Experimental studies on the combined effect of radiation and UFT: 2. fractionated treatments combining UFT and X ray radiation

The combined effects of fractionated radiation and UFT, which is a mixture of tegafur (FT) and uracil, have been studied using C3H mouse mammary carcinoma. The tumor was implanted in the right hind legs of and irradiated with 300R daily for either 10 or 15 days. UFT (FT 15mg/kg + uracil 33.6mg/kg) was intra-gastrically administered 2 hr. before irradiation. Dose modifying factor (DMF) of UFT obtained from the tumor growth delay assay was 1.52 for 10 fractions (3,000R) and 1.27 for 15 fractions (4,500R). The continuous administrations of UFT for one month after combination treatment suppressed the tumor regrowth. It is suggested that UFT is a useful radiosensitizer for concurrent fractionated radiation and useful adjuvant agent after radiation therapy.     

Clinical study of RU 23908 (nilutamide) in prostatic cancer

To investigate the efficacy and the safety of RU23908 for the treatment of prostatic cancer, an early phase 2 study with the oral administration of 150 or 300 mg daily was performed in 47 patients with stage C or D prostatic cancer at 15 institutions from April 1987 to June 1988. Forty patients were evaluable for efficacy. Concerning the effect on the object lesion, the results of the overall evaluation revealed that complete or partial response (CR + PR) was obtained in 34 of the 40 cases (85.0%). As to the effect classified by site, CR + PR were observed in 35 out of the 40 cases with primary lesion (87.5%), in 10 of the 22 cases with bone metastasis (45.5%), in 5 of the 6 cases with lymph node metastasis (83.3%) and CR was observed in one case with lung metastasis. In the PAP evaluation, 33 out of the 34 cases were judged to be CR + PR (97.1%). The improvement rate of clinical symptoms was 88.9% for bone pain, 83.3% for dysuria and 45.5% for performance status. Adverse reactions were observed in 29 of the 47 cases (61.7%) investigated and 7 cases (14.9%) were withdrawn. During the study period of 12 weeks and the subsequent period of continued administration, 6 cases (12.8%) and 2 possible cases of interstitial pneumonia were diagnosed. From the above results, the treatment of prostatic cancer with RU23908 150 mg/day or 300 mg/day in combination with surgical castration showed an excellent clinical effect compared to conventional endocrine therapy, but has a problem of safety. Therefore, this drug may be expected to be a highly useful therapeutic drug, if safely is improved in the future by reviewing the dose.     

Enhanced extracellular dopamine level may be the fundamental neuropharmacological basis of cross-behavioral sensitization between methamphetamine and cocaine--an in vivo dialysis study in freely moving rats

Intracerebral dialysis was used to study the mechanism underlying cross-behavioral sensitization between methamphetamine (MAP) and cocaine. The challenge injection of cocaine caused a significantly greater increase in striatal perfusate dopamine (DA) levels in MAP-pretreated rats than in saline-pretreated rats. Similarly, the challenge injection of MAP caused a significantly greater increase in extracellular DA levels in cocaine-pretreated rats than in control rats. These results suggest that an enhancement in striatal DA efflux may play an important role in cross-behavioral sensitization between MAP and cocaine.     

Quantitative variations of lymphocyte subsets in various kinds of cancer patients in the terminal stage

Immunological studies of the peripheral blood were made in terminal breast cancer and terminal abdominal cancer patients. Two immunological parameters were studied: (1) lymphocyte subsets and (2) proliferative response to PHA. A decrease in the number of OKT-3(+) cells and an increase in that of OKT-8(+) cells were observed in abdominal cancer. It was suggested that the immunological status in abdominal cancer is more suppressive than in breast cancer. Increases in the number of OK-M1(+) cells and Leu-7(+) cells were observed in breast cancer. It is suggested that cytotoxic lymphocytes increase in number in breast cancer more than in abdominal cancer.     

Myocardial protection of the pressure overload hypertrophied heart in human cardiac surgery by acceleration of anaerobic glycolysis.

BACKGROUND: Because of the decreased tolerance to ischemia and increased reperfusion injury in hypertrophied myocardium, myocardial hypertrophy is a well known risk factor for cardiac surgery. We have previously demonstrated in a left ventricular hypertrophy (LVH) model that a highly buffered cardioplegic solution (HBS) that provided glucose as a substrate and promoted anaerobic glycolysis during ischemia afforded superior myocardial protection when compared to standard formulations. And we reported the superiority of this cardioplegia in human cardiac surgery. METHODS: In this study, 16 patients with aortic stenosis (AS) and LVH receiving HBS were reviewed and compared to another patient group with AS and LVH who received either cold blood cardioplegia (CBC; n=5) or glucose insulin potassium (GIK; n=6). RESULTS: Postoperative cardiac index was better in the HBS group than the other two groups with similar or lower catecholamine. CK-MB was lower in HBS group than GIK group, but this was not significant. Only one DC cardioversion was required in the HBS group, whereas 2 DC in the CBC group and total 7 DC in the GIK group. CONCLUSIONS: We found that histidine buffered cardioplegic solution provided comparable or better pump performance after surgery with relatively lower inotropic requirement, less DC cardioversion and homologous blood requirements for left ventricular hypertrophied heart associated with aortic stenosis.     

Renal cell carcinoma extending into the vena cava: a multi-institute study.

The present paper reports the clinical results from cases of renal cell carcinoma with vena caval tumor thrombus. Fifty patients were entered into the study between 1980 and 1989. The primary tumor and vena caval tumor thrombus were completely removed in 39 (78%) patients, and 41 (82%) received postoperative treatment. The overall 12-, 36-, 60- and 90-month actuarial survival rates were 72, 41, 19 and 10%, respectively. Only tumor stage affected survival, however, other factors such as tumor grade, nodal status, metastatic status and level of vena caval involvement not affecting it. Postoperative interferon (IFN) treatment affected survival, whereas degree of curative surgery did not. The results of our study were, however, examined retrospectively in several institutes. Further investigation of the postoperative treatment for renal cell carcinoma with vena caval tumor thrombus will be necessary.     

Study on adhesion mechanism of MMA-TBBO resin to dentin. A model experiment using decalcified dentin

As a model experiment to understand the mechanism of adhesion of the MMA-TBBO resin to dentin, MMA-TBBO was polymerized using a decalcified dentin sheet treated with aqueous citric acid (CA) solutions of copper fluoride (CF), ferric fluoride (FF), or ferric chloride (FC), which are usually used as treating agents in the bonding of the resin to dentin. The curing time for MMA-TBBO resin was considerably reduced on the decalcified dentin sheet treated with FC-CA, CF-CA or FF-CA at an appropriate concentration. Polymerization of MMA-TBBO resin was accelerated in the presence of a fluoride ion. Molecular weight of PMMA depended on the site of polymerization; PMMA polymerization inside the decalcified dentin sheet gave the highest and that outside gave the lowest molecular weight in the presence of an appropriate amount of ferric or cupric ion. These results suggested that ferric compounds adsorbed to decalcified dentin are involved in the polymerization of MMA and thus will influence the bond strength of the MMA-TBBO resin to dentin.     

Reconstruction of basement membrane in recombinants of epidermis and dermis of chick embryonic skin in vitro: An electron microscopic study

The tarsometatarsal skin from 13-day-old chick embryos was treated with EDTA and/or Dispase to separate it into epidermis and dermis, and the basal lamina was removed. The isolated epidermis and dermis were then recombined and cultured on Millipore filters in a chemically defined medium (BGJb). Beginning at 3–4 days after recombination, short fragments of new basal lamina and subbasal dense plaque were formed along the epidermal basal cell outer surface immediately subjacent to hemidesmosomes. After 6–8 days of culture, fragments of the basal lamina started to fuse together and the lamina became progressively continuous. At the same time, anchoring fibrils were formed to attach to the basal lamina. The hemidesmosome formation preceded the basement membrane formation. When normal embryonic epidermis was recombined with retinolpretreated dermis and cultured for 7 days in BGJb, short fragments of the basal lamina, the subbasal dense plaque, and anchoring fibrils were formed, but the basement membrane remained discontinuous with many interruptions in the interspace between hemidesmosomes. These results demonstrate that pretreatment of dermis with retinol causes the changes noted in the basement membrane.