Modified pharmacokinetic modulating chemotherapy using 5-fluorouracil,UFT, and taxotere (docetaxel) for advanced gastric cancer

The efficacy of neoadjuvant chemotherapy for advanced gastric carcinoma is controversial. Moreover, a standard regimen for such chemotherapy has not been clearly established. Pharmacokinetic modulating chemotherapy (PMC), a combination of infused 5-fluorouracil and oral uracil-tegafur, has been proven to be highly effective for the treatment of colorectal carcinoma. We report two patients with advanced gastric carcinoma successfully treated with PMC and infused taxotere (TXT; docetaxel). Preoperative treatment with PMC and TXT significantly decreased the depth of wall penetration of the tumor in one patient and reduced the size of the tumor in the other patient. In both patients, there were significant chemotherapeutic effects on the primary tumor and on regional lymph nodes pathologically. Preoperative PMC plus TXT produced primary tumor downstaging, leading to improved resectability. The responsiveness of metastatic cancer cells in the regional lymph nodes suggested the possibility of nodal downstaging by this regimen.     

Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer

Background. Both docetaxel (TXT) and irinotecan (CPT-11) are active chemotherapeutic agents for gastric cancer. We designed a biweekly administration regimen of TXT combined with CPT-11 for 4 weeks as one cycle in patients with inoperable or recurrent gastric cancer, and conducted a dose-escalation study. Methods. Patients with histologically confirmed gastric cancer were treated with the regimen. The dosage levels of TXT and CPT-11 were as follows: level 1, 30mg/m² and 50mg/m²; level 2, 35 and 50mg/m²; level 3, 40 and 50mg/m²; level 4, 40 and 60mg/m²; and level 5, 50 and 60mg/m². The dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. Results. Grade 4 neutropenia was observed at level 3, but no other DLT was observed at less than level 4 during the first cycle. However, three patients at level 3 could not continue treatment without a decrease in the dosage after the second cycle. Based on these results, level 2 was considered to be the clinically recommended dosages. Conclusion. Biweekly TXT and CPT-11 was well tolerated. The recommended dosages of TXT and CPT-11 for a phase II trial are 35mg/m² and 50mg/m², respectively.     

Gene expression of neuropeptide Y in the nucleus of the solitary tract is activated in rats under restricted daily feeding but not under 48-h food deprivation

The two neuropeptide Y (NPY) systems innervating the hypothalamic paraventrivular nucleus were examined regarding their roles in the prefeeding corticosterone peak developed under restricted daily feeding (RF). Protein and mRNA levels of NPY were measured in the arcuate nucleus (ARC) and the nucleus of the solitary tract (NST) in rats under 48-h food deprivation (48-hFD), RF, and 72-h food deprivation imposed after RF (post-RF 72-hFD) with 7 days of ad libitum feeding in between. NPY protein and mRNA levels in the ARC significantly increased with 48-hFD and decreased with re-feeding, whereas those in the NST were not changed by 48-hFD. When rats had RF imposed with free access to food from 10.00 to 12.00 h (lights on from 06.00 to 18.00 h) for 3 weeks, NPY concentrations in the ARC increased at 10.00 h, just prior to the daily meal, but those in the NST did not change significantly throughout the period examined. On the other hand, NPY mRNA levels in both the ARC and NST increased before the meal supply and remained high for 4 h after feeding. Under post-RF 72-hFD, the prefeeding peak of NPY mRNA was detected in the NST, but NPY mRNA levels in the ARC were continuously high throughout the 24-h period. These findings indicate that the NPY neurons from the NST are specifically activated by RF, whereas those from the ARC are generally stimulated by an increased food demand.     

Comparative study of short-term anxiolytic potency of alprazolam and tandospirone in psychiatric outpatients with anxiety disorders

Anxiolytic potency of 1 week of treatment with alprazolam or tandospirone in psychiatric outpatients with anxiety disorders was evaluated by changes in the scores on the Hamilton Anxiety Scale and the State and Trait Anxiety Inventory and in the saliva level of free-3-methoxy-4-hydroxyphenylglycol (free-MHPG). Saliva level of free-MHPG was significantly reduced by 1 week of treatment with alprazolam but not with tandospirone. Reductions in the HAS score after 1 week of drug treatment were greater in patients treated with alprazolam than in those treated with tandospirone. These results indicate that the short-term anxiolytic potency of alprazolam is greater than that of tandospirone and that the saliva level of MHPG would be a useful marker for the evaluation of the therapeutic potency of anxiolytic agents. Copyright 2001 John Wiley & Sons, Ltd.     

融合表达β趋化因子受体5NH2端膜外第一襻及其特异抗体F(ab′)2的制备

目的：研究β趋化因子受体５（ＣＣＲ５）ＮＨ２端膜外第一襻结构域的功能及其特异抗体Ｆ（ａｂ′）２的制备。方法：计算机分析趋化因子超基因家族,定位超基因家族中同源顺序最低的结构域ＮＨ２端膜外结构域,ＰＣＲ扩增出该结构域１１４个核苷酸序列。构建融合表达载体ｐＧＥＸ－ＩＮ／ＮＲ５,经测序鉴定正确后,在Ｅ．ｃｏｌｉ中表达,经纯化后免疫新西兰兔。蛋白Ａ亲和层析和胰蛋白酶消化ＩｇＧ,经Ｓｅｐｈａｒｏｓｅ－１２柱层析制备Ｆ（ａｂ′）２。结果：经还原和非还原聚丙烯酰胺凝胶电泳和ＦＡＸ分析证明得到抗ＣＣＲ５ＮＨ２端的特异性抗体。结论：本方法为一简捷快速的特定功能结构域抗体Ｆ（ａｂ′）２制备方法,对研究该基因在体内的表达及生物学功能提供了重要的实验材料,同时也对超基因家族中亚家族特异抗体研制提供了一种研究思路和方法。     

Paradoxical increases in serum levels of highly chlorinated PCBs in aged women in clear contrast to robust decreases in dietary intakes from 1980 to 2003 in Japan

Objective  Exposure to polychlorinated biphenyls (PCBs) is considered to have culminated between 1950 and 1970 in Japan, and exposure through diet, the major exposure route, has decreased significantly over the last 10 years. The primary goal of the present study was to investigate the long-term trends and congener profiles of serum and dietary levels of PCBs using historical samples. Methods  Using banked samples collected in 1980, 1995, and 2003 surveys, we determined the daily intakes and serum concentrations of 13 PCB congeners (#74, #99, #118, #138, #146, #153, #156, #163, #164, #170, #180, #182, and #187) in women. Results  The total daily PCB intake [ng/day, geometric mean (geometric standard deviation)] decreased significantly from 523 (2.5) in 1980 to 63 (3.2) in 2003. The serum total PCB level (ng/g lipid) in women <40 years of age decreased significantly from 185 (1.8) in 1980 to 68 (1.8) in 2003. In contrast, the level in women >50 years of age increased significantly from 125 (1.7) in 1980 to 242 (1.7) in 2003. Specifically, the serum concentrations of hexa (#138, #146, #153, #156, #163, and #164) and hepta (#170, #180, #182, and #187) congeners increased significantly. A comparison of the serum PCB levels of women born from 1940 to 1953 revealed that their serum total PCB level was significantly higher in the 2003 survey [242 (1.7), n = 9] than in the 1995 [128 (2.0), n = 17] surveys. This increase in the total PCB level was attributable to increases in the hepta congener groups. Conclusion  Present results suggest a decreased rate of elimination of hepta congeners with aging in females, rather than a birth-generation phenomenon.     

Long-term control of sacral metastasis from rectal cancer with S-1 + radiation treatment (RT) and mFOLFOX6 combination therapy--a case report

Combined chemotherapy including 5-FU plus radiation treatment resulted in a synergistic effect has been reported. S-1 enhances a radiation response of colon cancer cell line xenografts. Also the effectiveness of S-1 + radiation therapy has been reported. A 66-year-old man underwent a low anterior resection for lower rectal cancer. Adjuvant chemotherapy was not performed due to Stage II rectal cancer. Twenty months after the operation, solitary sacral bone metastasis was found during the postoperative work-up. S-1 (120 mg/day) combined with radiotherapy was performed on days 1-14 and 21-35. Radiation (3 Gy) was administered a total of 45 Gy on days 1-5, 7-12 and 35-40. Moreover, the reduction was judged as complete response after 11 courses of mFOLFOX 6. There has been no sign of recurrence for 44 months. It suggested that local control therapy (S-1 + radiation) plus systemic chemotherapy (mFOLFOX6) was one of the promising effective therapies for single sacral bone metastasis of rectal cancer.     

The application of a variable-pressure scanning electron microscope with energy dispersive X-ray microanalyser to the diagnosis of electrocution: a case report

We describe here a case of accidental electrocution. A 48-year-old male was found dead in his room. At autopsy, there was a current mark on the right thumb and big toe. Histological examination revealed that the skin wound had the characteristics of a current mark, including vacuolation and elongation of the cell nuclei. We could also identify titanium metallization on the skin surface of the current mark using a variable-pressure scanning electron microscope (VP-SEM) equipped with energy dispersive X-ray microanalyser (EDX). The autopsy finding and the subsequent investigation support the conclusion that the cause of his death was electrocution. Our result shows that the VP-SEM with EDX is a useful tool for the forensic diagnosis of electrocution.