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.

Effect of hyperthermia on hippocampal synaptic transmission and CA3 kindling in developing rats.

The effect of hyperthermia on excitatory synaptic transmission in the hippocampal CA1 area in response to contralateral CA3 stimuli at 23-26 days of age and the influence of hyperthermia-induced seizures (HS) on the kindling phenomenon induced by CA3 stimulation at 27-29 days of age were investigated in developing rats. When hyperthermia (43.6 +/- 0.

The combined antitumour effect of a new 5-fluorouracil derivative, BOF-A2, and radiation in vivo.

We examined the combined effect of radiation and 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 the liver, on murine tumors. Subcutaneous 8-mm-diameter SCCVII tumours grown in the right thigh of C3H/He mice were used. The mice were locally irradiated with single doses of 10-30 Gy or five fractions of 4 Gy for 5 days, alone or in combination with BOF-A2.

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.

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.

Adverse events associated with MMR vaccines in Japan.

The largest nationwide active surveillance of four Measles-Mumps-Rubella (MMR) vaccines was conducted in Japan. A total of 1255 pediatricians actively participated in the study, which comprised 8.6% of all members of the Japanese Pediatric Society.

Development of an MR simulator: experimental verification of geometric distortion and clinical application.

Purpose: To evaluate the geometric distortion on magnetic resonance (MR) images obtained with a permanent magnet system and determine the usefulness of MR imaging-assisted x-ray simulation in radiation therapy treatment planning (RTTP).

Materials And Methods: The authors measured the distortion on MR images of grid-pattern phantoms. MR imaging-assisted x-ray simulation was performed with skin markers in 14 patients with bone tumors.

Development of an integrated radiotherapy network system.

Purpose: To introduce the process of developing an integrated radiotherapy network.

Methods And Materials: We developed a new radiotherapy treatment-planning system in 1987 that we named the Computer Tomography (CT) simulator. CT images were immediately transported to multiimage monitors and to a planning computer, and treatment planning could be performed with the patient lying on the CT couch.

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.

FDG-PET evaluation of therapeutic effects on VX2 liver tumor.

Unlabelled: Transplanted VX2 liver tumor in the rabbit is an experimental liver tumor model in which 18F-2-fluoro-2-deoxy-D-glucose (FDG) accumulates to a 3.5-fold level that surrounds normal liver tissue. In this study, changes in FDG uptake were assessed in this liver tumor model after transcatheter arterial embolization (TAE) and radiotherapy.

Combined effects of an angiogenesis inhibitor (TNP-470) and hyperthermia.

TNP-470, a synthetic analogue of fumagillin first isolated from Aspergillus fumigatus, is known to be a potent anti-angiogenic compound. The combined effects on tumour growth and tumour angiogenesis of TNP-470 and hyperthermia were investigated. The tumour used was SCCVII carcinoma of the C3H/He mouse.

A case of bronchial cast.

We report a case of bronchial cast in a boy 1 year and 5 months old. Bronchial casts often obstruct the main bronchi, causing dyspnea and hypoxia. The bronchial cast was studied pathologically, with findings of eosinophilia and neutrophilic infiltration; the cast seemed to involve an allergic reaction.

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.

Relation of the enhancement of entorhinal tetanic responses by 50-Hz amygdala stimulation to the progression of kindling in the rat.

We recorded entorhinal tetanic responses to 50-Hz kindling stimulations applied at the amygdala in conscious rats, which produced facilitation and depression during the train pulses, in order to analyze the relationship of the changes in the tetanic responses to the development of both after-discharges (ADs) and behavioral seizures. Facilitation was always produced in the earlier tetanic responses and was followed by depression which reached a quasi-steady level in the later tetanic responses during each kindling stimulation. To estimate the changes in magnitude of the excitatory synaptic activation in the tetanic responses, with reference to the development of seizure stages, tetanic responses which produced the same behavioral seizure stage in each rat were averaged and the area between the negative (excitatory) potentials and the baseline of the averaged tetanic response was measured in terms of mV x ms.

Manganese chloride treatment does not protect against acute radiation injury of skin or crypt cells.

Metallothionein (MT), the synthesis of which can be induced by metalloelement administration, is a known radical scavenger. This study investigated the possible protective effect of MT against acute radiation injury. Manganese chloride (10 mg of manganese/kg) was administered intraperitoneally to male C3H/He mice 24 h prior to irradiation.

Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series): radiosensitization efficiency and toxicity.

Purpose: A new 2-nitroimidazole nucleoside radiosensitizer, PR-350 (1-[1',3',4'-trihydroxy-2'-butoxy]-methyl-2-nitroimidazole), has been reported to be as efficient as and less toxic than etanidazole. This compound is racemic, and it was recently optically resolved into two isomers, PR-68 (2'R,3'S type) and PR-69 (2'S,3'R type). The other two isomers, PR-28 (2'S,3'S type) and PR-44 (2'R,3'R type), were asymmetrically synthesized.

Effects of pentobarbital on entorhinal tetanic responses and the progression of afterdischarges during the early course of amygdala kindling in rats.

We investigated the relationship between the progress of afterdischarges (AD) and the development of facilitated entorhinal tetanic responses by amygdala kindling stimulations in conscious and pentobarbital (PB)-treated rats. The entorhinal responses consisted of deep negative components and the following shallow positive components. The negative potential (mean +/- SE) reflecting excitatory synaptic activation in the test response evoked by a single stimulation (600 microA) before kindling stimulations was greater in PB-treated rats (1.

Histopathological evaluation of gastric mucosal environments in peptic ulcer using the endoscopic 5-point gastric biopsy method.

Although a strong association has been established between chronic Helicobacter pylori infection and peptic ulcers, the role of H. pylori is not necessarily causative because there are many patients infected with H. pylori who do not develop peptic ulcer.

Subacute sclerosing panencephalitis aggravated during the intraventricular interferon administration therapy.

Human lymphoblastoid interferon-alpha was given by intraventricular administration via an Ommaya reservoir to a woman who entered Jabbour stage III at the age of 25 years. The first dose was of 150,000 IU, and daily doses were gradually increased; the total dose over a 42-day period was 33,550,000 IU. The patient's neurological disability index score before this treatment was 56.

Assessment of micronucleus induction in SCCVII cells treated with bioreductive agents, WIN 59075 (SR 4233) and mitomycin C, under aerobic and hypoxic conditions.

WIN 59075 (SR4233, tirapazamine) is a promising bioreductive antitumor agent preferentially more toxic to hypoxic cells and presently undergoing phase I clinical trials. In this investigation, we have examined the applicability of the cytokinesis-block micronucleus assay to assess the effects of bioreductive agents. SCCVII tumor cells were treated with WIN 59075 or mitomycin C at various concentrations under aerobic and hypoxic conditions.

Combined effects of buthionine sulfoximine and cepharanthine on cytotoxic activity of doxorubicin to multidrug-resistant cells.

We studied the potentiation of doxorubicin (DOX) activity in multidrug-resistant (MDR) cells by buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, and by cepharanthine (CE), which interacts with P-glycoprotein. The glutathione (GSH) of MDR cells was approximately 1.5-fold greater than that of the parental cell line.

Three-dimensional treatment planning for maxillary cancer using a CT simulator.

Purpose: The results of three-dimensional treatment planning using a computed tomography simulator were evaluated in patients with maxillary cancer.

Methods And Materials: Treatment planning was done in 25 patients using an x-ray simulator and plain x-ray films (1979-1982, group 1) in 34 patients using an x-ray simulator and computed tomography films (1983-1987, group 2), in 24 patients using a computed tomography simulator (1988-1992, group 3). The number of patients with Stage IV disease increased in the order of group 1 to group 3.

KIN-804 vs. KU-2285 as a radiosensitizer for clinical use.

Purpose: The in vitro and in vivo effects of two promising hypoxic cell radiosensitizers, KIN-804 (KIN) and KU-2285 (KU), were compared using four types of assays, and the acute toxicity and pharmacokinetics of KIN were investigated to evaluate the clinical applicability of the compounds.

Methods And Materials: To evaluate the in vitro effect at low radiation doses (1-4.5 Gy), the cytokinesis-block micronucleus (MN) assay using SCCVII or EMT-6 cells and the chromosomal aberration (CA) assay using EMT-6 cells were performed.