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Biomedical subjects

Y Shibamoto

Publications and source records attributed to Y Shibamoto.

At least 73 records · Page 4Linked to original sources
PubMed1997

Primary testicular non-Hodgkin's lymphoma: a clinical study and review of the literature.

Non-Hodgkin's lymphoma (NHL) of the testis is a rare disease, and treatment outcome is generally poor. In this retrospective study, we investigated treatment results for testicular NHL in an attempt to develop an effective treatment policy for this disease. The survival rate and characteristics were retrospectively analyzed in eight patients with NHL of the testis who were treated between 1969 and 1991 at Kyoto University Hospital, Department of Radiology. Four patients were at stage IEA, one at stage IIEA, and three at stage IVEA. Of the eight testicular lymphomas, six were classed as intermediate grade lymphomas and two as high-grade lymphomas according to the Working Formulation. All of the eight patients received orchiectomy. Six patients received combined chemotherapy and radiation therapy as the primary treatment for the disease. One patient each was treated with radiation therapy alone or combination chemotherapy alone. The 5-year overall and disease-free survival rate was 45 and 33%, respectively. Even though almost all of the patients had received combination chemotherapy, high incidence of relapse in the central nervous system (CNS) was observed. Prophylactic treatment against such recurrence may be necessary to improve the treatment outcome of patients with testicular NHL.

Adult↗
PubMed1997

Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.

PURPOSE: To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS: Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17. RESULTS: The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity. CONCLUSION: Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration.

Adult↗
PubMed1996

Reoxygenation after single irradiation in rodent tumors of different types and sizes.

PURPOSE: To investigate the variation of reoxygenation patterns after single irradiation in murine tumors of different types and sizes. METHODS AND MATERIALS: Whole-body single irradiation of 13 to 15 Gy was delivered to 10 mm RIF1 tumors of C3H/He mice, 22 mm SCCVII tumors of C3H/He mice, and 16 mm EMT6 tumors of Balb/c mice. Thereafter, changes in the hypoxic fraction with time were determined by the paired survival curve method. The data were compared with the results we had ++previously obtained with 10 mm SCCVII and 10 mm EMT6 tumors. RESULTS: The hypoxic fraction at 1 h after the priming irradiation was 26% for 10 mm RIF1 tumors, 48% for 10 mm SCCVII tumors, and 100% for 10 mm EMT6 tumors. Thus, RIF1 and SCCVII tumors, both of which have few necrotic areas, showed rapid reoxygenation, whereas EMT6 tumors, which have large necrotic areas, reoxygenated slowly. Although the hypoxic fraction returned to the pretreatment level within 72 h in 10 mm SCCVII and 10 mm EMT6 tumors, it did not in 10 mm RIF1 tumors. In contrast, the patterns of reoxygenation were similar between 22 mm and 10 mm SCCVII tumors and between 16 mm and 10 mm EMT6 tumors. CONCLUSION: The three tumors showed different patterns of reoxygenation. Tumors that have a low proportion of necrosis may reoxygenate rapidly. However, tumor size appeared to have less influence on the pattern of reoxygenation.

Animals↗
PubMed1996

Effect of interfraction interval in hyperfractionated radiotherapy with or without concurrent chemotherapy for stage III nonsmall cell lung cancer.

PURPOSE: To explore the influence of interfraction interval in hyperfractionated radiotherapy (HFX RT) with or without concurrent chemotherapy for Stage III nonsmall cell lung cancer. METHODS AND MATERIALS: One hundred sixty-nine patients treated in a randomized study were retrospectively analyzed. Group I patients were treated by HFX RT with 1.2 Gy twice daily with a total dose of 64.8 Gy in 27 treatment days, while Groups II and III patients were treated by the same HFX RT and concurrent chemotherapy with carboplatin and etoposide (every week in Group II and every other week in Group III). Interfraction intervals of either 4.5-5 h or 5.5-6 h were used for each patient. RESULTS: Patients treated with shorter interfraction intervals (4.5-5 h) had a better prognosis than those treated with longer intervals (5.5-6 h) (median survival: 22 vs. 7 months; 5-year survival rate: 27% vs. 0%, p = 0.00000). This phenomenon was observed in all treatment groups. Patients > or = 60 years of age, with Stage IIIA disease, or with previous weight loss < or = 5% were treated more often with the shorter intervals than those < 60 years, with Stage IIIB disease, or with weight loss > 5%, respectively, but in all of these subgroups of patients, the shorter intervals were associated with a better prognosis. Multivariate analysis showed that the interfraction interval was an independent prognostic factor, together with sex, age, performance status, and stage. The shorter intervals were associated with an increased incidence of acute high grade toxicity, but not with an increase in late toxicity. CONCLUSION: Patients treated with shorter interfraction intervals (4.5-5 h) appeared to have a better survival than those treated with longer intervals (5.5-6 h). Prospective randomized studies are warranted to further investigate the influence of interfraction interval in HFX RT.

Age Factors↗
PubMed1996

High-dose intraoperative radiotherapy for unresectable pancreatic cancer.

PURPOSE: The results of high-dose intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for unresectable pancreatic cancer were analyzed to evaluate the possible advantages of IORT in combination with EBRT. METHODS AND MATERIALS: Between 1983 and 1993, 115 patients with unresectable adenocarcinoma of the pancreas (53 with non-Stage IV disease and 62 with Stage IV disease) were treated with EBRT + IORT (55 patients), EBRT alone (44 patients), or IORT alone (16 patients). In non-Stage IV patients, the use of EBRT alone was due to the unavailability of IORT and the use of IORT alone was due to refusal of EBRT. The IORT dose was 30-33 Gy and the EBRT dose was 40-60 Gy. A historical control group comprised of 101 patients undergoing palliative surgery alone was also analyzed. RESULTS: Both non-Stage IV and Stage IV patients receiving EBRT with or without IORT had a better prognosis than the nonirradiated historical controls. Among non-Stage IV patients, the median survival of the EBRT + IORT group (8.5 months) and the EBRT group (8 months) was similar, although survival from 12 to 18 months was higher in the former group (38% vs. 10% at 12 months, p = 0.018, and 19% vs. 0% at 18 months, p = 0.023). In Stage IV patients, the prognosis was not influenced by the type of radiotherapy. Multivariate analysis revealed that a pretreatment carbohydrate antigen (CA) 19-9 level < 1000 U/ml was associated with better survival. In non-Stage IV patients with a CA 19-9 level < 1000 U/ ml, EBRT + IORT appeared to produce a better survival than EBRT alone (p = 0.047). This was supported by multivariate analysis. CONCLUSION: High-dose IORT + EBRT may be more effective than EBRT alone in patients with unresectable but localized pancreatic cancer and a low CA 19-9 level.

Adenocarcinoma↗
PubMed1996

A phase I study of a hypoxic cell sensitizer KU-2285 in combination with conventional radiotherapy.

A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given orally to 14 patients. The daily dose ranged from 0.5 to 2.0 g and the total dose given ranged from 0.8 to 28 g/m2. Possible toxicities observed were vomiting in two patients, muscle cramping in one and multiple joint pain in one. All these complications were mild and transient and no other toxicity was observed. The peak serum concentration of KU-2285 was 25-30 micrograms/ml at the dose of 1 g/m2. The cumulative toxicity of KU-2285 appears to be relatively low and further clinical trials seem to be warranted.

Administration, Oral↗
PubMed1996

Radiotherapy for primary squamous cell carcinoma of the trachea.

Twenty-two patients with tracheal squamous cell carcinoma were treated by radiotherapy alone. Nine patients were treated with 60 Gy between 1982 and 1987 and 13 with 70 Gy between 1988 and 1993 using conventional fractionation. The median survival was 24 months and the 5-year survival rate was 27%. Patients receiving 70 Gy had a slightly better prognosis than those receiving 60 Gy, but the difference was not significant. Patients with mediastinal lymph node involvement had a significantly worse prognosis. Delayed tracheal toxicity tended to be higher in the 70 Gy group.

Carcinoma, Squamous Cell↗
PubMed1996

Combined effect of clinically relevant doses of emitefur, a new 5-fluorouracil derivative, and radiation in murine tumours.

We investigated the combined effect of radiation and clinically relevant doses of emitefur (BOF-A2), a newly developed anti-cancer agent consisting of a masked form of 5-fluorouracil (5-FU) and a potent inhibitor of 5-FU degradation, in two types of murine tumours. In preliminary pharmacokinetic studies, the area under the curve for 5-FU in plasma, after administration of 12.5 mg kg-1 and 25 mg kg-1 emitefur in mice, appeared to be similar to that obtained on the first day and that on the seventh day, respectively, after starting administration of 400-600 mg day-1 in humans. These doses (12.5 and 25 mg kg-1) of emitefur were evaluated either alone or in combination with single (15 Gy), five-fraction (4 Gy each) or ten-fraction (2.8 Gy each) irradiation using a tumour growth delay assay for SCCVII tumours and in combination with four-fraction (5 Gy each) irradiation using an in vivo-in vitro assay for EMT6 tumours. The anti-tumour and radiation-enhancing effects of 12.5 mg kg-1 emitefur were not significant in any except the ten-fraction experiment. On the other hand, multiple doses of 25 mg kg-1 emitefur given either alone or in combination with radiation produced marked effects. The mean tumour growth delay time (the time to double in volume for treated tumours minus that for untreated tumours) was 8.1 days for five administrations of 25 mg kg-1 emitefur. 10.4 days for five fractions of 4 Gy and 22.1 days for five treatments with the combination of the two. Thus, the increase in growth delay afforded by this combination was at least additive. The effect of four fractions of 5 Gy with 25 mg kg-1 emitefur in EMT6 tumours was lower than that of four fractions of 7.5 Gy, but the effect of five fractions of 4 Gy with this dose of emitefur in SCCVII tumours was similar to the effect of five fractions of 6 Gy, and the effect of ten fractions of 2.8 Gy with 25 mg kg-1 emitefur was much higher than that of ten fractions of 4.2 Gy. In conclusion, emitefur given either alone or in combination with radiation appears to have a significant anti-tumour effect even at clinically relevant dose levels, although a threshold dose exists between 12.5 and 25 mg kg-1. Further clinical studies of this compound are warranted.

Animals↗
PubMed1996

Comparison of in vivo efficacy of hypoxic cytotoxin tirapazamine and hypoxic cell radiosensitizer KU-2285 in combination with single and fractionated irradiation.

Development of strategies to eradicate radioresistant hypoxic cells would be of great benefit for clinical radiotherapy. In the present study, the in vivo effects of a promising hypoxic cytotoxin, tirapazamine (3-amino-1,2,4-benzotriazine 1,4-di-N-oxide), were examined in comparison with those of KU-2285, one of the best hypoxic cell radiosensitizers, in combination with both single and fractionated irradiation. The tumor response was assessed by the standard in vivo-in vitro clonogenic assay using SCCVII tumors in C3H mice and EMT-6/KU tumors in Balb/c mice with different characteristics of tumor hypoxia. With single-dose irradiation (18 Gy), both tirapazamine and KU-2285 showed significant enhancement of cell killing in a dose-dependent manner, but tirapazamine was more effective for SCCVII tumors with acutely hypoxic cells, while KU-2285 was more effective for EMT-6/KU tumors predominantly with chronically hypoxic cells. In fractionated irradiation regimens (4 fractions of 5 Gy at 12 h intervals), tirapazamine showed more marked combined effects at 10 and 20 mg/kg than KU2285 at 100-200 mg/kg in both SCCVII and EMT-6/KU tumors. We concluded that the effectiveness of KU-2285 and tirapazamine was correlated with the nature of tumor hypoxia with single-dose irradiation, whereas tirapazamine appeared more potent than KU-2285 with fractionated irradiation. These findings suggest the potential usefulness of tirapazamine in clinical fractionated radiotherapy.

Animals↗
PubMed1996

Changes in cell proliferative parameters of SCCVII and EMT6 murine tumors after single-dose irradiation.

To understand better the repopulation kinetics of tumor cells after radiotherapy, we investigated changes in cell proliferative parameters after single-dose irradiation of SCCVII tumors in C3H/He mice and EMT6 tumors in Balb/c mice. The following parameters were determined 0-15 days after single irradiation at 20 or 30 Gy; dividing fraction (DF), potential doubling time (Tpot), number of clonogenic cells per tumor (Ncln), and volume doubling time (Tvol). DF and Tpot were determined by in vivo-in vitro cytokinesis-block assay with cytochalasin B, Ncln was measured by in vivo-in vitro colony-forming assay, and Tvol was determined by growth delay assay. In both tumors, longer Tpot and lower DF and Ncln were obtained for 3-4 days after irradiation, but in SCCVII tumors these values returned to the pretreatment levels 9 days after irradiation. In EMT6 tumors, Tpot, DF, and Ncln did not return to the pretreatment levels even 12 days after irradiation. In the regrowth phase of both tumors following irradiation at 20 Gy, Tvol was longer than the pretreatment level, although Tpot was similar in SCCVII and only slightly longer in EMT6. Therefore, the cell loss factor in the regrowth phase was considered to be higher than the pretreatment level in both tumors. From the results, recruitment of previously quiescent cells into the proliferative pool in these tumors was suggested to contribute to repopulation after radiation.

Animals↗
PubMed1996

Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study.

PURPOSE: To investigate the efficacy of concurrent hyperfractionated radiation therapy (HFX RT) and low-dose daily chemotherapy (CHT) in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between January 1990 and December 1991, 131 patients with histologically or cytologically confirmed stage III NSCLC, Karnofsky performance status (KPS) > or = 50, and no previous therapy were randomly treated as follows: group I, HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy (n = 66); and group II, same HFX RT with CHT consisting of 50 mg of carboplatin (CBDCA) and 50 mg of etoposide (VP-16) given on each RT day (n = 65). RESULTS: Group II patients had a significantly longer survival time than group I patients, with a median survival of 22 versus 14 months and 4-year survival rates of 23% versus 9% (P = .021). The median time to local recurrence and 4-year local recurrence-free survival rate were also significantly higher in group II than in group I (25 v 20 months and 42% v 19% respectively, P = .015). In contrast, the distant metastasis-free survival rate did not significantly differ in the two groups (P = .33). The two groups showed similar incidence of acute and late high-grade toxicity (P = .44 and .75, respectively). No treatment-related toxicity was observed. CONCLUSION: The combination of HFX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control.

Adult↗
PubMed1996

Non-Hodgkin's lymphoma of the thyroid. A clinical study of twenty-two cases.

Non-Hodgkin's lymphoma (NHL) of the thyroid gland is a rare disease. In the present study, the survival rate and characteristics were retrospectively analyzed in 22 patients with stage IE and IIE thyroid NHL treated with radiotherapy with or without combination chemotherapy. Seventeen NHL had histological evidence of lymphoma of mucosa-associated lymphoid tissue (MALT) type. The 5-year survival rate was 85% in all patients, with 100% and 63% respectively, for stage IE and stage IIE patients. The highly significant factor correlated with decreased determinate survival was concomitant stridor.

Adult↗
PubMed1996

Tirapazamine: hypoxic cytotoxicity and interaction with radiation as assessed by the micronucleus assay.

We investigated the cytotoxicity and the interaction with low-dose radiation (1-4Gy) of tirapazamine by the in vitro cytokinesis-block micronucleus (MN) assay. Murine SCCVII and human melanoma (G-361) cells were treated with tirapazamine under aerobic or hypoxic conditions for 1 h and the MN frequency was determined using cytochalasin-B. The cells were also treated with or without tirapazamine or KU-2285 (hypoxic cell sensitiser) under hypoxic conditions and irradiated with or without reaeration of the cell suspensions. A dose-dependent increase of MN frequency was observed by tirapazamine treatment and the hypoxic toxicity ratio was about 130 for SCCVII and 37 for G-361. The radiation dose-response curves of MN frequency suggested that the interaction of tirapazamine with irradiation appeared to be essentially additive in both cell lines. In contrast, the dose-response curve became steeper by KU-2285 treatment. Combined effects of tirapazamine and irradiation on the hypoxic cells were much higher than the radiation effect on aerobic cells at low doses, while the effects of KU-2285 did not exceed that of aerobic irradiation. In conclusion, tirapazamine appeared to be superior to hypoxic radiosensitisers at clinically relevant doses, not because of aerobic radiosensitisation but because of its potent hypoxic cytotoxicity additive to radiation effect.

Animals↗