Complex genetic nature of sex-independent transmission ratio distortion in Asian rice species: the involvement of unlinked modifiers and sex-specific mechanisms.

Transmission ratio distortion (TRD), in which one allele is transmitted more frequently than the opposite allele, is presumed to act as a driving force in the emergence of a reproductive barrier. TRD acting in a sex-specific manner has been frequently observed in interspecific and intraspecific hybrids across a broad range of organisms. In contrast, sex-independent TRD (siTRD), which results from preferential transmission of one of the two alleles in the heterozygote through both sexes, has been detected in only a few plant species. We previously reported an S(6) locus-mediated siTRD, in which the S(6) allele from an Asian wild rice strain (Oryza rufipogon) was transmitted more frequently than the S(6)(a) allele from an Asian cultivated rice strain (O. sativa) through both male and female gametes in heterozygous plants. Here, we report on the effect of a difference in genetic background on S(6) locus-mediated siTRD, based on the analysis using near-isogenic lines and the original wild strain as a parental strain for crossing. We found that the degree of TRD through the male gametes varied depending on the genetic background of the female (pistil) plants. Despite the occurrence of TRD through both male and female gametes, abnormality was detected in ovules, but not in pollen grains, in the heterozygote. These results suggest the involvement of unlinked modifiers and developmentally distinct, sex-specific genetic mechanisms in S(6) locus-mediated siTRD, raising the possibility that siTRD driven by a single locus may be affected by multiple genetic factors harbored in natural populations.

Anti-tumour effects of localized hyperthermia on an experimental bone tumour using an intramedullary nail.

A new localized hyperthermia system for an experimental bone tumour in the rabbit tibia was developed. This system was composed of an induction coil, generator and a Kirschner wire, which was inserted into the medullary canal of the tibia as a heat-generating ferromagnetic implant. The metastatic bone tumour model was created by implantation of VX2 carcinoma in the medullary canal of the tibia diaphysis. The days after VX2 implantation, hyperthermia was induced for 50 min. Three weeks after the treatment, rabbits were sacrificed for histological and radiological evaluation. According to the semi-quantitative scoring system, anti-tumour effects of the single dose of hyperthermia was noted radiologically (p < 0.01) and histologically (p < 0.05) where the temperature was at a sufficient level to cause hyperthermia (> 42.5 degrees C). This new heating method, which is relatively simple and clinically applicable, appears to be promising for the treatment of metastatic tumours of the long bone.

[A case of advanced gastric cancer successfully treated with resection after FEP (5-FU, epirubicin, CDDP) combined chemotherapy].

We reported an experience with an advanced gastric cancer patient with direct invasion into liver and metastases to liver, who had responded extremely well to an FEP combined chemotherapy. He had curatively undergone total gastrectomy with partial hepatectomy and enlarged lymph node dissection. The patient received three courses of 5-FU (750 mg/m2/day, for four days, continuous infusion), epirubicin (30 mg/m2, on day 1, i.v.), CDDP (17.5 mg/m2/day, on days 1, 2, 3, 4 i.v.) every 3 weeks in our hospital. No remarkable side effect was encountered. Partial response in the primary and invasive lesions was observed by X-P, endoscopy and CTscan. Accordingly, we could perform curative resection of the stomach with lymph nodes and parts of liver. The effect (partial response) of neoadjuvant chemotherapy was confirmed by histological examinations. FEP combined chemotherapy appears useful as a neoadjuvant approach to advanced gastric cancer.

Hyperthermic treatment of canine tibia through RF inductive heating of an intramedullary nail: a new experimental approach to hyperthermia for metastatic bone tumours.

Although the incidence of metastatic bone tumours is recently increasing, the local control rate of conventional treatment modalities is not satisfactory. If an intramedullary nail for the fixation of a weakened bone with metastatic lesions can be used as a heat-generating material for hyperthermia, the treatment result is expected to improve. This new approach to hyperthermic treatment of bone tumours has been investigated in a canine tibia. An intramedullary nail made of stainless steel was put into a medullary canal of a canine tibia. The leg was exposed to an alternating magnetic field of 100 kHz in the frequency and 100 Oe in the maximum intensity. The nail was inductively heated for 60 min. The temperature of the nail > 50 degrees C and the cancellous bone 5 mm from the nail was heated to a therapeutic temperature, 42.5 degrees C. After a bone labelling with tetracycline and calcein, the dogs were killed 2, 4 and 12 weeks after the heating. The area of osteonecrosis was evaluated by fluorescence microscopy analysis. The heated cancellous bone around the nail showed osteonecrosis in 2 weeks after the treatment, but it recovered completely in 12 weeks. This experiment has demonstrated the heating capability of the new hyperthermic technique and minimal toxicity to the bone, and suggests the clinical application to metastatic bone tumours.

Localized hyperthermic treatment of experimental bone tumors with ferromagnetic ceramics.

Localized hyperthermic treatment was carried out with use of a metastatic bone tumor model in rabbits. The experimental bone tumor was created by transplantation of pieces of tumor line VX2 into the medullary canal of rabbit tibiae. Two weeks after the transplantation, a ferromagnetic ceramic pin was inserted in the medullary canal. Then, hyperthermia (HT) of the tumor was accomplished with use of an alternating magnetic field for 50 min. All the rabbits were killed 5 weeks after tumor transplantation, and the therapeutic effect was evaluated histologically and roentgenographically. Almost all the tumor cells within the bone marrow were killed by this procedure. The area of tumor necrosis in the HT group was significantly larger than in the control group. The pathological fracture rate and displacement rate were reduced significantly by this treatment (38.5 and 0%) compared with the controls (92.3 and 92.3%). Therefore, HT with the use of ferromagnetic ceramics was effective for local control of malignant bone tumors and seems to be a promising new method of treatment.

A heat-generating bioactive glass-ceramic for hyperthermia.

Glass plates of the chemical composition: CaO (29.0), SiO 2 (31.0), Fe 2O 3 (40.0), B 2O 3 (3.0), P 2O 5 (3.0) in weight ratio were heated to 1050 degrees C at a rate of 5 degrees C/min and then cooled to laboratory temperature. The resulting glass-ceramic containing magnetite and wollastonite crystals showed high-saturation magnetization. The bonding ability of this new glass-ceramic to bone tissue was evaluated using rabbit tibiae, and compared with glass of the same composition. This glass-ceramic formed a Ca, P-rich layer on its surface and bonded tightly with bone within 8 weeks of implantation. However, the glass did not form this Ca, P-rich layer, nor had it bonded with bone at 25 weeks. The bone-heating ability of this glass-ceramic was investigated by applying a max. 300-Oe, 100-kHz magnetic field. The granules of the glass-ceramic filled in the rabbit tibiae heated the whole surrounding bone to more than 42 degrees C and maintained this temperature for 30 min. Bioactive ceramics reinforce the mechanical strength of bone tissue. Furthermore, this heat-generating bioactive glass-ceramic can be used for hyperthermic treatment of bone tumors.

Hypersensitivity of human tumor xenografts lacking O6-alkylguanine-DNA alkyltransferase to the anti-tumor agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitros ourea.

Human tumor cell strains having different activities of O6-alkylguanine-DNA alkyltransferase (ATR) were transplanted into nude mice and chemotherapeutic responses of tumor xenografts were compared after intraperitoneal injection of the anti-tumor drug 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). The tumor strains used were four Mer+ strains possessing high ATR activity and three Mer- strains lacking this activity. Included in these Mer+ strains was a clone 5'dD which expresses the Escherichia coli ATR in Mer- HeLa cells and thus shows the Mer+ phenotype. All the Mer- tumor xenografts were much more sensitive than tumors of Mer+ strains, including the clone 5'dD; after the highest ACNU dose (three injections of 50 mg/kg), some Mer- tumors disappeared completely and the growth of other tumors was severely retarded, whereas all Mer+ tumors continued to grow. These results demonstrate that ATR activity in tumor cells is a major determinant of tumor response to ACNU, and further suggest that measurement of ATR activity in biopsy specimens may provide a useful guide to predict the response to chemotherapy.