Thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in hepatocellular carcinoma and metastatic liver cancer

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with various cancers. We tried to prove the correlation of TP and DPD expression in hepatocellular carcinoma (HCC) and liver metastasis. We quantified TP and DPD levels by an enzyme-linked immunosorbent assay (ELISA) in the tumor (T) and adjacent normal tissue (N) obtained from 8 HCC patients, and 11 liver metastasis patients together with 9 of their primary cancers. TP levels were higher in the primary cancer, liver metastasis, and HCC compared with each adjacent tissue. TP levels were higher in HCC than in liver metastasis, and TP levels in the adjacent tissues of HCC were also higher than those in adjacent tissues of liver metastasis. TP levels were higher in liver metastasis than in primary cancer, and TP levels in adjacent tissues of liver metastasis were also higher than those in adjacent tissues of primary cancer. However, there were no differences in TP T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. DPD levels were lower in the liver metastasis compared with the adjacent liver tissues, and DPD levels in liver metastasis or its adjacent liver tissues were higher than those in primary cancer or its adjacent tissues. There were no differences in DPD T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. Thus, we demonstrated that TP was highly expressed in liver malignancy. We may be able to increase the success of anticancer chemotherapy for liver malignancy while decreasing the side effects by analysis of T/N ratios in TP, DPD, and TP/DPD in addition to TP expression.     

Randomized phase II study comparing mitomycin, cisplatin plus doxifluridine with cisplatin plus doxifluridine in advanced unresectable gastric cancer

Various chemotherapies have been used to treat inoperable gastric cancer. Most combination therapies include cisplatin (CDDP) and fluoropyrimidine (5-FUs), which are thought of as key drugs. In the present study, we randomly compared mitomycin (MMC) and CDDP plus doxifluridine (5'-DFUR), which is an oral 5-FU and an intermediate metabolite of capecitabine (Xeloda), with CDDP plus 5'-DFUR in advanced unresectable gastric cancer. Regimen A was CDDP (70 mg/m2, by 2-hour intravenous drip infusion on day 1), MMC (7 mg/m2, injected intravenously on day 2), and oral 5'-DFUR (1200 mg/m2, on days 4 to 7, 11 to 14, 18 to 21 and 25 to 28; 3 days rest and 4 days administration). Regimen B was identical to regimen A without MMC. RESULTS: The response rate was 25.0% (8/32 patients) in Regimen A, 17.2% (5/29) in Regimen B (p=0.541). The median survival time was 241 days in Regimen A and 179 days in Regimen B (p=0.498). In Regimen A, although no significant difference was observed, end points such as response rate and suvival improved. Thus, we concluded that a randomized controlled phase III study with more subjects should be conducted.     

Clinical outcomes of stereotactic radiotherapy for stage I non-small cell lung cancer using a novel irradiation technique: patient self-controlled breath-hold and beam switching using a combination of linear accelerator and CT scanner

We have developed a novel irradiation technique for lung cancer that combines a linear accelerator and CT scanner with patient-controlled breath-hold and radiation beam switching. We applied this technique to stereotactic three-dimensional (3D) conformal radiotherapy for stage I non-small cell lung cancer (NSCLC) and evaluated the primary therapeutic outcomes. A total of 35 patients with stage I (15 IA, 20 IB) primary NSCLC (20 adeno, 13 squamous cell, and 2 others) were treated with this technique. Patients ranged from 65 to 92 years old (median, 78 years). Twenty-three (66%) patients were medically inoperable due to mainly chronic pulmonary disease or high age. Three-dimensional treatment plans were made using 10 different non-coplanar dynamic arcs. The total dose of 60 Gy was delivered in 10 fractions (over 5-8 days) at the minimum dose point in the planning target volume (PTV) using a 6 MV X-ray. After adjusting the isocenter of the PTV to the planned position by a unit comprising CT and linear accelerator, irradiation was performed under patient-controlled breath-hold and radiation beam switching. All patients completed the treatment course without complaint. Complete response (CR) and partial response (PR) rates were 8/35 (23%) and 25/35 (71%), respectively. Pulmonary complications of National Cancer Institute-Common Toxicity Criteria grade >2 were noted in three (9%) patients. During follow-up (range, 6-30 months; median, 13 months), two (6%) patients developed local progression and five (14%) developed distant or regional lymph node metastases. Two-year overall survival rates for total patients and medically operable patients were 58 and 83%, respectively. In conclusion, this new irradiation technique, utilizing patient-controlled radiation beam switching under self-breath-hold after precise alignment of the isocenter, allows safe high-dose stereotactic radiotherapy with sufficient margins around the CTV and reduced treatment times. Based on the initial results, excellent local control with minimal complications is expected for stage I NSCLC.     

Clinical and immunological studies on patients with Graves' disease preoperatively treated with corticosteroids and iodides

The purpose of this study was to evaluate the acute effects of corticosteroid and iodide preoperative therapy in patients with Graves' disease in terms of thyroid function and immunological parameters. The above combination was prescribed for 4 patients who had experienced severe side effects from antithyroid drugs (ATD) in order to reduce the possibility of post-thyroidectomy thyroid storm. Corticosteroids were employed daily for four days, and iodides were given daily for two weeks prior to thyroidectomy. The free T₃ values decreased rapidly to euthyroid levels following the administration of both drugs, although the free T₄ values were still much higher than normal in 3 of the 4 patients at the time of surgery. By comparison, 3 of 8 patients treated with ATD also had thyroid hormone levels above normal. Studies of lymphocyte subsets revealed that the percentage of helper T cells was significantly less in the corticosteroidiodide treatment group than in the control and ATD groups. It is thus possible that postoperative thyroid storm might be prevented through corticosteroid-iodide therapy by virtue of the reduction of free T₃ values to within the normal range by the time of surgery. The acute suppression of helper T cells was another result of this form of therapy observed.     

Circulating renin in essential hypertension: an evaluation of its significance in the Japanese population

Plasma renin activity (PRA) was measured in 139 healthy subjects and 200 patients with essential hypertension. There was an obvious relationship between the PRA levels and aging. Elevated PRA values were obtained only in younger subjects under 20 years of age, while the PRA levels were very low only in advanced ages over 60 years.In essential hypertensive subjects, subnormal resting PRA was found in 23.5 per cent, normal PRA in 64.5 per cent, and high PRA in 12 per cent. A marked impairment of renal function and severe retinal changes were observed in the patient with high resting PRA values. On the contrary, hypertensive complications of the kidney and ocular fundi were mild in the patients with low resting PRA values.A reaction of renin secretion was studied in 161 patients with essential hypertension. There were no apparent relationships between the responsiveness of the renin system to intravenous furosemide following upright posture and hypertensive vascular injury.     

Effect of self-etching primer containing N-acryloyl aspartic acid on enamel adhesion.

OBJECTIVES: A previous study demonstrated that N-acryloyl aspartic acid (N-AAsp) aqueous solution is useful as a self-etching primer for dentin adhesion. The purpose of this study was to evaluate whether N-AAsp solution can be used for enamel etching, when compared with phosphoric acid. METHODS: N-AAsp was synthesized by the reaction of DL-aspartic acid and acryloyl chloride. The experimental self-etching primers were prepared by dissolving N-AAsp in water at various concentrations up to 20 wt%. The tensile bond strength of resin to bovine enamel was measured after the enamel was treated with the N-AAsp primers. The 40 wt% H(3)PO(4) was used for comparison. The treated enamel surfaces and the resin-enamel interfaces were also observed with a scanning electron microscope. RESULTS: The tensile bond strength to enamel increased linearly with the increasing N-AAsp concentration and reached the same value as that to enamel etched with 40 wt% H(3)PO(4) when N-AAsp concentration was 20 wt%, even though the etching ability of 20 wt% N-AAsp was inferior to 40 wt% H(3)PO(4). Regardless of the concentration of N-AAsp, the bond strength to enamel was the same as that to dentin reported in our previous study. SIGNIFICANCE: The 20 wt% N-AAsp aqueous solution showed enamel bonding equivalent to 40 wt% H(3)PO(4) in addition to the advantage of eliminating the rinse step with water. Based on the results obtained in this study along with those obtained in a previous study, it was concluded that 20 wt% N-AAsp aqueous solution is a promising self-etching primer to simultaneously treat enamel and dentin.     

Evaluation of adhesive defects using an ultrasonic pulse-reflection technique

The purpose of this study was to examine the application of an ultrasonic pulse-reflection technique for the evaluation of adhesive defects. First, the sonic velocities in the enamel and dentin of human molars and bovine incisors were measured with a pulsar receiver attached to an ultrasonic transducer. The identification of the dentino-enamel junction and pulp-dentin interface using the ultrasonic method based on intrinsic sonic velocities showed good agreement with the actual measured thicknesses. Next, a cemented restoration with artificial faults was prepared. Half of the Au-Ag-Pd alloy plate area was cemented to the dentin slab using luting resin cement. The adhesive interface was evaluated with a high-resolution ultrasonic imaging system. Clear internal faults were evident from the ultrasonic tomogram. The findings of this study suggest that the ultrasonic pulse-reflection technique may be useful for inspecting and imaging structural defects of adhesive interfaces.