Preliminary results of phase I trial of oral uracil/tegafur (UFT), leucovorin plus irinotecan and radiation therapy for patients with locally recurrent rectal cancer

BACKGROUND: Surgical attempts for locally recurrent rectal cancer often fail due to local re-recurrence and distant metastasis. Preoperative chemoradiation may enhance better local control and survival. The aim of this study was to assess the safety of oral uracil and tegafur (UFT) plus leucovorin (LV), and irinotecan combined with radiation and determine the maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of the triple drug regimen. PATIENTS AND METHODS: Patients with locally recurrent rectal cancer received escalating doses of irinotecan on days 1, 8, 15, and 22 (starting at 30 mg/m(2), with 10 mg increments between consecutive cohorts) and fixed doses of UFT (300 mg/m(2)) plus LV (75 mg/day) on days 3 to 7, 10 to 14, 17 to 21, and 24 to 28. Radiation was given 5 days per week totaling 40 to 50 Gy (2Gy/day). RESULTS: Six patients were treated at the starting dose, and 2 received the full scheduled chemoradiotherapy. The other 4 patients had grade 3 diarrhea and diarrhea was the DLT. One patient had partial response and he had subsequently radical surgical resection. Median progression free survival for local recurrence was 320 days. CONCLUSION: Irinotecan plus UFT/LV with concomitant radiotherapy in patients with locally recurrent rectal cancer was not feasible due to diarrhea in this setting. Modification of the treatment is needed

「情報処理学会論文誌：教育とコンピュータ」の現状と展望

2017年度 情報処理学会関西支部.支部大会 2017年9月25日(月) 大阪大学中之島センタ

Higher Serum Brain-Derived Neurotrophic Factor Levels Are Associated With a Lower Risk of Cognitive Decline: A 2-Year Follow Up Study in Community-Dwelling Older Adults

ObjectiveTo assess the relationship of serum brain-derived neurotrophic factor (BDNF) levels with the subsequent short-term decline in cognitive functioning in community-dwelling older adults.DesignTwo-year prospective, observational study.Setting and ParticipantsThe study included 405 adults aged 65–84 years, initially free of a dementia diagnosis who were living in Tokyo, Japan.MethodsParticipants underwent health assessments at baseline (2011) and follow-up (2013). Serum BDNF levels and scores from the Montreal Cognitive Assessment-Japanese version (MoCA-J) were systematically measured. Logistic regression was used to estimate the odds of cognitive decline between baseline and follow-up assessments in the full MoCA-J scale (operationally defined as a decrease of two or more points), as well as in MoCA-J subscales (decline of one or more points in a specific subscale), as a function of serum BDNF level, adjusting for baseline demographics, prevalent chronic diseases, and baseline cognitive scores.ResultsAmong individuals who performed worse on the full MoCA-J at baseline (i.e., scores in the bottom quartile [≤21], which is consistent with a mild cognitive impairment status), but not among those who performed better (top 3 quartiles), those with highest baseline serum BDNF levels (top quartile) had lower odds of subsequent decline in the full MoCA-J scale than those with lowest (bottom quartile); i.e., odds ratio (OR): 0.10 (95% confidence interval [CI]: 0.02–0.62; p = 0.013). Regarding MoCA-J subscales, adjusted odds of decline in the executive function subscale, but not in the other five subscales, were substantially low among those with highest baseline serum BDNF levels (top quartile), as compared to those with the lowest (bottom quartile), i.e., OR: 0.27 (95% CI:0.13–0.60; p < 0.001).Conclusion and ImplicationsHigher serum BDNF levels were associated with a lower risk of decline in cognitive function in a sample of community-dwelling older Japanese adults. Risk varied across cognitive subdomains and according to baseline cognition. This warrants further research to evaluate the added-value of serum BDNF in health promotion initiatives directed toward cognitive decline prevention in community-dwelling older adults

Pyridoxal 5′-phosphate and related metabolites in hypophosphatasia: Effects of enzyme replacement therapy

Objective To investigate the utility of serum pyridoxal 5′-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) as a diagnostic marker of hypophosphatasia (HPP) and an indicator of the effect of, and patient compliance with, enzyme replacement therapy (ERT), we measured PLP, PL, and PA concentrations in serum samples from HPP patients with and without ERT. Methods Blood samples were collected from HPP patients and serum was frozen as soon as possible (mostly within one hour). PLP, PL, and PA concentrations were analyzed using high-performance liquid chromatography with fluorescence detection after pre-column derivatization by semicarbazide. We investigated which metabolites are associated with clinical phenotypes and how these metabolites change with ERT. Results Serum samples from 20 HPP patients were analyzed. The PLP-to-PL ratio and PLP concentration were elevated in all HPP patients. They correlated negatively with serum alkaline phosphatase (ALP) activity and showed higher values in more severe phenotypes (perinatal severe and infantile HPP) compared with other phenotypes. PL concentration was reduced only in perinatal severe HPP. ERT reduced the PLP-to-PL ratio to mildly reduced or low-normal levels and the PLP concentration was reduced to normal or mildly elevated levels. Urine phosphoethanolamine (PEA) concentration did not return to normal levels with ERT in most patients. Conclusions The serum PLP-to-PL ratio is a better indicator of the effect of ERT for HPP than serum PLP and urine PEA concentrations, and a PLP-to-PL ratio of <4.0 is a good indicator of the effect of, and patient compliance with, ERT

エニワ ニ オケル ハナ ノ マチズクリ ノ ケイセイ ト シミン カツドウ

本研究は、北海道恵庭市における「花のまちづくり」の形成に関わるプロセスを検討し、市民と行政の協働による「花のまちづくり」活動の現況と課題を探究することを目的とする。恵庭の「花のまちづくり」は、北海道内有数の花苗の生産地という地域の特性を生かして形成されたものである。そして特筆すべきは、市民主導で始まったまちづくりという点である。その市民主導のまちづくりを支えたのが、「花いっぱい文化協会」と「花苗生産組合」である。花苗の流通を「花いっぱい文化協会」が斡旋し、「花苗生産組合」が供給するというシステムが、「花のまちづくり」形成の基盤である。市民活動と両者との連携、行政の支援が、「花のまちづくり」の構造である。恵庭の「花のまちづくり」は、北海道内有数の花苗の生産地という地域資源を活用し、新たな価値を創造するまちづくりである

マチズクリ ニ オケル シャカイテキ キョウユウ シホン ノ ヤクワリ ニ カンスル ケンキュウ : オビヒロ ノ モリ ノ ジレイ ケンキュウオ トオシテ

本研究は、まちづくりの基盤を成すものを社会的共有資本として捉え、その役割について考察することを目的とする。社会的共有資本とは、社会を持続的に維持することを可能にし、地域に住む人々が共有する社会的装置として考える。帯広の森の事例研究を通して、社会的共有資本の連携・蓄積が、市民活動を活性化し、好循環が生まれ、持続可能なまちづくりの進展を可能とすることを明らかにできた。地域を維持する力としての社会的共有資本は、まちづくりの基盤を支える豊かな関係性の源泉として重要な役割を果たしている