large, whereas diffuse- or ring-CE tumors were relatively small. A complete response (CR) or partial response was obtained with 77% of the no-CE tumors, 64% of the diffuse-CE tumors, and 50% of the ring-CE tumors. The CR rate was higher in the tumors with a smaller volume. The 5-year survival rates for diffuse-CE, no-CE, and ring-CE tumors were 33, 15, and 0%, respectively. The 5-year survival rate was 56% for tumors smaller than 6 cm3, 16% for tumors between 6 and 20 cm3, and 0% for tumors larger than 20 cm3. In conclusion, (a) ring-CE tumors exhibited a poor prognosis; and (b) a diffuse-CE tumor, or a small or middle-sized no-CE tumor is most likely to be controlled by conventional radiation therapy.

Adolescent↗
PubMed1989

KIH-802: 2-nitroimidazole-1-acetohydroxamate as a hypoxic cell radiosensitizer.

We have identified potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802) as a hypoxic cell radiosensitizer potentially superior to Miso. The water-soluble acetohydroxamates of 2-nitroimidazole (KIH-802; free acid 801) and 4-nitroimidazole (KIH-852) were designed, synthesized, and evaluated by in vitro and in vivo screening against EMT6 cells. Enhancement ratios of KIH-802 and 801 were 1.92 and 1.68, respectively, compared with 1.58 for MISO all at 1 mM. These acetohydroxamates are also expected to be more effective in vitro than SR-2508 based on our previous experiments. In vivo ERs of KIH-802, 801, and 852 were 1.75, 1.50, and 1.35, respectively, compared with 1.57 for MISO all at the same dose of 200 mg/kg. The data clearly show that the addition of an acetohydroxamic acid moiety to the 2-nitroimidazole skeleton can enhance radiosensitizing ability.

Animals↗
PubMed1989

Importance of tumor affinity of nitroazoles in hypoxic radiosensitization.

In vitro and in vivo sensitizing activities of a variety of nitroazole derivatives including misonidazole (MISO), SR-2508, and RSU-1069 were correlated by the aid of pharmacokinetic measurements of the drug uptake in animal solid tumors. The sensitizer enhancement ratio in vivo (SERvivo) on solid tumors increased linearly with the square root of administrated dose (Ds). The specific activity (A) in vivo of nitroazoles was evaluated from the square-root empirical relationship, SERvivo = 1.00 + A D1/2S. The intratumor concentration of nitroazoles at a given time t after administration was in proportion to the DS, in which the proportional constant was defined as the tumor-affinity factor FT,t. The absolute molar activity alpha M defined by A(M/FT,t)1/2, where M is the molecular weight of nitroazoles, showed a linear relationship with the SER in vitro (SERvitro) at 1 mM of sensitizers. The sensitizer dose required to achieve an SERvivo of 1.5 (DS,1.5) decreased and thus the overall sensitizing efficiency on animal solid tumors increased as the FT,t became greater.

Animals↗
PubMed1989

Characteristics of fluorinated nitroazoles as hypoxic cell radiosensitizers.

Types of 2-nitroimidazoles and 3-nitro-1,2,4-triazoles bearing one or two fluorine atoms on their side chains were synthesized to evaluate their physicochemical properties, radiosensitizing effects, and toxicity. The reduction potential of the compounds containing one fluorine was similar to that of misonidazole (MISO), whereas that of the difluorinated compounds was slightly higher. Both mono- and difluorinated compounds had an in vitro sensitizing activity comparable to or slightly higher than that of MISO. The fluorinated 3-nitrotriazoles were almost as efficient as the 2-nitroimidazoles with the same substituent. In vivo, some of the compounds were up to twice more efficient than MISO, whereas others were as efficient as MISO. Toxicity in terms of LD50/7 in mice was quite variable depending on the side-chain structure; the amide derivatives were less toxic than MISO, whereas the alcohol and ether derivatives were more toxic. In view of the radiosensitizing effect and toxicity in vivo, at least one compound, KU-2285 (a 2-nitroimidazole with an N1-substituent of: CH2CF2CONHCH2CH2OH) has been found to be as useful a hypoxic cell sensitizer as SR-2508.

Animals↗
PubMed1989

The effect of arterial oxygen content on the results of radiation therapy for epidermoid bronchogenic carcinoma.

Anemia is believed to be an important prognostic factor in treating cancer patients by radiation therapy. One possible explanation for this is tumor oxygenation. With respect to tumor oxygenation, the arterial oxygen content (CaO2) may be of more importance than the hemoglobin (Hb) level. This study shows the relationship between the CaO2 and tumor response to radiation therapy. Forty-two patients with epidermoid bronchogenic carcinoma, treated by irradiation alone between April 1982 and March 1986, were reviewed. Regression of the tumor after radiation therapy was calculated as a percent change in the tumor area. Arterial oxygen partial pressure (PaO2), Hb level, and percent oxygen saturation of Hb in arterial blood (SaO2) were measured within 2 weeks of commencement of radiation therapy and the CaO2 was calculated. The rank correlation coefficients between the maximum percent regression of the tumor and the PaO2, the Hb level and the CaO2 were 0.36, 0.34, and 0.46, respectively. Statistical analyses of the data indicate that the group of patients with CaO2 over 14.5 ml/dl exhibited greater tumor regression and longer survival periods than the group of patients with CaO2 below 14.5 ml/dl. Similarly patients with PaO2 over 90 mmHg or Hb level over 11 g/dl, exhibited significantly greater tumor regression and longer survival periods than those with PaO2 below 90 mmHg and Hb level below 11 g/dl. There were no significant differences in the length of survival periods with respect solely to the Hb level or the PaO2. It was concluded that the CaO2 is more important than the Hb level in determining tumor response to radiation therapy. This is considered as important indirect evidence of the existence of hypoxic fractions of cells in human tumors.

Adult↗
PubMed1989

A new, potent 2-nitroimidazole nucleoside hypoxic cell radiosensitizer, RP170.

The radiosensitizing activity, acute toxicity and pharmacokinetics of RP170, a new hypoxic cell radiosensitizer, were compared with those of misonidazole (MISO) and SR2508. RP170 belongs to the group of 2-nitroimidazole nucleosides, which are designed to be selectively excluded from the neural tissue. The reduction potential of RP170 was similar to that of MISO and SR2508. The partition coefficients in octanol/water of RP170, MISO, and SR2508 were 0.094, 0.35, and 0.021, respectively. The radiosensitizing activity of RP170 was similar to that of MISO and SR2508 in vitro and in vivo. There was no significant difference in the radiosensitizing activity of RP170 in vivo between intravenous and intraperitoneal administration. The acute toxicity of RP170 was the same as that of SR2508. Pharmacokinetic evaluation showed that the concentration of RP170 in the brain was as low as that of SR2508. RP170 is expected to have the same radiosensitizing effects as MISO and SR2508, and to be less neurotoxic than MISO.

Animals↗
PubMed1989

Radiosensitizing hypoxic cells with new 3-nitro-1,2,4-triazole derivatives in vitro and in vivo.

The new regioisomer derivatives 4a-f and 5a-f of 3-nitro-1,2,4-triazole (3-NTR) were synthesized for the development of new radiosensitizers of hypoxic cancer cells for radiotherapy. N(2)-Substituted 3-NTR derivatives 5a-f were stronger radiosensitizers of hypoxic cells in vitro (Chinese hamster V79 cells) than N(1)-substituted 3-NTR derivatives 4a-f, but in vivo they were weaker (SCCVII carcinoma cells inoculated into C3H/He mouse).

Animals↗
PubMed1989

[Results of conventional radiotherapy in malignant gliomas:].

Results of radiotherapy for 164 supratentorial malignant gliomas were analyzed based on recent histological subclassification into glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). Patients with AA had a better prognosis than those with GBM. The 5-year survival rate was 1% for GBM and 16% for AA. The size of radiation field did not influence survival significantly, and whole brain radiation appeared of no benefit. Survival time prolonged with an increase of radiation dose between 45 Gy and 72 Gy. The optimal radiotherapy for the disease is discussed.

Adolescent↗
PubMed1989

[Hypoxia and reoxygenation in experimental tumors].

Hypoxic fractions (HF) and reoxygenation of various murine tumors were studies using a paired survival assay. All irradiations were given to whole-body of mice without anesthesia or physical restraint, both of which can increase HF artificially. HF's of 4 different tumors of 1 cm in diameter were between 4.5% and 14%. Thus, variation of HF due to tumor type was quite small. HF was roughly correlated with tumor size and proportion of necrotic areas. Reoxygenation was examined in two tumor systems, and it occurred rapidly (within 1 hr after radiation) in one tumor but rather slowly in another.

Animals↗
PubMed1988

Relationship between heat-induced vascular damage and thermosensitivity in four mouse tumors.

The relationship between heat-induced vascular damage and thermosensitivity was studied using four mouse transplantable tumors. The tumors used were spontaneous mammary carcinoma, SCC VII carcinoma, EMT6 sarcoma, and B16 melanoma. Under cultured conditions, B16 was more thermosensitive at 43 degrees C and 44 degrees C than SCC VII or EMT6. The in vivo tumor response to heat was evaluated by the growth delay after heating at 44 degrees C for 30 min. Among the four tumors, SCC VII was the most thermosensitive in vivo followed by EMT6, whereas B16 and spontaneous mammary carcinoma were thermoresistant. Vascular damage was studied quantitatively up to 24 h after heating by using microangiography. The order of the four tumors in vascular damage was well correlated with the tumor response in vivo. Histologically, tumor vessels of spontaneous mammary carcinoma were supported by connective tissues, and those of B16 had dense endothelial cells, compared to sparse endothelial cells of SCC VII and EMT6. Our findings suggest that variability in heat sensitivity of tumors is related to variation in the histological structure of tumor vasculature. That is, tumor vasculature with perivascular connective tissues and/or dense endothelial cells is less heat labile than that composed only of sparse endothelial cells.

Animals↗
PubMed1988

Treatment results of intracranial germinoma as a function of the irradiated volume.

Between 1962 and 1986, 70 patients were treated with radiation for confirmed or suspected intracranial germinoma at our hospital. The diagnosis was based on histology in 30 cases, cerebrospinal fluid (CSF) cytology in 12 cases, and on clinical and radiological findings in the remaining 28 cases. The target of radiation was the primary tumor site in 34 cases (Group A), the entire neuraxis in 22 cases (Group B), the whole brain in 4 cases (Group C), and the ventricle plus spine in 6 cases (Group D). Four patients were not included in the above groups for various reasons. The average radiation dose was 50-55 Gy to the tumor, 30 Gy to the whole brain, and 24 Gy to the spinal axis. The 5- and 10-year survival rates of the 68 primary cases in which radiotherapy was completed were 86% and 79%, respectively. The survival and relapse-free survival rates for the above 4 groups did not differ significantly, although slightly better results were seen in Groups B and C. Five cases in Groups A and D developed intracranial recurrence, 4 adjacent to the primary site but 1 distant from it, whereas no intracranial recurrence was found in the whole-brain-treated groups (B and C). One patient in Group B developed spinal metastasis, which was possibly due to inadequate radiation fields, and another in Group B developed abdominal metastasis via the shunt tube. Craniospinal irradiation should be administered to the patients with demonstrated meningeal seeding or with a positive CSF cytology. For cytology-negative cases with no evident metastasis, irradiation of the tumor plus a wide margin is usually sufficient, but craniospinal irradiation should be considered when the disease extends along the ventricular walls or is present in both pineal and suprasellar regions.

Adolescent↗
PubMed1988

Microangiographic and histologic analysis of the effects of hyperthermia on murine tumor vasculature.

The effects of hyperthermia on murine tumor vasculature were studied by microangiography and histological examination. The tumors used were SCC VII carcinoma and mammary adenocarcinoma of syngeneic C3H/He mice. For the quantitative analysis of microangiographic changes, the percent (%) vascular area, which was defined as the percentage of opacified tumor vessel area to the entire tumor area, was determined in each microangiogram. The % vascular area after heating in a water bath at 44 degrees C for 30 min was minimized 24 hr after heating in both types of tumors. The histologic study revealed that the initial decrease of the % vascular area was due to congestion, thrombosis, and rupture of tumor vessels, and its subsequent increase was due to angiogenesis. SCC VII was more heat sensitive than mammary adenocarcinoma in terms of tumor growth delay, and tumor vessels of SCC VII were more vulnerable to heat than those of mammary adenocarcinoma. Histological examinations showed a marked difference in the architecture of vessels between the two types of tumors. Tumor vessels of mammary adenocarcinoma were supported by a connective tissue band, whereas those of SCC VII consisted of a single endothelial cell layer. Our findings suggest that the tumor vessels supported by a connective tissue band are less sensitive to heat than those without such support. The vascular damage of SCC VII was temperature dependent, and the critical temperature at which dramatic vascular damage appeared was between 42.7 degrees C and 43.7 degrees C.

Angiography↗
PubMed1988

[Developments in the experimental methods of evaluating hypoxic cell sensitizers].

Recent developments in the evaluation methods for hypoxic cell sensitizers were reported with emphasis on the following 3 points. (1) A new sensitizer-screening system consisting of the EMT 6 single cell, spheroid, and solid tumor was proposed by us and was found to be a useful, sophisticated system. (2) In the in vivo experiments, irradiation conditions for mice and the drug dose level influenced the hypoxic fraction of tumors significantly. Investigators must always take these facts into consideration when doing in vivo experiments. (3) Three new compounds recently developed in Japan proved to be superior to misonidazole.

Animals↗