The effect of N6-butyrylcordycepin on potentially lethal damage repair in vivo.
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Animals↗
Biomedical subjects
Y Shibamoto
Publications and source records attributed to Y Shibamoto.
Recovery from potentially lethal damage after X-irradiation in three experimental tumors in mice.
Potentially lethal damage repair or recovery (PLDR) after X-irradiation was examined in three experimental murine tumors, EMT6 sarcoma, SCCVII carcinoma and RIF1 sarcoma, by an in vivo-in vitro assay. All tumors were transplanted subcutaneously (SC) and, in the case of EMT6, also intradermally (id), in the thighs of syngeneic mice. Apparent PLDR was observed at high dose levels in the id and sc EMT6 sarcomas and in the sc SCCVII carcinoma, but not in the sc RIF1 sarcoma. In both id EMT6 and SCCVII tumors, PLDR appeared to be complete within 9 hr after X-irradiation. Dose-modifying factors due to PLDR evaluated at the surviving fraction of 0.01 were 1.34, 1.15, 1.24 and 0.97 for id EMT6, sc EMT6, SCCVII and RIF1 tumors, respectively. The amount of PLDR correlated inversely with the velocity of tumor growth in vivo, suggesting that slowly growing tumors might be proficient in PLDR. Although PLDR in id EMT6 and SCCVII tumors was evident in the dose range above 15 Gy, the capacity to recovery from PLD became smaller at lower doses; in SCCVII tumors, this phenomenon was negligible below 7.5 Gy. PLDR did not seem to be a major factor influencing the radiocurability of these murine tumors, especially at low dose levels.
Animals↗
[Effects of fast neutrons, X-rays and mixed irradiation regimen on C3H mammary tumors and skin of ICR mice].
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Animals↗
[Radiotherapy for carcinoma of digestive organs].
Clinical results of intraoperative radiotherapy (IOR) applied to carcinomas of the stomach, pancreas, and rectum were reported. In stomach cancer, the 5-year survival rates of patients treated by operation alone were 93.0% for stage I, 61.2% for stage II, 36.8% for stage III and 0% for stage IV. On the other hand, the 5-year survival rates of patients treated by IOR were 90.2% for stage I, 77.0% for stage II, 54.4% for stage III and 15.3% for stage IV. It has been demonstrated that IOR has definite effects on locally advanced gastric cancer. In pancreatic cancer, the median survival times for all patients treated by operation alone, IOR and IOR+ external beams were 3.5 months, 4.5 months and 8 months respectively. The median survival times of stage III patients treated by operation alone, IOR and IOR+ external beams were 5.5 months, 5.5 months and 12 months respectively. Our clinical results suggest that prolongation of life can be expected in patients who are treated by IOR followed by external beams and stage III is best indicated. In rectal cancer, it was found that stage IV as classified according to the rules for colorectal cancer studies in Japan is best indicated for IOR from the analysis of the survival figures. In stage IV patients, those who received operation alone could not survive more than 50 months while about 50% of those who were treated by IOR are alive 50 months after the treatment.
Combined Modality Therapy↗
[Recent advances in hypoxic cell radiosensitizer].
The comparative studies on the radiosensitizing efficacy of misonidazole (MISO) and SR-2508, a new 2-nitroimidazole which is less neurotoxic than MISO, were performed using C3H/He mouse mammary tumors. The enhancement ratios of 1.42 for 0.5 mmole/kg of MISO and 1.82 for 1.5 mmole/kg of SR-2508, the equitoxic dose to MISO, were obtained when each drug was administered in combination with a single dose of radiation. When the radiation was delivered in three and five fractions, enhancement ratios decreased to 1.15 and 1.11 for MISO while they remained at 1.40 and 1.34 for SR-2508 respectively. Potentiating effect of diethyl maleate (DEM) on the radiosensitization of MISO was also studied using the same experimental tumor. Although DEM, in itself, has a radiosensitizing effect in the dose range of more than 600mg/kg combined use of DEM and MISO showed more efficient synergism, e.g., the enhancement ratio of 0.5 mmole/kg of MISO increased from 1.42 to 2.06 when it was given in combination with 760 mg/kg of DEM. However, synergistic effects of MISO and DEM observed were dependent upon given dose of each drug. i.e.
Animals↗
Intraoperative radiation therapy for gastric cancer.
From among 115 patients who were treated by intraoperative radiation therapy (IORT), 94 patients were classified according to the histologic findings. The control 127 patients who were treated by operation alone during the same period were also histologically classified, and survivals were compared between the two groups. No difference in the survivals of patients with stage I was observed for the two groups. On the other hand, the survivals of patients with stages II through IV who were treated by IORT increased by nearly 10% to 20% at 5 years. A comparative study was also performed on the survivals between patients treated by IORT and those treated by operation alone according to the presence or absence of the serosal invasion and the grade of the lymph node metastasis. The number of patients treated by IORT in whom the serosal invasion and the lymph node metastasis were histologically examined was 57. The 171 control patients who underwent operation alone were examined histologically in the same fashion, and survivals for the two groups were compared. IORT did not afford any benefit if the lymph node metastasis was limited within n1 group or serosal invasion was not found. On the other hand, the 5-year survival rates for patients who were treated by IORT increased by nearly 10% when the serosal invasion was observed and by nearly 18% when n2 and n3 lymph node metastases were found.
Combined Modality Therapy↗
Embolization of collateral vessels using mechanically detachable coils in young children with congenital heart disease.
Our objective was to evaluate the usefulness of embolizing collateral vessels using mechanically detachable coils (MDCs) in children aged 3 years or younger with congenital heart disease. The subjects were 8 children with congenital heart disease featuring collateral vessels (age 18 days-3 years): 3 with a single ventricle, 2 with the tetralogy of Fallot, 2 with pulmonary atresia, and 1 with a ventricular septal defect. The embolized vessels were the major aortopulmonary collateral artery (MAPCA) in 5 patients, the persistent left superior vena cava in 2, and the coronary arteriovenous fistula in 1. A 4 or a 5 F catheter was used as the guiding device, and embolization was performed using MDCs and other conventional coils introduced through the microcatheter. One patient had growth of new MAPCAs after embolization, and these MAPCAs were also embolized with MDCs. Thus, a total of 9 embolization procedures were performed in 8 patients. Complete occlusion of the collateral vessels was achieved in 8 of 9 procedures (89%). Seven of 8 patients (88%) had uneventful courses after embolization, and MDC procedures appeared to play important roles in avoiding coil migration and achievement of safe coil embolization. One patient who underwent MAPCA embolization showed no improvement in heart function and died 2 months and 19 days later. Embolization of collateral vessels using MDCs in young children with congenital heart disease can be an effective procedure and a valuable adjunct to surgical management.
Child, Preschool↗
Superior mesenteric artery stent-graft placement in a patient with pseudoaneurysm developing from a pancreatic pseudocyst.
Pseudoaneurysm is a relatively rare but serious complication of pancreatitis which is often fatal. We report successful stent-graft placement in the superior mesenteric artery in a 45-year-old man with a pancreatic pseudocyst that grew during therapy for chronic pancreatitis and developed into a pseudoaneurysm. After a stent graft was inserted in the superior mesenteric artery, the pseudoaneurysm disappeared and no further complications developed. Stentgraft placement was considered to be a useful therapy for pseudoaneurysms in the superior mesenteric arterial region.
Aneurysm, False↗
Assessment of micronucleus induction in murine SCCVII cells treated with various anticancer agents.
The possibility of using the cytokinesis-block micronucleus (MN) assay as a rapid test of chemosensitivity was investigated. SCCVII murine carcinoma cells growing exponentially in vitro were treated for 1 h under aerobic conditions with various concentrations of 11 anticancer agents: mitomycin C, doxorubicin, epirubicin, cisplatin, carboplatin, etoposide, vincristine, 5-fluorouracil, methotrexate, nimustine and dacarbazine. After removing the drugs, cytochalasin B (1.5 micrograms/ml) was added to block cytoplasmic but not nuclear division. At various times during culture, the proportions of binucleate cells (BNC) and multinucleate cells in the total cell population, and the mean number of micronuclei per single BNC were determined. Cell survival was also determined using the standard colony formation assay and was compared with the MN frequency. Maximal percentage of BNC was usually reached at 24-30 h of culture, except for cells treated with doxorubicin and epirubicin, in which it was reached at 30-72 h. All drugs induced formation of micronuclei and dose-response curves for MN frequency were obtained using the data at peak percentage of BNC times. For all drugs, MN frequency increased with concentration, but at the highest concentrations used (which are considered to be overly toxic) the MN frequency was rather lower. This decrease in MN frequency was largely attributable to the decrease in percent BNC. When the data at the highest concentrations of all drugs were excluded, a correlation was found between MN frequency and surviving fraction (r = 0.85). Therefore, it was concluded that the cytokinesis-block MN assay can be used to assess sensitivity of at least some tumor cells to appropriate concentrations of various chemotherapeutic agents.
Animals↗
Long-term control of multiple lung metastases from osteosarcoma obtained by conventional radiotherapy: a case report.
An osteosarcoma patient whose lung metastases were successfully treated with radiotherapy is reported. The patient developed multiple lung metastases repeatedly after successful treatment of the primary lesion in his femur. Resection of the lung metastases was performed 5 times during 4 years (12 metastatic nodules in total). One of the specimens was evaluated using the micronucleus test, which suggested moderate radiosensitivity of the tumor. He further developed 2 metastases 19 months after the last operation, and these tumors were treated with conventional radiation with 60 and 64 Gy, respectively. The tumors regressed slowly after radiation and disappeared later. Although he developed another lung metastasis 2 years later, the lesion was also treated with radiation with 66 Gy and all of the 3 irradiated tumors are now under control at 43 months after the first radiotherapy and 15 months after the second one. Our experience would suggest that some (at least) metastatic osteosarcomas have reasonable radiosensitivity, and radiation therapy including radiosurgery may be a good alternative to surgery in patients for whom operation is not indicated.
Adolescent↗
In vivo efficacy and pharmacokinetics of a new hypoxic cell radiosensitizer doranidazole in SUIT-2 human pancreatic cancer xenografted in mouse pancreas.
A new 2-nitroimidazole radiosensitizer doranidazole is now undergoing clinical evaluation in combination with intraoperative radiotherapy for unresectable pancreatic cancer. However, there have been no laboratory data on its effect against pancreatic cancer. This study was undertaken to clarify the efficacy and pharmacokinetics of doranidazole in a human pancreatic cancer SUIT-2 xenografted in the pancreas of nude mice. The tumor-bearing mice were irradiated to the upper abdomen using electron beams with or without prior administration of doranidazole. The tumors were excised 3-6 days later and their weight was measured. Doranidazole given alone had no antitumor effect, but it had radiosensitizing effects when 100, 150, or 200 mg/kg of the drug was combined with single 5 Gy irradiation. The tumor/serum ratios for doranidazole concentration were 0.3-0.4, but the concentrations in the tumor were similar to those in the surrounding normal pancreas. At doses of 100 mg/kg or higher, concentrations of doranidazole in the pancreatic tumor appeared to be sufficient to obtain definite radiosensitization.
Animals↗
Concurrent chemoradiotherapy combined with intraoperative radiotherapy for locally advanced pancreatic cancer: a feasibility study.
Initial clinical results of concurrent chemoradiotherapy combined with high-dose intraoperative radiotherapy (IOR) for locally advanced pancreatic cancer were analyzed. Between June 1996 and May 1999, 6 patients with locally advanced pancreatic cancer without distant metastasis were treated with preoperative concurrent chemoradiotherapy followed by IOR. Preoperative radiation therapy was given by the dynamic arc conformal technique with a daily fraction of 1.8 Gy to a total dose of 45 Gy in 5 weeks. Cisplatin (5 mg/day for 4 weeks) and 5-fluorouracil (250 mg/day for 5 weeks) were administered continuously during preoperative radiation therapy. IOR as a single dose of 28 or 30 Gy was given to the gross tumor volume using electron beams of 15- to 22-MeV. Concurrent chemoradiotherapy was well tolerated, although all of the patients complained of nausea and fatigue. Two patients developed grade III leukopenia. No other serious acute toxicity was noted. The median survival time of the 6 patients was 17.5 months, which was significantly longer than that of our historical control treated with external radiation therapy with IOR (8 months), although the difference in survival was borderline significant (p=0.068). Concurrent chemoradiotherapy followed by high-dose IOR was well tolerated in patients with locally advanced pancreatic cancer, and the initial clinical results appeared promising.
Adult↗
Estimation of time parameter of LQ-model in fractionated radiotherapy of medulloblastoma.
PURPOSE: To estimate the dose required to counteract accelerated proliferation, gamma/alpha, of medulloblastoma (MB) cells during fractionated radiotherapy. MATERIALS AND METHODS: Sixty-five patients with MB (local control rate at 5 years: 73%) treated between 1980 and 1990 at our university hospitals were analyzed. The gamma/alpha was estimated by applying the profile likelihood method to Cox's proportional hazards model including the maximum value of time-incorporated biologically effective dose, tBEDmax. The tBEDmax was conditionally calculated with various settings of alpha/beta, time to kick off accelerated proliferation, Tk, and gamma/alpha. Pretreatment T-stage, log(age+1), extent of removal, and use of chemotherapy and immunotherapy were also included in the multivariate model. RESULTS: When alpha/beta was taken to be 10 Gy, the estimate of gamma/alpha was 0.52 Gy/day (95% confidence limits: 0.29-0.75) for 0 day of Tk and was 0.55 Gy/day (0.30-0.80) for 21 days of Tk. The gamma/alpha values tended to be larger in the T3 subgroup and in the non-total removal subgroup than in all patients, by about 0.05 Gy/day and 0.1 Gy/day, respectively. When alpha/beta was taken to be 25 Gy, the estimated values were about 0.05 Gy/day smaller than these values. CONCLUSION: The estimated gamma/alpha values were considerably large. Therefore, it is preferable to take this consumed dose per day into consideration in planning and conducting treatments for MB.
Cerebellar Neoplasms↗
Combined treatment using radiotherapy for carcinoma of the pancreas involving the adjacent vessels.
The prognosis of pancreatic duct carcinoma is determined mainly by the degree of local invasion, particularly of the portal system and/or associated arteries supplying the carcinoma. Intraoperative (25-36.5 Gy of betatron) and/or external (14.4-25.6 Gy, preoperatively, and 24-61.2 Gy, postoperatively, using lineac photon beams) radiotherapy was combined with pancreatectomy or by-pass surgery for patients with pancreatic carcinoma involving the surrounding vessels but with no distant metastases. Twelve- and 24-month survival rates were 25.9% and 3.2%, respectively, in patients with pancreatectomy (n = 35) and 6.4% and 0%, respectively, in patients with by-pass operations (n = 32). However, in patients with combined surgery and radiotherapy the prognosis was markedly improved to 12- and 24-month survival rates of 33.5% and 20.1%, respectively, for patients with pancreatectomy (n = 13) and rates of 25% and 13%, respectively, for patients with by-pass operations (n = 8). Moreover, radiotherapy produced a significant advantage for local control of pain in patients with unresectable pancreatic carcinoma. This suggests that combined treatment using radiotherapy will be a valuable therapeutic improvement for patients presenting advanced pancreatic carcinoma with vessel involvement.
Carcinoma, Intraductal, Noninfiltrating↗
Studies in radiosensitizing effects of misonidazole and SR-2508 on C3H/He mouse mammary tumors.
The radiosensitizing efficacy of SR-2508, a new 2-nitroimidazole, which is less neurotoxic than misonidazole (MISO) was studied using transplantable mammary carcinoma of C3H/He mice. Tumor responses to treatments were evaluated by growth-delay time assay. In single irradiations, the enhancement ratios of 0.5 mmole/kg of MISO and 1.5 mmole/kg of SR-2508, which were equitoxic to C3H/He mice, were 1.42 and 1.84 respectively. In fractionated irradiations with three fractions over two days or five fractions over four days, the enhancement ratios of 1.5 mmole/kg of SR-2508 were 1.40 and 1.34 respectively. On the other hand the enhancement ratios of MISO at the above mentioned dose in respective fractionated irradiations were 1.15 or 1.11. SR-2508 is considered promising as a hypoxic cell radiosensitizer for clinical use.
Animals↗
Intraoperative radiotherapy and hyperthermia for unresectable pancreatic cancer.
Intraoperative radiotherapy (IORT) is a safe and efficient method of delivering a high single dose of radiation to a target. IORT has a significant effect on abdominal pain and back pain in patients with unresectable pancreatic cancer, but IORT alone is not so effective in improving the prognosis. The combination of IORT with external beam radiotherapy (EBRT) can achieve a higher local control rate than EBRT alone, although most previous studies have not necessarily indicated any improvement in survival. We recently found that high-dose IORT (30 Gy) + EBRT (40-60 Gy) was more effective than EBRT alone in patients with a CA 19-9 level < 1000 U/ml. Thus, IORT plus EBRT can be recommended for unresectable but localized pancreatic cancer associated with low tumor marker levels. Hyperthermia combined with radiation or chemotherapy is another possible treatment strategy, but no effective method of delivering external regional hyperthermia has yet been established. Thermometry is another problem with external hyperthermia. At present, intraoperative hyperthermia given in combination with IORT seems to be the best method of heating a pancreatic tumor adequately, but its efficacy is still unclear.
Adult↗