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Combination chemotherapy with THP, CDDP and 5-FU for squamous cell carcinoma of the head and neck was conducted in 13 institutions in Hyogo Prefecture as a multi-institutional cooperative study. In the initial study (Nov. 1990-Nov. 1993), THP was administered intravenously at 20 mg/m2 on day 1, CDDP at 80 mg/m2 on day 2, and 5-FU at 1,000 mg/body/day in a continuous drip infusion for 120 hours from day 2 to day 6. In the second study (May, 1996-Mar. 1998), THP was administered at 20 mg/m2 on day 1, 5-FU at 10 mg/kg/day from day 1 to day 5, and CDDP at 70 mg/m2 on day 6 in the same way as the initial study. Forty-nine patients (Stage I in 3, Stage II in 12 including 2 recurrent cases, Stage III in 6, Stage IV in 28 including 3 recurrent cases; 1 course chemotherapy in 13 and 2 or more courses in 36) were subjected as complete cases in the initial study, and 36 patients (Stage I in 5 including one recurrent case, Stage II in 11 including 1 recurrent case, Stage III in 9 including 2 recurrent cases, Stage IV in 11 including one recurrent case; 1 course in 18 and 2 or more courses in 18) in the second. The overall response rate was 65.3% (CR in 3 cases) in the initial study and 63.9% (CR in 5 cases) in the second. Primary cases showed a response rate of 65.9% (29/44) in the initial study and 71.0% (22/31) in the second, whereas recurrent cases showed a 60.0% (3/5) response rate in the initial study and a 20.0% (1/5) rate in the second. Treatment-naive patients showed a response rate of 72.7% (24/33) in the initial study and 71.0% (22/31) in the second, whereas previously treated patients showed a 50.0% (8/16) response rate in the initial study and a 20.0% (1/5) rate in the second. Adverse reactions of more than Grade 3 in the initial study were leukopenia in 18.4%, thrombocytopenia in 8.2%, decrease of hemoglobin in 6.1%, loss of hair in 6.1%, anorexia in 36.7%, nausea and vomiting in 26.5%, and diarrhea in 4.1%, whereas those of Grade 3 in the second study were decrease of hemoglobin in 2.8%, anorexia in 22.2% and nausea and vomiting in 8.3%. From these results, it is suggested that the regimen in the second study was more useful than that in the initial study.

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BACKGROUND: Group I introns share a conserved core region consisting of two domains, P8-P3-P7 and P4-P6, joined by four base-triples. We showed previously that the T4 td intron can perform phosphoester transfer reactions at two splice sites in the absence of both P4-P6 and the conserved base-triples, whereas it is barely able to perform the intact splicing reaction due to the difficulty of conducting the sequential reactions. RESULTS: Based on previous findings, we constructed a bimolecular ribozyme lacking a large portion of P4-P6 and the base-triples from the Tetrahymena intron, on the assumption that the long-range interactions of the peripheral regions in the two RNAs can compensate for the deteriorated core. The bimolecular ribozyme performed the intact splicing reaction. CONCLUSION: The present analysis indicates that the base-triples are nonessential, but that L4 and the distal part of P4 in P4-P6 are important for conducting the splicing reaction. The reconstituted self-splicing ribozyme provides an amenable system for analysing the role(s) of elements in the core region in the self-splicing reaction mechanism.

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To investigate the mechanism of decrease of serum DPP IV activity in oral cancer patients, we analyzed the expression of DPP IV in peripheral blood T lymphocytes of oral cancer patients and healthy subjects. Consequently, serum DPP IV activity was found to correlate significantly with the number of peripheral blood lymphocytes (PBL), T lymphocytes and CD26 (identified as DPP IV)+ T lymphocytes in healthy subjects, and the number of PBL and CD26+ T lymphocytes in cancer patients. However, the numbers of PBL and T lymphocytes were significantly less in cancer patients than in healthy subjects. Although the number of CD26+ T lymphocytes was somewhat greater in cancer patients than in healthy subjects, serum DPP IV activity was significantly lower in cancer patients. DPP IV activity and amount of CD26 in T lymphocyte plasma membranes were much less in cancer patients than in healthy subjects. These findings suggest that a decrease in the number of T lymphocytes and the small amount of DPP IV in their plasma membrane may contribute to the decrease of serum DPP IV activity in cancer patients.

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The purpose of this study was to examine tooth strains in Class II preparations. A Class II cavity was prepared in 16 permanent premolars, and a strain gauge was attached to the buccal surface of each tooth. Each cavity was then restored with bonded amalgam, bonded gallium, composite, or composite with a resin liner. The tooth strains created by these four restorations were determined and evaluated with a strain indicator. The results of this study indicated that composite restorations with and without resin liner created much greater strains to tooth structure than did bonded amalgam and bonded gallium restorations. The application of resin liner before placement of the composite was effective for decreased tooth strain.

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Combined effect of bleomycin (BLM) and N-solanyl-N, N'-bis (3, 4-di-methoxy-benzyl)-ethylenediamine (SDB-ethylenediamine), a synthetic isoprenoid was studied on 3 oral squamous carcinoma cell lines (SCCTF, SCCKN, SCCRY) and clonal cell lines from SCCRY in vitro and on transplantable nude mouse tumors. The cytotoxicity of SDB-ethylenediamine varied among those cell lines in vitro. SDB-ethylenediamine potentiated more than 2-fold the cytotoxic effect of BLM in 6 cell lines, but no distinct correlation was found between cytotoxicity of SDB-ethylenediamine and potentiation by BLM. Compared with verapamil, the cytotoxic effect of BLM was potentiated 3.9-fold by SDB-ethylenediamine in SCCTF. The growth of the transplantable nude mouse tumors (SCCRY and SCCTF) was strongly suppressed when BLM was combined with SDB-ethylenediamine. Correlation between BLM resistance and potentiation of BLM by SDB-ethylenediamine was not observed in this experiment.

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To evaluate the effect of UFT as a postoperative adjuvant chemotherapeutic agent for a patient with tongue cancer complicating chronic renal failure, we measured a dynamic change of serum tegafur (FT), 5-FU and uracil concentrations in hemodialysis. When the patient administered 200 mg of UFT orally one hr before hemodialysis, serum 5 FU concentration was 0.051 micrograms/ml at the beginning of hemodialysis, then rapidly increased to 0.396 micrograms/ml at maximum one hr later and thereafter decreased to the initial level after 4 hrs, the end of hemodialysis. Even after hemodialysis, however, 5-FU maintained the effective serum concentration. On the other hand, serum FT and uracil levels showed a slight change during hemodialysis. The maximum concentrations of FT and uracil were 3.154 micrograms/ml and 0.540 micrograms/ml respectively, after 3 hrs of dialysis. We next measured serum levels of 5-FU, FT and uracil during two days without hemodialysis treatment. Although their serum levels were increased after UFT administration, those were decreased to the initial level on the next day, indicating no drug accumulation. These results suggest that UFT was safe and useful as a postoperative adjuvant chemotherapeutic agent in a cancer patient being performed hemodialysis.

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We examined the change of sensitivity to antitumour agents by repeated treatment with bleomycin (BLM) using two oral squamous carcinoma cell lines, SCCTF and SCCKN. SCCTF exhibited minimal sensitivity to BLM and strong heterogeneity in BLM sensitivity, whereas SCCKN was highly sensitive to BLM and showed weak heterogeneity. When SCCTF was treated continuously with low-dose BLM (0.1 microgram/ml) but not intermittently with high-dose BLM (1 microgram/ml), the BLM sensitivity was rapidly decreased to acquire drug resistance. On the other hand, SCCKN was completely killed by the same treatments. To investigate the mechanism of induction of resistance in SCCTF, BLM-sensitive and -resistant clones, TF-S and TF-R, were isolated and analysed. Consequently, TF-R showed decreased cellular accumulation and retention of BLM, increased BLM hydrolase activity and elevated DNA repair activity concomitant with increased poly(ADP-ribose) polymerase activity as compared with TF-S. Therefore, it was suggested that antitumour drug-resistant clones were selectively grown from heterogeneous tumour cell population.

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The purpose of this study was to evaluate the sealing ability of a dentinal apical plug treated with a bonding agent. Ninety human lower premolars were used. The teeth were divided into three groups. in groups 1 and 2, to prepare an apical isthmus of 1 mm in length, the first apical seat was prepared with a #45 K file 1 mm short of the anatomical apex and with a #60 K file 2 mm short for the second apical seat. Dry dentin fillings were packed in the apical isthmus with a #60 K file. In group 1, the root canal was obturated with gutta-percha and Canals root canal sealer by the lateral condensation method. In group 2, following an application of the bonding agent to the plug, the root canal was obturated in the same way. In group 3 (control), a single apical seat was prepared with a #60 K file 1 mm short of the apex and the root canal was obturated similarly. The teeth of three groups were immersed in a 1% methylene blue solution for 1, 2, and 4 wk. Dye penetration depth from the apical foramen was determined. Group 2 showed no leakage after 4 wk. Groups 1 and 3 showed dye penetration into the root canal, and in these two groups dye penetration increased with time.

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Soft mouth guards are effective to prevent traumatic injury in the maxillofacial region. In this study, we tried to find out the effect of soft mouth guards on the distribution and the magnitude of occlusal force using the T-Scan system. Ten adult subjects volunteered to exert maximum biting force wearing three different types of soft mouth guards. With the limitation of the T-scan system reported in our previous article, following results were obtained. 1) Occlusal forces were more evenly distributed with soft mouth guards than without them. 2) Softer mouth guards were more effective for occlusal force distribution. 3) Since occlusal relationship between mouth guards and mandibular arch could alter the distribution pattern a great deal, occlusion of mouth guards should be examined more carefully.

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Mouth guards are effective to prevent traumatic injury in maxillofacial region during sports activities. This study was conducted to investigate the influence of wearing mouth guards on occlusal force distribution with the T-scan system. With comparison to the value of average occlusal force level per occlusal point (OFL) on natural dentition and wearing conventional full arch bite plane, following results were obtained. 1) Difference of OFL within the same dental arch became smaller when mouth guards were on. 2) Statistically significant difference in OFL was not found between two mouth guards with different hardness. 3) During three seconds clenching, OFL in posterior region changed great deal at the initiation but stayed at about the same level after that.

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