A new cancer diagnostic system based on a CDK profiling technology

AbstractA series of molecular pathological investigations of the molecules that stimulate the cyclin dependent kinases (CDK1, 2, 4, and 6) have led to enormous accumulation of knowledge of the clinical significance of these molecules for cancer diagnosis. However, the molecules have yet to be applied to clinical cancer diagnosis, as there is no available technology for application of the knowledge in a clinical setting. We hypothesized that the direct measurement of CDK activities and expressions (CDK profiling) might produce clinically relevant values for the diagnosis. This study investigated the clinical relevance of CDK profiling in gastrointestinal carcinoma tissues by using originally developed expression and activity analysis methods. We have established novel methods and an apparatus for analyzing the expression and activities of the CDK molecules in lysate of tumor tissue in a clinical setting, and examined 30 surgically dissected gastrointestinal carcinomas and corresponding normal mucosal specimens. We demonstrate here that remarkably elevated CDK2 activity is evident in more than 70% of carcinoma tissues. Moreover, a G1-CDK activity profiling accurately mirrored the differences in proliferation between tumor and normal colonic tissues. Our results suggest that CDK profiling is a potent molecular–clinical approach to complement the conventional pathological diagnosis, and to further assist in the individualized medications

Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): A study protocol for a multicenter randomized phase III trial

金沢大学附属病院泌尿器科Background: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. Methods/design: The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. Discussion: Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. Trial registration: University hospital Medical Information Network (UMIN) Center identifier UMIN000015529. Registrated 11/1/2014. © 2017 The Author(s)

地域包括ケアシステムにおける訪問看護ステーションの経営状況と事業所特性及び地域特性，経営管理との関連―全国と群馬県の比較―

目的：全国及び群馬県の訪問看護ステーション（以下，ST）の経営状況と事業所特性及び地域特性，経営管理との関連を明らかにし，比較検討する． 方法：全国2,000人及び群馬県163人のST管理者を対象とし，自記式質問紙調査を実施した．有効回答は全国473人，群馬県55人で，経営状況と各項目との関連はχ2検定及びKruskal-Wallis検定を，さらに経営状況を目的変数とするロジスティック回帰分析を行った． 結果：全国では，看護師常勤・看護師非常勤・事務職員非常勤の従業者数，1人1日平均訪問回数，北海道・東北地域，収支のモニタリングが黒字に関連していた．群馬県では関連がみられず，全国に比して赤字のST割合が多く，経営管理の得点が低かった． 結論：経営状況の改善には，ST規模の拡大やST管理者の収支のモニタリングに焦点を当てた行動の有効性が示唆された．群馬県では，経営管理に関する分析の強化が必要である．Objectives: The financial status of home-visit nursing stations (STs) was analyzed in relation to business office characteristics, local community characteristics and business management, and the results between Gunma Prefecture and all prefectures in Japan were compared. Methods: A self-administered questionnaire survey was completed by 163 ST managers in Gunma Prefecture and 2000 ST managers from all over Japan. Valid responses were collected from 55 managers from Gunma Prefecture and 473 managers from all over Japan. The association between management status with each variable was analyzed by the chisquare test and Kruskal-Wallis test. In addition, logistic regression analysis was carried out with the status of management as the dependent variable. Results: For STs all prefectures in Japan, profitable business (black-ink balance) was associated with the number of employees (full-time nurses, part-time nurses and part-time clerical staff), the mean number of care receiver homes visited daily by each nurse, the district (Hokkaido/Tohoku) and revenue/expenditure balance monitoring. In Gunma Prefecture, the percentage of red-ink operation STs was higher and the score for business management was lower than in all prefectures in Japan. Conclusions: These results suggest that management actions focusing on expansion of the scale of STs and on revenue/ expenditure balance monitoring by ST managers are effective in improving the status of management. In Gunma Prefecture, reinforcement of how to analyze business management is needed.原

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

金沢大学医薬保健研究域医学系The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society

Clinical implications of serum autotoxin in regular follow up after pediatric living donor liver transplantation for biliary atresia

Background: : Pediatric patients sometimes develop graft fibrosis after living donor liver transplant (LDLT). Autotaxin is a recently developed serum marker for hepatic fibrosis. We studied the relationship between serum autotaxin levels and histological findings in patients after LDLT for biliary atresia (BA). Methods: Information on patients aged <19 years who received LDLT for BA and were followed for at least 1 year after LDLT was gathered. Autotaxin levels were compared with pathological fibrosis scores. Results: The study included 52 patients, of whom 4 patients had no fibrosis (F0), 36 patients had F1 fibrosis, and 12 patients had F2. The median serum autotaxin level was 0.89 mg/L. In patients with portal vein (PV) complications such as stenosis or thrombosis (n = 7), the mean autotoxin level was 1.25 mg/L compared with 0.95 mg/L in patients without PV complications (p = 0.004). Among patients without PV complications, the mean autotaxin level was 0.90, 0.88, and 1.18 mg/L in F0, F1, and F2 fibrosis, respectively. The mean autotaxin was higher in F2 fibrosis than in F0 or F1 fibrosis (p<0.05). Autotoxin had a high area under the curve (0.86) with the cut-off level of 0.897 mg/L. Conclusion: Serum autotaxin is a novel marker for liver fibrosis in patients after pediatric LDLT for BA. Type of study: : Study of Diagnostic Test. Level of evidence: : Level II

Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): a study protocol for a multicenter randomized phase III trial

Abstract Background Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. Methods/design The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. Discussion Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. Trial registration University hospital Medical Information Network (UMIN) Center identifier UMIN000015529 . Registrated 11/1/2014